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Frontiers in Behavioral Neuroscience
Individual and Social Behaviors
Nuno Sousa
Life and Health Sciences Research Institute, School of Medicine, University of Minho, Portugal
José M. Delgado-García
Universidad Pablo de Olavide, Spain
Mikhail Lebedev
Duke University, United States
Conclusion and Discussion
Front. Behav. Neurosci., 24 May 2016 | https://doi.org/10.3389/fnbeh.2016.00090
Single Neurons in the Insular Cortex of a Macaque Monkey Respond to Skin Brushing: Preliminary Data of the Possible Representation of Pleasant Touch
Laura Clara Grandi* and Marzio Gerbella
Department of Neuroscience, Physiology Unit, University of Parma, Parma, Italy
Pleasant touch may serve as a foundation for affiliative behavior, providing a mechanism for the formation and maintenance of social bonds among conspecifics. In humans, this touch is usually referred to as the caress. Dynamic caressing performed on the hairy skin with a velocity of 1–10 cm/s is perceived as being pleasant and determines positive cardio-physiological effects. Furthermore, imaging human studies show that affiliative touch activates the posterior insular cortex (pIC). Recently, it was demonstrated that pleasant touch in monkeys (i.e., sweeping in a grooming-like manner) is performed with velocities similar to those characteristics of human caress (9.31 cm/s), and causes similarly positive autonomic effects, if performed with velocity of 5 cm/s and 10 cm/s, but not lower or higher. Due to similarities between the human caress and non-human primate sweeping, we investigated for the first time whether single neurons of the perisylvian regions (secondary somatosensory cortex [SII] and pIC) of a rhesus monkey can process sweeping touch differently depending on the stimulus speed. We applied stimulation with two speeds: one that optimally induces positive cardio-physiological effects in the monkey who receives it, and includes the real speed of sweep (5–15 cm/s, sweep fast), and a non-optimal speed (1–5 cm/s, sweep slow). The results show that single neurons of insular cortex differently encode the stimulus speed. In particular, even the majority of recorded somatosensory neurons (82.96%) did not discriminate the two speeds, a small set of neurons (16.59%) were modulated just during the sweep fast. These findings represent the first evidence that single neurons of the non-human primates insular cortex can code affiliative touch, highlighting the similarity between human and non-human primates' social touch systems. This study constitutes an important starting point to carry out deeper investigation on neuronal processing of pleasant sweeping in the central nervous system.
The sense of touch is a critical and necessary sense for our experience of the world in daily life, not only to haptically explore objects but also to communicate both negative and positive messages during social interactions (Hertenstein et al., 2006a,b). Human studies show that the affiliative touch involving the hairy side of the skin is a dynamic touch which activates specific unmyelinated fibers, the C-fibers, well-known as present not only in humans but also in various mammals, including non-human primates (Zotterman, 1939; Douglas and Ritchie, 1957; Bessou et al., 1971; Iggo and Kornhuber, 1977; Kumazawa and Perl, 1978; Johansson et al., 1988; Nordin, 1990; Vallbo et al., 1995; Morrison, 2012). These fibers are modulated by a dynamic touch performed on the hairy side of the skin with a specific speed of 1–10 cm/s, while they decrease their firing rate if the speed of stimulation is lower than 1 cm/s or higher than 10 cm/s (about 30 cm/s). Indeed, their curve of stimulation has the characteristic upside down U-firing shape with the maximal firing rate for the speed 1–10 cm/s (Vallbo et al., 1995; Löken et al., 2009; Morrison, 2012). This tactile stimulation perceived by means of C-fibers is pleasant for the subjects who receive it (Löken et al., 2009), and it was demonstrated to determine positive physiological effects toward the vagal modulation (Field et al., 1986; Tsao, 2007; Garnera et al., 2008; Russell et al., 2008; Billhult et al., 2009; Diego and Field, 2009; Lindgren et al., 2012; Field, 2014; Schroeder et al., 2014). Concerning the cortical processing, these fibers project to the superficial lamina I and inner lamina II of the spinal dorsal horn (Kumazawa and Perl, 1978; Light and Perl, 1979; Sugiura et al., 1986). Information conveyed by C-fibers are relayed, at higher levels, by the ventromedial posterior thalamic nucleus to the dorsal posterior insular cortex (pIC; Olausson et al., 2002, 2008a,b, 2010; Björnsdotter et al., 2009), to the orbitofrontal cortex (a key area for hedonic processing), to the postero-superior temporal sulcus (STS), the medial prefrontal cortex, the dorso-anterior cingulate cortex, and the pregenual anterior cingulate cortex (Kringelbach and Rolls, 2004; McGlone et al., 2007, 2012; Gordon et al., 2013; Ellingsen et al., 2014). These anatomical data are consistent with the idea that these fibers belong to the interoceptive system, and play a pivotal role in the encoding of the pleasantness and emotional component of interpersonal touch. Noteworthy that although to what extent these areas specifically process pleasant touch it remains largely unexplored, the insular cortex, primarily the posterior part, appears to have an especially important role (Olausson et al., 2002, 2010; Björnsdotter et al., 2009).
The affective touch has strong significance not only for humans but also for all social mammals, including non-human primates (Dunbar, 2010). Nevertheless, the knowledge about the mechanisms behind the codification of pleasant touch in monkeys is very poor. Indeed, there are no monkey studies exploring the neural correlate of the pleasantness of touch. Only recently, a role of C-fibers during pleasant sweeping movements associated with grooming, the most important social behavior among monkeys, was hypothesized (Dunbar, 2010). The sweeping can be described as the hand action that the agent monkey performs during grooming to move the hair of the recipient monkey in order to select an area of skin to be picked, for removing any ectoparasites and vegetation trapped in the fur. Thus, this action does not merely have a hygienic function, but also contains an affiliative meaning, as the caress in humans. Until now, only indirect evidence exists in support of this hypothesis. Brain lesion studies (Kling and Steklis, 1976) and single neurons recordings (Ishida et al., 2014) demonstrated that the inner perisylvian regions (secondary somatosensory cortex [SII] and pIC) seems to be involved in the encoding of the grooming behavior of monkeys. In terms of autonomic modulation, it is well known that grooming determines relaxation in monkeys. In particular, a decrement of the heart rate (HR) during received grooming (Boccia, 1989; Boccia et al., 1989; Aureli et al., 1999) and a reduction of the cortisol levels during both passive (Gust et al., 1993) and active grooming (Shutt et al., 2007) were demonstrated. Recently, it was also reported that both the single hand actions of grooming, picking (Grandi and Ishida, 2015) and sweeping (Grandi et al., 2015) determined similar autonomic effects in terms of the HR and heart rate variability (HRV). In particular, the sweeping that determined the decrement of HR and increment of HRV, and therefore of the vagal tone, was performed with speeds of 5 and 10 cm/s, which are similar velocities to those associated with human C-fibers' activation. Furthermore, a pilot kinematic study showed that the velocity of real sweeping is 9.31 cm/s, and therefore it is in the range of the optimal velocity (1–10 cm/s) to activate the C-fibers in humans (Grandi et al., 2015). Finally, the positive autonomic effects were also reported in terms of body temperature changes. In fact, the sweep on the back of a male rhesus monkey occurring with a velocity in the range of 5–10 cm/s determined an increment of the nose skin temperature, parallel to the increment of the HRV and decrement of HR (Grandi and Heinzl, 2015). The increment of nose skin temperature could indicate the positive meaning of stimulation in non-human primates (Ioannou et al., 2015).
Because the pIC appears to have a key role for coding the affiliative interpersonal touch in humans (Olausson et al., 2002, 2008a,b, 2010), and for triggering social behavior in non-human primates (Kling and Steklis, 1976; Ishida et al., 2014; Jezzini et al., 2015), here we investigated the modulation of single neurons in the pIC and in the adjacent SII region of a macaque monkey during the above cited dynamic tactile stimulation considered pleasant for non-human primates: sweeping. We applied stimulation with two velocities: one that optimally induce positive cardio-physiological effects and includes the real speed of sweep (5–15 cm/s, sweep fast) and a non-optimal speed (1–5 cm/s, sweep slow). The present study represents the first evidence of the insular representation of such affiliative touch in non-human primates, and an indirect evidence of a modulatory role of C-fibers in the cortical coding of the pleasant touch.
The experiment was performed on one 5-year-old male Macaca mulatta (5.5 kg). Since the monkey had been used as the subject of another previous electrophysiological experiment, he was already habituated to sitting on a primate chair, interacting with the experimenters and performing a fixation task, as described below (Figure 1A). Moreover, the head fixation system (Crist Instruments) and a circular (2 cm diameter) stainless steel chamber (Narishige, Japan) were implanted on the left hemisphere under general anesthesia (ketamine hydrochloride, 5 mg/kg i.m. and medetomidine hydrochloride, 0.1 mg/kg i.m.), followed by post-surgical pain medication. The study was performed by first recording on the left hemisphere, and then, once the recording sessions in that hemisphere were finished, the circular (2 cm diameter) stainless steel chamber (Narishige, Japan) was implanted on the right hemisphere. The correct position of both chambers to reach the interested deep brain area in order to record it was established based on the fMRI of that monkey's brain. All surgical procedures were the same as described previously in Ishida et al. (2013). All experimental protocols were approved by the Veterinarian Animal Care and Use Committee of the University of Parma, and complied with European law on the humane care and use of laboratory animals. The monkey was kept in an individual primate cage consisting of a full metallic grid (Tecniplast S.p.A. Buguggiate, VA, Italy). The cage was 180 cm in height, 90 cm in width, and 120 cm in depth. In the middle of the vertical side of the cage, it was possible to insert one or two panels for the monkey to sit on. The litter was located immediately below the cage. In the bottom part of the cage two containers were located, one for water and the other for food, which were replenished by the experimenter. The monkey was provided with food and water once daily, typically in the morning. Inside the cage, the monkey had access to toys, mirrors, and swings. Furthermore, the monkey had visual, auditory, and olfactory contact with others and was able to touch and groom with the neighboring monkeys. The cage was in an air-conditioned room maintained at a consistent temperature of 25–26°C. The well-being and health condition of the monkey was constantly monitored by the institutional veterinary doctor of the University of Parma, Italy.
Figure 1. (A) Somatosensory task: Sweep Slow and Sweep Fast. The two sweeping were randomly applied, but for both the task was the following: (1) Green_On—Green_Off: the green light-emitting diode (LED) turned on for 0.5–2 s. We requested monkey to fixate the LED for all duration. (2) Red_On: the green LED switched to red and the experimenter moved the hand toward the monkey's body part to be stimulated. We requested monkey to maintain the fixation. (3) Trg2_On—Trg2_Off: the experimenter touched the monkey (Trg2_On). The red LED switched off and the green LED was turned on until the sensory stimulation was finished (Trg2_Off). We requested monkey to maintain the fixation until the end of the sweeping. (4) Once the sweep had finished, the green LED switched off and after 0.8–1 s the monkey received drops of juice as a reward. After 1.5–2 s, the next trial began. From the end of stimulation to the start of the next trial we did not request the monkey to carry out any fixation task, but just to maintain the hands in their position. (B) The two epochs employed for statistical analyses. (1) Baseline: from 500 to 900 ms after Green_On (total of 400 ms); and (2) Stimulation: from Trg2_On to Trg2_Off. (For details see "Recording of Behavioral Events and Definition of Epochs of Interest" Section).
Definition of Receptive Field
Each isolated neurons in SII and pIC was clinically tested in order to identify the property and the localization and the length of receptive field (RF). The clinical tests consisted of passive static and dynamic touch on all body parts, bilaterally. The touch was applied with the monkey's eyes closed and open. Each neuron showing a clear passive RF was then tested with more structural task (see "Apparatus and Behavioral Paradigm" Section; Figure 1A).
Apparatus and Behavioral Paradigm
During the recording sessions, the monkey had to perform a fixation task while receiving sensory stimulation from the experimenter, on the RF identified during clinical test (see "Definition of Receptive Field" Section). The task consisted of two passive dynamic somatosensory stimulations (sweeps), randomly applied to the RF of each neuron: (1) sweep with a speed of 1–5 cm/s (we defined this condition as sweep slow); and (2) sweep with a speed of 5–15 cm/s (we defined this condition as sweep fast). The stimulations were manually applied by the experimenter, who was trained to apply the stimulation through the two velocity ranges and with the same pressure irrespective of the speed. The exact applied velocity was calculated offline and confirmed.
The body part and the direction of stimulation selected to test each neuron were those that best elicited the neuron activity, as identified during clinical tests. The stimulation covered all lengths of the RF.
During the total length of the task, the monkey had to maintain the hand contralateral to the recording hemisphere on a metal cylinder (diameter 3 cm, height 2.5 cm) fixed to a plane close to the monkey's body, and the ipsilateral one on the plane. A light-emitting diode (LED) was located in front of the monkey at a distance of 80 cm, which the monkey had to fixate for the duration of the task. The task (Figure 1A) consisted of:
1. Green_On—Green_Off: The green LED turned on for 0.5–2 s.
2. Red_On: The green LED switched to red and the experimenter moved the hand toward the monkey's body part to be stimulated.
3. Trg2_On—Trg2_Off: The experimenter touched the monkey (Trg2_On). The red LED switched off and the green LED was turned on until the sensory stimulation was finished (Trg2_Off).
4. Once the sweep had finished, the green LED switched off and after 0.8–1 s the monkey received drops of juice as a reward. After 1.5–2 s, the next trial began. From the end of stimulation to the start of the next trial we did not request the monkey to carry out any fixation task, but just to maintain the hands in their position.
We recorded from SII and from the pIC, in particular the disgranular insular cortex (dI) and the granular insular cortex (Ig), in both the left and right hemispheres. For each penetration, the correct depth was estimated on the basis of the properties in the different regions above, from the first neuronal activity detection in the convexity. The position of the chambers was decided based on the magnetic resonance of the monkey in order to reach more effectively the maximal possible length of the SII, dI and Ig. In the right hemisphere, the extracellular single unit recordings were carried out utilizing varnish-insulated tungsten microelectrodes (length 100 mm, impedance 1.5–3.0 MΩ at 1 kHz; FHC, USA), while we clinically tested the neurons in the recording site, each 300 μm.
In the left hemisphere, the neuronal recordings were performed by means of a 16 channel V-probe (@ Plexon). Both the V-probe and the tungsten microelectrodes were inserted vertically (90°) into the cortex through the intact dura matter via a hydraulic microdriver manipulator (Narishige, Japan). Each isolated single neuron in each of the 16 channels was first clinically tested. Then, following the first recording session, we moved down the V-probe in case the probe had not covered the entire area of interest, in order to conduct a second recording session. During the second recording session we considered solely the channels where we discriminated new single neurons and neurons not already recorded in the first session.
In both the left and right hemispheres, once we reached the white matter at the end of the recording sessions, we moved down the V-probe/tungsten electrode until we reached the next cortex, in order to physiologically confirm the recording site. The neuronal activity was recorded by a Plexon system. Then, both the analogic and digital signals acquired on-line were sent to a personal computer and stored for subsequent analysis, while the off-line analysis was conducted using a specific Offline Sorter Software (OmniPlexTM).
Recording of Behavioral Events and Definition of Epochs of Interest
During the task, the starting and the switching off of each LED was monitored by LabView-based Software. Distinct contact-sensitive devices (Crist Instruments) were utilized to detect the maintaining of the hands' position, and when the experimenter began and finished touching the monkey's body. These devices provided a transistor-transistor logic (TTL) signal, which enabled the monitoring of the monkey's performance. The eye position was monitored by an eye tracking camera (ISCAN Camera, ETL-200), with the eye position signals, together with the TTL events generated during task execution, being sent to the LabView-based Software so that the progress of the task could be monitored. Based on the TTL and eye position signals, the software enabled us to automatically interrupt the trial if the monkey broke fixation and/or the hands' position. In such instances, no reward was delivered. The monkey always received the same amount of juice as a reward following the correct performance of each trial. Based on the digital signals related to the LED and the two events determined by the contact between the hand of the experimenter and the body of the monkey, we defined two different epochs of interest (Figure 1B) for statistical analysis of the neuronal responses: (1) Baseline: from 500 to 900 ms after Green_On (total of 400 ms); and (2) Stimulation: from Trg2_On to Trg2_Off. The time interval from 500 to 900 ms after the Green_On (total of 400 ms) was selected as the baseline, since this interval was situated after the trial had commenced and before the monkey had received the sensory stimulation. In this interval, the monkey did not see the hand of the experimenter since he had to fixate on the LED and did not know when and which kind of sweep he would receive. The time interval selected for the stimulation was the exact interval of the duration of sensory stimulation for each condition and each trial. Since the stimulation was manually performed by the experimenter, and thus without any strictly on-line control of the applied speed, prior to commencing any analysis we verified that the speed of each trial in each of the two conditions was performed with the velocity in the desired range; that is, 1–5 cm/s and 5–15 cm/s for the Sweep Slow and Sweep Fast, respectively. In order to calculate the speed, the cm range for each of the tested body parts was divided by the exact time of the respective stimulation. The time of stimulation for each trial was calculated by extracting the time of Trg2_Off from that of Trg2_On.
Data Analyses and Classification of the Recorded Neurons
Single units were isolated on-line and off-line analysis was carried out utilizing a specific Offline Sorter Software (OmniPlexTM).
Definition of Task-Related Neurons
Neurons were defined as being task-related if they significantly varied their discharge during a stimulation epoch in at least one of the two conditions in comparison to the baseline. The data's normality and equality of variance (for each parameter in each condition) were verified with the Kolmogorov Smirnov and Levene tests, respectively. In order to identify the task-related neurons we performed repeated measures of 2 × 2 ANOVA (factors: Conditions and Epochs), followed by Bonferroni post hoc testing in the case of significant epochs and/or interaction condition × epochs' effect (p < 0.05). The post hoc was executed to enable investigation of possible differences: (1) between the epochs in each condition; (2) between the conditions in each epoch; and (3) between the conditions independent of the epochs.
The neurons highlighting the epochs' effect but not the statistical differences between the stimulation epochs of the conditions were classified as speed unselective (SU) neurons. The neurons showing the statistical difference between the stimulation epochs of the two conditions were instead defined as speed selective (SS) neurons. Among the second category, we identified them as fast selective if they showed the stimulation epoch of sweep fast that was statistically higher than the one of the sweep slow; and vice versa for the slow selective neurons.
The raster and histograms of the single unit data revealed the firing rate (spike/s) as normalized for the maximal value between the two conditions in each single unit. The alignment was the Trg2_On, and therefore when the experimenter began the stimulation of the monkey's body.
Correlation Analyses
In order to investigate if the neuronal discharge of SS neurons correlated with the velocity of the applied speed for each trial, or if they were selective for the range of velocity, we performed correlation analysis. As a control, we also conducted the same analysis for the SU neurons. Since both categories presented a linear correlation, even at a different percentage, we performed the Mann-Whitney U Test to compare the distribution of R-square.
Population Analyses
Population analyses were performed on categories of neurons, classified on the basis of the results of the above-described analyses, and taking into consideration the single-neuron responses calculated as normalized activity (spike/s) in 20 ms bins, in the two tasks (sweep fast and sweep slow). The normalized activity for each neuron was calculated as follows: the mean activity was calculated every 20 ms bins in all the recorded trials of every experimental condition to be compared. Then, the absolute highest activity value was employed to divide the value of each single bin in all conditions (normalized mean activity, ranging from 0 to 1).
The histograms described the moving average of 60 ms of the normalized activity, for each of the two trials. The alignment was the moment when the experimenter touched the body of the monkey.
In order to investigate the bins where the two conditions significantly differed from one another in terms of population, we performed the 2-pairs t-test (p < 0.05) for each of the three populations. This took into account each 20 ms (one bin) from the Trg2_On, and therefore when the experimenter began the stimulation to the monkey's body, until 2 s had elapsed. We selected 2 s as the maximal time to analyze the population data since the stimulation (both sweep fast and sweep slow) were completed within 2 s. A minimum of three bins were selected for significance. For the population analysis we did not consider the slow selective neuron in the population of SS neurons. All statistical analyses were carried out using Statistica Software (StatSoft).
Anatomical Definition of the Recording Sites
In order to accurately identify the location of the recording sites, at the conclusion of the recording sessions and 10 days prior to sacrificing the monkey, electrolytic lesions (10 μA cathodic pulses, duration 10 s) were performed in both the hemispheres (Bonini et al., 2011). Specifically, for each hemisphere, known coordinates of the external borders of the recorded regions were selected and in each of them four lesions were made at different depths. Then, the monkey was deeply anesthetized with an overdose of sodium thiopental and perfused consecutively with saline, 3.5–4% paraformaldehyde, and 5% glycerol, prepared in a 0.1 M phosphate buffer and at pH 7.4, through the left cardiac ventricle. The brain was then blocked coronally on a stereotaxic apparatus, removed from the skull, photographed, and placed in 10% buffered glycerol for 3 days and 20% buffered glycerol for 4 days (Gerbella et al., 2014). Finally, it was cut frozen into coronal sections of 60 μm thickness, and the sections obtained will be processed with Nissl staining (0.1% thionin in 0.1 M acetate buffer, pH 3.7) in order to identify the electrolytic lesions.
Figures 6B and 6C present a section of the right hemisphere in which at least three penetrations located in the insular cortex and in the adjacent SII region were clearly visible. The section is taken at a mid-anterior level of the recorded region. The histological analysis confirmed that all the recording sites were located in the pIC or in the adjacent SII region.
We recorded a total of 223 task-related somatosensory neurons from both the right and the left SII, dI cortex and Ig cortex of one male rhesus monkey (Macaca mulatta). In particular, we recorded 107 neurons in the right hemisphere and 116 neurons in the left hemisphere. Since the recording sites were deep brain areas, the correct depth of each penetration was estimated on the basis of the physiological properties of the areas above the region of interest. Once the region of interest was reached, each isolated neuron was tested in order to identify the location and extension of its RF (see "Definition of Receptive Field" Section) and with the sweeping task (see "Apparatus and Behavioral Paradigm" Section; Figure 1A). Sensory neurons were considered as task-related only if they responded significantly during dynamic stimulation of their RFs during the task (see "Definition of Task-Related Neurons" Section). The location of neurons' RFs where the sweeping was applied in the context of the task are presented in Table 1. All the isolated neurons had bilateral RFs, but the stimulation was always applied on the contralateral side.
Table 1. Localization of receptive fields of task related neurons, SS and SU neurons.
Speed Selectivity of Task-Related Neurons
Task-related neurons were divided into two categories: speed selective (SS) and speed unselective (SU) neurons. The SS neurons showed a significant main effect of the factor Epoch and of the interaction between the factors Condition and Epoch. Therefore, they were modulated in one or both of the two sweeping stimulations, with the neuronal activity during one stimulation being significantly higher than the neuronal modulation during the other. The SU neurons only showed a significant main effect for the factor Epoch, thus being modulated during both the slow and fast sweeping, with no significant difference between the two.
Among the 223 task-related neurons, 38 (17.04%) were SS and all of them were facilitated neurons. Table 1 shows the location of RFs of the SS neurons. Thirty-seven out of the thirty eight SS neurons were fast selective. Among the fast selective neurons, 14 were activated during both sweeping conditions, but the neuronal discharge during the stimulation epoch of the Sweep Fast was higher than the firing rate during the stimulation epoch of the Sweep Slow. Twenty-three out of the thirty seven fast selective neurons were only activated during the sweep fast condition, but not the sweep slow. Figure 2A shows an example of a SS neuron activated only during the Sweep Fast (fast selective), while Figure 2B shows an example of a SS neuron activated during both the fast and slow sweep, although the modulation during the sweep fast was higher than during the sweep slow (fast selective). Finally, just 1 out of the 38 was a slow selective neuron (Figure 2C), since it was only activated during the sweep slow and not during the sweep fast. One hundred and eighty-five of the two hundred and twenty three neurons (82.96%) were classified as SU neurons (Figure 2D) since they were modulated during both the conditions, but they did not discriminate between them. Table 1 shows the location of the RFs of SU neurons. Forty-eight out of one hundred and eighty five (25.94%) of the SU neurons were suppressed neurons, since their firing rate during the stimulation epoch decreased significantly relative to that during baseline, independently from the conditions.
Figure 2. (A) Example of speed selective (SS) neuron (Fast Selective). The neuron was only modulated during the Sweep Fast. The neuron was recorded in the right hemisphere and the receptive field (RF) was located on the hairy side of the bilateral hand. (B) Example of SS neuron (Fast Selective). The neuron was modulated during both sweeping velocities, but the activity during the Sweep Fast was higher than that during the Sweep Slow. The neuron was recorded in the right hemisphere and the RF was located on the hairy side of the bilateral hand. (C) Slow Selective neuron, activated only during the Sweep Slow. The neuron was recorded in the left hemisphere and the RF was located on the bilateral hairy side of the mouth. (D) Example of speed unselective (SU) neuron. The neuron was modulated during both sweeping speeds, independently of the velocity. The neuron was recorded in the right hemisphere and the RF was located on the bilateral hairy side of the hand. The stimulation was performed on the contralateral side, from the distal (fingers) to the proximal part (near wrist). In (A–D) the histograms are aligned at the starting point of the stimulation, indicated by the light blue triangles. The end of the stimulation is indicated by the green triangles. The time between the red dots and yellow circles indicates the baseline, while the time between the light blue and green triangles represents the stimulation epoch. The histograms are normalized for the maximal spike/s value between the two conditions.
These results highlight that a small set (N = 38) of task-related neurons discharge differently depending on the speed with which the passive touch stimulation was applied. Interestingly, just 1 out of 38 SS neurons showed higher modulation during slow stimulation (1–5 cm/s), while the remaining 37 neurons demonstrated selectivity for the fast stimulation (5–15 cm/s).
Relationship Between Stimulation Speed and Firing Rate
The stimulus speed in each trial of the two tasks was not fixed as it was dependent on the experimenter's movement, ranging from 1 to 5 cm/s during the sweep slow and from 5 to 15 cm/s during the sweep fast. In order to investigate more precisely the relation between the firing rate of each trial and the real applied velocity, we performed a trial-based correlation analysis (see "Correlation Analyses" Section) that considered the firing rate (spike/s) during the stimulation epoch and the speed (from 1 to 15 cm/s), independently from the condition (fast or slow) the trial was associated with.
The analysis evidenced that all the 38 SS neurons display statistically significant linear correlation between the speed of stimulation and the firing rate (spike/s). Among the SU neurons, only a minor part showed a significant correlation (21 out of 185, 11.35%).
The results indicate that SS neurons show a stronger relationship between firing rate and stimulus speed than SU neurons (χ2 = 17.26; df = 1; p < 0.001).
Moreover, in order to better investigate the potential similarity between the speed/firing rate relationship among SS and SU neurons, we compared the distribution of R-square obtained in the two categories (Figure 3). The Mann-Whitney U Test indicated that the R-square of the SS neurons (median = 0.33) is higher (p < 0.001) than the R-square of the SU neurons (median = 0.18), thus speed variation account for a greater part of the variability of SS than SU neurons discharge.
Figure 3. Distribution of the R-square values of the SS and SU neurons showing significant correlation between the speed of the stimulus and the firing rate. The lines indicate the median value for the SS (in green) and SU neurons (in blue). In order to investigate the potential similarity between the speed/firing rate correlation of SS neurons and the correlation showed by the SU neurons, we compared the distribution of R-square obtained in the two groups. The Mann-Whitney U Test indicates that the R-square of the SS neurons (median = 0.33) is higher (p < 0.001) than the R-square of the SU neurons (median = 0.18), thus speed variation account for a greater part of the variability of SS than SU neurons discharge.
Population analyses were performed in order to explore the time course and intensity of the population activity by taking into account three different groups of neurons, that is: (1) SS neurons, and SU neurons; (2) with; and (3) without speed/firing rate significant correlation. Figures 4A–C describe the results of the population analyses (see "Population Analyses" Section). The activation profile of SS neuronal population (Figure 4A) showed that these cells were activated during both types of sweeping but the activation was higher during the sweep fast than the sweep slow, particularly from 80 to 280 ms after the alignment point (stimulus onset).
Figure 4. Time course of the activity of neuronal populations aligned (gray line) on the tactile stimulation onset in the both conditions, Sweep Fast and Sweep Slow. Green lines indicate the time course of activity during Sweep Fast, while blue lines represent the time course of activity during Sweep Slow. On the Y axis is represented the normalized activity of the neuronal populations, while on the X axis is represented the time (sec). (A) The population of the SS neurons is activated stronger during the Sweep Fast compared with the Sweep Slow, in particular from 80 ms after alignment to 280 ms. (B) The population of the SU neurons showing correlation between the speed of stimulation and firing rate. From 40 ms after the alignment to 220 ms, the population is activated stronger during the Sweep Fast than Sweep Slow, while from 460 to 680 ms the activity is higher during the Sweep Slow than during the Sweep Fast. (C) The population of the SU neurons that did not show correlation between the speed of sweeping and the firing rate. The population does not discriminate between the speed of stimulation and the two tasks do not differ from each other. In (A–C) the activity is in alignment when the experimenter touched the monkey's body. The median times of the end of sweep fast and sweep slow are indicated with the green and blue markers, respectively, above each population plot. Shaded areas around each marker represent the 25th and 75th percentile times. In (A,B) the light green shaded regions indicate the period in which the paired samples t-tests evidence a significant separation of the two curves (p < 0.05).
Figure 4B shows the activation profile of SU neurons endowed with significant speed/firing rate correlation at the single neuron level. Similarly to the neuronal population of Figure 4A, these neurons discharged stronger during sweep fast relative to sweep slow from 40 to 220 ms after the alignment point, but the Sweep Slow induced a sustained discharge stronger than that during sweep fast later on from 460 to 680 ms after the alignment.
Moreover, from the profile of the modulation it is possible to notice that the modulation during the Sweep Fast and Sweep Slow began from the alignment, but unlike the SS population the activity did not drop at a similar timing. Instead, during the Sweep Fast the activity decreased approximately in a similar manner as the activity during the Sweep Fast of the SS population. During the Sweep Slow the activity remained stable for the entire length of the condition. Therefore, the population was modulated during both conditions for the full duration of the stimulation, from the alignment until after 2 s.
Figure 4C shows the activation profile of SU neurons with no significant speed/firing rate correlation at the single neuron level. The results evidenced the lack of any statistically significant difference between the response profile associated to the two sweeping conditions.
Histological Analyses Confirmed the Recording Sites
The histological analyses based on the location of the electrolytic lesions, confirmed that the recorded sites, as expected from magnetic resonance data, are virtually all located in the pIC and in the adjacent SII region (Figures 6B,C). Figure 5 shows an unfolded map of the lateral fissure of both the left and the right hemisphere in which the blue and green areas represent the whole recorded region. In antero-posterior terms, this region starts from about the rostral-most part of the central sulcus and extends posteriorly from this point for 5 mm.
Figure 5. A 2D reconstruction of the lateral fissure of the left (A) and right (B) hemisphere, aligned to the middle of the insula; the continuous lines mark the lips of the sulcus, the border of the insula with the upper and lower bank of the sulcus, and the fundus. The blue area indicates the recorded region related to the SU neurons, while the green area indicates the recorded area of the SS neurons. The arrow marks the rostral-most level of the central sulcus (C).
Figure 6. (A) Distribution of the SS and SU neurons in relation of the depths. (B) Drawing of the section in which the dashed box indicates the location of the photomicrograph in (C). The arrow indicates the depth of track showed in (C). (C) High power photomicrograph of Nissl section from the right hemisphere in which it is possible to identify tracks of the recording electrode through the insular cortex and SII region. Abbreviations: L, lateral fissure; SII, secondary somatosensory cortex; ST, temporal sulcus; C, central sulcus.
The measurements of the depth of each penetration revealed that the SS task related neurons appear virtually all located in the insular region. In fact, almost all these neurons were recorded at a depth compatible with that of the insula, that is from 11 to 21.8 mm below to the convexity (Figure 6A). In contrast, the SU neurons, since involving a larger sector, extending from 7 mm to 22.5 mm of depth appear located not only in pIC but also in SII (Figure 6A).
The analysis of the representation of the different RFs of both SS and SU neurons showed that the face representation tended to extend, in most of the recorded sites, more ventrally respect to the other RFs (Figure 7). In this analysis the RFs of mouth, cheek, and face were merged in a unique RF, that is the face, whereas the RFs of back and upper body were merged in the upper body RF, since back RF involved especially the dorsal part of the posterior body.
Figure 7. Distribution of the task related neurons in relation to the localization of RFs.
Due to the key role of the pIC in the coding of affiliative interpersonal touch in humans (Olausson et al., 2002, 2008a,b, 2010), and its hypothetical involvement in social behavior in non-human primates (Kling and Steklis, 1976; Ishida et al., 2014; Jezzini et al., 2015), here we investigated for the first time the activity of single neurons of the dysgranular and granular parts of this region (dI and Ig, respectively) of the macaque monkey during a dynamic tactile stimulation, considered pleasant for non-human primates, that is, sweeping. Sweeping is a common dynamic hand action that monkeys perform during grooming to move the hair and identify the skin sites to be picked in order to remove ectoparasites or vegetation trapped within. Even though grooming has primarily a hygienic function, it has been hypothesized that this behavior has also a social role (Maestripieri, 1993; Dunbar, 2010; McFarland and Majolo, 2011). The social function hypothesis is supported in part by studies demonstrating the positive autonomic effects of grooming (Boccia, 1989; Boccia et al., 1989; Aureli et al., 1999; Dunbar, 2010). In fact, the induced relaxation could be considered an indirect evidence that grooming creates social bonds among conspecific belonging to the same social group. Even though numerous behavioral studies supporting the social function of the grooming, there are no evidence related the real mechanisms at the basis of the affiliative role of this behavior. However recently, Dunbar (2010) supposed that the positive autonomic effects of grooming could be not due from this behavior per se but referable to the sweeping. In this respect it is noteworthy that sweeping activates specific unmyelinated fibers, the C-fibers (Dunbar, 2010) for which a specific role in encoding pleasant touch was supposed (Vallbo et al., 1995; Löken et al., 2009; Morrison, 2012).
Although, as of today, it remains largely unexplored to what extent specific cortical areas receive the somatosensory information conveyed by these fibers and thus how the cortex process the pleasant touch, human studies suggest that the insular cortex, primarily the posterior part, appears to constitute a crucial node for encoding this sensation (Olausson et al., 2002, 2010; Björnsdotter et al., 2009). An intriguing hypothesis came taking together these observations: as well the purely sensory cortices (SI and SII) are involved in the encoding the discriminative aspect of the touch, pIC could have a crucial role in the processing the emotional counterpart of this sensation. To test this hypothesis, in the present study we investigated the role of single neurons of SII and of the pIC during sweeping. In detail, we applied the sweeping with two speeds: one that optimally (5–15 cm/s, sweep fast) induce positive cardio physiological effects on the monkey that receive it (Grandi and Heinzl, 2015), and includes the real speed of sweep (Grandi et al., 2015) and a non-optimal speed (1–5 cm/s, sweep slow; Grandi et al., 2015).
We recorded a total of 223 task-related neurons, 38 of which were categorized as SS (SS; 17.04%), and 185 as SU (SU; 82.96%). The majority of the task-related neurons were SU neurons since they were modulated during the tactile stimulation, independently of the applied speed. Thirty seven out of thirty eight SS neurons coded for the fast speed (5–15 cm/s) since they were preferentially activated when sweeping was performed in the range of 5–15 cm/s. Just 1 of the 38 SS neurons discharged specifically when the speed was lower than 5 cm/s. The firing rate of all the SS neurons was correlated with the applied speed. Although the SU neurons did not discriminate the speed, a small percentage of them showed a positive correlation between their firing rate and the applied speed, even though this correlation appears to be significantly lower than that of the SS neurons. Moreover, even at the single neuron level this set of SU neurons endowed with a significant correlation did not discriminate between the two ranges of velocities, they did so at the population level. Finally, the SU neurons showing differential activity between the two speeds at the population level, but not at the single neurons' level, and the correlation between their firing rate during the sweeping and the applied speed, could represent an intermediate population of neurons. The analyses of the locations of the recorded sites showed that, nevertheless the SU neurons are located in both the pIC and the adjacent SII region, the SS neurons appear almost at all locations in the posterior insula. Furthermore, the analysis of the depth in which both the task related neurons are recorded in relation to their RFs, showed that the representation of the face tended to extend ventrally to the representation of the hand/arm, in complete agreement with the somatotopy observed in previous functional studies and connectional investigations (Schneider et al., 1993; Caruana et al., 2011; Jezzini et al., 2012, 2015; Gerbella et al., 2014). Considered as a whole the insular region here investigated is a node of a network of frontal, cingulate, temporal, and parietal areas and limbic subcortical structures, and thus is a site of integration of sensory, emotional, motor, and social information (Mesulam and Mufson, 1982a,b; Chikama et al., 1997; Ongür et al., 1998; Stefanacci and Amaral, 2002; Barbas, 2007; Gothard et al., 2007; Grabenhorst and Rolls, 2011; Padoa-Schioppa and Cai, 2011; Jezzini et al., 2015). In particular, the connections with the prefrontal and the orbitofrontal cortex, the amygdala, the ventral striatum, the mediodorsal nucleus of the thalamus, the lateral hypothalamus, and the ventral tegmental area could represent the neural substrate for, on one side encoding the emotional aspects of sensory stimuli and integrating them with reward and memory information and on the other side for triggering the vegetative responses (as the decrease in the heart rhythm; see also below) accompanying the skin brushing/pleasant touch. Summarizing, the aforementioned anatomical data supporting the idea that our insular sector has, besides a direct involvement in the perception of sensory emotional and social stimuli, also a direct role to elicit the appropriate behavioral and visceromotor responses in line with the notion that the insula is endowed with an enactive component intrinsic to each social and emotional behavior (Di Cesare et al., 2015; Jezzini et al., 2015).
Since the majority of SS neurons encode for the optimal speed (5–15 cm/s), the present study represents the first single neurons' evidence of the role of insular cortex in the encoding of pleasant touch in non-human primates. In a recent review, Dunbar (2010) proposed that the soft touch arising from sweeping might activate the C-fibers. Human studies demonstrated that C-fibers are activated by the interpersonal pleasant touch performed on the hairy skin with the speed of 1–10 cm/s. This stimulus is perceived as pleasant by the subject who receives it and as a consequence, it can determine a positive physiological effect (e.g., the decrement of the HR) and modulates specific brain areas (such as the insular cortex) involved in the emotional processing of the peripheral somatosensory stimulation (Björnsdotter et al., 2009; Löken et al., 2009; Morrison et al., 2011).
Our results are in line with existing mentioned human imaging studies (McGlone et al., 2007; Olausson et al., 2010; Gordon et al., 2013). Nevertheless, our preliminary data showed that single neurons of the insular cortex are modulated differently in relation to touch performed at speeds of 1–5 cm/s (slow) or 5–15 cm/s (fast), even if both velocities are within the 1–10 cm/s range. The discrepancy between the human results that highlighted that stimulation at 1–10 cm/s activated the insular cortex, and our results could be explained by the different hairy skin properties of the monkey, which presents as thick fur in comparison to humans, and therefore suggests a possible difference in the density of the C-fibers. Further studies will be necessary to investigate in greater depth the single neurons' activity in the insular cortex and SII during sweeping, and consequently to the direct activation of C-fibers. Studies in that direction would investigate more precise the relationship between the modulation of single neurons of insular cortex and the speed of stimulation. We hypothesize that the action of sweeping with a robotic device perfectly maintains the same speed, trial after trials, providing a precise understanding of how the single neuronal activity is modulated by different speed and a comprehension of how real biological sweeping differs from the artificial one made by a robotic device (Shokur et al., 2013). Another interesting issue could be to investigate the single neuron activity during sweeping observation in order to address the possibility of presence of mirror-like activity related to touch (Blakemore et al., 2005; Schaefer et al., 2013).
The tactile stimulation modulating the C-fibers, and therefore the vagal tone and the insular cortex, is employed as a therapy in patients suffering from depression and chronic pain, in cancer patients undertaking invasive therapy, and also to reduce the stress and increase the wellbeing of healthy people (Field et al., 1986; Tsao, 2007; Garnera et al., 2008; Russell et al., 2008; Billhult et al., 2009; Diego and Field, 2009; Lindgren et al., 2012; Field, 2014; Schroeder et al., 2014). In the same manner, here we demonstrated that human sweeping modulated the monkey insular cortex. Moreover, the positive physiological effects of sweeping were shown (Grandi and Ishida, 2015; Grandi et al., 2015). Due to these neuronal modulations, autonomic responses and the affiliative value of sweeping and grooming for monkeys, human sweeping could have the potential to reduce the stress of single-housed caged experimental non-human primates, in addition to human grooming (Grandi and Ishida, 2015), with this being recently proposed as a method to improve the welfare of experimental animals (Reinhardt and Reinhardt, 2008).
Moreover, recently (Shokur et al., 2013), it was demonstrated that, in monkey, primary somatosensory and primary motor neurons respond to the observation of an avatar arm being brushing when the stimulation was preceded by the physical touch. Therefore, the physical touch determines the illusion that the avatar arm being integral part of own body, as the rubber hand illusion in humans. This study, since investigating the effect of brushing in terms of expanding of body schema, appears especially important for the development of neuroprostheses and artificial limbs. In the respect of the present results further investigations using virtual sweeping, could be useful to understand if and how the body schema change in relation to affiliative sensory stimulation, in order to test, in last resort, the possibility to implement pleasant touch as therapy for patients with prosthesis.
Taken together, the data available up to now and the results presented here support the hypothesis that the sweeping motion: (1) is performed at a speed similar to that which activates human C-fibers; (2) determines similar positive autonomic effects evoked by the C-fibers' activation in humans; and (3) is coded at single neuron level in the same brain regions involved in the processing of the gentle caress in humans. Finally, notwithstanding that the present results were obtained from only one monkey, and so caution is required in the interpretation, our findings are the first evidence highlighting the role of insular cortex in the encoding of pleasant touch in non-human primates. The study highlights the similarity between human and non-human primates' social touch systems, and can be considered as an important starting point in order to investigate in greater depth pleasant sweeping at the central nervous system level.
LCG: performed the experiment, designed the experimetal tasks, analyzed neuronal data, analyzed histological data, wrote article. MG: analyzed histological data, wrote article.
We thank Federica Paterno for her help during experimental sessions. We extend our gratitudine to Professor Giacomo Rizzolatti. This experiment was in part supported by the European Commission Grant Cogsystem FP7-250013 awarded to Giacomo Rizzolatti.
Aureli, F., Preston, S. D., and de Waal, F. B. M. (1999). Heart rate responses to social interactions in free-moving rhesus macaques (Macaca mulatta): a pilot study. J. Comp. Psychol. 113, 59–65. doi: 10.1037/0735-7036.113.1.59
Barbas, H. (2007). Flow of information for emotions through temporal and orbitofrontal pathways. J. Anat. 211, 237–249. doi: 10.1111/j.1469-7580.2007.00777.x
Bessou, P., Burgess, P. R., Perl, E. R., and Taylor, C. B. (1971). Dynamic properties of mechanoreceptors with unmyelinated (C) fibers. J. Neurophysiol. 34, 116–131.
Billhult, A., Lindholm, C., Gunnarsson, R., and Stener-Victorin, E. (2009). The effect of massage on immune function and stress in women with breast cancer–a randomized controlled trial. Auton. Neurosci. 150, 111–115. doi: 10.1016/j.autneu.2009.03.010
Björnsdotter, M., Löken, L., Olausson, H., Vallbo, A., and Wessberg, J. (2009). Somatotopic organization of gentle touch processing in the posterior insular cortex. J. Neurosci. 29, 9314–9320. doi: 10.1523/JNEUROSCI.0400-09.2009
Blakemore, S. J., Bristow, D., Bird, G., Frith, C., and Ward, J. (2005). Somatosensory activations during the observation of touch and a case of vision-touch synaesthesia. Brain 128, 1571–1583. doi: 10.1093/brain/awh500
Boccia, M. L. (1989). Comparison of the physical characteristics of grooming in two species of macaques (Macaca Nemestrina and M. Radiata). J. Comp. Psychol. 103, 177–183. doi: 10.1037/0735-7036.103.2.177
Boccia, M. L., Reite, M., and Laudenslager, M. (1989). On the physiology of grooming in a pigtail macaque. Physiol. Behav. 45, 667–670. doi: 10.1016/0031-9384(89)90089-9
Bonini, L., Serventi, F. U., Simone, L., Rozzi, S., Ferrari, P. F., and Fogassi, L. (2011). Grasping neurons of monkey parietal and premotor cortices encode action goals at distinct levels of abstraction during complex action sequences. J. Neurosci. 15, 5876–5886. doi: 10.1523/JNEUROSCI.5186-10.2011
Caruana, F., Jezzini, A., Sbriscia-Fioretti, B., Rizzolatti, G., and Gallese, V. (2011). Emotional and social behaviors elicited by electrical stimulation of the insula in the macaque monkey. Curr. Biol. 21, 195–199. doi: 10.1016/j.cub.2010.12.042
Chikama, M., McFarland, N. R., Amaral, D. G., and Haber, S. N. (1997). Insular cortical projections to functional regions of the striatum correlate with cortical cytoarchitectonic organization in the primate. J. Neurosci. 17, 9686–9705.
Di Cesare, G., Di Dio, C., Marchi, M., and Rizzolatti, G. (2015). Expressing our internal states and understanding those of others. Proc. Natl. Acad. Sci. U S A 112, 10331–10335. doi: 10.1073/pnas.1512133112
Diego, M. A., and Field, T. (2009). Moderate pressure massage elicits a parasympathetic nervous system response. Int. J. Neurosci. 119, 630–638. doi: 10.1080/00207450802329605
PubMed Abstract | CrossRef Full Text
Douglas, W. W., and Ritchie, J. M. (1957). On the frequency of firing of mammalian nonmedullated nerve fibers. J. Physiol. 139, 400–407. doi: 10.1113/jphysiol.1957.sp005900
Dunbar, R. I. (2010). The social role of touch in humans and primates: behavioural function and neurobiological mechanisms. Neurosci. Biobehav. Rev. 2, 260–268. doi: 10.1016/j.neubiorev.2008.07.001
Ellingsen, D. M., Wessberg, J., Chelnokova, O., Olausson, H., Laeng, B., and Leknes, S. (2014). In touch with your emotions: oxytocin and touch change social impressions while others' facial expressions can alter touch. Psychoneuroendocrinology 39, 11–20. doi: 10.1016/j.psyneuen.2013.09.017
Field, T. (2014). Massage therapy research review. Complement. Ther. Clin. Pract. 20, 224–229. doi: 10.1016/j.ctcp.2014.07.002
Field, T. M., Schanberg, S. M., Scafidi, F., Bauer, C. R., Vega-Lahr, N., Garcia, R., et al. (1986). Tactile/kinesthetic stimulation effects on preterm neonates. Pediatrics 77, 654–658.
Garnera, B., Phillips, L. J., Schmidt, H.-M., Markuleva, C., O'Connor, J., Wood, S. J., et al. (2008). Pilot study evaluating the effect of massage therapy on stress, anxiety and aggression in a young adult psychiatric inpatient unit. Aust. N. Z. J. Psychiatry 42, 414–422. doi: 10.1080/00048670801961131
Gerbella, M., Baccarini, M., Borra, E., Rozzi, S., and Luppino, G. (2014). Amygdalar connections of the macaque areas 45A and 45B. Brain Struct. Funct. 219, 831–842. doi: 10.1007/s00429-013-0538-2
Gordon, I., Voos, A. C., Bennett, R. H., Bolling, D. Z., Pelphrey, K. A., and Kaiser, M. D. (2013). Brain mechanisms for processing affective touch. Hum. Brain Mapp. 4, 914–922. doi: 10.1002/hbm.21480
Gothard, K. M., Battaglia, F. P., Erickson, C. A., Spitler, K. M., and Amaral, D. G. (2007). Neural responses to facial expression and face identity in the monkey amygdala. J. Neurophysiol. 97, 1671–1683. doi: 10.1152/jn.00714.2006
Grabenhorst, F., and Rolls, E. T. (2011). Value, pleasure and choice in the ventral prefrontal cortex. Trends Cogn. Sci. 15, 56–67. doi: 10.1016/j.tics.2010.12.004
Grandi, L. C., and Heinzl, E. (2015). Use of infrared thermography, heart rate and heart rate variability in studying effect of sweeps in rhesus monkey. Auton. Neurosci. 192:78. doi: 10.1016/j.autneu.2015.07.080
Grandi, L. C., and Ishida, H. (2015). The physiological effect of human grooming on the heart rate and the heart rate variability of laboratory non-human primates: a pilot study in male rhesus monkeys. Front. Vet. Sci. 2:50. doi: 10.3389/fvets.2015.00050
Grandi, L. C., Roda, F., and Ishida, H. (2015). Physiological effect of sweeping grooming movements in macaque monkey: preliminary data. Int. J. Primatol. 4:126. doi: 10.4172/2167-6801.1000126
Gust, D. A., Gordon, T. P., Hambright, M. K., and Wilson, M. E. (1993). Relationship between social factors and pituitary: adrenocortical activity in female rhesus monkeys (Macaca mulatta). Horm. Behav. 27, 318–331. doi: 10.1006/hbeh.1993.1024
Hertenstein, M. J., Keltner, D., App, B., Bulleit, B. A., and Jaskolka, A. R. (2006a). Touch communicates distinct emotions. Emotion 6, 528–533. doi: 10.1037/1528-3542.6.3.528
Hertenstein, M. J., Verkamp, J. M., Kerestes, A. M., and Holmes, R. M. (2006b). The communicative functions of touch in humans, nonhuman primates and rats: a review and synthesis of the empirical research. Genet. Soc. Gen. Psychol. Monogr. 132, 5–94. doi: 10.3200/mono.132.1.5-94
Iggo, A., and Kornhuber, H. H. (1977). A quantitative study of C-mechanoreceptors in hairy skin of the cat. J. Physiol. 271, 549–565. doi: 10.1113/jphysiol.1977.sp012014
Ioannou, S., Chotard, H., and Davila-Ross, M. (2015). No strings attached: physiological monitoring of rhesus monkeys (Macaca mulatta) with thermal imaging. Front. Behav. Neurosci. 9:160. doi: 10.3389/fnbeh.2015.00160
Ishida, H., Fornia, L., Grandi, L. C., Umiltà, M. A., and Gallese, V. (2013). Somato-motor haptic processing in posterior inner perisylvian region (SII/pIC) of the macaque monkey. PLoS One 8:e69931. doi: 10.1371/journal.pone.0069931
Ishida, H., Grandi, L. C., Bimbi, M., and Rizzolatti, G. (2014). "Neural activity in the inner perisylvian regions (SII/Insula) of the macaque monkey," in 9th FENS Forum of Neuroscience, Federation of European Neuroscience Societies (FENS), Abstract Number: FENS-1304, 2014, Milan.
Jezzini, A., Caruana, F., Stoianov, I., Gallese, V., and Rizzolatti, G. (2012). Functional organization of the insula and inner perisylvian regions. Proc. Natl. Acad. Sci. U S A 109, 10077–10082. doi: 10.1073/pnas.1200143109
Jezzini, A., Rozzi, S., Borra, E., Gallese, V., Caruana, F., and Gerbella, M. (2015). A shared neural network for emotional expression and perception: an anatomical study in the macaque monkey. Front. Behav. Neurosci. 9:243. doi: 10.3389/fnbeh.2015.00243
Johansson, R. S., Trulsson, M., Olsson, K. A., and Abbs, J. H. (1988). Mechanoreceptive afferent activity in the infraorbital nerve in man during speech and chewing movements. Exp. Brain Res. 72, 209–214. doi: 10.1007/bf00248519
Kling, A., and Steklis, H. D. (1976). A neural substrate for affiliative behavior in nonhuman primates. Brain Behav. Evol. 13, 216–238. doi: 10.1159/000123811
Kringelbach, M. L., and Rolls, E. T. (2004). The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Prog. Neurobiol. 5, 341–372. doi: 10.1016/j.pneurobio.2004.03.006
Kumazawa, T., and Perl, E. R. (1978). Excitation of marginal and substantia gelatinosa neurons in the primate spinal cord: indications of their place in dorsal horn functional organization. J. Comp. Neurol. 177, 417–434. doi: 10.1002/cne.901770305
Light, A. R., and Perl, E. R. (1979). Spinal termination of functionally identified primary afferent neurons with slowly conducting myelinated fibers. J. Comp. Neurol. 186, 133–150. doi: 10.1002/cne.901860203
Lindgren, L., Westling, G., Brulin, C., Lehtipalo, S., Andersson, M., and Nyberg, L. (2012). Pleasant human touch is represented in pregenual anterior cingulate cortex. Neuroimage 59, 3427–3432. doi: 10.1016/j.neuroimage.2011.11.013
Löken, L. S., Wessberg, J., Morrison, I., McGlone, F., and Olausson, H. (2009). Coding of pleasant touch by unmyelinated afferents in humans. Nat. Neurosci. 5, 547–548. doi: 10.1038/nn.2312
Maestripieri, D. (1993). Vigilance costs of allogrooming in macaque mothers. Am. Nat. 141, 744–753. doi: 10.1086/285503
McFarland, R., and Majolo, B. (2011). Grooming coercion and the post-conflict trading of social services in wild barbary macaques. PLoS One 6:e26893. doi: 10.1371/journal.pone.0026893
McGlone, F., Olausson, H., Boyle, J. A., Jones-Gotman, M., Dancer, C., Guest, S., et al. (2012). Touching and feeling: differences in pleasant touch processing between glabrous and hairy skin in humans. Eur. J. Neurosci. 35, 1782–1788. doi: 10.1111/j.1460-9568.2012.08092.x
McGlone, F., Valbo, A. B., Olausson, H., Löken, L., and Wessberg, J. (2007). Discriminative touch and emotional touch. Can. J. Exp. Psychol. 61, 173–183. doi: 10.1037/cjep2007019
Mesulam, M. M., and Mufson, E. J. (1982a). Insula of the old world monkey. II: Afferent cortical input and comments on the claustrum. J. Comp. Neurol. 212, 23–37. doi: 10.1002/cne.902120103
Mesulam, M. M., and Mufson, E. J. (1982b). Insula of the old world monkey. III: Efferent cortical output and comments on function. J. Comp. Neurol. 212, 38–52. doi: 10.1002/cne.902120104
Morrison, I. (2012). CT afferents. Curr. Biol. 3, R77–R78. doi: 10.1016/j.cub.2011.11.032
Morrison, I., Löken, L. S., Minde, J., Wessberg, J., Perini, I., Nennesmo, I., et al. (2011). Reduced C-afferent fiber density affects perceived pleasantness and empathy for touch. Brain 4, 1116–1126. doi: 10.1093/brain/awr011
Nordin, M. (1990). Low-threshold mechanoreceptive and nociceptive units with unmyelinated (C) fibers in the human supraorbital nerve. J. Physiol. 426, 229–240. doi: 10.1113/jphysiol.1990.sp018135
Olausson, H., Cole, J., Rylander, K., McGlone, F., Lamarre, Y., Wallin, B. G., et al. (2008a). Functional role of unmyelinated tactile afferents in human hairy skin: sympathetic response and perceptual localization. Exp. Brain Res. 184, 135–140. doi: 10.1007/s00221-007-1175-x
Olausson, H., Cole, J., Vallbo, A. B., McGlone, F., Elam, M., Krämer, H. H., et al. (2008b). Unmyelinated tactile afferents have opposite effects on insular and somatosensory cortical processing. Neurosci. Lett. 436, 128–132. doi: 10.1016/j.neulet.2008.03.015
Olausson, H., Lamarre, Y., Backlund, H., Morin, C., Wallin, B. G., Starck, G., et al. (2002). Unmyelinated tactile afferents signal touch and project to insular cortex. Nat. Neurosci. 5, 900–904. doi: 10.1038/nn896
Olausson, H., Wessberg, J., Morrison, I., McGlone, F., and Vallbo, A. B. (2010). The neurophysiology of unmyelinated tactile afferents. Neurosci. Biobehav. Rev. 2, 185–191. doi: 10.1016/j.neubiorev.2008.09.011
Ongür, D., An, X., and Price, J. L. (1998). Prefrontal cortical projections to the hypothalamus in macaque monkeys. J. Comp. Neurol. 401, 480–505. doi: 10.1002/(sici)1096-9861(19981130)401:4<480::aid-cne4>3.0.co;2-f
Padoa-Schioppa, C., and Cai, X. (2011). The orbitofrontal cortex and the computation of subjective value: consolidated concepts and new perspectives. Ann. N Y Acad. Sci. 1239, 130–137. doi: 10.1111/j.1749-6632.2011.06262.x
Reinhardt, V., and Reinhardt, A. (2008). Environmental Enrichment and Refinement for Nonhuman Primates Kept in Research Laboratories. Washington DC: Animal Welfare Institute.
Russell, N. C., Sumler, S. S., Beinhorn, C. M., and Frenkel, M. A. (2008). Role of massage therapy in cancer care. J. Altern. Complement. Med. 14, 209–214. doi: 10.1089/acm.2007.7176
Schaefer, M., Rotte, M., Heinze, H.-J., and Denke, C. (2013). Mirror-like brain responses to observed touch and personality dimensions. Front. Hum. Neurosci. 7:227. doi: 10.3389/fnhum.2013.00227
Schneider, R. J., Friedman, D. P., and Mishkin, M. (1993). A modality-specific somatosensory area within the insula of the rhesus monkey. Brain Res. 621, 116–120. doi: 10.1016/0006-8993(93)90305-7
Schroeder, B., Doig, J., and Premkumar, K. (2014). The effects of massage therapy on multiple sclerosis patients' quality of life and leg function. Evid. Based Compl. Alternat. Med. 2014:640916. doi: 10.1155/2014/640916
Shokur, S., O'Doherty, J. E., Winans, J. A., Bleuler, H., Lebedev, M. A., and Nicolelis, M. A. (2013). Expanding the primate body schema in sensorimotor cortex by virtual touches of an avatar. Proc. Natl. Acad. Sci. U S A 110, 15121–15126. doi: 10.1073/pnas.1308459110
Shutt, K., MacLarnon, A., Heistermann, M., and Semple, S. (2007). Grooming in barbary macaques: better to give than to receive? Biol. Lett. 3, 231–233. doi: 10.1098/rsbl.2007.0052
Stefanacci, L., and Amaral, D. G. (2002). Some observations on cortical inputs to the macaque monkey amygdala: an anterograde tracing study. J. Comp. Neurol. 451, 301–323. doi: 10.1002/cne.10339
Sugiura, Y., Lee, C. L., and Perl, E. R. (1986). Central projections of identified, unmyelinated (C) afferent fibers innervating mammalian skin. Science 234, 358–361. doi: 10.1126/science.3764416
Tsao, C. I. J. (2007). Effectiveness of massage therapy for chronic, non-malignant pain: a review. Evid. Based Complement. Alternat. Med. 4, 165–179. doi: 10.1093/ecam/nel109
Vallbo, A. B., Olausson, H., Wessberg, J., and Kakuda, N. (1995). Receptive field characteristics of tactile units with myelinated afferents in hairy skin of human subjects. J. Physiol. 483, 783–795. doi: 10.1113/jphysiol.1995.sp020622
Zotterman, Y. (1939). Touch, pain and tickling: an electro-physiological investigation on cutaneous sensory nerves. J. Physiol. 95, 1–28. doi: 10.1113/jphysiol.1939.sp003707
Keywords: single neurons, perisylvian region, insular cortex, Macaca mulatta, pleasant touch, grooming
Citation: Grandi LC and Gerbella M (2016) Single Neurons in the Insular Cortex of a Macaque Monkey Respond to Skin Brushing: Preliminary Data of the Possible Representation of Pleasant Touch. Front. Behav. Neurosci. 10:90. doi: 10.3389/fnbeh.2016.00090
Received: 05 February 2016; Accepted: 26 April 2016;
Published: 24 May 2016.
Nuno Sousa, University of Minho, Portugal
José M. Delgado-García, University Pablo de Olavide, Spain
Mikhail Lebedev, Duke University, USA
Copyright © 2016 Grandi and Gerbella. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Laura Clara Grandi, lauraclara.grandi@nemo.unipr.it


text:
Fact Check: do 89% of businesses really support Remain
Britain Stronger in Europe campaign claim
Immigration and the economy have taken centre stage in the British EU referendum. The future economic performance of the UK in particular its growth, job and wealth creation prospects depends on how business fares. This helps explain why business attitudes to the referendum have regularly been published in the run-up.
The Britain Stronger in Europe campaign relies on one such survey in its campaign literature. Conducted by the Council of British Chambers of Commerce in Europe (COBCOE), it found that 89% of member businesses were opposed to a UK exit from the EU, while only 7% were in favour. The claim is regularly repeated by voices on the Remain side as evidence of the economic damage that a Brexit would cause. So is it accurate?
In fact, it turns out that the survey does not include any UK businesses. Instead, it reflects the views of the members of a total of 38 national chambers of commerce in countries ranging from Austria to Israel to Ukraine. This appears to make it quite a strange survey for Remain to be relying on.
When you look at other business surveys, several things stand out. They too tend to back Remain if a little less decisively and the balance of opinion is much tighter with smaller companies than larger ones. The CBIs survey in March of nearly 800 UK companies found 84% backing Remain among large companies and 71% among smaller ones.
The British Chambers of Commerce survey of 2,200 members from May found 54% backed Remain compared to 37% against. The smallest businesses were more narrowly in favour, however.
A TNS survey in June of more than 500 small and medium-sized companies found 38% backed Remain and 37% Leave. Yet a new academic survey of UK skippers and boat owners in the fishing industry found that 92% favour a Brexit. This all raises interesting questions about the differences between various businesses.
Scottish echoes
During the Scottish independence referendum of 2014, I conducted extensive research into business attitudes. Despite close to 50 referendums on various issues across Europe since 2011 alone, there has been very little systematic research of this kind into business opinion.
I found business attitudes to an independence referendum are generally driven by a small number of variables: where the business is headquartered; the ownership structure; the jurisdiction where the balance of its trade takes place; and the most advantageous place for foreign direct investment by multinationals. Having applied the same framework to the EU referendum, it turns out the same variables apply.
Business leaders of UK-headquartered listed companies, or multinationals with subsidiary headquarters in the UK with significant trade in the EU, have been the most perplexed by a vote to leave and most willing to relocate business investment elsewhere. That is why 36 heads of FTSE 100 companies signed an open letter arguing for a Remain vote, and 95% of members of the British American Business Association oppose a Brexit.
Heads of privately-owned companies with comparable EU trading interests also oppose a Brexit, though without the same shareholder pressures they tend to be more willing to soldier on with UK investments if it comes to pass. Think about Sir Richard Branson and the Virgin group, for instance.
People who run private companies whose trade is more global are either ambivalent or in favour of leaving if they can identify a specific benefit for their business. Lord Bamford, the chairman of building group JCB who came out in favour of Leave recently, is a prime example of the latter. Companies of this sort are a minority, however.
Business leaders most in favour of Leave are the ones who mainly trade at home and see a cost advantage or a greater ability to influence the political process after separation. Tim Martin of pub chain Wetherspoons fits into this category.
It appears misleading for the Remain side to be using the COBCOE survey, though business surveys do generally lean towards the same point of view. Bigger businesses are pro-Remain unless their sales are primarily either global or UK-focused while small and medium-sized businesses trading predominantly at home take a different view.
Sectors with a strong view one way or the other are driven by their own motivations for instance UK fishermen tend to feel unfairly constrained by fishing quotas allocated by the European Common Fisheries Policy.
On the whole, however, the business case for Brexit doesnt appear to add up.
Michael Danson, professor of enterprise policy, Heriot-Watt University
This piece has identified that, as with many of the claims made by all sides in the EU referendum, Britain Stronger in Europe has been rather fast and loose with presenting COBCOEs statistics. Nevertheless it is believable that firms successfully doing business internationally would support the status quo, while those struggling at home may have different concerns or else reflect the divisions within the country as a whole.
Some questions in business surveys are poorly posed or ambiguous does good for business mean for my firm, for trade, or for the economy as a whole? Are these mutually compatible, or is what is good for a multinational contrary to the needs of smaller companies? As with the Scottish referendum, companies opinions seem dominated by self-interest, which never necessarily means in all our interests.
Apart from misleading us over business opinion with the COBCOE survey, Britain Stronger in Europe also promotes many campaign slides that play up the worst case scenario in the short-term forecasts of banks, treasuries and international bodies all of which undermine the objectivity of its message. These contrast different futures under the same free-market regime rather than presenting an alternative inclusive EU agenda that could lead to a different future for the continent.
This article originally said that the BCCs survey had micro-businesses backing Brexit. This has now been corrected.
Author: Brad MacKay | The Conversation

redpajama_set_name: RedPajamaCommonCrawl


Where Are FileMaker 10 Saved Find Data Stored?
FileMaker 10 saved find information is stored with the users security account. This means the user can access their saved find information when logged into the database from a different machine but using the same security account.
Newer PostLogical Breaks In FileMaker SubSummary Report Data - Your Thoughts?


The Burlington Magazine Contemporary Art Writing Prize seeks to discover talented young writers on contemporary art, with the winner receiving £1000 and the opportunity to publish a review of a contemporary art exhibition in The Burlington Magazine.
Since its founding in 1903, The Burlington Magazine has always considered the art of the present to be as worthy of study as the art of the past. The Burlington Contemporary Art Writing Prize advances the Magazine's commitment to the study of contemporary art by encouraging aspiring young writers to critically engage with its forms and ideas. The Prize also promotes clear, concise and well-structured writing that is able to navigate complicated territory without recourse to over-complex language.
Alex Farquharson is the incoming Director of Tate Britain, London. Before taking up this position in November 2015, Farquharson was the founding Director of Nottingham Contemporary (2007 to 2015). He has been a visiting tutor and Research Fellow at the Royal College of Art, London, and he sits on the Arts Council's acquisition committee.
Lynne Cooke is a renowned scholar of modern and contemporary art, and Curator of Special Projects in Modern Art at the National Gallery of Art, Washington DC. Prior to this she was the Deputy Director and chief curator at the Museo centro de arte de Reina Sofia, Madrid (2008 to 2012), curator at the Dia Art Foundation (1991 to 2008), and a co-curator of the Venice Biennale in 1986.
The deadline for submissions is Monday 29th February 2016.
Contenders should submit one unpublished review of a contemporary art exhibition. 'Contemporary' is defined as art produced since 2000.
The review should be no more than 1000 words in length and may include up to three low-resolution images.
The submitted review must be written in English (although the art considered may be international).


10 people are diagnosed with sarcoma in the UK everyday and 50% of those don't survive longer than 5 years...These odds are not pretty, but you can help change that!
Thank you for visiting my page. We are supporting Sarcoma UK, the only cancer charity in the UK focused on all types of sarcoma. Sarcoma is a cancer of the bone and soft tissue. It is one of the hardest to diagnose, and difficult to treat.
I was diagnosed with Chondrosarcoma last year and had a bilateral internal hemipelvectomy and a partial resection of the bladder to rid me of a tumour roughly 11cm around. It was major surgery and the recovery has been/is tough, but I'm thankful for my surgeons for trying as usually for a tumour the size and position of mine means losing leg(s)!
I want to do all I can to support Sarcoma UK, so when my friend Jason said he was planning to ride (from our home town of Launceston in Cornwall) to London for charity with a group of people I know and would I like to join them and do the ride for Sarcoma UK I jumped at the chance.
By donating to my page, you will fund vital research projects looking for better treatments. Your donation will also raise awareness of the symptoms of sarcoma to help patients get an early diagnosis - Sarcoma is usually the size of a baked bean tin when diagnosed. If sarcoma is diagnosed when it is smaller than a golf ball, it would increase the chance of survival by at least 20%.
A massive thank you to the Unity Support Riders who guided us through the traffic from Camberley to London, we all felt like VIPs and we can't thank you enough!


OMG why no PING ?!!
i would love to see a video on your most disappointing clubs of the year.
M2!did not make the list wow Rick!
hey Rick, any chance you could do your top putters?
Rick those clubs…. Titleist and Cobra….they are really 2017 models, they aint in shops yet, so kinda unfair to bring them in.
I know it wasn't in your top three but your review of the Cobra King F6 Baffler 4-5 wood was life changing for me in the world of fairway woods. Got it in stock shaft extra stiff. The rails are almost unfair with turf interaction and bad lies. Thanks Rick! Huge fan.
Keep up the great work Rick! Looking forward to 2017!
I just picked up the Ping G 3 wood. I was testing out the Callaway GBB and M2/M1. The M1/M2 I wasnt making good contact and wasnt getting very good shots with but the Callaway GBB and Ping G I was making 220/230s but ultimately went with the stiff Ping G. Cant wait to try it out with year.
What about the best rescue clubs…..
Are you going to do Top 3 Hybrids?
Morning Rick, how about one of the most important things that most golfers don't really consider, the golf ball review, could you do a video with rob to see what ball is better for different swing speeds, not necessarily distance but overall performance including spin, feel, etc. Just a thought for 2017 happy new year.
Most enjoyable series Rick your reviews has certainly made my job easier in recommending equipment for customers as well as myself. Have a good New Year and I look forward to seeing more in 2017.
Hi Rick is the cobra f7 not a 2017 club ? as the release date (U.K.) is Jan 2017 ?
Are there not going to be a putter review made ? most important club in the bag !
No Ping G, no M2… interesting! I am definitely interested in the Cobra.
Rick. I really wish you would go more in depth with shaft combos and heads. Other than that, your content is spot on.
Rick, I'm a 15 year old golfer looking for a good, FORGIVING hybrid. I've been thinking king F7. Any others I should consider? Please help. Thanks.


As the year is closing soon we'd like to thank all of you for sharing the ride, and wish you all Happy Holidays!
This year has once again been quite an exceptional one for Jolla. It's been a time of reorganizing ourselves after the financial crisis we faced at the end of 2015, and a time to refine our strategy and targets. What is now clearer than ever, is that we are a software company, providing the coolest and most independent mobile OS solution for various kinds of partners and users around the world.
However, this does not take away from our love for mobile products, and if you're a community member or otherwise like to have Sailfish OS powering your devices, we can assure you that we're committed to work on new Jolla community devices in the coming year. As promised earlier, we will share a separate blog post about our plans in this area soon.
Earlier this year, our co-founder Sami Pienimäki took the captain's seat, and he will write a more comprehensive analysis of the past year, and most importantly pave the way forward – we'll have his first blog post out during the early weeks of January.
As we've always strived to be transparent and honest, I also want to use this opportunity to touch briefly on the Jolla Tablet refund program, which some of you have been asking about. We are committed to refunding the second half of the tablet refund amount, and we will commence with that as our financial situation allows. The exact timing of this is dependent on Jolla's future financing. We truly appreciate your continued patience with this project.
Finally, a B-I-G thanks for this year to our C-beta group, our early access software group, our partners and customers, and all of you using Sailfish OS around the world!
– Jolla had no new real products for sale.
– Refunds not yet completed for crowd funding people (like myself).
– Little work done on open sourcing the Sailfish OS.
2016 was no better than 2015 and Jolla continues to be on life support. What do we have to look forward to this year?
Do we know anything about the last phase of returning our money?
Will it be the first of the year?
Thanks for all the great work in 2016, the updates were highly appreciated. I am looking forward to new phone (!) hardware that can also be used in the USA.
Btw, thanks for your work. You are doing an unique OS, which is exactly what the current phone market needs, wishing the best for your success!
Merry christmas to you all. Rest and peace. Next year in motion again. 🙂 Hopefully these community equipment and devices should include also SFOS watch….
Thanks for all your great work this year. Looking forward to what Jolla has in store for 2017.
And thank you for your hard work !
After surviving 2016, Jolla sapling has become Jolla shrub, now it is matter of time that it becomes tree and start bearing fruits. Enjoy well earned rest, leave the finances to Ukko Perkele.. 🙂 ..
Merry Christmas and a successful year 2017. It is remarkable what the Jolla Team has accomplished so far. In a world where a few big players are dominating the world of mobile operating systems it is important that alternatives like Sailfish OS exist, giving users freedom and protection of their privacy.
Happy Holidays to the Jolla team and thank you for all the ongoing support and development for my Jolla phone and SailfishOS!
and thanks for keeping the boat afloat.
Got to say I'm more fussed about the future of the project than the tablet refund, because where do we go unless Jolla moves forward? If you want to be tracked then its android, Ithings or (fsm preserve us) winphones. Maybe the new Nokia will get on board.
So if we want the ecosystem to survive, encourage the team. Go sailors, put the rigging up, and surf the waves.
Great Refund 2016 & Happy New Refund 2017!
Why do your captain always using pink clothing?
@Dave999 please stop talking this way! I'm pissed off like you but there is no need to attack people as you do it now.Happy holidays to all.
im not pissed off at all. I feel more sad when thinking about the tablet scam.
Do you remember the Boss clothing at the jPhone announcement. Yes, pink suite?
For some reason I really like how the Sailfish development crew looks in real life. I mean, their appearance says "programmer", not "manager" or "hipster". The people on this photo are exactly who I want to trust the development of my phone's operating system.
Merry Christmas though! Keep up the good work, and hire some more women!
I see Dave999 is still unable to get over the fact that he wasn't among those who got a Jolla tablet before they ran out of components after the manufacturer had taken a good chunk of them as payment when Jolla was unable to pay them on time.
Still, I wonder what he'll do once his life's meaning is taken from him when he gets his refund? Will he start to complain about how late the refund was and how Jolla should have gone bankrupt rather than pay him back this late or that he wasn't given a free Jolla C for his troubles?
Yes, I wonder that too. He will probobly cook some quality food, adding a fine wine. And to top the second refund off, fire up a victory cigar.
Given that we actually will see the second refund.
Wouldn't it be funny if just before then last refunds go out they suddenly just went "lol!!1 we're not giving out any more refunds when we actually spent all the money on making the tablet. learn 2 crowdfun newbs".
We all know you'd probably lose your mind and wreck your apartment seeing how much of an obsession getting your refund has become and how you still fail to understand how crowdfunding actually works.
You are once again repeating all that oligophrenic gibberish ("IGG is not a shop" etc.) which was popular about a year ago, and was dispelled time and again. That makes you look kinda like a retard. Maybe you should change that.
I know you like to cling onto the idea that crowdfunding doesn't come with any risks, but it does. Projects can fail and they do.
In this case they spent all the money they got, and several times more from other funding sources, on developing and making the tablets. Unfortunately due to things that were outside of their control, most importantly relating to that non-crowdfunded money, thing went wrong and they found themselves in a situation where they didn't have enough parts to fill all the orders and weren't able to buy any more parts.
@L-A-G I think you have misjudged the whole situation. Like most things related to the jPad. Unfortunately, too many missjudgements was done. Can't blame you though, since that is your right to do so.
2017 is a new year and if jolla can limit the misses and achieve some hits you might get an epic year!
No, *you* clearly misjudged the Jolla Tablet project with the way you seem to have assumed it was like buying a finished product from a store rather than pre-purchasing a product very much still in development from a non-established company.
When you realize this and combine it with what actually happened behind the scenes, the whole "I got scammed" attitude becomes completely stupid.
If you don't want to take risks like this again, then refrain from ever backing any crowdfunding project.
Hope 2017 will bring a powerful ChinaPhone with Sailfish OS (or at least value for money) and Whatsapp working via WiFi. Switched back to Android because of this, sad!
Happy new year, and don't forget that people need phones and tablets with Sailfish OS.
We need Sailfish devices early in 2017 !
Jolla is the most ethical company ever and did so much for Sailfish in 2017.
So? how ethical it is to misuse thefunds for the tablet to develop an OS, ONLY, then tell the backers: "Well guys, screw you… no tablet and with luck we might eveb get you your money back after 1-2 yess of waiting (aka forced free credit) if THAT is the most ethical company ever… i have a few bridges to sell you.
Nice picture of a band of con artists… where is the rest of my refund?


text:
Revlon tells bankruptcy judge its stock may be worthless
(Bloomberg) — Revlon Inc . told the judge overseeing the cosmetics giant's bankruptcy that shareholders don't need a special, company-funded committee to represent them in the Chapter 11 case because there's no evidence the equity is worth anything.
Most Read by Bloomberg
The company urged U.S. Bankruptcy Judge David S. Jones in Manhattan to reject the minority owners' request in part because low bond prices suggest the stock has little hope of a recovery. The company also argued that shareholder interests are already well represented in the case by majority owner MacAndrews & Forbes, as well as other groups
In bankruptcy, formal equity committees are rare because all creditors must be paid in full before shareholders are allowed to recover any of their investment.
The committee representing unsecured creditors also asked Jones to reject a shareholder committee.
"Revlon stock trades have all the outward appearance of so-called 'meme' stocks," the commission said in its objection, referring to stocks whose value rises only because of Internet chatter and not for economic reasons.
Revlon shares fell as much as 34% to $5.62 on Monday before rebounding to around $8.22, leaving them down about 3% for the day. That price is up from just $1.17 in June.
Almost all of the official commission is appointed by the Office of the U.S. Trustee, a division of the U.S. Department of Justice that acts as a watchdog in corporate bankruptcies. In the case of Revlon, the office appointed an unsecured creditors' committee, but last month overruled shareholders.
The shareholder group, which claims to own 4.7 percent of Revlon's common stock not held by insiders, asked Jones on Aug. 9 to order the U.S. trustee to appoint a panel. The stock closed at about $8 that day.
Forcing Revlon to fund lawyers and other advisers for a minority group of shareholders would be a waste of money, the company said in court filings. Official committees have their advisers' fees paid by the bankrupt company.
Shareholders say recent prices suggest a chance to get something back
Revlon filed for bankruptcy in June as a global supply chain crisis squeezed the debt-ridden company as it struggled to tap into a broader boom in cosmetics sales driven by social media influencers.
Investor Ron Perelman's MacAndrews & Forbes holding company owns about 85% of Revlon.
The case is Revlon Inc., 22-10760, U.S. Bankruptcy Court for the Southern District of New York.
(Adds comment from Revlon's court filing in second paragraph and clarifies minority stock ownership in eighth paragraph.)
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text:
CPS3 software
Call of Duty 4 for PS3 will be Awesome
I'm doing a little tapdance of joy right now. I was reading a thread over at the NeoGAF forums where 402 (an IW employee) had several interesting things to say about the PS3 version of CoD4:
There should be no doubts about the quality of the PS3 version, it's received the same exact development focus and time as the Xbox 360 and PC version and will have all the same features. We put a lot of work into the PS3 version to ensure it had an equally as impressive multiplayer portion with a constant 60 FPS just like all the others and a full multiplayer set up with lobbies, parties, profiles, splitscreen, and everything else you expect from multiplayer on all platforms.
The video you linked for some reason mixed random Xbox 360 footage in there, however the event in San Francisco had all PS3's for multiplayer and Single player, PC's for Single and Multiplayer and Xbox 360 only for single player.
Yes, the PS3 version will have the same matchmaking set-up as the Xbox 360 including the Party System, LAN Party, and Splitscreen set-ups for offline play. We essentially built in the Xbox Live functionality 360 users are used to so that the PS3 users can enjoy the same features, functionality, and MP set-up as everyone else.
We just had a Preview event in San Francisco where press got hands on time with the Single Player and Multiplayer portion of the PS3 version of the game, so some of those previews should be hitting rather soon (if not hitting already) which will hopefully let you see just how equal all the platforms really are.
You'll be able to use your PS3 Friends list.
Someone else who was at the event had this to say:
Just a heads-up, guys: the embargo for the event last week lifts tomorrow morning at 9AM PST. There'll be plenty of previews going up then, but I don't think ATVI will mind me saying this: the game rocks, and they had all three versions up and running at the event.
They. Are. Identical.
Believe me, it's even weirder to type that than it was to see it all in motion. Good gawd the game looks amazing. The online is going to steal people's lives away…
Amazing! I have my 4 player splitscreen with profiles! Yay!
Call of Duty 4 for PS3
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BADLAND: Game of the Year Edition Out Today... May 26, 2015 | EdEN
engadget disses PS3 (kinda) October 12, 2005 | Blackstaffer


Since the NFL Mock Draft Database has been doing it's weekly Mock Munch of the week's most updated Mocks, QB Sam Bradford has always been the leader at #4. Not anymore. Add in Jimmy Clausen.
Our Mock Database now consists of 208 mocks draft, 166 of which have been updated in January. Of those, 21 have been updated over the past two days. For the Mock Munch, we munched together the mock drafts updated between 1/21 and 1/28, a total of 76 mocks. This is interesting. Of the 76 most updated mocks, 58 project the Redskins to take a Quarterback while only 18 project Offensive tackle.


DALLAS (AP) - Authorities say a neighbor came across three bodies outside a home in East Texas and told her son to call police, who found two more people dead inside.
Polk County sheriff's officials previously said a woman who was found safe and locked inside a bedroom closet was the first to alert authorities. Sheriff's Capt. Rickie Childers clarified Tuesday that the woman was found in the bedroom but was not involved in contacting police.
Authorities said Monday that Carlos and Lynda Delaney were shot to death at their Blanchard home along with their granddaughter, Ashley Delaney, her husband, Randy Horn, and a 15-month-old child who was not identified.


text:
Following CRT's announcement on 6th November 2018 of up to 240 redundancies across its middle management roles, we can reveal that all the staff in the CRT Devizes office are facing possible redundancy. A statutory three-month consultation period with the relevant trade unions began on 12th November. A large number of CRT staff belong to Unite.
One staff member in Devizes commented "I hope this will not mean the end of a local presence here". Up to 2009, when BW carried out an earlier restructuring exercise, the K&A was run from Gloucester, where the recently appointed regional director for Wales and the South West, Richard Thomas, is based.
CRT claims that the redundancies are necessary to "improve customer service and to engage with local communities", but we do not see how reducing or closing a local office will achieve that objective.
CRT was restructured into six larger regional units in July this year when K&A Manager Mark Evans lost his job. However, at the eleventh hour, avoiding redundancy, Mr Evans was appointed to the post of Head of CRT's directly managed moorings, now re-branded 'Waterside Moorings'. Mr Evans took over from Jenny Whitehall who has retired, and is now also based in Gloucester.
We understand that enforcement staff such as Enforcement Officers (now re-branded in an Orwellian move as "Boat Licence Customer Support Officers") Corrine Rotherham and Matthew Preston are not facing redundancy, as enforcement is to continue to be managed centrally as it has been since 2009. However according to sources in CRT, some local enforcement staff will move to be managed by the new regional directors rather than centrally.
Earlier in 2018 Head of Boating Enforcement Denise Yelland left CRT; her role has been taken over by Matthew Aymes. Around the same time CRT brought part of its legal operation evicting liveaboard boaters back in house, which it had outsourced to its solicitors Shoosmiths, employing solicitor Lucy Barry from Shoosmiths. We also understand that former K&A Manager Mark Stephens, who moved to a senior role in the national team overseeing engineering works in 2015, has left CRT along with a number of other experienced staff who had worked for BW and CRT for many years.
You can read CRT's announcement here 39213-canal-and-river-trust-begins-consultation-to-move-greater-resource-into-regional-customer-focussed-roles
http://kanda.boatingcommunity.org.uk/mark-stephens-to-leave-ka/
http://kanda.boatingcommunity.org.uk/ka-manager-made-redundant-in-crt-restructuring/
http://kanda.boatingcommunity.org.uk/important-please-respond-to-crts-boat-licensing-review-consultation-by-18th-december-2017/
https://unitetheunion.org/
http://www.bargee-traveller.org.uk/crt-wastes-nearly-half-a-million-on-lawyers-fees-in-a-year/
https://www.legalfutures.co.uk/latest-news/solicitors-from-hell-founder-wins-surprise-high-court-victory
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text:
Police are investigating a dramatic fatal crash on Tauranga's Chapel Street
About 20 people dived into Tauranga Harbour in a desperate rescue attempt, after a car plunged into the water and began sinking fast with people inside about 5pm.
Police say one person died, while St John says three others were treated for injuries at the scene.