the cochlear implant ( ci ) transforms acoustic signals from the environment into electric impulses , which are then used to stimulate intact fibers of the auditory nerve . with this treatment , individuals with profound hearing loss ( hl )
current technology and speech processing strategies allow many ci recipients to achieve impressive accuracy in open - set speech recognition , and the ci is arguably the most effective neural prosthesis ever developed [ 13 ] . however , the success of the outcome depends both on duration of deafness prior to implantation [ 4 , 5 ] and on the onset of deafness before ( prelingually ) [ 47 ] or after ( postlingually )   critical stages in the acquisition of language . in many cases ,
the greatest gains of performance occur in the first three months of use [ 911 ] .
the dramatic improvements following implantation not only demonstrate the efficiency of the ci technology , but also point to the role of cortical plasticity as a means to reactivate brain function .  
plasticity is a term used to describe the reorganization of the central nervous system by means of synaptic changes and rewiring of neural circuits . in cases of cochlear implantation , neural plasticity associated with deprivation of auditory input and adaptation to the absence of stimuli is of particular interest .
reduced input to the brain from impaired auditory pathways results in significant changes in the central auditory system   and is accompanied by a recruitment of deprived cortices in response to input from the intact senses [ 1317 ] .
when auditory input to the brain is reintroduced , this novel auditory experience may itself induce additional plasticity .
the sensory reafferentation provided by the ci thus offers a unique opportunity to study the effects of preceding deafness on functional brain organization .   in normal - hearing ( nh )
adults , language processing is associated with extensive frontal activation in the left cerebral hemisphere , including the anterior ( brodmann 's areas ( ba ) 45 and 47 ) and posterior ( ba 44 and 45 ) parts of the left inferior frontal gyrus ( lifg ) , the latter often referred to as broca 's area [ 19 , 20 ] . traditionally , this area is mainly assigned an expressive language function , but several studies show a relationship between the perception of language and left frontal activity , both when stimuli are presented aurally [ 2124 ] and visually [ 2428 ] .
neuroimaging experiments comparing auditory responses of ci users and normal - hearing control participants , while listening to speech or complex nonspeech , generally reveal bilateral activity in the primary and secondary auditory cortices , including both superior and middle temporal gyri [ 12 , 2934 ] .
one consistent outcome of these studies is the more dominant right temporal activity of ci users listening to speech , that is , the observation of more bilateral activity than would be expected on the basis of the classical presumption of left - lateralized activity of language processing in normal - hearing .
however , in these studies , activation of other classic language regions such as broca 's area was not a consistent finding .
naito and colleagues found broca 's area to be activated only when the ci participants silently repeated sentences [ 31 , 36 ] .
compared brain activity in experienced ci users according to their levels of speech comprehension performance .
they found that , unlike ci users with low speech comprehension , single words and speech yielded raised activity in the left inferior prefrontal cortex ( lipc ) in ci users with excellent speech perception .  
some observed activations outside the classic language areas , including anterior cingulate , parietal regions , and left hippocampus , have been attributed to nonspecific attentional mechanisms and memory in ci users [ 31 , 32 ] .
furthermore , some studies have reported convincing evidence of visual activity in response to auditory stimuli or auditory activity in response to visual stimuli in ci users .
although much debate about the identity of the brain systems that are changed and the mechanisms that mediate these changes exists , the general belief is that this cross - modal reorganization is associated with the strong visual speech - reading skills developed by ci users during the period of deafness , which are maintained or even improved after cochlear implantation , despite progressive recovery of auditory function [ 5 , 11 , 33 , 3841 ] .
the possible reasons for these mixed results may include differences in experimental paradigms , small sample sizes , heterogeneous populations , variance in statistical thresholds , and a lack of longitudinal control of plasticity . with the present study , we tested the cortical mechanisms underlying the restoration of hearing and speech perception in the first six - month period following implant switch - on .
we expected to see inactive neuronal pathways reactivated in ci recipients , within three to six months of switch - on , and engagement of cortical areas resembling those of normal - hearing control participants . furthermore , in previous findings , notwithstanding , we expected to see broca 's area involved in speech perception . finally , we expected to see a difference in the progress of adaptation and the involvement of cortical areas between ci users with postlingual hearing loss and ci users with prelingual hearing loss .
over the course of two years , patients who were approved for implantation were contacted by mail and invited to take part in the research project , including positron emission tomography ( pet ) and speech perception measures . from a total of 41 patients ,
15 accepted and were included in the study ( 6 women , 9 men , mage = 51.8 , age , range : 2173 years ) .
four participants had a prelingual onset of hl , indicated by their estimated age at onset of deafness and main use of signed language as communicative strategy .
the remaining 11 participants had a postlingual or progressive onset of hl , as indicated by their main use of residual hearing , supported by lip - reading .
in accordance with local practice , all ci participants followed standard aural / oral therapy for six months in parallel with the study .
the therapy program includes weekly one - hour individually adapted sessions and trains speech perception and articulation .  
table 1 lists the demographic and clinical data for the 15 participants . to obtain a normal - hearing reference , we recruited a group of nh adults ( 4 women , 2 men , mage = 54.29 years , age range : 4764 years ) for a single pet / test session .
all nh participants met the criteria for normal - hearing by passing a full audiometric test .
the study was conducted at the pet center , aarhus university hospital , denmark , in accordance with the declaration of helsinki , and approved by the research ethics committee of the central denmark region .
nh participants underwent pet once , while ci participants were tested consecutively at three points of time : ( 1 ) within 14 days after switch - on of the implant ( baseline , bl ) , ( 2 ) after three - months ( midpoint , mp ) , and ( 3 ) after six months ( endpoint , ep ) . for purposes of analysis ,
two subgroups were identified as ( 1 ) the postlingual ( post ) hl subgroup ( n = 11 ) and ( 2 ) the prelingual ( pre ) hl subgroup ( n = 4 ) .
the hagerman test is an open - set test which presents sentences organized in lists of ten .
the sentences have identical name - verb - number - adjective - noun structures , which the participant is required to repeat .
normally , the test is presented in background noise . however , considering the participants ' inexperience with the implant , we removed the background noise .
the participants were given one training list with feedback and two trial lists without feedback ( max .
sound was played back on a laptop computer through an active loudspeaker ( fostex 6301b , fostex company , japan ) placed in front of the participant .
the stimuli were presented at 65  db sound pressure level ( spl ) , and ci users were instructed to use their preferred ci settings during the entire test session and to adjust their processors to a comfortable loudness level .
furthermore , participants who used a hearing aid were instructed to turn it off and leave it plugged in .
the ci participants performed the hagerman tests in separate sessions at the same milestones as selected for pet data acquisition ( bl , mp , and ep ) .
the nh group performed a single hagerman test along with their pet scan session . to identify effects of time
, we performed a repeated measures analysis of variance . due to nonnormal distributions in the data , this was done using a nonparametric friedman 's anova in the post and pre subgroups separately .
post hoc tests and between - group analyses were performed by mann - whitney nonparametric tests and bonferroni corrected at alpha 0.016 .
the hag data were analyzed in spss and plotted with sigmaplot for windows 11.0 ( systat software inc . ) . 

a high - resolution t1-weighted mr scan was acquired prior to pet scanning . in the case of ci participants ,
all participants were examined in 2 conditions : ( 1 ) multitalker babble ( bab ) from multiple simultaneous speakers with a complexity close to that of speech and perceived by the listeners as speech - like but devoid of meaning   and ( 2 )  running  speech ( rs ) , narrating the history of a familiar geographical locality at the rate of 142 words per minute , generated in danish by a standard female voice .
the stimuli were played back on a laptop computer in the freeware sound editor software audacity ( http://audacity.sourceforge.net/ ) and delivered directly from the computer 's headphone jack to the external input port of the implant speech processor .
bimodally aided participants removed their hearing aid and were fitted with an earplug in the nonimplanted ear during the tomography .
these measures were taken to preclude background noise and possible cross - talk from the contralateral ear .
the nh participants listened to the stimuli binaurally through a pair of headphones ( akg , k 271 ) .
all stimuli were presented at the most comfortable level . to define this level , participants were exposed to the two stimuli once before the tomography . in the tomograph , prior to bolus injection , participants had no information about the nature of the next stimulus , but they were instructed to listen attentively in all cases .
after each of the four scans , participants were required to describe what they had heard and , if possible , review the content of the narration .  

pet . positron emission tomography ( pet ) is a molecular imaging method that yields brain activity , by means of detecting changes in regional cerebral blood flow ( rcbf ) .
this is done by computing and comparing the spatial distributions of the uptake of a blood flow tracer .
pet measurements are generally limited with respect to spatial and temporal resolution and the invasiveness of the procedure , which requires injection of oxygen-15-labelled water . in this case , however , anatomical and temporal specificity could not have been improved by using functional magnetic resonance imaging ( fmri ) , as the auditory implants are not mri compatible . in addition , pet is an almost noiseless imaging modality , which is useful for both ci participants and for the study of speech .
finally , because only the head of the participant is positioned in the tomograph , compared with the whole body imposition of fmri , it is possible to communicate visually with the participant during tomography .
we measured raised or reduced cerebral activity as the change of the brain uptake of h2  o oxygen-15-labeled water , which matches the distribution of cerebral blood flow ( cbf ) , using an ecat exact hr 47 tomograph ( siemens / cti ) .
emission scans were initiated at 60,000 true counts per second after repeated intravenous bolus injections of doses of tracer with an activity of 500  mbq ( 13.5  mci ) .
the tomography took place in a darkened room with participants ' eyes closed . the babble and running speech conditions
the uptake lasted 90 seconds ( single frame ) at intervals of 10  min .
after correction for scatter and measured attenuation , each pet frame was reconstructed with filtered back projection and smoothed with a postreconstruction 10  mm gaussian filter resulting in a resolution of 11  mm full - width - at - half - maximum ( fwhm ) .
rules of regulation mean that participants who volunteer for scientific experiments may receive a total maximum radiation of 6 millisieverts ( msv ) within one year . here
, the total radiation dose administered over the three times of scanning was approximately 5.58  msv . due to these restrictions , no preoperative baseline scans could be acquired .  
participants ' mr images were co - registered to an mr template averaged across 85 individual mr scans in talairach space , using a combination of linear and nonlinear transformations .
each summed pet emission recording was linearly coregistered to the corresponding mr image using automated algorithms . to smooth the pet images for individual anatomical differences and variation in gyral anatomy ,
images were blurred with a gaussian filter resulting in final 14  mm at full - width half - maximum ( fwhm ) isotropic resolution .
all images were processed using statistical parametric mapping 8 ( spm8 ; wellcome neuroimaging department , uk , ( http://www.fil.ion.ucl.ac.uk/spm/ ) ) .
local maxima of activation clusters were identified using the montreal neurological institute ( mni ) coordinate system and then cross - referenced with a standard anatomical brain coordinate atlas .
differences in global activity were controlled using proportional normalization ( gray matter average per volume ) .
significance threshold for task main effects was set to p < 0.05 , family wise error ( fwe ) corrected for multiple comparisons .
we tested the effect of side of implant and type of implant in a separate preanalysis .
as we found neither main effects nor interactions with functional data involving these variables , we concluded that these factors had no significant effect on the results .
the first analysis identified the main effects of time , speech / babble contrast , and history of hearing loss ( post hl versus pre hl ) and possible interactions between these effects in the whole brain , across ci participants .
this analysis was performed as a single spm matrix in a factorial 3-way design with time , contrast , and subgroup as factors . to define a region - of - interest ( roi )
analysis  2 . the second analysis identified possible main effects of contrast , time , and interactions between these factors in the inferior frontal gyrus ( ifg ) , more specifically broca 's area ( ba 44/45 ) .
this analysis was performed as two 2-way factorial analyses of the post hl and the pre hl subgroups separately . to define a region - of - interest ( roi )
, we created a mask based on bilateral inferior frontal gyri ( broca 's region ) , including the putative brodmann regions 44 , 45 , and 47 using the wfu pick - atlas .  

the third analysis investigated main effects of contrast and group ( ci versus nh ) at the ci baseline and possible interactions between these effects .
this analysis was performed as a single spm matrix in a factorial 2-way design with condition and group as factors . to define a roi
we found a main effect of speech / babble contrast across ci participants , regardless of subgroup , in bilateral superior temporal gyri ( f(1,78 ) = 60.14 ) .
a t - test confirmed that the effect was driven by higher activity during running speech ( table 2 ; figure 1 ) .
there was no significant main effect of time or group , nor any interaction between the effects .
the roi analysis revealed significant interaction between the effects of contrast and group in ba 21/22 in the left superior temporal gyrus ( f(1,78 ) = 20.42 ) ( table 2 ; figure 2 ) .
a plot of contrast estimates showed a difference between running speech and babble that was larger in the postlingual subgroup than in the prelingual subgroup ( figure 2 ) . in the bilateral ifg roi analysis
, we found a main effect of speech / babble contrast in ba 47 in the postlingual subgroup .
a t - test confirmed that the effect was driven by higher activity during running speech .
furthermore , we found a main effect of time in left ifg ( broca 's area ba 45 ; f(2,60 ) = 14.19 ; p = 0.006 , fwe corrected ) ( figure 3 ) , with no significant interaction between contrast and time .
the prelingual subgroup had no main effects in the bilateral ifg roi analysis ( table 3 ) .
we found a main effect of speech / babble contrast across the ci and nh groups bilaterally in superior temporal gyri , in the left middle temporal gyrus , and in the right inferior parietal lobule .
t - tests showed that the superior temporal gyri bilaterally and the left middle temporal gyrus were more active during running speech , while the right inferior parietal lobule was more active during babble .
a t - test showed that this effect was due to higher activity of this area in the nh group than in the ci group .
no interaction was found between the effect of contrast and the effect of group in whole - brain analysis ( table 4 ) . the roi analysis based on the main effect of contrast yielded a main effect of ci versus nh in secondary auditory cortex including ba 22 in the right superior temporal gyrus .
a t - test showed that this effect was due to higher activity of this area in the nh group than in the ci group .
furthermore , in the roi analysis , we found an interaction between the effect of speech / babble contrast and the effect of group in the right inferior parietal lobule ( table 4 ) .
we found a significant effect of time in the post group ( (2,2 ) = 19.62 , p < 0.001 ) , but not in the pre group .
post hoc tests showed that the effect was driven by the 51.3 percentage points endpoint gain ( mann - whitney u = 12.5 , p = 0.002 ) .
furthermore , the post group scored significantly higher than the pre group at all three points of measurement ( bl : mann - whitney u = 0.000 , p = 0.004 ; mp : mann - whitney u = 0.000 , p = 0.004 ; ep : mann - whitney u = 0.000 , p = 0.004 ) .
ceiling performance ( 100% correct ) was observed in all nh participants ( figure 4 ) .
in this study , we aimed to examine the plastic changes which underlie the recovery of hearing after cochlear implantation .
our results showed that across all ci recipients and all points of measurement , the bilateral middle and superior temporal gyri ( including , more specifically , brodmann areas 21 and 22 ) were significantly more active when participants listened to running speech than when they listened to multi - talker babble .
thus , on average , the auditory brain regions , known to be involved in the processing of complex auditory stimuli [ 4951 ] displayed a clear distinction between speech - like noise and speech in recently implanted ci recipients .
this confirms that both hemispheres are involved in the speech perception process , even during monaural auditory stimulation [ 29 , 36 , 52 , 53 ] .
furthermore , the results showed a difference in the way ci recipients with postlingual hearing loss and recipients with prelingual hearing loss distinguish between speech and babble .
the ci users with postlingual hearing loss displayed a greater activation during speech than during babble in ba 21 and 22 in the left superior temporal gyrus , indicating differential processing of the stimuli by the two subgroups .
we speculate that the postlingually deaf listeners disengage attention when they are presented with the incomprehensible babble stimulus .
in contrast , the prelingually deaf ci listeners may be equally attentive to the two stimuli , regardless of their nature , as reflected in undifferentiated activity .
the postlingual subgroup not only possessed a moderate level of speech perception at baseline ( within 14 days after switch - on of the implant ) , but also made significant gains in performance , the majority of which occurred in the first three month period .
in contrast , the prelingual subgroup had no baseline speech perception and only modest , if any , progress during the study period .
this finding is consistent with expectation and implies an association between behavioral performance and brain activity related to the history of hearing loss . in prelingual deafness
, the neuronal connections of the auditory pathways ( e.g. , measured as cortical auditory evoked potentials ) may not be established in the appropriate time window of opportunity [ 5456 ] . the subsequent electric stimulation at some time in adulthood may produce some hearing sensation , but the discrimination of sounds and time intervals remain defective [ 57 , 58 ] . the findings are compatible with naito et al . , who suggested that the reduced speech activation in prelingually deaf implant users could be explained by insufficient development of neuronal networks or their degeneration due to prolonged deafness .
follow - up studies in the present population may provide interesting insight into the degree to which speech perception progresses in the prelingual subgroup in the long term .
we found a main effect of time exclusively in broca 's area , and only in the postlingual subgroup .
this is in line with recent studies showing that , in ci users , the activation of broca 's area during speech processing is negatively correlated with the duration of deafness and positively correlated with the progress in the restoration of speech comprehension [ 7 , 8 , 37 , 59 ] .
this indicates that the changes in the auditory recovery process are most profoundly manifested in this specific area , which is associated with speech perception and production .
this suggests that the area becomes increasingly activated , regardless of whether the stimulus makes semantic sense or not , or is active in the distinction between sense and nonsense .
however , the absence of difference between speech and babble in broca 's area may also be explained by an increasingly high activity at rest in ci patients , as reported by strelnikov et al . .
our whole - brain analysis revealed a significant activation of bilateral superior temporal gyri and left middle temporal gyrus during speech across ci participants at baseline and nh individuals .
, who , in addition to bilateral superior temporal gyri , found significant speech activation in the right middle temporal gyrus , the left posterior inferior frontal gyrus ( broca 's area ) , and the left hippocampus in both normal participants and ci users .
these further findings could be explained by the use of silence as contrast relative to the use of babble in the present study .
interestingly , even though the nh participants received unilateral stimulation ( 6 right ; 6 left ) , the naito study found no significant difference in any brain area in either nh participants or ci users between right ear stimulation and left ear stimulation .
the significant involvement of the right parietal lobule in the ci participants during babble suggests that , at this initial stage of the ci adaptation , ci listeners , unlike nh individuals , need to pay attention to the speech - like noise to determine its possible character . the observation that during speech stimulation the nh participants involved the caudate nucleus more than the ci participants
may be explained by a reduction of the effort needed by the nh participants to deal with the well - known task of receiving a message .
the caudate nucleus is a part of the striatum , which subserves among other tasks the learning of slowly modulated skills or habits . to the normal - hearing listener ,
the reception of auditory information is an every - day experience similar to following a known route ; for example , see wallentin et al .   for a similar argument .
in contrast , to ci listeners , auditory stimuli are nonhabitual in the strongest sense of the word , thus relying on other sources of processing .
interestingly , naito et al .   made a similar finding and speculated that though the caudate nucleus has been associated with various tasks ranging from sensorimotor tasks to pure thinking , the result may provide further evidence that the area has cognitive function and shows increased activity along with the increased activity in cortical language areas .
in contrast to the significantly higher right - lateralized activation observed in nh individuals in the present study , giraud et al .   showed a left - lateralized activation of temporal and frontal regions in nh controls .
however , direct comparison between the two studies is difficult as there are several differences in study design and implant experience of the participants .
found increased activity in right cerebellar cortex when running speech was comprehended relative to babble , but only in ci listeners with high speech comprehension .
the authors speculated that this could be due to cognitive work of cerebellum subserving verbal working memory or a contribution of the right cerebellar hemisphere to precise representation of temporal information for phonetic processing .
however , this finding was not replicated in the present study , which may reflect differences in duration of implant use and a mixture of speech comprehension levels .
giraud and colleagues   consistently demonstrated activation of areas ba 17/18 in the visual cortex when ci users responded to meaningful sounds .
the authors argued that the process was associated with improvement of lip - reading proficiency , which is supported by findings in a behavioral study by rouger .
a similar cross - modal interaction between vision and hearing was not replicated in the current study .
the giraud study involved repetition of words and syllables and naming of environmental sounds , contrasted with noise bursts , as opposed to the current study , which involved passive listening to a story contrasted with speech - like noise .
furthermore , sound was presented in free field , whereas in the current study , the auditory stimuli bypassed the microphones of the speech processor and were fed directly to the auxiliary input . finally , the strict conservative statistical methods used here preclude reporting of results that are not statistically significant when corrected for multiple comparisons . in scandinavia as in most european countries , cochlear implantation is administered by the public health care system and offered for free to all patients who meet the clinical implantation criteria ( < 40% open - set word - recognition scores ) .
this includes patients with a prelingual hearing loss , despite recognition that these patients may have very limited linguistic benefit . as a result of this policy ,
the group of ci users in general is very heterogeneous , which was also the case in this study . while the difference in group size was far from optimal and
may have confounded the results , we maintain that it is of high importance to also study cortical activity in prelingually deaf patients following cochlear implantation . in a previous study involving music training
, we found that while little gain was achieved in speech perception , prelingual deafness did not preclude acquisition of some aspects of music perception .
this implies that plastic changes take place also in the long - term deaf brain and that specific training measures could help these patients in achieving improved implant outcome [ 58 , 63 ] .
our normal - hearing control group had a less optimal size , which may have made direct comparisons between groups less valid than desired . however , ethical restrictions limit the number of healthy participants in studies involving pet .
as stated , the degree of deafness ( i.e. , residual hearing ) varied across subjects and may have influenced the adaptation to the implant .
unfortunately , a correlation analysis between preoperative speech understanding and pet and behavioral results was not possible since such data were not available for all participants .
the present pet study tested brain activation patterns in a group of recently implanted adult ci recipients and a group of normal - hearing controls , who listened to speech and nonspeech stimuli .
ci listeners with postlingual hearing loss showed differential activation of left superior temporal gyrus during speech and speech - like stimuli , unlike ci listeners with prelingual hearing loss .
this group difference was also reflected in a behavioral advantage for patients with postlingual hearing loss .
furthermore , broca 's area was activated as an effect of time , but only in ci listeners with postlingual hearing loss .
comparison of the ci listeners and the normal - hearing controls revealed significantly higher activation of the caudate nucleus in the normal - hearing listeners .
the study demonstrates that processing of the information provided by the cochlear implant is highly related to the history of hearing loss .
patients whose hearing loss occurred after the acquisition of language involve brain areas associated with speech comprehension , which is not the case for patients whose hearing loss occurred before the acquisition of language .
finally , the findings confirm the key role of broca 's area in restoration of speech perception , but only in individuals in whom broca 's area has been active prior to the loss of hearing .
 the most dramatic progress in the restoration of hearing takes place in the first months after cochlear implantation . to map the brain activity underlying this process 
 , we used positron emission 
 tomography at three time points : within 14 days , three months , and six months after switch - on . 
 fifteen recently implanted adult implant recipients listened to running speech or speech - like noise in four sequential pet sessions at each milestone . 
 ci listeners with postlingual hearing loss showed differential activation of left superior temporal gyrus during speech and speech - like stimuli , unlike ci listeners with prelingual hearing loss . 
 furthermore , broca 's area was activated as an effect of time , but only in ci listeners with postlingual hearing loss . 
 the study demonstrates that adaptation to the cochlear implant is highly related to the history of hearing loss . 
 speech processing in patients whose hearing loss occurred after the acquisition of language involves brain areas associated with speech comprehension , which is not the case for patients whose hearing loss occurred before the acquisition of language . 
 finally , the findings confirm the key role of broca 's area in restoration of speech perception , but only in individuals in whom broca 's area has been active prior to the loss of hearing . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusion