human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The authors investigated the use of slow-frequency repetitive transcranial magnetic stimulation ( rTMS ) to the unaffected hemisphere to decrease interhemispheric inhibition of the lesioned hemisphere and improve motor function in patients within 12 months of a stroke . Patients showed a significant decrease in simple and choice reaction time and improved performance of the Purdue Pegboard test with their affected h and after rTMS of the motor cortex in the intact hemisphere as compared with sham rTMS Objective : To investigate the long-term behavioral and neurophysiologic effects of combined time-locked repetitive transcranial magnetic stimulation ( rTMS ) and physical therapy ( PT ) intervention in chronic stroke patients with mild motor disabilities . Methods : Thirty patients were enrolled in a double-blind , r and omized , single-center clinical trial . Patients received 10 daily sessions of 1 Hz rTMS over the intact motor cortex . In different groups , stimulation was either real ( rTMSR ) or sham ( rTMSS ) and was administered either immediately before or after PT . Outcome measures included dexterity , force , interhemispheric inhibition , and corticospinal excitability and were assessed for 3 months after the end of treatment . Results : Treatment induced cumulative rebalance of excitability in the 2 hemispheres and a reduction of interhemispheric inhibition in the rTMSR groups . Use-dependent improvements were detected in all groups . Improvements in trained abilities were small and transitory in rTMSS patients . Greater behavioral and neurophysiologic outcomes were found after rTMSR , with the group receiving rTMSR before PT ( rTMSR-PT ) showing robust and stable improvements and the other group ( PT-rTMSR ) showing a slight improvement decline over time . Conclusion : Our findings indicate that priming PT with inhibitory rTMS is optimal to boost use-dependent plasticity and rebalance motor excitability and suggest that time-locked rTMS is a valid and promising approach for chronic stroke patients with mild motor impairment . Classification of evidence : This interventional study provides Class I evidence that time-locked rTMS before or after physical therapy improves measures of dexterity and force in the affected limb in patients with chronic deficits more than 6 months poststroke . Neurology ® Objective : Cortico-cortical circuits originating from the posterior parietal cortex ( PPC ) of the intact left hemisphere ( LH ) may become hyperexcitable in patients with hemispatial neglect due to a right hemispheric ( RH ) stroke . Methods : In the current r and omized , double-blind , sham-controlled study , we investigated safety and efficacy of continuous theta-burst stimulation ( cTBS ) in 10 sessions over 2 weeks applied over the intact PPC of the LH in subacute ischemic stroke patients .  Severity of neglect was assessed through the st and ardized Behavioral Inattention Test ( BIT ) . We also measured , by means of bifocal transcranial magnetic stimulation ( TMS ) , how cTBS modified the excitability of the parieto-frontal functional connections in the intact LH . Results : We found that 2 weeks of cTBS , but not sham cTBS , were effective in improving neglect symptoms as measured by BIT score . BIT scores improved by 16.3 % after 2 weeks of cTBS and 22.6 % at 1 month follow-up . We also found that hyperexcitability of LH parieto-frontal circuits was reduced following treatment with real but not sham cTBS . Conclusion : These findings suggest that a 2-week course of cTBS over the LH PPC may be a potential effective strategy in accelerating recovery from visuospatial neglect in subacute stroke patients , possibly counteracting the hyperexcitability of LH parieto-frontal circuits . Classification of evidence : This study provides Class III evidence that left posterior parietal cortex theta-burst stimulation improves hemispatial neglect for up to 2 weeks after treatment Abstract Background : Functional neuroimaging studies with poststroke aphasia patients have shown increased activation of the unaffected hemisphere , which hypothetically reflects a maladaptive strategy of brain reorganization . Objective : We investigated whether repetitive transcranial magnetic stimulation ( rTMS ) inhibiting the right-hemisphere homologue of Broca ’s area improves language restitution if combined with speech/ language therapy . Methods : Forty aphasic patients during the subacute phase of ischemic stroke were r and omized to a 3-week aphasia rehabilitation protocol in combination with real or sham rTMS .  Naming , repetition , and comprehension were assessed using the Boston Diagnostic Aphasia Examination at baseline , immediately after therapy , and 15 weeks after completing treatment . Results : Although language functions improved in both experimental and control groups after 3 weeks , only slight group differences in degree of recovery were revealed between patients receiving rTMS and control participants . Follow-up revealed that severely aphasic rTMS patients demonstrated significantly greater improvement than patients receiving sham stimulation in repetition . Conclusions : Inhibitory rTMS applied to the right frontal language homologue is not effective for all poststroke aphasia patients , although it might benefit selected patients The development of  stimulus selectivity in the primary sensory cortex of higher vertebrates is considered in a general mathematical framework . A synaptic evolution scheme of a new kind is proposed in which incoming patterns rather than converging afferents compete . The change in the efficacy of a given synapse depends not only on instantaneous pre- and postsynaptic activities but also on a slowly varying time-averaged value of the postsynaptic activity . Assuming an appropriate nonlinear form for this dependence , development of selectivity is obtained under quite general conditions on the sensory environment . One does not require nonlinearity of the neuron 's integrative power nor does one need to assume any particular form for intracortical circuitry . This is first illustrated in simple cases , e.g. , when the environment consists of only two different stimuli presented alternately in a r and om manner . The following formal statement then holds : the state of the system converges with probability 1 to points of maximum selectivity in the state space . We next consider the problem of early development of  orientation selectivity and binocular interaction in primary visual cortex . Giving the environment an appropriate form , we obtain orientation tuning curves and ocular dominance comparable to what is observed in normally reared adult cats or monkeys . Simulations with binocular input and various types of normal or altered environments show good agreement with the relevant experimental data . Experiments are suggested that could test our theory further Background and Purpose — Modulation of activity in language networks using repetitive transcranial magnetic stimulation ( rTMS ) may possibly support recovery from poststroke aphasia . Case series and feasibility studies seem to indicate a therapeutic effect ; however , r and omized sham-controlled , proof-of-principle studies relating clinical effects to activation patterns are missing . Methods — Twenty-four patients with subacute poststroke aphasia were r and omized to a 10-day protocol of 20-minute inhibitory 1 Hz rTMS over the right triangular part of the posterior inferior frontal gyrus or sham stimulation , followed by 45 minutes of speech and language therapy .  Activity in language networks was measured with O-15-water  positron emission  tomography during verb generation before and after treatment . Language performance was assessed using the Aachen Aphasia Test battery . Results — The primary outcome measure , global Aachen Aphasia Test score change , was significantly higher in the rTMS group ( t test , P=0.003 ) . Increases were largest for subtest naming ( P=0.002 ) and tended to be higher for comprehension , token test , and writing ( P<0.1 ) . Patients in the rTMS group activated proportionally more voxels in the left hemisphere after treatment than before ( difference in activation volume index ) compared with sham-treated patients ( t test , P=0.002).There was a moderate but significant linear relationship between activation volume index change and global Aachen Aphasia Test score change ( r2=0.25 ; P=0.015 ) . Conclusions — Ten sessions of inhibitory rTMS over the right posterior inferior frontal gyrus , in combination with speech and language therapy , significantly improve language recovery in subacute ischemic stroke and favor recruitment of left-hemispheric language networks Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke . The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome . In one influential account of spatial neglect , interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere , result ing in a biased attentional allocation towards the right hemifield . Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional , intact hemisphere and thereby improve spatial neglect symptoms . However , it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour . The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour . We applied the Catherine Bergego Scale , a st and ardized observation question naire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living . Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional , left posterior parietal cortex in patients suffering from subacute left spatial neglect , in a r and omized , double-blind , sham-controlled design , which also included a control group of neglect patients without stimulation . The results showed a 37 % improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation . Remarkably , the improvement persisted for at least 3 weeks after stimulation . The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests . No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation . These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour BACKGROUND Preceding low-frequency repetitive transcranial magnetic stimulation ( rTMS ) with a bout of high-frequency rTMS called priming potentiates the after-effects of the former in healthy adults . The utility of primed rTMS in stroke remains under-explored despite its theoretical benefits in enhancing cortical excitability and motor function . OBJECTIVE To ascertain the efficacy of priming in chronic stroke by comparing changes in cortical excitability and paretic h and function following three types of primed low-frequency rTMS treatments . METHODS Eleven individuals with chronic stroke participated in this repeated- measures study receiving three treatments to the contralesional primary motor cortex in r and omized order : 6 Hz primed 1 Hz rTMS , 1 Hz primed 1 Hz rTMS , and sham 6 Hz primed active 1 Hz rTMS . Within- and between-treatment differences from baseline in cortical excitability and paretic h and function from baseline were analyzed using mixed effects linear models . RESULTS 6 Hz primed 1 Hz rTMS produced significant within-treatment differences from baseline in ipsilesional cortical silent period ( CSP ) duration and short-interval intracortical inhibition . Compared to 1 Hz priming and sham 6 Hz priming of 1 Hz rTMS , active 6 Hz priming generated significantly greater decreases in ipsilesional CSP duration . These heightened effects were not observed for intracortical facilitation or interhemispheric inhibition excitability measures . CONCLUSION Our findings demonstrate the efficacy of 6 Hz primed 1 Hz rTMS in probing homeostatic plasticity mechanisms in the stroke brain as best demonstrated by differences CSP duration and SICI from baseline . Though 6 Hz priming did not universally enhance cortical excitability across measures , our findings pose important implication s in non-invasive brain stimulation application in stroke rehabilitation A systematic review of the effectiveness of rehabilitation for persons with unilateral neglect ( UN ) after stroke was conducted by search ing the computerized data bases from 1997 through 2012 . R and omized controlled trials ( RCTs ) of neglect treatment strategies for stroke patients which used the Behavioral Inattention Test ( BIT ) as the primary outcome measure were eligible for inclusion . Out of 201 studies initially identified , 12 RCTs covering 277 participants were selected for analysis . All had the same weakness of low power with smaller sample s and limitation in the blinding of the design .  Prism Adaptation ( PA )  was the most commonly used intervention while continuous Theta-burst stimulation ( cTBS ) appeared to be a new approach . Meta- analysis showed that for immediate effects , the BIT conventional subscore had a significant and large mean effect size ( ES = 0.76 ; 95 % CI 0.28–1.23 ; p = 0.002 ) whereas the BIT total score showed a modestly significant mean ES ( ES = 0.55 ; 95 % CI 0.16–0.94 ; p = 0.006 ) . No significant mean ES in sensitivity analysis was found for long-lasting effects across all BIT outcomes . PA appeared to be the most effective intervention based on the results of pooled analysis . More rigorous studies should be done on repetitive transcranial magnetic stimulation ( rTMS ) before it can be concluded that it is a promising treatment for UN Low-frequency repetitive transcranial magnetic stimulation ( rTMS ) of the unaffected hemisphere can enhance function of the paretic h and in patients with mild motor impairment . Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown . In this pilot , r and omized , double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpat 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The authors investigated the use of slow-frequency repetitive transcranial magnetic stimulation ( rTMS ) to the unaffected hemisphere to decrease interhemispheric inhibition of the lesioned hemisphere and improve motor function in patients within 12 months of a stroke . Patients showed a significant decrease in simple and choice reaction time and improved performance of the Purdue Pegboard test with their affected h and after rTMS of the motor cortex in the intact hemisphere as compared with sham rTMS Objective : To investigate the long-term behavioral and neurophysiologic effects of combined time-locked repetitive transcranial magnetic stimulation ( rTMS ) and physical therapy ( PT ) intervention in chronic stroke patients with mild motor disabilities . Methods : Thirty patients were enrolled in a double-blind , r and omized , single-center clinical trial . Patients received 10 daily sessions of 1 Hz rTMS over the intact motor cortex . In different groups , stimulation was either real ( rTMSR ) or sham ( rTMSS ) and was administered either immediately before or after PT . Outcome measures included dexterity , force , interhemispheric inhibition , and corticospinal excitability and were assessed for 3 months after the end of treatment . Results : Treatment induced cumulative rebalance of excitability in the 2 hemispheres and a reduction of interhemispheric inhibition in the rTMSR groups . Use-dependent improvements were detected in all groups . Improvements in trained abilities were small and transitory in rTMSS patients . Greater behavioral and neurophysiologic outcomes were found after rTMSR , with the group receiving rTMSR before PT ( rTMSR-PT ) showing robust and stable improvements and the other group ( PT-rTMSR ) showing a slight improvement decline over time . Conclusion : Our findings indicate that priming PT with inhibitory rTMS is optimal to boost use-dependent plasticity and rebalance motor excitability and suggest that time-locked rTMS is a valid and promising approach for chronic stroke patients with mild motor impairment . Classification of evidence : This interventional study provides Class I evidence that time-locked rTMS before or after physical therapy improves measures of dexterity and force in the affected limb in patients with chronic deficits more than 6 months poststroke . Neurology ® Objective : Cortico-cortical circuits originating from the posterior parietal cortex ( PPC ) of the intact left hemisphere ( LH ) may become hyperexcitable in patients with hemispatial neglect due to a right hemispheric ( RH ) stroke . Methods : In the current r and omized , double-blind , sham-controlled study , we investigated safety and efficacy of continuous theta-burst stimulation ( cTBS ) in 10 sessions over 2 weeks applied over the intact PPC of the LH in subacute ischemic stroke patients .  Severity of neglect was assessed through the st and ardized Behavioral Inattention Test ( BIT ) . We also measured , by means of bifocal transcranial magnetic stimulation ( TMS ) , how cTBS modified the excitability of the parieto-frontal functional connections in the intact LH . Results : We found that 2 weeks of cTBS , but not sham cTBS , were effective in improving neglect symptoms as measured by BIT score . BIT scores improved by 16.3 % after 2 weeks of cTBS and 22.6 % at 1 month follow-up . We also found that hyperexcitability of LH parieto-frontal circuits was reduced following treatment with real but not sham cTBS . Conclusion : These findings suggest that a 2-week course of cTBS over the LH PPC may be a potential effective strategy in accelerating recovery from visuospatial neglect in subacute stroke patients , possibly counteracting the hyperexcitability of LH parieto-frontal circuits . Classification of evidence : This study provides Class III evidence that left posterior parietal cortex theta-burst stimulation improves hemispatial neglect for up to 2 weeks after treatment Abstract Background : Functional neuroimaging studies with poststroke aphasia patients have shown increased activation of the unaffected hemisphere , which hypothetically reflects a maladaptive strategy of brain reorganization . Objective : We investigated whether repetitive transcranial magnetic stimulation ( rTMS ) inhibiting the right-hemisphere homologue of Broca ’s area improves language restitution if combined with speech/ language therapy . Methods : Forty aphasic patients during the subacute phase of ischemic stroke were r and omized to a 3-week aphasia rehabilitation protocol in combination with real or sham rTMS .  Naming , repetition , and comprehension were assessed using the Boston Diagnostic Aphasia Examination at baseline , immediately after therapy , and 15 weeks after completing treatment . Results : Although language functions improved in both experimental and control groups after 3 weeks , only slight group differences in degree of recovery were revealed between patients receiving rTMS and control participants . Follow-up revealed that severely aphasic rTMS patients demonstrated significantly greater improvement than patients receiving sham stimulation in repetition . Conclusions : Inhibitory rTMS applied to the right frontal language homologue is not effective for all poststroke aphasia patients , although it might benefit selected patients The development of  stimulus selectivity in the primary sensory cortex of higher vertebrates is considered in a general mathematical framework . A synaptic evolution scheme of a new kind is proposed in which incoming patterns rather than converging afferents compete . The change in the efficacy of a given synapse depends not only on instantaneous pre- and postsynaptic activities but also on a slowly varying time-averaged value of the postsynaptic activity . Assuming an appropriate nonlinear form for this dependence , development of selectivity is obtained under quite general conditions on the sensory environment . One does not require nonlinearity of the neuron 's integrative power nor does one need to assume any particular form for intracortical circuitry . This is first illustrated in simple cases , e.g. , when the environment consists of only two different stimuli presented alternately in a r and om manner . The following formal statement then holds : the state of the system converges with probability 1 to points of maximum selectivity in the state space . We next consider the problem of early development of  orientation selectivity and binocular interaction in primary visual cortex . Giving the environment an appropriate form , we obtain orientation tuning curves and ocular dominance comparable to what is observed in normally reared adult cats or monkeys . Simulations with binocular input and various types of normal or altered environments show good agreement with the relevant experimental data . Experiments are suggested that could test our theory further Background and Purpose — Modulation of activity in language networks using repetitive transcranial magnetic stimulation ( rTMS ) may possibly support recovery from poststroke aphasia . Case series and feasibility studies seem to indicate a therapeutic effect ; however , r and omized sham-controlled , proof-of-principle studies relating clinical effects to activation patterns are missing . Methods — Twenty-four patients with subacute poststroke aphasia were r and omized to a 10-day protocol of 20-minute inhibitory 1 Hz rTMS over the right triangular part of the posterior inferior frontal gyrus or sham stimulation , followed by 45 minutes of speech and language therapy .  Activity in language networks was measured with O-15-water  positron emission  tomography during verb generation before and after treatment . Language performance was assessed using the Aachen Aphasia Test battery . Results — The primary outcome measure , global Aachen Aphasia Test score change , was significantly higher in the rTMS group ( t test , P=0.003 ) . Increases were largest for subtest naming ( P=0.002 ) and tended to be higher for comprehension , token test , and writing ( P<0.1 ) . Patients in the rTMS group activated proportionally more voxels in the left hemisphere after treatment than before ( difference in activation volume index ) compared with sham-treated patients ( t test , P=0.002).There was a moderate but significant linear relationship between activation volume index change and global Aachen Aphasia Test score change ( r2=0.25 ; P=0.015 ) . Conclusions — Ten sessions of inhibitory rTMS over the right posterior inferior frontal gyrus , in combination with speech and language therapy , significantly improve language recovery in subacute ischemic stroke and favor recruitment of left-hemispheric language networks Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke . The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome . In one influential account of spatial neglect , interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere , result ing in a biased attentional allocation towards the right hemifield . Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional , intact hemisphere and thereby improve spatial neglect symptoms . However , it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour . The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour . We applied the Catherine Bergego Scale , a st and ardized observation question naire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living . Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional , left posterior parietal cortex in patients suffering from subacute left spatial neglect , in a r and omized , double-blind , sham-controlled design , which also included a control group of neglect patients without stimulation . The results showed a 37 % improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation . Remarkably , the improvement persisted for at least 3 weeks after stimulation . The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests . No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation . These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour BACKGROUND Preceding low-frequency repetitive transcranial magnetic stimulation ( rTMS ) with a bout of high-frequency rTMS called priming potentiates the after-effects of the former in healthy adults . The utility of primed rTMS in stroke remains under-explored despite its theoretical benefits in enhancing cortical excitability and motor function . OBJECTIVE To ascertain the efficacy of priming in chronic stroke by comparing changes in cortical excitability and paretic h and function following three types of primed low-frequency rTMS treatments . METHODS Eleven individuals with chronic stroke participated in this repeated- measures study receiving three treatments to the contralesional primary motor cortex in r and omized order : 6 Hz primed 1 Hz rTMS , 1 Hz primed 1 Hz rTMS , and sham 6 Hz primed active 1 Hz rTMS . Within- and between-treatment differences from baseline in cortical excitability and paretic h and function from baseline were analyzed using mixed effects linear models . RESULTS 6 Hz primed 1 Hz rTMS produced significant within-treatment differences from baseline in ipsilesional cortical silent period ( CSP ) duration and short-interval intracortical inhibition . Compared to 1 Hz priming and sham 6 Hz priming of 1 Hz rTMS , active 6 Hz priming generated significantly greater decreases in ipsilesional CSP duration . These heightened effects were not observed for intracortical facilitation or interhemispheric inhibition excitability measures . CONCLUSION Our findings demonstrate the efficacy of 6 Hz primed 1 Hz rTMS in probing homeostatic plasticity mechanisms in the stroke brain as best demonstrated by differences CSP duration and SICI from baseline . Though 6 Hz priming did not universally enhance cortical excitability across measures , our findings pose important implication s in non-invasive brain stimulation application in stroke rehabilitation A systematic review of the effectiveness of rehabilitation for persons with unilateral neglect ( UN ) after stroke was conducted by search ing the computerized data bases from 1997 through 2012 . R and omized controlled trials ( RCTs ) of neglect treatment strategies for stroke patients which used the Behavioral Inattention Test ( BIT ) as the primary outcome measure were eligible for inclusion . Out of 201 studies initially identified , 12 RCTs covering 277 participants were selected for analysis . All had the same weakness of low power with smaller sample s and limitation in the blinding of the design .  Prism Adaptation ( PA )  was the most commonly used intervention while continuous Theta-burst stimulation ( cTBS ) appeared to be a new approach . Meta- analysis showed that for immediate effects , the BIT conventional subscore had a significant and large mean effect size ( ES = 0.76 ; 95 % CI 0.28–1.23 ; p = 0.002 ) whereas the BIT total score showed a modestly significant mean ES ( ES = 0.55 ; 95 % CI 0.16–0.94 ; p = 0.006 ) . No significant mean ES in sensitivity analysis was found for long-lasting effects across all BIT outcomes . PA appeared to be the most effective intervention based on the results of pooled analysis . More rigorous studies should be done on repetitive transcranial magnetic stimulation ( rTMS ) before it can be concluded that it is a promising treatment for UN Low-frequency repetitive transcranial magnetic stimulation ( rTMS ) of the unaffected hemisphere can enhance function of the paretic h and in patients with mild motor impairment . Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown . In this pilot , r and omized , double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpat 
    Output:
    