Binith Cheeran - Academia.edu (original) (raw)

Papers by Binith Cheeran

Research paper thumbnail of Motor cortical physiology in patients and asymptomatic carriers of parkin gene mutations

Movement Disorders, 2008

Autosomal recessive parkin (PARK2) gene-related parkinsonism may be phenotypically and pathophysi... more Autosomal recessive parkin (PARK2) gene-related parkinsonism may be phenotypically and pathophysiologically distinct from idiopathic Parkinson's disease (PD). Furthermore, asymptomatic subjects carrying a single parkin mutation (''parkin carriers'') may show striatal dopaminergic dysfunction and increased cortical movement-related activation. Here, we used transcranial magnetic stimulation (TMS) to study corticospinal and intracortical excitability in manifesting parkin patients and asymptomatic carriers. We studied resting and active motor thresholds (RMT/AMT), central motor conduction time (CMCT), active recruitment curves, short-interval intracortical inhibition (SICI) and facilitation (ICF), SICI recruitment curve, and cortical silent period (CSP) in 8 patients ''off'' medication, 7 carriers, and two groups of age-matched controls (n 5 21). Patients had longer CMCTs compared to controls with a significant negative correlation between CMCT duration and onset age (r 5 20.83, P 5 0.04). Carriers had increased RMT/AMT; the time course of SICI/ICF and the duration of CSP were normal in both patients and carriers; however slight abnormalities in the recruitment of SICI were found in the carriers. Prolonged CMCT and normal cortical inhibitory mechanisms in parkin patients may be of value in the differentiation from idiopathic PD. The subclinical electrophysiological abnormalities found in carriers may represent underlying compensatory mechanisms.

Research paper thumbnail of Functional interplay between posterior parietal and ipsilateral motorcortex revealed by twin-coil transcranial magnetic stimulation duringreach planning toward contralateral space

Posterior parietal cortex (PPC) has connections with motor and premotor cortex, thought to transf... more Posterior parietal cortex (PPC) has connections with motor and premotor cortex, thought to transfer information relevant for planning movements in space. We used twin-coil transcranial magnetic stimulation (tcTMS) methods to show that the functional interplay between human right PPC and ipsilateral motor cortex (M1) varies with current motor plans. tcTMS during the reaction time of a reach task revealed facilitatory influences of right PPC on right M1 only when planning a (contralateral) leftward rather than rightward reach, at two specific time intervals (50 and 125 ms) after an auditory cue. The earlier reach-direction-specific facilitatory influence from PPC on M1 occurred when subjects were blindfolded or when the targets were presented briefly, so that visual feedback corrections could not occur. PPC-M1 interplay was similar within the left hemisphere but was specific to (contralateral) rightward planned reaches, with peaks at 50 and 100 ms. Functional interplay between human parietal and motor cortex is enhanced during early stages of planning a reach in the contralateral direction.

Research paper thumbnail of Inter-individual Variability in Response to Non-invasive Brain Stimulation Paradigms

Background: Non-invasive Brain Stimulation (NIBS) paradigms are unique in their ability to safely... more Background: Non-invasive Brain Stimulation (NIBS) paradigms are unique in their ability to safely modulate cortical plasticity for experimental or therapeutic applications. However, increasingly, there is concern regarding inter-individual variability in the efficacy and reliability of these paradigms. Hypothesis: Inter-individual variability in response to NIBS paradigms would be better explained if a multimodal distribution was assumed. Methods: In three different sessions for each subject (n ¼ 56), we studied the Paired Associative Stimulation (PAS 25 ), Anodal transcranial DC stimulation (AtDCS) and intermittent theta burst stimulation (iTBS) protocols. We applied cluster analysis to detect distinct patterns of response between individuals. Furthermore, we tested whether baseline TMS measures (such as short intracortical inhibition (SICI), resting motor threshold (RMT)) or factors such as time of day could predict each individual's response pattern.

Research paper thumbnail of A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS

The Journal of physiology, 2008

The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence synap... more The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence synaptic plasticity in the adult brain and shows a common single nucleotide polymorphism (BDNF Val66Met) in the normal population that is associated with differences in hippocampal volume and episodic memory. It is also thought to influence possible synaptic changes in motor cortex following a simple motor learning task. Here we extend these studies by using new non-invasive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) techniques that directly test the excitability and plasticity of neuronal circuits in human motor cortex in subjects at rest. We investigated whether the susceptibility to TMS probes of plasticity is significantly influenced by the BDNF polymorphism. Val66Met carriers were matched with Val66Val individuals and tested on the following protocols: continuous and intermittent theta burst TMS; median nerve paired associative stimulation;...

Research paper thumbnail of Hyperexcitability of parietal-motor functional connections in the intact left-hemisphere of patients with neglect

Brain : a journal of neurology, 2008

Hemispatial neglect is common after unilateral brain damage, particularly to perisylvian structur... more Hemispatial neglect is common after unilateral brain damage, particularly to perisylvian structures in the right-hemisphere (RH). In this disabling syndrome, behaviour and awareness are biased away from the contralesional side of space towards the ipsilesional side. Theoretical accounts of this in terms of hemispheric rivalry have speculated that the intact left-hemisphere (LH) may become hyper-excitable after a RH lesion, due to release of inhibition from the damaged hemisphere. We tested this directly using a novel twin-coil transcranial magnetic stimulation (TMS) approach to measure excitability within the intact LH of neglect patients. This involved applying a conditioning TMS pulse over left posterior parietal cortex (PPC), in order to test its effect on the amplitude of motor evoked potentials (MEPs) produced by a subsequent test pulse over left motor cortex (M1). Twelve RH stroke patients with neglect, an age-matched group of eight RH stroke patients without neglect, and 10 h...

Research paper thumbnail of TMS activation of interhemispheric pathways between the posterior parietal cortex and the contralateral motor cortex

The Journal of physiology, 2009

Using a twin coil transcranial magnetic stimulation (tc-TMS) approach we have previously demonstr... more Using a twin coil transcranial magnetic stimulation (tc-TMS) approach we have previously demonstrated that facilitation may be detected in the primary motor cortex (M1) following stimulation over the ipsilateral caudal intraparietal sulcus (cIPS). Here we tested the interhemispheric interactions between the IPS and the contralateral motor cortex (M1). We found that conditioning the right cIPS facilitated contralateral M1 when the conditioning stimulus had an intensity of 90% resting motor threshold (RMT) but not at 70% or 110% RMT. Facilitation was maximal when the interstimulus interval (ISI) between cIPS and M1 was 6 or 12 ms. These facilitatory effects were mediated by interactions with specific groups of interneurons in the contralateral M1. In fact, short intracortical inhibition (SICI) was reduced following cIPS stimulation. Moreover, additional comparison of facilitation of responses evoked by anterior-posterior versus posterior-anterior stimulation of M1 suggested that facil...

Research paper thumbnail of Focal stimulation of the posterior parietal cortex increases the excitability of the ipsilateral motor cortex

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 20, 2007

Paired-pulse transcranial magnetic stimulation (TMS) has been applied as a probe to test function... more Paired-pulse transcranial magnetic stimulation (TMS) has been applied as a probe to test functional connectivity within distinct cortical areas of the human motor system. Here, we tested the interaction between the posterior parietal cortex (PPC) and ipsilateral motor cortex (M1). A conditioning TMS pulse over the right PPC potentiates motor evoked-potentials evoked by a test TMS pulse over the ipsilateral motor cortex, with a time course characterized by two phases: an early peak at 4 ms interstimulus interval (ISI) and a late peak at 15 ms ISI. Activation of this facilitatory pathway depends on the intensity of stimulation, because the effects are induced with a conditioning stimulus of 90% resting motor threshold but not at lower or higher intensities. Similar results were obtained testing the ipsilateral interaction in the left hemisphere with a slightly different time course. In control experiments, we found that activation of this facilitatory pathway depends on the direction ...

Research paper thumbnail of The effect of BDNF val66met polymorphism on visuomotor adaptation

Experimental brain research, 2012

Brain-derived neurotrophic factor (BDNF) plays an important role in learning, memory, and brain p... more Brain-derived neurotrophic factor (BDNF) plays an important role in learning, memory, and brain plasticity. Humans with a val66met polymorphism in the BDNF gene have reduced levels of BDNF and alterations in motor learning and short-term cortical plasticity. In the current study, we sought to further explore the role of BDNF in motor learning by testing human subjects on a visuomotor adaptation task. In experiment 1, 21 subjects with the polymorphism (val/met) and 21 matched controls (val/val) were tested during learning, short-term retention (45 min), long-term retention (24 h), and de-adaptation of a 60° visuomotor deviation. We measured both mean error as well as rate of adaptation during each session. There was no difference in mean error between groups; however, val/met subjects had a reduced rate of adaptation during learning as well as during long-term retention, but not short-term retention or de-adaptation. In experiment 2, 12 val/met and 12 val/val subjects were tested on ...

Research paper thumbnail of The nature of tremor circuits in parkinsonian and essential tremor

Brain : a journal of neurology, 2014

Tremor is a cardinal feature of Parkinson's disease and essential tremor, the two most common... more Tremor is a cardinal feature of Parkinson's disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient's own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson's disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50-77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34-74 years). Stimulation at near-to tremor frequency entrained trem...

Research paper thumbnail of The contribution of transcranial magnetic stimulation in the diagnosis and in the management of dementia

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2014

Transcranial magnetic stimulation (TMS) is emerging as a promising tool to non-invasively assess ... more Transcranial magnetic stimulation (TMS) is emerging as a promising tool to non-invasively assess specific cortical circuits in neurological diseases. A number of studies have reported the abnormalities in TMS assays of cortical function in dementias. A PubMed-based literature review on TMS studies targeting primary and secondary dementia has been conducted using the key words "transcranial magnetic stimulation" or "motor cortex excitability" and "dementia" or "cognitive impairment" or "memory impairment" or "memory decline". Cortical excitability is increased in Alzheimer's disease (AD) and in vascular dementia (VaD), generally reduced in secondary dementias. Short-latency afferent inhibition (SAI), a measure of central cholinergic circuitry, is normal in VaD and in frontotemporal dementia (FTD), but suppressed in AD. In mild cognitive impairment, abnormal SAI may predict the progression to AD. No change in cortical exc...

Research paper thumbnail of transcranial magnetic stimulation and patients with cortical or subcortical dysfunction Neural networks engaged in milliseconds and seconds time processing: evidence from

Several studies have suggested that the cerebellum has an important role in timing of subsecond i... more Several studies have suggested that the cerebellum has an important role in timing of subsecond intervals. Previous studies using transcranial magnetic stimulation (TMS) to test this hypothesis directly have produced inconsistent results. Here we used 1-Hz repetitive TMS (rTMS) for 10 min over the right or left cerebellar hemisphere to interfere transiently with cerebellar processing to assess its effect on the performance of a finger-tapping task. Subjects tapped with their right index finger for 1 min (synchronization phase) with an auditory or visual cue at 0.5, 1, or 2 Hz; they continued for a further 1 min at the same rate with no cues (continuation phase). The blocks of trials were performed in a random order. rTMS of the cerebellum ipsilateral to the movement increased the variability of the intertap interval but only for movements at 2 Hz that were made while subjects were synchronizing with an auditory cue. There was no effect on the continuation phase of the task when the cues were no longer present or on synchronization with a visual cue. Similar results were seen after stimulation over the contralateral dorsal premotor cortex but not after rTMS over supplementary motor area. There was no effect after rTMS over the ipsilateral right cervical nerve roots or over the ipsilateral primary motor cortex. The results support the hypothesis of neural network for event-related timing in the subsecond range that involves a cerebellar-premotor network.

Research paper thumbnail of Ventral premotor to primary motor cortical interactions during noxious and naturalistic action observation

Neuropsychologia, 2010

Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral pre... more Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral premotor cortex (PMv), are thought to be activated during the observation of actions performed by others. However, it is not known how the connections between these areas become active during action observation or whether these connections are modulated by the volitional component induced by the action observed. In this study, using a paired pulse transcranial magnetic stimulation (ppTMS) method, we evaluated the excitability of PMv-M1 connections during the observation of videos showing a human hand reaching to grasp a ball (naturalistic grasping video) or a switched on soldering iron (noxious grasping video). The results show that the observation of the naturalistic grasping action increased the M1 excitability and changed the strength of the PMv-M1 connections. The observation of the noxious grasping action did not induce any change in the excitability of the PMv-M1 connections throughout the video, but the strength of PMv-M1 connectivity was reduced. These results demonstrate that the PMv-M1 connections are modulated differently depending on whether the action observed would or would not be performed in real life.

Research paper thumbnail of Altered dorsal premotor–motor interhemispheric pathway activity in focal arm dystonia

Movement Disorders, 2008

Given the possible role of dorsal premotor cortex (PMd) in the pathophysiology of dystonia, we us... more Given the possible role of dorsal premotor cortex (PMd) in the pathophysiology of dystonia, we used transcranial magnetic stimulation (TMS) methods to study PMd and PMdprimary motor cortex (M1) interactions in patients with focal arm dystonia. Here, we tested the connectivity between left PMd and right M1 as well as the intracortical excitability of PMd in 11 right-handed patients with focal arm/hand dystonia and nine age-matched healthy controls. The results showed that excitability of the inhibitory connection between PMd and M1 was reduced in patients, but there was no significant difference to healthy subjects in the excitability of the facilitatory connection. A triple stimulation technique in which pairs of TMS pulses are given over PMd and their interaction measured in terms of the effect on the baseline PMd-M1 connection failed to reveal the usual pattern of interaction between the pairs of PMd stimuli. Indeed, the results in patients were similar to those seen in a group of young healthy subjects after the excitability of PMd had been changed by pretreatment with high-frequency rTMS. We suggest that reduced transcallosal inhibition from the PMd may be involved in the altered pattern of abnormal muscle contractions of agonists and antagonists (overflow).

Research paper thumbnail of Relationship between Non-invasive Brain Stimulation-induced plasticity and capacity for motor learning

Research paper thumbnail of Motor cortical physiology in patients and asymptomatic carriers of parkin gene mutations

Movement Disorders, 2008

Autosomal recessive parkin (PARK2) gene-related parkinsonism may be phenotypically and pathophysi... more Autosomal recessive parkin (PARK2) gene-related parkinsonism may be phenotypically and pathophysiologically distinct from idiopathic Parkinson's disease (PD). Furthermore, asymptomatic subjects carrying a single parkin mutation (''parkin carriers'') may show striatal dopaminergic dysfunction and increased cortical movement-related activation. Here, we used transcranial magnetic stimulation (TMS) to study corticospinal and intracortical excitability in manifesting parkin patients and asymptomatic carriers. We studied resting and active motor thresholds (RMT/AMT), central motor conduction time (CMCT), active recruitment curves, short-interval intracortical inhibition (SICI) and facilitation (ICF), SICI recruitment curve, and cortical silent period (CSP) in 8 patients ''off'' medication, 7 carriers, and two groups of age-matched controls (n 5 21). Patients had longer CMCTs compared to controls with a significant negative correlation between CMCT duration and onset age (r 5 20.83, P 5 0.04). Carriers had increased RMT/AMT; the time course of SICI/ICF and the duration of CSP were normal in both patients and carriers; however slight abnormalities in the recruitment of SICI were found in the carriers. Prolonged CMCT and normal cortical inhibitory mechanisms in parkin patients may be of value in the differentiation from idiopathic PD. The subclinical electrophysiological abnormalities found in carriers may represent underlying compensatory mechanisms.

Research paper thumbnail of Functional interplay between posterior parietal and ipsilateral motorcortex revealed by twin-coil transcranial magnetic stimulation duringreach planning toward contralateral space

Posterior parietal cortex (PPC) has connections with motor and premotor cortex, thought to transf... more Posterior parietal cortex (PPC) has connections with motor and premotor cortex, thought to transfer information relevant for planning movements in space. We used twin-coil transcranial magnetic stimulation (tcTMS) methods to show that the functional interplay between human right PPC and ipsilateral motor cortex (M1) varies with current motor plans. tcTMS during the reaction time of a reach task revealed facilitatory influences of right PPC on right M1 only when planning a (contralateral) leftward rather than rightward reach, at two specific time intervals (50 and 125 ms) after an auditory cue. The earlier reach-direction-specific facilitatory influence from PPC on M1 occurred when subjects were blindfolded or when the targets were presented briefly, so that visual feedback corrections could not occur. PPC-M1 interplay was similar within the left hemisphere but was specific to (contralateral) rightward planned reaches, with peaks at 50 and 100 ms. Functional interplay between human parietal and motor cortex is enhanced during early stages of planning a reach in the contralateral direction.

Research paper thumbnail of Inter-individual Variability in Response to Non-invasive Brain Stimulation Paradigms

Background: Non-invasive Brain Stimulation (NIBS) paradigms are unique in their ability to safely... more Background: Non-invasive Brain Stimulation (NIBS) paradigms are unique in their ability to safely modulate cortical plasticity for experimental or therapeutic applications. However, increasingly, there is concern regarding inter-individual variability in the efficacy and reliability of these paradigms. Hypothesis: Inter-individual variability in response to NIBS paradigms would be better explained if a multimodal distribution was assumed. Methods: In three different sessions for each subject (n ¼ 56), we studied the Paired Associative Stimulation (PAS 25 ), Anodal transcranial DC stimulation (AtDCS) and intermittent theta burst stimulation (iTBS) protocols. We applied cluster analysis to detect distinct patterns of response between individuals. Furthermore, we tested whether baseline TMS measures (such as short intracortical inhibition (SICI), resting motor threshold (RMT)) or factors such as time of day could predict each individual's response pattern.

Research paper thumbnail of A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS

The Journal of physiology, 2008

The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence synap... more The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence synaptic plasticity in the adult brain and shows a common single nucleotide polymorphism (BDNF Val66Met) in the normal population that is associated with differences in hippocampal volume and episodic memory. It is also thought to influence possible synaptic changes in motor cortex following a simple motor learning task. Here we extend these studies by using new non-invasive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) techniques that directly test the excitability and plasticity of neuronal circuits in human motor cortex in subjects at rest. We investigated whether the susceptibility to TMS probes of plasticity is significantly influenced by the BDNF polymorphism. Val66Met carriers were matched with Val66Val individuals and tested on the following protocols: continuous and intermittent theta burst TMS; median nerve paired associative stimulation;...

Research paper thumbnail of Hyperexcitability of parietal-motor functional connections in the intact left-hemisphere of patients with neglect

Brain : a journal of neurology, 2008

Hemispatial neglect is common after unilateral brain damage, particularly to perisylvian structur... more Hemispatial neglect is common after unilateral brain damage, particularly to perisylvian structures in the right-hemisphere (RH). In this disabling syndrome, behaviour and awareness are biased away from the contralesional side of space towards the ipsilesional side. Theoretical accounts of this in terms of hemispheric rivalry have speculated that the intact left-hemisphere (LH) may become hyper-excitable after a RH lesion, due to release of inhibition from the damaged hemisphere. We tested this directly using a novel twin-coil transcranial magnetic stimulation (TMS) approach to measure excitability within the intact LH of neglect patients. This involved applying a conditioning TMS pulse over left posterior parietal cortex (PPC), in order to test its effect on the amplitude of motor evoked potentials (MEPs) produced by a subsequent test pulse over left motor cortex (M1). Twelve RH stroke patients with neglect, an age-matched group of eight RH stroke patients without neglect, and 10 h...

Research paper thumbnail of TMS activation of interhemispheric pathways between the posterior parietal cortex and the contralateral motor cortex

The Journal of physiology, 2009

Using a twin coil transcranial magnetic stimulation (tc-TMS) approach we have previously demonstr... more Using a twin coil transcranial magnetic stimulation (tc-TMS) approach we have previously demonstrated that facilitation may be detected in the primary motor cortex (M1) following stimulation over the ipsilateral caudal intraparietal sulcus (cIPS). Here we tested the interhemispheric interactions between the IPS and the contralateral motor cortex (M1). We found that conditioning the right cIPS facilitated contralateral M1 when the conditioning stimulus had an intensity of 90% resting motor threshold (RMT) but not at 70% or 110% RMT. Facilitation was maximal when the interstimulus interval (ISI) between cIPS and M1 was 6 or 12 ms. These facilitatory effects were mediated by interactions with specific groups of interneurons in the contralateral M1. In fact, short intracortical inhibition (SICI) was reduced following cIPS stimulation. Moreover, additional comparison of facilitation of responses evoked by anterior-posterior versus posterior-anterior stimulation of M1 suggested that facil...

Research paper thumbnail of Focal stimulation of the posterior parietal cortex increases the excitability of the ipsilateral motor cortex

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 20, 2007

Paired-pulse transcranial magnetic stimulation (TMS) has been applied as a probe to test function... more Paired-pulse transcranial magnetic stimulation (TMS) has been applied as a probe to test functional connectivity within distinct cortical areas of the human motor system. Here, we tested the interaction between the posterior parietal cortex (PPC) and ipsilateral motor cortex (M1). A conditioning TMS pulse over the right PPC potentiates motor evoked-potentials evoked by a test TMS pulse over the ipsilateral motor cortex, with a time course characterized by two phases: an early peak at 4 ms interstimulus interval (ISI) and a late peak at 15 ms ISI. Activation of this facilitatory pathway depends on the intensity of stimulation, because the effects are induced with a conditioning stimulus of 90% resting motor threshold but not at lower or higher intensities. Similar results were obtained testing the ipsilateral interaction in the left hemisphere with a slightly different time course. In control experiments, we found that activation of this facilitatory pathway depends on the direction ...

Research paper thumbnail of The effect of BDNF val66met polymorphism on visuomotor adaptation

Experimental brain research, 2012

Brain-derived neurotrophic factor (BDNF) plays an important role in learning, memory, and brain p... more Brain-derived neurotrophic factor (BDNF) plays an important role in learning, memory, and brain plasticity. Humans with a val66met polymorphism in the BDNF gene have reduced levels of BDNF and alterations in motor learning and short-term cortical plasticity. In the current study, we sought to further explore the role of BDNF in motor learning by testing human subjects on a visuomotor adaptation task. In experiment 1, 21 subjects with the polymorphism (val/met) and 21 matched controls (val/val) were tested during learning, short-term retention (45 min), long-term retention (24 h), and de-adaptation of a 60° visuomotor deviation. We measured both mean error as well as rate of adaptation during each session. There was no difference in mean error between groups; however, val/met subjects had a reduced rate of adaptation during learning as well as during long-term retention, but not short-term retention or de-adaptation. In experiment 2, 12 val/met and 12 val/val subjects were tested on ...

Research paper thumbnail of The nature of tremor circuits in parkinsonian and essential tremor

Brain : a journal of neurology, 2014

Tremor is a cardinal feature of Parkinson's disease and essential tremor, the two most common... more Tremor is a cardinal feature of Parkinson's disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient's own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson's disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50-77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34-74 years). Stimulation at near-to tremor frequency entrained trem...

Research paper thumbnail of The contribution of transcranial magnetic stimulation in the diagnosis and in the management of dementia

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2014

Transcranial magnetic stimulation (TMS) is emerging as a promising tool to non-invasively assess ... more Transcranial magnetic stimulation (TMS) is emerging as a promising tool to non-invasively assess specific cortical circuits in neurological diseases. A number of studies have reported the abnormalities in TMS assays of cortical function in dementias. A PubMed-based literature review on TMS studies targeting primary and secondary dementia has been conducted using the key words "transcranial magnetic stimulation" or "motor cortex excitability" and "dementia" or "cognitive impairment" or "memory impairment" or "memory decline". Cortical excitability is increased in Alzheimer's disease (AD) and in vascular dementia (VaD), generally reduced in secondary dementias. Short-latency afferent inhibition (SAI), a measure of central cholinergic circuitry, is normal in VaD and in frontotemporal dementia (FTD), but suppressed in AD. In mild cognitive impairment, abnormal SAI may predict the progression to AD. No change in cortical exc...

Research paper thumbnail of transcranial magnetic stimulation and patients with cortical or subcortical dysfunction Neural networks engaged in milliseconds and seconds time processing: evidence from

Several studies have suggested that the cerebellum has an important role in timing of subsecond i... more Several studies have suggested that the cerebellum has an important role in timing of subsecond intervals. Previous studies using transcranial magnetic stimulation (TMS) to test this hypothesis directly have produced inconsistent results. Here we used 1-Hz repetitive TMS (rTMS) for 10 min over the right or left cerebellar hemisphere to interfere transiently with cerebellar processing to assess its effect on the performance of a finger-tapping task. Subjects tapped with their right index finger for 1 min (synchronization phase) with an auditory or visual cue at 0.5, 1, or 2 Hz; they continued for a further 1 min at the same rate with no cues (continuation phase). The blocks of trials were performed in a random order. rTMS of the cerebellum ipsilateral to the movement increased the variability of the intertap interval but only for movements at 2 Hz that were made while subjects were synchronizing with an auditory cue. There was no effect on the continuation phase of the task when the cues were no longer present or on synchronization with a visual cue. Similar results were seen after stimulation over the contralateral dorsal premotor cortex but not after rTMS over supplementary motor area. There was no effect after rTMS over the ipsilateral right cervical nerve roots or over the ipsilateral primary motor cortex. The results support the hypothesis of neural network for event-related timing in the subsecond range that involves a cerebellar-premotor network.

Research paper thumbnail of Ventral premotor to primary motor cortical interactions during noxious and naturalistic action observation

Neuropsychologia, 2010

Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral pre... more Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral premotor cortex (PMv), are thought to be activated during the observation of actions performed by others. However, it is not known how the connections between these areas become active during action observation or whether these connections are modulated by the volitional component induced by the action observed. In this study, using a paired pulse transcranial magnetic stimulation (ppTMS) method, we evaluated the excitability of PMv-M1 connections during the observation of videos showing a human hand reaching to grasp a ball (naturalistic grasping video) or a switched on soldering iron (noxious grasping video). The results show that the observation of the naturalistic grasping action increased the M1 excitability and changed the strength of the PMv-M1 connections. The observation of the noxious grasping action did not induce any change in the excitability of the PMv-M1 connections throughout the video, but the strength of PMv-M1 connectivity was reduced. These results demonstrate that the PMv-M1 connections are modulated differently depending on whether the action observed would or would not be performed in real life.

Research paper thumbnail of Altered dorsal premotor–motor interhemispheric pathway activity in focal arm dystonia

Movement Disorders, 2008

Given the possible role of dorsal premotor cortex (PMd) in the pathophysiology of dystonia, we us... more Given the possible role of dorsal premotor cortex (PMd) in the pathophysiology of dystonia, we used transcranial magnetic stimulation (TMS) methods to study PMd and PMdprimary motor cortex (M1) interactions in patients with focal arm dystonia. Here, we tested the connectivity between left PMd and right M1 as well as the intracortical excitability of PMd in 11 right-handed patients with focal arm/hand dystonia and nine age-matched healthy controls. The results showed that excitability of the inhibitory connection between PMd and M1 was reduced in patients, but there was no significant difference to healthy subjects in the excitability of the facilitatory connection. A triple stimulation technique in which pairs of TMS pulses are given over PMd and their interaction measured in terms of the effect on the baseline PMd-M1 connection failed to reveal the usual pattern of interaction between the pairs of PMd stimuli. Indeed, the results in patients were similar to those seen in a group of young healthy subjects after the excitability of PMd had been changed by pretreatment with high-frequency rTMS. We suggest that reduced transcallosal inhibition from the PMd may be involved in the altered pattern of abnormal muscle contractions of agonists and antagonists (overflow).

Research paper thumbnail of Relationship between Non-invasive Brain Stimulation-induced plasticity and capacity for motor learning