Frank Mastaglia - Academia.edu (original) (raw)

Papers by Frank Mastaglia

Research paper thumbnail of Transcranial magnetic stimulation reveals asymmetrical efficacy of intracortical circuits in primary motor cortex

Experimental brain …, Jan 1, 2004

The efficacy of inhibitory and excitatory intracortical circuits acting on the representation of ... more The efficacy of inhibitory and excitatory intracortical circuits acting on the representation of an intrinsic hand muscle in the primary motor cortex of both hemispheres was measured with paired transcranial magnetic stimuli in right-handed subjects. Both intracortical inhibition (measured with an interstimulus interval of 3 ms) and intracortical facilitation (measured with an interstimulus interval of 16 ms) developed more rapidly with increasing conditioning stimulus intensity in the dominant than the non-dominant hand. We conclude that the intracortical circuits in the primary motor cortex are more potent in the dominant than the non-dominant hemisphere, and hypothesize that this difference is a factor in the asymmetrical dexterity associated with hand preference.

Research paper thumbnail of DEPOSITION OF AMYLOID (A4) PROTEIN IN THE CEREBRAL CORTEX IN PARKINSON??S DISEASE (PD)

Alzheimer Disease & Associated Disorders, 1988

Research paper thumbnail of Transcranial magnetic stimulation of the human frontal eye field

Journal of the Neurological Sciences, 1996

The region of cortex over which transcranial magnetic stimulation (TMS) can delay saccadic eye mo... more The region of cortex over which transcranial magnetic stimulation (TMS) can delay saccadic eye movement was investigated. With TMS delivered in the reaction time foreperiod of auditory-triggered saccades, saccade onset could be delayed by up to 60 ms. The area of cortex over which TMS could delay saccade onset was located near the inter-aural line, approximately 6 cm lateral to the vertex, and was situated between areas over which TMS could generate motor evoked potentials in muscles of the hand and face. It is concluded that this area corresponds to the human frontal eye field and is closely associated with the motor strip, at a level between the representations of the hand and the face, and that stimulation of this region can interfere with the programming and execution of externally triggered saccades.

Research paper thumbnail of Johnson 2013 Clinical and posturographic correlates of falling in Parkinson's disease

Research paper thumbnail of Interactive effects of GPI stimulation and levodopa on postural control in Parkinson's disease

Gait & Posture, 2015

Postural instability is a major source of disability in idiopathic Parkinson&... more Postural instability is a major source of disability in idiopathic Parkinson's disease (IPD). Deep brain stimulation of the globus pallidus internus (GPI-DBS) improves clinician-rated balance control but there have been few quantitative studies of its interactive effects with levodopa (L-DOPA). The purpose of this study was to compare the short-term and interactive effects of GPI-DBS and L-DOPA on objective measures of postural stability in patients with longstanding IPD. Static and dynamic posturography during a whole-body leaning task were performed in 10 IPD patients with bilateral GPI stimulators under the following conditions: untreated (OFF); L-DOPA alone; DBS alone; DBS+L-DOPA, and in 9 healthy Control subjects. Clinical status was assessed using the UPDRS and AIMS Dyskinesia Scale. Static sway was greater in IPD patients in the OFF state compared to the Control subjects and was further increased by L-DOPA and reduced by GPI-DBS. In the dynamic task, L-DOPA had a greater effect than GPI-DBS on improving Start Time, but reduced the spatial accuracy and directional control of the task. When the two therapies were combined, GPI-DBS prevented the L-DOPA induced increase in static sway and improved the accuracy of the dynamic task. The findings demonstrate GPI-DBS and L-DOPA have differential effects on temporal and spatial aspects of postural control in IPD and that GPI-DBS counteracts some of the adverse effects of L-DOPA. Further studies on larger numbers of patients with GPI stimulators are required to confirm these findings and to clarify the contribution of dyskinesias to impaired dynamic postural control.

Research paper thumbnail of Cytokines in immune-mediated inflammatory myopathies: cellular sources, multiple actions and therapeutic implications

Clinical and experimental immunology, 2014

The idiopathic inflammatory myopathies are a heterogeneous group of disorders characterised by di... more The idiopathic inflammatory myopathies are a heterogeneous group of disorders characterised by diffuse muscle weakness and inflammation. A common immunopathogenic mechanism is the cytokine-driven infiltration of immune cells into the muscle tissue. Recent studies have further dissected the inflammatory cell types and associated cytokines involved in the immune-mediated myopathies and other chronic inflammatory and autoimmune disorders. In this review we outline the current knowledge of cytokine expression profiles and cellular sources in the major forms of inflammatory myopathy and detail the known mechanistic functions of these cytokines in the context of inflammatory myositis. Furthermore, we discuss how the application of this knowledge may lead to new therapeutic strategies for the treatment of the inflammatory myopathies, in particular for cases resistant to conventional forms of therapy.

Research paper thumbnail of The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications

Neuromuscular disorders : NMD, 2014

The idiopathic inflammatory myopathies are a heterogeneous group of autoimmune muscle disorders w... more The idiopathic inflammatory myopathies are a heterogeneous group of autoimmune muscle disorders with distinct clinical and pathological features and underlying immunopathogenic mechanisms. Traditionally, CD4(+) Th1 cells or CD8(+) cytotoxic effector T cells and type I/II interferons have been primarily implicated in the pathogenesis of the inflammatory myopathies. The presence of IL-17A producing cells in the inflamed muscle tissue of myositis patients and the results of in vitro studies suggest that IL-17A and the Th17 pathway may also have a key role in these diseases. The contribution of IL-17A to other chronic inflammatory and autoimmune diseases has been well established and clinical trials of IL-17A inhibitors are now at an advanced stage. However the precise role of IL-17A in the various forms of myositis and the potential for therapeutic targeting is currently unknown and warrants further investigation.

Research paper thumbnail of Spatio-temporal mapping of evoked cerebral activity

Electroencephalography and clinical neurophysiology, 1984

A technique is described for the colour-coded display of averaged scalp electrical activity at 40... more A technique is described for the colour-coded display of averaged scalp electrical activity at 40 instants in time. An application of this technique to the pattern reversal visual evoked potential is discussed, showing the value of spatio-temporal mapping in the interpretation of multichannel evoked potential recordings.

Research paper thumbnail of Dipole source derivation. Application to the half-field pattern evoked potential

International journal of bio-medical computing, 1985

Dipole modelling is a technique for estimating the location of sources of electrical activity in ... more Dipole modelling is a technique for estimating the location of sources of electrical activity in the brain responsible for the generation of surface recorded potentials on the human scalp. A detailed description of this technique is given with a modification that allows for possible activity at the reference electrode during the surface potential measurement. The application of this technique to localisation of the source of the principal components of the left half-field pattern visual evoked potential is described.

Research paper thumbnail of Averaging, spatio-temporal mapping and dipole modelling of focal epileptic spikes

Electroencephalography and clinical neurophysiology, 1986

A computer-based technique is described for the acquisition, spatio-temporal mapping and dipole m... more A computer-based technique is described for the acquisition, spatio-temporal mapping and dipole modelling of epileptic spike events. Spike acquisition is operator-controlled and subsequent data processing is performed off-line. Preliminary averaging and topographical display of wave forms provide complementary information on the spike field. The method promises to be a useful adjunct to conventional EEG in spike analysis.

Research paper thumbnail of Presaccadic spike potential. Relation to eye movement direction

Electroencephalography and clinical neurophysiology, 1986

The spike potential (SP) which precedes horizontal saccadic eye movement has been shown to arise ... more The spike potential (SP) which precedes horizontal saccadic eye movement has been shown to arise in the agonist lateral and medial rectus muscles of the two eyes. To determine whether other extra-ocular muscles also generate an SP, recordings were carried out in normal subjects performing vertical and oblique as well as horizontal saccades. An SP was recorded before saccades in all directions. The potential was highest in amplitude with horizontal or oblique abducting saccades and was higher in amplitude with vertical upgoing than downgoing saccades.

Research paper thumbnail of Cerebral events preceding self-paced and visually triggered saccades. A study of presaccadic potentials

Electroencephalography and clinical neurophysiology, 1985

The cerebral potentials preceding self-paced and visually triggered saccadic eye movements were s... more The cerebral potentials preceding self-paced and visually triggered saccadic eye movements were studied using multichannel recording and spatio-temporal mapping techniques, and the contribution to these potentials of stimulus-evoked activity and the electro-oculographic field was investigated. A premotor positivity (PMP) and negativity (PMN) comparable to those associated with movements of the extremities were found with both self-paced and triggered saccades, but there were differences in the amplitude, duration and topography of these potentials in the different types of eye movement. The slope of the PMP was greater for visually triggered than for self-paced saccades and its slope and duration were influenced by the predictability of the triggering stimulus, the slope being greater and the duration shorter with predictable than with unpredictable stimuli. The characteristics of this potential are compatible with an origin from saccade-related and visually sensitive neurons in par...

Research paper thumbnail of Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy

Seizure, 2015

Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibi... more Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibility of a paradoxical excitatory effect of GABA in epilepsy has been suggested, but has not been investigated in vivo. We investigated pre- and post-synaptic GABAergic mechanisms in patients with idiopathic generalised epilepsy (IGE). In 10 patients and 12 control subjects we explored short- and long-interval intracortical inhibition (SICI, LICI; post-synaptic GABAA and GABAB-mediated respectively) and long-interval intracortical facilitation (LICF; pre-synaptic disinhibition) using transcranial magnetic stimulation. While post-synaptic GABAB-mediated inhibition was unchanged in IGE (p=0.09), LICF was reduced compared to controls (controls: 141±17% of baseline; untreated patients: 107±12%, p=0.2; treated patients: 79±10%, p=0.003). GABAA-mediated inhibition was reduced in untreated patients (response amplitude 56±4% of baseline vs. 26±6% in controls, p=0.004) and normalised with treatment (37±12%, p=0.5 vs. controls). When measured during LICI, GABAA-mediated inhibition became excitatory in untreated IGE (response amplitude 120±10% of baseline, p=0.017), but not in treated patients. Pre- and post-synaptic GABA-mediated inhibitory mechanisms are altered in IGE. The findings lend in vivo support to evidence from experimental models and in vitro studies of human epileptic brain tissue that GABA may have a paradoxical excitatory role in ictogenesis.

Research paper thumbnail of Topography of excitatory and inhibitory muscle responses evoked by transcranial magnetic stimulation in the human motor cortex

Neuroscience Letters, 1993

Transcranial magnetic stimulation of the motor cortex produces a motor-evoked potential (MEP) in ... more Transcranial magnetic stimulation of the motor cortex produces a motor-evoked potential (MEP) in the electromyogram followed by a silent period (SP) which is thought to be due to cortical inhibition. In this study, the topography and size of the cortical areas from which an MEP and SP are evoked in the abductor pollicis brevis muscle (APB) of the hand were compared. The SP area was found to be large, encompassing and surrounding the MEP area. These findings infer the existence of an inhibitory surround limiting the excitatory area for APB in the human motor cortex.

Research paper thumbnail of Breakdown in central motor control can be attenuated by motor practice and neuro-modulation of the primary motor cortex

Neuroscience, 2012

Other uses, including reproduction and distribution, or selling or licensing copies, or posting t... more Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited.

Research paper thumbnail of Changes in corticomotor excitability and inhibition after exercise are influenced by hand dominance and motor demand

Neuroscience, 2012

Previous studies on handedness have often reported functional asymmetries in corticomotor excitab... more Previous studies on handedness have often reported functional asymmetries in corticomotor excitability (CME) associated with voluntary movement. Recently, we have shown that the degree of post-exercise corticomotor depression (PED) and increase in short-interval cortical inhibition (SICI) after a repetitive finger movement task was less when the task was performed at a maximal voluntary rate (MVR) than when it was performed at a submaximal sustainable rate (SR). In the current study, we have compared the time course of PED and SICI in the dominant (DOM) and nondominant (NDOM) hands after an MVR and SR finger movement task to determine the influence of hand dominance and task demand. We tracked motor-evoked potential (MEP) amplitude from the first dorsal interosseous muscle of the DOM and NDOM hand for 20 min after a 10-s index finger flexion-extension task at MVR and SR. For all hand-task combinations, we report a period of PED and increased SICI lasting for up to 8 min. We find that the least demanding task, one that involved index finger movement of the DOM hand at SR, was associated with the greatest change in PED and SICI from baseline (63.6؎5.7% and 79؎2%, P<0.001, PED and SICI, respectively), whereas the most demanding task (MVR of the NDOM hand) was associated with the least change from baseline (PED: 88.1؎3.6%, SICI: 103؎2%; P<0.001). Our findings indicate that the changes in CME and inhibition associated with repetitive finger movement are influenced both by handedness and the degree of demand of the motor task and are inversely related to task demand, being smallest for an MVR task of the NDOM hand and greatest for an SR task of the DOM hand. The findings provide additional evidence for differences in neuronal processing between the dominant and nondominant hemispheres in motor control.

Research paper thumbnail of Saccadic eye movements in multiple sclerosis*

Neuro-Ophthalmology, 1982

Research paper thumbnail of Genetic polymorphisms of the N-acetyltransferase genes and risk of Parkinson's disease

Research paper thumbnail of The α-synuclein gene is not a major risk factor in familial Parkinson disease

Research paper thumbnail of Changes in corticomotor excitation and inhibition during prolonged submaximal muscle contractions

Muscle & Nerve, 1997

Changes in motor evoked potential (MEP) amplitude, post-MEP silent period duration, and interpola... more Changes in motor evoked potential (MEP) amplitude, post-MEP silent period duration, and interpolated twitch torque were measured using transcranial magnetic (TMS) and electrical (TES) stimulation during a 20% maximum voluntary contraction of the elbow flexors sustained to exhaustion. TMS- and TES-induced MEP amplitude increased progressively over the contraction period up until the point of exhaustion. The TMS-induced silent period was prolonged only during the second half of the contraction period, the time course being different from that of the MEP responses, whereas the TES-induced silent period did not change. The findings indicate that corticomotor excitability increases during a sustained submaximal voluntary contraction and that, as fatigue develops, there is a progressive buildup of intracortical inhibition. This may represent a mechanism whereby corticomotor output is maintained at an appropriate level to preserve optimal motor unit firing frequencies during a fatiguing contraction.

Research paper thumbnail of Transcranial magnetic stimulation reveals asymmetrical efficacy of intracortical circuits in primary motor cortex

Experimental brain …, Jan 1, 2004

The efficacy of inhibitory and excitatory intracortical circuits acting on the representation of ... more The efficacy of inhibitory and excitatory intracortical circuits acting on the representation of an intrinsic hand muscle in the primary motor cortex of both hemispheres was measured with paired transcranial magnetic stimuli in right-handed subjects. Both intracortical inhibition (measured with an interstimulus interval of 3 ms) and intracortical facilitation (measured with an interstimulus interval of 16 ms) developed more rapidly with increasing conditioning stimulus intensity in the dominant than the non-dominant hand. We conclude that the intracortical circuits in the primary motor cortex are more potent in the dominant than the non-dominant hemisphere, and hypothesize that this difference is a factor in the asymmetrical dexterity associated with hand preference.

Research paper thumbnail of DEPOSITION OF AMYLOID (A4) PROTEIN IN THE CEREBRAL CORTEX IN PARKINSON??S DISEASE (PD)

Alzheimer Disease & Associated Disorders, 1988

Research paper thumbnail of Transcranial magnetic stimulation of the human frontal eye field

Journal of the Neurological Sciences, 1996

The region of cortex over which transcranial magnetic stimulation (TMS) can delay saccadic eye mo... more The region of cortex over which transcranial magnetic stimulation (TMS) can delay saccadic eye movement was investigated. With TMS delivered in the reaction time foreperiod of auditory-triggered saccades, saccade onset could be delayed by up to 60 ms. The area of cortex over which TMS could delay saccade onset was located near the inter-aural line, approximately 6 cm lateral to the vertex, and was situated between areas over which TMS could generate motor evoked potentials in muscles of the hand and face. It is concluded that this area corresponds to the human frontal eye field and is closely associated with the motor strip, at a level between the representations of the hand and the face, and that stimulation of this region can interfere with the programming and execution of externally triggered saccades.

Research paper thumbnail of Johnson 2013 Clinical and posturographic correlates of falling in Parkinson's disease

Research paper thumbnail of Interactive effects of GPI stimulation and levodopa on postural control in Parkinson's disease

Gait & Posture, 2015

Postural instability is a major source of disability in idiopathic Parkinson&amp;amp;amp;amp;... more Postural instability is a major source of disability in idiopathic Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (IPD). Deep brain stimulation of the globus pallidus internus (GPI-DBS) improves clinician-rated balance control but there have been few quantitative studies of its interactive effects with levodopa (L-DOPA). The purpose of this study was to compare the short-term and interactive effects of GPI-DBS and L-DOPA on objective measures of postural stability in patients with longstanding IPD. Static and dynamic posturography during a whole-body leaning task were performed in 10 IPD patients with bilateral GPI stimulators under the following conditions: untreated (OFF); L-DOPA alone; DBS alone; DBS+L-DOPA, and in 9 healthy Control subjects. Clinical status was assessed using the UPDRS and AIMS Dyskinesia Scale. Static sway was greater in IPD patients in the OFF state compared to the Control subjects and was further increased by L-DOPA and reduced by GPI-DBS. In the dynamic task, L-DOPA had a greater effect than GPI-DBS on improving Start Time, but reduced the spatial accuracy and directional control of the task. When the two therapies were combined, GPI-DBS prevented the L-DOPA induced increase in static sway and improved the accuracy of the dynamic task. The findings demonstrate GPI-DBS and L-DOPA have differential effects on temporal and spatial aspects of postural control in IPD and that GPI-DBS counteracts some of the adverse effects of L-DOPA. Further studies on larger numbers of patients with GPI stimulators are required to confirm these findings and to clarify the contribution of dyskinesias to impaired dynamic postural control.

Research paper thumbnail of Cytokines in immune-mediated inflammatory myopathies: cellular sources, multiple actions and therapeutic implications

Clinical and experimental immunology, 2014

The idiopathic inflammatory myopathies are a heterogeneous group of disorders characterised by di... more The idiopathic inflammatory myopathies are a heterogeneous group of disorders characterised by diffuse muscle weakness and inflammation. A common immunopathogenic mechanism is the cytokine-driven infiltration of immune cells into the muscle tissue. Recent studies have further dissected the inflammatory cell types and associated cytokines involved in the immune-mediated myopathies and other chronic inflammatory and autoimmune disorders. In this review we outline the current knowledge of cytokine expression profiles and cellular sources in the major forms of inflammatory myopathy and detail the known mechanistic functions of these cytokines in the context of inflammatory myositis. Furthermore, we discuss how the application of this knowledge may lead to new therapeutic strategies for the treatment of the inflammatory myopathies, in particular for cases resistant to conventional forms of therapy.

Research paper thumbnail of The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications

Neuromuscular disorders : NMD, 2014

The idiopathic inflammatory myopathies are a heterogeneous group of autoimmune muscle disorders w... more The idiopathic inflammatory myopathies are a heterogeneous group of autoimmune muscle disorders with distinct clinical and pathological features and underlying immunopathogenic mechanisms. Traditionally, CD4(+) Th1 cells or CD8(+) cytotoxic effector T cells and type I/II interferons have been primarily implicated in the pathogenesis of the inflammatory myopathies. The presence of IL-17A producing cells in the inflamed muscle tissue of myositis patients and the results of in vitro studies suggest that IL-17A and the Th17 pathway may also have a key role in these diseases. The contribution of IL-17A to other chronic inflammatory and autoimmune diseases has been well established and clinical trials of IL-17A inhibitors are now at an advanced stage. However the precise role of IL-17A in the various forms of myositis and the potential for therapeutic targeting is currently unknown and warrants further investigation.

Research paper thumbnail of Spatio-temporal mapping of evoked cerebral activity

Electroencephalography and clinical neurophysiology, 1984

A technique is described for the colour-coded display of averaged scalp electrical activity at 40... more A technique is described for the colour-coded display of averaged scalp electrical activity at 40 instants in time. An application of this technique to the pattern reversal visual evoked potential is discussed, showing the value of spatio-temporal mapping in the interpretation of multichannel evoked potential recordings.

Research paper thumbnail of Dipole source derivation. Application to the half-field pattern evoked potential

International journal of bio-medical computing, 1985

Dipole modelling is a technique for estimating the location of sources of electrical activity in ... more Dipole modelling is a technique for estimating the location of sources of electrical activity in the brain responsible for the generation of surface recorded potentials on the human scalp. A detailed description of this technique is given with a modification that allows for possible activity at the reference electrode during the surface potential measurement. The application of this technique to localisation of the source of the principal components of the left half-field pattern visual evoked potential is described.

Research paper thumbnail of Averaging, spatio-temporal mapping and dipole modelling of focal epileptic spikes

Electroencephalography and clinical neurophysiology, 1986

A computer-based technique is described for the acquisition, spatio-temporal mapping and dipole m... more A computer-based technique is described for the acquisition, spatio-temporal mapping and dipole modelling of epileptic spike events. Spike acquisition is operator-controlled and subsequent data processing is performed off-line. Preliminary averaging and topographical display of wave forms provide complementary information on the spike field. The method promises to be a useful adjunct to conventional EEG in spike analysis.

Research paper thumbnail of Presaccadic spike potential. Relation to eye movement direction

Electroencephalography and clinical neurophysiology, 1986

The spike potential (SP) which precedes horizontal saccadic eye movement has been shown to arise ... more The spike potential (SP) which precedes horizontal saccadic eye movement has been shown to arise in the agonist lateral and medial rectus muscles of the two eyes. To determine whether other extra-ocular muscles also generate an SP, recordings were carried out in normal subjects performing vertical and oblique as well as horizontal saccades. An SP was recorded before saccades in all directions. The potential was highest in amplitude with horizontal or oblique abducting saccades and was higher in amplitude with vertical upgoing than downgoing saccades.

Research paper thumbnail of Cerebral events preceding self-paced and visually triggered saccades. A study of presaccadic potentials

Electroencephalography and clinical neurophysiology, 1985

The cerebral potentials preceding self-paced and visually triggered saccadic eye movements were s... more The cerebral potentials preceding self-paced and visually triggered saccadic eye movements were studied using multichannel recording and spatio-temporal mapping techniques, and the contribution to these potentials of stimulus-evoked activity and the electro-oculographic field was investigated. A premotor positivity (PMP) and negativity (PMN) comparable to those associated with movements of the extremities were found with both self-paced and triggered saccades, but there were differences in the amplitude, duration and topography of these potentials in the different types of eye movement. The slope of the PMP was greater for visually triggered than for self-paced saccades and its slope and duration were influenced by the predictability of the triggering stimulus, the slope being greater and the duration shorter with predictable than with unpredictable stimuli. The characteristics of this potential are compatible with an origin from saccade-related and visually sensitive neurons in par...

Research paper thumbnail of Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy

Seizure, 2015

Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibi... more Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibility of a paradoxical excitatory effect of GABA in epilepsy has been suggested, but has not been investigated in vivo. We investigated pre- and post-synaptic GABAergic mechanisms in patients with idiopathic generalised epilepsy (IGE). In 10 patients and 12 control subjects we explored short- and long-interval intracortical inhibition (SICI, LICI; post-synaptic GABAA and GABAB-mediated respectively) and long-interval intracortical facilitation (LICF; pre-synaptic disinhibition) using transcranial magnetic stimulation. While post-synaptic GABAB-mediated inhibition was unchanged in IGE (p=0.09), LICF was reduced compared to controls (controls: 141±17% of baseline; untreated patients: 107±12%, p=0.2; treated patients: 79±10%, p=0.003). GABAA-mediated inhibition was reduced in untreated patients (response amplitude 56±4% of baseline vs. 26±6% in controls, p=0.004) and normalised with treatment (37±12%, p=0.5 vs. controls). When measured during LICI, GABAA-mediated inhibition became excitatory in untreated IGE (response amplitude 120±10% of baseline, p=0.017), but not in treated patients. Pre- and post-synaptic GABA-mediated inhibitory mechanisms are altered in IGE. The findings lend in vivo support to evidence from experimental models and in vitro studies of human epileptic brain tissue that GABA may have a paradoxical excitatory role in ictogenesis.

Research paper thumbnail of Topography of excitatory and inhibitory muscle responses evoked by transcranial magnetic stimulation in the human motor cortex

Neuroscience Letters, 1993

Transcranial magnetic stimulation of the motor cortex produces a motor-evoked potential (MEP) in ... more Transcranial magnetic stimulation of the motor cortex produces a motor-evoked potential (MEP) in the electromyogram followed by a silent period (SP) which is thought to be due to cortical inhibition. In this study, the topography and size of the cortical areas from which an MEP and SP are evoked in the abductor pollicis brevis muscle (APB) of the hand were compared. The SP area was found to be large, encompassing and surrounding the MEP area. These findings infer the existence of an inhibitory surround limiting the excitatory area for APB in the human motor cortex.

Research paper thumbnail of Breakdown in central motor control can be attenuated by motor practice and neuro-modulation of the primary motor cortex

Neuroscience, 2012

Other uses, including reproduction and distribution, or selling or licensing copies, or posting t... more Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited.

Research paper thumbnail of Changes in corticomotor excitability and inhibition after exercise are influenced by hand dominance and motor demand

Neuroscience, 2012

Previous studies on handedness have often reported functional asymmetries in corticomotor excitab... more Previous studies on handedness have often reported functional asymmetries in corticomotor excitability (CME) associated with voluntary movement. Recently, we have shown that the degree of post-exercise corticomotor depression (PED) and increase in short-interval cortical inhibition (SICI) after a repetitive finger movement task was less when the task was performed at a maximal voluntary rate (MVR) than when it was performed at a submaximal sustainable rate (SR). In the current study, we have compared the time course of PED and SICI in the dominant (DOM) and nondominant (NDOM) hands after an MVR and SR finger movement task to determine the influence of hand dominance and task demand. We tracked motor-evoked potential (MEP) amplitude from the first dorsal interosseous muscle of the DOM and NDOM hand for 20 min after a 10-s index finger flexion-extension task at MVR and SR. For all hand-task combinations, we report a period of PED and increased SICI lasting for up to 8 min. We find that the least demanding task, one that involved index finger movement of the DOM hand at SR, was associated with the greatest change in PED and SICI from baseline (63.6؎5.7% and 79؎2%, P<0.001, PED and SICI, respectively), whereas the most demanding task (MVR of the NDOM hand) was associated with the least change from baseline (PED: 88.1؎3.6%, SICI: 103؎2%; P<0.001). Our findings indicate that the changes in CME and inhibition associated with repetitive finger movement are influenced both by handedness and the degree of demand of the motor task and are inversely related to task demand, being smallest for an MVR task of the NDOM hand and greatest for an SR task of the DOM hand. The findings provide additional evidence for differences in neuronal processing between the dominant and nondominant hemispheres in motor control.

Research paper thumbnail of Saccadic eye movements in multiple sclerosis*

Neuro-Ophthalmology, 1982

Research paper thumbnail of Genetic polymorphisms of the N-acetyltransferase genes and risk of Parkinson's disease

Research paper thumbnail of The α-synuclein gene is not a major risk factor in familial Parkinson disease

Research paper thumbnail of Changes in corticomotor excitation and inhibition during prolonged submaximal muscle contractions

Muscle & Nerve, 1997

Changes in motor evoked potential (MEP) amplitude, post-MEP silent period duration, and interpola... more Changes in motor evoked potential (MEP) amplitude, post-MEP silent period duration, and interpolated twitch torque were measured using transcranial magnetic (TMS) and electrical (TES) stimulation during a 20% maximum voluntary contraction of the elbow flexors sustained to exhaustion. TMS- and TES-induced MEP amplitude increased progressively over the contraction period up until the point of exhaustion. The TMS-induced silent period was prolonged only during the second half of the contraction period, the time course being different from that of the MEP responses, whereas the TES-induced silent period did not change. The findings indicate that corticomotor excitability increases during a sustained submaximal voluntary contraction and that, as fatigue develops, there is a progressive buildup of intracortical inhibition. This may represent a mechanism whereby corticomotor output is maintained at an appropriate level to preserve optimal motor unit firing frequencies during a fatiguing contraction.