Muscle length effect on corticospinal excitability during maximal concentric, isometric and eccentric contractions of the knee extensors.

NEW FINDINGS: What is the central question of this study? Does sensory input from peripheral mechanoreceptors determine the specific neural control of eccentric contractions? How corticospinal excitability (i.e. muscle responses to motor cortex stimulation) is affected by muscle length has never been investigated during eccentric contractions. What is the main finding and its importance? Muscle length does not influence corticospinal excitability during concentric and isometric maximal contractions, but does during eccentric maximal contractions. This indicates that neural control in eccentric contractions differs from that in concentric and isometric contractions. Neural control of eccentric contractions differs from that of concentric and isometric contractions, but no previous study has compared responses to motor cortex stimulations at long muscle lengths during such contraction types. In this study, we compared the effect of muscle length on corticospinal excitability between maximal concentric, isometric and eccentric contractions of the knee extensors. Twelve men performed 12 maximal concentric, isometric and eccentric voluntary contractions (36 contractions in total), separated by a 5 min rest between contraction types. The 12 contractions for the same contraction type were performed every 10 s, and transcranial magnetic stimulations (first eight contractions) and electrical femoral nerve stimulations (last four contractions) were superimposed alternately at 75 and 100 deg of knee flexion. Average motor evoked potential amplitude, normalized to the maximal M wave amplitude (MEP/M) and cortical silent period duration were calculated for each angle and compared among the contraction types. The MEP/M was lower (-23 and -28%, respectively) during eccentric than both concentric and isometric contractions at 75 deg, but similar between contraction types at 100 deg (P < 0.05). The cortical silent period duration was shorter (-12 and -10%, respectively) during eccentric than both concentric and isometric contractions at 75 deg, but longer (+11 and +9%, respectively) during eccentric contractions at 100 deg (P < 0.05). These results show that corticospinal excitability during eccentric contractions is angle dependent such that cortical inhibitory processes are greater with no alteration of corticospinal excitability at 100 deg, whereas this control is reversed at 75 deg.

Augmenting Plasticity Induction in Human Motor Cortex by Disinhibition Stimulation.

Cellular studies showed that disinhibition, evoked pharmacologically or by a suitably timed priming stimulus, can augment long-term plasticity (LTP) induction. We demonstrated previously that transcranial magnetic stimulation evokes a period of presumably GABA(B)ergic late cortical disinhibition (LCD) in human primary motor cortex (M1). Here, we hypothesized that, in keeping with cellular studies, LCD can augment LTP-like plasticity in humans. In Experiment 1, patterned repetitive TMS was applied to left M1, consisting of 6 trains (intertrain interval, 8 s) of 4 doublets (interpulse interval equal to individual peak I-wave facilitation, 1.3-1.5 ms) spaced by the individual peak LCD (interdoublet interval (IDI), 200-250 ms). This intervention (total of 48 pulses applied over ∼45 s) increased motor-evoked potential amplitude, a marker of corticospinal excitability, in a right hand muscle by 147% ± 4%. Control experiments showed that IDIs shorter or longer than LCD did not result in LTP-like plasticity. Experiment 2 indicated topographic specificity to the M1 hand region stimulated by TMS and duration of the LTP-like plasticity of 60 min. In conclusion, GABA(B)ergic LCD offers a powerful new approach for augmenting LTP-like plasticity induction in human cortex. We refer to this protocol as disinhibition stimulation (DIS).

Movement-generated afference paired with transcranial magnetic stimulation: an associative stimulation paradigm.

BACKGROUND: A peripheral nerve stimulus can enhance or suppress the evoked response to transcranial magnetic stimulation (TMS) depending on the latency of the preceding peripheral nerve stimulation (PNS) pulse. Similarly, somatosensory afference from the passively moving limb can transiently alter corticomotor excitability, in a phase-dependent manner. The repeated association of PNS with TMS is known to modulate corticomotor excitability; however, it is unknown whether repeated passive-movement associative stimulation (MAS) has similar effects. METHODS: In a proof-of-principal study, using a cross-over design, seven healthy subjects received in separate sessions: (1) TMS (120% of the resting motor threshold-RMT, optimal site for Flexor Carpi Radialis) with muscle at rest; (2) TMS paired with cyclic passive movement during extension cyclic passive movement (400 pairs, 1 Hz), with the intervention order randomly assigned. Normality was tested using the Kolmogorov-Smirnov test, then compared to pre-intervention baseline using repeated measures ANOVA with a Dunnet multiple comparisons test. RESULTS: MAS led to a progressive and significant decrease in the motor evoked potential (MEP) amplitude over the intervention (R(2) = 0.6665, P < 0.0001), which was not evident with TMS alone (R(2) = 0.0068, P = 0.641). Post-intervention excitability reduction, only present with MAS intervention, remained for 20 min (0-10 min = 68.2 ± 4.9%, P < 0.05; 10-20 min = 73.3 ± 9.7%, P < 0.05). CONCLUSION: The association of somatosensory afference from the moving limb with TMS over primary motor cortex in healthy subjects can be used to modulate corticomotor excitability, and may have therapeutic implications.

Clinical and posturographic correlates of falling in Parkinson's disease.

Various clinical tests and balance scales have been used to assess postural stability and the risk of falling in patients with idiopathic Parkinson's disease (IPD). Quantitative posturography allows a more objective assessment but the findings in previous studies have been inconsistent and few studies have investigated which posturographic measures correlate best with a history of falling. The purpose of this study was to determine the efficacy of clinical tests, balance scales, and stable-platform posturography in detecting postural instability and discriminating between fallers and non-fallers in a home-dwelling PD cohort. Forty-eight PD subjects (Hoehn & Yahr stage 1-3) and 17 age-matched controls had the following assessments: Activities-specific Balance Confidence scale, Berg Balance Scale, Unified Parkinson's Disease Rating Scale (UPDRS) (motor), pull-test, timed up-and-go, static posturography, and dynamic posturography to assess multidirectional leaning balance. Of the clinical assessments, all but the pull-test were closely correlated with a history of falling. Static posturography discriminated between PD fallers and controls but not between PD fallers and non-fallers, whereas dynamic posturography (reaction time, velocity, and target hit-time) also discriminated between fallers and non-fallers. Our findings suggest that this combination of clinical and posturographic measures would be useful in the prospective assessment of falls risk in PD patients. A further prospective study is now required to assess their predictive value. © 2013 Movement Disorder Society.

Reversal of TMS-induced motor twitch by training is associated with a reduction in excitability of the antagonist muscle.

BACKGROUND: A single session of isolated repetitive movements of the thumb can alter the response to transcranial magnetic stimulation (TMS), such that the related muscle twitch measured post-training occurs in the trained direction. This response is attributed to transient excitability changes in primary motor cortex (M1) that form the early part of learning. We investigated; (1) whether this phenomenon might occur for movements at the wrist, and (2) how specific TMS activation patterns of opposing muscles underlie the practice-induced change in direction. METHODS: We used single-pulse suprathreshold TMS over the M1 forearm area, to evoke wrist movements in 20 healthy subjects. We measured the preferential direction of the TMS-induced twitch in both the sagittal and coronal plane using an optical goniometer fixed to the dorsum of the wrist, and recorded electromyographic (EMG) activity from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles. Subjects performed gentle voluntary movements, in the direction opposite to the initial twitch for 5 minutes at 0.2 Hz. We collected motor evoked potentials (MEPs) elicited by TMS at baseline and for 10 minutes after training. RESULTS: Repetitive motor training was sufficient for TMS to evoke movements in the practiced direction opposite to the original twitch. For most subjects the effect of the newly-acquired direction was retained for at least 10 minutes before reverting to the original. Importantly, the direction change of the movement was associated with a significant decrease in MEP amplitude of the antagonist to the trained muscle, rather than an increase in MEP amplitude of the trained muscle. CONCLUSIONS: These results demonstrate for the first time that a TMS-twitch direction change following a simple practice paradigm may result from reduced corticospinal drive to muscles antagonizing the trained direction. Such findings may have implications for training paradigms in neurorehabilitation.

Rapid slowing of maximal finger movement rate: fatigue of central motor control?

Exploring the limits of the motor system can provide insights into the mechanisms underlying performance deterioration, such as force loss during fatiguing isometric muscle contraction, which has been shown to be due to both peripheral and central factors. However, the role of central factors in performance deterioration during dynamic tasks has received little attention. We studied index finger flexion/extension movement performed at maximum voluntary rate (MVR) in ten healthy subjects, measuring movement rate and amplitude over time, and performed measures of peripheral fatigue. During 20 s finger movements at MVR, there was a decline in movement rate beginning at 7-9 s and continuing until the end of the task, reaching 73% of baseline (P < 0.001), while amplitude remained unchanged. Isometric maximum voluntary contraction force and speed of single ballistic flexion and extension finger movements remained unchanged after the task, indicating a lack of peripheral fatigue. The timing of finger flexor and extensor EMG burst activity changed during the task from an alternating flexion/extension pattern to a less effective co-contraction pattern. Overall, these findings suggest a breakdown of motor control rather than failure of muscle force generation during an MVR task, and therefore that the mechanisms underlying the early decline in movement rate are central in origin.

Plasticity in neurological disorders and challenges for noninvasive brain stimulation (NBS).

There has been considerable interest in trialing NBS in a range of neurological conditions, and in parallel the range of NBS techniques available continues to expand. Underpinning this is the idea that NBS modulates neuroplasticity and that plasticity is an important contributor to functional recovery after brain injury and to the pathophysiology of neurological disorders. However while the evidence for neuroplasticity and its varied mechanisms is strong, the relationship to functional outcome is less clear and the clinical indications remain to be determined. To be maximally effective, the application of NBS techniques will need to be refined to take into account the diversity of neurological symptoms, the fundamental differences between acute, longstanding and chronic progressive disease processes, and the differential part played by functional and dysfunctional plasticity in diseases of the brain and spinal cord.

NeuroMeasure: A Software Package for Quantification of Cortical Motor Maps Using Frameless Stereotaxic Transcranial Magnetic Stimulation.

The recent enhanced sophistication of non-invasive mapping of the human motor cortex using MRI-guided Transcranial Magnetic Stimulation (TMS) techniques, has not been matched by refinement of methods for generating maps from motor evoked potential (MEP) data, or in quantifying map features. This is despite continued interest in understanding cortical reorganization for natural adaptive processes such as skill learning, or in the case of motor recovery, such as after lesion affecting the corticospinal system. With the observation that TMS-MEP map calculation and quantification methods vary, and that no readily available commercial or free software exists, we sought to establish and make freely available a comprehensive software package that advances existing methods, and could be helpful to scientists and clinician-researchers. Therefore, we developed NeuroMeasure, an open source interactive software application for the analysis of TMS motor cortex mapping data collected from Nexstim® and BrainSight®, two commonly used neuronavigation platforms. NeuroMeasure features four key innovations designed to improve motor mapping analysis: de-dimensionalization of the mapping data, fitting a predictive model, reporting measurements to characterize the motor map, and comparing those measurements between datasets. This software provides a powerful and easy to use workflow for characterizing and comparing motor maps generated with neuronavigated TMS. The software can be downloaded on our github page: https://github.com/EdwardsLabNeuroSci/NeuroMeasure. AIM: This paper aims to describe a software platform for quantifying and comparing maps of the human primary motor cortex, using neuronavigated transcranial magnetic stimulation, for the purpose of studying brain plasticity in health and disease.

Clinical improvement with intensive robot-assisted arm training in chronic stroke is unchanged by supplementary tDCS.

BACKGROUND: Intensive robot-assisted arm training in the chronic phase of stroke recovery can lead to clinical improvement. Combinatorial therapeutic approaches are sought to further optimize stroke recovery. Transcranial direct current stimulation (tDCS) is one candidate to combine with robotic training, as transient increases in excitability and improvements in motor behavior have separately been reported. OBJECTIVE: To determine whether tDCS, delivered prior to robotic training, could augment clinical improvement. METHODS: We conducted a dual-site, randomized controlled trial in 82 chronic ischemic stroke patients (inclusion > 6 m post-injury, dominant hemisphere, first stroke; residual hemiparesis) who were split into two groups to receive tDCS (M1-SO montage, anode ipsilesional, 5×7 cm electrodes, 2 mA, 20 mins) or sham tDCS, prior to robotic upper-limb training (12 weeks; 36 sessions; shoulder-elbow robot or wrist robot on alternating sessions). The primary end-point was taken after 12 weeks of training, and assessed with the Upper Extremity Fugl-Meyer impairment scale (FM). Corticomotor conduction was assessed with transcranial magnetic stimulation (TMS). RESULTS: For the combined group (n = 82; post-training) robotic training increased the FM by 7.36 points compared to baseline (p < 0.0001). There was no difference in the FM increase between the tDCS and sham groups (6.97 and 7.73 respectively, p = 0.46). In both groups, clinically meaningful improvement (≥5 points) from baseline was evident in the majority of patients (56/77), was sustained six months later (54/72), and could be attained in severe, moderate and mild baseline hemiparesis. Clinical improvement was associated with increased excitability in the affected hemisphere as assessed by resting motor threshold (pre-post p = 0.029; pre-post 6 months p = 0.029), but not with threshold-adjusted assessment of MEP amplitude (pre-post p = 0.09; pre-post 6 months p = 0.15). Participants with motor evoked potentials were more likely to improve clinically than those without (17/18, 94%, versus 39/59, 66%, p = 0.018). CONCLUSIONS: Our study confirms the benefit of intensive robot-assisted training in stroke recovery, and indicates that conventional tDCS does not confer further advantage to robotic training. We also showed that corticospinal integrity, as assessed by TMS, is a predictor of clinically meaningful response to intensive arm therapy in chronic stroke.

Enhanced corticomotor excitability with dynamic fatiguing exercise of the lower limb in multiple sclerosis.

OBJECTIVE: To determine if task performance and fatigability during rapid repetitive exercise of the lower limb differ in a group of MS subjects compared to a control group, and what central changes accompany the development of fatigue and the period of recovery. METHODS: Transcranial magnetic stimulation (TMS) was used to compare motor evoked potential (MEP) responses between 10 clinically definite MS subjects (7F, 33-64 years of age; EDSS or= 4/5) and 13 control subjects during and after 5 bouts of a 15-second maximum rate foot-tapping task performed at 1 minute intervals. RESULTS: Maximum voluntary contraction (MVC) force of ankle dorsiflexion was lower (15 %) in the MS group compared to controls; however there were no differences in the rate of foot tapping. The rate of foot tapping decreased during each bout of exercise to a comparable degree in both groups, but there was no overall deterioration in performance across the 5 repeat bouts in either group. MS subjects showed a greater decline in strength than controls after exercise (20.7+/-7.7% vs. 6+/-3.6%; p<0.05). MEP amplitude increased significantly for the exercised limb in both groups, but the increase was greater in MS subjects (65.9+/-27% vs. 31+/-19.6%; MS vs. control; p<0.05). MEP amplitude also increased for the non-exercised limb in controls (40.6+/-15.6%, p<0.01) but not in MS subjects. CONCLUSIONS: Mild to moderately affected MS subjects can perform a fatiguing exercise requiring a high level of central motor control but this is associated with a greater strength loss and increase in corticomotor excitability compared to unaffected individuals. SIGNIFICANCE: Central adaptive processes are likely to have a significant role in maintaining task performance in MS.

Spike-timing-related plasticity is preserved in Parkinson's disease and is enhanced by dopamine: evidence from transcranial magnetic stimulation.

We sought to investigate the effects of dopamine on motor cortical plasticity in Parkinson's disease (PD) using a novel interventional transcranial magnetic stimulation protocol that targets spike-timing-dependent plasticity (iTMS). Six patients (3F, mean age 62 years) with mild-moderate PD (mean disease duration 6 years, UPDRS-off 13, UPDRS-on 3, H&Y stage 2, daily levodopa dosage 450 mg) were studied off and on levodopa on separate days. Paired TMS pulses at resting motor threshold with an inter-stimulus interval of 1.5 ms were given over the hand area of the motor cortex for 20 min at 0.2 Hz. Single-pulse motor evoked potential (MEP) amplitude and visually cued simple reaction time (SRT) were measured before and after iTMS. When on levodopa, MEP amplitude increased to 278+/-36% of baseline (p<0.01), and when off levodopa to 157+/-13% of baseline (p=0.02). All patients showed a significantly greater increase in MEP amplitude when on levodopa than off levodopa (p=0.01). SRT was reduced to 95% baseline after iTMS off levodopa (p=0.02), but did not change on levodopa. These findings indicate that motor cortex plasticity to iTMS is preserved in mild-moderate PD. The effects of this spike-timing-related TMS protocol on cortical excitability were consistent and were enhanced by levodopa. The results support the important role of dopamine in regulating synaptic plasticity and justify a larger crossover study to assess the therapeutic effects of iTMS in PD.

Robotic Arm Rehabilitation in Chronic Stroke Patients With Aphasia May Promote Speech and Language Recovery (but Effect Is Not Enhanced by Supplementary tDCS).

Objective: This study aimed to determine the extent to which robotic arm rehabilitation for chronic stroke may promote recovery of speech and language function in individuals with aphasia. Methods: We prospectively enrolled 17 individuals from a hemiparesis rehabilitation study pairing intensive robot assisted therapy with sham or active tDCS and evaluated their speech (N = 17) and language (N = 9) performance before and after a 12-week (36 session) treatment regimen. Performance changes were evaluated with paired t-tests comparing pre- and post-test measures. There was no speech therapy included in the treatment protocol. Results: Overall, the individuals significantly improved on measures of motor speech production from pre-test to post-test. Of the subset who performed language testing (N = 9), overall aphasia severity on a standardized aphasia battery improved from pre-test baseline to post-test. Active tDCS was not associated with greater gains than sham tDCS. Conclusions: This work indicates the importance of considering approaches to stroke rehabilitation across different domains of impairment, and warrants additional exploration of the possibility that robotic arm motor treatment may enhance rehabilitation for speech and language outcomes. Further investigation into the role of tDCS in the relationship of limb and speech/language rehabilitation is required, as active tDCS did not increase improvements over sham tDCS.

Repetitive Transcranial Magnetic Stimulation of the Brain: Mechanisms from Animal and Experimental Models.

Since the development of transcranial magnetic stimulation (TMS) in the early 1980s, a range of repetitive TMS (rTMS) protocols are now available to modulate neuronal plasticity in clinical and non-clinical populations. However, despite the wide application of rTMS in humans, the mechanisms underlying rTMS-induced plasticity remain uncertain. Animal and in vitro models provide an adjunct method of investigating potential synaptic and non-synaptic mechanisms of rTMS-induced plasticity. This review summarizes in vitro experimental studies, in vivo studies with intact rodents, and preclinical models of selected neurological disorders-Parkinson's disease, depression, and stroke. We suggest that these basic research findings can contribute to the understanding of how rTMS-induced plasticity can be modulated, including novel mechanisms such as neuroprotection and neurogenesis that have significant therapeutic potential.

Improved grasp function with transcranial direct current stimulation in chronic spinal cord injury.

BACKGROUND: Recovering hand function has important implications for improving independence of patients with tetraplegia after traumatic spinal cord injury (SCI). Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique that has potential to improve motor function. OBJECTIVE: To investigate the effects of one session of 1 mA, 2 mA, and sham anodal tDCS (a-tDCS) in the upper extremity (hand) motor performance (grasp and lease) in patients with chronic cervical SCI. METHODS: Eleven participants with incomplete SCI were randomized to receive 20 minutes of 1 mA, 2 mA, or sham stimulation over the targeted motor cortex over three separated sessions. Hand motor performance was measured by a hand robotic evaluation (kinematics) and the Box and Blocks (BB) test before and after the stimulation period. RESULTS: A significant improvement on the grasp mean to peak speed ratio (GMP) was observed in the 2 mA group (pre: 0.38±0.02; post: 0.43±0.03; mean±SEM; p = 0.031). There was no statistically significant difference in BB test results, however the 2 mA intervention showed a positive trend for improvement. CONCLUSIONS: A single session of 2 mA of a-tDCS showed gains in hand motor function in patients with chronic SCI that were not observed in functional clinical scales. The use of robotic kinematics showed promising results in assessing small changes in motor performance. Further studies are necessary to determine whether tDCS can be an effective long-term rehabilitation strategy for individuals with SCI.

Optimising conservative management of chronic low back pain: study protocol for a randomised controlled trial.

BACKGROUND: Lower back pain is a global health issue affecting approximately 80% of people at some stage in their life. The current literature suggests that any exercise is beneficial for reducing back pain. However, as pain is a subjective evaluation and physical deficits are evident in low back pain, using it as the sole outcome measure to evaluate superiority of an exercise protocol for low back pain treatment is insufficient. The overarching goal of the current clinical trial is to implement two common, conservative intervention approaches and examine their impact on deficits in chronic low back pain. METHODS/DESIGN: Forty participants, 25-45 years old with chronic (>3 months), non-specific low back pain will be recruited. Participants will be randomised to receive either motor control and manual therapy (n = 20) or general strength and conditioning (n = 20) exercise treatments for 6 months. The motor control/manual therapy group will receive twelve 30-min sessions, ten in the first 3 months (one or two per week) and two in the last 3 months. The general exercise group will attend two 1-hour sessions weekly for 3 months, and one or two a week for the following 3 months. Primary outcome measures are average lumbar spine intervertebral disc T2 relaxation time and changes in thickness of the transversus abdominis muscle on a leg lift using magnetic resonance imaging (MRI). Secondary outcomes include muscle size and fat content, vertebral body fat content, intervertebral disc morphology and water diffusion measured by MRI, body composition using dual energy X-ray absorptiometry, physical function through functional tests, changes in corticospinal excitability and cortical motor representation of the spinal muscles using transcranial magnetic stimulation and self-reported measure of pain symptoms, health and disability. Outcome measures will be conducted at baseline, at the 3-month follow-up and at 6 months at the end of intervention. Pain, depressive symptomology and emotions will be captured fortnightly by questionnaires. DISCUSSION: Chronic low back pain is ranked the highest disabling disorder in Australia. The findings of this study will inform clinical practice guidelines to assist with decision-making approaches where outcomes beyond pain are sought for adults with chronic low back pain. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12615001270505 . Registered on 20 November 2015.

Central motor drive and perception of effort during fatigue in multiple sclerosis.

OBJECTIVE: To determine if task performance and fatiguability during repeated low-level contractions of an intrinsic hand muscle differ in a group of MS subjects compared with a control group, and what central changes accompany the development of fatigue and the period of recovery, whether these measures are related to subjective ratings of fatigue or perception of effort. METHODS: Force of index finger abduction, rating of perceived effort, and motor evoked potential amplitude and silent period duration were measured during and after a 20-min. intermittent submaximal (40%) contraction of the first dorsal interosseous muscle in 23 clinically definite MS subjects with mild-moderate symptoms, and 15 controls. RESULTS: Rating of perceived effort increased at a greater rate in the MS group than in control subjects during exercise, and this was associated with larger increases in both MEP amplitude and silent period duration. CONCLUSIONS: Submaximal fatiguing exercise is associated with an enhanced central motor drive and increased perception of effort in MS. SIGNIFICANCE: MS subjects can increase central drive during fatiguing exercise to a greater degree than controls, but this is associated with greater perceived exertion. These factors may underlie the more general complaint of fatigue experienced by people with MS.

Repetitive paired-pulse TMS at I-wave periodicity markedly increases corticospinal excitability: a new technique for modulating synaptic plasticity.

OBJECTIVE: We hypothesised that facilitatory I-wave interaction set up by paired-pulse transcranial magnetic stimulation delivered with I-wave periodicity (iTMS) may reinforce trans-synaptic events and provide a means for modulating synaptic plasticity and cortical excitability. Our objective was to determine whether prolonged iTMS can increase corticospinal excitability, and whether this form of stimulation can have lasting aftereffects. METHODS: Paired stimuli of equal strength with a 1.5 ms inter-stimulus interval were delivered for 30 min at a rate of 0.2 Hz. Motor threshold and motor evoked potential (MEP) amplitude to single-pulse TMS was compared before and after intervention. RESULTS: Paired-pulse MEP amplitude increased linearly throughout the period of iTMS, and had increased five-fold by the end of the stimulation period. Single-pulse MEP amplitude was increased a mean of four-fold for 10 min after stimulation. Motor threshold was unaffected. CONCLUSIONS: iTMS is an effective method for increasing excitability of the human motor cortex, and probably acts by increasing synaptic efficacy. SIGNIFICANCE: Reinforcement of trans-synaptic events by iTMS may provide a means to investigate and modulate synaptic plasticity in the brain.

Differential activation of frontal lobe areas by lexical and semantic language tasks: a functional magnetic resonance imaging study.

To determine whether frontal lobe regions, including Broca's area, dorsolateral prefrontal cortex (DLPFC) and supplementary motor area (SMA), are differentially activated during lexical and semantic language tasks, we used functional magnetic resonance imaging in eight healthy right-handed subjects silently performing two semantic tasks (adjective and verb generation) and a lexical retrieval task (noun recall). Activation was observed in Broca's area, DLPFC and SMA for all tasks. Broca's area activation was approximately doubled during the semantic tasks compared with the lexical task (verbs vs nouns: 19.1+/-4.5 vs 8.9+/-1.6 voxels, p=0.02; adjectives vs nouns 24.4+/-7.5 vs 10.1+/-2.8 voxels, p=0.04); however, there were no significant differences in the DLFPC or SMA across tasks. We conclude that Broca's area is more active during tasks that have a semantic content, whereas areas involved in preparatory processing (SMA) and memory retrieval (DLPFC) are engaged equally during both types of task.

Motor cortex reorganisation in Parkinson's disease.

Transcranial magnetic stimulation mapping of the motor cortical projection to the hand was performed in a group of patients with Parkinson's disease (PD) of variable duration to determine whether there is evidence of cortical reorganisation. Map shifts were found in the majority of PD cases (12/15), in untreated early cases as well as treated cases of longer duration, and there was a correlation between inter-side difference in the severity of PD symptoms (Unified Parkinson's Disease Rating Scale) and interhemispheric map displacement (r=0.60; P=0.018). These findings indicate that there is reorganisation of the corticomotor representation of the hand in PD, even at a relatively early stage of the disease, and suggest a dynamic process of reorganisation in the motor cortex due to an increase in the pallidal inhibitory inputs to the thalamo-cortical projections.