Interhemispheric effects of high and low frequency rTMS in healthy humans.

OBJECTIVE: We investigated whether repetitive transcranial magnetic stimulation (rTMS) applied to the right motor cortex modified the excitability of the unstimulated left motor cortex. METHODS: Interhemispheric effects of 0.5 and 5 Hz subthreshold rTMS over the right motor cortex were examined by single pulse and paired pulse TMS and by transcranial electrical stimulation (TES) applied to the unstimulated left motor cortex. The effects of (a) 1800 pulses real and sham rTMS with 5 Hz, (b) 180 pulses real and sham rTMS with 0.5 Hz and (c) 1800 pulses real rTMS with 0.5 Hz were studied. RESULTS: Following 5 Hz right motor rTMS motor evoked potential (MEP) amplitudes induced by single pulse TMS over the left motor cortex increased significantly. Intracortical inhibition (ICI) and facilitation (ICF) and MEP amplitudes evoked by TES were unchanged. Sham stimulation had no influence on motor cortex excitability. After 180 pulses right motor cortex rTMS with 0.5 Hz a significant decrease of left motor ICF, but no change in single pulse MEP amplitudes was found. A similar trend was observed with 1800 pulses rTMS with 0.5 Hz. CONCLUSIONS: High frequency right motor rTMS can increase left motor cortex excitability whereas low frequency right motor rTMS can decrease it. These effects outlast the rTMS by several minutes. The underlying mechanisms mediating interhemispheric excitability changes are likely to be frequency dependent.     

One hertz repetitive transcranial magnetic stimulation over dorsal premotor cortex enhances offline motor memory consolidation for sequence‐specific implicit learning

Consolidation of motor memories associated with skilled practice can occur both online, concurrent with practice, and offline, after practice has ended. The current study investigated the role of dorsal premotor cortex (PMd) in early offline motor memory consolidation of implicit sequence‐specific learning. Thirty‐three participants were assigned to one of three groups of repetitive transcranial magnetic stimulation (rTMS) over left PMd (5 Hz, 1 Hz or control) immediately following practice of a novel continuous tracking task. There was no additional practice following rTMS. This procedure was repeated for 4 days. The continuous tracking task contained a repeated sequence that could be learned implicitly and random sequences that could not. On a separate fifth day, a retention test was performed to assess implicit sequence‐specific motor learning of the task. Tracking error was decreased for the group who received 1 Hz rTMS over the PMd during the early consolidation period immediately following practice compared with control or 5 Hz rTMS. Enhanced sequence‐specific learning with 1 Hz rTMS following practice was due to greater offline consolidation, not differences in online learning between the groups within practice days. A follow‐up experiment revealed that stimulation of PMd following practice did not differentially change motor cortical excitability, suggesting that changes in offline consolidation can be largely attributed to stimulation‐induced changes in PMd. These findings support a differential role for the PMd in support of online and offline sequence‐specific learning of a visuomotor task and offer converging evidence for competing memory systems.     

Contribution of transcranial magnetic stimulation in restless legs syndrome: pathophysiological insights and therapeutical approaches

Transcranial magnetic stimulation (TMS) may offer a reliable means to characterize significant pathophysiologic and neurochemical aspects of restless legs syndrome (RLS). Namely, TMS has revealed specific patterns of changes in cortical excitability and plasticity, in particular dysfunctional inhibitory mechanisms and sensorimotor integration, which are thought to be part of the pathophysiological mechanisms of RLS rather than reflect a non-specific consequence of sleep architecture alteration.If delivered repetitively, TMS is able to transiently modulate the neural activity of the stimulated and connected areas. Some studies have begun to therapeutically use repetitive TMS (rTMS) to improve sensory and motor disturbances in RLS. High-frequency rTMS applied over the primary motor cortex or the supplementary motor cortex, as well as low-frequency rTMS over the primary somatosensory cortex, seem to have transient beneficial effects. However, further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up are needed in order to corroborate preliminary results.Thus, we performed a systematic search of all the studies that have used TMS and rTMS techniques in patients with RLS.     

Subthreshold prefrontal repetitive transcranial magnetic stimulation reduces motor cortex excitability

The prefrontal cortex plays an important role in central motor control. We have examined whether prefrontal repetitive transcranial magnetic stimulation (rTMS) induces changes of motor cortex excitability determined by motor evoked potentials (MEPs) following single-pulse TMS. We studied 18 healthy volunteers stimulated at 5 Hz with 10% subthreshold prefrontal vs. occipital rTMS for 12 s. MEPs from the flexor carpi radialis muscle after single-pulse vertex stimulation were recorded during rTMS at 0, 4, 8, and 12 s. MEP areas decreased significantly after 8 s of prefrontal rTMS (P < 0. 05) but not after occipital rTMS. We conclude that rTMS of the prefrontal cortex may inhibit the primary motor areas.     

Neural correlates of dual‐task practice benefit on motor learning: a repetitive transcranial magnetic stimulation study

Dual‐task practice has been previously shown to enhance motor learning when both primary and secondary tasks engage similar cognitive processes. In the present study, participants practiced a finger sequence task with the non‐dominant hand under a single‐task condition (i.e. without a probe task) or a dual‐task condition in which a probe choice reaction time (CRT) task was presented during the preparation phase (before movement onset) of the finger task. It was hypothesised that by engaging similar ‘planning’ processes, the dual‐task condition may facilitate the activation of shared ‘planning’ circuitry that includes dorsal premotor cortex (dPM), an important neural substrate for CRT task performance and movement preparation. Repetitive transcranial magnetic stimulation (rTMS; 1 Hz) was applied to the contralateral dPM immediately following practice. Motor learning was assessed by a retention test conducted ~ 24 h after practice. Consistent with our previous results, the dual‐task condition enhanced learning compared with the single‐task condition. rTMS applied to dPM attenuated the dual‐task practice benefit on motor learning. In contrast, rTMS to M1 did not attenuate the dual‐task practice benefit, suggesting the rTMS effect was specific to dPM. Our findings suggest a unique role of dPM in mediating the dual‐task practice effect on motor learning.     

Repetitive transcranial magnetic stimulation at 1Hz and 5Hz produces sustained improvement in motor function and disability after ischaemic stroke

Background: Repetitive transcranial magnetic stimulation (rTMS) is a simple and non‐invasive method of augmenting motor recovery after stroke, probably mediated by restoring inter‐hemispheric activation balance. This placebo‐controlled pilot study examined the possible benefit of stimulating the lesioned hemisphere (5‐Hz rTMS) or inhibiting the contra‐lesional hemisphere (1‐Hz rTMS) on clinical recovery of motor function in patients with ischaemic stroke and assessed the sustainability of the response. Methods: Sixty patients with ischaemic stroke (>1 month from onset) with mild‐to‐moderate hemiparesis were randomized to receive 10 daily sessions of either sham rTMS, 5‐Hz ipsi‐lesional rTMS or 1‐Hz contra‐lesional rTMS, in addition to a standard physical therapy protocol. Serial assessments were made over a period of 12 weeks by the thumb‐index finger tapping test (FT), Activity Index (AI) score and the modified Rankin Scale (mRS). Results: In contrast to control patients, those receiving active rTMS as ipsi‐lesional 5‐Hz stimulation or 1‐Hz contra‐lesional stimulation showed statistically significant improvement on the FT test, AI scores and mRS score at 2 weeks, and the effect was sustained over the 12‐week observation period. No significant adverse events were observed during treatment in either group. Conclusions: Repetitive TMS has beneficial effects on motor recovery that can be translated to clinically meaningful improvement in disability in patients with post‐stroke hemiparesis, with a well‐sustained effect. The similarity of inhibitory and stimulatory rTMS in producing these effects supports the inter‐hemispheric balance hypothesis and encourages further research into their use in long‐term neurorehabilitation programmes of patients with stroke.     

Improvement of motor performance and modulation of cortical excitability by repetitive transcranial magnetic stimulation of the motor cortex in Parkinson's disease.

OBJECTIVE: To assess the effects of focal motor cortex stimulation on motor performance and cortical excitability in patients with Parkinson's disease (PD). METHODS: Repetitive transcranial magnetic stimulation (rTMS) was performed on the left motor cortical area corresponding to the right hand in 12 'off-drug' patients with PD. The effects of subthreshold rTMS applied at 0.5 Hz (600 pulses) or at 10 Hz (2000 pulses) using a 'real' or a 'sham' coil were compared to those obtained by a single dose of l-dopa. The assessment included a clinical evaluation by the Unified Parkinson's Disease Rating Scale and timed motor tasks, and a neurophysiological evaluation of cortical excitability by single- and paired-pulse TMS techniques. RESULTS: 'Real' rTMS at 10 or 0.5 Hz, but not 'sham' stimulation, improved motor performance. High-frequency rTMS decreased rigidity and bradykinesia in the upper limb contralateral to the stimulation, while low-frequency rTMS reduced upper limb rigidity bilaterally and improved walking. Concomitantly, 10 Hz rTMS increased intracortical facilitation, while 0.5 Hz rTMS restored intracortical inhibition. CONCLUSIONS: Low- and high-frequency rTMS of the primary motor cortex lead to significant but differential changes in patients with PD both on clinical and electrophysiological grounds. The effects on cortical excitability were opposite to previous observations made in healthy subjects, suggesting a reversed balance of cortical excitability in patients with PD compared to normals. However, the underlying mechanisms of these changes remain to determine, as well as the relationship with clinical presentation and response to l-dopa therapy. SIGNIFICANCE: The present study gives some clues to appraise the role of the primary motor cortex in PD. Clinical improvement induced by rTMS was too short-lasting to consider therapeutic application, but these results support the perspective of the primary motor cortex as a possible target for neuromodulation in PD.     

Short-lasting impairment of temperature perception by high frequency rTMS of the sensorimotor cortex.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has become a useful tool for investigating and even modulating human brain function. RTMS of the human motor cortex can produce changes in excitability that outlast the period of stimulation. To investigate the persistent effect of high-frequency rTMS of sensorimotor cortex (SM1) on somatosensory function. METHODS: We evaluated the thermal thresholds (cold and warm sensation) in 14 normal subjects before and after a short train of 5Hz rTMS over the SM1 or occipital cortex (OC). RESULTS: Threshold for cold perception was increased immediately after rTMS of the left SM1 and no effects at all were noticed after OC stimulation. There was a slight, not significant, increase of warm threshold immediately after the rTMS of the left SM1 and no effects at all were noticed after OC stimulation. CONCLUSIONS: High frequency rTMS over primary sensorimotor cortex seems to modulate sensory function related to thermal (cold) perception. SIGNIFICANCE: The method may be useful for both the study of normal human physiology of temperature perception and for rTMS based manipulation of brain plasticity in patients with sensory disturbances.     

Repetitive Transcranial Magnetic Stimulation Elicits Rate-Dependent Brain Network Responses in Non-Human Primates

BackgroundTranscranial magnetic stimulation (TMS) has the potential to treat brain disorders by tonically modulating firing patterns in disease-specific neural circuits. The selection of treatment parameters for clinical repetitive transcranial magnetic stimulation (rTMS) trials has not been rule based, likely contributing to the variability of observed outcomes.ObjectiveTo utilize our newly developed baboon (Papio hamadryas anubis) model of rTMS during position-emission tomography (PET) to quantify the brain's rate–response functions in the motor system during rTMS.MethodsWe delivered image-guided, suprathreshold rTMS at 3 Hz, 5 Hz, 10 Hz, 15 Hz and rest (in separate randomized sessions) to the primary motor cortex (M1) of the lightly anesthetized baboon during PET imaging; we also administered a (reversible) paralytic to eliminate any somatosensory feedback due to rTMS-induced muscle contractions. Each rTMS/PET session was analyzed using normalized cerebral blood flow (CBF) measurements; statistical parametric images and the resulting areas of significance underwent post-hoc analysis to determine any rate-specific rTMS effects throughout the motor network.ResultsThe motor system's rate–response curves were unimodal and system wide—with all nodes in the network showing highly similar rate response functions—and an optimal network stimulation frequency of 5 Hz.Conclusion(s)These findings suggest that non-invasive brain stimulation may be more efficiently delivered at (system-specific) optimal frequencies throughout the targeted network and that functional imaging in non-human primates is a promising strategy for identifying the optimal treatment parameters for TMS clinical trials in specific brain regions and/or networks.     

Short-term and long-term plasticity interaction in human primary motor cortex

Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short‐ and long‐term forms of synaptic plasticity, resembling short‐term potentiation (STP) and long‐term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5‐Hz rTMS interferes with LTP/LTD‐like plasticity induced by intermittent and continuous theta‐burst stimulation (iTBS and cTBS). The effects induced by 5‐Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5‐Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5‐Hz rTMS. Interactions between 5‐Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5‐Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5‐Hz rTMS and TBS, and delivering one and ten 5‐Hz rTMS trains. We also investigated whether 5‐Hz rTMS induces changes in intracortical excitability tested with paired‐pulse transcranial magnetic stimulation. When given alone, 5‐Hz rTMS induced short‐lasting and iTBS/cTBS induced long‐lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5‐Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS‐induced after‐effects disappeared. The 5‐Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5‐Hz rTMS abolishes iTBS/cTBS‐induced LTP/LTD‐like plasticity through non‐homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short‐term and long‐term rTMS‐induced plasticity in human M1.     

Short-lasting impairment of tactile perception by 0.9Hz-rTMS of the sensorimotor cortex

To test whether low-frequency repetitive transcranial magnetic stimulation (rTMS) of sensorimotor cortex (SM1) has prolonged effects on somatosensory function, eight subjects were given 900 TMS pulses over the left hand SM1 (0.9Hz, 90% of the resting motor threshold) or at sites 3 cm anterior or posterior to it. Tactile threshold of the right hand was increased for a short duration after rTMS over SM1, but two-point discrimination and median nerve SEPs were unaffected after rTMS at any sites.     

Abnormal plasticity of the sensorimotor cortex to slow repetitive transcranial magnetic stimulation in patients with writer's cramp.

Previous studies demonstrated functional abnormalities in the somatosensory system, including a distorted functional organization of the somatosensory cortex (S1) in patients with writer's cramp. We tested the hypothesis that these functional alterations render S1 of these patients more susceptible to the "inhibitory" effects of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) given to S1. Seven patients with writer's cramp and eight healthy subjects were studied. Patients also received rTMS to the motor cortex hand area (M1). As an outcome measure, short-latency afferent inhibition (SAI) was tested. SAI was studied in the relaxed first dorsal interosseous muscle using conditioning electrical stimulation of the index finger and TMS pulses over the contralateral M1. Baseline SAI did not differ between groups. S1 but not M1 rTMS reduced SAI in patients. rTMS had no effects on SAI in healthy subjects. Because SAI is mediated predominantly at a cortical level in the sensorimotor cortex, we conclude that there is an abnormal responsiveness of this area to 1 Hz rTMS in writer's cramp, which may represent a trait toward maladaptive plasticity in the sensorimotor system in these patients.     

Modulatory effects of 5Hz rTMS over the primary somatosensory cortex in focal dystonia—An fMRI‐TMS study

Dystonia is associated with impaired somatosensory ability. The electrophysiological method of repetitive transcranial magnetic stimulation (rTMS) can be used for noninvasive stimulation of the human cortex and can alter cortical excitability and associated behavior. Among others, rTMS can alter/improve somatosensory discrimation abilities, as shown in healthy controls. We applied 5Hz‐rTMS over the left primary somatosensory cortex (S1) in 5 patients with right‐sided writer's dystonia and 5 controls. We studied rTMS effects on tactile discrimination accuracy and concomitant rTMS‐induced changes in hemodynamic activity measured by functional magnetic resonance imaging (fMRI). Before rTMS, patients performed worse on the discrimination task than controls even though fMRI showed greater task‐related activation bilaterally in the basal ganglia (BG). In controls, rTMS led to improved discrimination; fMRI revealed this was associated with increased activity of the stimulated S1, bilateral premotor cortex and BG. In dystonia patients, rTMS had no effect on discrimination; fMRI showed similar cortical effects to controls except for no effects in BG. Improved discrimination after rTMS in controls is linked to enhanced activation of S1 and BG. Failure of rTMS to increase BG activation in dystonia may be associated with the lack of effect on sensory discrimination in this group and may reflect impaired processing in BG‐S1 connections. Alternatively, the increased BG activation seen in the baseline state without rTMS may reflect a compensatory strategy that saturates a BG contribution to this task. © 2010 Movement Disorder Society     

高低频重复经颅磁刺激治疗卒中后上肢痉挛的对照研究

目的 探讨高、低频重复经颅磁刺激（repetitive transcranial magnetic stimulation,rTMS）大脑初级运动皮层（M1区）治疗卒中后上肢痉挛的临床疗效及差异。      

Repetitive transcranial magnetic stimulation as treatment of poststroke depression: a preliminary study.

BACKGROUND: Depression has a significant impact on poststroke recovery and mortality. There are a proportion of patients with poststroke depression (PSD) who do not respond to antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) might be a safe and effective alternative in these refractory cases. METHODS: We conducted a randomized, parallel, double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD. After discontinuing antidepressants, patients were randomly assigned to receive 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores, response and remission rates. Patients completed a neuropsychological battery at baseline and after completing the protocol. RESULTS: When compared with sham stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms. This reduction was not influenced by patient's age, type or location of stroke, volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex. However, there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes. There were no significant changes in cognitive functioning between the active and the sham stimulation groups. In addition, there were few and mild adverse effects that were equally distributed among groups. CONCLUSIONS: Taken together, these preliminary findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke.     

Suppression of ipsilateral motor cortex facilitates motor skill learning

The primary motor cortex (M1) plays a critical role in early aspects of motor skill learning. Given the notion of inter-hemispheric competition, unilateral disruption of M1 may increase excitability of the unaffected motor cortex and thus improve motor learning with the ipsilateral hand. We applied slow-frequency repetitive transcranial magnetic stimulation (rTMS) before the initiation of practice of a simple motor skill. Participants were randomly divided into three stimulation groups: (i) ipsilateral M1; (ii) contralateral M1; and (iii) Cz (control site). The mean execution time and error rate were recorded in four sessions distributed over 2 days. Disruption of M1 with rTMS slowed down skill acquisition with the contralateral hand, albeit non significantly, but paradoxically enhanced learning with the ipsilateral hand. This was evidenced by a significant decrease of execution time at the end of day 1 in the group that received rTMS over the ipsilateral M1 compared with both control groups (Cz and contralateral M1 stimulation). This supports the notion of inter-hemispheric competition and provides novel insights that may be applicable to neurorehabilitation.     

Comparison of monophasic versus biphasic stimulation in rTMS over premotor cortex: SEP and SPECT studies

OBJECTIVE: To optimize the clinical uses of repetitive transcranial magnetic stimulation (rTMS), we compared the effects of rTMS on somatosensory-evoked potentials (SEPs) and regional cerebral blood flow (rCBF) using different phases (monophasic vs. biphasic) or frequencies (0.2Hz vs. 0.8Hz) of stimulation. METHODS: In the first experiment, different phases were compared (0.2Hz monophasic vs. 0.2Hz biphasic). Biphasic 1Hz or sham condition served as controls. The second experiment was to explore the effect of frequencies (0.2Hz vs. 0.8Hz) using the monophasic stimulation. Substhreshold TMS was applied 250 times over the left premotor cortex. Single photon emission computed tomography (SPECT) was performed before and after monophasic 0.2Hz or biphasic 1Hz rTMS. RESULTS: Monophasic rTMS of both 0.2 and 0.8Hz significantly increased the ratio of N30 amplitudes as compared with sham rTMS, whereas biphasic stimulation showed no significant effects. SPECT showed increased rCBF in motor cortices after monophasic 0.2Hz rTMS, but not after biphasic 1Hz stimulation. CONCLUSIONS: Monophasic rTMS exerted more profound effects on SEPs and rCBF than biphasic rTMS over the premotor cortex. SIGNIFICANCE: Monophasic rTMS over the premotor cortex could be clinically more useful than biphasic rTMS.     

Stimulus intensity and coil characteristics influence the efficacy of rTMS to suppress cortical excitability.

OBJECTIVE: Low-frequency repetitive transcranial magnetic stimulation (rTMS) can reduce cortical excitability. Here we examined whether inhibitory after effects of low-frequency rTMS are influenced by stimulus intensity, the type of TMS coil and re-afferent sensory stimulation. METHODS: In fifteen healthy volunteers, we applied 900 biphasic pulses of 1Hz rTMS to the left primary motor cortex (M1) at an intensity that was 10% below or 15% above resting motor threshold. For rTMS, we used two different figure-of-eight shaped coils (Magstim or Medtronic coil) attached to the same stimulator. We recorded motor evoked potentials (MEPs) evoked with the same set-up used for rTMS (MEP-rTMS) before and twice after rTMS. Using a different TMS setup, we also applied monophasic pulses to the M1 in order to assess the effects of rTMS on corticospinal excitability, intracortical paired-pulse excitability and the duration of the cortical silent period (CSP). In a control experiment, the same measurements were performed after 15min of 1Hz repetitive electrical nerve stimulation (rENS) of the right ulnar nerve. RESULTS: Analysis of variance revealed an interaction between intensity, coil and time of measurement (p<0.035), indicating that the effect of 1Hz rTMS on MEP-rTMS amplitude depended on the intensity and the type of coil used for rTMS. Suppression of corticospinal excitability was strongest after suprathreshold 1Hz rTMS with the Medtronic coil (p<0.01 for both post-rTMS measurements relative to pre-intervention baseline). Regardless of the type of coil, suprathreshold but not subthreshold rTMS transiently prolonged the CSP and attenuated paired-pulse facilitation. Suprathreshold 1Hz rENS also induced a short-lasting inhibition of MEP-rTMS. CONCLUSIONS: Both the stimulation intensity and the type of TMS coil have an impact on the after effects of 1Hz rTMS. Re-afferent feedback activation may at least in part account for the stronger suppression of corticospinal excitability by suprathreshold 1Hz rTMS. SIGNIFICANCE: These data should be considered when rTMS is used as a therapeutic means.     

Facilitating effect of 15-Hz repetitive transcranial magnetic stimulation on tactile perceptual learning

Recent neuroimaging studies have revealed that tactile perceptual learning can lead to substantial reorganizational changes of the brain. We report here for the first time that combining high-frequency (15 Hz) repetitive transcranial magnetic stimulation (rTMS) over the primary somatosensory cortex (SI) with tactile discrimination training is capable of facilitating operant perceptual learning. Most notably, increasing the excitability of SI by 15-Hz rTMS improved perceptual learning in spatial, but not in temporal, discrimination tasks. These findings give causal support to recent correlative data obtained by functional magnetic resonance imaging studies indicating a differential role of SI in spatial and temporal discrimination learning. The introduced combination of rTMS and tactile discrimination training may provide new therapeutical potentials in facilitating neuropsychological rehabilitation of functional deficits after lesions of the somatosensory cortex.     

Volumetric effects of motor cortex injury on recovery of ipsilesional dexterous movements

Damage to the motor cortex of one hemisphere has classically been associated with contralateral upper limb paresis, but recent patient studies have identified deficits in both upper limbs. In non-human primates, we tested the hypothesis that the severity of ipsilesional upper limb motor impairment in the early post-injury phase depends on the volume of gray and white matter damage of the motor areas of the frontal lobe. We also postulated that substantial recovery would accompany minimal task practice and that ipsilesional limb recovery would be correlated with recovery of the contralesional limb. Gross (reaching) and fine hand motor functions were assessed for 3–12 months post-injury using two motor tests. Volumes of white and gray matter lesions were assessed using quantitative histology. Early changes in post-lesion motor performance were inversely correlated with white matter lesion volume indicating that larger lesions produced greater decreases in ipsilesional hand movement control. All monkeys showed improvements in ipsilesional hand motor skill during the post-lesion period, with reaching skill improvements being positively correlated with total lesion volume indicating that larger lesions were associated with greater ipsilesional motor skill recovery. We suggest that reduced trans-callosal inhibition from the lesioned hemisphere may play a role in the observed skill improvements. Our findings show that significant ipsilesional hand motor recovery is likely to accompany injury limited to frontal motor areas. In humans, more pronounced ipsilesional motor deficits that invariably develop after stroke may, in part, be a consequence of more extensive subcortical white and gray matter damage.