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Background and Purpose: Several clinical measures and biomarkers are associated with motor recovery after stroke, but none are used to guide rehabilitation for individual patients. The objective of this study was to evaluate the implementation of upper limb predictions in stroke rehabilitation, by combining clinical measures and biomarkers using the Predict Recovery Potential (PREP) algorithm., Methods: Predictions were provided for patients in the implementation group (n=110) and withheld from the comparison group (n=82). Predictions guided rehabilitation therapy focus for patients in the implementation group. The effects of predictive information on clinical practice (length of stay, therapist confidence, therapy content, and dose) were evaluated. Clinical outcomes (upper limb function, impairment and use, independence, and quality of life) were measured 3 and 6 months poststroke. The primary clinical practice outcome was inpatient length of stay. The primary clinical outcome was Action Research Arm Test score 3 months poststroke., Results: Length of stay was 1 week shorter for the implementation group (11 days; 95% confidence interval, 9-13 days) than the comparison group (17 days; 95% confidence interval, 14-21 days; P =0.001), controlling for upper limb impairment, age, sex, and comorbidities. Therapists were more confident ( P =0.004) and modified therapy content according to predictions for the implementation group ( P <0.05). The algorithm correctly predicted the primary clinical outcome for 80% of patients in both groups. There were no adverse effects of algorithm implementation on patient outcomes at 3 or 6 months poststroke., Conclusions: PREP algorithm predictions modify therapy content and increase rehabilitation efficiency after stroke without compromising clinical outcome., Clinical Trial Registration: URL: http://anzctr.org.au. Unique identifier: ACTRN12611000755932., (© 2017 American Heart Association, Inc.)

Background and Purpose: Recovery of upper-limb motor impairment after first-ever ischemic stroke is proportional to the degree of initial impairment in patients with a functional corticospinal tract (CST). This study aimed to investigate whether proportional recovery occurs in a more clinically relevant sample including patients with intracerebral hemorrhage and previous stroke., Methods: Patients with upper-limb weakness were assessed 3 days and 3 months poststroke with the Fugl-Meyer scale. Transcranial magnetic stimulation was used to test CST function, and patients were dichotomized according to the presence of motor evoked potentials in the paretic wrist extensors. Linear regression modeling of Δ Fugl-Meyer score between 3 days and 3 months was performed, with predictors including initial impairment (66 - baseline Fugl-Meyer score), age, sex, stroke type, previous stroke, comorbidities, and upper-limb therapy dose., Results: One hundred ninety-two patients were recruited, and 157 completed 3-month follow-up. Patients with a functional CST made a proportional recovery of 63% (95% confidence interval, 55%-70%) of initial motor impairment. The recovery of patients without a functional CST was not proportional to initial impairment and was reduced by greater CST damage., Conclusions: Recovery of motor impairment in patients with intact CST is proportional to initial impairment and unaffected by previous stroke, type of stroke, or upper-limb therapy dose. Novel interventions that interact with the neurobiological mechanisms of recovery are needed. The generalizability of proportional recovery is such that patients with intracerebral hemorrhage and previous stroke may usefully be included in interventional rehabilitation trials., Clinical Trial Registration: URL: http://www.anzctr.org.au. Unique identifier: ANZCTR12611000755932., (© 2017 American Heart Association, Inc.)

Reactive response inhibition (RI) is the cancellation of a prepared response when it is no longer appropriate. Selectivity of RI can be examined by cueing the cancellation of one component of a prepared multi-component response. This substantially delays execution of other components. There is debate regarding whether this response delay is due to a selective neural mechanism. Here we propose a computational activation threshold model (ATM) and test it against a classical "horse-race" model using behavioural and neurophysiological data from partial RI experiments. The models comprise both facilitatory and inhibitory processes that compete upstream of motor output regions. Summary statistics (means and standard deviations) of predicted muscular and neurophysiological data were fit in both models to equivalent experimental measures by minimizing a Pearson Chi-square statistic. The ATM best captured behavioural and neurophysiological dynamics of partial RI. The ATM demonstrated that the observed modulation of corticomotor excitability during partial RI can be explained by nonselective inhibition of the prepared response. The inhibition raised the activation threshold to a level that could not be reached by the original response. This was necessarily followed by an additional phase of facilitation representing a secondary activation process in order to reach the new inhibition threshold and initiate the executed component of the response. The ATM offers a mechanistic description of the neural events underlying RI, in which partial movement cancellation results from a nonselective inhibitory event followed by subsequent initiation of a new response. The ATM provides a framework for considering and exploring the neuroanatomical constraints that underlie RI., Competing Interests: The authors have declared that no competing interests exist.

The use of arm weight support (WS) to optimize movement quality may be an avenue for improved upper limb stroke rehabilitation; however, the underlying neurophysiological effects of WS are not well understood. Rehabilitation exercises may be performed when sitting or standing, but the interaction of posture with WS has not been examined until now. We explored the effect of posture with WS on corticomotor excitability (CME) in healthy adults. Thirteen participants performed static shoulder abduction in two postures (sitting and standing) at three levels of WS (0, 45, and 90 % of full support). Transcranial magnetic stimulation of primary motor cortex was used to elicit motor-evoked potentials (MEPs) in eight upper limb muscles. Stimulus-response (SR) curves were fitted to the MEP data using nonlinear regression. Whole-body posture interacted with WS to influence tonic activity and CME in all muscles examined. SR curve parameters revealed greater CME when standing compared to sitting for upper arm muscles, but lower CME to the shoulder, forearm, and hand. Distal to the shoulder, tonic activity and CME were modulated independent of any explicit differences in task requirements. Overall, these results support a model of integrated upper limb control influenced by whole-body posture and WS. These findings have implications for the application of WS in settings such as upper limb rehabilitation after stroke.

Aerobic exercise can enhance neuroplasticity although presently the neural mechanisms underpinning these benefits remain unclear. One possible mechanism is through effects on primary motor cortex (M1) function via down-regulation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The aim of the present study was to examine how corticomotor excitability (CME) and M1 intracortical inhibition are modulated in response to a single bout of moderate intensity aerobic exercise. Ten healthy right-handed adults were participants. Single- and paired-pulse transcranial magnetic stimulation was applied over left M1 to obtain motor-evoked potentials in the right flexor pollicis brevis. We examined CME, cortical silent period (SP) duration, short- and long-interval intracortical inhibition (SICI, LICI), and late cortical disinhibition (LCD), before and after acute aerobic exercise (exercise session) or an equivalent duration without exercise (control session). Aerobic exercise was performed on a cycle ergometer for 30 min at a workload equivalent to 60 % of maximal cardiorespiratory fitness (VO 2 peak; heart rate reserve = 75 ± 3 %, perceived exertion = 13.5 ± 0.7). LICI was reduced at 10 (52 ± 17 %, P = 0.03) and 20 min (27 ± 8 %, P = 0.03) post-exercise compared to baseline (13 ± 4 %). No significant changes in CME, SP duration, SICI or LCD were observed. The present study shows that GABA B -mediated intracortical inhibition may be down-regulated after acute aerobic exercise. The potential effects this may have on M1 plasticity remain to be determined.

The selective serotonin reuptake inhibitor fluoxetine significantly enhances adult visual cortex plasticity within the rat. This effect is related to decreased gamma-aminobutyric acid (GABA) mediated inhibition and identifies fluoxetine as a potential agent for enhancing plasticity in the adult human brain. We tested the hypothesis that fluoxetine would enhance visual perceptual learning of a motion direction discrimination (MDD) task in humans. We also investigated (1) the effect of fluoxetine on visual and motor cortex excitability and (2) the impact of increased GABA mediated inhibition following a single dose of triazolam on post-training MDD task performance. Within a double blind, placebo controlled design, 20 healthy adult participants completed a 19-day course of fluoxetine ( n = 10, 20 mg per day) or placebo ( n = 10). Participants were trained on the MDD task over the final 5 days of fluoxetine administration. Accuracy for the trained MDD stimulus and an untrained MDD stimulus configuration was assessed before and after training, after triazolam and 1 week after triazolam. Motor and visual cortex excitability were measured using transcranial magnetic stimulation. Fluoxetine did not enhance the magnitude or rate of perceptual learning and full transfer of learning to the untrained stimulus was observed for both groups. After training was complete, trazolam had no effect on trained task performance but significantly impaired untrained task performance. No consistent effects of fluoxetine on cortical excitability were observed. The results do not support the hypothesis that fluoxetine can enhance learning in humans. However, the specific effect of triazolam on MDD task performance for the untrained stimulus suggests that learning and learning transfer rely on dissociable neural mechanisms.

Paired-pulse transcranial magnetic stimulation (TMS) can be used to probe inhibitory activity in primary motor cortex (M1). Recruitment of descending volleys with TMS depends on the induced current direction in M1. Anterior-posterior (AP) stimulation preferentially activates late indirect- (I-) waves that are most susceptible to paired-pulse TMS. Threshold tracking TMS can assess intracortical inhibition; however, previous studies have only used a current direction that preferentially recruits early I-waves [posterior-anterior (PA)]. Our objective was to examine intracortical inhibition with threshold tracking TMS designed to preferentially recruit early vs. late I-waves with PA and AP stimulation respectively. Electromyographic recordings were obtained from the right first dorsal interosseous muscle of 15 participants (21-50 years). Motor evoked potentials elicited by TMS over left M1 were recorded for PA, AP and lateromedial (LM) induced currents, with I-wave recruitment calculated as the onset latency difference between PA-LM and AP-LM. Short- and long-interval intracortical inhibition (SICI and LICI) were examined across a range of conditioning stimulus intensities and interstimulus intervals (3 and 100-260 ms) with threshold tracking TMS for PA and AP stimulation. SICI and LICI were greater for AP compared with PA current direction using threshold tracking. In addition, the efficacy of late I-wave recruitment was associated with the extent of SICI for AP but not PA stimulation, and was not associated with LICI. These findings indicate that threshold tracking with an AP-induced current provides a more robust and sensitive measure of M1 intracortical inhibition than PA., (© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Marked distortions in sense of agency can be induced by hypnosis in susceptible individuals, including alterations in subjective awareness of movement initiation and control. These distortions, with associated disability, are similar to those experienced with Conversion Disorder (CD), an observation that has led to the hypothesis that hypnosis and CD share causal mechanisms. The purpose of this review is to explore the relationships among motor imagery (MI), hypnotic susceptibility, and CD, then to propose how MI ability may contribute to hypnotic responding and CD. Studies employing subjective assessments of mental imagery have found little association between imagery abilities and hypnotic susceptibility. A positive association between imagery abilities and hypnotic susceptibility becomes apparent when objective measures of imagery ability are employed. A candidate mechanism to explain motor responses during hypnosis is kinaesthetic MI, which engages a strategy that involves proprioception or the "feel" of movement when no movement occurs. Motor suppression imagery (MSI), a strategy involving inhibition of movement, may provide an alternate objective measurable phenomenon that underlies both hypnotic susceptibility and CD. Evidence to date supports the idea that there may be a positive association between kinaesthetic MI ability and hypnotic susceptibility. Additional evidence supports a positive association between hypnotic susceptibility and CD. Disturbances in kinaesthetic MI performance in CD patients indicate that MI mechanisms may also underlie CD symptoms. Further investigation of the above relationships is warranted to explain these phenomena, and establish theoretical explanations underlying sense of agency., (Copyright © 2016. Published by Elsevier Ltd.)

Daily activities often require sudden cancellation of preplanned movement, termed response inhibition. When only a subcomponent of a whole response must be suppressed (required here on Partial trials), the ensuing component is markedly delayed. The neural mechanisms underlying partial response inhibition remain unclear. We hypothesized that Partial trials would be associated with nonselective corticomotor suppression and that GABAB receptor-mediated inhibition within primary motor cortex might be responsible for the nonselective corticomotor suppression contributing to Partial trial response delays. Sixteen right-handed participants performed a bimanual anticipatory response inhibition task while single- and paired-pulse transcranial magnetic stimulation was delivered to elicit motor evoked potentials in the left first dorsal interosseous muscle. Lift times, amplitude of motor evoked potentials, and long-interval intracortical inhibition were examined across the different trial types (Go, Stop-Left, Stop-Right, Stop-Both). Go trials produced a tight distribution of lift times around the target, whereas those during Partial trials (Stop-Left and Stop-Right) were substantially delayed. The modulation of motor evoked potential amplitude during Stop-Right trials reflected anticipation, suppression, and subsequent reinitiation of movement. Importantly, suppression was present across all Stop trial types, indicative of a "default" nonselective inhibitory process. Compared with blocks containing only Go trials, inhibition increased when Stop trials were introduced but did not differ between trial types. The amount of inhibition was positively correlated with lift times during Stop-Right trials. Tonic levels of inhibition appear to be proactively modulated by task context and influence the speed at which unimanual responses occur after a nonselective "brake" is applied., (Copyright © 2016 the American Physiological Society.)

Dual-hemisphere transcranial direct current stimulation over the primary motor cortex (M1-M1 tDCS) is assumed to modulate neural excitability in a polarity-dependent manner and improve motor performance of the hand. In the proximal upper limb, the neurophysiological and behavioural after-effects of M1-M1 tDCS are not well known. This study investigated the after-effects of M1-M1 tDCS on contralateral, ipsilateral and transcallosal excitability to the proximal upper limb muscle biceps brachii (BB). Circle tracing was used to assess motor performance before and after tDCS as this task requires coordination of proximal and distal musculature. Sixteen healthy right-handed adults participated in the study, each receiving M1-M1 tDCS (1 mA, 15 min) or sham tDCS in separate sessions. The anode was positioned over right M1 and cathode over left M1. M1-M1 tDCS suppressed transcallosal inhibition from the M1 under the cathode (P < 0.045). No other neurophysiologic or behavioural effects were observed (P > 0.6). The study provides important information regarding inconsistent neurophysiological and behavioural changes following tDCS that have implications for future tDCS research on the motor system.

Background: Recovery of upper limb function is important for regaining independence after stroke., Objective: To test the effects of priming upper limb physical therapy with intermittent theta burst stimulation (iTBS), a form of noninvasive brain stimulation., Methods: Eighteen adults with first-ever chronic monohemispheric subcortical stroke participated in this randomized, controlled, triple-blinded trial. Intervention consisted of priming with real or sham iTBS to the ipsilesional primary motor cortex immediately before 45 minutes of upper limb physical therapy, daily for 10 days. Changes in upper limb function (Action Research Arm Test [ARAT]), upper limb impairment (Fugl-Meyer Scale), and corticomotor excitability, were assessed before, during, and immediately, 1 month and 3 months after the intervention. Functional magnetic resonance images were acquired before and at one month after the intervention., Results: Improvements in ARAT were observed after the intervention period when therapy was primed with real iTBS, but not sham, and were maintained at 1 month. These improvements were not apparent halfway through the intervention, indicating a dose effect. Improvements in ARAT at 1 month were related to balancing of corticomotor excitability and an increase in ipsilesional premotor cortex activation during paretic hand grip., Conclusions: Two weeks of iTBS-primed therapy improves upper limb function at the chronic stage of stroke, for at least 1 month postintervention, whereas therapy alone may not be sufficient to alter function. This indicates a potential role for iTBS as an adjuvant to therapy delivered at the chronic stage., (© The Author(s) 2015.)

Paired-pulse transcranial magnetic stimulation (TMS) can be used to examine intracortical inhibition in primary motor cortex (M1), termed short-interval intracortical inhibition (SICI). To our knowledge, SICI has only been demonstrated in contralateral motor evoked potentials (MEPs). Ipsilateral MEPs (iMEPs) are assumed to reflect excitability of an uncrossed oligosynaptic pathway, and can sometimes be evoked in proximal upper-limb muscles using high-intensity TMS. We examined whether iMEPs in the biceps brachii (BB) would be suppressed by subthreshold conditioning, therefore demonstrating SICI of iMEPs. TMS was delivered to the dominant M1 to evoke conditioned (C) and nonconditioned (NC) iMEPs in the nondominant BB of healthy participants during weak bilateral elbow flexion. The conditioning stimulus intensities tested were 85%, 100%, and 115% of active motor threshold (AMT), at 2 ms and 4 ms interstimulus intervals (ISI). The iMEP ratio (C/NC) was calculated for each condition to assess the amount of inhibition. Inhibition of iMEPs was present at 2 ms ISI with 100% and 115% AMT (bothP< 0.03), mediated by a reduction in persistence and size (allP< 0.05). To our knowledge, this is the first demonstration of SICI of iMEPs. This technique may be useful as a tool to better understand the role of ipsilateral M1 during functional motor tasks., (Copyright © 2016 the American Physiological Society.)

Children with unilateral cerebral palsy (CP) typically present with largely divergent upper limb sensorimotor deficits and individual differences in response to upper limb rehabilitation. This review summarizes how early brain damage can cause dramatic deviations from the normal anatomy of sensory and motor tracts, resulting in unique "wiring patterns" of the sensorimotor system in CP. Based on the existing literature, we suggest that corticospinal tract (CST) anatomy and integrity constrains sensorimotor function of the upper limb and potentially also the response to treatment. However, it is not possible to infer CST (re)organization from clinical presentation alone and conventional biomarkers, such as time of insult, location, and lesion extent seem to have limited clinical utility. Here, we propose a theoretical framework based on a detailed examination of the motor system using behavioral, neurophysiological, and magnetic resonance imaging measures, akin to those used to predict potential for upper limb recovery of adults after stroke. This theoretical framework might prove useful because it provides testable hypotheses for future research with the goal to develop and validate a clinical assessment flowchart to categorize children with unilateral CP.

Complex regional pain syndrome (CRPS) type I is characterized by somatosensory and motor deficits, and abnormalities have been reported for primary somatosensory (S1) and motor cortex (M1) excitability. For the latter, reduced short-latency intracortical inhibition (SICI) has been demonstrated in the somatotopic representation of the affected side. Recently, an intervention of applying anesthetic cream to the forearm has been shown to modulate both somatosensory deficits (eg, spatial tactile resolution [STR]) and SICI measured in hand muscles. We examined the efficacy of this intervention in patients with CRPS I. Cutaneous anesthesia of the forearm of the affected side was used to increase SICI of hand muscles and decrease impaired STR of the affected limb. In a double-blinded placebo-controlled study, we enrolled 12 patients with unilateral CRPS I of the hand in the chronic state. Before and after intervention, we measured motor evoked potentials of the first dorsal interosseus to obtain SICI and STR of both hand sides. Patients showed decreased STR on the tip of the thumb of their affected side, which improved after anesthetic cream but not after placebo application. Hand motor function of the affected side improved after anesthetic cream but not after placebo. Pain intensity was not modulated after intervention. At both hemispheres, SICI was decreased compared with reference values but selectively increased at the intervention side only after analgesic cream and not after placebo. Temporary deafferentation of an area neighbouring the CRPS-affected region can modulate neuropathological characteristics of CRPS and might be a promising strategy for therapeutic interventions.

Objective: For most patients, resolution of upper limb impairment during the first 6 months poststroke is 70% of the maximum possible. We sought to identify candidate mechanisms of this proportional recovery. We hypothesized that proportional resolution of upper limb impairment depends on ipsilesional corticomotor pathway function, is mirrored by proportional recovery of excitability in this pathway, and is unaffected by upper limb therapy dose., Methods: Upper limb impairment was measured in 93 patients at 2, 6, 12, and 26 weeks after first-ever ischemic stroke. Motor evoked potentials (MEPs) and motor threshold were recorded from extensor carpi radialis using transcranial magnetic stimulation, and fractional anisotropy (FA) in the posterior limbs of the internal capsules was determined with diffusion-weighted magnetic resonance imaging., Results: Initial impairment score, presence of MEPs and FA asymmetry were the only predictors of impairment resolution, indicating a key role for corticomotor tract function. By 12 weeks, upper limb impairment resolved by 70% in patients with MEPs regardless of their initial impairment, and ipsilesional rest motor threshold also resolved by 70%. Resolution of impairment was insensitive to upper limb therapy dose., Interpretation: These findings indicate that upper limb impairment resolves by 70% of the maximum possible, regardless of initial impairment, but only for patients with intact corticomotor function. Impairment resolution seems to reflect spontaneous neurobiological processes that involve the ipsilesional corticomotor pathway. A better understanding of these mechanisms could lead to interventions that increase resolution of impairment above 70%., (© 2015 American Neurological Association.)

Background: Weight support of the arm (WS) can be used in stroke rehabilitation to facilitate upper limb therapy, but the neurophysiological effects of this technique are not well understood. While an overall reduction in muscle activity is expected, the mechanism by which WS may alter the expression of muscle synergies has not been examined until now. We explored the neurophysiological effect of WS on the selectivity of biceps brachii (BB) activation in healthy adults., Methods: Thirteen participants completed counterbalanced movement tasks in a repeated measures design. Three levels of WS (0, 45, and 90 % of full support) were provided to the arm using a commercial device (Saebo Mobile Arm Support). At each level of WS, participants maintained a flexed shoulder posture while performing rhythmic isometric elbow flexion (BB agonist) or forearm pronation (BB antagonist). Single-pulse transcranial magnetic stimulation of primary motor cortex was used to elicit motor-evoked potentials (MEPs) in BB 100-300 ms before muscle contraction. Baseline muscle activity and MEP amplitude were the primary dependent measures. Effects of movement TASK and SUPPORT LEVEL were statistically analyzed using linear mixed effects models., Results: As expected, with increased support tonic activity was reduced across all muscles. This effect was greatest in the anti-gravity muscle anterior deltoid, and evident in biceps brachii and pronator teres as well. For BB MEP amplitude, TASK and SUPPORT LEVEL, interacted such that for elbow flexion, MEP amplitudes were smaller with incrementally greater WS whereas, for forearm pronation MEP amplitudes were smaller only at high WS., Conclusions: Weight support of the arm influences corticomotor selectivity of biceps brachii. WS may impact coordination independently of a global reduction in muscle activity. The amount of supportive force applied to the arm influences the neuromechanical control profile for the limb. These findings may inform the application of WS in upper limb stroke rehabilitation.

Failure to suppress antagonist muscles can lead to movement dysfunction, such as the abnormal muscle synergies often seen in the upper limb after stroke. A neurophysiological surrogate of upper limb synergies, the selectivity ratio (SR), can be determined from the ratio of biceps brachii (BB) motor evoked potentials to transcranial magnetic stimulation prior to forearm pronation versus elbow flexion. Surprisingly, cathodal transcranial direct current stimulation (c-TDCS) over ipsilateral primary motor cortex (M1) reduces (i.e. improves) the SR in healthy adults, and chronic stroke patients. The ability to suppress antagonist muscles may be exacerbated at high movement rates. The aim of the present study was to investigate whether the selective muscle activation of the biceps brachii (BB) is dependent on altering frequency demands, and whether the c-tDCS improvement of SR is dependent on task frequency. Seventeen healthy participants performed repetitive isometric elbow flexion and forearm pronation at three rates, before and after c-tDCS or sham delivered to ipsilateral left M1. Ipsilateral c-tDCS improved the SR in a frequency dependent manner by selectively suppressing BB antagonist excitability. Our findings confirm that c-tDCS is an effective tool for improving selective muscle activation, and provide novel evidence for its efficacy at rates of movement where it is most likely to benefit task performance.

Muscle synergies describe common patterns of co- or reciprocal activation that occur during movement. After stroke, these synergies change, often in stereotypical ways. The mechanism underlying this change reflects damage to key motor pathways as a result of the stroke lesion, and the subsequent reorganization along the neuroaxis, which may be further detrimental or restorative to motor function. The time course of abnormal synergy formation seems to lag spontaneous recovery that occurs in the initial weeks after stroke. In healthy individuals, motor cortical activity, descending via the corticospinal tract (CST) is the predominant driver of voluntary behavior. When the CST is damaged after stroke, other descending pathways may be up-regulated to compensate. The contribution of these pathways may emerge as new synergies take shape at the chronic stage after stroke, as a result of plasticity along the neuroaxis. The location of the stroke lesion and properties of the secondary descending pathways and their regulation are then critical for shaping the synergies in the remaining motor behavior. A consideration of the integrity of remaining descending motor pathways may aid in the design of new rehabilitation therapies.

A key issue in the field of noninvasive brain stimulation (NIBS) is the accurate localization of scalp positions that correspond to targeted cortical areas. The current gold standard is to combine structural and functional brain imaging with a commercially available "neuronavigation" system. However, neuronavigation systems are not commonplace outside of specialized research environments. Here we describe a technique that allows for the use of participant-specific functional and structural MRI data to guide NIBS without a neuronavigation system. Surface mesh representations of the head were generated using Brain Voyager and vectors linking key anatomical landmarks were drawn on the mesh. Our technique was then used to calculate the precise distances on the scalp corresponding to these vectors. These calculations were verified using actual measurements of the head and the technique was used to identify a scalp position corresponding to a brain area localized using functional MRI.

Parkinson's disease (Pd) is the second most prevalent degenerative neurological condition worldwide. Improving and sustaining quality of life is an important goal for Parkinson's patients. Key areas of focus to achieve this goal include earlier diagnosis and individualized treatment. In this review the authors discuss impulse control in Pd and examine how measures of impulse control from a response inhibition task may provide clinically useful information (a) within an objective test battery to aid earlier diagnosis of Pd and (b) in postdiagnostic Pd, to better identify individuals at risk of developing impulse control disorders with dopaminergic medication.

Partial weight support may hold promise as a therapeutic adjuvant during rehabilitation after stroke by providing a permissive environment for reducing the expression of abnormal muscle synergies that cause upper limb impairment. We explored the neurophysiological effects of upper limb weight support in 13 healthy young adults by measuring motor-evoked potentials (MEPs) from transcranial magnetic stimulation (TMS) of primary motor cortex and electromyography from anterior deltoid (AD), biceps brachii (BB), extensor carpi radialis (ECR), and first dorsal interosseous (FDI). Five levels of weight support, varying from none to full, were provided to the arm using a commercial device (Saebo Mobile Arm Support). For each level of support, stimulus-response (SR) curves were derived from MEPs across a range of TMS intensities. Weight support affected background EMG activity in each of the four muscles examined (P < 0.0001 for each muscle). Tonic background activity was primarily reduced in the AD. Weight support had a differential effect on the size of MEPs across muscles. After curve fitting, the SR plateau for ECR increased at the lowest support level (P = 0.004). For FDI, the SR plateau increased at the highest support level (P = 0.0003). These results indicate that weight support of the proximal upper limb modulates corticomotor excitability across the forearm and hand. The findings support a model of integrated control of the upper limb and may inform the use of weight support in clinical settings., (© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Purpose of Review: This review presents recent developments in the prediction of motor recovery after stroke; explores whether rehabilitation interventions delivered during the spontaneous recovery process can improve outcomes; and identifies the first trials to focus on the rate rather than extent of motor recovery (Supplementary Digital Content 1)., Recent Findings: Two recent studies have attempted to accelerate the rate of motor recovery during the first few weeks after stroke, with neuromodulation techniques designed to facilitate excitability of the ipsilesional motor cortex. One trial using transcranial direct current stimulation was negative, and the other trial using bilateral priming was positive. These contrasting results may be explained by important differences in trial design. This new focus on modifying rate, rather than extent, of motor recovery is in line with accumulating evidence that the motor recovery plateau is largely determined by the extent of damage to descending motor pathways, which is currently untreatable., Summary: Interventions that facilitate neural plasticity and reorganization may accelerate recovery of motor function during the spontaneous recovery period, without affecting final outcome. This may represent a useful new approach for future trials conducted during rehabilitation at the subacute stage of stroke.

Background: Motor deficits after a stroke are thought to be compounded by the development of asymmetric interhemispheric inhibition. Bilateral priming was developed to rebalance this asymmetry and thus improve therapy efficacy., Objective: This study investigated the effect of bilateral priming before Wii-based Movement Therapy to improve rehabilitation after stroke., Methods: Ten patients who had suffered a stroke (age, 23-77 years; 3-123 months after stroke) underwent a 14-day program of Wii-based Movement Therapy for upper limb rehabilitation. Formal Wii-based Movement Therapy sessions were immediately preceded by 15 minutes of bilateral priming, whereby active flexion-extension of the less affected wrist drove mirror-symmetric passive movements of the more affected wrist through a custom device. Functional movement was assessed at weeks 0 (before therapy), 3 (after therapy), and 28 (follow-up) using the Wolf Motor Function Test (WMFT), upper limb Fugl-Meyer Assessment (FMA), upper limb range of motion, and Motor Activity Log (MAL). Case-matched controls were patients who had suffered a stroke who received Wii-based Movement Therapy but not bilateral priming., Results: Upper limb functional ability improved for both groups on all measures tested. Posttherapy improvement on the FMA for primed patients was twice that of the unprimed patients (37.3% vs 14.6%, respectively) and was significantly better maintained at 28 weeks (P = .02). Improvements on the WMFT and MAL were similar for both groups, but the pattern of change in range of motion was strikingly different., Conclusions: Bilateral priming before Wii-based Movement Therapy led to a greater magnitude and retention of improvement compared to control, especially measured with the FMA. These data suggest that bilateral priming can enhance the efficacy of Wii-based Movement Therapy, particularly for patients with low motor function after a stroke., (© The Author(s) 2014.)

Aim: To explore the relationship between motor cortical and descending motor pathway reorganization, lesion type, and upper limb function in youth with unilateral cerebral palsy (CP)., Methods: Twenty participants with unilateral CP (mean age 15 ± 3 years; 11 males) completed a range of upper limb functional measures. Structural MRI, diffusion-weighted, and functional MRI were conducted to determine type and extent of brain lesion, descending white matter integrity, and whole-brain activity during affected hand use. Single pulse transcranial magnetic stimulation (TMS) (n = 12) was used to examine functional integrity of the corticospinal pathway as well as primary motor cortex intracortical and interhemispheric inhibition from motor-evoked potentials and silent periods., Results: Fractional anisotropy measures within the posterior limb of the internal capsule were a predictor of upper limb function (R (2) = 0.41, F = 11.3, p = 0.004). Participants with periventricular lesions tended to have better upper limb function [F(2, 17) = 42.48, p < 0.0001]. Five participants with evidence of cortical reorganization and functional ipsilateral projections to their affected hand had worse upper limb function. Deficits in intracortical and interhemispheric inhibitory mechanisms were found in participants with worse upper limb function (Melbourne Assessment of Unilateral Upper Limb Function: Mann Whitney p = 0.02)., Conclusion: Neuroimaging and TMS can provide useful information related to hand function of individuals with unilateral CP and may have potential to assist as a predictive tool and/or guide rehabilitation.

Motor learning requires practice over a period of time and depends on brain plasticity, yet even for relatively simple movements, there are multiple practice strategies that can be used for skill acquisition. We investigated the role of intracortical inhibition in the primary motor cortex (M1) during motor skill learning. Event-related transcranial magnetic stimulation (TMS) was used to assess corticomotor excitability and inhibition thought to involve synaptic and extrasynaptic γ-aminobutyric acid (GABA). Short intracortical inhibition (SICI) was assessed using 1- and 2.5-ms interstimulus intervals (ISIs). Participants learned a novel, sequential pinch-grip task on a computer in either a repetitive or interleaved practice structure. Both practice structures showed equivalent levels of motor performance at the end of acquisition and at retention 1 wk later. There was a novel task-related modulation of 1-ms SICI. Repetitive practice elicited a greater reduction of 1- and 2.5-ms SICI, i.e., disinhibition, between rest and task acquisition, compared with interleaved practice. These novel findings support the use of a repetitive practice structure for motor learning because the associated effects within M1 have relevance for motor rehabilitation., (Copyright © 2014 the American Physiological Society.)

Propriospinal premotoneurons (PN) are essential for accurate control of the upper limb. They receive bilateral input from premotor (PM) and primary motor (M1) cortices. In humans, excitability of PNs can be estimated from motor-evoked potentials (MEPs) by pairing a descending volley using transcranial magnetic stimulation (TMS) to summate with an ascending volley from peripheral nerve stimulation at the C3-C4 level of the spinal cord. Transcranial direct current stimulation (tDCS) alters excitability of cortical and subcortical areas. A recent study demonstrated that cathodal tDCS can suppress facilitatory (FAC) and inhibitory (INH) components of PN excitability, presumably via effects on corticoreticulospinal neurons (Bradnam LV, Stinear CM, Lewis GN, Byblow WD. J Neurophysiol 103: 2382-2389, 2010). The present study investigated the effects of bilateral tDCS with healthy subjects. The cathode was placed over left dorsal PM or M1 and the anode over right M1 in separate sessions (PM-M1, M1-M1, or Sham). TMS of right M1 elicited MEPs in left biceps brachii across a range of TMS intensities chosen to examine PN-mediated FAC and INH. Conditioning was applied using median nerve stimulation with an interstimulus interval that coincided with TMS and peripheral volleys summating at the C3-C4 level. All participants showed FAC at TMS intensities near active motor threshold and INH at slightly higher intensities. After tDCS, FAC was reduced for M1-M1 compared with Sham but not after PM-M1 stimulation. Contrary to an earlier study with cathodal tDCS, INH was unchanged across all sessions. The difference between these and earlier findings may relate to dual- vs. single-hemisphere M1 stimulation. M1-M1 tDCS may be a useful adjuvant to techniques that aim to reduce upper limb impairment after stroke., (Copyright © 2014 the American Physiological Society.)

The integrity of descending white matter pathways, measured by fractional anisotropy from DW-MRI, is a key prognostic indicator of motor recovery after stroke. Barriers to translation of fractional anisotropy measures into routine clinical practice include the time required for manually delineating volumes of interest (VOIs), and inter-examiner variability in this process. This study investigated whether registering and then editing template volumes of interest 'as required' would improve inter-examiner reliability compared with manual delineation, without compromising validity. MRI was performed with 30 sub-acute stroke patients with motor deficits (mean NIHSS = 11, range 0-17). Four independent examiners manually delineated VOIs for the posterior limbs of the internal capsules on T1 images, or edited template VOIs that had been registered to the T1 images if they encroached on ventricles or basal ganglia. Fractional anisotropy within each VOI and interhemispheric asymmetry were then calculated. We found that 13/30 registered template VOIs required editing. Edited template VOIs were more spatially similar between examiners than the manually delineated VOIs (p = 0.005). Both methods produced similar asymmetry values that correlated with clinical scores with near perfect levels of agreement between examiners. Contralesional fractional anisotropy correlated with age when edited template VOIs were used but not when VOIs were manually delineated. Editing template VOIs as required is reliable, increases the validity of fractional anisotropy measurements in the posterior limb of the internal capsule, and is less time-consuming compared to manual delineation. This approach could support the use of FA asymmetry measures in routine clinical practice.

Background: Amblyopia is a neurodevelopmental disorder of vision that is associated with abnormal patterns of neural inhibition within the visual cortex. This disorder is often considered to be untreatable in adulthood because of insufficient visual cortex plasticity. There is increasing evidence that interventions that target inhibitory interactions within the visual cortex, including certain types of noninvasive brain stimulation, can improve visual function in adults with amblyopia., Objective: We tested the hypothesis that anodal transcranial direct current stimulation (a-tDCS) would improve visual function in adults with amblyopia by enhancing the neural response to inputs from the amblyopic eye., Methods: Thirteen adults with amblyopia participated and contrast sensitivity in the amblyopic and fellow fixing eye was assessed before, during and after a-tDCS or cathodal tDCS (c-tDCS). Five participants also completed a functional magnetic resonance imaging (fMRI) study designed to investigate the effect of a-tDCS on the blood oxygen level-dependent response within the visual cortex to inputs from the amblyopic versus the fellow fixing eye., Results: A subgroup of 8/13 participants showed a transient improvement in amblyopic eye contrast sensitivity for at least 30 minutes after a-tDCS. fMRI measurements indicated that the characteristic cortical response asymmetry in amblyopes, which favors the fellow eye, was reduced by a-tDCS., Conclusions: These preliminary results suggest that a-tDCS deserves further investigation as a potential tool to enhance amblyopia treatment outcomes in adults.

Amblyopia is a neurodevelopmental disorder of vision caused by abnormal visual experience during early childhood that is often considered to be untreatable in adulthood. Recently, it has been shown that a novel dichoptic videogame-based treatment for amblyopia can improve visual function in adult patients, at least in part, by reducing inhibition of inputs from the amblyopic eye to the visual cortex. Non-invasive anodal transcranial direct current stimulation has been shown to reduce the activity of inhibitory cortical interneurons when applied to the primary motor or visual cortex. In this double-blind, sham-controlled cross-over study we tested the hypothesis that anodal transcranial direct current stimulation of the visual cortex would enhance the therapeutic effects of dichoptic videogame-based treatment. A homogeneous group of 16 young adults (mean age 22.1 ± 1.1 years) with amblyopia were studied to compare the effect of dichoptic treatment alone and dichoptic treatment combined with visual cortex direct current stimulation on measures of binocular (stereopsis) and monocular (visual acuity) visual function. The combined treatment led to greater improvements in stereoacuity than dichoptic treatment alone, indicating that direct current stimulation of the visual cortex boosts the efficacy of dichoptic videogame-based treatment. This intervention warrants further evaluation as a novel therapeutic approach for adults with amblyopia.

Hand and foot movements are made more reliably when both limbs move in the same direction at the same time (isodirectional) compared with when they are made in opposite directions (anisodirectional). We hypothesized that M1 intracortical facilitation may subserve hand-foot coordination and reveal correlates that explain the preference for hand-foot movements to be performed in an isodirectional pattern. To test our hypothesis we investigated behavioral kinematics of hand-foot coordination (experiment 1) and neurophysiological measures of corticomotor excitability and intracortical facilitation (experiment 2) in 17 healthy young adults. As expected, coordination became unstable in the anisodirectional pattern but not the isodirectional pattern, as confirmed in measures of wrist and ankle relative phase error and stability (both P < 0.001). Short-latency paired-pulse TMS was used to elicit motor evoked potentials (MEPs) and produce short-latency intracortical facilitation (sICF) in right extensor carpi radialis (ECR) and flexor carpi radialis (FCR) in the presence and absence of right ankle plantarflexion/dorsiflexion (P < 0.015). An isodirectional preference was confirmed by facilitation of FCR MEPs and TMS-induced wrist flexion during ankle plantarflexion (both P < 0.025) but no evidence of modulation of any particular "I wave" during foot movement compared with rest. A novel finding was the association between loss of stability of the anisodirectional pattern (experiment 1) and the modulation of corticomotor excitability in support of the isodirectional pattern (experiment 2) (P < 0.05). The preference for isodirectional hand-foot movements appears not to depend on M1 intracortical facilitation.

In humans the two cerebral hemispheres have essential roles in controlling the upper limb. The purpose of this article is to draw attention to the potential importance of ipsilateral descending pathways for functional recovery after stroke, and the use of non-invasive brain stimulation (NBS) protocols of the contralesional primary motor cortex (M1). Conventionally NBS is used to suppress contralesional M1, and to attenuate transcallosal inhibition onto the ipsilesional M1. There has been little consideration of the fact that contralesional M1 suppression may also reduce excitability of ipsilateral descending pathways that may be important for paretic upper limb control for some patients. One such ipsilateral pathway is the cortico-reticulo-propriospinal pathway (CRPP). In this review we outline a neurophysiological model to explain how contralesional M1 may gain control of the paretic arm via the CRPP. We conclude that the relative importance of the CRPP for motor control in individual patients must be considered before using NBS to suppress contralesional M1. Neurophysiological, neuroimaging, and clinical assessments can assist this decision making and facilitate the translation of NBS into the clinical setting.

Temporary deafferentation of the upper limb, with ischemic or anesthetic nerve block, has rapid effects on sensorimotor cortex. Cutaneous anesthesia of the forearm has recently been found to improve sensory and motor function of the paretic hand in chronic stroke patients. However, the neurophysiological mechanisms are unknown. The aim of this study was to investigate the behavioral and neurophysiological effects of cutaneous forearm anesthesia. Twenty-five healthy right-handed adults participated in this double-blind, randomized study. Participants completed two sessions, with either a topical anesthesia cream (EMLA) or placebo applied to their left forearm in each session. Thresholds for cutaneous sensation and spatial acuity of the left hand were measured before and after the intervention. Transcranial magnetic stimulation was used to measure corticomotor excitability and short-interval intracortical inhibition in the left first dorsal interosseous and abductor digiti minimi muscles before and after the intervention. Manual dexterity was assessed with the grooved pegboard task after the intervention in each session. Left-hand dexterity improved to a greater extent after treatment with EMLA than placebo, and this was related to improved spatial acuity at the fingertips. Corticomotor excitability remained stable, and short-interval intracortical inhibition increased after EMLA treatment. We have confirmed and extended previous reports that cutaneous forearm anesthesia results in improved spatial acuity and manual dexterity of the ipsilateral hand. The neurophysiological mechanisms involve an increase in intracortical inhibition, which may improve the precision of voluntary movement. These results lend support to the therapeutic application of EMLA in movement rehabilitation.

Cathodal transcranial direct current stimulation (c-tDCS) can reduce excitability of neurons in primary motor cortex (M1) and may facilitate motor recovery after stroke. However, little is known about the neurophysiological effects of tDCS on proximal upper limb function. We hypothesized that suppression of contralesional M1 (cM1) excitability would produce neurophysiological effects that depended on the severity of upper limb impairment. Twelve patients with varying upper limb impairment after subcortical stroke were assessed on clinical scales of upper limb spasticity, impairment, and function. Magnetic resonance imaging was used to determine lesion size and fractional anisotropy (FA) within the posterior limbs of the internal capsules indicative of corticospinal tract integrity. Excitability within paretic M1 biceps brachii representation was determined from motor-evoked potentials during selective isometric tasks, after cM1 sham stimulation and after c-tDCS. These neurophysiological data indicate that c-tDCS improved selective proximal upper limb control for mildly impaired patients and worsened it for moderate to severely impaired patients. The direction of the neurophysiological after effects of c-tDCS was strongly related to upper limb spasticity, impairment, function, and FA asymmetry between the posterior limbs of the internal capsules. These results indicate systematic variation of cM1 for proximal upper limb control after stroke and that suppression of cM1 excitability is not a "one size fits all" approach.

The ability to prevent unwanted movement is fundamental to human behavior. When healthy adults must prevent a subset of prepared actions, execution of the remaining response is markedly delayed. We hypothesized that the delay may be sensitive to the degree of similarity between the prevented and continued actions. Fifteen healthy participants performed an anticipatory response inhibition task that required bilateral index finger extension or thumb abduction with homogeneous digit pairings, or a heterogeneous pairing of a combination of the two movements. We expected that the uncoupling of responses required for selective movement prevention would be more difficult with homogeneous (same digit, homologous muscles) than heterogeneous pairings (different digits, nonhomologous muscles). Measures of response times (and asynchrony between digits) during action execution, stopping performance, and electromyography from EIP (index finger extension) and APB (thumb abduction) were analyzed. As expected, selective trials produced a delay in the remaining movement compared with execution trials. Successful performance in the selective condition occurred via suppression of the entire prepared response and subsequent selective reinitiation of the remaining component. Importantly, the delayed reinitiation of motor output was sensitive to the degree of similarity between responses, occurring later but at a faster rate with homogeneous digits. There were persistent aftereffects from the selective condition on the motor system, which indicated greater levels of inhibition and a higher gain were necessary to successfully perform selective trials with homogeneous pairings. Overall, the results support a model of inhibition of a unitary response and selective reinitiation, rather than selective inhibition.

Stroke is a leading cause of adult disability and the recovery of motor function is important for independence in activities of daily living. Predicting motor recovery after stroke in individual patients is difficult. Accurate prognosis would enable realistic rehabilitation goal-setting and more efficient allocation of resources. The aim of this study was to test and refine an algorithm for predicting the potential for recovery of upper limb function after stroke. Forty participants were prospectively enrolled within 3 days of ischaemic stroke. First, shoulder abduction and finger extension strength were graded 72 h after stroke onset to compute a shoulder abduction and finger extension score. Secondly, transcranial magnetic stimulation was used to assess the functional integrity of descending motor pathways to the affected upper limb. Third, diffusion-weighted magnetic resonance imaging was used to assess the structural integrity of the posterior limbs of the internal capsules. Finally, these measures were combined in the PREP algorithm for predicting an individual's potential for upper limb recovery at 12 weeks, measured with the Action Research Arm Test. A cluster analysis was used to independently group patients according to Action Research Arm Test score at 12 weeks, for comparison with predictions from the PREP algorithm. There was excellent correspondence between the cluster analysis of Action Research Arm Test score at 12 weeks and predictions made with the PREP algorithm. The algorithm had positive predictive power of 88%, negative predictive power of 83%, specificity of 88% and sensitivity of 73%. This study provides preliminary data in support of the PREP algorithm for the prognosis of upper limb recovery in individual patients. PREP may enable tailored planning of rehabilitation and more accurate stratification of patients in clinical trials.

Motor imagery (MI) increases corticomotor excitability and modulates intracortical inhibition. This study aimed to relate these neurophysiological mechanisms to imagery quality. Twenty-three healthy adults participated. First, the ability to vividly and accurately imagine performing a finger-to-thumb opposition task was evaluated by calculating a MI index (MII) based on psychological, behavioural and psychophysiological measurements. These scores were used to distinguish good from poor imagers. Transcranial magnetic stimulation was then used to assess modulation of corticomotor excitability, short-interval intracortical inhibition (sICI) and short-interval intracortical facilitation (sICF). Participants imagined abduction of their right thumb paced by a 1-Hz metronome. Single and paired magnetic stimuli were delivered at rest, while listening to the metronome, and during or between imagined movements. Corticomotor excitability was facilitated in the right opponens pollicis for good and poor imagers during MI, and this was positively correlated to the MII score. Poor imagers also facilitated corticomotor excitability of the right abductor digiti minimi, which was not involved in the movement. No interactions were found with sICI and sICF for good imagers, whereas poor imagers recruited intracortical facilitation while imagining. Accurate MI performance was characterised by muscle-specific temporal modulation of corticomotor excitability., (© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

Repetitive mirror symmetric bilateral upper limb may be a suitable priming technique for upper limb rehabilitation after stroke. Here we demonstrate neurophysiological and behavioural after-effects in healthy participants after priming with 20 minutes of repetitive active-passive bimanual wrist flexion and extension in a mirror symmetric pattern with respect to the body midline (MIR) compared to an control priming condition with alternating flexion-extension (ALT). Transcranial magnetic stimulation (TMS) indicated that corticomotor excitability (CME) of the passive hemisphere remained elevated compared to baseline for at least 30 minutes after MIR but not ALT, evidenced by an increase in the size of motor evoked potentials in ECR and FCR. Short and long-latency intracortical inhibition (SICI, LICI), short afferent inhibition (SAI) and interhemispheric inhibition (IHI) were also examined using pairs of stimuli. LICI differed between patterns, with less LICI after MIR compared with ALT, and an effect of pattern on IHI, with reduced IHI in passive FCR 15 minutes after MIR compared with ALT and baseline. There was no effect of pattern on SAI or FCR H-reflex. Similarly, SICI remained unchanged after 20 minutes of MIR. We then had participants complete a timed manual dexterity motor learning task with the passive hand during, immediately after, and 24 hours after MIR or control priming. The rate of task completion was faster with MIR priming compared to control conditions. Finally, ECR and FCR MEPs were examined within a pre-movement facilitation paradigm of wrist extension before and after MIR. ECR, but not FCR, MEPs were consistently facilitated before and after MIR, demonstrating no degradation of selective muscle activation. In summary, mirror symmetric active-passive bimanual movement increases CME and can enhance motor learning without degradation of muscle selectivity. These findings rationalise the use of mirror symmetric bimanual movement as a priming modality in post-stroke upper limb rehabilitation.

Both mental rotation (MR) and motor imagery (MI) involve an internalization of movement within motor and parietal cortex. Transcranial magnetic stimulation (TMS) techniques allow for a task-dependent investigation of the interhemispheric interaction between these areas. We used image-guided dual-coil TMS to investigate interactions between right inferior parietal lobe (rIPL) and left primary motor cortex (M1) in 11 healthy participants. They performed MI (right index-thumb pinching in time with a 1 Hz metronome) or hand MR tasks, while motor evoked potentials (MEPs) were recorded from right first dorsal interosseous. At rest, rIPL conditioning 6 ms prior to M1 stimulation facilitated MEPs in all participants, whereas this facilitation was abolished during MR. While rIPL conditioning 12 ms prior to M1 stimulation had no effect on MEPs at rest, it suppressed corticomotor excitability during MI. These results support the idea that rIPL forms part of a distinct inhibitory network that may prevent unwanted movement during imagery tasks.

Transcranial direct current stimulation (tDCS) is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN), was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex.

Objective: To evaluate use-dependent plasticity (UDP) before and after training under metronome-paced and self-paced conditions., Methods: Twelve healthy adults were recruited to this cross-over, pseudo-randomized, repeated measures study. Participants performed wrist extension training that was either self-paced, or externally-paced to an auditory metronome at their preferred movement frequency or at a more demanding frequency. Motor evoked potentials from transcranial magnetic stimulation of left primary motor cortex were recorded in right extensor carpi radialis (ECR) and flexor carpi radialis (FCR) to assess corticomotor excitability. The direction and velocity of TMS-evoked wrist movement (stimulus-evoked velocity, SEV) were measured before and after training to evaluate UDP., Results: The most persistent UDP occurred when training was metronome-paced at the participant's preferred movement frequency. This training protocol produced spatially selective modulation of resting ECR and FCR corticomotor excitability and directional tuning of TMS-evoked wrist movement toward the trained direction. Metronome-paced training at a more demanding frequency resulted in nonspecific facilitation of resting corticomotor excitability, and did not alter TMS-evoked wrist movement., Conclusions: These novel findings indicate that externally-paced training at the individual's preferred frequency facilitates UDP., Significance: UDP underpins motor recovery after stroke. Externally-paced training may be a useful adjunct to movement rehabilitation therapy., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Task-specific focal dystonia is thought to have a neurological basis where stereotypical synchronous inputs and maladaptive plasticity play a role. As afferent input is a powerful driver of cortical reorganization, we propose that a period of asynchronous afferent stimulation may reverse maladaptive cortical changes and alleviate symptoms. Using transcranial magnetic stimulation (TMS), 3 hand muscles were mapped in 10 dystonics and 10 healthy controls. Mapping occurred before and after 1 h of nonassociative stimulation (NAS) to first dorsal interosseous (FDI) and abductor pollicis brevis (APB). Participants performed grip lift, handwriting, and cyclic drawing before and after NAS. Prior to NAS, dystonics had larger maps, and the centers of gravity (CoGs) of the FDI and APB maps were closer together. Dystonics demonstrated impairments in grip-lift, handwriting, and cyclic drawing tasks. Following NAS, map size was reduced in all muscles in dystonic participants and FDI and APB CoGs moved further apart. Among dystonics, NAS produced a reduction in movement variability during cyclic drawing. Thus, 1 h of NAS can reduce the magnitude, and increase the separation, of TMS representational maps. We suggest that these changes reflect some normalization of the representational abnormalities seen in focal dystonia and provide initial, limited evidence that such changes are associated with improvements in circle drawing.

After stroke, the function of primary motor cortex (M1) between the hemispheres may become unbalanced. Techniques that promote a re-balancing of M1 excitability may prime the brain to be more responsive to rehabilitation therapies and lead to improved functional outcomes. The present study examined the effects of Active-Passive Bilateral Therapy (APBT), a putative movement-based priming strategy designed to reduce intracortical inhibition and increase excitability within the ipsilesional M1. Thirty-two patients with upper limb weakness at least 6 months after stroke were randomized to a 1-month intervention of self-directed motor practice with their affected upper limb (control group) or to APBT for 10-15 min prior to the same motor practice (APBT group). A blinded clinical rater assessed upper limb function at baseline, and immediately and 1 month after the intervention. Transcranial magnetic stimulation was used to assess M1 excitability. Immediately after the intervention, motor function of the affected upper limb improved in both groups (P < 0.005). One month after the intervention, the APBT group had better upper limb motor function than control patients (P < 0.05). The APBT group had increased ipsilesional M1 excitability (P < 0.025), increased transcallosal inhibition from ipsilesional to contralesional M1 (P < 0.01) and increased intracortical inhibition within contralesional M1 (P < 0.005). None of these changes were found in the control group. APBT produced sustained improvements in upper limb motor function in chronic stroke patients and induced specific and sustained changes in motor cortex inhibitory function. We speculate that APBT may have facilitated plastic reorganization in the brain in response to motor therapy. The utility of APBT as an adjuvant to physical therapy warrants further consideration.

Determining whether a person with stroke has reached their full potential for recovery is difficult. While techniques such as transcranial magnetic stimulation (TMS) and MRI have some prognostic value, their role in rehabilitation is undefined. This study used TMS and MRI to determine which factors predict functional potential, defined as an individual's capacity for further functional improvement at least 6 months following stroke. We studied 21 chronic stroke patients with upper limb impairment. The functional integrity of the corticospinal tracts (CSTs) was assessed using TMS and functional MRI. The presence or absence of motor-evoked responses (MEPs) to TMS in the affected upper limb, and the lateralization of cortical activity during affected hand use were determined. The structural integrity of the CST was assessed using MRI, and diffusion tensor imaging was used to measure the asymmetry in fractional anisotropy (FA) of the internal capsules. A multiple linear regression analysis was performed, to predict both clinical score at inception and change in clinical score for 17 patients who completed a 30 day programme of motor practice with the affected upper limb. The main findings were that in patients with MEPs, meaningful gains were still possible 3 years after stroke, although the capacity for improvement declined with time. In patients without MEPs, functional potential declines with increasing CST disruption, with no meaningful gains possible if FA asymmetry exceeds a value of 0.25. This study is the first to demonstrate the complementary nature of TMS and MRI techniques in predicting functional potential in chronic stroke patients. An algorithm is proposed for the selection of individualized rehabilitation strategies, based on the prediction of functional potential. These strategies could include neuromodulation using a range of emerging techniques, to prime the motor system for a plastic response to rehabilitation.

Purpose: To determine whether a model of two subtypes of yips is supported by evidence from a range of physiological, behavioral, and psychological measures., Methods: Fifteen golfers who experience yips symptoms while putting (mean age 58.1 yr, SD 13.6 yr), and nine golfers with no yips symptoms (mean age 39.6 yr, SD 19.3 yr) were recruited. Participants completed a golf history questionnaire to determine their playing experience and the nature of any yips symptoms experienced. In experiment 1, participants performed a putting task while electromyographic data were recorded from the forearm flexors and extensors and biceps brachii, bilaterally. The task was performed in two sessions, under low-pressure and high-pressure experimental conditions. The high-pressure condition was intended to increase anxiety through the use of a monetary incentive, video-taping of performance, and the presence of a confederate who provided negative feedback. Participants' state of anxiety was assessed using a questionnaire before each of the experimental sessions. In experiment 2, participants completed a task that required the inhibition of an anticipated response. Their accuracy and ability to inhibit their response was determined., Results: The golfers who experienced yips could be categorized according to whether they reported mainly movement-related symptoms (Type I) or anxiety-related symptoms (Type II). The Type I group exhibited greater muscle activity during putting and greater errors and less inhibition of the anticipated response task. The Type II group exhibited greater changes in cognitive anxiety and normal performance of the anticipated response task., Conclusion: This study provides evidence in support of two yips subtypes. Type I is related to impaired movement initiation and execution, whereas Type II is related to performance anxiety.

Objective: This study investigated whether kinesthetic and/or visual imagery could alter the contingent negative variation (CNV) for patients with Parkinson's disease (PD)., Methods: The CNV was recorded in six patients with PD and seven controls before and after a 10min block of imagery. There were two types of imagery employed: kinesthetic and visual, which were evaluated on separate days., Results: The global field power (GFP) of the late CNV did not change after the visual imagery for either group, nor was there a significant difference between the groups. In contrast, kinesthetic imagery resulted in significant group differences pre-, versus post-imagery GFPs, which was not present prior to performing the kinesthetic imagery task. In patients with PD, the CNV amplitudes post-, relative to pre-kinesthetic imagery, increased over the dorsolateral prefrontal regions and decreased in the ipsilateral parietal regions. There were no such changes in controls., Conclusions: A 10-min session of kinesthetic imagery enhanced the GFP amplitude of the late CNV for patients but not for controls., Significance: While the study needs to be replicated with a greater number of participants, the results suggest that kinesthetic imagery may be a promising tool for investigations into motor changes, and may potentially be employed therapeutically, in patients with Parkinson's disease.

Most studies of motor imagery have examined motor cortex function during imagery of dominant hand movement. The aim of this study was to examine the modulation of excitability in the dominant and non-dominant corticomotor pathways during kinesthetic motor imagery of unimanual and bimanual movement. Transcranial magnetic stimulation (TMS) was applied over the contralateral motor cortex (M1) to elicit motor-evoked potentials (MEPs) in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles of each hand, in two separate sessions. Transcutaneous electrical stimuli were also delivered to the median nerve at each wrist, to elicit F-waves from APB. Fifteen right-handed volunteers imagined unimanual and bimanual phasic thumb movements, paced with a 1-Hz auditory metronome. Stimuli were delivered at rest, and either 50 ms before (ON phase), or 450 ms after (OFF phase), the metronome beeps. Significant MEP amplitude facilitation occurred only in right APB, during the ON phase of motor imagery of the right hand and both hands. Significant temporal modulation of right APB MEP amplitude was observed during motor imagery of right, left and bimanual performance. F-wave persistence and amplitude were unaffected by imagery. These results demonstrate that the motor imagery is lateralized to the left (dominant) hemisphere, which is engaged by imagery of each hand separately, and bimanual imagery. This finding has implications for the use of motor imagery in rehabilitation.

Focal hand dystonia (FHD) is a movement disorder that is also associated with impaired sensory function and sensorimotor integration. The aim of this study was to assess the modulation of inhibitory function in the motor cortex during the performance of four motor tasks (isometric pinch grip, writing, texture discrimination, and a phasic control task) in 8 FHD and 8 control subjects. The affected hands of the FHD subjects and the dominant hands of the control subjects were tested. Inhibitory function was assessed using transcranial magnetic stimulation to evoke a silent period in the ongoing electromyographic activity of the target muscle (first dorsal interosseous). There was no difference between FHD subjects and control subjects in silent period duration, which was significantly longer during the phasic texture discrimination and phasic control task than during the isometric pinch or writing. This finding suggests that the phasic nature of the task may increase cortical inhibitory function, rather than the sensory discrimination task itself. The accuracy of texture discrimination was significantly lower in FHD subjects than in control subjects. Sensory discrimination tasks do not appear to directly modulate the inhibitory processes responsible for the duration of the silent period., ((c) 2005 Movement Disorder Society.)

Previous studies have shown that the excitability of corticomotor projections to forearm muscles exhibit phasic modulation during passive movement (flexion-extension) about the wrist joint. We examined the stimulus-response properties of flexor carpi radialis (FCR) and extensor carpi radialis (ECR) to transcranial magnetic stimulation (TMS) applied over the contralateral motor cortex while the wrist was moved passively at two different sinusoidal frequency-amplitude relationships. Movement velocity (and therefore, the rate of change in muscle length) at the time of stimulation was held constant. Motor evoked potential (MEP) amplitudes were facilitated during passive muscle shortening and suppressed during passive muscle lengthening with suppression being more evident at higher stimulation intensities. For both FCR and ECR, during the shortening phase, responses were facilitated during the large amplitude movement relative to the small amplitude movement. It is suggested that the altered gain may be related to the thixotropic properties of muscle.

The release of short interval intracortical inhibition (SICI) induced by passive bimanual movement was assessed in dominant and non-dominant primary motor cortices (M1). Dual-pulse focal transcranial magnetic stimulation (TMS) was delivered over M1 while the limbs were at rest, and during the mid-flexion phase of contralateral rhythmical wrist flexion-extension. Test and conditioned responses were recorded from flexor carpi radialis (FCR) when the wrist was passively moving alone, during bimanual mirror symmetric passive synchronous movement, and during bimanual passive asynchronous movement. Tonic inhibition was released to a greater extent in the non-dominant M1 than in the dominant M1 during synchronous mirror symmetric movement. This interhemispheric asymmetry was not evident during asynchronous movement. The findings support the idea that the dominant M1 has the capacity to disinhibit homologous representations in the contralateral M1 during synchronous movement, but the non-dominant M1 does not reciprocate to the same extent.