Implicit sequence‐specific motor learning after subcortical stroke is associated with increased prefrontal brain activations: An fMRI Study

Implicit motor learning is preserved after stroke, but how the brain compensates for damage to facilitate learning is unclear. We used a random effects analysis to determine how stroke alters patterns of brain activity during implicit sequence‐specific motor learning as compared to general improvements in motor control. Nine healthy participants and nine individuals with chronic, right focal subcortical stroke performed a continuous joystick‐based tracking task during an initial functional magnetic resonance images (fMRI) session, over 5 days of practice, and a retention test during a separate fMRI session. Sequence‐specific implicit motor learning was differentiated from general improvements in motor control by comparing tracking performance on a novel, repeated tracking sequence during early practice and again at the retention test. Both groups demonstrated implicit sequence‐specific motor learning at the retention test, yet substantial differences were apparent. At retention, healthy control participants demonstrated increased blood oxygenation level dependent (BOLD) response in left dorsal premotor cortex (PMd; BA 6) but decreased BOLD response left dorsolateral prefrontal cortex (DLPFC; BA 9) during repeated sequence tracking. In contrast, at retention individuals with stroke did not show this reduction in DLPFC during repeated tracking. Instead implicit sequence‐specific motor learning and general improvements in motor control were associated with increased BOLD response in the left middle frontal gyrus BA 8, regardless of sequence type after stroke. These data emphasize the potential importance of a prefrontal‐based attentional network for implicit motor learning after stroke. This study is the first to highlight the importance of the prefrontal cortex for implicit sequence‐specific motor learning after stroke. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Transcallosal connection patterns of opposite dorsal premotor regions support a lateralized specialization for action and perception

Lateralization of higher brain functions requires that a dominant hemisphere collects relevant information from both sides. The right dorsal premotor cortex (PMd), particularly implicated in visuomotor transformations, was hypothesized to be optimally located to converge visuospatial information from both hemispheres for goal‐directed movement. This was assessed by probabilistic tractography and a novel analysis enabling group comparisons of whole‐brain connectivity distributions of the left and right PMd in standard space (16 human subjects). The resulting dominance of contralateral PMd connections was characterized by right PMd connections with left visual and parietal areas, indeed supporting a dominant role in visuomotor transformations, while the left PMd showed dominant contralateral connections with the frontal lobe. Ipsilateral right PMd connections were also stronger with posterior parietal regions, relative to the left PMd connections, while ipsilateral connections of the left PMd were stronger with, particularly, the anterior cingulate, the ventral premotor and anterior parietal cortex. The pattern of dominant right PMd connections thus points to a specific role in guiding perceptual information into the motor system, while the left PMd connections are consistent with action dominance based on a lead in motor intention and fine precision skills.     

Effects of subthalamic nucleus stimulation on actual and imagined movement in Parkinson's disease : a PET study

BACKGROUND: PET studies in moderately affected Parkinson's disease (PD) patients reveal abnormal cerebral activation during motor execution and imagery, but the effects of subthalamic nucleus (STN) stimulation are not well established. OBJECTIVES: to assess the effect of STN stimulation on cerebral activation during actual and imagined movement in patients with advanced PD. METHODS: seven severely affected PD patients treated with bilateral STN stimulation were studied with PET and H(2)(15)O. The following conditions were investigated: (1). rest; (2). motor execution of a sequential predefined joystick movement with the right hand and (3). motor imagery of the same task. Patients were studied with and without left STN stimulation while right stimulator remained off. RESULTS: Without STN stimulation, the primary motor cortex was activated only during motor execution whereas the dorsolateral prefrontal cortex (DLPFC) was activated only during motor imagery. An activation of the supplementary motor area (SMA) was seen during both motor execution and motor imagery. Left STN stimulation during motor execution increased the regional cerebral blood flow (rCBF) bilaterally in the prefrontal cortex including DLPFC, in the left thalamus and putamen. In addition, a reduction of rCBF was noted in the right primary motor cortex, inferior parietal lobe and SMA. Under left STN stimulation, during motor imagery, rCBF increased bilaterally in the DLPFC and in the left thalamus and putamen and decreased in the left SMA and primary motor cortex. CONCLUSION: STN stimulation during both motor execution and imagery tends to improve the functioning of the frontal-striatal-thalamic pathway and to reduce the recruitment of compensatory motor circuits notably in motor, premotor and parietal cortical areas.     

Network dynamics engaged in the modulation of motor behavior in stroke patients

Stroke patients with motor deficits typically feature enhanced neural activity in several cortical areas when moving their affected hand. However, also healthy subjects may show higher levels of neural activity in tasks with higher motor demands. Therefore, the question arises to what extent stroke‐related overactivity reflects performance‐level‐associated recruitment of neural resources rather than stroke‐induced neural reorganization. We here investigated which areas in the lesioned brain enable the flexible adaption to varying motor demands compared to healthy subjects. Accordingly, eleven well‐recovered left‐hemispheric chronic stroke patients were scanned using functional magnetic resonance imaging. Motor system activity was assessed for fist closures at increasing movement frequencies performed with the affected/right or unaffected/left hand. In patients, an increasing movement rate of the affected hand was associated with stronger neural activity in ipsilesional/left primary motor cortex (M1) but unlike in healthy controls also in contralesional/right dorsolateral premotor cortex (PMd) and contralesional/right superior parietal lobule (SPL). Connectivity analyses using dynamic causal modeling revealed stronger coupling of right SPL onto affected/left M1 in patients but not in controls when moving the affected/right hand independent of the movement speed. Furthermore, coupling of right SPL was positively coupled with the “active” ipsilesional/left M1 when stroke patients moved their affected/right hand with increasing movement frequency. In summary, these findings are compatible with a supportive role of right SPL with respect to motor function of the paretic hand in the reorganized brain.     

Rostrocaudal functional gradient among the pre‐dorsal premotor cortex,dorsal premotor cortex and primary motor cortex in goal‐directed motor behaviour

The dorsal premotor cortex residing in the dorsolateral aspect of area 6 is a rostrocaudally elongated area that is rostral to the primary motor cortex (M1) and caudal to the prefrontal cortex. This region, which is subdivided into rostral [pre‐dorsal premotor cortex (pre‐PMd)] and caudal [dorsal premotor cortex proper (PMd)] components, probably plays a central role in planning and executing actions to achieve a behavioural goal. In the present study, we investigated the functional specializations of the pre‐PMd, PMd, and M1, because the synthesis of the specific functions performed by each area is considered to be essential. Neurons were recorded while monkeys performed a conditional visuo‐goal task designed to include separate processes for determining a behavioural goal (reaching towards a right or left potential target) on the basis of visual object instructions, specifying actions (direction of reaching) to be performed on the basis of the goal, and preparing and executing the action. Neurons in the pre‐PMd and PMd retrieved and maintained behavioural goals without encoding the visual features of the visual object instructions, and subsequently specified the actions by multiplexing the goals with the locations of the targets. Furthermore, PMd and M1 neurons played a major role in representing the action during movement preparation and execution, whereas the contribution of the pre‐PMd progressively decreased as the time of the actual execution of the movement approached. These findings revealed that the multiple processing stages necessary for the realization of an action to accomplish a goal were implemented in an area‐specific manner across a functional gradient from the pre‐PMd to M1 that included the PMd as an intermediary.     

Subcortical contributions to effective connectivity in brain networks supporting imitation

Using functional magnetic resonance imaging (fMRI), we investigated effective connectivity in brain networks supporting imitation. Despite extensive reports of regional functional specialization underlying action perception, action execution and imitation, our understanding of the potential contribution of subcortical sites is limited, as is our knowledge of how regions displaying functional specialization interact with each other on a system level. While in the scanner, participants performed a simple imitation paradigm with three conditions: Observe trials, in which participants passively viewed a human actor executing a sequence of four finger presses on a keypad; Imitate trials, in which participants imitated the actor's finger presses on a keyboard; and Execute trials, in which participants also executed finger presses but did so based on visuospatial cues in the absence of the actor's hand. Relative to the Execute condition, Imitate trials evoked significantly more activity in superior and inferior parietal lobules (SPL, IPL), posterior superior temporal sulcus (pSTS), and in a ventral aspect of dorsal premotor cortex (PMd). Psychophysiological interaction (PPI) analysis, a means of assessing effective connectivity, revealed significant interactions with regions of cerebellar lobule VII from seeds both in the right pSTS and right SPL, such that activity in these sites was more highly correlated during imitation. A similar interaction was found between right pSTS and left IPL. These results clarify the role of cortical regions supporting action observation, action execution and imitation, and highlight the role the cerebellum may play in facilitating both motor and nonmotor aspects of imitation.     

Brain activity during non-automatic motor production of discrete multi-second intervals

It has been suggested that the different patterns of brain activity observed during paced finger tapping and non-movement related timing tasks, with medial premotor cortex (supplementary motor cortex, pre and proper) and ipsilateral cerebellum dominating the former, and dorsolateral prefrontal cortex (DLPFC) the latter, might be related to differing motor demands. Since paced finger tapping often consists of automatic movement (requiring little overt attention), while non-motor timing is attentionally modulated, the difference could also be related to attentional processing. Here, we observed timing related activity in both medial premotor cortex and DLPFC, with non-timing related activity in other areas, including ipsilateral cerebellum, when subjects performed non-automatic motor timing. This result shows that, in time measurement, medial premotor activation is not specific to automatic movement, and DLPFC activity is not specific to non-motor tasks.     

Coding complexity in the human motor circuit

Cortical oscillatory dynamics are known to be critical for human movement, although their functional significance remains unclear. In particular, there is a strong beta (15–30 Hz) desynchronization that begins before movement onset and continues during movement, before rebounding after movement termination. Several studies have connected this response to motor planning and/or movement selection operations, but to date such studies have examined only the early aspects of the response (i.e., before movement) and a limited number of parameters. In this study, we used magnetoencephalography (MEG) and a novel motor sequence paradigm to probe how motor plan complexity modulates peri‐movement beta oscillations, and connectivity within activated circuits. We also examined the dynamics by imaging beta activity before and during movement execution and extracting virtual sensors from key regions. We found stronger beta desynchronization during complex relative to simple sequences in the right parietal and left dorsolateral prefrontal cortex (DLPFC) during movement execution. There was also an increase in functional connectivity between the left DLPFC and right parietal shortly after movement onset during complex but not simple sequences, which produced a significant conditional effect (i.e., complex > simple) that was not attributable to differences in response amplitude. This study is the first to demonstrate that complexity modulates the dynamics of the peri‐movement beta ERD, which provides crucial new data on the functional role of this well‐known oscillatory motor response. These data further suggest that execution of complex motor behavior may recruit key regions of the fronto‐parietal network, in addition to traditional sensorimotor regions. Hum Brain Mapp 36:5155–5167, 2015. © 2015 Wiley Periodicals, Inc.     

Brain changes following four weeks of unimanual motor training: Evidence from behavior,neural stimulation,cortical thickness,and functional MRI

Although different aspects of neuroplasticity can be quantified with behavioral probes, brain stimulation, and brain imaging assessments, no study to date has combined all these approaches into one comprehensive assessment of brain plasticity. Here, 24 healthy right‐handed participants practiced a sequence of finger‐thumb opposition movements for 10 min each day with their left hand. After 4 weeks, performance for the practiced sequence improved significantly (P < 0.05 FWE) relative to a matched control sequence, with both the left (mean increase: 53.0% practiced, 6.5% control) and right (21.0%; 15.8%) hands. Training also induced significant (cluster p‐FWE < 0.001) reductions in functional MRI activation for execution of the trained sequence, relative to the control sequence. These changes were observed as clusters in the premotor and supplementary motor cortices (right hemisphere, 301 voxel cluster; left hemisphere 700 voxel cluster), and sensorimotor cortices and superior parietal lobules (right hemisphere 864 voxel cluster; left hemisphere, 1947 voxel cluster). Transcranial magnetic stimulation over the right (“trained”) primary motor cortex yielded a 58.6% mean increase in a measure of motor evoked potential amplitude, as recorded at the left abductor pollicis brevis muscle. Cortical thickness analyses based on structural MRI suggested changes in the right precentral gyrus, right post central gyrus, right dorsolateral prefrontal cortex, and potentially the right supplementary motor area. Such findings are consistent with LTP‐like neuroplastic changes in areas that were already responsible for finger sequence execution, rather than improved recruitment of previously nonutilized tissue. Hum Brain Mapp 38:4773–4787, 2017. © 2017 Wiley Periodicals, Inc.     

Comparison of unilateral and bilateral complex finger tapping-related activation in premotor and primary motor cortex

Sixteen healthy right-handed subjects performed a complex finger-tapping task that broadly activates the motor and premotor regions, including primary motor (M1), ventral premotor (PMv), and dorsal premotor (PMd) cortex. This task was performed with the right hand only, left hand only and both hands simultaneously. Behavioral performance and the possibility of mirror movements were controlled through the use of MRI-compatible gloves to monitor finger movements. Using spatially normalized ROIs from the Human Motor Area Template (HMAT), comparisons were made of the spatial extent and location of activation in the left and right motor regions between all three tasks. During unilateral right and left hand tapping, ipsilateral precentral gyrus activation occurred in all subjects, mainly in the PMv and PMd. Ipsilateral M1 activation was less consistent and shifted anteriorly within M1, towards the border of M1 and premotor cortex. Regions of ipsilateral activation were also activated during contralateral and bilateral tasks. Overall, 83%/70%/58% of the ipsilaterally activated voxels in M1/PMd/PMv were also activated during contralateral and bilateral tapping. The mean percent signal change of spatially overlapping activated voxels was similar in PMv and PMd between all three tasks. However, the mean percent signal change of spatially overlapping M1 activation was significantly less during ipsilateral tapping compared with contra- or bilateral tapping. Results suggest that the ipsilateral fMRI activation in unilateral motor tasks may not be inhibitory in nature, but rather may reflect part of a bilateral network involved in the planning and/or execution of tapping in the ipsilateral hand.     

Functional connectivity of cortical motor areas in the resting state in Parkinson's disease

Parkinson's disease (PD) patients have difficulty in initiating movements. Previous studies have suggested that the abnormal brain activity may happen not only during performance of self‐initiated movements but also in the before movement (baseline or resting) state. In the current study, we investigated the functional connectivity of brain networks in the resting state in PD. We chose the rostral supplementary motor area (pre‐SMA) and bilateral primary motor cortex (M1) as “seed” regions, because the pre‐SMA is important in motor preparation, whereas the M1 is critical in motor execution. FMRIs were acquired in 18 patients and 18 matched controls. We found that in the resting state, the pattern of connectivity with both the pre‐SMA or the M1 was changed in PD. Connectivity with the pre‐SMA in patients with PD compared to normal subjects was increased connectivity to the right M1 and decreased to the left putamen, right insula, right premotor cortex, and left inferior parietal lobule. We only found stronger connectivity in the M1 with its own local region in patients with PD compared to controls. Our findings demonstrate that the interactions of brain networks are abnormal in PD in the resting state. There are more connectivity changes of networks related to motor preparation and initiation than to networks of motor execution in PD. We postulate that these disrupted connections indicate a lack of readiness for movement and may be partly responsible for difficulty in initiating movements in PD. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Theta Burst Stimulation over the human primary motor cortex modulates neural processes involved in movement preparation

ObjectiveTo test whether inhibitory continuous Theta Burst (cTBS) transcranial magnetic stimulation (TMS) can alter neural activity involved in planning and execution of a self-paced movement.MethodsIn seven subjects, cTBS was applied over either the left or right primary motor cortex (left M1 and right M1) and the left dorsal premotor cortex (left PMd) in different experimental sessions. Motor evoked potentials (MEP) at rest were measured as well as the two main components of the movement related cortical potential (MRCP), the Bereitschaftspotential (BP) and the negative slope (NS’), prior to self-paced right thumb opposition.ResultscTBS suppressed contralateral MEPs when it was applied over left M1, right M1 and left PMd. In addition, cTBS over left M1, but not at any other location, reduced the amplitude of the NS’ and tended to shorten the BP onset without changing EMG activity associated with voluntary muscular output. There was a significant correlation between the percent suppression of the MEP and the reduction in amplitude of the total MRCP (BP + NS’).ConclusionscTBS can produce long-lasting effects on brain activity involved in the preparation and execution of a volitional movement.SignificanceThe fact that movement was not compromised while brain activity changed suggests that the motor system of healthy subjects operates with a safety factor that can adjust patterns of activation to compensate for the partial disruption caused by cTBS.     

Neural substrates of low‐frequency repetitive transcranial magnetic stimulation during movement in healthy subjects and acute stroke patients. A PET study

The aim of the study was to investigate, with an rTMS/PET protocol, the after‐effects induced by 1‐Hz repetitive transcranial magnetic stimulation (rTMS) in the regional cerebral blood flow (rCBF) of the primary motor cortex (M1) contralateral to that stimulated during a movement. Eighteen healthy subjects underwent a baseline PET scan followed, in randomized order, by a session of Real/Sham low‐frequency (1 Hz) subthreshold rTMS over the right M1 for 23 min. The site of stimulation was fMRI‐guided. After each rTMS session (real or sham), subjects underwent behavioral hand motor tests and four PET scans. During the first two scans, ten subjects (RH group) moved the right hand ipsilateral to the stimulated site and eight subjects (LH group) moved the left contralateral hand. All remained still during the last two scans (rest). Two stroke patients underwent the same protocol with rTMS applied on contralesional M1. Compared with Sham‐rTMS, Real‐rTMS over the right M1 was followed by a significant increase of rCBF during right hand movement in left S1M1, without any significant change in motor performance. The effect lasted less than 1 h. The same rTMS‐induced S1M1 overactivation was observed in the two stroke patients. Commissural connectivity between right dorsal premotor cortex and left M1 after real‐rTMS was observed with a psychophysiological interaction analysis in healthy subjects. No major changes were found for the left hand. These results give further arguments in favor of a plastic commissural connectivity between M1 both in healthy subjects and in stroke patients, and reinforce the potential for therapeutic benefit of low‐frequency rTMS in stroke rehabilitation. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Modulating neural oscillations by transcranial static magnetic field stimulation of the dorsolateral prefrontal cortex: A crossover,double‐blind,sham‐controlled pilot study

Transcranial static magnetic field stimulation (tSMS) is a novel non‐invasive brain stimulation technique that has been shown to locally increase alpha power in the parietal and occipital cortex. We investigated if tSMS locally increased alpha power in the left or right prefrontal cortex, as the balance of left/right prefrontal alpha power (frontal alpha asymmetry) has been linked to emotional processing and mood disorders. Therefore, altering frontal alpha asymmetry with tSMS may serve as a novel treatment to psychiatric diseases. We performed a crossover, double‐blind, sham‐controlled pilot study to assess the effects of prefrontal tSMS on neural oscillations. Twenty‐four right‐handed healthy participants were recruited and received left dorsolateral prefrontal cortex (DLPFC) tSMS, right DLPFC tSMS, and sham tSMS in a randomized order. Electroencephalography data were collected before (2 min eyes‐closed, 2 min eyes‐open), during (10 min eyes‐open), and after (2 min eyes‐open) stimulation. In contrast with our hypothesis, neither left nor right tSMS locally increased frontal alpha power. However, alpha power increased in occipital cortex during left DLPFC tSMS. Right DLPFC tSMS increased post‐stimulation fronto‐parietal theta power, indicating possible relevance to memory and cognition. Left and right DLPFC tSMS increased post‐stimulation left hemisphere beta power, indicating possible changes to motor behavior. Left DLPFC tSMS also increased post‐stimulation right frontal beta power, demonstrating complex network effects that may be relevant to aggressive behavior. We concluded that DLPFC tSMS modulated the network oscillations in regions distant from the location of stimulation and that tSMS has region specific effects on neural oscillations.     

Altered frontostriatal coupling in pre‐manifest Huntington’s disease: effects of increasing cognitive load

Background and purpose: Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre‐symptomatic individuals with the Huntington’s disease (HD) gene mutation (pre‐HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre‐HD individuals. Methods: Sixteen healthy controls and sixteen pre‐HD subjects were studied using functional MRI and a verbal working memory task with increasing cognitive load. Load‐dependent functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) was investigated by means of psychophysiological interactions. Results: In pre‐HD subjects, aberrant functional connectivity of the left DLPFC was found at high working memory load levels only. Compared with healthy controls, pre‐HD individuals exhibited lower connectivity strength in the left putamen, the right anterior cingulate and the left medial prefrontal cortex. Pre‐HD individuals close to the onset of motor symptoms additionally exhibited lower connectivity strength in the right putamen and the left superior frontal cortex. The connectivity strength in the left putamen was associated with several clinical measures including CAG repeat length, Unified Huntington's Disease Rating Scale motor score and predicted years to manifest symptom onset. Conclusion: These findings suggest that early prefrontal connectivity abnormalities in pre‐HD individuals are modulated by cognitive demand.     

Effect of high frequency repetitive transcranial magnetic stimulation on reaction time,clinical features and cognitive functions in patients with Parkinson’s disease

The aim of the present study was to investigate the effects of one session of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left dorsal premotor cortex (PMd) and left dorsolateral prefrontal cortex (DLPFC) on choice reaction time in a noise-compatibility task, and cognitive functions in patients with Parkinson’s disease (PD). Clinical motor symptoms of PD were assessed as well. Ten patients with PD entered a randomized, placebo-controlled study with a crossover design. Each patient received 10 Hz stimulation over the left PMd and DLPFC (active stimulation sites) and the occipital cortex (OCC; a control stimulation site) in the OFF motor state, i.e. at least after 12 h of dopaminergic drugs withdrawal. Frameless stereotaxy was used to target the optimal position of the coil. For the evaluation of reaction time, we used a noise-compatibility paradigm. A short battery of neuropsychological tests was performed to evaluate executive functions, working memory, and psychomotor speed. Clinical assessment included a clinical motor evaluation using part III of the Unified Parkinson’s Disease Rating Scale. Statistical analysis revealed no significant effect of rTMS applied over the left PMd and/or DLPFC in patients with PD in any of the measured parameters. In this study, we did not observe any effect of one session of high frequency rTMS applied over the left PMd and/or DLPFC on choice reaction time in a noise-compatibility task, cognitive functions, or motor features in patients with PD. rTMS applied over all three stimulated areas was well tolerated and safe in terms of the cognitive and motor effects.     

The interaction of perceived control and Gambler's fallacy in risky decision making: An fMRI study

Limited recent evidence implicates the anterior/posterior cingulate (ACC/PCC) and lateral prefrontal networks as the neural substrates of risky decision‐making biases such as illusions of control (IoC) and gambler's fallacy (GF). However, investigation is lacking on the dynamic interactive effect of those biases during decision making. Employing a card‐guessing game that independently manipulates trial‐by‐trial perceived control and gamble outcome among 29 healthy female participants, we observed both IoC‐ and GF‐type behaviors, as well as an interactive effect of previous control and previous outcome, with GF‐type behaviors only following computer‐selected, but not self‐selected, outcomes. Imaging results implicated the ACC and left dorsolateral prefrontal cortex (DLPFC) in agency processing, and the cerebellum and right DLPFC in previous outcome processing, in accordance with past literature. Critically, the right inferior parietal lobule (IPL) exhibited significant betting‐related activities to the interaction of previous control and previous outcome, showing more positive signals to previous computer‐selected winning versus losing outcomes but the reverse pattern following self‐selected outcomes, as well as responding to the interactive effect of control and outcome during feedback. Associations were also found between participants' behavioral sensitivity to the interactive effect of previous control and previous outcome, and right IPL signals, as well as its functional connectivity with neural networks implicated in agency and previous outcome processing. We propose that the right IPL provides the neural substrate for the interaction of perceived control and GF, through coordinating activities in the anterior and posterior cingulate cortices and working conjunctively with lateral PFC and other parietal networks. Hum Brain Mapp 37:1218–1234, 2016. © 2016 Wiley Periodicals, Inc .     

Abnormal connectivity of the sensorimotor network in patients with MS: A multicenter fMRI study

In this multicenter study, we used dynamic causal modeling to characterize the abnormalities of effective connectivity of the sensorimotor network in 61 patients with multiple sclerosis (MS) compared with 74 age‐matched healthy subjects. We also investigated the correlation of such abnormalities with findings derived from structural MRI. In a subgroup of subjects, diffusion tensor (DT) MRI metrics of the corpus callosum and the left corticospinal tract (CST) were also assessed. MS patients showed increased effective connectivity relative to controls between: (a) the left primary SMC and the left dorsal premotor cortex (PMd), (b) the left PMd and the supplementary motor areas (SMA), (c) the left secondary sensorimotor cortex (SII) and the SMA, (d) the right SII and the SMA, (e) the left SII and the right SII, and (f) the right SMC and the SMA. MS patients had relatively reduced effective connectivity between the left SMC and the right cerebellum. No interaction was found between disease group and center. Coefficients of altered connectivity were weakly correlated with brain T2 LV, but moderately correlated with DT MRI‐measured damage of the left CST. In conclusion, large multicenter fMRI studies of effective connectivity changes in diseased people are feasible and can facilitate studies with sample size large enough for robust outcomes. Increased effective connectivity in the patients for the simple motor task suggests local network modulation contributing to enhanced long‐distance effective connectivity in MS patients. This extends and generalizes previous evidence that enhancement of effective connectivity may provide an important compensatory mechanism in MS. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Right-shift for non-speech motor processing in adults who stutter

Introduction

In adults who do not stutter (AWNS), the control of hand movement timing is assumed to be lateralized to the left dorsolateral premotor cortex (PMd). In adults who stutter (AWS), the network of speech motor control is abnormally shifted to the right hemisphere. Motor impairments in AWS are not restricted to speech, but extend to non-speech orofacial and finger movements. We here investigated the lateralization of finger movement timing control in AWS.

Methods

We explored PMd function in 14 right-handed AWS and 15 age matched AWNS. In separate sessions, they received subthreshold repetitive transcranial magnetic stimulation (rTMS) for 20 min at 1 Hz over the left or right PMd, respectively. Pre- and post-stimulation participants were instructed to synchronize their index finger taps of either hand with an isochronous sequence of clicks presented binaurally via earphones. Synchronization accuracy was measured to quantify the effect of the PMd stimulation.

Results

In AWNS inhibition of left PMd affected synchronization accuracy of the left hand. Conversely, in AWS TMS over the right PMd increased the asynchrony of the left hand.

Conclusions

The present data indicate an altered functional connectivity in AWS in which the right PMd seems to be important for the control of timed non-speech movements. Moreover, the laterality-shift suggests a compensatory role of the right PMd to successfully perform paced finger tapping.     

Site‐specific effects of mental practice combined with transcranial direct current stimulation on motor learning

Mental practice can induce significant neural plasticity and result in motor performance improvement if associated with motor imagery tasks. Given the effects of transcranial direct current stimulation (tDCS) on neuroplasticity, the current study tested whether tDCS, using different electrode montages, can increase the neuroplastic effects of mental imagery on motor learning. Eighteen healthy right‐handed adults underwent a randomised sham‐controlled crossover experiment to receive mental training combined with either sham or active anodal tDCS of the right primary motor cortex (M1), right supplementary motor area, right premotor area, right cerebellum or left dorsolateral prefrontal cortex (DLPFC). Motor performance was assessed by a blinded rater using: non‐dominant handwriting time and legibility, and mentally trained task at baseline (pre) and immediately after (post) mental practice combined with tDCS. Active tDCS significantly enhances the motor‐imagery‐induced improvement in motor function as compared with sham tDCS. There was a specific effect for the site of stimulation such that effects were only observed after M1 and DLPFC stimulation during mental practice. These findings provide new insights into motor imagery training and point out that two cortical targets (M1 and DLPFC) are significantly associated with the neuroplastic effects of mental imagery on motor learning. Further studies should explore a similar paradigm in patients with brain lesions.