Differential dopaminergic modulation of spontaneous cortico-subthalamic activity in Parkinson's disease.

Pathological oscillations including elevated beta activity in the subthalamic nucleus (STN) and between STN and cortical areas are a hallmark of neural activity in Parkinson's disease (PD). Oscillations also play an important role in normal physiological processes and serve distinct functional roles at different points in time. We characterised the effect of dopaminergic medication on oscillatory whole-brain networks in PD in a time-resolved manner by employing a hidden Markov model on combined STN local field potentials and magnetoencephalography (MEG) recordings from 17 PD patients. Dopaminergic medication led to coherence within the medial and orbitofrontal cortex in the delta/theta frequency range. This is in line with known side effects of dopamine treatment such as deteriorated executive functions in PD. In addition, dopamine caused the beta band activity to switch from an STN-mediated motor network to a frontoparietal-mediated one. In contrast, dopamine did not modify local STN-STN coherence in PD. STN-STN synchrony emerged both on and off medication. By providing electrophysiological evidence for the differential effects of dopaminergic medication on the discovered networks, our findings open further avenues for electrical and pharmacological interventions in PD.

Multimodal Neuroimaging Using Concurrent EEG/fNIRS for Poststroke Recovery Assessment: An Exploratory Study.

BACKGROUND: Persistent motor deficits are very common in poststroke survivors and often lead to disability. Current clinical measures for profiling motor impairment and assessing poststroke recovery are largely subjective and lack precision. OBJECTIVE: A multimodal neuroimaging approach was developed based on concurrent functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) to identify biomarkers associated with motor function recovery and document the poststroke cortical reorganization. METHODS: EEG and fNIRS data were simultaneously recorded from 9 healthy controls and 18 stroke patients during a hand-clenching task. A novel fNIRS-informed EEG source imaging approach was developed to estimate cortical activity and functional connectivity. Subsequently, graph theory analysis was performed to identify network features for monitoring and predicting motor function recovery during a 4-week intervention. RESULTS: The task-evoked strength at ipsilesional primary somatosensory cortex was significantly lower in stroke patients compared with healthy controls (P < .001). In addition, across the 4-week rehabilitation intervention, the strength at ipsilesional premotor cortex (PMC) (R = 0.895, P = .006) and the connectivity between bilateral primary motor cortices (M1) (R = 0.9, P = .007) increased in parallel with the improvement of motor function. Furthermore, a higher baseline strength at ipsilesional PMC was associated with a better motor function recovery (R = 0.768, P = .007), while a higher baseline connectivity between ipsilesional supplementary motor cortex (SMA)-M1 implied a worse motor function recovery (R = -0.745, P = .009). CONCLUSION: The proposed multimodal EEG/fNIRS technique demonstrates a preliminary potential for monitoring and predicting poststroke motor recovery. We expect such findings can be further validated in future study.

Assessment of cortical reorganization and preserved function in phantom limb pain: a methodological perspective.

Phantom limb pain (PLP) has been associated with reorganization in primary somatosensory cortex (S1) and preserved S1 function. Here we examined if methodological differences in the assessment of cortical representations might explain these findings. We used functional magnetic resonance imaging during a virtual reality movement task, analogous to the classical mirror box task, in twenty amputees with and without PLP and twenty matched healthy controls. We assessed the relationship between task-related activation maxima and PLP intensity in S1 and motor cortex (M1) in individually-defined or group-conjoint regions of interest (ROI) (overlap of task-related activation between the groups). We also measured cortical distances between both locations and correlated them with PLP intensity. Amputees compared to controls showed significantly increased activation in M1, S1 and S1M1 unrelated to PLP. Neural activity in M1 was positively related to PLP intensity in amputees with PLP when a group-conjoint ROI was chosen. The location of activation maxima differed between groups in S1 and M1. Cortical distance measures were unrelated to PLP. These findings suggest that sensory and motor maps differentially relate to PLP and that methodological differences might explain discrepant findings in the literature.

Assessment of neuroplasticity in late-life depression with transcranial magnetic stimulation.

BACKGROUND: Studies using Transcranial Magnetic Stimulation (TMS), a non-invasive method of brain stimulation, have implicated impaired neuroplasticity in the pathophysiology of depression in younger adults. The role of neuroplasticity in late-life depression (LLD) has not yet been explored using TMS. OBJECTIVE: This study aimed at evaluating motor cortical neuroplasticity using paired associative stimulation (PAS). Single-pulse TMS was used to induce motor-evoked potentials (MEP) in the contralateral hand muscle before and after PAS. The potentiation of MEP amplitudes after PAS was used as an indirect index of associative plasticity and long-term potentiation (LTP) (i.e. PAS-LTP). RESULTS: 48 older adults with depression and 34 age-matched healthy controls (HC) were compared. PAS- LTP was successfully induced in 68.8% of older adults with depression and 47.1% of HC. At the group level, older adults with depression failed to show statistically significant induction of neuroplasticity, which was observed in HC. However, no significant differences were observed between the two groups for PAS-LTP. CONCLUSION: Our results suggest that associative plasticity does not differ substantially between older adults with depression and age-matched HC. Continued research is needed to more comprehensively understand the role of neuroplasticity in the pathophysiology of LLD.

Assessment of motor cortex excitability and inhibition during a cognitive task in individuals with concussion.

PRIMARY OBJECTIVE: To examine the function of the motor cortex during executive function tasks in individuals with concussion, relative to healthy controls. METHODS AND PROCEDURES: Transcranial magnetic stimulation (TMS) was used to assess motor cortex excitability and inhibition acutely, within 72 hours, and over two months, post-concussion in 23 participants, nine individuals with concussion and 14 controls. Participants performed a cognitive task during TMS to determine the impact of cognitive task on the motor cortex. MAIN OUTCOMES AND RESULTS: Resting motor threshold (p = 0.02) and motor-evoked potential (MEPRest) amplitude (p = 0.03) were different between groups, both suggesting greater corticospinal excitability in individuals with concussion. Cortical silent period (CSP) duration was greater at 72 hours (p = 0.03), one month (p = 0.003) and two months (p = 0.05) in individuals with concussion, suggesting increased intracortical inhibition. The performance of a cognitive task caused an increase in MEPRest (p = 0.006) and CSP (p = 0.04), compared to baseline in both groups, but no interaction of condition by group (p ≥ 0.91) for either measure. CONCLUSION: Simultaneously performing a cognitive task during motor cortex assessments increased corticospinal excitability and intracortical inhibition; however, the increase was not different between groups.

Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease.

Transcranial magnetic stimulation (TMS) is a noninvasive technique that has provided important information about cortical function across an array of neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia, Parkinson's disease, and related extrapyramidal disorders. Application of TMS techniques in neurodegenerative diseases has provided important pathophysiological insights, leading to the development of pathogenic and diagnostic biomarkers that could be used in the clinical setting and therapeutic trials. Abnormalities of TMS outcome measures heralding cortical hyperexcitability, as evidenced by a reduction of short-interval intracortical inhibition and increased in motor-evoked potential amplitude, have been consistently identified as early and intrinsic features of amyotrophic lateral sclerosis (ALS), preceding and correlating with the ensuing neurodegeneration. Cortical hyperexcitability appears to form the pathogenic basis of ALS, mediated by trans-synaptic glutamate-mediated excitotoxic mechanisms. As a consequence of these research findings, TMS has been developed as a potential diagnostic biomarker, capable of identifying upper motor neuronal pathology, at earlier stages of the disease process, and thereby aiding in ALS diagnosis. Of further relevance, marked TMS abnormalities have been reported in other neurodegenerative diseases, which have varied from findings in ALS. With time and greater utilization by clinicians, TMS outcome measures may prove to be of utility in future therapeutic trial settings across the neurodegenerative disease spectrum, including the monitoring of neuroprotective, stem-cell, and genetic-based strategies, thereby enabling assessment of biological effectiveness at early stages of drug development.

The supination assessment task: An automated method for quantifying forelimb rotational function in rats.

BACKGROUND: Neurological injuries or disease can impair the function of motor circuitry controlling forearm supination, and recovery is often limited. Preclinical animal models are essential tools for developing therapeutic interventions to improve motor function after neurological damage. Here we describe the supination assessment task, an automated measure of quantifying forelimb supination in the rat. NEW METHOD: Animals were trained to reach out of a slot in a cage, grasp a spherical manipulandum, and supinate the forelimb. The angle of the manipulandum was measured using a rotary encoder. If the animal exceeded the predetermined turn angle, a reward pellet was delivered. This automated task provides a large, high-resolution dataset of turn angle over time. Multiple parameters can be measured including success rate, peak turn angle, turn velocity, area under the curve, and number of rotations per trial. The task provides a high degree of flexibility to the user, with both software and hardware parameters capable of being adjusted. RESULTS: We demonstrate the supination assessment task can effectively measure significant deficits in multiple parameters of rotational motor function for multiple weeks in two models of ischemic stroke. COMPARISON WITH EXISTING METHODS: Preexisting motor assays designed to measure forelimb supination in the rat require high-speed video analysis techniques. This operant task provides a high-resolution, quantitative end-point dataset of turn angle, which obviates the necessity of video analysis. CONCLUSIONS: The supination assessment task represents a novel, efficient method of evaluating forelimb rotation and may help decrease the cost and time of running experiments.

Relationship between functional connectivity and motor function assessment in stroke patients with hemiplegia: a resting-state functional MRI study.

INTRODUCTION: Resting-state functional magnetic resonance imaging (fMRI) has been used to examine the brain mechanisms of stroke patients with hemiplegia, but the relationship between functional connectivity (FC) and treatment-induced motor function recovery has not yet been fully investigated. This study aimed to identify the brain FC changes in stroke patients and study the relationship between FC and motor function assessment using the resting-state fMRI. METHODS: Seventeen stroke patients with hemiplegia and fifteen healthy control subjects (HCSs) were recruited in this study. We compared the FC between the ipsilesional primary motor cortex (M1) and the whole brain of the patients with the FC of the HCSs and studied the FC changes in the patients before and after conventional rehabilitation and motor imagery therapy. Additionally, correlations between the FC change and motor function of the patients were studied. RESULTS: Compared to the HCSs, the FC in the patient group was significantly increased between the ipsilesional M1 and the ipsilesional inferior parietal cortex, frontal gyrus, supplementary motor area (SMA), and contralesional angular and decreased between the ipsilesional M1 and bilateral M1. After the treatment, the FC between the ipsilesional M1 and contralesional M1 increased while the FC between the ipsilesional M1 and ipsilesional SMA and paracentral lobule decreased. A statistically significant correlation was found between the FC change in the bilateral M1 and the Fugl-Meyer assessment (FMA) score change. CONCLUSION: Our results revealed an abnormal motor network after stroke and suggested that the FC could serve as a biomarker of motor function recovery in stroke patients with hemiplegia.

An automated task for the training and assessment of distal forelimb function in a mouse model of ischemic stroke.

BACKGROUND: Behavioral models relevant to stroke research seek to capture important aspects of motor skills typically impaired in human patients, such as coordination of distal musculature. Such models may focus on mice since many genetic tools are available for use only in that species and since the training and behavioral demands of mice can differ from rats even for superficially similar behavioral readouts. However, current mouse assays are time consuming to train and score, especially in a manner producing continuous quantification. An automated assay of mouse forelimb function may provide advantages for quantification and speed, and may be useful for many applications including stroke research. NEW METHOD: We present an automated assay of distal forelimb function. In this task, mice reach forward, grip and pull an isometric handle with a prescribed force. The apparatus partially automates the training process so that mice can be trained quickly and simultaneously. RESULTS: Using this apparatus, it is possible to measure long-lasting impairment in success rate, force pulled, latency to pull, and latency to success up to 22 weeks following photothrombotic cortical strokes in mice. COMPARISON WITH EXISTING METHOD(S): This assessment measures forelimb function as do pellet reach tasks, but it utilizes a different motion and provides automatic measures that can ease and augment the research process. CONCLUSIONS: This high-throughput behavioral assay can detect long-lasting motor impairments, eliminates the need for subjective scoring, and produces a rich, continuous data set from which many aspects of the reach and grasp motion can be automatically extracted.

Functional MRI in clinical practice: Assessment of language and motor for pre-surgical planning.

Functional magnetic resonance imaging (fMRI) has been widely used for pre-neurosurgical planning and may eventually become a routine pre-surgical imaging modality. The validity of fMRI for clinical application depends on various factors such as proper task selection, correct statistical analysis and threshold setting with appropriate patient cooperation. This study was performed on 40 patients with different types of brain mass lesions or hippocampal sclerosis to assess the role of appropriate patient selection for achieving a reliable fMRI result. Accurate and reproducible fMRI strongly depends on the patient's cooperation. In this study we observed that a pre-test mock fMRI session held by a radiologist may help to predict which patients are more or less suitable candidates for fMRI.

Altering Effort Costs in Parkinson's Disease with Noninvasive Cortical Stimulation.

In Parkinson's disease (PD), the human brain is capable of producing motor commands, but appears to require greater than normal subjective effort, particularly for the more-affected side. What is the nature of this subjective effort and can it be altered? We used an isometric task in which patients produced a goal force by engaging both arms, but were free to assign any fraction of that force to each arm. The patients preferred their less-affected arm, but only in some directions. This preference was correlated with lateralization of signal-dependent noise: the direction of force for which the brain was less willing to assign effort to an arm was generally the direction for which that arm exhibited greater noise. Therefore, the direction-dependent noise in each arm acted as an implicit cost that discouraged use of that arm. To check for a causal relationship between noise and motor cost, we used bilateral transcranial direct current stimulation of the motor cortex, placing the cathode on the more-affected side and the anode on the less-affected side. This stimulation not only reduced the noise on the more-affected arm, it also increased the willingness of the patients to assign force to that arm. In a 3 d double-blind study and in a 10 d repeated stimulation study, bilateral stimulation of the two motor cortices with cathode on the more-affected side reduced noise and increased the willingness of the patients to exert effort. This stimulation also improved the clinical motor symptoms of the disease. SIGNIFICANCE STATEMENT: In Parkinson's disease, patients are less willing to assign force to their affected arm. Here, we find that this pattern is direction dependent: directions for which the arm is noisier coincide with directions for which the brain is less willing to assign force. We hypothesized that if we could reduce the noise on the affected arm, then we may increase the willingness for the brain to assign force to that arm. We found a way to do this via noninvasive cortical stimulation. In addition to reducing effort costs associated with the affected arm, the cortical stimulation also improved clinical motor symptoms of the disease.

Assessment of quantitative corticospinal tract diffusion changes in patients affected by subcortical gliomas using common available navigation software.

OBJECTIVE: The aim of this study is to analyze the quantitative DTI parameters of the CST in patients suffering from subcortical gliomas affecting the CST using generally available navigation software. METHODS: A retrospective study was conducted on 22 subjects with diagnosis of primary cerebral glioma and preoperative motor deficits. Exclusion criteria were: involvement of motor cortex, lesion involving both hemispheres, previous surgical treatment. All patients were studied using magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) sequences. Volume, fractional anisotropy (FA) and mean diffusivity value (MD) of the entire CSTs were estimated. Moreover, distance from midline, diameters, FA and MD were calculated on axial images at the point of minimal distance between tumor and CST. Statistical analysis was performed. RESULTS: There was a statistically significant difference of CST volume between affected and non-affected hemispheres (p<0.01). Mean overall/local FA, overall/local MD and sagittal diameter of CST were also significantly different between the two sides (p<0.05). Correlation tests resulted positive between the shift of CST and overall/local MD. Moreover there is significance between CST volume of tumor hemisphere and preoperative duration of motor deficits (p<0.05). CONCLUSION: The present study has demonstrated for the first time a significant difference of DTI based quantitative parameters of the CST between a tumor affected and a non-affected hemisphere in patients with a corresponding motor deficit. This preliminary data suggests a correlation between DTI based integrity of CST and its function.

Assessment of corticospinal excitability after traumatic spinal cord injury using MEP recruitment curves: a preliminary TMS study.

STUDY DESIGN: Transcranial magnetic stimulation study. OBJECTIVES: To further investigate the corticospinal excitability changes after spinal cord injury (SCI), as assessed by means of transcranial magnetic stimulation (TMS). SETTING: Merano (Italy) and Salzburg (Austria). METHODS: We studied resting motor threshold (RMT), motor evoked potential (MEP) amplitude and recruitment curve in five subjects with good recovery after traumatic incomplete cervical SCI. RESULTS: RMT did not differ significantly between patients and controls, whereas the slope of MEP recruitment curve was significantly increased in the patients. CONCLUSION: This abnormal finding may represent an adaptive response after SCI. The impaired ability of the motor cortex to generate proper voluntary movement may be compensated by increasing spinal excitability. The easily performed measurement of MEP recruitment curve may provide a useful additional tool to improve the assessment and monitoring of motor cortical function in subjects with SCI. Increasing our knowledge of the corticospinal excitability changes in the functional recovery after SCI may also support the development of effective therapeutic strategies.

Assessment of hemodialysis impact by Polysulfone membrane on brain plasticity using BOLD-fMRI.

PURPOSE: Hemodialysis (HD) is considered the most common alternative for overcoming renal failure. Studies have shown the involvement of HD membrane in the genesis of oxidative stress (OS) which has a direct impact on the brain tissue and is expected to be involved in brain plasticity and also reorganization of brain function control. The goal of this paper was to demonstrate the sensitivity of the blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) to characterize the OS before and after the HD session. PATIENTS, MATERIALS AND METHODS: Twelve male patient-volunteers following chronic HD for more than 6months were recruited among 86 HD-patients. All patients underwent identical assessment immediately before and after the full HD-session. This consisted of full biological assessment, including malondialdehyde (MDA) and total antioxidant activity (TAOA); and brain BOLD-fMRI using the motor paradigm in block-design. RESULTS: Functional BOLD-fMRI maps of motor area M1 were obtained from the HD patient before and after the hemodialysis session, important decrease in the intensity of brain activation of the motor area after HD, and important increase of the size of the volume of brain activation were observed, these changes are reflecting brain plasticity that is well correlated to OS levels. Individual patients MDA and TAOA before and after the hemodialysis sessions demonstrated a clear and systematic increase of the OS after HD (P-value=0.03). Correlation of BOLD-fMRI maximal signal intensity and volume of activated cortical brain area behaviors to MDA and total TAOA were close to 1. CONCLUSION: OS is systematically increased in HD-patients after the HD-process. Indeed, the BOLD-fMRI shows a remarkable sensitivity to brain plasticity studied cortical areas. Our results confirm the superiority of the BOLD-fMRI quantities compared to the biological method used for assessing the OS while not being specific, and reflect the increase in OS generated by the HD. BOLD-fMRI is expected to be a suitable tool for evaluating the plasticity process evolution in hemodialysis brain patients.

Assessment of inter-hemispheric imbalance using imaging and noninvasive brain stimulation in patients with chronic stroke.

OBJECTIVE: To determine how interhemispheric balance in stroke, measured using transcranial magnetic stimulation (TMS), relates to balance defined using neuroimaging (functional magnetic resonance [fMRI], diffusion-tensor imaging [DTI]) and how these metrics of balance are associated with clinical measures of upper-limb function and disability. DESIGN: Cross sectional. SETTING: Laboratory. PARTICIPANTS: Patients with chronic stroke (N = 10; age, 63 ± 9 y) in a population-based sample with unilateral upper-limb paresis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Interhemispheric balance was measured with TMS, fMRI, and DTI. TMS defined interhemispheric differences in the recruitment of corticospinal output, size of the corticomotor output maps, and degree of mutual transcallosal inhibition that they exerted on one another. fMRI studied whether cortical activation during the movement of the paretic hand was lateralized to the ipsilesional or to the contralesional primary motor cortex (M1), premotor cortex (PMC), and supplementary motor cortex (SMA). DTI was used to define interhemispheric differences in the integrity of the corticospinal tracts projecting from the M1. Clinical outcomes tested function (upper extremity Fugl-Meyer [UEFM]) and perceived disability in the use of the paretic hand (Motor Activity Log [MAL] amount score). RESULTS: Interhemispheric balance assessed with TMS relates differently to fMRI and DTI. Patients with high fMRI lateralization to the ipsilesional hemisphere possessed stronger ipsilesional corticomotor output maps (M1: r = .831, P = .006; PMC: r = .797, P = .01) and better balance of mutual transcallosal inhibition (r = .810, P = .015). Conversely, we found that patients with less integrity of the corticospinal tracts in the ipsilesional hemisphere show greater corticospinal output of homologous tracts in the contralesional hemisphere (r = .850, P = .004). However, an imbalance in integrity and output do not relate to transcallosal inhibition. Clinically, although patients with less integrity of corticospinal tracts from the ipsilesional hemisphere showed worse impairments (UEFM) (r = -.768, P = .016), those with low fMRI lateralization to the ipsilesional hemisphere had greater perception of disability (MAL amount score) (M1: r = .883, P = .006; PMC: r = .817, P = .007; SMA: r = .633, P = .062). CONCLUSIONS: In patients with chronic motor deficits of the upper limb, fMRI may serve to mark perceived disability and transcallosal influence between hemispheres. DTI-based integrity of the corticospinal tracts, however, may be useful in categorizing the range of functional impairments of the upper limb. Further, in patients with extensive corticospinal damage, DTI may help infer the role of the contralesional hemisphere in recovery.

Assessment of cognitive engagement in stroke patients from single-trial EEG during motor rehabilitation.

We propose a novel method for monitoring cognitive engagement in stroke patients during motor rehabilitation. Active engagement reflects implicit motivation and can enhance motor recovery. In this study, we used electroencephalography (EEG) to assess cognitive engagement in 11 chronic stroke patients while they executed active and passive motor tasks involving grasping and supination hand movements. We observed that the active motor task induced larger event-related desynchronization (ERD) than the passive task in the bilateral motor cortex and supplementary motor area (SMA). ERD differences between tasks were observed during both initial and post-movement periods . Additionally, differences in beta band activity were larger than differences in mu band activity . EEG data was used to help classify each trial as involving the active or passive motor task. Average classification accuracy was 80.7 ±0.1% for grasping movement and 82.8 ±0.1% for supination movement. Classification accuracy using a combination of movement and post-movement periods was higher than in other cases . Our results support using EEG to assess cognitive engagement in stroke patients during motor rehabilitation.

fMRI assessment of neuroplasticity in youths with neurodevelopmental-associated motor disorders after piano training.

BACKGROUND: Damage to the developing brain may lead to lifelong motor impairments namely of the hand function. Playing an instrument combines the execution of gross and fine motor movements with direct auditory feedback of performance and with emotional value. This motor-associated sensory information may work as a self-control of motor performance in therapeutic settings. AIMS: The current study examined the occurrence of neuronal changes associated to piano training in youths with neurodevelopmental-associated hand motor deficits. METHODS: Functional magnetic resonance imaging responses evoked during a finger tapping task in a group of ten youths with neuromotor impairments that received individualized piano lessons for eighteen months were analyzed. Functional imaging data obtained before and after the piano training was compared to that obtained from a similar group of six youths who received no training during the same period of time. RESULTS: Dynamic causal modeling of functional data indicated an increase in positive connectivity from the left primary motor cortical area to the right cerebellum from before to after the piano training. CONCLUSIONS: A wide variability across patients was observed and further studies remain necessary to clarify the neurophysiological basis of the effects of piano training in hand motor function of patients with neurodevelopmental motor disorders.

Assessment of biofeedback rehabilitation in post-stroke patients combining fMRI and gait analysis: a case study.

BACKGROUND: The ability to walk independently is a primary goal for rehabilitation after stroke. Gait analysis provides a great amount of valuable information, while functional magnetic resonance imaging (fMRI) offers a powerful approach to define networks involved in motor control. The present study reports a new methodology based on both fMRI and gait analysis outcomes in order to investigate the ability of fMRI to reflect the phases of motor learning before/after electromyographic biofeedback treatment: the preliminary fMRI results of a post stroke subject's brain activation, during passive and active ankle dorsal/plantarflexion, before and after biofeedback (BFB) rehabilitation are reported and their correlation with gait analysis data investigated. METHODS: A control subject and a post-stroke patient with chronic hemiparesis were studied. Functional magnetic resonance images were acquired during a block-design protocol on both subjects while performing passive and active ankle dorsal/plantarflexion. fMRI and gait analysis were assessed on the patient before and after electromyographic biofeedback rehabilitation treatment during gait activities. Lower limb three-dimensional kinematics, kinetics and surface electromyography were evaluated. Correlation between fMRI and gait analysis categorical variables was assessed: agreement/disagreement was assigned to each variable if the value was in/outside the normative range (gait analysis), or for presence of normal/diffuse/no activation of motor area (fMRI). RESULTS: Altered fMRI activity was found on the post-stroke patient before biofeedback rehabilitation with respect to the control one. Meanwhile the patient showed a diffuse, but more limited brain activation after treatment (less voxels). The post-stroke gait data showed a trend towards the normal range: speed, stride length, ankle power, and ankle positive work increased. Preliminary correlation analysis revealed that consistent changes were observed both for the fMRI data, and the gait analysis data after treatment (R > 0.89): this could be related to the possible effects BFB might have on the central as well as on the peripheral nervous system. CONCLUSIONS: Our findings showed that this methodology allows evaluation of the relationship between alterations in gait and brain activation of a post-stroke patient. Such methodology, if applied on a larger sample subjects, could provide information about the specific motor area involved in a rehabilitation treatment.

Costs of control: decreased motor cortex engagement during a Go/NoGo task in Tourette's syndrome.

Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by an impaired ability to inhibit unwanted behaviour. Although the presence of chronic motor and vocal tics defines Tourette's syndrome, other distinctive behavioural features like echo- and coprophenomena, and non-obscene socially inappropriate behaviour are also core features. We investigated neuronal activation during stimulus-driven execution and inhibition of prepared movements in Tourette's syndrome. To this end, we performed event-related functional magnetic resonance imaging and structural diffusion tensor imaging in 15 moderately affected uncomplicated patients with 'pure' Tourette's syndrome and 15 healthy control participants matched for age and gender. Subjects underwent functional magnetic resonance imaging during a Go/NoGo reaction time task. They had to withhold a prepared finger movement for a variable time until a stimulus instructed them to either execute (Go) or inhibit it (NoGo). Tics were monitored throughout the experiments, combining surface electromyogram, video recording, and clinical assessment in the scanner. Patients with Tourette's syndrome had longer reaction times than healthy controls in Go trials and made more errors in total. Their functional brain activation was decreased in left primary motor cortex and secondary motor areas during movement execution (Go trials) but not during response inhibition (NoGo trials) compared with healthy control subjects. Volume of interest analysis demonstrated less task-related activation in patients with Tourette's syndrome in primary and secondary motor cortex bilaterally, but not in the basal ganglia and cortical non-motor areas. They showed reduced co-activation between the left primary sensory-motor hand area and a network of contralateral sensory-motor areas and ipsilateral cerebellar regions. There were no between-group differences in structural connectivity of the left primary sensory-motor cortex as measured by diffusion tensor imaging-based probabilistic tractography. Our results link reduced sensory-motor cortical activation during movement execution to a decreased co-activation between the sensory-motor cortex and other brain areas involved in motor processing. These functional changes in patients with Tourette's syndrome might result from adaptive reorganization in fronto-parietal brain networks engaged in motor and behavioural control, possibly triggered by abnormal processing and presumably overactivity in cortico-striato-cortical circuits. This might enable patients with Tourette's syndrome to better suppress unwanted movements but comes at a price of behavioural deficits in other domains.

Effect of early and late rehabilitation onset in a chronic rat model of ischemic stroke- assessment of motor cortex signaling and gait functionality over time.

The aim of the present study was to investigate the effects of ischemic stroke and onset of subsequent rehabilitation of gait function in rats. Nine male Sprague-Dawley rats were instrumented with a 16-channel intracortical (IC) electrode array. An ischemic stroke was induced within the hindlimb area of the left motor cortex. The rehabilitation consisted of a repetitive training paradigm over 28 days, initiated on day one ("Early-onset", 5 rats) and on day seven, ("Late-onset", 4 rats). Data were obtained from IC microstimulation tests, treadmill walking tests, and beam walking tests. Results revealed an expansion of the hindlimb representation within the motor cortex area and an increased amount of cortical firing rate modulation for the "Early-onset" group but not for the "Late-onset" group. Kinematic data revealed a significant change for both intervention groups. However, this difference was larger for the "Early-onset" group. Results from the beam walking test showed functional performance deficits following stroke which returned to pre-stroke level after the rehabilitative training. The results from the present study indicate the existence of a critical time period following stroke where onset of rehabilitative training may be more effective and related to a higher degree of true recovery.