Hand Motor Deficits Research Articles

Dexterity in the Acute Phase of Stroke: Impairments and Neural Substrates

Background Stroke can impair manual dexterity, leading to loss of independence following incomplete recovery. Enhancing our understanding of dexterity impairment may improve neurorehabilitation. Objectives The study aimed to measure dexterity components in acute stroke patients with and without hand motor deficits, compare them to those of healthy controls (HC), and to explore the neural substrates involved in specific components of dexterity. Methods We used the Dextrain Manipulandum to quantify fine finger force control, finger selection accuracy, coactivation, and reaction time (RT). Dexterity was evaluated twice (2 days apart) in 74 patients and 14 HC. Voxel-Lesion-Symptom-Mapping (VLSM) was used to analyze the relationship between tissue damage and dexterity. Results. Due to severe paresis or fatigue, 24 patients could not perform these tasks. In 50 patients (included 4.6 ± 3.3 days post-stroke), finger force control improved (P < .001), as it did in HC (P = .03) who performed better than patients on both evaluations. Accuracy of finger selection did not improve significantly in any group, but the HC performed better on both evaluations. Unexpectedly, coactivation was better in patients than in HC at D3 (P = .03). There were no between-group differences in RT. VLSM showed that damage to the superior temporal gyrus (STG) impaired finger force control while damage to the posterior limb of the internal capsule (PLIC) impaired finger selectivity. Conclusions Acute stroke affecting the STG or PLIC impaired selective components of dexterity. Patients with mild to moderate impairment showed better finger force control and accuracy selection within 48 hours, suggesting the feasibility of detecting early dexterity improvements.

SURG-40. AWAKE CRANIOTOMY IN A MIDDLE-INCOME COUNTRY. CHALLENGES AND TECHNICAL NUANCES

Abstract OBJECTIVES Describe the first experience in this technically challenging procedure RESULTS on morbidity INTRODUCTION Awake craniotomy allows for maximal safe resection and lower incidence of adverse events. Nonetheless, it represents a technical challenge. METHODS We enroll forty patients, 18 women, and 22 men. Due to the lack of a navigation system, craniometrics points became paramount to craniotomy planning. Ultrasound is used to compensate for brain shift and confirm the tumor's exact location. We engaged in cortical and subcortical mapping and clinical evaluation of motor and sensory functions. Linguistic tests were applied. The first 24 hours are in the ICU, and an MRI is obtained. RESULTS The mean age was 51, and the mean Karfnosky scale was 80. The median size was 12 cm3. Locations were: Thirteen precentral gyri. Ten insular cortex. Eight cingulate gyri. Six supplementary motor gyri Two Supramarginal gyri. One paracentral lobe tumor. Four patients had obese morbidity, three had depression, and two had a midline displacement treated with steroids. Intraoperative, we encountered three seizures managed with cold saline, two speech arrest, and one transient hand motor deficit. Post-op adverse events were one central facial paralysis, one upper limb, and one lower limb paresthesias; all improved after 72 hours. The median length of stay is 48 hours. The median extent of resection is 93%. The mean KPS was 80 at discharge. We undertook a median of 18 months follow-up. 38 Glioblastomas(GMB) and 2 Low-Grade Gliomas(LGG) were found. The standard oncology treatment was Temozolomide and stereotaxic radiosurgery(SRS). The median time from surgery to SRS was 4.3 months. The median SRS marginal and maximal dose were 15Gy and 26Gy. The median overall survival(OS) was sixteen months, and the Progression-free survival(PFS) was ten months. CONCLUSION An awake craniotomy without the navigation system is possible; however, careful planning is essential.

Enhancing Upper Limb Recovery and Reducing Stress and Anxiety Through Non-Immersive Virtual Reality in Subacute and Chronic Stroke Survivors: An Experimental Study

Introduction: Stroke is the third-leading cause of major long-term disability and the second-leading cause of mortality worldwide. Paralysis, paresis (muscle weakness), spasticity, difficulty walking, difficulty controlling motions, and limb discomfort are frequent limb impairments. Nearly 80% of stroke survivors are affected. Stroke survivors suffer with physical disabilities in addition to a reduced quality of life in terms of their health, a higher degree of worry, and a loss of independence. With a prevalence of 55% to 75%, hand motor deficits are the most prevalent post-stroke.1 The most common impairment is motor dysfunction, which affects 90% of stroke survivors with some kind of upper limb motor disability. Motor dysfunction is a strong indicator of poor functional recovery. The most typical post-stroke symptom is hemiparesis.1 Objectives: The study's objective was to use a virtual reality system to enhance upper limb strength and function in hemiparesis. The study's secondary goal was to lessen tension and anxiety in stroke Survivors. Methods: This research was experimental. A patient was chosen from UEM Hospital in Jaipur, Rajasthan, based on inclusion and exclusion criteria. Upper Extremity Functional Index (UEFI) and Depression Anxiety Stress Scale (DASS-21) were employed as outcome measures to evaluate the patients. Result: The outcome of the post-intervention data revealed that the Upper Extremity Functional Index (UEFI) had significant values of P.311. P .002 was used to determine the importance of the Depression Anxiety Stress Scale (DASS-21). That indicates that following the intervention, all outcome indicators showed a considerable improvement. Conclusion: The post-intervention values of the depression anxiety stress scale (DASS 21) and the upper extremity functional index (UEFI) both indicated a substantial improvement. In order to improve strength and upper limb functions following hemiparesis and to lessen tension and anxiety as a result of the handicap, a low-cost VR system might be employed.

Neurodata Tracker: Software for computational assessment of hand motor skills based on optical motion capture in a virtual environment.

Deficits affecting hand motor skills negatively impact the quality of life of patients. The NeuroData Tracker platform has been developed for the objective and precise evaluation of hand motor deficits. We describe the design and development of the platform and analyse the technological feasibility and usability in a relevant clinical setting. A software application was developed in Unity (C#) to obtain kinematic data from hand movement tracking by a portable device with two cameras and three infrared sensors (leap motion®). Four exercises were implemented: (a) wrist flexion-extension (b) finger-grip opening-closing (c) finger spread (d) fist opening-closing. The most representative kinematic parameters were selected for each exercise. A script in Python was integrated in the platform to transform real-time kinematic data into relevant information for the clinician. The application was tested in a pilot study comparing the data provided by the tool from ten healthy subjects without any motor impairment and ten patients diagnosed with a stroke with mild to moderate hand motor deficit. The NeuroData Tracker allowed the parameterization of kinematics of hand movement and the issuance of a report with the results. The comparison of the data obtained suggests the feasibility of the tool for detecting differences between patients and healthy subjects. This new platform based on optical motion capturing provides objective measurement of hand movement allowing quantification of motor deficits. These findings require further validation of the tool in larger trials to verify its usefulness in the clinical setting.

Elective brachial plexus decompression in neurogenic thoracic outlet syndrome

We aimed to evaluate functional outcome following elective brachial plexus decompression by compressive fibrous band resection and limited on-demand bone abnormality resection in patients with neurogenic thoracic outlet syndrome (N-TOS). A retrospective continuous observational study was conducted in 17 patients (15 women and 2 men), with a mean age of 42 years, operated on between 2013 and 2021. Twenty brachial plexus decompressions were performed, for 13 objective and 7 subjective N-TOSs, including 3 recurrent N-TOSs. At last follow-up, outcomes were evaluated in terms of residual pain, paresthesia and hand motor deficit, plus patient-reported assessment and Quick-DASH functional scoring. No postoperative complications occurred. At a median follow-up of 12 months (range 6–48 months), complete pain relief and paresthesia resolution were found in 11/15 and 9/14 cases, respectively. All patients reported that their symptoms had improved. In contrast, hand muscle atrophy persisted in all cases (n = 11). Sensorimotor recovery seemed to be poorer and mean Quick-DASH score better in objective than subjective N-TOS patients. Elective brachial plexus decompression seemed to be a safe procedure, providing constant improvement in subjective symptoms related to lower trunk irritation. However, nerve release did not provide hand muscle recovery in patients with objective N-TOS. Level of evidenceIV.

Precision Capsular Infarct Modeling to Produce Hand Motor Deficits in Cynomolgus Macaques.

Stroke research in non-human primates (NHPs) with gyrencephalic brains is a critical step in overcoming the translational barrier that limits the development of new pharmaceutical and rehabilitative strategies for stroke. White-matter stroke (WMS) has a unique pathophysiology from gray-matter stroke and is not well understood because of a lack of pertinent animal models. To create a precise capsular infarct model in the cynomolgus macaque, we first used electrical stimulation to map hand movements, followed by viral tracing of the hand motor fibers (hMFs). This enabled us to identify stereotactic targets in the posterior limb of the internal capsule (PLIC). Neural tracing showed that hMFs occupy the full width of the PLIC, owing to overlap with the motor fibers for the leg. Furthermore, the hMFs were distributed in an oblique shape, requiring coronal tilting of the target probe. We used the photothrombotic infarct lesioning technique to precisely destroy the hMFs within the internal capsule. Double-point infarct lesioning that fully compromised the hMFs resulted in persistent hand motor and walking deficits whereas single-point lesioning did not. Minor deviations in targeting failed to produce persistent motor deficits. Accurate stereotactic targeting with thorough involvement of motor fibers is critical for the production of a capsular infarct model with persistent motor deficits. In conclusion, the precision capsular infarct model can be translated to the NHP system to show persistent motor deficits and may be useful to investigate the mechanism of post-stroke recovery as well as to develop new therapeutic strategies for the WMS.

Acute ischaemic stroke alters the brain's preference for distinct dynamic connectivity states.

Acute ischaemic stroke disturbs healthy brain organization, prompting subsequent plasticity and reorganization to compensate for the loss of specialized neural tissue and function. Static resting state functional MRI studies have already furthered our understanding of cerebral reorganization by estimating stroke-induced changes in network connectivity aggregated over the duration of several minutes. In this study, we used dynamic resting state functional MRI analyses to increase temporal resolution to seconds and explore transient configurations of motor network connectivity in acute stroke. To this end, we collected resting state functional MRI data of 31 patients with acute ischaemic stroke and 17 age-matched healthy control subjects. Stroke patients presented with moderate to severe hand motor deficits. By estimating dynamic functional connectivity within a sliding window framework, we identified three distinct connectivity configurations of motor-related networks. Motor networks were organized into three regional domains, i.e. a cortical, subcortical and cerebellar domain. The dynamic connectivity patterns of stroke patients diverged from those of healthy controls depending on the severity of the initial motor impairment. Moderately affected patients (n = 18) spent significantly more time in a weakly connected configuration that was characterized by low levels of connectivity, both locally as well as between distant regions. In contrast, severely affected patients (n = 13) showed a significant preference for transitions into a spatially segregated connectivity configuration. This configuration featured particularly high levels of local connectivity within the three regional domains as well as anti-correlated connectivity between distant networks across domains. A third connectivity configuration represented an intermediate connectivity pattern compared to the preceding two, and predominantly encompassed decreased interhemispheric connectivity between cortical motor networks independent of individual deficit severity. Alterations within this third configuration thus closely resembled previously reported ones originating from static resting state functional MRI studies post-stroke. In summary, acute ischaemic stroke not only prompted changes in connectivity between distinct networks, but it also caused characteristic changes in temporal properties of large-scale network interactions depending on the severity of the individual deficit. These findings offer new vistas on the dynamic neural mechanisms underlying acute neurological symptoms, cortical reorganization and treatment effects in stroke patients.

Functional and structural plasticity following action observation training in multiple sclerosis

Background: Hand motor deficits contribute to multiple sclerosis (MS)-related disability. Action observation training (AOT) is promising to improve upper limb function in neurologic patients. Objectives: In this preliminary study, we investigated AOT effects on dominant-hand motor performance in MS patients with upper limb motor impairment and performed an explorative analysis of their anatomical and functional magnetic resonance imaging (MRI) substrates. Methods: In total, 46 healthy controls (HC) and 41 MS patients with dominant-hand motor impairment were randomized to AOT (HC-AOT = 23; MS-AOT = 20; watching daily-life action videos and execution) or control-training (HC-Control = 23; MS-Control = 21; watching landscapes videos and execution). Behavioral, structural, and functional (at rest and during object manipulation) MRI scans were acquired before and after a 2-week training. Results: After training, MS groups improved in right upper limb functions, mainly in AOT group (p from 0.02 to 0.0001). All groups showed regional increased and decreased gray matter volume, with specific AOT effects in fronto-temporal areas in MS-AOT (p < 0.001), without white matter (WM) integrity modifications. Increased and reduced recruitments of the action observation matching system and its connections in MS-AOT were found (p < 0.001). Motor improvements were correlated with volumetric and functional MRI modifications (r from −0.78 to 0.77, p < 0.001). Conclusion: The 10-day AOT promotes clinical improvements in MS patients through structural and functional modifications of the action observation matching system.

The combined effect of non-invasive cortical stimulation and motor training on hand motor deficit in chronic stroke

A growing body of evidence supports the effectiveness of transcranial direct current stimulation (tDCS) in rehabilitation of patients with hand motor impairment in the chronic phase of stroke. Furthermore, it is assumed that the combination of stimulation- and practice-induced plasticity may be especially beneficial. Aim is to compare the combined effects of anodal tDCS and specific motor training (MT) to sham tDCS and MT (control) on hand motor deficit in patients with chronic stroke. A total of 30 patients were randomly assigned to an active treatment group (real tDCS + MT) or a control group (sham tDCS + MT) in this parallel, two-arm, double-blind, sham-controlled study. MT was administered for 45 min/day (10 sessions) and preceded by 20 minutes of either 2 mA anodal tDCS or sham tDCS over the ipsilesional primary motor cortex. A modified Jebsen–Taylor Hand Function Test (mJTt) was the primary outcome measure, with handgrip dynamometer and upper limb Fugl–Meyer (ULFM) assessments as secondary outcomes. A subset of 21 patients was additionally evaluated by transcranial magnetic stimulation measures of the primary motor cortex excitability The ANCOVA, controlling for baseline status (T0), showed a statistically significant time × group interaction for mJTt due to a statistically significant change over time in the active tDCS group compared to the sham tDCS group. In the active tDCS group, the mJTt time was significantly shorter both at the end of treatment (T2 vs. T0, decrease of 35.36 ± 22.90 s or 28.42 ± 14.56%) and at the follow-up (T3 vs. T0, decrease of 24.21 ± 24.66 s or 19.98 ± 17.49%). The active motor threshold decreased and the MEP amplitude increased. Our findings suggest that hand motor deficits in chronic stroke survivors can be reduced when intensive MT is primed with anodal tDCS over the ipsilesional primary motor cortex.

Motor and Perceptual Recovery in Adult Patients with Mild Intellectual Disability.

Introduction The relationship between intellectual disability (ID) and hand motor coordination and speed-accuracy, as well as the effect of aging on fine motor performance in patients with ID, has been previously investigated. However, only a few data are available on the impact of the nonpharmacological interventions in adult patients with long-term hand motor deficit. Methods Fifty adults with mild ID were enrolled. A group of thirty patients underwent a two-month intensive ergotherapic treatment that included hand motor rehabilitation and visual-perceptual treatment (group A); twenty patients performing conventional motor rehabilitation alone (group B) served as a control group. Data on attention, perceptual abilities, hand dexterity, and functional independence were collected by a blind operator, both at entry and at the end of the study. Results After the interventions, group A showed significantly better performance than group B in all measures related to hand movement from both sides and to independence in activities of daily living. Discussion Multimodal integrated interventions targeting visual-perceptual abilities and motor skills are an effective neurorehabilitative approach in adult patients with mild ID. Motor learning and memory-mediated mechanisms of neural plasticity might underlie the observed recovery, suggesting the presence of plastic adaptive changes even in the adult brain with ID.

P 167 The functional role of contralesional motor areas in the first days after stroke – an fMRI-guided online TMS-study

Introduction Neuroimaging studies in stroke patients with hemiparesis have shown altered brain activation in the contralesional hemisphere including the primary motor cortex (M1), dorsal premotor cortex (dPMC) and anterior intraparietal sulcus (aIPS) already in the first week after stroke ( Rehme et al., 2011 ). The role of these regions for motor recovery is still under debate, with some studies suggesting a supportive influence ( Lotze et al., 2006 ) while other point to a maladaptive role ( Nowak et al., 2008 ). Especially functional reorganization in the early phase after stroke is not well understood, although this phase might be critical for non-invasive interventions aiming at supporting recovery of function ( Grefkes and Fink, 2016 ). We here used fMRI-guided online TMS applied over the contralesional M1, dPMC and aIPS of first-ever stroke patients with hand motor deficits in order to probe their role for movements of the paretic hand. Methods FMRI data were recorded from 13 patients 1–8 days after first-ever ischemic stroke and 14 age-matched healthy volunteers during index finger tapping in order to localize task-related activation in the contralesional hemisphere. Each subjects’ individual maxima in the contralesional M1, dPMC and aIPS were then used as targets to apply short trains of rTMS (10 Hz trains, 90% of rMT) time locked to task execution (online-TMS). Sham stimulation served as a control condition and was conducted at 90% of rMT, tilted over the parieto-occipital vertex in order to minimize interference with the motor system. Task performance was measured using a 3D motion analysis system. Imaging data were preprocessed and analyzed using SPM8 and the MarsBar toolbox. Results The severity of stroke as assessed by the NIHSS showed a positive correlation with the partients’ activation peaks in contralesional M1, indicating higher levels of activity in more affected patients. TMS application over the individual fMRI maxima led to differential effects on motor performance. In contralesional M1 and dPMC, TMS interference with local activity led to a normalization of kinematics in patients showing higher activation during paretic hand movements. This finding implies that early increases of neural activity in these regions after stroke rather represent a maladaptive process interfering with motor performance of the stroke-affected hand. In contrast, TMS-Effects with aIPS led to an increase of tapping amplitude and peak velocity across the patient group, thus normalizing performance. Conclusion The present study examined the role of contralesional M1, dPMC and aIPS activity for motor performance in early subacute stroke patients. While higher activation of M1 and dPMC in the first week after stroke were related to an improvement of motor fluency during online TMS interference, stimulation also of lower activation in contralesional aIPS led to a normalization of spatial aspects of motor performance. These findings suggest a disturbing influence of all examined regions on different features of movement kinematics already during the first days after stroke in mildly to moderately affected patients.

Temporary Nerve Block at Selected Digits Revealed Hand Motor Deficits in Grasping Tasks.

Peripheral sensory feedback plays a crucial role in ensuring correct motor execution throughout hand grasp control. Previous studies utilized local anesthesia to deprive somatosensory feedback in the digits or hand, observations included sensorimotor deficits at both corticospinal and peripheral levels. However, the questions of how the disturbed and intact sensory input integrate and interact with each other to assist the motor program execution, and whether the motor coordination based on motor output variability between affected and non-affected elements (e.g., digits) becomes interfered by the local sensory deficiency, have not been answered. The current study aims to investigate the effect of peripheral deafferentation through digital nerve blocks at selective digits on motor performance and motor coordination in grasp control. Our results suggested that the absence of somatosensory information induced motor deficits in hand grasp control, as evidenced by reduced maximal force production ability in both local and non-local digits, impairment of force and moment control during object lift and hold, and attenuated motor synergies in stabilizing task performance variables, namely the tangential force and moment of force. These findings implied that individual sensory input is shared across all the digits and the disturbed signal from local sensory channel(s) has a more comprehensive impact on the process of the motor output execution in the sensorimotor integration process. Additionally, a feedback control mechanism with a sensation-based component resides in the formation process for the motor covariation structure.

Does Contralesional Hand Function After Neonatal Stroke Only Depend on Lesion Characteristics?

In children having suffered from neonatal arterial ischemic stroke, the relationship between contralesional hand performance and structural changes in brain areas remote from the infarct site was examined. Using voxel-based morphometry, we correlated contralesional gross manual dexterity assessed by the box and block test and whole-brain gray and white-matter volume changes on high-resolution magnetic resonance imaging in 37 7-year-old post-neonatal arterial ischemic stroke children. We also compared the volume of the identified structures with magnetic resonance imaging data of 10 typically developing age-matched children. Areas showing the highest positive correlation with the box and block test scores were ipsilesional mediodorsal thalamus, contralesional cerebellar lobule VIIa Crus I, and ipsilesional corticospinal tract at the level of superior corona radiata, the posterior limb of the internal capsule, and the cerebral peduncle and the ipsilesional body of corpus callosum. When compared with typically developing age-matched children, post-neonatal arterial ischemic stroke children with severe contralesional hand motor deficit exhibited significant volume reductions in these structures (except the cerebellum), whereas no differences were found with those with good manual dexterity. No negative correlation was found between box and block test scores and brain areas. Contralesional hand performance after neonatal arterial ischemic stroke is correlated with atrophy in brain areas directly or functionally connected but anatomically remote from the infarct. Our study suggests a role of the cerebellar lobule VIIa Crus I and mediodorsal thalamus in manual dexterity. URL: https://clinicaltrials.gov. Unique identifier: NCT02511249.

Shaping Early Reorganization of Neural Networks Promotes Motor Function after Stroke.

Neural plasticity is a major factor driving cortical reorganization after stroke. We here tested whether repetitively enhancing motor cortex plasticity by means of intermittent theta-burst stimulation (iTBS) prior to physiotherapy might promote recovery of function early after stroke. Functional magnetic resonance imaging (fMRI) was used to elucidate underlying neural mechanisms. Twenty-six hospitalized, first-ever stroke patients (time since stroke: 1–16 days) with hand motor deficits were enrolled in a sham-controlled design and pseudo-randomized into 2 groups. iTBS was administered prior to physiotherapy on 5 consecutive days either over ipsilesional primary motor cortex (M1-stimulation group) or parieto-occipital vertex (control-stimulation group). Hand motor function, cortical excitability, and resting-state fMRI were assessed 1 day prior to the first stimulation and 1 day after the last stimulation. Recovery of grip strength was significantly stronger in the M1-stimulation compared to the control-stimulation group. Higher levels of motor network connectivity were associated with better motor outcome. Consistently, control-stimulated patients featured a decrease in intra- and interhemispheric connectivity of the motor network, which was absent in the M1-stimulation group. Hence, adding iTBS to prime physiotherapy in recovering stroke patients seems to interfere with motor network degradation, possibly reflecting alleviation of post-stroke diaschisis.

Individual prediction of chronic motor outcome in the acute post-stroke stage: Behavioral parameters versus functional imaging.

Several neurobiological factors have been found to correlate with functional recovery after brain lesions. However, predicting the individual potential of recovery remains difficult. Here we used multivariate support vector machine (SVM) classification to explore the prognostic value of functional magnetic resonance imaging (fMRI) to predict individual motor outcome at 4-6 months post-stroke. To this end, 21 first-ever stroke patients with hand motor deficits participated in an fMRI hand motor task in the first few days post-stroke. Motor impairment was quantified assessing grip force and the Action Research Arm Test. Linear SVM classifiers were trained to predict good versus poor motor outcome of unseen new patients. We found that fMRI activity acquired in the first week post-stroke correctly predicted the outcome for 86% of all patients. In contrast, the concurrent assessment of motor function provided 76% accuracy with low sensitivity (<60%). Furthermore, the outcome of patients with initially moderate impairment and high outcome variability could not be predicted based on motor tests. In contrast, fMRI provided 87.5% prediction accuracy in these patients. Classifications were driven by activity in ipsilesional motor areas and contralesional cerebellum. The accuracy of subacute fMRI data (two weeks post-stroke), age, time post-stroke, lesion volume, and location were at 50%-chance-level. In conclusion, multivariate decoding of fMRI data with SVM early after stroke enables a robust prediction of motor recovery. The potential for recovery is influenced by the initial dysfunction of the active motor system, particularly in those patients whose outcome cannot be predicted by behavioral tests.

P108. The effect of task effort on recovery-related brain activity following motor stroke assessed with FMRI and EEG

Introduction Spontaneous recovery of motor deficits after stroke evolve at a rather unpredictable fashion regarding the time and extend of skill reacquisition (Langhorne et al., Lancet, 2011). Previous longitudinal studies investigating brain activity during recovery from hand motor deficits point to an early overactivation of the motor network with a decrease back to near normal patterns later after stroke (Rehme et al., Neuroimage, 2012). Since patients regain force and skill during recovery, changes in neural activation over time could be explained by a decreased relative task effort over time. Such a behavioral bias could affect neuroimaging findings and their interpretation in regard to recovery, a question not or not sufficiently accounted for in previous studies. The aim of the present study was to systematically investigate the influence of task effort on recovery-related brain activation. We addressed the question whether keeping either task effort or task output constant leads to differing patterns of recovery-related brain activation over time within a “constant output-constant effort” design. We speculated that due to the recovery-related increase in manual power, the two experimental conditions show different evolutions of brain activity patterns with constant output reflecting stronger changes over time. Since electroencephalography and functional magnetic resonance imaging measure different aspects of brain activation, we used a multimodal approach. Methods We assessed brain activity with functional magnetic resonance imaging (FMRI, blood oxygenation level dependent signal (BOLD)) and EEG based task-related spectral-power within lower alpha, upper alpha, beta band, in a longitudinal design covering the acute (3–5 d post stroke), subacute (30 days) and early chronic (90 days) phase after an ischemic infarction causing a hand motor deficit. At every time point, patients ( n = 12 (EEG)/8 (FMRI), m = 6, age 66.67 ± 9.03 (mean ± std), 4 left hemispheric lesions) performed whole hand grips with both 5 kg constant output and 20% of the current individual maximal force (constant effort). Results Patients showed significant recovery over time (increase in grip force over time, p p Conclusion This longitudinal study demonstrates in mildly affected patients that task-related brain activity significantly decreases over time as suggested previously. The main finding was that the dynamic change of brain activation over time did not relate to the effort necessary to perform the task at each measurement time point. In detail, this shows that the task effort had no significant effect on the slope of brain activity decrease in the course of recovery. These data suggest that the decline of motor task-related brain activity during recovery is largely reflecting adaptive processes in the course of neuronal reorganization and is not influenced significantly by behavioral/cognitive differences, such as effort, over time. Using multimodal imaging, two independent measures of neural activity (BOLD, EEG power) support this finding, mutually validating methodological assessment of brain activation and augmenting the explanatory power.

P105. Network dynamics engaged in the modulation of motor behavior in chronic stroke patients

Background Affected hand movements are associated with a successive increase of neural activity in both hemispheres in the first weeks after stroke, which then return to levels observed in healthy controls, particularly in patients making full motor recovery. Little is known about the changes of the interplay of brain regions that enable the modulation of motor performance after stroke. In healthy subjects, an important feature of faster hand movements is mediated by a more effective coupling between distinct cortical and subcortical motor areas. But the mechanisms underlying the dynamic modulation of motor behavior in stroke patients related to motor impairment and recovery thereof are still unclear. Methods We, therefore, investigated 10 chronic stroke patients with mild to moderate unilateral hand motor deficits and 10 healthy, age-matched controls by using functional magnetic resonance imaging (fMRI). Motor system activity was assessed by fist closures at different movement frequencies (0.5 Hz, 1.0 Hz, and 2.0 Hz) performed with the affected/right or unaffected/left hand. Results When chronic stroke patients moved their affected, right hand, the fMRI data revealed a stronger frequency-dependent increase of neural activity within both the dorsolateral premotor cortex (PMd) and the superior parietal lobe (SPL), contralateral to the lesioned hemisphere as compared to healthy controls. Conclusion Our findings suggest a critical contribution of contralateral PMd and SPL in the flexible adaption of the brain to varying motor demands in chronic stroke patients controlling temporal and spatial preciseness of recovered complex hand movements in the contralesional hemisphere.

V37. Interactions between primary and secondary motor areas for recovered hand functions after stroke

Objectives Goal oriented hand movements are the final product of complex interplay between multiple cortical regions of the frontoparietal cortex. Following stroke, recovery of function might be related to structural and functional modifications in the surviving brain networks. Strikingly, the ventral premotor cortex (PMv) plays a crucial role in the sensorimotor processing engaged in shaping finger movements and shares extensive reciprocal projections to the primary motor cortex (M1), making the PMv a promising structure involved in hand motor recovery after stroke. By instance, mapping studies in stroke animal models consistently showed that improvement in forelimb motor performance was associated with reorganization within the PMv. However, precise functional interactions between the PMv and the M1 in the process of hand motor recovery have not been investigated in stroke patients. Paired-pulse transcranial magnetic stimulation (pp-TMS) was used in order to evaluate PMv-M1 interactions in stroke patients and healthy controls. To further disentangle whether recovery-related changes are specific to PMv-M1 or apparent in all interactions between primary and secondary motor areas after stroke, connectivity between posterior parietal cortex (PPC) and M1 have been also assessed. Methods 22 patients (aged 62.3 ± 9.8 SD) with mild to severe unilateral hand motor deficit and 20 healthy controls (aged 59.7 ± 20.9 SD) participated in the present study. Within experiment-1, PMv-M1 interactions were investigated by using neuronavigated-ppTMS in both the affected and unaffected hemisphere, considering 6 interstimulus intervals (ISI; 2, 4, 6, 8, 10 and 15 ms) between conditioning and test pulse. In experiment-2, PPC-M1 interactions were investigated targeting two PPC regions: the anterior intraparietal sulcus (aIPS) and the caudal intraparietal sulcus (cIPS). Results Experiment-1: A consistent difference between patients and controls, with a group by ISI interaction, has been observed for both the affected (F = 14.9, p Conclusions The present pp-TMS approach enabled us to assess in vivo the specific contributions of individual brain areas to recovery of function after stroke. These findings demonstrate changes in interareal connectivity between the PMv and the M1 associated with recovered hand motor function. These data support a paramount role of the PMv within the process of functional reorganization and successful hand motor recovery, as suggested in previous animal work, contributing significantly to the understanding of the mechanisms underlying cortical reorganization after focal brain lesions.

Neuroradiological findings expand the phenotype of OPA1-related mitochondrial dysfunction

ObjectiveOPA1 mutations are responsible for more than half of autosomal dominant optic atrophy (ADOA), a blinding disease affecting the retinal ganglion neurons. In most patients the clinical presentation is restricted to the optic nerve degeneration, albeit in 20% of them, additional neuro-sensorial symptoms might be associated to the loss of vision, as frequently encountered in mitochondrial diseases. This study describes clinical and neuroradiological features of OPA1 patients. MethodsTwenty two patients from 17 families with decreased visual acuity related to optic atrophy and carrying an OPA1 mutation were enrolled. Patients underwent neuro-ophthalmological examinations. Brain magnetic resonance imaging (T1, T2 and flair sequences) was performed on a 1.5-Tesla MR Unit. Twenty patients underwent 2-D proton spectroscopic imaging. ResultsBrain imaging disclosed abnormalities in 12 patients. Cerebellar atrophy mainly involving the vermis was observed in almost a quarter of the patients; other abnormalities included unspecific white matter hypersignal, hemispheric cortical atrophy, and lactate peak. Neurological examination disclosed one patient with a transient right hand motor deficit and ENT examination revealed hearing impairment in 6 patients. Patients with abnormal MRI were characterized by: (i) an older age (ii) more severe visual impairment with chronic visual acuity deterioration, and (iii) more frequent associated deafness. ConclusionsOur results demonstrate that brain imaging abnormalities are common in OPA1 patients, even in those with normal neurological examination. Lactate peak, cerebellar and cortical atrophies are consistent with the mitochondrial dysfunction related to OPA1 mutations and might result from widespread neuronal degeneration.

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

BackgroundDamage 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. AimsThe current study examined the occurrence of neuronal changes associated to piano training in youths with neurodevelopmental-associated hand motor deficits. MethodsFunctional 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. ResultsDynamic 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. ConclusionsA 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.