Impact of multidomain preventive strategies on functional brain connectivity in older adults with cognitive complaint: Subset from the Montpellier center of the ancillary MAPT-MRI study.

Introduction: The impact of multi-domain preventive interventions on older adults, in particular on those with higher risk to develop Alzheimer's disease (AD), could be beneficial, as it may delay cognitive decline. However, the precise mechanism of such positive impact is not fully understood and may involve brain reserve and adaptability of brain functional connectivity (FC). Methods: To determine the effect of multidomain interventions (involving physical activity, cognitive training, nutritional counseling alone or in combination with omega-3 fatty acid supplementation and vs. a placebo) on the brain, longitudinal FC changes were assessed after 36 months of intervention on 100 older adults (above 70 year-old) with subjective cognitive complaints. Results: No global change in FC was detected after uni or multidomain preventive interventions. However, an effect of omega-3 fatty acid supplementation dependent on cognitive decline status was underlined for frontoparietal, salience, visual and sensorimotor networks FC. These findings were independent of the cortical thickness and vascular burden. Discussion: These results emphasize the importance of patient stratification, based on risk factors, for preventive interventions.

Language reorganization after resection of low-grade gliomas: an fMRI task based connectivity study.

Few studies addressed the evolution of brain activity before and after brain tumor resection. Using a fMRI naming task, we evaluated possible underlying plasticity phenomena. Thirty-two patients with left low-grade gliomas (16 women; age = 38.6 ± 8.31 years) and 19 healthy controls (7 women; age = 42.4 ± 12.1) were included in the study. An overt picture-naming task (DO80) was performed pre and post (3 months) surgery, as well as within the MRI in a covert manner. Exams included an injected 3DT1, a T2FLAIR, a DTI and a GE-EPI (task) sequence. Activations maps were compared with picture naming score, FA and MD maps were estimated, a VLSM analysis was performed on tumor masks, and disconnectome maps were reconstructed. Pre-surgery, the left parahippocampal gyrus (LPH) was inversely associated with task performance. Increased pre-post surgery left lingual gyrus (LLG) activity was found related to decreased picture naming performance. The evolution of left lingual gyrus (LLG) activity was negatively associated with the evolution of picture naming performance. In controls, the LPH was functionally connected to the right precentral gyrus (RPCG) and slightly to the LLG. This was not clearly retrieved in the patient group. Preoperatively, the LLG was connected to the left planum temporale and to the right lingual gyrus. The same result was found for controls. Postoperatively, the LLG was only connected to the RPCG. No association was found between evolution of FA/MD and evolution of picture naming performance. There is not one unique pattern of pre- and postoperative plasticity concerning picture-naming performance in DLGG patients.

Rehabilitation of the upper arm early after stroke: Video games versus conventional rehabilitation. A randomized controlled trial.

BACKGROUND: Few rehabilitation methods have proven their efficacy in increasing sensori-motor recovery and/or function of the upper limb (UL) after stroke. Video games (VGs) are promising tools in this indication. OBJECTIVE: To compare UL rehabilitation by using VGs and conventional rehabilitation (CR) in patients with sub-acute stroke. DESIGN: Single-blind, multicentric trial, with central randomization and stratification by center. SETTING: Physical and rehabilitation medicine departments of 2 university hospitals. PARTICIPANTS: Adults within 3 months after a first vascular cerebral accident, with UL Fugl Meyer Score (UL-FMS)<30/66 and without major cognitive impairment. INTERVENTION: A 45-min additional session of conventional occupational therapy (OT) or a VG-based OT session as add-on therapy to usual rehabilitation programs, 5 days/week for 6 weeks. MAIN OUTCOME MEASURES: Primary outcome: UL-FMS. Secondary outcome: Box and Block Test (BBT), Wolf Motor Function test (WMFT), Motor Activity Log (MAL), Barthel Index and quality of life (SF-36). RESULTS: We included 51 patients (20 women) at a mean (SD) of 27.2 (19.4) days post-stroke (mean age 58 years [range 24-83]), 26 in the CR group and 25 in the VG group (23 in each group at 6-month follow-up). The mean duration of the additional rehabilitation session was similar in both groups: 29.3 (4.3) vs 28.0 (4.4) min in CR and VG groups. Shoulder pain occurred in 4 patients in the VG group versus 7 in the CR group. At day 45, gain in UL-FMS did not significantly differ between the groups (CR mean 17.8 [14.6] vs VG 24.1 [14.8]; P=0.10), whereas gain in BBT was doubled in the VG group (CR 7.4 [12.2] vs VG 15.7 [16.3]; P=0.02). At 6-month follow-up, the study was inconclusive about between-group differences in UL-FMS, BBT and other criteria. Post-hoc analysis showed that gains in UL-FMS or BBT were significantly higher in the VG than CR group for patients included within 30 days post-stroke. CONCLUSION: In general, we cannot conclude that video gaming and conventional OT led to different long-term sensorimotor recovery of the UL after sub-acute stroke. However, when applied within the first month after stroke, video gaming was more efficient than conventional rehabilitation on both sensorimotor recovery and gross grasping function. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01554449).

Transient immediate postoperative homotopic functional disconnectivity in low-grade glioma patients.

Background and purpose: The aim of this longitudinal study is to evaluate large-scale perioperative resting state networks reorganization in patients with diffuse low-grade gliomas following awake surgery. Materials and methods: Eighty-two patients with diffuse low-grade gliomas were prospectively enrolled and underwent awake surgical resection. Resting-state functional images were acquired at three time points: preoperative (MRI-1), immediate postoperative (MRI-2) and three months after surgery (MRI-3). We simultaneously performed perfusion-weighted imaging. Results: Comparing functional connectivity between MRI-1 and MRI-2, we observed a statistically significant functional homotopy decrease in cortical and subcortical supratentorial structures (P < 0.05). A functional homotopy increase was observed between MRI-2 and MRI-3 in parietal lobes, cingulum and putamen (P < 0.05). No significant functional connectivity modification was noticed between MRI-1 and MRI-3. Regional cerebral blood flow appeared transiently reduced on MRI-2 (P < 0.05). No correlation between neurological deficit and interhemispheric connectivity results was found. Conclusion/interpretation: We found a supratentorial widely distributed functional homotopy disruption between preoperative and immediate postoperative time points with a complete restitution three months after surgery with simultaneous variation of regional cerebral blood flow.

Modified Brain Activations of the Nondamaged Hemisphere During Ipsilesional Upper-Limb Movement in Persons With Initial Severe Motor Deficits Poststroke.

BACKGROUND: Poststroke, the ipsilesional upper limb shows slight but substantial and long-term motor deficits. OBJECTIVE: To define brain activation patterns during a gross motor flexion/extension task of the ipsilesional elbow early poststroke before and after rehabilitation, in relation to the corresponding kinematic characteristics at each time point. METHOD: Simultaneous analysis of kinematic features (amplitude, frequency, smoothness, and trajectory of movement) and of corresponding functional magnetic resonance imaging activations (block-design). A total of 21 persons with subacute initial severe stroke (Fugl-Meyer score <30/66) participated twice: within the first 2 months poststroke (V0) and after 6 weeks of rehabilitation (V1). Results at both time points were compared with activation patterns and kinematics of 13 healthy controls. RESULTS: Compared with controls ( a) movements of the ipsilesional upper-limb poststroke were smaller (V0 + V1) and less smooth (V0 + V1) and ( b) participants poststroke showed additional recruitment of the contralesional middle temporal gyrus (V0) and rolandic opercularis involved in movement visualization (V0 + V1), whereas they lacked activation of the supramarginal gyrus (V0 + V1). Over time, participants poststroke showed an extended activation of the contralesional sensorimotor cortex at V0. CONCLUSION: Movements of the ipsilesional upper limb within an initially severe stroke group were not only atypical in motor outcome, but seemed to be controlled differently. Together the observed changes pointed toward an overall disturbance of the bihemispheric motor network poststroke, marked by ( a) a possible despecialization of the nondamaged hemisphere and ( b) the employment of alternative control strategies to ensure optimal task execution.

Kinematics in the brain: unmasking motor control strategies?

In rhythmical movement performance, our brain has to sustain movement while correcting for biological noise-induced variability. Here, we explored the functional anatomy of brain networks during voluntary rhythmical elbow flexion/extension using kinematic movement regressors in fMRI analysis to verify the interest of method to address motor control in a neurological population. We found the expected systematic activation of the primary sensorimotor network that is suggested to generate the rhythmical movement. By adding the kinematic regressors to the model, we demonstrated the potential involvement of cerebellar-frontal circuits as a function of the irregularity of the variability of the movement and the primary sensory cortex in relation to the trajectory length during task execution. We suggested that different functional brain networks were related to two different aspects of rhythmical performance: rhythmicity and error control. Concerning the latter, the partitioning between more automatic control involving cerebellar-frontal circuits versus less automatic control involving the sensory cortex seemed thereby crucial for optimal performance. Our results highlight the potential of using co-registered fine-grained kinematics and fMRI measures to interpret functional MRI activations and to potentially unmask the organisation of neural correlates during motor control.

Trajectory formation principles are the same after mild or moderate stroke.

When we make rapid reaching movements, we have to trade speed for accuracy. To do so, the trajectory of our hand is the result of an optimal balance between feed-forward and feed-back control in the face of signal-dependant noise in the sensorimotor system. How far do these principles of trajectory formation still apply after a stroke, for persons with mild to moderate sensorimotor deficits who recovered some reaching ability? Here, we examine the accuracy of fast hand reaching movements with a focus on the information capacity of the sensorimotor system and its relation to trajectory formation in young adults, in persons who had a stroke and in age-matched control participants. We find that persons with stroke follow the same trajectory formation principles, albeit parameterized differently in the face of higher sensorimotor uncertainty. Higher directional errors after a stroke result in less feed-forward control, hence more feed-back loops responsible for segmented movements. As a consequence, movements are globally slower to reach the imposed accuracy, and the information throughput of the sensorimotor system is lower after a stroke. The fact that the most abstract principles of motor control remain after a stroke suggests that clinicians can capitalize on existing theories of motor control and learning to derive principled rehabilitation strategies.

The reorganization of motor network in hemidystonia from the perspective of deep brain stimulation.

Hemidystonia is usually 'secondary' to structural lesions within the cortico-striato-pallido-thalamic or the cerebello-thalamo-cortical loops. Globus pallidus internus Deep Brain Stimulation (GPi DBS) is a validated technique in the treatment of primary dystonia and still under assessment for secondary dystonia. Results of DBS in hemidystonia are limited and heterogeneous. Further knowledge concerning motor network organization after focal brain lesions might contribute to the understanding of this mitigated response to DBS and to the refinement of DBS indications and techniques in secondary dystonia. This study aimed to identify movement-related functional magnetic resonance imaging (fMRI) activation patterns in a group of hemidystonic patients in comparison to healthy controls (HC). Further analysis assessed recruitment pattern in different patient subgroups defined according to clinical and radiological criteria relevant to GPi DBS eligibility (hyperkinetic/hypokinetic and prepallidal/postpallidal). Eleven patients and nine HC underwent fMRI with a block-design alternating active and rest conditions. The motor paradigm consisted of self-paced elbow flexion-extension movements. The main results were as follows: single-subject studies revealed several activation patterns involving motor-related network regions; both ipsilesional and contralesional hemispheres showed abnormal patterns of activity; compared with HC, hemidystonic patients showed decreased brain activity in ipsilesional thalamus, pallidal and temporal areas during affected arm task execution; 'hypokinetic' subgroup was commonly related to widespread bilateral overactivity. This study provides additional arguments for case-by-case assessment of DBS surgery indication and target selection in hemidystonia. Single-lead approach might be unable to modulate a highly disorganized network activity in certain patients with this clinical syndrome.

The contribution of kinematics in the assessment of upper limb motor recovery early after stroke.

BACKGROUND: Kinematic assessment of upper limb motor recovery after stroke may be related to clinical scores while being more sensitive and reliable than clinical evaluation alone. OBJECTIVE: To identify the potential of kinematics in assessing upper limb recovery early poststroke. METHODS: Thirteen patients were included within 1 month poststroke and evaluated once a week for 6 weeks and at 3 months with (a) the Fugl-Meyer Assessment (FMA) and (b) kinematic analysis of reach-to-grasp movements. The link between clinical and kinematic data was identified using mixed model with random coefficient analysis. RESULTS: Movement time, trajectory length, directness, smoothness, mean and maximum velocity of the hand were sensitive to change over time and distinguished between movements of paretic, nonparetic, and healthy control limbs. The FMA score increased with movement smoothness over time, explaining 62.5% of FMA variability. CONCLUSION: Kinematic analysis of reach-to-grasp movements is relevant to assess upper limb recovery early poststroke, and is linked to the FMA. Kinematics could provide more accurate real-time indicators of patients' recovery as compared with the sole use of clinical scores, although it remains challenging to establish the universality of the reaching model in relation to motor recovery after stroke.

Motor recovery of the ipsilesional upper limb in subacute stroke.

OBJECTIVE: To investigate the time-related changes in motor performance of the ipsilesional upper limb in subacute poststroke patients by using clinical and kinematic assessments. DESIGN: Observational, longitudinal, prospective, monocentric study. SETTING: Physical medicine and rehabilitation department. PARTICIPANTS: Stroke patients (n=19; mean age, 62.9y) were included less than 30 days after a first unilateral ischemic/hemorrhagic stroke. The control group was composed of age-matched, healthy volunteers (n=9; mean age, 63.1y). INTERVENTIONS: Clinical and kinematic assessments were conducted once a week during 6 weeks and 3 months after inclusion. Clinical measures consisted of Fugl-Meyer Assessment, Box and Block Test (BBT), Nine-Hole Peg Test (9HPT), and Barthel Index. We used a 3-dimensional motion recording system during a reach-to-grasp task to analyze movement smoothness, movement time, and peak velocity of the hand. Healthy controls performed both clinical (BBT and 9HPT) and kinematic evaluation within a single session. MAIN OUTCOME MEASURES: BBT and 9HPT. RESULTS: Recovery of ipsilesional upper arm capacities increased over time and leveled off after a 6-week period of rehabilitation, corresponding to 9 weeks poststroke. At study discharge, patients demonstrated similar ipsilesional clinical scores to controls but exhibited less smooth reaching movements. We found no effect of the hemispheric side of the lesion on ipsilesional motor deficits. CONCLUSIONS: Our findings provide evidence that ipsilesional motor capacities remain impaired at least 3 months after stroke, even if clinical tests fail to detect the impairment. Focusing on this lasting ipsilesional impairment through a more detailed kinematic analysis could be of interest to understand the specific neural network underlying ipsilesional upper-limb impairment.

Somatosensory-related limitations for bimanual coordination after stroke.

BACKGROUND: Bimanual coordinated movements may be impaired after stroke, so an assessment of causes is necessary to optimize rehabilitation strategies. OBJECTIVE: We assessed the role of afference-based sources of coordination, including phase entrainment and error correction based on visual and somatosensory feedback. METHODS: In all, 10 persons with unilateral chronic stroke and 8 age-matched controls participated in a kinesthetic tracking protocol, in which the hemiparetic upper limb was passively driven by the machine. The task consisted of matching the trajectory of the driven limb as accurately as possible with the freely moving limb in 2 conditions: eyes closed and eyes open. We analyzed the continuous relative phase (CRP), the mean absolute difference between positions (ADP) between the positions of the 2 limbs, and the jerk of the matching limb. RESULTS: Coordination instability (CRP standard deviation) and mean ADP were significantly higher for patients with eyes closed, compared with patients with eyes open, controls with eyes closed, and controls with eyes open. Moreover, the jerk was higher for the nonparetic limb of patients than for the control group. Thus, the nonparetic limb did not produce optimally smooth movements even as the motor-driven paretic limb did. CONCLUSION: Besides deficits caused by interhemispheric competition and motor execution of the paretic limb, somatosensory feedback is a limiting factor in bimanual coordination after stroke. The findings have clinical implications pertaining to the design and individualization of efficient bimanual movement therapy.

Changes in bimanual coordination during the first 6 weeks after moderate hemiparetic stroke.

BACKGROUND: Better understanding of how bimanual coordination changes over the first weeks of recovery after stroke is required to address the potential utility for bimanual rehabilitation. Three-dimensional kinematic analysis can provide quantitative assessment of unimanual and bimanual movements. OBJECTIVE: To assess the natural evolution of reaching kinematics during standard poststroke rehabilitation, focusing on bimanual coordination. METHODS: A total of 12 hemiparetic, moderately impaired patients were included within 30 days after a first unilateral ischemic/hemorrhagic stroke; 7 kinematic assessments were performed once a week for 6 weeks and at 3 months after inclusion. The reach-to-grasp task was performed in 3 different conditions: unimanual with the healthy limb (UN), unimanual with the paretic limb (UP), and bimanual (BN/BP). RESULTS: For the paretic limb, movement fluency (number of movement units and total movement time) was lower for bimanual reaching compared with unimanual reaching. For bimanual reaching, (1) movement kinematics were similar for both limbs, (2) recovery patterns of both limbs followed a similar profile with a plateau phase at 6 weeks poststroke, and (3) intertrial variability of between-hands synchronization decreased over sessions, although the mean delays remained the same. CONCLUSIONS: Bimanual coordination started to become efficient 6 weeks after onset of stroke, so for patients such as those we tested, this time could be most opportune to start bimanual-oriented rehabilitation. The challenge in future research includes determining the characteristics of patients who may best benefit from bimanual therapy.

People post-stroke perceive movement fluency in virtual reality.

We investigated the visual perception of biological movement by people post-stroke, using minimal kinematic displays. A group of twenty patients and a group of twelve age-matched healthy controls were asked to judge movement fluency. The movements to judge were either displayed as an end-point dot or as a stick-figure of the arm and trunk. It was found that the perception of movement fluency was preserved post-stroke, however, with an increase in the variability of judgment. Moreover, the end-point dot representation ameliorated what was perceived and judged, presumably by directing attention to the important kinematic cues: smoothness and directness of the trajectory. We conclude that, despite perception of actions is influenced by the ability of the observer to execute the observed movement, hemiparesis has a mild effect on the perception of biological movement. Yet, a valuable virtual learning environment for upper-limb rehabilitation should be implemented to provide the observer with neither too much, nor too little information to maximize learning.