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Background: Stroke survivors are known to suffer from post-stroke depression (PSD). However, the likelihood of structural changes in the brains of PSD patients has not been explored. This study aims to extract changes in the gray matter of these patients and test how these changes account for the PSD symptoms. Methods: High-resolution T1 weighted images were collected from 23 PSD patients diagnosed with subcortical stroke. Voxel-based morphometry and support vector machine analyses were used to analyze the data. The results were compared with those collected from 33 non-PSD patients. Findings: PSD group showed decreased gray matter volume (GMV) in the left middle frontal gyrus (MFG), and increased GMV in the right anterior cingulate gyrus (ACG) when compared to the non-PSD patients. The changes in GMVs in the MFG and ACG suggest possible systemic involvement of the prefrontal-limbic network resulting in PSD after brain lesions which is likely to be independent from the location of the lesions. Furthermore, the combined GMV values of the MFG and ACG distinguished 81% of the PSD from the non-PSD patients (76·5% sensitivity and 87·5% specificity). Interpretation: The MFG-ACG model suggests that the PSD diagnosis is likely to attribute to abnomrmality in the prefrontal-limbic network. Reduced emotional control resulting in hyperactive emotional processing seems to aggravate the PSD symptoms of the post-stroke patients. Funding: This study was supported by the Department of Rehabilitation Medicine, Nanjing Drum Tower Hospital and the University Research Facility of Behavioral and Systems Neuroscience (UBSN), The Hong Kong Polytechnic University. Declaration of Interest: The authors declare no potential conflicts of interest. Ethical Approval: The research protocol and implementation were in accordance with the "Declaration of Helsinki". Written informed consent was obtained from each patient and the ethics approval was obtained from the research committee of the hospital in which the study was conducted.

Subcortical aphasia results from damage to subcortical regions, but the exact underlying mechanism is unclear. We investigated the influence of arcuate fasciculus (AF) damage on the severity of subcortical aphasia after stroke using brain diffusion tensor imaging (DTI). We enrolled subjects from the “Stroke Outcome Prediction (STOP)” database: 41 patients with first-ever, left hemispheric subcortical stroke (33 with hemorrhagic, eight with ischemic stroke) who underwent the Western Aphasia Battery (WAB) evaluation and DTI. We performed a correlation analysis between lesion volume (LV) and the DTI parameters of the AF, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), and AF type, and the WAB scores, and a classification and regression tree (CART) analysis to identify significant neuroimaging predictors for subcortical aphasia. FA significantly correlated with the aphasia quotient (AQ) and the naming score, and LV with the AQ and several WAB subtests (fluency, repetition, naming). At the subgroup level, FA and AF type showed significant correlations with the AQ, comprehension, and naming in the ischemic stroke group, while LV was associated with naming in the hemorrhagic stroke group. LV and FA were significant predictors of the AQ in all subjects, while FA was the only predictor of the language score in the hemorrhagic stroke group. Damage to the AF may be an important underlying mechanism of subcortical aphasia, and the FA value representing the integrity of the AF is an important predictor of the severity of subcortical aphasia.

Highlights • The left UF damage is associated with PSSA language impairment severity. • The left UF FA is decreased and correlated with language impairment in PSSA. • The left temporal pole ALFF is associated with PSSA language impairment and recovery. • Our results support the disconnection theory in PSSA pathology and recovery., Aphasia, one of the most common cognitive impairments after stroke, is commonly considered to be a cortical deficit. However, many studies have reported cases of post subcortical stroke aphasia (PSSA). The pathology and recovery mechanism of PSSA remain unclear. This study aimed to investigate PSSA mechanism through a multimodal magnetic resonance imaging (MRI) approach and a two-session study design (baseline and one month after treatment). Thirty-six PSSA patients and twenty-four matched healthy controls (HC) were included. All patients had subcortical infarctions involving left subcortical white matter for 1 to 6 months. The patients underwent MRI scan and Western Aphasia Battery (WAB) examination before and after one month’s comprehensive treatment. Region-wise lesion-symptom mapping (RLSM), tractography, fractional anisotropy (FA), and amplitude of low-frequency fluctuations (ALFF) analysis were conducted. After MRI preprocessing and exclusion, FA analysis included 35 patients pre-treatment and 16 patients post-treatment. ALFF analysis included 30 patients pre-treatment and 14 patients post-treatment. We found: 1) the amount of damage in the left uncinate fasciculus (UF) was associated with WAB aphasia quotient (AQ); 2) the left UF FA and left temporal pole (TP) ALFF were decreased and positively correlated with WAB-AQ, spontaneous speech, and naming in PSSA patients; and 3) PSSA patients showed increased left TP ALFF when their language ability recovered after treatment. The left TP ALFF change was positively correlated with AQ change. Our results demonstrate the importance of left UF and left TP (one of the cortical terminals of the left UF) in PSSA pathology and recovery. These results may further provide support for the disconnection theory in the mechanism of PSSA.

Glucose hypometabolism in cortical structures after functional disconnection is frequently reported in patients with white matter diseases such as subcortical stroke. However, the molecular and cellular mechanisms have been poorly elucidated. Here we show, in an animal model of internal capsular infarct, that GABA-synthesizing reactive astrocytes in distant cortical areas cause glucose hypometabolism via tonic inhibition of neighboring neurons. We find that reversal of aberrant astrocytic GABA synthesis, by pharmacological inhibition and astrocyte-specific gene silencing of MAO-B, reverses the reduction in cortical glucose metabolism. Moreover, induction of aberrant astrocytic GABA synthesis by cortical injection of putrescine or adenovirus recapitulates cortical hypometabolism. Furthermore, MAO-B inhibition causes a remarkable recovery from post-stroke motor deficits when combined with a rehabilitation regimen. Collectively, our data indicate that cortical glucose hypometabolism in subcortical stroke is caused by aberrant astrocytic GABA and MAO-B inhibition and that attenuating cortical hypometabolism can be a therapeutic approach in subcortical stroke.

Patients with stroke often exhibit evidence of abnormal functional connectivity (FC). However, whether and how anatomical distance affects FC at rest remains unclear in patients with chronic subcortical stroke. Eighty-six patients with chronic (more than six months post-onset) subcortical stroke (44 left-sided patients and 42 right-sided patients) with different degrees of functional recovery, and 75 matched healthy controls underwent resting-state functional magnetic resonance imaging scanning. Positive functional connectivity strength (FCS) was computed for each voxel in the brain using a data-driven whole-brain resting state FCS method, which was further divided into short- and long-range FCS. Compared with healthy controls, patients with left-sided infarctions exhibited stronger global- and long-range FCS in the left sensorimotor cortex (SMC), and no significant intergroup difference was found for short-range FCS. No significant differences were found between the patients with right-sided infarctions and healthy controls for global, long- and short-range FCS. These findings suggested that the positive FCS alteration was connection-distance dependent within patients with left-sided chronic subcortical stroke. Also, a positive correlation was found between the FCS in the left SMC and the accuracy of the Flanker test, reflecting a compensatory FCS alteration for altered attention and executive function abilities exhibited by those with left-sided stroke.

Regaining the function of an impaired limb is highly desirable in individuals experiencing paralysis. One possible avenue to achieve this goal is through rewiring of preserved neural structures to bridge the interrupted pathway using a brain-computer interface. Here we demonstrated that monkeys with subcortical stroke were able to learn to use an artificial cortico-muscular connection (ACMC), brain-controlled functional electrical stimulation to the hand muscles, to regain volitional control of a paralyzed hand. In a targeted manner, the ACMC induced reorganization of cortical activities among an extensive cortical area; the modulating high-gamma activity became concentrated around an arbitrarily selected cortical site controlling stimulation to the muscles. This reorganization could be reset and rapidly reorganized to a new cortical site. Thus, the ACMC imparted a new function for muscle control to a connected cortical site and triggered cortical reorganization in order to restore impaired motor function after stroke.

Movements of the paretic hand in patients with chronic subcortical stroke are associated with high interhemispheric inhibition (IHI) targeting the motor cortex in the lesioned hemisphere relative to healthy controls. The purpose of this investigation was to determine whether this abnormality also involves IHI operating during movements of the non-paretic hand. Here, we studied IHI in the process of generation of voluntary index finger movements by the paretic and non-paretic hands in a simple reaction time paradigm in a group of patients with chronic subcortical stroke. With movements of the non-paretic index finger, IHI targeting the contralateral primary motor cortex ((c)M1) decreased progressively to turn into facilitation at around movement onset, similar to healthy controls. In contrast, movements of the paretic index finger resulted in significantly deeper inhibition at all premovement timings relative to the non-paretic hand. In conclusion, these results document a deeper premovement IHI with paretic than non-paretic hand movements of patients with chronic subcortical stroke, a possible mechanism underlying deficits in motor control.

Five patients with left striatocapsular infarction were studied twice with PET during auditory-cued right thumb-index tapping, around 2 months after stroke and again around 8 months after stroke. At PET1 and PET2, the ipsilesional primary sensorimotor (SM1) activation peak Talairach coordinates were compared to those from seven aged-matched healthy controls. At PET1, there was a significant posterior displacement of SM1 activation peak, which confirms a previous report and may represent unmasking/disinhibition of motor representations. Over time, there was no significant change in the coordinates, and no significant correlation between coordinate changes from PET1 to PET2 and concomitant motor recovery. The implications of posterior displacement of SM1 activation peak for recovery therefore remain elusive.

Introduction Since early days after stroke, the brain undergoes a complex reorganization to allow compensatory mechanisms that promote functional recovery. Characterizing specific neurophysiological markers of motor recovery after stroke could improve clinical decision making. Objectives: To track the time-course of motor cortical reorganization in a stroke patients group, and to individuate the neurophysiological markers associated to clinical outcome. Patients & methods Ten patients in the sub-acute phase of ischemic subcortical stroke were evaluated within 20 days and after 40, 60 and 180 days after stroke. For each time-point, cortical reactivity and cortical oscillations changes, evoked by 80 single TMS pulses, were assessed over the motor cortex of the affected and unaffected hemisphere, combining TMS-EEG. These measurements were paralleled with motor and clinical evaluations. Repeated measures ANOVA and Friedman test were used to evaluate changes over time of all measures. Results Our data showed specific cortical oscillatory activity changes in the alpha band, in a specific time point of the longitudinal evaluation only in the affected hemisphere. Stroke patients showed a significant increase in TMS-evoked alpha oscillations, as highlighted by spectral perturbation analysis. Notably, these changes occurred at 60 days after stroke, indicating that crucial mechanisms of cortical reorganization occur in this short-time window. Moreover, a cortical reactivity increase was observed at 40 days after stroke onset in affected hemisphere respect to other times and respect to unaffected hemisphere. These changes coincided with the clinical and behavioural amelioration. Conclusion For the first time, this study demonstrates the possibility to track longitudinally the motor cortical changes following stroke, by means a multimodal approach. These findings could allow, not only to identify neurophysiological markers of stroke pathophysiology, but also to provide new insight into how and when neuromodulatory interventions could drive neuroplasticity in a functional direction.

WCN 2013 No: 1745 Topic: 2 — Movement Disorders Posterior SMA syndrome after subcortical stroke: Contralateral akinesia reversed by visual control N. Radman, S. Cacioppo, L. Spierer, E. Schmidlin, E. Mayer, J.-M. Annoni. Laboratory for Cognitive and Neurological Sciences, Department for Medicine, Neurology, University of Fribourg, Fribourg, Switzerland; High Performance Electrical Neuroimaging Laboratory, CCSN, Department of Psychology, University of Chicago, Chicago, IL, USA; Department of Medicine, Physiology, University of Fribourg, Fribourg, Switzerland; Departement of Neurology, Geneva University Hospital