Behavioral and Neurophysiological Mechanisms of Recovery Post-Stroke

Strokes can affect very different behavioral domains causing deficits in language, memory, visual attention and movement. This range of deficits is caused by stroke lesions that occur in different locations, and it reflects both the local structural damage as well as remote and widespread neurophysiological abnormalities of structurally normal regions of the brain. The recovery of behavioral deficits depends both on psychosocial factors like age and education, whose brain substrates are presently poorly defined, structural variables such as lesion size and location, and neurobiological repair mechanisms both locally near the lesion and network-wide. In the current work we hypothesized that behavioral recovery can be divided in two classes: ‘domain-general’ that influence recovery of deficits across multiple domains of function; and, ‘domain-specific’ that differ in different functions. At the neurobiological level, we test the hypothesis that domain-specific normalization of abnormal patterns of synchronization occurring across multiple networks at the acute stage represents one of the major neurophysiological correlates of behavioral recovery. Specifically, I will focus on the recovery of attention deficits post-stroke, as seen in the syndrome of hemispatial neglect. Recovery of neurological deficits reaches a maximum by 3 months post-stroke, and then plateaus in a similar manner across domains without reaching normal performance. The best predictor of chronic performance in each domain of function is the severity of initial deficit that relates proportionally to the amount of recovery (domain-general). However, specific variables such as education level and lesion location differentially improve the prediction of recovery in specific domains (domain-specific). Domain general components likely reflect mechanisms of spontaneous recovery that are activated after a stroke, whereas the domain-specific factors may include those related to compensatory strategies. Independent of initial severity, the improvement of acutely depressed inter-hemispheric functional connectivity or synchrony across attention, sensory, and motor networks, and a restoration of the normally negative (anti-) correlation between dorsal attention/motor regions and default-mode/frontoparietal regions, robustly predicts recovery of attention deficits post-stroke. These findings are consistent with a normalization of neurophysiological patterns in relationship to behavioral recovery, and a tendency of damaged brain networks to return to normal levels of integration/segregation, which are optimal for information processing

The effects of hemodynamic lag on functional connectivity and behavior after stroke

Stroke disrupts the brain's vascular supply, not only within but also outside areas of infarction. We investigated temporal delays (lag) in resting state functional magnetic resonance imaging signals in 130 stroke patients scanned two weeks, three months and 12 months post stroke onset. Thirty controls were scanned twice at an interval of three months. Hemodynamic lag was determined using cross-correlation with the global gray matter signal. Behavioral performance in multiple domains was assessed in all patients. Regional cerebral blood flow and carotid patency were assessed in subsets of the cohort using arterial spin labeling and carotid Doppler ultrasonography. Significant hemodynamic lag was observed in 30% of stroke patients sub-acutely. Approximately 10% of patients showed lag at one-year post-stroke. Hemodynamic lag corresponded to gross aberrancy in functional connectivity measures, performance deficits in multiple domains and local and global perfusion deficits. Correcting for lag partially normalized abnormalities in measured functional connectivity. Yet post-stroke FC-behavior relationships in the motor and attention systems persisted even after hemodynamic delays were corrected. Resting state fMRI can reliably identify areas of hemodynamic delay following stroke. Our data reveal that hemodynamic delay is common sub-acutely, alters functional connectivity, and may be of clinical importance

Early diffusion evidence of retrograde transsynaptic degeneration in the human visual system

We investigated whether diffusion tensor imaging (DTI) indices of white matter integrity would offer early markers of retrograde transsynaptic degeneration (RTD) in the visual system after stroke Objective: We investigated whether diffusion tensor imaging (DTI) indices of white matter integrity would offer early markers of retrograde transsynaptic degeneration (RTD) in the visual system after stroke. Methods: We performed a prospective longitudinal analysis of the sensitivity of DTI markers of optic tract health in 12 patients with postsynaptic visual pathway stroke, 12 stroke controls, and 28 healthy controls. We examined group differences in (1) optic tract fractional anisotropy (FA-asymmetry), (2) perimetric measures of visual impairment, and (3) the relationship between FA-asymmetry and perimetric assessment. Results: FA-asymmetry was higher in patients with visual pathway lesions than in control groups. These differences were evident 3 months from the time of injury and did not change significantly at 12 months. Perimetric measures showed evidence of impairment in participants with visual pathway stroke but not in control groups. A significant association was observed between FA-asymmetry and perimetric measures at 3 months, which persisted at 12 months. Conclusions: DTI markers of RTD are apparent 3 months from the time of injury. This represents the earliest noninvasive evidence of RTD in any species. Furthermore, these measures associate with measures of visual impairment. DTI measures offer a reproducible, noninvasive, and sensitive method of investigating RTD and its role in visual impairment

Stronger prediction of motor recovery and outcome post-stroke by cortico-spinal tract integrity than functional connectivity

<div><p>Objectives</p><p>To examine longitudinal changes in structural and functional connectivity post-stroke in patients with motor impairment, and define their importance for recovery and outcome at 12 months.</p><p>Methods</p><p>First-time stroke patients (N = 31) were studied at 1–2 weeks, 3 months, and 12 months post-injury with a validated motor battery and resting-state fMRI to measure inter-hemispheric functional connectivity (FC). Fractional anisotropy (FA) of the cortico-spinal tract (CST) was derived from diffusion tensor imaging as a measure of white matter organization. ANOVAs were used to test for changes in FC, FA, and motor performance scores over time, and regression analysis related motor outcome to clinical and neuroimaging variables.</p><p>Results</p><p>FA of the ipsilesional CST improved significantly from 3 to 12 months and was strongly correlated with motor performance. FA improved even in the absence of direct damage to the CST. Inter-hemispheric FC also improved over time, but did not correlate with motor performance at 12 months. Clinical variables (early motor score, education level, and age) predicted 80.4% of the variation of motor outcome, and FA increased the predictability to 84.6%. FC did not contribute to the prediction of motor outcome.</p><p>Conclusions</p><p>Stroke causes changes to the CST microstructure that can account for behavioral variability even in the absence of demonstrable lesion. Ipsilesional CST undergoes remodeling post-stroke, even past the three-month window when most of the motor recovery happens. FA of the CST, but not inter-hemispheric FC, can improve to the prediction of motor outcome based on early motor scores.</p></div

The Berlin Brain–Computer Interface: Non-Medical Uses of BCI Technology

Brain–computer interfacing (BCI) is a steadily growing area of research. While initially BCI research was focused on applications for paralyzed patients, increasingly more alternative applications in healthy human subjects are proposed and investigated. In particular, monitoring of mental states and decoding of covert user states have seen a strong rise of interest. Here, we present some examples of such novel applications which provide evidence for the promising potential of BCI technology for non-medical uses. Furthermore, we discuss distinct methodological improvements required to bring non-medical applications of BCI technology to a diversity of layperson target groups, e.g., ease of use, minimal training, general usability, short control latencies

Normalization of network connectivity in hemispatial neglect recovery

We recently reported that spatial and nonspatial attention deficits in stroke patients with hemispatial neglect are correlated at 2 weeks postonset with widespread alterations of interhemispheric and intrahemispheric functional connectivity (FC) measured with resting-state functional magnetic resonance imaging across multiple brain networks. The mechanisms underlying neglect recovery are largely unknown. In this study, we test the hypothesis that recovery of hemispatial neglect correlates with a return of network connectivity toward a normal pattern, herein defined as "network normalization.