Dopaminergic mesolimbic structural reserve is positively linked to better outcome after severe stroke.

The concept of brain reserve capacity has emerged in stroke recovery research in recent years. Imaging-based biomarkers of brain health have helped to better understand outcome variability in clinical cohorts. Still, outcome inferences are far from being satisfactory, particularly in patients with severe initial deficits. Neurorehabilitation after stroke is a complex process, comprising adaption and learning processes, which, on their part, are critically influenced by motivational and reward-related cognitive processes. Amongst others, dopaminergic neurotransmission is a key contributor to these mechanisms. The question arises, whether the amount of structural reserve capacity in the dopaminergic system might inform about outcome variability after severe stroke. For this purpose, this study analysed imaging and clinical data of 42 severely impaired acute stroke patients. Brain volumetry was performed within the first 2 weeks after the event using the Computational Anatomy Toolbox CAT12, grey matter volume estimates were collected for seven key areas of the human dopaminergic system along the mesocortical, mesolimbic and nigrostriatal pathways. Ordinal logistic regression models related regional volumes to the functional outcome, operationalized by the modified Rankin Scale, obtained 3-6 months after stroke. Models were adjusted for age, lesion volume and initial impairment. The main finding was that larger volumes of the amygdala and the nucleus accumbens at baseline were positively associated with a more favourable outcome. These data suggest a link between the structural state of mesolimbic key areas contributing to motor learning, motivational and reward-related brain networks and potentially the success of neurorehabilitation. They might also provide novel evidence to reconsider dopaminergic interventions particularly in severely impaired stroke patients to enhance recovery after stroke.

Altered microstructure of the contralesional ventral premotor cortex and motor output after stroke.

Cortical thickness analyses have provided valuable insights into changes in cortical brain structure after stroke and their association with recovery. Across studies though, relationships between cortical structure and function show inconsistent results. Recent developments in diffusion-weighted imaging of the cortex have paved the way to uncover hidden aspects of stroke-related alterations in cortical microstructure, going beyond cortical thickness as a surrogate for cortical macrostructure. We re-analysed clinical and imaging data of 42 well-recovered chronic stroke patients from 2 independent cohorts (mean age 64 years, 4 left-handed, 71% male, 16 right-sided strokes) and 33 healthy controls of similar age and gender. Cortical fractional anisotropy and cortical thickness values were obtained for six key sensorimotor areas of the contralesional hemisphere. The regions included the primary motor cortex, dorsal and ventral premotor cortex, supplementary and pre-supplementary motor areas, and primary somatosensory cortex. Linear models were estimated for group comparisons between patients and controls and for correlations between cortical fractional anisotropy and cortical thickness and clinical scores. Compared with controls, stroke patients exhibited a reduction in fractional anisotropy in the contralesional ventral premotor cortex (P = 0.005). Fractional anisotropy of the other regions and cortical thickness did not show a comparable group difference. Higher fractional anisotropy of the ventral premotor cortex, but not cortical thickness, was positively associated with residual grip force in the stroke patients. These data provide novel evidence that the contralesional ventral premotor cortex might constitute a key sensorimotor area particularly susceptible to stroke-related alterations in cortical microstructure as measured by diffusion MRI and they suggest a link between these changes and residual motor output after stroke.

Quantifying and Examining Reserve in Symptomatic Former National Football League Players.

BACKGROUND: Repetitive head impacts (RHI) from contact sports have been associated with cognitive and neuropsychiatric disorders. However, not all individuals exposed to RHI develop such disorders. This may be explained by the reserve hypothesis. It remains unclear if the reserve hypothesis accounts for the heterogenous symptom presentation in RHI-exposed individuals. Moreover, optimal measurement of reserve in this population is unclear and likely unique from non-athlete populations. OBJECTIVE: We examined the association between metrics of reserve and cognitive and neuropsychiatric functioning in 89 symptomatic former National Football League players. METHODS: Individual-level proxies (e.g., education) defined reserve. We additionally quantified reserve as remaining residual variance in 1) episodic memory and 2) executive functioning performance, after accounting for demographics and brain pathology. Associations between reserve metrics and cognitive and neuropsychiatric functioning were examined. RESULTS: Higher reading ability was associated with better attention/information processing (ß=0.25; 95% CI, 0.05-0.46), episodic memory (ß=0.27; 95% CI, 0.06-0.48), semantic and phonemic fluency (ß=0.24; 95% CI, 0.02-0.46; ß=0.38; 95% CI, 0.17-0.59), and behavioral regulation (ß=-0.26; 95% CI, -0.48, -0.03) performance. There were no effects for other individual-level proxies. Residual episodic memory variance was associated with better attention/information processing (ß=0.45; 95% CI, 0.25, 0.65), executive functioning (ß=0.36; 95% CI, 0.15, 0.57), and semantic fluency (ß=0.38; 95% CI, 0.17, 0.59) performance. Residual executive functioning variance was associated with better attention/information processing (ß=0.44; 95% CI, 0.24, 0.64) and episodic memory (ß=0.37; 95% CI, 0.16, 0.58) performance. CONCLUSION: Traditional reserve proxies (e.g., years of education, occupational attainment) have limitations and may be unsuitable for use in elite athlete samples. Alternative approaches of reserve quantification may prove more suitable for this population.

Age at First Exposure to Tackle Football is Associated with Cortical Thickness in Former Professional American Football Players.

Younger age at first exposure (AFE) to repetitive head impacts while playing American football increases the risk for later-life neuropsychological symptoms and brain alterations. However, it is not known whether AFE is associated with cortical thickness in American football players. Sixty-three former professional National Football League players (55.5 ± 7.7 years) with cognitive, behavioral, and mood symptoms underwent neuroimaging and neuropsychological testing. First, the association between cortical thickness and AFE was tested. Second, the relationship between clusters of decreased cortical thickness and verbal and visual memory, and composite measures of mood/behavior and attention/psychomotor speed was assessed. AFE was positively correlated with cortical thickness in the right superior frontal cortex (cluster-wise P value [CWP] = 0.0006), the left parietal cortex (CWP = 0.0003), and the occipital cortices (right: CWP = 0.0023; left: CWP = 0.0008). A positive correlation was found between cortical thickness of the right superior frontal cortex and verbal memory (R = 0.333, P = 0.019), and the right occipital cortex and visual memory (R = 0.360, P = 0.012). In conclusion, our results suggest an association between younger AFE and decreased cortical thickness, which in turn is associated with worse neuropsychological performance. Furthermore, an association between younger AFE and signs of neurodegeneration later in life in symptomatic former American football players seems likely.