Dietary modifications leading to weight loss have been suggested as a means to improve brain health. In morbid obesity, bariatric surgery (BARS)—including different procedures, such as vertical sleeve gastrectomy (VSG), gastric banding (GB), or Roux-en-Y gastric bypass (RYGB) surgery—is performed to induce rapid weight loss. Combining reduced food intake and malabsorption of nutrients, RYGB might be most effective, but requires life-long follow-up treatment. Here, we tested 40 patients before and six months after surgery (BARS group) using a neuropsychological test battery and compared them with a waiting list control group. Subsamples of both groups underwent structural MRI and were examined for differences between surgical procedures. No substantial differences between BARS and control group emerged with regard to cognition. However, larger gray matter volume in fronto-temporal brain areas accompanied by smaller volume in the ventral striatum was seen in the BARS group compared to controls. RYGB patients compared to patients with restrictive treatment alone (VSG/GB) had higher weight loss, but did not benefit more in cognitive outcomes. In sum, the data of our study suggest that BARS might lead to brain structure reorganization at long-term follow-up, while the type of surgical procedure does not differentially modulate cognitive performance.

Background: Aphasia is a recognized presenting symptom of thalamic lesions. Little is known regarding its frequency and phenotype. We examined the frequency of thalamic aphasia following Isolated Acute unilateral ischemic Lesions in the Thalamus (IALT) with respect to lesion location. Furthermore, we characterized thalamic aphasia according to affected language domains and severity. Methods: Fifty-two patients with IALT were analyzed [44% female, median age: 73 years (IQR: 60–79)]. Lesion location was determined using 3-Tesla magnetic resonance imaging and categorized as anterior, posterior, paramedian or inferolateral. Standardized language assessment was performed using the validated Aphasia checklist (ACL) directly after symptom onset. Aphasia was defined as an ACL sum score of < 135 (range: 0–148). Results: Of 52 patients, 23 (44%) fulfilled the ACL diagnostic criteria for aphasia, including nearly all lesion locations and both sides. The average ACL sum score was 132 ± 11 (range: 98–147). Aphasia was characterized by deficits within domains of complex understanding of speech and verbal fluency. Patients with left anterior IALT were most severely affected, having significantly lower ACL scores than all other patients (117 ± 13 vs. 135 ± 8; p < 0.001). In particular, aphasia in patients with left anterior IALT was characterized by significantly worse performance in the rating of verbal communication, verbal fluency, and naming (all p ≤ 0.001). Conclusion: Aphasia occurs in almost half of patients with focal thalamic lesions. Thalamic aphasia is not confined to one predefined thalamic lesion location, but language deficits are particularly pronounced in patients with left anterior IALT presenting with a distinct pattern.

Thalamic aphasia results from focal thalamic lesions that cause dysfunction of remote but functionally connected cortical areas due to language network perturbation. However, specific local and network-level neural substrates of thalamic aphasia remain incompletely understood. Using lesion symptom mapping, we demonstrate that lesions in the left ventrolateral and ventral anterior thalamic nucleus are most strongly associated with aphasia in general and with impaired semantic and phonemic fluency and complex comprehension in particular. Lesion network mapping (using a normative connectome based on fMRI data from 1000 healthy individuals) reveals a Thalamic aphasia network encompassing widespread left-hemispheric cerebral connections, with Broca’s area showing the strongest associations, followed by the superior and middle frontal gyri, precentral and paracingulate gyri, and globus pallidus. Our results imply the critical involvement of the left ventrolateral and left ventral anterior thalamic nuclei in engaging left frontal cortical areas, especially Broca’s area, during language processing.

Background: Variants of the Circle of Willis (vCoW) may impede correct identification of ischemic lesion patterns and stroke etiology. We assessed reclassifications of ischemic lesion patterns due to vCoW. Methods: We analyzed vCoW in patients with acute ischemic stroke from the 1000+ study using time-of-flight magnetic resonance angiography (TOF MRA) of intracranial arteries. We assessed A1 segment agenesis or hypoplasia in the anterior circulation and fetal posterior cerebral artery in the posterior circulation. Stroke patterns were classified as one or more-than-one territory stroke pattern. We examined associations between vCoW and stroke patterns and the frequency of reclassifications of stroke patterns due to vCoW. Results: Of 1000 patients, 991 had evaluable magnetic resonance angiography. At least one vCoW was present in 37.1%. VCoW were more common in the posterior than in the anterior circulation (33.3% vs. 6.7%). Of 238 patients initially thought to have a more-than-one territory stroke pattern, 20 (8.4%) had to be reclassified to a one territory stroke pattern after considering vCoW. All these patients had fetal posterior cerebral artery and six (30%) additionally had carotid artery disease. Of 753 patients initially presumed to have a one-territory stroke pattern, four (0.5%) were reclassified as having more-than-one territory pattern. Conclusions: VCoW are present in about one in three stroke patients and more common in the posterior circulation. Reclassifications of stroke lesion patterns due to vCoW occurred predominantly in the posterior circulation with fetal posterior cerebral artery mimicking multiple territory stroke pattern. Considering vCoW in these cases may uncover symptomatic carotid disease.

The contribution of age‐related structural brain changes to the well‐established link between aging and cognitive decline is not fully defined. While both age‐related regional brain atrophy and cognitive decline have been extensively studied, the specific mediating role of age‐related regional brain atrophy on cognitive functions is unclear. This study introduces an open‐source software tool with a graphical user interface that streamlines advanced whole‐brain mediation analyses, enabling researchers to systematically explore how the brain acts as a mediator in relationships between various behavioral and health outcomes. The tool is showcased by investigating regional brain volume as a mediator to determine the contribution of age‐related brain volume loss toward cognition in healthy aging. We analyzed regional brain volumes and cognitive testing data (Montreal Cognitive Assessment [MoCA]) from a cohort of 131 neurologically healthy adult participants (mean age 50 ± 20.8 years, range 20–79, 73% females) drawn from the Aging Brain Cohort Study at the University of South Carolina. Using our open‐source tool developed for evaluating brain‐behavior associations across the brain and optimized for exploring mediation effects, we conducted a series of mediation analyses using participant age as the predictor variable, total MoCA and MoCA subtest scores as the outcome variables, and regional brain volume as potential mediators. Age‐related atrophy within specific anatomical networks was found to mediate the relationship between age and cognition across multiple cognitive domains. Specifically, atrophy in bilateral frontal, parietal, and occipital areas, along with widespread subcortical regions mediated the effect of age on total MoCA scores. Various MoCA subscores were influenced by age through atrophy in distinct brain regions. These involved prefrontal regions, sensorimotor cortex, and parieto‐occipital areas for executive function subscores, prefrontal and temporo‐occipital regions, along with the caudate nucleus for attention and concentration subscores, frontal and parieto‐occipital areas, alongside connecting subcortical areas such as the optic tract for visuospatial subscores and frontoparietal areas for language subscores. Brain‐based mediation analysis offers a causal framework for evaluating the mediating role of brain structure on the relationship between age and cognition and provides a more nuanced understanding of cognitive aging than previously possible. By validating the applicability and effectiveness of this approach and making it openly available to the scientific community, we facilitate the exploration of causal mechanisms between variables mediated by the brain.

Aphasia severity after stroke varies widely and is not fully explained by lesion size or location. We propose that incorporating the brain’s sensorimotor-association (S-A) gradient, reflecting cortical hierarchy, offers a biologically grounded framework for predicting language outcomes. In 236 individuals with chronic left-hemisphere stroke, we examine whether the hierarchical position of lesions in language-specific (LS) and domain-general (DG) areas modulates aphasia severity. We parcellate lesions using a cortical atlas and weigh them by each region’s S-A rank. We apply hierarchical linear regression to test whether S-A ranking and its interaction with lesion volume improves prediction of Western Aphasia Battery-Revised Aphasia Quotient (WAB-R-AQ) scores. Across models, lesion volume in lower S-A regions is more detrimental than in higher-order areas. The LS-only model yields the highest explanatory power (adjusted R² = 0.426). These findings reveal that cortical hierarchy shapes post-stroke language outcomes and should be considered in future models of aphasia recovery.