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There is evidence from neuroimaging that the prefrontal cortex may be involved in establishing task set activity in advance of presentation of the task itself. To find out whether it plays an essential role, we examined patients with unilateral lesions of the rostral prefrontal cortex. They were first instructed as to whether to perform a spatial or a verbal working memory task and then given spatial and verbal items after a delay of 4 - 12 s. The patients showed an increase in switch costs, making more errors by repeating what they had done on the previous trial. They were able to establish regional task set activity during the instruction delay, as evidenced by sustained changes in the blood oxygenation level-dependent signal in caudal frontal regions. However, in contrast to healthy controls, they were less able to maintain functional connectivity among the surviving task-related brain regions, as evidenced by reduced correlations between them during instruction delays. The results suggest that the left rostral prefrontal cortex is indeed required for establishing a cognitive set but that the essential function is to support the functional connectivity among the task-related regions. [ABSTRACT FROM AUTHOR]

Diffusion-Weighted Imaging (DWI) and tractography allow noninvasive mapping of the structural connections of the brain, and may provide important information for optimizing Deep Brain Stimulation (DBS) treatment. The hyperdirect pathway (HDP), connecting the subthalamic nucleus (STN) with motor cortex, is assumed to play a key role in mediating the beneficial effects of DBS. Less is known about the HDP, connecting the STN to prefrontal regions, and whether this might play a role in adverse effects of DBS on cognitive function. This study aims to apply recent methodological advances in DWI acquisition and analysis to generate a connectivity-based map of the STN. This can be combined with postoperative electrode position localization with the aim of guiding postoperative stimulation management. By combining high spatial and angular resolution DWI data with state-of-the-art tractography frameworks (Constrained Spherical Deconvolution based probabilistic tractography) we delineated connections to the STN from motor cortex (MC) and prefrontal (PF) regions. Analyzing these connections, we identified regions of the STN that were dominated by MC or PF connectivity. Post-operative electrode positions were identified and correlated to manual STN segmentations and cortico-subthalamic motor connectivity using in-house Matlab tools. Our method can delineate a motor connectivity gradient going from high in the dorsolateral aspect of the STN to low towards the antero-medial aspect. We also examined the motor connectivity gradient at each electrode contact point in seven patients with Parkinson's Disease at 3 month follow up. We found no clear relationship between the 'active' (therapeutic) electrode contact and degree of STN-motor connectivity. However, when analyzing the electrode position with the manually delineated STN outline, we find that in 12/14 DBS leads the active contact is the one with the largest or second to largest STN volume coverage. Further analysis will be carried out to model the volume and connectivity of STN tissue stimulated with patient-specific stimulation parameters. These preliminary results are promising and in line with the previously established anatomy of the STN. This framework could potentially help both neurosurgeons during pre-operative STN targeting and clinicians in optimizing the post-operative testing and management of stimulation settings. [ABSTRACT FROM AUTHOR]

APOE-ɛ4 is a genetic risk factor for Alzheimer's disease (AD). AD is associated with reduced cerebral blood flow (CBF) and with microvascular changes that limit the transport of oxygen from blood into brain tissue: reduced microvascular cerebral blood volume and high relative transit time heterogeneity (RTH). Healthy APOE-ɛ4 carriers reveal brain regions with elevated CBF compared with carriers of the common ɛ3 allele. Such asymptomatic hyperemia may reflect microvascular dysfunction : a vascular disease entity characterized by suboptimal tissue oxygen uptake, rather than limited blood flow per se. Here, we used perfusion MRI to show that elevated regional CBF is accompanied by reduced capillary blood volume in healthy APOE-ɛ4 carriers (carriers) aged 30-70 years compared with similarly aged APOE-ɛ3 carriers (noncarriers). Younger carriers have elevated hippocampal RTH and more extreme RTH values throughout both white matter (WM) and cortical gray matter (GM) compared with noncarriers. Older carriers have reduced WM CBF and more extreme GM RTH values than noncarriers. Across all groups, lower WM and hippocampal RTH correlate with higher educational attainment, which is associated with lower AD risk. Three days of dietary nitrate supplementation increased carriers' WM CBF but caused older carriers to score worse on two of six aggregate neuropsychological scores. The intervention improved late recall in younger carriers and in noncarriers. The APOE-ɛ4 gene is associated with microvascular changes that may impair tissue oxygen extraction. We speculate that vascular risk factor control is particularly important for APOE-ɛ4 carriers' healthy aging., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)