Effects of subclinical depression on prefrontal-striatal model-based and model-free learning.

Depression is characterized by deficits in the reinforcement learning (RL) process. Although many computational and neural studies have extended our knowledge of the impact of depression on RL, most focus on habitual control (model-free RL), yielding a relatively poor understanding of goal-directed control (model-based RL) and arbitration control to find a balance between the two. We investigated the effects of subclinical depression on model-based and model-free learning in the prefrontal-striatal circuitry. First, we found that subclinical depression is associated with the attenuated state and reward prediction error representation in the insula and caudate. Critically, we found that it accompanies the disrupted arbitration control between model-based and model-free learning in the predominantly inferior lateral prefrontal cortex and frontopolar cortex. We also found that depression undermines the ability to exploit viable options, called exploitation sensitivity. These findings characterize how subclinical depression influences different levels of the decision-making hierarchy, advancing previous conflicting views that depression simply influences either habitual or goal-directed control. Our study creates possibilities for various clinical applications, such as early diagnosis and behavioral therapy design.

Pre-obesity and obesity impacts on passive joint range of motion.

Despite the prevalence of pre-obesity and obesity, the physical capabilities of pre-obese/obese individuals are not well documented. As an effort to address this, this study investigated the pre-obesity and obesity impacts on joint range of motion (RoM) for twenty-two body joint motions. A publicly available passive RoM dataset was analysed. Three BMI groups (normal-weight, pre-obese, and obese [Class I]) were statistically compared in joint RoM. The pre-obese and obese groups were found to have significantly smaller RoM means than the normal-weight for elbow flexion and supination, hip extension and flexion, knee flexion and ankle plantar flexion. The pre-obese and obese groups exhibited no significant inter-group mean RoM differences except for knee flexion; for knee flexion, the obese group had significantly smaller RoM means than the pre-obese. The findings would be useful for designing work tasks and products/systems for high BMI individuals and developing digital human models representing differently sized individuals. Practitioner summary: This study investigated the pre-obesity and obesity impacts on joint range of motion (RoM) by comparing three participant groups: normal-weight; pre-obese and obese. The pre-obese and obese groups had significantly smaller RoM means than the normal-weight for elbow flexion and supination; hip extension and flexion; knee flexion and ankle plantar flexion. ABBREVIATIONS: ANCOVA: Analysis of Covariance; BMI: Body Mass Index; CI: Confidence Interval; RoM: Range of Motion; SPSS: Statistical Package for the Social Sciences.

Alterations of Structural Network Efficiency in Early-Onset and Late-Onset Alzheimer's Disease.

BACKGROUND AND PURPOSE: Early- and late-onset Alzheimer's disease (EOAD and LOAD, respectively) share the same neuropathological hallmarks of amyloid and neurofibrillary tangles but have distinct cognitive features. We compared structural brain connectivity between the EOAD and LOAD groups using structural network efficiency and evaluated the association of structural network efficiency with the cognitive profile and pathological markers of Alzheimer's disease (AD). METHODS: The structural brain connectivity networks of 80 AD patients (47 with EOAD and 33 with LOAD) and 57 healthy controls were reconstructed using diffusion-tensor imaging. Graph-theoretic indices were calculated and intergroup differences were evaluated. Correlations between network parameters and neuropsychological test results were analyzed. The correlations of the amyloid and tau burdens with network parameters were evaluated for the patients and controls. RESULTS: Compared with the age-matched control group, the EOAD patients had increased global path length and decreased global efficiency, averaged local efficiency, and averaged clustering coefficient. In contrast, no significant differences were found in the LOAD patients. Locally, the EOAD patients showed decreases in local efficiency and the clustering coefficient over a wide area compared with the control group, whereas LOAD patients showed such decreases only within a limited area. Changes in network parameters were significantly correlated with multiple cognitive domains in EOAD patients, but only with Clinical Dementia Rating Sum-of-Boxes scores in LOAD patients. Finally, the tau burden was correlated with changes in network parameters in AD signature areas in both patient groups, while there was no correlation with the amyloid burden. CONCLUSIONS: The impairment of structural network efficiency and its effects on cognition may differ between EOAD and LOAD.

Mental status changes during elexacaftor/tezacaftor / ivacaftor therapy.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA, Trikafta) is the newest Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator drug approved by the Food and Drug Administration. Post-marketing reports with earlier CFTR modulators suggest these medications can impact mood, and in clinical trials an adverse effect of headache was reported with all currently approved CFTR modulators. However, there are no other documented reports of mental status changes during clinical trials or in post-marketing reports with elexacaftor/tezacaftor/ivacaftor. In this case series, we describe 6 patients who reported "mental fogginess" or other mental status changes shortly after initiation of this drug. The mechanism of this patient-reported side effect is still unclear. All patients noticed a change within the first 3 months of therapy. The management differed in each case, with all four cystic fibrosis (CF) care teams utilizing a patient-centered decision-making approach to address this concern.