Biology subjects

Khalife, S.

Publications and source records attributed to Khalife, S..

3 recordsLinked to original sources

bioRxiv2026

An updated roadmap for brain-mental health associations in the UK Biobank

The UK Biobank offers an unprecedented opportunity to examine associations between brain imaging and mental health at scale, but their magnitude and replicability remain unclear. We correlated 17,580 imaging-derived phenotypes across seven MRI modalities with 309 mental health phenotypes in 8,415 participants, split into discovery and validation subsets. Associations were generally small (median |r| = 0.018; top 1% of 0.108), and they replicated poorly: only 9.0% of significant discovery associations were significant in validation. Eating disorders showed the largest effects of any mental disorders but replicated in only 6.0% of cases, whereas substance use showed the highest replication (14.5%). Susceptibility-weighted imaging produced the most replicable imaging associations. Longitudinal changes in brain and mental health measures were weakly related. We provide an interactive dashboard that returns the effect-size and replicability benchmarks for any combination of mental health category and imaging modality, supporting variable selection and study design in UK Biobank research.

neuroscience↗

bioRxiv2025

MRI-Derived Markers of Acute and Chronic Inflammatory Processes in the VTA Associated with Depression

BackgroundDepression is a leading cause of disability worldwide, with inflammation increasingly recognized as a contributing factor. Inflammatory processes can disrupt the brains reward circuitry, particularly the ventral tegmental area (VTA), which is central to dopamine-mediated motivation and reward. This study investigates whether MRI-derived markers sensitive to neuroinflammation and microstructure in the VTA are associated with depression diagnosis and symptom severity. MethodsWe analyzed diffusion weighted imaging and quantitative susceptibility mapping data from 32,495 UK Biobank participants, including 3,807 individuals with ICD-10 diagnosed depression. Metrics sensitive to neuroinflammation (free water [FW], isotropic volume fraction [ISOVF], magnetic susceptibility) and microstructure (intracellular volume fraction [ICVF], orientation dispersion index [ODI] volume) were extracted from the VTA. Group differences between the major depression group and BMI, sex, and age-matched healthy controls were assessed using ANOVAs and linear regression was used to predict acute symptom severity based on Recent Depressive Symptoms scores. ResultsParticipants with depression diagnosis had significantly higher FW (p < 0.001) and ISOVF (p = 0.001) compared to HCs, indicating increased extracellular processes such as inflammation in the VTA. Lower ISOVF ({beta} = -0.46, p = 0.017) and higher ICVF ({beta} = 0.34, p = 0.007) and ODI ({beta} = 0.49, p = 0.004) were associated with higher depression severity, independent of depressive diagnosis history. ConclusionsOur findings reveal distinct patterns of VTA microstructural changes associated with depression history versus acute depressive symptom severity, suggesting different underlying pathophysiological mechanisms. Distinct patterns of neuroinflammation may differentiate acute from chronic depression, informing targeted interventions.

neuroscience↗

bioRxiv2022

Fast event-related mapping of fingertip population receptive fields in human somatosensory and motor cortex

fMRI studies that investigate somatotopic tactile representations in the human cortex typically use either block or phase-encoded stimulation designs. Event-related (ER) designs allow for more flexible and unpredictable stimulation sequences than the other methods, but they are less efficient. Here we compared an efficiency-optimized fast ER design (2.8s average intertrial interval, ITI) to a conventional slow ER design (8s average ITI) for mapping voxelwise fingertip tactile tuning properties in the sensorimotor cortex of 6 participants at 7 Tesla. The fast ER design yielded more reliable responses compared to the slow ER design, but with otherwise similar tuning properties. Concatenating the fast and slow ER data, we demonstrate in each individual brain the existence of two separate somatotopically-organized tactile representations of the fingertips, one in the primary somatosensory cortex (S1) on the post-central gyrus, and the other shared across the motor and pre-motor cortices on the pre-central gyrus. In both S1 and motor representations, fingertip selectivity decreased progressively, from narrowly-tuned Brodmann areas 3b and 4a respectively, towards associative parietal and frontal regions that responded equally to all fingertips, suggesting increasing information integration along these two pathways. In addition, fingertip selectivity in S1 decreased from the cortical representation of the thumb to that of the pinky. Significance StatementSensory and motor cortices in the human brain contain map-like representations of the body in which adjacent brain regions respond to adjacent body parts. The properties of these somatotopic maps provide important insight into how tactile and motor information is processed by the brain. Here, we describe an efficient mapping method using functional MRI to measure somatotopic maps and their tuning properties. We used a fast event-related sequence to map the five fingers of the left hand in six human participants, and show that this method is more efficient than a conventional, slower event-related design. Furthermore, we confirm previously-identified tuning properties of fingertip representations in somatosensory cortex, and reveal a hitherto unknown tactile fingertip map in the motor cortex.

neuroscience↗