Biology subjects

Khatib, D.

Publications and source records attributed to Khatib, D..

4 recordsLinked to original sources

bioRxiv2026

Trauma-Exposed Adolescents Show Reduced Cortical Glutamate Modulation during Inhibitory Control with Negative Emotional Stimuli

BackgroundChildhood trauma exposure (TE) may heighten negative emotional responses, overwhelm cognitive control, and increase risk for anxiety disorders. Cognitive control is facilitated by glutamatergic (Glu) excitatory neurotransmission within the dorsal anterior cingulate cortex (dACC). Dynamic changes in dACC Glu levels were investigated using {superscript 1}H functional magnetic resonance spectroscopy (1H fMRS) to assess the impact of negative emotional processing on neural mechanisms supporting cognitive control in TE-youth. MethodsFifty adolescents were categorized into two TE-Groups: Higher (Mtrauma=6{+/-}1events) and Lower (Mtrauma=3{+/-}1events). 1H fMRS from the dACC was acquired during an inhibitory motor control task requiring tapping responses to stimuli under two Response Modes, "NonSelective" (100% response) and "Selective" (80% response, 20% inhibition), executed with two Stimuli Conditions, "Squares" (no emotion) and "Faces" (emotion). Glu modulation (relative to basal levels) was tested across TE-Group, Stimuli Condition, and their interaction. Within each Stimuli Condition, Glu modulation was tested across Response Modes by TE-Group. ResultsWe observed a 2-way interaction of TE-Group x Stimuli Condition ({chi}2=4.66, p=0.031). Post-hoc tests revealed significantly lower Glu modulation in Higher TE vs Lower TE (p=.023) during Faces but not Squares. This Glu modulation did not differ across Response Modes. Within the Higher TE-Group, Glu was significantly reduced during Faces compared to Squares (p<.001). Basal dACC Glu levels did not differ between groups. ConclusionsTE-Group differences in adolescent dACC Glu modulation were observed during cognitive control performed with emotional, but not non-emotional, stimuli, highlighting the value of 1H fMRS for detecting trauma-related differences in task-related excitatory neurochemical dynamics.

neuroscience↗

bioRxiv2025

Learning evoked centrality dynamics in the schizophrenia brain: Entropy, heterogeneity and inflexibility of brain networks

BackgroundBrain network dynamics are responsive to task induced fluctuations, but such responsivity may not hold in schizophrenia (SCZ). We introduce and implement Centrality Dynamics (CD), a method developed specifically to capture task-driven dynamic changes in graph theoretic measures of centrality. We applied CD to fMRI data in SCZ and Healthy Controls (HC) acquired during a learning paradigm. MethodsfMRI (3T Siemens Verio) was acquired in 88 participants (49 SCZ). Time series were extracted from 246 functionally defined cerebral nodes. We applied a dynamic widowing technique to estimate 280 partially overlapping connectomes (30,135 region-pairs in each connectome). In each connectome we calculated every nodes Betweenness Centrality (BC) before building 246 unique time series (representing a nodes CD) from a nodes BC in successive connectomes. Next, in each group nodes were clustered based on similarities in CD. ResultsClustering gave rise to fewer sub-networks in SCZ, and these were formed by nodes with greater functional heterogeneity. These sub-networks also showed greater ApEn (indicating greater stochasticity) but lower amplitude variability (suggesting less adaptability to task-induced dynamics). Higher ApEn was associated with worse clinical symptoms. LimitationsCentrality Dynamics is a new method for network discovery in health and schizophrenia but will need further extension to other tasks and psychiatric conditions, before we achieve a fuller understanding of its promise. ConclusionThe brains functional connectome is not static under task-driven conditions, and characterizing the dynamics of the connectome will provide new insight on the dysconnection syndrome that is schizophrenia. Centrality Dynamics provides novel characterization of task-induced changes in the brains connectome and shows that in the schizophrenia brain, learning-evoked sub-network dynamics were less responsive to learning evoked changes and showed greater stochasticity.

neuroscience↗

bioRxiv2025

α-Synuclein Activates the PI3K/AKT Pathway to Drive Lipid Droplets Accumulation: Implications for Parkinson's Disease

Growing evidence supports a metabolic component in Parkinsons disease (PD). - Synuclein (-Syn), a protein central to the onset and progression of PD, facilitates the accumulation of neuronal lipid droplets, which are implicated in disease pathology. We report that AKT is hyper-phosphorylated in PD brains and show that -Syn enhances p110 activity by facilitating palmitoylated Ras localization to the plasma membrane, driving lipid droplet accumulation through PI3K/AKT/mTOR and PPAR{gamma} activation. Phosphorylation of -Syn at Ser129 correlates positively with the localization of Ras to the membrane fraction and with accumulation of lipid droplets. In-vivo treatment of young, asymptomatic -SynA53T transgenic mice with GDC-0084 (paxalisib), a blood- brain barrier-permeable PI3K inhibitor, restored healthy AKT activity levels, reduced levels of PSer129 and -Syn oligomers, decreased neuronal lipid droplet accumulation, and promoted lysosomal clustering. These findings establish a role for -Syn in p110 activation during early, asymptomatic stages of the disease and highlight the therapeutic potential of PI3K inhibition as a disease-modifying strategy. Highlight-Syn activates PI3K/AKT by promoting the localization of palmitoylated Ras to membranes, linking metabolic dysfunction to PD.

neuroscience↗

bioRxiv2022

Experience, not time, determines representational drift in the hippocampus

Memories of past events can be recalled long after the event, indicating stability. But new experiences are also integrated into existing memories, indicating plasticity. In the hippocampus, spatial representations are known to remain stable, but have also been shown to drift over long periods of time. We hypothesized that experience, more than the passage of time, is the driving force behind memory plasticity. We compared the stability of place cells in the hippocampus of mice traversing two similar, familiar tracks for different durations. We found that the more time spent in an environment, the greater the representational drift, regardless of the total elapsed time. Our results suggest that spatial representation is a dynamic process, related to the ongoing experiences within a specific context, and is related to the accumulation of new memories rather than to passive forgetting. HighlightsO_LIRepresentational drift is related to experience within an environment. C_LIO_LIRepresentational drift is a dynamic context-wide process. C_LIO_LIPlace cell number decreases with experience, spatial information content increases. C_LI

neuroscience↗