Biology subjects

Haroon, H.

Publications and source records attributed to Haroon, H..

3 recordsLinked to original sources

bioRxiv2026

Distinct nigral and brainstem pathology markers map onto separable subthalamic electrophysiological signatures in Parkinson's disease

Subthalamic local field potentials (LFPs) are increasingly used as physiomarkers of the symptomatic state in Parkinsons disease, but their relationship to the underlying neurodegenerative pathology remains unclear. Here, we combined OFF-medication subthalamic LFP recordings with quantitative MRI markers of nigral and brainstem pathology in 33 people with Parkinsons disease. Distinct pathological markers mapped onto dissociable electrophysiological components. Substantia nigra pars compacta susceptibility was associated with increased occupancy, duration and rate of low-{beta} bursts, whereas nigral free water was associated with greater low-frequency aperiodic offset and a steeper slope. Pedunculopontine nucleus free-water- corrected axial diffusivity was selectively associated with high-frequency aperiodic activity, and this relationship strengthened with increasing nigral susceptibility, consistent with dopaminergic-state- dependent influences of extranigral pathology on subthalamic physiology. Only low-frequency aperiodic offset was also associated with contralateral bradykinesia. These findings indicate that the subthalamic LFP is not a unitary readout of dopamine loss or motor state, but an integrated physiological signal in which pathology across interconnected systems is expressed through separable oscillatory and aperiodic components. Chronically implanted devices may therefore provide physiological readouts of underlying disease biology alongside control signals for adaptive therapy.

neuroscience↗

bioRxiv2025

Caspase-dependent ablation of indirect medium spiny neurons projecting to external globus pallidus promotes compulsive ethanol-seeking and drinking behaviors

The dorsomedial striatum (DMS) is primarily recognized for regulating goal-directed reward-seeking behaviors, while the dorsolateral striatum (DLS) is predominantly associated with movement and habitual behaviors. In this study, we sought to investigate two pathways, direct medium spiny neuron (dMSN) and indirect medium spiny neuron (iMSN) in the two dorsal striatal subregions (DMS and DLS) in ethanol-seeking and drinking behaviors. Here, we selectively ablated iMSNDMS[->]GPe and iMSNDLS[->]GPe and trained mice to exhibit goal-directed and habitual reward-seeking behaviors using random ratio (RR) and random interval (RI) operant conditioning, respectively. We found that partial ablation of iMSNDLS[->]GPe exhibited increased resilience to bitter-tasting ethanol solution when subjected to quinine adulterated reward in operant conditioning paradigms, suggesting compulsive-like seeking behavior. Consistently, in a separate cohort of mice, we found that the iMSNDLS[->]GPe ablated mice show higher preference and consumption of quinine adulterated ethanol solution than control mice in two-bottle choice continuous access drinking, with increasing quinine concentration and exhibit more compulsive-like behavior. On the other hand, ablation of iMSNDMS[->]GPe resulted in insensitivity to satiety-based reward devaluation in RR-trained mice, consistent with a shift toward habitual behavior but no change in compulsive ethanol-seeking and drinking behavior. Together, our findings demonstrate that DLS iMSN function is essential in inhibiting compulsive-like behavior.

neuroscience↗

bioRxiv2020

The Effects of Social Stress on Memory: If, How and When

Physical stress, such as from the cold-pressor test, has been robustly associated with altered memory retrieval, but it is not yet clear whether the same happens following psychosocial stress. Studies using psychosocial stressors report mixed effects on memory, leading to uncertainty about the common cognitive impact of both forms of stress. The current study uses a stepped replication design, with four near-identical experiments, each differing by a single critical factor. In three experiments we induced psychosocial stress after participants encoded word stimuli, then assessed retrieval after a prolonged delay. These experiments found no group level influence of postencoding stress on recognition of neutral words or cued recall of word-pairs, but a small effect on recollection of semantically-related words. There was, however, some indication of positive relationships within the stress group between measures of stress (cortisol in experiment 1 and self-reported-anxiety in experiment 3) and recollection of single word stimuli. In the fourth experiment, we found that psychosocial stress immediately before retrieval did not influence word recognition. Overall, our findings demonstrate that psychosocial stress has a typically modest impact on memory, lower than previously claimed, but that individual differences in stress responsivity, particularly for tasks that tap recollection, may help to explain variability in previous findings.

neuroscience↗