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Senthilkumar, P.

Publications and source records attributed to Senthilkumar, P..

3 recordsLinked to original sources

Deep Learning to Predict Future Cognitive Decline: A Multimodal Approach Using Brain MRI and Clinical Data

Predicting the trajectory of clinical decline in aging individuals is a pressing challenge, especially for people with mild cognitive impairment, Alzheimers disease, Parkinsons disease, or vascular dementia. Accurate predictions can guide treatment decisions, identify risk factors, and optimize clinical trials. In this study, we compared two deep learning approaches for forecasting changes, over a 2-year interval, in the Clinical Dementia Rating scale sum of boxes score (sobCDR). This is a key metric in dementia research, and scores range from 0 (no impairment) to 18 (severe impairment). To predict decline, we trained a hybrid convolutional neural network that integrates 3D T1-weighted brain MRI scans with tabular clinical and demographic features (including age, sex, body mass index (BMI), and baseline sobCDR). We benchmarked its performance against AutoGluon, an automated multimodal machine learning framework that selects an appropriate neural network architecture. Our results demonstrate the importance of combining image and tabular data in predictive modeling for clinical applications. Deep learning algorithms can fuse image-based brain signatures and tabular clinical data, with potential for personalized prognostics in aging and dementia.

neuroscience↗

Endogenous opioid dynamics in the dorsal striatum sculpt neural activity to control goal-directed action

Endogenous neuropeptides are uniquely poised to regulate neuronal activity and behavior across multiple timescales. Traditional studies ascribing neuropeptide contributions to behavior lack spatiotemporal precision. The endogenous opioid dynorphin is highly enriched in the dorsal striatum, known to be critical for regulating goal-directed behavior. However, the locus, the precise timescale, or functional role of endogenous dyn-KOR signaling on goal-directed behavior is unknown. Here, we report that local, time-locked dynorphin release from the dorsomedial striatum is necessary and sufficient for goal-directed behavior using a suite of high resolution modern approaches including in vivo two-photon imaging, neuropeptide biosensor detection, conditional deletions and time-locked optogenetic manipulations. We discovered that glutamatergic axon terminals from the basolateral amygdala evoke striatal dynorphin release, resulting in retrograde presynaptic GPCR inhibition during behavior. Collectively, our findings isolate a causal role for endogenous neuropeptide release at rapid timescales, and subsequent GPCR activity for tuning and promoting fundamental goal-directed behaviors.

neuroscience↗

Opioid-driven disruption of the septal complex reveals a role for neurotensin- expressing neurons in withdrawal

Because opioid withdrawal is an intensely aversive experience, persons with opioid use disorder (OUD) often relapse to avoid it. The lateral septum (LS) is a forebrain structure that is important in aversion processing, and previous studies have linked the lateral septum (LS) to substance use disorders. It is unclear, however, which precise LS cell types might contribute to the maladaptive state of withdrawal. To address this, we used single-nucleus RNA-sequencing to interrogate cell type specific gene expression changes induced by chronic morphine and withdrawal. We discovered that morphine globally disrupted the transcriptional profile of LS cell types, but Neurotensin-expressing neurons (Nts; LS-Nts neurons) were selectively activated by naloxone. Using two-photon calcium imaging and ex vivo electrophysiology, we next demonstrate that LS-Nts neurons receive enhanced glutamatergic drive in morphine-dependent mice and remain hyperactivated during opioid withdrawal. Finally, we showed that activating and silencing LS-Nts neurons during opioid withdrawal regulates pain coping behaviors and sociability. Together, these results suggest that LS-Nts neurons are a key neural substrate involved in opioid withdrawal and establish the LS as a crucial regulator of adaptive behaviors, specifically pertaining to OUD.

neuroscience↗