Biology subjects

Alagapan, S.

Publications and source records attributed to Alagapan, S..

5 recordsLinked to original sources

bioRxiv2025

Longitudinal Changes in Cortical Response Dynamics with Deep Brain Stimulation to the Subcallosal Cingulate for Treatment-Resistant Depression

Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is a promising intervention for treatment-resistant depression, yet objective biomarkers that track recovery remain limited. This study examined longitudinal changes in stimulation-evoked potentials (SEPs) to characterize how SCC-driven cortical communication evolves during treatment. Ten patients across three SCC-DBS trials underwent high-density EEG recordings at 4 and 24 weeks. SEP features were extracted from source-localized SCC signals and related to clinical outcomes and fractional anisotropy (FA) of midcingulate cingulum. Cortical responses showed a consistent reduction in latency and an increase in magnitude over time, indicating faster and stronger electrocortical signaling with chronic stimulation. Higher baseline midcingulate FA predicted greater latency acceleration, linking SEP timing to white-matter integrity. These findings identify temporal SEP dynamics as candidate mechanistic biomarkers that reflect circuit engagement during SCC-DBS and offer a pathway toward physiology-guided optimization of neuromodulation for depression. HighlightsO_LIReduced latency of stimulation evoked potential after 6 months of DBS C_LIO_LILarger cortical evoked response to single pulse perturbation after 6 months of DBS C_LIO_LIBaseline myelin integrity in MCC predicts magnitude of change in EP latency C_LI

neuroscience↗

bioRxiv2025

Ephaptic coupling and power fluctuations in depression

The initial therapeutic exposure to DBS during implantation surgery has reproducible acute behavioral effects that carry over without further stimulation. We analyzed LFP data from the first month following brief therapeutic intraoperative DBS. Data were recorded from the subcallosal cingulate cortex (SCC). During this month no further stimulation was applied. Recent studies have identified beta power fluctuations in LFP data as an acute putative depression biomarker of this exposure. However, a detailed description of neural dynamics underlying brain power fluctuations is missing. Here, we consider how these fluctuations are related to brain itinerancy, that is neural activity changes between stable and unstable states. We also provide a proof of principle study that these dynamics can be described using two new dynamical systems measures: instability frequency and relative wandering time. These capture interactions between neural activity and the mesoscale oscillatory electric fields generated by it. The two measures seem to split low vs. high HDRS scores within a small patient cohort. They are motivated by the cytoelectric coupling hypothesis, that suggests that efficient information processing results from mesoscale electric fields; and that the re-emergence of depression symptoms might result from altered electric fields. Whether the new measures reflect general mechanisms of rapid antidepressant action remains to be tested.

neuroscience↗

bioRxiv2023

Neural Interoceptive Processing is Modulated by Deep Brain Stimulation for Treatment Resistant Depression

BackgroundA critical advance in depression research is to clarify the hypothesized role of interoceptive processing in neural mechanisms of treatment efficacy. This study tests whether cortical interoceptive processing, as indexed by the heartbeat-evoked potential (HEP), is modulated by deep brain stimulation (DBS) to the subcallosal cingulate (SCC) for treatment resistant depression (TRD). MethodsEight patients with TRD were enrolled in a study of SCC DBS safety and efficacy. Electroencephalography (EEG) and symptom severity measures were sampled in a laboratory setting over the course of a six-month treatment protocol. The primary outcome measure was an EEG-derived HEP, which reflects cortical processing of heartbeat sensation. Cluster-based permutation analyses were used to test the effect of stimulation and time in treatment on the HEP. The change in signal magnitude after treatment was correlated with change in depression severity as measured by the 17-item Hamilton Depression Rating Scale. ResultsHEP amplitude was greater after 24 weeks of treatment (t(7)=-4.40, p=.003, g=-1.38, 95% Cl [-2.3, -0.42]), and this change was inversely correlated with latency of treatment response (rho = -0.75, 95% Cl [-0.95, -0.11], p=.03). An acute effect of DBS was also observed, but as a decrease in HEP amplitude (t(6) =6.66, p<.001, g=2.19, 95% Cl [0.81, 3.54]). HEP differences were most pronounced over left posterior sensors from 405-425 ms post-stimulus. ConclusionBrain-based evidence substantiates a theorized link between interoception and depression, and suggests an interoceptive contribution to the mechanism of treatment efficacy with deep brain stimulation for severe depression.

neuroscience↗

bioRxiv2019

Network-targeted, multi-site direct cortical stimulation enhances working memory by modulating phase lag of low frequency oscillations

Working memory, an important component of cognitive control, is supported by the coordinated activation of a network of cortical regions in the frontal and parietal cortices. Oscillations in theta and alpha frequency bands are thought to coordinate these network interactions. Thus, targeting multiple nodes of the network with brain stimulation at the frequency of interaction may be an effective means of modulating working memory. We tested this hypothesis by identifying regions that are functionally connected in theta and alpha frequency bands and intracranially stimulating both regions simultaneously in participants undergoing invasive monitoring. We found that in-phase stimulation resulted in improvement in performance compared to sham stimulation. In contrast, anti-phase stimulation did not affect performance. In-phase stimulation resulted in decreased phase lag between regions within working memory network while anti-phase stimulation resulted in increased phase lag suggesting that shorter phase lag in oscillatory connectivity may lead to better performance. The results support the idea that phase lag may play a key role in information transmission across brain regions. More broadly, brain stimulation strategies that aim to improve cognition may be better served targeting multiple nodes of brain networks.

neuroscience↗

bioRxiv2018

Low-frequency direct cortical stimulation of left superior frontal gyrus enhances working memory performance

The neural substrates of working memory are spread across prefrontal, parietal and cingulate cortices and are thought to be coordinated through low frequency cortical oscillations in the theta (3 - 8 Hz) and alpha (8 - 12 Hz) frequency bands. While the functional role of many subregions have been elucidated using neuroimaging studies, the role of superior frontal gyrus (SFG) is not yet clear. Here, we combined electrocorticography and direct cortical stimulation in three patients implanted with subdural electrodes to assess if superior frontal gyrus is indeed involved in working memory. We found left SFG exhibited task-related modulation of oscillations in the theta and alpha frequency bands specifically during the encoding epoch. Stimulation at the frequency matched to the endogenous oscillations resulted in reduced reaction times in all three participants. Our results support the causal role of SFG in working memory and suggest that SFG may coordinate working memory through low-frequency oscillations thus bolstering the feasibility of targeting oscillations for restoring cognitive function.

neuroscience↗