Hadar, P. | bioRxiv Science

bioRxiv2024

Theta-burst direct electrical stimulation remodels human brain networks

Patterned brain stimulation is a powerful therapeutic approach for treating a wide range of brain disorders. In particular, theta-burst stimulation (TBS), characterized by rhythmic bursts of 3-8 Hz mirroring endogenous brain rhythms, is delivered by transcranial magnetic stimulation to improve cognitive functions and relieve symptoms of depression. However, the mechanism by which TBS alters underlying neural activity remains poorly understood. In 10 pre-surgical epilepsy participants undergoing intracranial monitoring, we investigated the neural effects of TBS. Employing intracranial EEG (iEEG) during direct electrical stimulation across 29 stimulation cortical locations, we observed that individual bursts of electrical TBS consistently evoked strong neural responses spanning broad cortical regions. These responses exhibited dynamic changes over the course of stimulation presentations including either increasing or decreasing voltage responses, suggestive of short-term plasticity in the amplitude of the local field potential voltage response. Notably, stronger stimulation augmented the mean amplitude and distribution of TBS responses , leading to greater proportion of recording sites demonstrating short-term plasticity. TBS responses were stimulation site-specific and propagated according to the underlying functional brain architecture, as stronger responses were observed in regions with strong baseline effective (cortico-cortical evoked potentials) and functional (low frequency phase locking) connectivity. Further, our findings enabled the predictions of locations where both TBS responses and change in these responses (e.g. short-term plasticity) were observed. Future work may focus on using pre-treatment connectivity alongside other biophysical factors to personalize stimulation parameters, thereby optimizing induction of neuroplasticity within disease-relevant brain networks.

neuroscience↗

bioRxiv2021

Fluctuations in functional connectivity associated with interictal epileptiform discharges (IEDs) in intracranial EEG

All epilepsies are defined by a propensity for recurrent seizures, characterized by hypersynchronous electrographic activity. Understanding this overarching property would be advanced by a thorough quantification of how the global synchrony of the epileptic brain responds to small perturbations that do not trigger seizures. Here, we leverage analysis of transient focal bursts of epileptiform activity, termed interictal epileptiform discharges (IEDs), to characterize this response. Specifically, we use a group of 145 participants implanted with intracranial EEG (iEEG) electrodes to quantify changes in five functional connectivity measures associated with three properties of IEDs: their presence, spread, and number. We perform this analysis in five frequency bands in order to contextualize our findings in relation to ongoing neural processes at different spatial and temporal scales. We find that, across frequency bands, both the presence and spread of IEDs tend to lead to independent increases of functional connectivity, but only in functional connectivity measures influenced by the amplitude, rather than the phase, of a signal. We find that these increases are not explained by simple subgroups of connections, such as the weakest connections in the brain, or only connections within the seizure onset zone. Evaluating patterns of similarity across different bands and measure combinations, we find that the presence of IEDs impacts high frequencies (gamma and high gamma) and low frequencies (theta, alpha, and beta) differently, although responses within each group are similar. Using grouped LASSO regression, we identify which individual-level features explain differences in functional connectivity changes associated with IEDs. While no single feature robustly explains observed differences, the most consistently included predictors across bands and measures are the rate of IEDs and the anatomical locus of IEDs. Overall, this work provides compelling evidence for increases in global synchrony associated with IEDs, and delivers a thorough exploration of different functional connectivity measures, frequency bands, and IED properties. These observations show a disruption of several types of ongoing neural dynamics associated with IEDs. Additionally, we provide a starting point for future models of how small perturbations affect neural systems and how those systems support the hypersynchrony seen in epilepsy.

neuroscience↗