Biology subjects

Marks, V. S.

Publications and source records attributed to Marks, V. S..

3 recordsLinked to original sources

bioRxiv2025

A clinical grade neurostimulation implant for hierarchical control of physiological activity

Bioelectronic implants for neurostimulation aim to steer disordered neurophysiological processes back towards a healthy state. However, physiology is subject to biological rhythms, including the circadian rhythm and the sleep-wake cycle. These predictable rhythms affect disease symptomatology, biomarkers used in closed-loop therapies, and a physiological systems expected response to stimulation. Therefore, therapeutic devices should incorporate feedforward elements to align algorithm parameters with predictable changes in physiological state, as a parallel of physiological rheostatic control. Here we introduce the DyNeuMo-2c, the first clinical-grade implant capable of delivering closed-loop neurostimulation while flexibly changing its functional configuration according to time of day. The device can chronically measure brain activity and motion state to track potential biomarker patterns in natural, out-of-clinic settings, allowing identification and targeting of patient-specific chronotypes. The system implements a hierarchical control flow, with baseline therapy set by a circadian scheduler, and adaptive policies layered to take effect based on specific biomarkers indicating patient and disease state. Using a benchtop validation setup, we demonstrate that the system has the required capabilities for delivering time-contingent closed-loop therapy in two established clinical use cases: Parkinsons disease and epilepsy. Next, we deploy the system in vivo to deliver closed-loop deep brain stimulation in a healthy non-human primate model of vigilance, highlighting the importance of synchronisation between device operation and physiological state in various conditions (task performance, unconstrained behaviour, and sleep). Time-of-day-dependent adaptation of closed-loop stimulation enabled modulation of both vigilance and behaviour. Overall, the novel device architecture provides a proof-of-concept for delivering time-contingent therapy in chronic therapeutic settings where biological rhythms are of key importance.

neuroscience↗

bioRxiv2022

Chronic modulation of human memory and thalamic-hippocampal theta activities.

Electrical stimulation is a powerful therapeutic tool for treating neurologic and neuropsychiatric disorders. Sensing and modulating electrophysiological biomarkers of memory over extended timescales is necessary for tracking and improving memory in humans. Here, we describe results from humans in their natural home environments using a novel, investigational system enabling chronic stimulation and multi-channel recording of anterior thalamic and hippocampal local field potentials during memory tasks. Four people with focal epilepsy performed a free recall verbal memory task repeatedly for up to fifty months on a touch-screen device with wireless signal acquisition with electrophysiology and behavioral data streaming to a cloud environment. Anterior thalamic-hippocampal spectral activities in the theta frequency range were found to correlate with memory processing, to predict task performance, and to be modulated by deep brain stimulation. Our results provide a new biomarker-based technology for chronic remote tracking of memory performance and modulation of the associated neural activities. One Sentence SummaryElectrical stimulation in the anterior thalamic nuclei modulates theta frequency activities and improves human verbal memory performance chronically.

neuroscience↗

bioRxiv2021

Independent dynamics of slow, intermediate, and fast intracranial EEG spectral activities during human memory formation

A wide spectrum of brain rhythms are engaged throughout the human cortex in cognitive functions. How the rhythms of various low and high frequencies are spatiotemporally coordinated across the human brain during memory processing is inconclusive. They can either be coordinated together across a wide range of the frequency spectrum or induced in specific bands. We used a large dataset of human intracranial electroencephalography (iEEG) to parse the spatiotemporal dynamics of spectral activities induced during formation of verbal memories. Encoding of words for subsequent free recall activated slow theta, intermediate alpha and beta, and fast gamma frequency power in discrete cortical sites. A majority of the electrode sites recorded activity in only one of these frequencies, except for the visual cortex where spectral power was induced across multiple bands. Each frequency band showed characteristic dynamics of the induced power specific to cortical area and hemisphere. The power of the low, intermediate, and fast activities propagated in distinct spatiotemporal patterns across the visual, temporal and prefrontal cortical areas as the words were presented for encoding. Our results suggest anatomically and temporally distributed spectral activities in the formation of human memory.

neuroscience↗