Publications by authors named "Timothy J Denison"

Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is an experimental therapy for treatment-resistant depression (TRD). Chronic SCC DBS leads to long-term changes in the electrophysiological dynamics measured from local field potential (LFP) during wakefulness, but it is unclear how it impacts sleep-related brain activity. This is a crucial gap in knowledge, given the link between depression and sleep disturbances, and an emerging interest in the interaction between DBS, sleep, and circadian rhythms.

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Biological rhythms pervade physiology and pathophysiology across multiple timescales. Because of the limited sensing and algorithm capabilities of neuromodulation device technology to-date, insight into the influence of these rhythms on the efficacy of bioelectronic medicine has been infeasible. As the development of new devices begins to mitigate previous technology limitations, we propose that future devices should integrate chronobiological considerations in their control structures to maximize the benefits of neuromodulation therapy.

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Chronic brain recordings suggest that seizure risk is not uniform, but rather varies systematically relative to daily (circadian) and multiday (multidien) cycles. Here, one human and seven dogs with naturally occurring epilepsy had continuous intracranial EEG (median 298 days) using novel implantable sensing and stimulation devices. Two pet dogs and the human subject received concurrent thalamic deep brain stimulation (DBS) over multiple months.

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Neurotechnological devices are failing to deliver on their therapeutic promise because of the time it takes to translate them from bench to clinic. In this Perspective, we reflect on lessons learned from medical device successes and failures and consider how such lessons might shape a strategic vision for translating neurotechnologies in the future. We articulate how the intentional design and deployment of "scientific platforms," from the technology stack of hardware and software through the supporting ecosystem, could catalyze a new wave of innovation, discovery, and therapy.

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Neuromodulation therapies offer a unique opportunity for translating brain-computer interface (BCI) technologies into a clinical setting. Several diseases such as Parkinson's disease are effectively treated by invasive device stimulation therapies, and the addition of sensing and algorithm technology is an obvious evolutionary expansion of capabilities. In addition, this infrastructure might enable a roadmap of novel BCI technologies.

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Advances in ambulatory intracranial EEG devices have enabled objective analyses of circadian and multiday seizure periodicities, and seizure clusters in humans. This study characterizes circadian and multiday seizure periodicities, and seizure clusters in dogs with naturally occurring focal epilepsy, and considers the implications of an animal model for the study of seizure risk patterns, seizure forecasting and personalized treatment protocols. In this retrospective cohort study, 16 dogs were continuously monitored with ambulatory intracranial EEG devices designed for humans.

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Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) was offered to chronic pain patients who had exhausted medical and surgical options. However, several patients developed recurrent seizures. This work was conducted to assess the effect of ACC stimulation on the brain activity and to guide safe DBS programming.

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Background: The use of Deep Brain Stimulation (DBS) as a potential therapy for treatment resistant epilepsy remains an area of active clinical investigation. We recently reported the first chronic evaluation of an implantable, clinical-grade system that permits concurrent stimulation and recording, in a large animal (ovine) model developed to study DBS for epilepsy.

Objective: In this study we extended this work to compare the effects of remote (anterior thalamic) and direct (hippocampal) stimulation on local field potential (LFP) activity and network excitability, and to assess closed-loop stimulation within this neural network.

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Article Synopsis
  • This study explores a new deep brain stimulation (DBS) system that can both stimulate and record brain activity, using sheep as a model for epilepsy treatment.
  • The research involved implanting DBS leads in specific brain areas and collecting data on their effects over a long period, revealing important patterns in neural activity.
  • The findings highlight the potential of this technology to enhance understanding of brain functions and improve treatments for conditions like epilepsy.
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Purpose: Our primary goal was to assess the effects of varying stimulus parameters on the electrically evoked cortical potentials (EECPs) in rabbits, which we intend to use as one measure of biocompatibility of implanted retinal prosthetic devices. We also sought to exclude contamination of waveforms recorded over the occipital cortex from electrical activity from the retina and the degree of reproducibility of EECP recordings.

Methods: A concentric bipolar platinum electrode or microfabricated 5x5 electrode array delivered current to the retina of 43 Dutch-belted rabbits while the EECP was recorded from extradural electrodes over the occipital cortex.

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