# Central thalamic deep brain stimulation to regulate arousal and cognition

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $622,811

## Abstract

Deep brain stimulation (DBS) is an established therapy for various movement disorders and is now being
investigated to treat a widening range of neurological and neuropsychiatric conditions. However, to fully realize
the promise of DBS as a therapy, we need to better understand how it modulates neuronal activity within both
the local DBS target and in the brain as a whole. The focus of this proposal is to advance a novel method of
field-shaping central thalamic-DBS (fsCT-DBS) to modulate arousal and cognition. Arousal regulation is
profoundly impacted in patients with structural brain injuries and is a common and untreated sequelae of many
patients suffering from neurodegenerative and neuropsychiatric illnesses. In prior work we discovered a novel
method of CT-DBS, where anodes and cathodes are separated across multiple implanted DBS leads within a
specific region of the central thalamus, here termed `field-shaping CT-DBS' (fsCT-DBS). Here we will
prospectively test and characterize behavioral performance of animals during fsCT-DBS. The central
hypothesis to be tested here is that robust regulation of arousal with fsCT-DBS arises through selective
delivery of electric stimulation to a specific fiber tract within the central thalamus, the medial aspect of the
dorsal thalamic tegmental tract (DTTm). This fiber tract consists of axons originating from central thalamic
nuclear groups and brainstem arousal centers that project to the anterior forebrain and are believed to play a
crucial role in supporting cognition through the regulation of activity levels and brain-wide communication. The
aims of this proposal seek to establish an anatomically accurate predictive biophysical model of the DTTm and
to systematically test new modes of fsCT-DBS to enhance the use and capacity of cognitive resources in
healthy behaving macaque monkeys. First, state-of-the-art biomedical imaging will be combined with ultrahigh-
resolution optical imaging to construct predictive biophysical models of the DTTm. Second, the effects of fsCT-
DBS on DTTm recruitment will be measured by comparing performance on a sustained attention/vigilance task
and in two paradigms requiring additional cognitive resources, a set-shifting categorization task and a working
memory task. The latter two tasks require cognitive flexibility, a faculty that is degraded in the majority of
patients with neuropsychiatric disorders and structural brain injuries. Third, the use of adaptive fsCT-DBS will
be explored using a new clinical-grade closed-loop DBS device. The identification and predictive biophysical
modeling of the local fsCT-DBS target, the DTTm, the use of multipolar field shaping to validate the model
predictions through behavior and large-scale physiology, and exploration of close-loop DBS are all highly
innovative aspects of this proposal as they will improve our understanding of how to precisely target fsCT-DBS
to robustly and reliability regulate anterior forebrain activity and support c...

## Key facts

- **NIH application ID:** 10130010
- **Project number:** 5R01NS111019-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** JONATHAN L BAKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $622,811
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130010

## Citation

> US National Institutes of Health, RePORTER application 10130010, Central thalamic deep brain stimulation to regulate arousal and cognition (5R01NS111019-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10130010. Licensed CC0.

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