Neuroelectric oscillations reflect synchronous excitability fluctuations in ensembles of neurons, ubiquitous in the waking (and sleeping) brain, and are believed to be fundamental instruments in adaptive brain function. Despite recent progress in understanding the physiological underpinnings and functional significance of neuronal oscillations, the cellular physiology of the reset and entrainment processes, that allow the brain to harness oscillations as building blocks of perception and cognition, are unclear. Recent findings suggest that it is possible to manipulate neuronal oscillations using weak transcranial electrical stimulation (TES) both with direct and alternating currents (tDCS and tACS respectively). This raises possibilities for causal manipulations that can help to confirm the role of specific oscillatory dynamics in specific aspects of perception and behavior, as well as the possibility of treating neuropsychiatric disorders in which disruptions of brain dynamics underlie cognitive deficits. We propose to examine effects of tDCS and tACS with a combination of electric field measurements and modelling, electrophysiological and behavioral measurements in awake-behaving macaque monkeys.
Our Specific Aims are: 1) Optimize models to target specific brain regions with tDCS and tACS. Widespread. macro-scale intracranial recordings with chronically-implanted, 48 channel stereotactic EEG (s-EEG) arrays will determine how intracranial electric fields are affected by stimulation parameters, e.g., intensity, frequency (tACS) and variations in stimulating electrode nu mber (up to 8) and positions. 2) Define physiological and behavioral effects of tDCS and tACS in active sensory processing. We will use a limited (24 channel) version of the macro-scale network analysis (AIM 1), along with micro-scale measures in monkeys performing auditory discriminations and making manual responses to targets. Micro-scale measures include laminar field potential (FP), current source density (CSD) and multiunit activity (MUA) profiles sampled with multielectrode arrays across the layers of selected neocortical areas. CSD and MUA analyses are used to define the profiles of synaptic activity (indexed by current sinks and sources) and envelope of concomitant neuronal firing across the cortical layers, thus linking stimulation effects to specific cell populations, circuits and physiological processes engaged in oscillatory dynamics. Measuring network and cell-circuit activity patterns during sensory processing, target detection and motor responding will provide robust and sensitive means to gauge electrical stimulation effects on brain dynamics underlying these key processes. Success will support and inform a broader effort to develop a more detailed concrete picture of the properties of neuronal ensembles that create brain rhythms and organize them to perform fundamental cognitive operations. Improved mechanistic understanding of brain stimulation effects may lead to improved brain stimulation protocols, treatments disorders such as schizophrenia, autism and ADHD, in which sensory entrainment at both low and high frequencies is demonstrably or putatively impaired.

Public Health Relevance

We propose exploratory intracranial studies to evaluate both electric fields and neural activity changes induced by TES in monkeys. Our goal is to develop a noninvasive stimulation approach to change neural dynamics in a way that facilitates sensory processing and improves behavioral performance, and one that we can understand at a detailed level that will facilitate future mechanistic studies. Our findings will have important implications for treating ADHD, autism and schizophrenia, as well as other disorders that entail disruption of normal rhythmic entrainment and temporal processing mechanisms in the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH110217-02
Application #
9262276
Study Section
Special Emphasis Panel (ZRG1-IFCN-Q (55)R)
Program Officer
Buhring, Bettina D
Project Start
2016-04-15
Project End
2018-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
2
Fiscal Year
2017
Total Cost
$181,912
Indirect Cost
$69,412
Name
Nathan Kline Institute for Psychiatric Research
Department
Type
Research Institutes
DUNS #
167204762
City
Orangeburg
State
NY
Country
United States
Zip Code
10962
Opitz, Alexander; Yeagle, Erin; Thielscher, Axel et al. (2018) On the importance of precise electrode placement for targeted transcranial electric stimulation. Neuroimage 181:560-567
Opitz, Alexander; Falchier, Arnaud; Linn, Gary S et al. (2017) Limitations of ex vivo measurements for in vivo neuroscience. Proc Natl Acad Sci U S A 114:5243-5246
Opitz, Alexander; Falchier, Arnaud; Yan, Chao-Gan et al. (2016) Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in humans and nonhuman primates. Sci Rep 6:31236