Regulation of arousal and performance of a healthy non-human primate using closed-loop central thalamic deep brain stimulation.

Application of closed-loop approaches in systems neuroscience and brain-computer interfaces holds great promise for revolutionizing our understanding of the brain and for developing novel neuromodulation strategies to restore lost function. The anterior forebrain mesocircuit (AFM) of the mammalian brain is hypothesized to underlie arousal regulation of the cortex and striatum, and support cognitive functions during wakefulness. Dysfunction of arousal regulation is hypothesized to contribute to cognitive dysfunctions in various neurological disorders, and most prominently in patients following traumatic brain injury (TBI).

Robust modulation of arousal regulation, performance, and frontostriatal activity through central thalamic deep brain stimulation in healthy nonhuman primates.

The central thalamus (CT) is a key component of the brain-wide network underlying arousal regulation and sensory-motor integration during wakefulness in the mammalian brain. Dysfunction of the CT, typically a result of severe brain injury (SBI), leads to long-lasting impairments in arousal regulation and subsequent deficits in cognition. Central thalamic deep brain stimulation (CT-DBS) is proposed as a therapy to reestablish and maintain arousal regulation to improve cognition in select SBI patients.

Modulation of arousal regulation with central thalamic deep brain stimulation.

To investigate the effects of central thalamic deep brain stimulation (CT/DBS) on behavior and frontal cortical function, we conducted experiments in an awake, behaving macaque monkey performing tasks that required sustained attention and working memory. Results of this preliminary study revealed that CT/DBS can lead to an improvement, a decrement, a mixed or have no effect on behavior.

Characterization of trial-to-trial fluctuations in local field potentials recorded in cerebral cortex of awake behaving macaque.

In analyzing neurophysiologic data, individual experimental trials are usually assumed to be statistically independent. However, many studies employing functional imaging and electrophysiology have shown that brain activity during behavioral tasks includes temporally correlated trial-to-trial fluctuations. This could lead to spurious results in statistical significance tests used to compare data from different interleaved behavioral conditions presented throughout an experiment.

Neurophysiological recordings in freely moving monkeys.

Recordings of neuronal activity in freely moving rats are common in experiments where electrical signals are transmitted using cables. Such techniques are not common in monkeys because their prehensile abilities are thought to preclude such techniques. However, analysis of brain mechanisms underlying spatial navigation and cognition require the subject to walk.

An automated food delivery system for behavioral and neurophysiological studies of learning and memory in freely moving monkeys.

We describe a custom-built feeder based on stepping motor technology controlled by a laboratory computer. The feeder dispenses a wide range of foods: any fruit, vegetable, or nut. The feeder allows the investigator to reward monkeys with different foods within a single experimental day.

Amelioration of dural granulation tissue growth for primate neurophysiology.

Four methods were tried in order to reduce the growth of granulation tissue on the dura. The best results were obtained using white petrolatum jelly, which almost completely suppressed the growth of granulation tissue when the recording chamber was filled with petrolatum. Collagen and acrylic seals were very effective in one monkey.

Making your next move: dorsolateral prefrontal cortex and planning a sequence of actions in freely moving monkeys.

Prefrontal damage disrupts planning, as measured by disorders of the activities of daily living (Humphreys & Forde, 1998; Shallice & Burgess, 1991). In a monkey model of this form of planning, a variant of the delayed alternation task was performed by freely moving monkeys. In a 16 x 16-ft.

Spatially directed movement and neuronal activity in freely moving monkey.

The abilities to plan a series of movements and to navigate within the environment require the functions of the frontal and ventromedial temporal lobes, respectively. Neuropsychological studies posit the existence of egocentric (prefrontal) and allocentric (ventromedial temporal) spatial frames of reference that mediate these functions. To examine neural mechanisms underlying egocentric and allocentric guidance of movement, we have developed behavioral and neurophysiological techniques for freely moving monkey.

A microelectrode drive for long term recording of neurons in freely moving and chaired monkeys.

An electrode drive is described for recordings of neurons in freely moving and chaired monkeys during the performance of behavioural tasks. The electrode drives are implanted for periods of up to 6 months, and can advance up to 42 electrodes using 14 independent drive mechanisms. The drive samples 288 points within a 12 mmx12 mm region, with 15 mm of electrode travel.