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).

Geometry of spiking patterns in early visual cortex: a topological data analytic approach.

In the brain, spiking patterns live in a high-dimensional space of neurons and time. Thus, determining the intrinsic structure of this space presents a theoretical and experimental challenge. To address this challenge, we introduce a new framework for applying topological data analysis (TDA) to spike train data and use it to determine the geometry of spiking patterns in the visual cortex.

Predicting task performance from biomarkers of mental fatigue in global brain activity.

Detection and early prediction of mental fatigue (i.e. shifts in vigilance), could be used to adapt neuromodulation strategies to effectively treat patients suffering from brain injury and other indications with prominent chronic mental fatigue.

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.

Responses to orientation discontinuities in V1 and V2: physiological dissociations and functional implications.

Segmenting the visual image into objects is a crucial stage of visual processing. Object boundaries are typically associated with differences in luminance, but discontinuities in texture also play an important role. We showed previously that a subpopulation of neurons in V2 in anesthetized macaques responds to orientation discontinuities parallel to their receptive field orientation.

Cannabinoid neuromodulation in the adult early visual cortex.

Sensory processing is an active process involving the interaction of ongoing cortical activity with incoming stimulus information. However, the modulators and circuits involved in this interaction are incompletely understood. One potential candidate is the cannabinoid-signaling system, which is known to modulate the dynamics of cortical networks.

Long-term expression and safety of administration of AAVrh.10hCLN2 to the brain of rats and nonhuman primates for the treatment of late infantile neuronal ceroid lipofuscinosis.

Late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal, lysosomal storage disorder caused by mutations in the CLN2 gene, results in a deficiency of tripeptidyl-peptidase I (TPP-I) activity in neurons. Our prior studies showed that delivery of the human CLN2 cDNA directly to the CNS, using an adeno-associated virus serotype 2 (AAV2) vector, is safe in children with LINCL. As a second-generation strategy, we have demonstrated that AAVrh.

Sparse coding and high-order correlations in fine-scale cortical networks.

Connectivity in the cortex is organized at multiple scales, suggesting that scale-dependent correlated activity is particularly important for understanding the behaviour of sensory cortices and their function in stimulus encoding. We analysed the scale-dependent structure of cortical interactions by using maximum entropy models to characterize multiple-tetrode recordings from primary visual cortex of anaesthetized macaque monkeys (Macaca mulatta). We compared the properties of firing patterns among local clusters of neurons (<300 microm apart) with those of neurons separated by larger distances (600-2,500 microm).

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.

Subpopulations of neurons in visual area v2 perform differentiation and integration operations in space and time.

The interconnected areas of the visual system work together to find object boundaries in visual scenes. Primary visual cortex (V1) mainly extracts oriented luminance boundaries, while secondary visual cortex (V2) also detects boundaries defined by differences in texture. How the outputs of V1 neurons are combined to allow for the extraction of these more complex boundaries in V2 is as of yet unclear.

Laminar and orientation-dependent characteristics of spatial nonlinearities: implications for the computational architecture of visual cortex.

A full understanding of the computations performed in primary visual cortex is an important yet elusive goal. Receptive field models consisting of cascades of linear filters and static nonlinearities may be adequate to account for responses to simple stimuli such as gratings and random checkerboards, but their predictions of responses to complex stimuli such as natural scenes are only approximately correct. It is unclear whether these discrepancies are limited to quantitative inaccuracies that reflect well-recognized mechanisms such as response normalization, gain controls, and cross-orientation suppression or, alternatively, imply additional qualitative features of the underlying computations.

A Bayesian statistical analysis of behavioral facilitation associated with deep brain stimulation.

Deep brain stimulation (DBS) is an established therapy for Parkinson's Disease and is being investigated as a treatment for chronic depression, obsessive compulsive disorder and for facilitating functional recovery of patients in minimally conscious states following brain injury. For all of these applications, quantitative assessments of the behavioral effects of DBS are crucial to determine whether the therapy is effective and, if so, how stimulation parameters can be optimized. Behavioral analyses for DBS are challenging because subject performance is typically assessed from only a small set of discrete measurements made on a discrete rating scale, the time course of DBS effects is unknown, and between-subject differences are often large.

Attentional modulation of adaptation in V4.

Adaptation and visual attention are two processes that alter neural responses to luminance contrast. Rapid contrast adaptation changes response size and dynamics at all stages of visual processing, while visual attention has been shown to modulate both contrast gain and response gain in macaque extrastriate visual cortex. Because attention aims to enhance behaviorally relevant sensory responses while adaptation acts to attenuate neural activity, the question we asked is, how does attention alter adaptation? We present here single-unit recordings from V4 of two rhesus macaques performing a cued target detection task.

Comparing spectra and coherences for groups of unequal size.

Spectra and coherences are standard measures of association within and between time series. These measures have several advantages over their time-domain counterparts, not the least of which is the ability to derive and estimate confidence intervals. However, comparing spectra and coherences between two groups of observation is a problem that has not received much attention.

Responses of V1 neurons to two-dimensional hermite functions.

Neurons in primary visual cortex are widely considered to be oriented filters or energy detectors that perform one-dimensional feature analysis. The main deviations from this picture are generally thought to include gain controls and modulatory influences. Here we investigate receptive field (RF) properties of single neurons with localized two-dimensional stimuli, the two-dimensional Hermite functions (TDHs).

Analysis of perisaccadic field potentials in the occipitotemporal pathway during active vision.

Eye movement potentials (EMPs) associated with saccades appear in both subcortical and cortical structures of the primate visual system. In this study, EMPs are recorded across sites in the occipitotemporal (OT) pathway of monkeys performing a pattern-recognition task. We characterize pair recordings of saccade-triggered local field potentials (LFPs) in early extrastriate and inferotemporal regions of the ventral visual pathway using time-frequency spectrograms.