Husam A. Katnani

Motor Functions of the Superior Colliculus

The mammalian superior colliculus (SC) and its nonmammalian homolog, the optic tectum, constitute a major node in processing sensory information, incorporating cognitive factors, and issuing motor commands. The resulting action-to orient toward or away from a stimulus-can be accomplished as an integrated movement across oculomotor, cephalomotor, and skeletomotor effectors. The SC also participates in preserving fixation during intersaccadic intervals. This review highlights the repertoire of movements attributed to SC function and analyzes the significance of results obtained from causality-based experiments (microstimulation and inactivation). The mechanisms potentially used to decode the population activity in the SC into an appropriate movement command are also discussed.

Order of operations for decoding superior colliculus activity for saccade generation

To help understand the order of events that occurs when generating saccades, we simulated and tested two commonly stated decoding models that are believed to occur in the oculomotor system: vector averaging (VA) and center-of-mass. To generate accurate saccades, each model incorporates two required criteria: 1) a decoding mechanism that deciphers a population response of the superior colliculus (SC) and 2) an exponential transformation that converts the saccade vector into visual coordinates. The order of these two criteria is used differently within each model, yet the significance of the sequence has not been quantified. To distinguish between each decoding sequence and hence, to determine the order of events necessary to generate accurate saccades, we simulated the two models. Distinguishable predictions were obtained when two simultaneous motor commands are processed by each model. Experimental tests of the models were performed by observing the distribution of endpoints of saccades evoked by weighted, simultaneous microstimulation of two SC sites. The data were consistent with the predictions of the VA model, in which exponential transformation precedes the decoding computation.

A Novel Brain Stimulation Technology Provides Compatibility with MRI

Clinical electrical stimulation systems — such as pacemakers and deep brain stimulators (DBS) — are an increasingly common therapeutic option to treat a large range of medical conditions. Despite their remarkable success, one of the significant limitations of these medical devices is the limited compatibility with magnetic resonance imaging (MRI), a standard diagnostic tool in medicine. During an MRI exam, the leads used with these devices, implanted in the body of the patient, act as an electric antenna potentially causing a large amount of energy to be absorbed in the tissue, which can lead to serious heat-related injury. This study presents a novel lead design that reduces the antenna effect and allows for decreased tissue heating during MRI. The optimal parameters of the wire design were determined by a combination of computational modeling and experimental measurements. The results of these simulations were used to build a prototype, which was tested in a gel phantom during an MRI scan. Measurement results showed a three-fold decrease in heating when compared to a commercially available DBS lead. Accordingly, the proposed design may allow a significantly increased number of patients with medical implants to have safe access to the diagnostic benefits of MRI.

A test of spatial temporal decoding mechanisms in the superior colliculus.

Population coding is a ubiquitous principle in the nervous system for the proper control of motor behavior. A significant amount of research is dedicated to studying population activity in the superior colliculus (SC) to investigate the motor control of saccadic eye movements. Vector summation with saturation (VSS) has been proposed as a mechanism for how population activity in the SC can be decoded to generate saccades. Interestingly, the model produces different predictions when decoding two simultaneous populations at high vs. low levels of activity. We tested these predictions by generating two simultaneous populations in the SC with high or low levels of dual microstimulation. We also combined varying levels of stimulation with visually induced activity. We found that our results did not perfectly conform to the predictions of the VSS scheme and conclude that the simplest implementation of the model is incomplete. We propose that additional parameters to the model might account for the results of this investigation.

The relative impact of microstimulation parameters on movement generation.

Microstimulation is widely used in neurophysiology to characterize brain areas with behavior and in clinical therapeutics to treat neurological disorder. Current intensity and frequency, which respectively influence activation patterns in spatial and temporal domains, are typically selected to elicit a desired response, but their effective influence on behavior has not been thoroughly examined. We delivered microstimulation to the primate superior colliculus while systematically varying each parameter to capture effects of a large range of parameter space. We found that frequency was more effective in driving output properties, whereas properties changed gradually with intensity. Interestingly, when different parameter combinations were matched for total charge, effects on behavioral properties became seemingly equivalent. This study provides a first level resource for choosing desired parameter ranges to effectively manipulate behavior. It also provides insights into interchangeability of parameters, which can assist clinical microstimulation that looks to appropriately control behavior within designated constraints, such as power consumption.

Local SAR near deep brain stimulation (DBS) electrodes at 64 and 127 MHz: A simulation study of the effect of extracranial loops

MRI may cause brain tissue around deep brain stimulation (DBS) electrodes to become excessively hot, causing lesions. The presence of extracranial loops in the DBS lead trajectory has been shown to affect the specific absorption rate (SAR) of the radiofrequency energy at the electrode tip, but experimental studies have reported controversial results. The goal of this study was to perform a systematic numerical study to provide a better understanding of the effects of extracranial loops in DBS leads on the local SAR during MRI at 64 and 127 MHz.

Time course of motor preparation during visual search with flexible stimulus-response association.

Whether allocation of visuospatial attention can be divorced from saccade preparation has been the subject of intense research efforts. A variant of the visual search paradigm, in which a feature singleton indicates that the correct saccade should be directed to it (prosaccade) or to the opposite distractor (antisaccade), has been influential in addressing this core topic. We performed a causal assessment of this controversy by delivering an air puff to one eye to invoke the trigeminal blink reflex as monkeys performed this visual search task. Blinks effectively remove saccadic inhibition and prematurely trigger impending saccades in reaction time tasks, thus providing a behavioral readout of the premotor plan. We found that saccades accompanied blinks during the initial allocation of attention epoch and that these movements were directed to the singleton for both prosaccade and antisaccade trials. Blinks evoked at later times were accompanied with saccades to the correct end point location: the singleton on prosaccade trials and the opposite distractor on antisaccade trials. These results provide support for concurrent encoding of visuospatial attention and saccade preparation during visual search behavior.

Neuromodulation for Obsessive-Compulsive Disorder

This article describes the basis for neuromodulation procedures for obsessive-compulsive disorder (OCD) and summarizes the literature on the efficacy of these interventions. Discussion includes neural circuitry underlying OCD pathology, the history and types of ablative procedures, the targets and modalities used for neuromodulation, and future therapeutic directions.

Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning

The primate brain has the remarkable ability of mapping sensory stimuli into motor behaviors that can lead to positive outcomes. We have previously shown that during the reinforcement of visual-motor behavior, activity in the caudate nucleus is correlated with the rate of learning. Moreover, phasic microstimulation in the caudate during the reinforcement period was shown to enhance associative learning, demonstrating the importance of temporal specificity to manipulate learning related changes. Here we present evidence that extends upon our previous finding by demonstrating that temporally coordinated phasic deep brain stimulation across both the nucleus accumbens and caudate can further enhance associative learning. Monkeys performed a visual-motor associative learning task and received stimulation at time points critical to learning related changes. Resulting performance revealed an enhancement in the rate, ceiling, and reaction times of learning. Stimulation of each brain region alone or at different time points did not generate the same effect.

Blink perturbation effects on saccades evoked by microstimulation of the superior colliculus.

Current knowledge of saccade-blink interactions suggests that blinks have paradoxical effects on saccade generation. Blinks suppress saccade generation by attenuating the oculomotor drive command in structures like the superior colliculus (SC), but they also disinhibit the saccadic system by removing the potent inhibition of pontine omnipause neurons (OPNs). To better characterize these effects, we evoked the trigeminal blink reflex by delivering an air puff to one eye as saccades were evoked by sub-optimal stimulation of the SC. For every stimulation site, the peak and average velocities of stimulation with blink movements (SwBMs) were lower than stimulation-only saccades (SoMs), supporting the notion that the oculomotor drive is weakened in the presence of a blink. In contrast, the duration of the SwBMs was longer, consistent with the hypothesis that the blink-induced inhibition of the OPNs could prolong the window of time available for oculomotor commands to drive an eye movement. The amplitude of the SwBM could also be larger than the SoM amplitude obtained from the same site, particularly for cases in which blink-associated eye movements exhibited the slowest kinematics. The results are interpreted in terms of neural signatures of saccade-blink interactions.