Verhein, J. R. | Search bioRxiv

bioRxiv2023

Methylphenidate modulates motor cortical dynamics and behavior

Methylphenidate (MPH, brand: Ritalin) is a common stimulant used both medically and non-medically. Though typically prescribed for its cognitive effects, MPH also affects movement. While it is known that MPH noncompetitively blocks the reuptake of catecholamines through inhibition of dopamine and norepinephrine transporters, a critical step in exploring how it affects behavior is to understand how MPH directly affects neural activity. This would establish an electrophysiological mechanism of action for MPH. Since we now have biologically-grounded network-level hypotheses regarding how populations of motor cortical neurons plan and execute movements, there is a unique opportunity to make testable predictions regarding how systemic MPH administration - a pharmacological perturbation - might affect neural activity in motor cortex. To that end, we administered clinically-relevant doses of MPH to Rhesus monkeys as they performed an instructed-delay reaching task. Concomitantly, we measured neural activity from dorsal premotor and primary motor cortex. Consistent with our predictions, we found dose-dependent and significant effects on reaction time, trial-by-trial variability, and movement speed. We confirmed our hypotheses that changes in reaction time and variability were accompanied by previously established population-level changes in motor cortical preparatory activity and the condition-independent signal that precedes movements. We expected changes in speed to be a result of changes in the amplitude of motor cortical dynamics and/or a translation of those dynamics in activity space. Instead, our data are consistent with a mechanism whereby the neuromodulatory effect of MPH is to increase the gain and/or the signal-to-noise of motor cortical dynamics during reaching. Continued work in this domain to better understand the brain-wide electrophysiological mechanism of action of MPH and other psychoactive drugs could facilitate more targeted treatments for a host of cognitive-motor disorders.

neuroscience↗

bioRxiv2020

An emergent population code in primary auditory cortex supports selective attention to spectral and temporal sound features

Textbook descriptions of primary sensory cortex (PSC) revolve around single neurons representation of low-dimensional sensory features, such as visual object orientation in V1, location of somatic touch in S1, and sound frequency in A1. Typically, studies of PSC measure neurons responses along few (1 or 2) stimulus and/or behavioral dimensions. However, real-world stimuli usually vary along many feature dimensions and behavioral demands change constantly. In order to illuminate how A1 supports flexible perception in rich acoustic environments, we recorded from A1 neurons while rhesus macaques performed a feature-selective attention task. We presented sounds that varied along spectral and temporal feature dimensions (carrier bandwidth and temporal envelope, respectively). Within a block, subjects attended to one feature of the sound in a selective change detection task. We find that single neurons tend to be high-dimensional, in that they exhibit substantial mixed selectivity for both sound features, as well as task context. Contrary to common findings in many previous experiments, attention does not enhance the single-neuron representation of attended features in our data. However, a population-level analysis reveals that ensembles of neurons exhibit enhanced encoding of attended sound features, and this population code tracks subjects performance. Importantly, surrogate neural populations with intact single-neuron tuning but shuffled higher-order correlations among neurons failed to yield attention-related effects observed in the intact data. These results suggest that an emergent population code not measurable at the single-neuron level might constitute the functional unit of sensory representation in PSC. SIGNIFICANCE STATEMENTThe ability to adapt to a dynamic sensory environment promotes a range of important natural behaviors. We recorded from single neurons in monkey primary auditory cortex while subjects attended to either the spectral or temporal features of complex sounds. Surprisingly, we find no average increase in responsiveness to, or encoding of, the attended feature across single neurons. However, when we pool the activity of the sampled neurons via targeted dimensionality reduction, we find enhanced population-level representation of the attended feature and suppression of the distractor feature. This dissociation of the effects of attention at the level of single neurons vs. the population highlights the synergistic nature of cortical sound encoding and enriches our understanding of sensory cortical function.

neuroscience↗