Focal optogenetic suppression in macaque area MT biases direction discrimination and decision confidence, but only transiently

Abstract

Insights from causal manipulations of brain activity depend on targeting the spatial and temporal scales most relevant for behavior. Using a sensitive perceptual decision task in monkeys, we examined the effects of rapid, reversible inactivation on a spatial scale previously achieved only with electrical microstimulation. Inactivating groups of similarly tuned neurons in area MT produced systematic effects on choice and confidence. Behavioral effects were attenuated over the course of each session, suggesting compensatory adjustments in the downstream readout of MT over tens of minutes. Compensation also occurred on a sub-second time scale: behavior was largely unaffected when the visual stimulus (and concurrent suppression) lasted longer than 350 ms. These trends were similar for choice and confidence, consistent with the idea of a common mechanism underlying both measures. The findings demonstrate the utility of hyperpolarizing opsins for linking neural population activity at fine spatial and temporal scales to cognitive functions in primates.

Contribution of Sensory Encoding to Measured Bias

“…There have been previous reports that causal manipulations of sensory areas can drive biases in behavioral choices. Electrical stimulation or optogenetic inactivation of direction-selective neurons in the sensory visual area MT can bias the monkey's choice toward or away from the neurons' preferred direction in two-alternative forced choice (2AFC) tasks, suggesting that manipulation of sensory areas can induce perceptual biases (Salzman et al, 1990;Ditterich et al, 2003;Fetsch et al, 2018). However, 2AFC tasks are criterion free and therefore not amenable to bias measured by SDT as in go/no-go tasks.…”

Stimulus dependent relationships between behavioral choice and sensory neural responses

“…This spans the range from single units , multiunit activity (Sanayei et al, 2018), and measurements resulting from different imaging techniques at different spatial scales like intrinsic imaging or fMRI (Choe et al, 2014;Thielscher and Pessoa, 2007;Runyan et al, 2017;Michelson et al, 2017). Given the increasing availability of population recordings, larger number of trials due to chronic recordings, and the advent of stimulation techniques to help to discriminate the origin of the choice-related signals (Cicmil et al, 2015;Tsunada et al, 2016;Yang et al, 2016;Lakshminarasimhan et al, 2018;Fetsch et al, 2018;Yu and Gu, 2018), we expect our tools to help gain new insights into the mechanisms of perceptual decisionmaking.…”

Primate optogenetics: Progress and prognosis

“…Vision. Optogenetic suppression was used to investigate the contribution of neural activity to visual discrimination by Afraz et al (47) and Fetsch et al (48). Both studies capitalized on the spatial clustering of neurons with similar tuning properties and extended the results of electrical microstimulation studies (49,50).…”

“…To investigate the neural basis of motion perception and decision confidence, Fetsch et al (48) inactivated regions of the middle temporal area (MT) using the red light-sensitive suppressive opsin, Jaws. Macaques were trained to report the direction of motion in random dot fields by making a saccade to a choice target or, alternatively, to a sure-bet target that delivered a guaranteed but smaller reward.…”

“…These models provide a rigorous framework for breaking a decision into simpler components, some of which may map onto neural activity in specific brain regions. Investigations of decisionmaking in monkeys are starting to employ optogenetic techniques to investigate this mapping (47,48,67), and tasks used to study decision-making in monkeys are being applied to the study of Parkinson's disease (156,157). The unification of optogenetics, modeling, and perceptual decision-making tasks may provide new insight into the cognitive deficits in Parkinson's disease.…”