Biology subjects

Corrigan, B. W.

Publications and source records attributed to Corrigan, B. W..

9 recordsLinked to original sources

bioRxiv2025

Subanesthetic Ketamine Disrupts Predictive Signaling in the Prefrontal Cortex

Corollary discharge (CD) signals allow the brain to predict and suppress the sensory consequences of its own actions, providing stability to perception and thought. Disruption of these predictive mechanisms has long been hypothesized to contribute to the disorganization of experience in schizophrenia, yet direct circuit-level evidence has been lacking. Here, we show that ketamine, a dissociative N-methyl-D-aspartate receptor (NMDAR) antagonist, at subanesthetic doses, selectively disrupts CD signaling in the lateral prefrontal cortex (LPFC)--a region thought to be the seed of mental representations and one of the most affected areas in schizophrenia. We recorded activity from 1,342 neurons in LPFC areas 8a and 9/46 of macaques performing a visuospatial working-memory task in a virtual environment, before and after subanesthetic ketamine administration. Ketamine impaired performance and increased overall firing rates but markedly suppressed saccade-related responses carrying CD signals. This led to decreased discriminability of eye movement signals. This finding links two major ideas in neuroscience research: the role of disrupted glutamate signaling and the failure of the brains predictive models. It provides evidence for how these mechanisms may interact in the prefrontal cortex to disturb the sense of reality.

neuroscience↗

bioRxiv2024

Conflict neurons in cingulate cortex of macaques

Conflict--the magnitude of co-activation of mutually incompatible response processes--was proposed to explain how cognitive control is invoked (Botvinick et al. 2001) and continues to engage debate (Becker et al. 2024). Original observations consistent with this construct emphasized the primary contribution of cingulate cortex (CC) based on human functional imaging (Botvinick et al., 1999; Carter et al., 2000) and electroencephalogram (Yeung, Botvinick, & Cohen, 2004). In countermanding tasks conflict arises through co-activation of competing GO and STOP processes (Boucher et al. 2007; Schall & Boucher 2007; Sajad et al. 2022). Single neuron activity representing conflict has been described in the supplementary motor cortex of human epilepsy patients (Fu et al., 2019; Sheth et al., 2012) and of macaque monkeys (Sajad, Errington, & Schall, 2022; Stuphorn, Taylor, & Schall, 2000) and in human cingulate cortex (Fu et al., 2019; Sheth et al., 2012) but not in monkey cingulate cortex (Ebitz & Platt, 2015; Ito, Stuphorn, Brown, & Schall, 2003; Nakamura, Roesch, & Olson, 2005). This lack of homology generated debate about the utility of macaques for investigation of cognitive control (Cole et al. 2009; Schall & Emeric 2010). With higher-resolution, less-biased samples, we re-examined the presence of a conflict signal in cingulate cortex of monkeys. Neurons modulating specifically when response conflict was maximal were found in cingulate cortex-- more commonly in the dorsal than the ventral bank. However, such neurons were much more common in supplementary motor cortex. These data confirm the presence of a conflict signal in medial frontal cortex and demonstrate that it can be found in a small fraction of neurons in cingulate cortex. Further research is needed to determine if the weak response conflict signal in cingulate cortex is sufficient or negligible.

neuroscience↗

bioRxiv2024

Spike frequency adaptation in primate lateral prefrontal cortex neurons results from interplay between intrinsic properties and circuit dynamics

Recordings of cortical neurons isolated from brain slices and dissociated from their networks, display intrinsic spike frequency adaptation (I-SFA) to a constant current input. Interestingly, extracellular recordings in behaving subjects also show extrinsic-SFA (E-SFA) in response to sustained visual stimulation. Because neurons are isolated from brain networks in slice recordings, it is challenging to infer how I-SFA contributes to E-SFA in interconnected brains during behavior. To investigate this, we recorded responses of macaque lateral prefrontal cortex neurons in vivo during a visually guided saccade task and in acute brain slices in vitro. Broad spiking (BS) putative pyramidal cells and narrow spiking (NS) putative inhibitory interneurons exhibited E-SFA in vivo. In acute brain slices, both cell types displayed I-SFA though their magnitudes differed. To investigate how in vitro I-SFA contributes to in vivo E-SFA, we developed a data-driven hybrid circuit model in which local NS neurons are driven by BS input. We observed that model NS cell responses show longer SFA than observed in vivo. Introducing inhibition of NS cells to the model circuit removed this discrepancy. Our results indicate that both I-SFA and inhibitory circuit dynamics contribute to E-SFA in LPFC neurons. They highlight the contribution of single neuron and network dependent computations to neural activity underlying behavior.

neuroscience↗

bioRxiv2024

Neural Ensembles in the Lateral Prefrontal Cortex Temporally Multiplex Task Features During Virtual Navigation

Neuronal populations can expand their information encoding capacity using mixed selective neurons. This is particularly prominent in association areas such as the Lateral Prefrontal Cortex (LPFC) that integrate information from multiple sensory systems. During naturalistic conditions where subjects have agency, it is unclear how LPFC neuronal ensembles process space and time varying information. Here we show that during a virtual navigation task that requires associative memory and decision making, individual neurons and neuronal ensembles in the LPFC time-multiplex their selectivity for different task features to fluidly encode the temporal contingencies of the task and the animals choice. Neurons in ventral regions showed more selectivity for non-spatial features, while dorsal regions showed selectivity for space and eye movements. These results demonstrate that during naturalistic tasks with fluid scenery and spatiotemporal dynamics, LPFC neurons and neuronal ensembles time-multiplex the components of their selectivity, expanding the spatiotemporal capacity of their neural codes.

neuroscience↗

bioRxiv2023

The hippocampus of the common marmoset is a GPS, but G is for gaze

The mammalian hippocampus has been compared to a Global Positioning System (GPS) that enables spatial navigation. This notion has been primarily drawn from studies conducted in nocturnal mammals, such as rats; that lack many adaptations to daylight vision compared to diurnal primates. Here we demonstrate that during foraging in a 3D maze, the common marmoset, a new world diurnal primate with foveal, stereo-color vision, predominantly uses rapid head-gaze shifts to visually explore their surroundings while remaining stationary, and then minimizes head movements to navigate towards goals. On the other hand, rats, mainly move their head at low velocities while locomoting to explore the environment using their whiskers. These differences in exploration-navigation strategies reflect the species sensory adaptations to different ecological niches. In the marmoset hippocampus CA3/CA1 regions putative pyramidal neurons show selectivity for 3D view, head direction, and less for place, but mainly mixed selectivity for combinations of these variables. Despite weak place selectivity, the spatial position of the animal in the maze can be decoded from the activity of small ensembles of mixed selective neurons. Inhibitory interneurons are tuned to 3D angular head velocity and translation speed, with most cells showing mixed selectivity for both variables. Finally, marmosets lack the rhythmic theta oscillations of local field potentials seen during locomotion in rats. Instead, they show resetting of theta oscillations triggered by head-gaze shifts that co-occurred with the activation of inhibitory interneurons, followed by various modulations in the activity of pyramidal cells. Our results show that the marmoset visual exploration/navigation strategies and the hippocampal neuronal specializations supporting them diverge from those observed in rats, reflecting the far-sensing capabilities of the marmoset visual system adapted to diurnal lifestyle.

neuroscience↗

bioRxiv2022

A method for chronic and semi-chronic microelectrode array implantation in deep brain structures using image guided neuronavigation

Precise targeting of deep brain structures in humans and large animal models has been a challenge for neuroscientists. Conventional protocols used in animal models typically require large access chambers which are prone to infection and involve assembly and implantation of complex microdrives for semi-chronic applications. Here we present a methodology for improving targeting of subcortical structures in large animals such as macaque monkeys, using image guided neuronavigation. Design of custom cranial caps allowed for incorporation of stable fiducial markers, required for increased targeting accuracy in neuronavigation procedures, resulting in an average targeting error of 1.6 mm over three implantations. Incorporation of anchor bolt chambers, commonly used in human neurosurgery, provided a minimally invasive entrance to the brain parenchyma, allowing for chronic recordings. By leveraging existing 3D printing technology, we fabricated an anchor bolt-mounted microdrive for semi-chronic applications. Our protocol leverages commercially available tools for implantation, decreases the risk of infection and complications of open craniotomies, and improves the accuracy and precision of chronic electrode implantations targeting deep brain structures in large animal models.

neuroscience↗

bioRxiv2022

Stable working memory and perceptual representations in macaque lateral prefrontal cortex during naturalistic vision in virtual environments

Primates use perceptual and mnemonic visuospatial representations to perform everyday functions. Neurons in the lateral prefrontal cortex (LPFC) have been shown to encode both of these representations during tasks where eye movements are strictly controlled and visual stimuli are reduced in complexity. This raises the question of whether perceptual and mnemonic representations encoded by LPFC neurons remain robust during naturalistic vision -- in the presence of a rich visual scenery and during eye movements. Here we investigate this issue by training macaque monkeys to perform working memory and perception tasks in a visually complex virtual environment that requires navigation using a joystick and allows for free visual exploration of the scene. We recorded the activity of 3950 neurons in the LPFC (areas 8a and 9/46) of two rhesus macaques using multi-electrode arrays, and measured eye movements using video tracking. We found that navigation trajectories to target locations and eye movement behavior differed between the perception and working memory tasks suggesting that animals employed different behavioral strategies. Single neurons were tuned to target location during cue encoding and working memory delay and neural ensemble activity was predictive of the animals behavior. Neural decoding of target location was stable throughout the working memory delay epoch. However, neural representations of similar target locations differed between the working memory and perception tasks. These findings indicate that during naturalistic vision, LPFC neurons maintain robust and distinct neural codes for mnemonic and perceptual visuospatial representations. Significance StatementWe show that LPFC neurons encode working memory and perceptual representations during a naturalistic task set in a virtual environment. We show that despite eye movement and complex visual input, neurons maintain robust working memory representations of space which are distinct from neuronal representations for perception. We further provide novel insight on the use of virtual environments to construct behavioral tasks for electrophysiological experiments.

neuroscience↗

bioRxiv2021

Different neural codes serve long and short-term memory functions in primate Hippocampus and Lateral Prefrontal Cortex during virtual navigation

The hippocampus (HPC) and the lateral prefrontal cortex (LPFC) are two cortical areas of the primate brain deemed essential to cognition. Here we hypothesize that the codes mediating neuronal communication in HPC and LPFC microcircuits have distinctively evolved to serve plasticity and memory function at different spatiotemporal scales. We used a virtual reality task in which animals navigated through a maze using a joystick and selected one of two targets in the arms of the maze according to a learned context-color rule. We found that neurons and neuronal populations in both regions encode similar information about the task. Moreover, we demonstrate that many HPC neurons concentrate spikes into bursts, whereas most layer II/III LPFC neurons sparsely distribute spikes over time. As the animals learned the task HPC neurons, but not LPFC neurons, increased their burst rate as a function of performance. When integrating spike rates over short intervals, HPC neuronal ensembles reached maximum decoded information with fewer neurons than LPFC ensembles. Our results show that during associative learning HPC principal cells concentrate spikes in bursts enabling temporal summation and fast synaptic plasticity in small populations of neurons and ultimately facilitating rapid encoding of associative memories. On the other hand, layers II/III LPFC pyramidal cells fire spikes more sparsely distributed in time and over a larger number of neurons. The latter would facilitate broadcasting of signals loaded in short term memory across neuronal populations without necessarily triggering fast synaptic plasticity.

neuroscience↗

bioRxiv2018

Flexible coding of memory and space in the primate hippocampus during virtual navigation

Hippocampal maps of space change across tasks. The mechanisms of this effect remain unclear. To examine this, we recorded activity of hippocampal neurons in monkeys navigating the same virtual maze during two different tasks: a foraging task requiring only cue guided navigation, and a memory task also requiring context-object association. Within each task, individual neurons had spatially-selective response fields, enabling a linear classifier to decode position in the virtual environment in each task. However, the population code did not generalize across tasks. This was due to sensory and mnemonic coding of non-spatial features and their associations by single neurons during each period of the associative memory task. Thus, sensory and mnemonic representations of non-spatial features shape maps of space in the primate hippocampus during virtual navigation. This may reflect a fundamental role of the hippocampus in compressing information from a variety of sources for efficient memory storage.

neuroscience↗