Lateral Prefrontal Cortex
lateral prefrontal cortex
Distinct contributions of different anterior frontal regions to rule-guided decision-making in primates: complementary evidence from lesions, electrophysiology, and neurostimulation
Different prefrontal areas contribute in distinctly different ways to rule-guided behaviour in the context of a Wisconsin Card Sorting Test (WCST) analog for macaques. For example, causal evidence from circumscribed lesions in NHPs reveals that dorsolateral prefrontal cortex (dlPFC) is necessary to maintain a reinforced abstract rule in working memory, orbitofrontal cortex (OFC) is needed to rapidly update representations of rule value, and the anterior cingulate cortex (ACC) plays a key role in cognitive control and integrating information for correct and incorrect trials over recent outcomes. Moreover, recent lesion studies of frontopolar cortex (FPC) suggest it contributes to representing the relative value of unchosen alternatives, including rules. Yet we do not understand how these functional specializations relate to intrinsic neuronal activities nor the extent to which these neuronal activities differ between different prefrontal regions. After reviewing the aforementioned causal evidence I will present our new data from studies using multi-area multi-electrode recording techniques in NHPs to simultaneously record from four different prefrontal regions implicated in rule-guided behaviour. Multi-electrode micro-arrays (‘Utah arrays’) were chronically implanted in dlPFC, vlPFC, OFC, and FPC of two macaques, allowing us to simultaneously record single and multiunit activity, and local field potential (LFP), from all regions while the monkey performs the WCST analog. Rule-related neuronal activity was widespread in all areas recorded but it differed in degree and in timing between different areas. I will also present preliminary results from decoding analyses applied to rule-related neuronal activities both from individual clusters and also from population measures. These results confirm and help quantify dynamic task-related activities that differ between prefrontal regions. We also found task-related modulation of LFPs within beta and gamma bands in FPC. By combining this correlational recording methods with trial-specific causal interventions (electrical microstimulation) to FPC we could significantly enhance and impair animals performance in distinct task epochs in functionally relevant ways, further consistent with an emerging picture of regional functional specialization within a distributed framework of interacting and interconnected cortical regions.
Reasoning Ability: Neural Mechanisms, Development, and Plasticity
Relational thinking, or the process of identifying and integrating relations between mental representations, is regularly invoked during reasoning. This mental capacity enables us to draw higher-order abstractions and generalize across situations and contexts, and we have argued that it should be included in the pantheon of executive functions. In this talk, I will briefly review our lab's work characterizing the roles of lateral prefrontal and parietal regions in relational thinking. I will then discuss structural and functional predictors of individual differences and developmental changes in reasoning.
Dissecting the neural circuits underlying prefrontal regulation of reward and threat responsivity in a primate
Gaining insight into the overlapping neural circuits that regulate positive and negative emotion is an important step towards understanding the heterogeneity in the aetiology of anxiety and depression and developing new treatment targets. Determining the core contributions of the functionally heterogenous prefrontal cortex to these circuits is especially illuminating given its marked dysregulation in affective disorders. This presentation will review a series of studies in a new world monkey, the common marmoset, employing pathway-specific chemogenetics, neuroimaging, neuropharmacology and behavioural and cardiovascular analysis to dissect out prefrontal involvement in the regulation of both positive and negative emotion. Highlights will include the profound shift of sensitivity away from reward and towards threat induced by localised activations within distinct regions of vmPFC, namely areas 25 and 14 as well as the opposing contributions of this region, compared to orbitofrontal and dorsolateral prefrontal cortex, in the overall responsivity to threat. Ongoing follow-up studies are identifying the distinct downstream pathways that mediate some of these effects as well as their differential sensitivity to rapidly acting anti-depressants.
The Challenge and Opportunities of Mapping Cortical Layer Activity and Connectivity with fMRI
In this talk I outline the technical challenges and current solutions to layer fMRI. Specifically, I describe our acquisition strategies for maximizing resolution, spatial coverage, time efficiency as well as, perhaps most importantly, vascular specificity. Novel applications from our group, including mapping feedforward and feedback connections to M1 during task and sensory input modulation and S1 during a sensory prediction task are be shown. Layer specific activity in dorsal lateral prefrontal cortex during a working memory task is also demonstrated. Additionally, I’ll show preliminary work on mapping whole brain layer-specific resting state connectivity and hierarchy.
Higher cognitive resources for efficient learning
A central issue in reinforcement learning (RL) is the ‘curse-of-dimensionality’, arising when the degrees-of-freedom are much larger than the number of training samples. In such circumstances, the learning process becomes too slow to be plausible. In the brain, higher cognitive functions (such as abstraction or metacognition) may be part of the solution by generating low dimensional representations on which RL can operate. In this talk I will discuss a series of studies in which we used functional magnetic resonance imaging (fMRI) and computational modeling to investigate the neuro-computational basis of efficient RL. We found that people can learn remarkably complex task structures non-consciously, but also that - intriguingly - metacognition appears tightly coupled to this learning ability. Furthermore, when people use an explicit (conscious) policy to select relevant information, learning is accelerated by abstractions. At the neural level, prefrontal cortex subregions are differentially involved in separate aspects of learning: dorsolateral prefrontal cortex pairs with metacognitive processes, while ventromedial prefrontal cortex with valuation and abstraction. I will discuss the implications of these findings, in particular new questions on the function of metacognition in adaptive behavior and the link with abstraction.
Unique Molecular Regulation of Prefrontal Cortex Confers Vulnerability to Cognitive Disorders
The Arnsten lab studies molecular influences on the higher cognitive circuits of the dorsolateral prefrontal cortex (dlPFC), in order to understand mechanisms affecting working memory at the cellular and behavioral levels, with the overarching aim of identifying the actions that render the dlPFC so vulnerable in cognitive disorders. Her lab has shown that the dlPFC has unique neurotransmission and neuromodulation compared to the classic actions found in the primary visual cortex, including mechanisms to rapidly weaken PFC connections during uncontrollable stress. Reduced regulation of these stress pathways due to genetic or environmental insults contributes to dlPFC dysfunction in cognitive disorders, including calcium dysregulation and tau phosphorylation in the aging association cortex. Understanding these unique mechanisms has led to the development of a new treatment, IntunivTM, for a variety of PFC disorders.
Mechanisms of Perceptual Learning
Perceptual learning (PL) is defined as long-term performance improvement on a perceptual task as a result of perceptual experience (Sasaki, Nanez& Watanabe, 2011, Nat Rev Neurosci, 2011). We first found that PL occurs for task-irrelevant and subthreshold features and that pairing task-irrelevant features with rewards is the key to form task-irrelevant PL (TIPL) (Watanabe, Nanez & Sasaki, Nature, 2001; Watanabe et al, 2002, Nature Neuroscience; Seitz & Watanabe, Nature, 2003; Seitz, Kim & Watanabe, 2009, Neuron; Shibata et al, 2011, Science). These results suggest that PL occurs as a result of interactions between reinforcement and bottom-up stimulus signals (Seitz & Watanabe, 2005, TICS). On the other hand, fMRI study results indicate that lateral prefrontal cortex fails to detect and thus to suppress subthreshold task-irrelevant signals. This leads to the paradoxical effect that a signal that is below, but close to, one’s discrimination threshold ends up being stronger than suprathreshold signals (Tsushima, Sasaki & Watanabe, 2006, Science). We confirmed this mechanism with the following results: Task-irrelevant learning occurs only when a presented feature is under and close to the threshold with younger individuals (Tsushima et al, 2009, Current Biol), whereas with older individuals who tend to have less inhibitory control task-irrelevant learning occurs with a feature whose signal is much greater than the threshold (Chang et al, 2014, Current Biol). From all of these results, we conclude that attention and reward play important but different roles in PL. I will further discuss different stages and phases in mechanisms of PL (Seitz et al, 2005, PNAS; Yotsumoto, Watanabe & Sasaki, Neuron, 2008; Yotsumoto et al, Curr Biol, 2009; Watanabe & Sasaki, 2015, Ann Rev Psychol; Shibata et al, 2017, Nat Neurosci; Tamaki et al, 2020, Nat Neurosci).
Dorsolateral prefrontal cortex is a key cortical locus for perceptual decisions
COSYNE 2023
Connectional subdivisions reflect neuronal features of the various sectors of the macaque ventrolateral prefrontal cortex
FENS Forum 2024
Dorsolateral prefrontal cortex neural modulation during heuristic behavior in a two-level decision-making task in macaque monkeys
FENS Forum 2024
Left dorsolateral prefrontal cortex to primary motor cortex interaction was inhibited in impulsive decision-making task
FENS Forum 2024