Frontal cortex

When making decisions, animals can employ many strategies, from relying on environmental stimuli to relying on internal biases. The roles of cortical regions in shaping these decision-making strategies remain unclear, often because we lack direct access to these internal variables. Here, we investigated how optogenetic inactivation of 29 motor, sensory, or association cortical regions affects decision-making strategies in 20 mice performing a virtual T-maze task in which they were rewarded for choosing the side with more visual cues. To determine mice’s underlying strategies on any trial, we f

…Before volitional movement begins, frontal cortex and striatum exhibit ramping spiking activity, with variable ramp slopes anticipating movement onsets. This activity in the cortico-basal ganglia loop may function as an adjustable ‘timer’, triggering actions at the desired timing. However, because the frontal cortex and striatum share similar ramping dynamics and are both necessary for timing behaviors, distinguishing their individual roles in this timer function remains challenging. To address this fundamental gap, we introduced two-re

At the core of intelligence is the capacity to solve new problems. To do so, the brain must generate novel thoughts and behaviors in a goal-directed manner. This creative capacity has been hypothesized to depend on cognitive operations resembling symbolic grammars, generative models with discrete atomic objects (i.e., symbols) that use rule-based operations to generate newly composed representations. Whether and how symbolic grammars are implemented in neural substrates remains unknown. Here we develop an interdisciplinary approach to study the neural implementation of a grammar for action, ce

Psychosis is a debilitating trans-diagnostic syndrome characterized by hallucinations and delusions (Rehm and Shield 2019). The thalamus and its cortical connections play a crucial role in the pathophysiology of psychosis (Onofrj et al. 2023; Moustafa et al. 2017). However, despite often referred to as one structure, the thalamus is composed of separate nuclei with distinct cortical connections (Sherman and Guillery 2006). Recent investigations revealed lower volumes of only the medial thalamic subnuclei in first-episode psychosis patients (Thalhammer et al., 2023, in revision). Correspondingl

…Further study in perirhinal cortex (PRh), area V2 of visu

The frontal cortex plays critical roles in learning and decision-making, particularly in representing reward-related variables such as reward magnitude and probability. Previous studies have identified frontal neural representations of these variables in expertly trained animals. However, it remains unknown how these representations emerge during learning from naive to expert. To address this gap, we use 2-photon microscopy to longitudinally record the activity of the same population of neurons in the dorsomedial frontal cortex. We record from head-fixed mice learning to perform Pavlovian or o

…wave PBM with an 810 nm wavelength on frontal cortex of healthy rats over five consecutive days (46.50J/cm2 for 12minutes in three cycles of 4 minutes). The study focuses on spatial reference memory assessed in the Morris Water

Brain aging is a relative process characterized by a progressive decline in homeostasis, stress responses and cognitive functions. At cellular level, it is associated with molecular markers such as telomere length and DNA methylation clocks, which are believed to capture different aspects of relative aging. Additionally, changes in histone modifications and gene transcription also occur. However, a complete description of epigenetic changes in middle- to old-aged brains is still missing. Here, we provide a comprehensive characterization of age-associated DNA methylation changes in the healthy

…The olfactory bulb and neocortex receive cholinergic basal forebrain inputs which degenerate in AD patients. Nicotinic acetylcholine receptors (nAChRs) in the brain play a crucial role in vasodilation in the neocortex induced by basal forebrain cholinergic activation or nicotine injection. Information about the sense of smell is conveyed by the olfactory nerve, or by the intranasal trigeminal nerve when irritating odors. We recently reported that nicotine potentiates the olfactory bulb vasodilation induced by olfactory nerv

…indicates that circuits in the frontal cortex may carry out these computations but the role of NMDAR has not been systematically tested. We developed an auditory two-alternative delayed-choice (2ADC) task for head-fixed mice

Neural oscillations play a crucial role in various cognitive processes within the mammalian brain. Beyond the spectral properties typically reported in the literature, the waveform shape of oscillatory activity offers valuable insights into local physiology, and is related to the underlying cortical circuitry and to dynamically changing or aberrant cortical states. Notwithstanding the importance of oscillatory waveform shape to gain insights into cortical physiology, how the waveform shape of ongoing oscillations differs across distant yet functionally and anatomically connected cortical areas

…activation and plasticity in the Frontal Cortex (FC). Perineuronal nets (PNNs), which enwrap the cell-body and proximal dendrites of neurons, have been proposed as a candidate mechanism for modulating neuroplasticity. We investigated the changes in activation (cFos expression) and in plasticity (PNN expression) in different regions of the FC through immunolabeling and confocal microscopy in rats selected as high or

…network into two parts, representing frontal and posterior cortices, to cru

Interactions between frontal cortex and hippocampus (HPC) play a key role in decision-making behaviors. Here, we test how these brain areas coordinate their representations of behavioral and cognitive variables in a task that requires both. We use a virtual reality task in which mice navigate in a T-maze and accumulate transiently visible and stochastic left/right cues to infer the correct reward location. Neural data is recorded acutely with up to 10 Neuropixel shanks simultaneously in bilateral HPC and medial prefrontal cortex (mPFC). To compare neural activity patterns, we analyze this data

Many decisions under uncertainty entail dynamic belief updating: multiple pieces of evidence informing about the state of the environment are accumulated across time to infer the environmental state, and choose a corresponding action. Traditionally, this process has been conceptualized as a linear and perfect (i.e., without loss) integration of sensory information along purely feedforward sensory-motor pathways. Yet, natural environments can undergo hidden changes in their state, which requires a non-linear accumulation of decision evidence that strikes a tradeoff between stability and flexibi

…Modularity and robustness of frontal cortex networks. Cell, 184(14):3717-3730.

Behavior-related neural dynamics in the frontal cortex is an emergent property of network connectivity. The network structure at the level of individual neurons, and its relationship to neural coding are largely unknown. We developed an optical method for rapid (500k pairwise connections / 30 minutes) mapping of effective connectivity in the neocortex in vivo. To this end, we combined 2-photon optogenetic stimulation of individual excitatory neurons and measurement of responses in non-stimulated neurons (‘effective connection’) using 2-photon volumetric calcium imaging. We applied this method

Interactions across the frontal cortex are critical for cognition. Animal studies suggest a role for mediodorsal thalamus (MD) in these interactions, but the computations performed and direct relevance to human reasoning are unclear. Here, inspired by animal work, we build a neural model to derive computational insights and find consistent evidence in fMRI data of humans performing the same probabilistic reversal learning task. We used a reservoir recurrent neural network as a model of the dorso-lateral prefrontal cortex (dlPFC) and found that adding an MD layer with multiplicative inputs to d

…precise and adaptive mechanism in the frontal cortex of non-human primates consistent with predictive processing of temporal events. We found that the speed of neural dynamics is precisely adjusted according to the average time of an expected stimulus. This speed adjustment, in turn, enables neurons to encode stimuli in terms of deviations from expectation. Th

…the brain, with an emphasis on frontal cortex. The results are not what we thought based on textbook notions of how the brain works. This talk is based on work led by Nick Steinmetz, Peter Zatka-Haas, Armin Lak, and Pip Coen, in the laboratory I s

According to the theory of predictive processing, expectations modulate neural activity so as to optimize the processing of sensory inputs expected in the current environment. While there is accumulating evidence that the brain indeed operates under this principle, most of the attention has been placed on mechanisms that rely on static coding properties of neurons. The potential contribution of dynamical features, such as those reflected in the evolution of neural population dynamics, has thus far been overlooked. In this talk, I will present evidence for a novel mechanism for predictive proce