Biology subjects

Langdon, A.

Publications and source records attributed to Langdon, A..

4 recordsLinked to original sources

bioRxiv2024

Chronic Ethanol Exposure Produces Persistent Impairment in Cognitive Flexibility and Decision Signals in the Striatum

Lack of cognitive flexibility is a hallmark of substance use disorders and has been associated with drug-induced synaptic plasticity in the dorsomedial striatum (DMS). Yet the possible impact of altered plasticity on real-time striatal neural dynamics during decision-making is unclear. Here, we identified persistent impairments induced by chronic ethanol (EtOH) exposure on cognitive flexibility and striatal decision signals. After a substantial withdrawal period from prior EtOH vapor exposure, male, but not female, rats exhibited reduced adaptability and exploratory behavior during a dynamic decision-making task. Reinforcement learning models showed that prior EtOH exposure enhanced learning from rewards over omissions. Notably, neural signals in the DMS related to the decision outcome were enhanced, while those related to choice and choice-outcome conjunction were reduced, in EtOH-treated rats compared to the controls. These findings highlight the profound impact of chronic EtOH exposure on adaptive decision-making, pinpointing specific changes in striatal representations of actions and outcomes as underlying mechanisms for cognitive deficits.

neuroscience↗

bioRxiv2023

Expectancy-related changes in firing of dopamine neurons depend on hippocampus

The orbitofrontal cortex (OFC) and hippocampus (HC) are both implicated in forming the cognitive or task maps that support flexible behavior. Previously, we used the dopamine neurons as a sensor or tool to measure the functional effects of OFC lesions (Takahashi et al., 2011). We recorded midbrain dopamine neurons as rats performed an odor-based choice task, in which errors in the prediction of reward were induced by manipulating the number or timing of the expected rewards across blocks of trials. We found that OFC lesions ipsilateral to the recording electrodes caused prediction errors to be degraded consistent with a loss in the resolution of the task states, particularly under conditions where hidden information was critical to sharpening the predictions. Here we have repeated this experiment, along with computational modeling of the results, in rats with ipsilateral HC lesions. The results show HC also shapes the map of our task, however unlike OFC, which provides information local to the trial, the HC appears to be necessary for estimating the upper-level hidden states based on the information that is discontinuous or separated by longer timescales. The results contrast the respective roles of the OFC and HC in cognitive mapping and add to evidence that the dopamine neurons access a rich information set from distributed regions regarding the predictive structure of the environment, potentially enabling this powerful teaching signal to support complex learning and behavior.

neuroscience↗

bioRxiv2018

Regional Striatal Cholinergic Involvement in Human Behavioural Flexibility

Animal studies have shown that the striatal cholinergic system plays a role in behavioural flexibility but, until recently, this system could not be studied in humans due to a lack of appropriate non-invasive techniques. Using proton magnetic resonance spectroscopy (1H-MRS) we recently showed that the concentration of dorsal striatal choline (an acetylcholine precursor) changes during reversal learning (a measure of behavioural flexibility) in humans. The aim of the present study was to examine whether regional average striatal choline was associated with reversal learning. We measured choline at rest in both the dorsal and ventral striatum using 1H-MRS and examined its relationship with performance on a probabilistic learning task with a reversal component. Task performance was described using a simple reinforcement learning model that dissociates the contributions of positive and negative prediction errors to learning. Average levels of choline in the dorsal striatum were associated with performance during reversal, but not during initial learning. Specifically, lower levels of choline in the dorsal striatum were associated with a lower number of perseverative trials. Moreover, choline levels explained inter-individual variance in perseveration over and above that explained by learning from negative prediction errors. These findings suggest that the dorsal striatal cholinergic system plays an important role in behavioural flexibility, in line with evidence from the animal literature and our previous work in humans. Additionally, this work provides further support for the idea of measuring choline with 1H-MRS as a non-invasive way of studying human cholinergic neurochemistry.\n\nSIGNIFICANCE STATEMENTBehavioural flexibility is a crucial component of adaptation and survival, as well as everyday living. Evidence from the animal literature shows the striatal cholinergic system is fundamental to reversal learning, a key paradigm for studying behavioural flexibility. However, this system remains understudied in humans, largely due to a lack of non-invasive techniques. Using proton magnetic resonance spectroscopy (1H-MRS), we showed that choline levels at rest in the dorsal striatum are associated with individual differences in performance specifically during reversal learning. These novel findings help to bridge the gap between animal studies of the striatal cholinergic system and human studies of basal ganglia function, by demonstrating the importance of cholinergic function in the dorsal striatum in human behavioural flexibility. Importantly, the methods described here can not only be applied to furthering our understanding of healthy human neurochemistry, but can also be applied to extending our understanding of cholinergic disorders.

neuroscience↗

bioRxiv2018

Thalamostriatal Interactions in Human Reversal Learning

Cognitive flexibility is crucial for adaptation and is disrupted in neuropsychiatric disorders and psychopathology. Human studies of flexibility using reversal learning tasks typically contrast error trials before and after reversal, which provides little information about the mechanisms that support learning and expressing a new response. However, animal studies suggest a specific role in this latter process for the connections between the dorsal striatum and the centromedian parafascicular (CM-Pf) thalamus, a system which may recruit the striatal cholinergic interneurons, but which is not well understood in humans. This study investigated the role of this system in human probabilistic reversal learning, specifically with respect to learning a new response strategy, contrasting its function to that of the better understood orbitoftontal-striatal systems. Using psychophysiological interaction (PPI) analysis of functional magnetic resonance imaging (fMRI) data we show that connectivity between the striatum and both the lateral orbitofrontal cortex (lOFC) and CM-Pf pathways increased during reversal, but not initial learning. However, while the strength of lOFC-striatal connectivity was associated with the speed of the reversal, the strength of CM-Pf-striatal connectivity was associated specifically with the quality of the reversal (reduced regressive errors). These findings expand our understanding of flexibility mechanisms in the human brain, bridging the gap with animal studies of this system.

neuroscience↗