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Cavanagh, J. F.

Publications and source records attributed to Cavanagh, J. F..

9 recordsLinked to original sources

Spatiotemporal Decoding of Explore-Exploit Decisions in the Human Brain

Adaptive behavior requires flexibly shifting between exploiting familiar rewards and exploring novel opportunities. These explore-exploit decisions are implemented via a distributed brain network--anchored in frontopolar cortex (FPC) and ventromedial prefrontal cortex (vmPFC)--that computes the total value of a given choice by weighting the immediate value of familiar options against the latent future value of exploration. Capturing the precise temporal dynamics of these neural computations across spatially distributed cortical networks is critical to resolving how the brain manages this tradeoff. Here, we combined magnetoencephalography (MEG) with partially observable Markov decision process (POMDP) modeling during a reinforcement learning task. By decoding POMDP-derived choice policies in MEG source space, we mapped the precise spatiotemporal emergence of explore-exploit decisions across the cortex. We demonstrate that explore-exploit policy implementation unfolds via a hierarchical functional dissociation across the rostral prefrontal cortex. During decision formation, the lateral FPC initiates the strategic shift toward exploration hundreds of milliseconds before choice execution. Conversely, vmPFC and orbitofrontal cortex (OFC) do not exhibit early significant divergence from the baseline exploitative trace on exploration trials, displaying only a delayed, transient peak prior to choice execution. Following feedback, the vmPFC and OFC transition to a sustained representation of the choices empirical value to update reward expectancies and guide future actions. Mapping reinforcement learning variables onto millisecond-resolved neural data reveals how the human brain resolves the explore-exploit dilemma: through early strategic initiation of exploration in the FPC, a delayed exploratory shift in vmPFC and OFC, and sustained outcome evaluation to optimize future actions.

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Distinct basal ganglia decision dynamics under conflict and uncertainty

The basal ganglia (BG) play a key role in decision-making, preventing impulsive actions in some contexts while facilitating fast adaptations in others. The specific contributions of different BG structures to this nuanced behavior remain unclear, particularly under varying situations of noisy and conflicting information that necessitate ongoing adjustments in the balance between speed and accuracy. Theoretical accounts suggest that dynamic regulation of the amount of evidence required to commit to a decision (a dynamic "decision boundary") may be necessary to meet these competing demands. Through the application of novel computational modeling tools in tandem with direct neural recordings from human BG areas, we find that neural dynamics in the theta band manifest as variations in a collapsing decision boundary as a function of conflict and uncertainty. We collected intracranial recordings from patients diagnosed with either Parkinsons disease (n=14) or dystonia (n=3) in the subthalamic nucleus (STN), globus pallidus internus (GPi), and externus (GPe) during their performance of a novel perceptual discrimination task in which we independently manipulated uncertainty and conflict. To formally characterize whether these task and neural components influenced decision dynamics, we leveraged modified diffusion decision models (DDMs). Behavioral choices and response time distributions were best characterized by a modified DDM in which the decision boundary collapsed over time, but where the onset and shape of this collapse varied with conflict. Moreover, theta dynamics in BG structures predicted the onset and shape of this collapse but differentially across task conditions. In STN, theta activity was related to a prolonged decision boundary (indexed by slower collapse and therefore more deliberate choices) during high-conflict situations. Conversely, rapid declines in GPe theta during low conflict conditions were related to rapidly collapsing boundaries and expedited choices, with additional complementary decision bound adjustments during high uncertainty situations. Finally, GPi theta effects were uniform across conditions, with increases in theta prolonging the collapse of decision bounds. Together, these findings provide a nuanced understanding of how our brain thwarts impulsive actions while nonetheless enabling behavioral adaptation amidst noisy and conflicting information.

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Hypoactivation of ventromedial frontal cortex in major depressive disorder: an MEG study of the Reward Positivity

BackgroundThe Reward Positivity (RewP) is sensitive and specific electrophysiological marker of reward receipt. These characteristics make it a compelling candidate marker of dysfunctional reward processing in major depressive disorder. We previously proposed that the RewP is a nexus of multiple aspects of reward variance, and that a diminished RewP in depression might only reflect a deficit in some of this variance. Specifically, we predicted a diminished ventromedial contribution in depression in the context of maintained reward learning. MethodsHere we collected magnetoencephalographic (MEG) recordings of reward receipt in 43 individuals with major depressive disorder (MDD group) and 38 healthy controls (CTL group). MEG allows effective source estimation due to the absence of volume conduction that compromises electroencephalographic recordings. ResultsThe MEG RewP analogue was generated by a broad set of cortical areas, yet only right ventromedial and right ventral temporal areas were diminished in MDD. These areas correlated with a principal component of anhedonia derived from multiple questionnaires. Compellingly, BA25 was the frontal region with the largest representation in both of these effects. ConclusionsThese findings not only advance our understanding underlying the computation of the RewP, but they also dovetail with convergent findings from other types of functional source imaging in depression, as well as from deep brain stimulation treatments. Together, these discoveries suggest that the RewP may be a valuable marker for objective assessment of reward affect and its disruption in major depression.

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Medication-Invariant Resting Aperiodic and Periodic Neural Activity in Parkinson's Disease

Parkinsons Disease (PD) has been associated with greater total power in canonical frequency bands (i.e., alpha, beta) of the resting electroencephalogram (EEG). However, PD has also been associated with a reduction in the proportion of total power across all frequency bands. This discrepancy may be explained by aperiodic activity (exponent and offset) present across all frequency bands. Here, we examined differences in the eyes-open and eyes-closed resting EEG of PD participants (N = 26) on and off medication, and age-matched controls (CTL; N = 26). We extracted power from canonical frequency bands using traditional methods (total alpha and beta power) and extracted separate parameters for periodic (parameterized alpha and beta power) and aperiodic activity (exponent and offset). Cluster-based permutation tests over spatial and frequency dimensions indicated that total alpha and beta power, and aperiodic exponent and offset were greater in PD participants, independent of medication status. After removing the exponent and offset, greater alpha power in PD (vs. CTL) was only present in eyes-open recordings and no reliable differences in beta power were observed. Differences between PD and CTLs in the resting EEG are likely driven by aperiodic activity, suggestive of greater relative inhibitory neural activity and greater neuronal spiking. Our findings suggest that resting EEG activity in PD is characterized by medication-invariant differences in aperiodic activity which is independent of the increase in alpha power with EO. This highlights the importance of considering aperiodic activity contributions to the neural correlates of brain disorders.

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Causal effects of prefrontal transcranial magnetic stimulation on dopamine-mediated reinforcement learning in healthy adults

Background10-Hz repetitive transcranial magnetic stimulation (rTMS) to the left dorsal lateral prefrontal cortex (DLPFC) has been shown to increase dopaminergic activity in the dorsal striatum, a region strongly implicated in reinforcement learning. However, the behavioural influence of this effect remains largely unknown. ObjectiveHere, we tested the causal effects of rTMS on behavioral and computational characteristics of reinforcement learning. Methods40 healthy individuals were randomized into Active and Sham rTMS groups. Each participant underwent one 10-Hz rTMS session (1500 pulses) in which stimulation was applied over the left DLPFC using a robotic arm. Participants then completed a reinforcement learning task sensitive to striatal dopamine functioning. Participants trial-to-trial training choices were modelled using a reinforcement learning model (Q-learning) that calculates separate learning rates associated with positive and negative reward prediction errors. ResultsSubjects receiving Active TMS exhibited an increased reward rate (number of correct responses per second of task activity) compared to the Sham rTMS group. Computationally, the Active rTMS group displayed a higher learning rate for correct trials (G) compared to incorrect trials (L). Finally, when tested with novel pairs of stimuli, the Active group displayed extremely fast reaction times, and a trend towards a higher reward rate. ConclusionsThe present study provided specific behavioral and computational accounts of altered striatal-mediated reinforcement learning induced by a proposed increase of dopamine activity by 10-Hz rTMS to the left DLPFC. Together, these findings bolster the use of TMS to target neurocognitive disturbances attributed to the dysregulation of dopaminergic-striatal circuits.

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Amphetamine alters the Reward Positivity in humans and mice

The bench-to-bedside development of pro-cognitive therapeutics for psychiatric disorders has been mired by translational failures. This is in part due to the absence of pharmacologically-sensitive cognitive biomarkers common to humans and rodents. Here, we describe a cross-species translational marker of reward processing that is sensitive to the dopamine agonist, d-amphetamine. Motivated by human electroencephalographic (EEG) findings, we recently reported that frontal midline delta-band power is also an electrophysiological biomarker of reward surprise in mice. In the current series of experiments, we determined the impact of parametric doses of d-amphetamine on this reward-related EEG response from humans (n=23) and mice (n=28) performing a probabilistic learning task. In humans, d-amphetamine (placebo, 10 mg, 20 mg) boosted the Reward Positivity event-related potential (ERP) component as well as the spectral delta-band representations of this signal. In mice, d-amphetamine (placebo, 0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg) boosted both reward and punishment ERP features, yet there was no modulation of spectral activities. In sum, the present results confirm the role of dopamine in the generation of the Reward Positivity in humans, and paves the way towards a pharmacologically valid biomarker of reward sensitivity across species.

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Timing variability and midfrontal ~4 Hz rhythms correlate with cognition in Parkinson's disease

Patients with Parkinsons disease (PD) can have significant cognitive dysfunction; however, the mechanisms for these cognitive symptoms are unknown. Here, we used scalp electroencephalography (EEG) to investigate the cortical basis for PD-related cognitive impairments during interval timing, which requires participants to estimate temporal intervals of several seconds. Time estimation is an ideal task demand for investigating cognition in PD because it is simple, requires medial frontal cortical areas, and recruits basic executive processes such as working memory and attention. However, interval timing has never been systematically studied in PD patients with cognitive impairments. We report three main findings. First, 71 PD patients had increased temporal variability compared to 37 demographically-matched controls, and this variability correlated with cognitive dysfunction as measured by the Montreal Cognitive Assessment (MOCA). Second, PD patients had attenuated ~4 Hz EEG oscillatory activity at midfrontal electrodes in response to the interval-onset cue, which was also predictive of MOCA. Finally, trial-by-trial linear mixed-effects modeling demonstrated that cue-triggered ~4 Hz power predicted subsequent temporal estimates as a function of PD and MOCA. Our data suggest that impaired cue-evoked midfrontal ~4 Hz activity predicts increased timing variability that is indicative of cognitive dysfunction in PD. These findings link PD-related cognitive dysfunction with cortical mechanisms of cognitive control, which could advance novel biomarkers and neuromodulation for PD.

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Neural signatures of arbitration between Pavlovian and instrumental action selection

Pavlovian associations drive approach towards reward-predictive cues, and avoidance of punishment-predictive cues. These associations "misbehave" when they conflict with correct instrumental behavior. This raises the question of how Pavlovian and instrumental influences on behavior are arbitrated. We test a computational theory according to which Pavlovian influence will be stronger when inferred controllability of outcomes is low. Using a model-based analysis of a Go/NoGo task with human subjects, we show that theta-band oscillatory power in frontal cortex tracks inferred controllability, and that these inferences predict Pavlovian action biases. Functional MRI data revealed an inferior frontal gyrus correlate of action probability and a ventromedial prefrontal correlate of outcome valence, both of which were modulated by inferred controllability.

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Frontal theta and beta oscillations during lower-limb movement in Parkinson’s disease

BackgroundMotor and cognitive dysfunction has been linked in patients with Parkinsons disease (PD). EEG theta and beta rhythms are reliably associated with cognitive and motor functions, respectively. We tested the hypothesis that PD patients with lower-limb abnormalities would exhibit abnormal beta and theta rhythms in the mid-frontal region during action initiation.\n\nMethodsWe recruited thirty-nine subjects, including PD patients with FOG (PDFOG+; n=13) and without FOG (PDFOG-; n=13), and demographically-matched healthy subjects (n=13). Scalp electroencephalogram (EEG) signals were collected during a lower-limb pedaling motor task, which required intentional initiation and stopping of a motor movement.\n\nResultsFOG scores were correlated with disease severity and cognition. PDFOG+ patients pedaled with reduced speed and decreased acceleration compared to PDFOG- patients and to controls. PDFOG+ patients exhibited attenuated theta-band (4-8 Hz) power and increased beta-band (13-30 Hz) power at mid-frontal electrode Cz during pedaling. Frontal theta- and beta-band oscillations also correlated with lower-limb movement in PD patients.\n\nConclusionsFrontal theta and beta oscillations are predictors of lower-limb motor symptoms in PD. These data provide insight into the mechanism of lower-limb dysfunction in PD, and could be used to design neuromodulation for PD-related lower-limb abnormalities.

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