It takes effort and time to tame one's impulses. Although medial prefrontal cortex (mPFC) is broadly implicated in effortful control over behavior, the subthalamic nucleus (STN) is specifically thought to contribute by acting as a brake on cortico-striatal function during decision conflict, buying time until the right decision can be made. Using the drift diffusion model of decision making, we found that trial-to-trial increases in mPFC activity (EEG theta power, 4–8 Hz) were related to an increased threshold for evidence accumulation (decision threshold) as a function of conflict. Deep brain stimulation of the STN in individuals with Parkinson's disease reversed this relationship, resulting in impulsive choice. In addition, intracranial recordings of the STN area revealed increased activity (2.5–5 Hz) during these same high-conflict decisions. Activity in these slow frequency bands may reflect a neural substrate for cortico–basal ganglia communication regulating decision processes.

In order to understand the exploitation/exploration trade-off in reinforcement learning, previous theoretical and empirical accounts have suggested that increased uncertainty may precede the decision to explore an alternative option. To date, the neural mechanisms that support the strategic application of uncertainty-driven exploration remain underspecified. In this study, electroencephalography (EEG) was used to assess trial-to-trial dynamics relevant to exploration and exploitation. Theta-band activities over middle and lateral frontal areas have previously been implicated in EEG studies of reinforcement learning and strategic control. It was hypothesized that these areas may interact during top-down strategic behavioral control involved in exploratory choices. Here, we used a dynamic reward-learning task and an associated mathematical model that predicted individual response times. This reinforcement-learning model generated value-based prediction errors and trial-by-trial estimates of exploration as a function of uncertainty. Mid-frontal theta power correlated with unsigned prediction error, although negative prediction errors had greater power overall. Trial-to-trial variations in response-locked frontal theta were linearly related to relative uncertainty and were larger in individuals who used uncertainty to guide exploration. This finding suggests that theta-band activities reflect prefrontal-directed strategic control during exploratory choices.

Hyperactive cortico-striatal circuits including the Anterior Cingulate Cortex (ACC) have been implicated to underlie obtrusive thoughts and repetitive behaviors in Obsessive-Compulsive Disorder (OCD). Larger Error-Related Negativities (ERNs) in OCD patients during simple flanker tasks have been proposed to reflect an amplified error signal in these hyperactive circuits. Such amplified error signals typically are associated with an adaptive change in response, yet in OCD these same repetitive responses persist to the point of distress and impairment. In contrast to this repetitive character of OC behavior, larger ERN amplitudes have been linked to better avoidance learning in reinforcement learning tasks. Study I thus investigated if OC symptomatology in non-patients predicted an enhanced ERN after suboptimal choices in a probabilistic learning task. Absent any behavioral differences, higher OC symptoms predicted smaller ERNs. Study II replicated this effect in an independent sample while also replicating findings of a larger ERN in a flanker task. There were no relevant behavioral differences in reinforcement learning or error monitoring as a function of symptom score. These findings implicate different, yet overlapping neural mechanisms underlying the negative deflection in the ERP following the execution of an erroneous motor response and the one following a suboptimal choice in a reinforcement learning paradigm. OC symptomatology may be dissociated in these neural systems, with hypoactivity in a system that enables learning to avoid maladaptive choices, and hyperactivity in another system that enables the same behavior to be repeated when it was assessed as not quite good enough the first time.

We examined the impact of physical activity (PA) on longitudinal change in hippocampal volume in cognitively intact older adults at varying genetic risk for the sporadic form of Alzheimer's disease (AD). Hippocampal volume was measured from structural magnetic resonance imaging (MRI) scans administered at baseline and at an 18-month follow-up in 97 healthy, cognitively intact older adults. Participants were classified as High or Low PA based on a self-report questionnaire of frequency and intensity of exercise. Risk status was defined by the presence or absence of the apolipoprotein E-epsilon 4 (APOE-ε4) allele. Four subgroups were studied: Low Risk/High PA (n = 24), Low Risk/Low PA (n = 34), High Risk/High PA (n = 22), and High Risk/Low PA (n = 17). Over the 18 month follow-up interval, hippocampal volume decreased by 3% in the High Risk/Low PA group, but remained stable in the three remaining groups. No main effects or interactions between genetic risk and PA were observed in control brain regions, including the caudate, amygdala, thalamus, pre-central gyrus, caudal middle frontal gyrus, cortical white matter (WM), and total gray matter (GM). These findings suggest that PA may help to preserve hippocampal volume in individuals at increased genetic risk for AD. The protective effects of PA on hippocampal atrophy were not observed in individuals at low risk for AD. These data suggest that individuals at genetic risk for AD should be targeted for increased levels of PA as a means of reducing atrophy in a brain region critical for the formation of episodic memories.