Dissociable profiles of generalization/discrimination in the human hippocampus during associative retrieval.

When encountering stimuli that vary slightly from previous experiences, neural signals within the CA3 and dentate gyrus (CA3 DG) hippocampal subfields are thought to facilitate mnemonic discrimination, whereas CA1 may be less sensitive to minor stimulus changes, allowing for generalization across similar events. Studies have also posited a critical role for CA1 in the comparison of events to memory-derived expectations, but the degree to which these processes are impacted by explicit retrieval demands is yet unclear. To evaluate extant accounts of hippocampal subfield function, we acquired high-resolution fMRI data as participants performed a task in which famous names were used to cue the retrieval of previously paired images. Although both left CA3 DG and CA1 showed match enhancement effects, responding more to original paired images (targets) than to never-before-seen images (novels), the sensitivity of these subfields to stimulus changes and task demands diverged. CA3 DG showed a goal-independent, yet highly specific, preference for previously encountered stimuli, responding equally strongly to targets and mispaired associates, while showing equally weak responses to close lures and novels. In contrast, recognition signals in CA1 were goal-dependent (i.e., not evoked by mispaired associates), yet accommodating of subtle stimulus differences, such that close lures evoked comparable activity as targets. © 2016 Wiley Periodicals, Inc.

Striatal dopamine D2/D3 receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans.

Impulsive behavior is thought to reflect a traitlike characteristic that can have broad consequences for an individual's success and well-being, but its neurobiological basis remains elusive. Although striatal dopamine D2-like receptors have been linked with impulsive behavior and behavioral inhibition in rodents, a role for D2-like receptor function in frontostriatal circuits mediating inhibitory control in humans has not been shown. We investigated this role in a study of healthy research participants who underwent positron emission tomography with the D2/D3 dopamine receptor ligand [¹8F]fallypride and BOLD fMRI while they performed the Stop-signal Task, a test of response inhibition. Striatal dopamine D2/D3 receptor availability was negatively correlated with speed of response inhibition (stop-signal reaction time) and positively correlated with inhibition-related fMRI activation in frontostriatal neural circuitry. Correlations involving D2/D3 receptor availability were strongest in the dorsal regions (caudate and putamen) of the striatum, consistent with findings of animal studies relating dopamine receptors and response inhibition. The results suggest that striatal D2-like receptor function in humans plays a major role in the neural circuitry that mediates behavioral control, an ability that is essential for adaptive responding and is compromised in a variety of common neuropsychiatric disorders.