Evidence supporting a time-limited hippocampal role in retrieving autobiographical memories.

The necessity of the human hippocampus for remote autobiographical recall remains fiercely debated. The standard model of consolidation predicts a time-limited role for the hippocampus, but the competing multiple trace/trace transformation theories posit indefinite involvement. Lesion evidence remains inconclusive, and the inferences one can draw from functional MRI (fMRI) have been limited by reliance on covert (silent) recall, which obscures dynamic, moment-to-moment content of retrieved memories. Here, we capitalized on advances in fMRI denoising to employ overtly spoken recall. Forty participants retrieved recent and remote memories, describing each for approximately 2 min. Details associated with each memory were identified and modeled in the fMRI time-series data using a variant of the Autobiographical Interview procedure, and activity associated with the recall of recent and remote memories was then compared. Posterior hippocampal regions exhibited temporally graded activity patterns (recent events > remote events), as did several regions of frontal and parietal cortex. Consistent with predictions of the standard model, recall-related hippocampal activity differed from a non-autobiographical control task only for recent, and not remote, events. Task-based connectivity between posterior hippocampal regions and others associated with mental scene construction also exhibited a temporal gradient, with greater connectivity accompanying the recall of recent events. These findings support predictions of the standard model of consolidation and demonstrate the potential benefits of overt recall in neuroimaging experiments.

Dynamic Content Reactivation Supports Naturalistic Autobiographical Recall in Humans.

Humans can vividly recall and re-experience events from their past, and these are commonly referred to as episodic or autobiographical memories. fMRI experiments reliably associate autobiographical event recall with activity in a network of "default" or "core" brain regions. However, as prior studies have relied on covert (silent) recall procedures, current understanding may be hampered by methodological limitations that obscure dynamic effects supporting moment-to-moment content retrieval. Here, fMRI participants (N = 40) overtly (verbally) recalled memories for ∼2 min periods. The content of spoken descriptions was categorized using a variant of the Autobiographical Interview (AI) procedure (Levine et al., 2002) and temporally re-aligned with BOLD data so activity accompanying the recall of different details could be measured. Replicating prior work, sustained effects associated with autobiographical recall periods (which are insensitive to the moment-to-moment content of retrieval) fell primarily within canonical default network regions. Spoken descriptions were rich in episodic details, frequently focusing on physical entities, their ongoing activities, and their appearances. Critically, neural activity associated with recalling specific details (e.g., those related to people or places) was transient, broadly distributed, and grounded in category-selective cortex (e.g., regions related to social cognition or scene processing). Thus, although a single network may generally support the process of vivid event reconstruction, the structures required to provide detail-related information shift in a predictable manner that respects domain-level representations across the cortex.SIGNIFICANCE STATEMENT Humans can vividly recall memories of autobiographical episodes, a process thought to involve the reconstruction of numerous distinct event details. Yet how the brain represents a complex episode as it unfolds over time remains unclear and appears inconsistent across experimental traditions. One hurdle is the use of covert (silent) in-scanner recall to study autobiographical memory, which prevents experimenter knowledge of what information is being retrieved, and when, throughout the remembering process. In this experiment, participants overtly described autobiographical memories while undergoing fMRI. Activity associated with the recall and description of specific details was transient, broadly distributed, and grounded in category-selective cortex. Thus, it appears that as events unfold mentally, structures are dynamically reactivated to support vivid recollection.

Adolescent development of inhibitory control and substance use vulnerability: A longitudinal neuroimaging study.

Previous research indicates that risk for substance use is associated with poor inhibitory control. However, it remains unclear whether at-risk youth follow divergent patterns of inhibitory control development. As part of the longitudinal National Consortium on Adolescent Neurodevelopment and Alcohol study, participants (N = 113, baseline age: 12-21) completed a rewarded antisaccade task during fMRI, with up to three time points. We examined whether substance use risk factors, including psychopathology (externalizing, internalizing) and family history of substance use disorder, were associated with developmental differences in inhibitory control performance and BOLD activation. Among the examined substance use risk factors, only externalizing psychopathology exhibited developmental differences in inhibitory control performance, where higher scores were associated with lower correct response rates (p = .013) and shorter latencies (p < .001) in early adolescence that normalized by late adolescence. Neuroimaging results revealed higher externalizing scores were associated with developmentally-stable hypo-activation in the left middle frontal gyrus (p < .05 corrected), but divergent developmental patterns of posterior parietal cortex activation (p < .05 corrected). These findings suggest that early adolescence may be a unique period of substance use vulnerability via cognitive and phenotypic disinhibition.

Meta-analysis and review of functional neuroimaging differences underlying adolescent vulnerability to substance use.

Adolescence is increasingly viewed as a sensitive period in the development of substance use disorders (SUDs). Neurodevelopmental 'dual-risk' theories suggest adolescent vulnerability to problematic substance use is driven by an overactive reward drive mediated by the striatum, and poor cognitive control mediated by the prefrontal cortex. To this end, there has been a growing number of neuroimaging studies examining cognitive and affective neural systems during adolescence for markers of vulnerability to problematic substance use. Here, we perform a coordinate-based meta-analysis on this emerging literature. Twenty-two task-based voxelwise fMRI studies with activation differences associated with substance use vulnerability, representative of approximately 1092 subjects, were identified through a systematic literature search (PubMed, Scopus) and coordinates of activation differences (N â€‹= â€‹190) were extracted. Adolescents were defined as 'at-risk' for problematic substance use based on a family history of SUD or through prospective prediction of substance use initiation or escalation. Multilevel kernel density analysis was used to identify the most consistent brain regions associated with adolescent substance use vulnerability. Across the included studies, substance use vulnerability was most reliably associated with activation differences in the striatum, where at-risk adolescents had hyper-activation in the dorsal subdivision (putamen). Follow-up analyses suggested striatal differences were driven by tasks sharing a motivational and/or reward component (e.g., monetary incentive) and common across subgroups of substance use risk (family history and prospective prediction studies). Analyses examining the role of psychiatric comorbidity revealed striatal activation differences were significantly more common in samples whose definition of substance use risk included cooccurring externalizing psychopathology. Furthermore, substance use risk meta-analytic results were no longer significant when excluding these studies, although this may reflect limitations in statistical power. No significant activation differences were observed in prefrontal cortex in any analysis. These results suggest striatal dysfunction, rather than prefrontal, may be a more primary neural feature of adolescent vulnerability to problematic substance use, possibly through a dimension of individual variability shared with externalizing psychopathology. However, our systematic literature search confirms this is still an emerging field. More studies, increased data sharing, and further quantitative integration are necessary for a comprehensive understanding of the neuroimaging markers of adolescent substance use risk.

Neural Correlates of Rewarded Response Inhibition in Youth at Risk for Problematic Alcohol Use.

Risk for substance use disorder (SUD) is associated with poor response inhibition and heightened reward sensitivity. During adolescence, incentives improve performance on response inhibition tasks and increase recruitment of cortical control areas (Geier et al., 2010) associated with SUD (Chung et al., 2011). However, it is unknown whether incentives moderate the relationship between response inhibition and trait-level psychopathology and personality features of substance use risk. We examined these associations in the current project using a rewarded antisaccade (AS) task (Geier et al., 2010) in youth at risk for substance use. Participants were 116 adolescents and young adults (ages 12-21) from the University of Pittsburgh site of the National Consortium on Adolescent Neurodevelopment and Alcohol [NCANDA] study, with neuroimaging data collected at baseline and 1 year follow up visits. Building upon previous work using this task in normative developmental samples (Geier et al., 2010) and adolescents with SUD (Chung et al., 2011), we examined both trial-wise BOLD responses and those associated with individual task-epochs (cue presentation, response preparation, and response) and associated them with multiple substance use risk factors (externalizing and internalizing psychopathology, family history of substance use, and trait impulsivity). Results showed that externalizing psychopathology and high levels of trait impulsivity (positive urgency, SUPPS-P) were associated with general decreases in antisaccade performance. Accompanying this main effect of poor performance, positive urgency was associated with reduced recruitment of the frontal eye fields (FEF) and inferior frontal gyrus (IFG) in both a priori regions of interest and at the voxelwise level. Consistent with previous work, monetary incentive improved antisaccade behavioral performance and was associated with increased activation in the striatum and cortical control areas. However, incentives did not moderate the association between response inhibition behavioral performance and any trait-level psychopathology and personality factor of substance use risk. Reward interactions were observed for BOLD responses at the task-epoch level, however, they were inconsistent across substance use risk types. The results from this study may suggest poor response inhibition and heightened reward sensitivity are not overlapping neurocognitive features of substance use risk. Alternatively, more subtle, common longitudinal processes might jointly explain reward sensitivity and response inhibition deficits in substance use risk.