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Neurobiological evidence in rodents indicates that threat extinction incorporates reward neurocircuitry. Consequently, incorporating reward associations with an extinction memory may be an effective strategy to persistently attenuate threat responses. Moreover, while there is considerable research on the short-term effects of extinction strategies in humans, the long-term effects of extinction are rarely considered. In a within-subjects fMRI study, we compared counterconditioning (a form of rewarded-extinction) to standard extinction, at recent (24 hours) and remote (∼1 month) retrieval tests. Relative to standard extinction, counterconditioning diminished 24-hour relapse of arousal and threat expectancy, and reduced activity in brain regions associated with the appraisal and expression of threat (e.g., thalamus, insula, periaqueductal gray). The retrieval of reward-associated extinction memory was accompanied by functional connectivity between the amygdala and the ventral striatum, whereas the retrieval of standard-extinction memories was associated with connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC). One-month later, the retrieval of both standard- and rewarded-extinction was associated with amygdala-vmPFC connectivity. However, only rewarded extinction created a stable memory trace in the vmPFC, identified through overlapping multivariate patterns of fMRI activity from extinction to 24-hour and 1-month retrieval. These findings provide new evidence that reward may generate a more stable and enduring memory trace of attenuated threat in humans.Significance StatementPrevalent treatments for pathological fear and anxiety are based on the principles of Pavlovian extinction. Unfortunately, extinction forms weak memories that only temporarily inhibit the retrieval of threat associations. Thus, to increase the translational relevance of extinction research, it is critical to investigate whether extinction can be augmented to form a more enduring memory, especially after long intervals. Here, we used a multi-day fMRI paradigm in humans to compare the short- and long-term neurobehavioral effects of aversive-to-appetitive counterconditioning, a form of augmented extinction. Our results provide novel evidence that including an appetitive stimulus during extinction can reduce short-term threat relapse and stabilize the memory trace of extinction in the vmPFC, for at least one month after learning.

A well-established finding in episodic memory research is that the likelihood of successful retrieval is affected by the ‘age’ of the targeted memory (i.e. based on the duration of the encoding-retrieval interval). Although such findings are usually interpreted in terms of the memory trace changing in quality or accessibility over time, there is growing evidence that retrieval also depends on how well search attempts can be strategically oriented. Here, we investigated the strategic orienting of retrieval processing, as indexed by event-related brain potentials (ERPs), when retrieval was aimed toward candidate memories of different ages. As retrieving remote versus recent memories is associated with increased difficulty, the current study was designed to dissociate the difficulty and memory age effects. Subjects encoded two lists of pictures separated by one week, with the items in each list presented once or four times. A series of memory tests targeting pictures from only one week-by-repetition condition at a time were then completed, while new pictures and those from the other conditions were rejected. Consistent with previous results, new-item ERPs were more positive over posterior scalp when recent compared to remote lists were targeted. Importantly, this difference remained when difficulty was matched, and the ERP correlates of difficulty were distinct in both timing and polarity from those of orienting. Together, these findings provide further support for the idea that the age of a targeted memory alone can lead to the adoption of retrieval orienting strategies.

Objective: Two of the most commonly abused substances by adolescents in the United States are alcohol and cannabis, both of which are associated with adverse medical and psychiatric outcom...

Two of the most commonly used illegal substances by adolescents are alcohol and cannabis. Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with poorer decision-making in adolescents. In adolescents, level of AUD symptomatology has been negatively associated with striatal reward responsivity. However, little work has explored the relationship with striatal reward prediction error (RPE) representation and the extent to which any augmentation of RPE by novel stimuli is impacted. One-hundred fifty-one adolescents participated in the Novelty Task while undergoing functional magnetic resonance imaging (fMRI). In this task, participants learn to choose novel or non-novel stimuli to gain monetary reward. Level of AUD symptomatology was negatively associated with both optimal decision-making and BOLD response modulation by RPE within striatum and regions of prefrontal cortex. The neural alterations in RPE representation were particularly pronounced when participants were exploring novel stimuli. Level of CUD symptomatology moderated the relationship between novelty propensity and RPE representation within inferior parietal lobule and dorsomedial prefrontal cortex. These data expand on an emerging literature investigating individual associations of AUD symptomatology levels versus CUD symptomatology levels and RPE representation during reinforcement processing and provide insight on the role of neuro-computational processes underlying reinforcement learning/decision-making in adolescents.

Despite extensive behavioral evidence of impairments in face processing and expression recognition in adults with alcohol or cannabis use disorders (AUD/CUD), neuroimaging findings have been inconsistent. Moreover, relatively little work has examined the relationship of AUD or CUD symptoms with face or expression processing within adolescents. Given the high prevalence of alcohol and cannabis use during adolescence, understanding how these usage behaviors interact with neural mechanisms supporting face and expression processing could have important implications for youth social and emotional functioning. In this study, adolescents (N = 104) responded to morphed fearful and happy expressions during fMRI and their level of AUD and/or CUD symptoms were related to the BOLD response data. We found that AUD and CUD symptom severity were both negatively related to responses to faces generally. However, whereas this relationship was shown for AUD within ventromedial prefrontal cortex and lingual gyrus, it was shown for CUD within rostromedial prefrontal cortex including anterior cingulate cortex. Additionally, AUD symptom levels were associated with differential responses within medial temporal pole and inferior parietal lobule as a function of expression. These results have potential implications for understanding the social and emotional functioning of adolescents with AUD and CUD symptoms.

Recent functional neuroimaging studies have attempted to understand the cognitive and neural bases of episodic memory retrieval, as well as the extent to which different retrieval judgments reflect qualitative as opposed to continuous changes in neural signals. The present study addressed this issue by investigating the reinstatement of episodic content according to the amount of information available at retrieval. Subjects encoded a series of words in the context of three distinct tasks, while a manipulation of presentation duration (4 or 8s) was also employed. A later recognition memory test was used to segregate trials according to whether or not they were accompanied by the recollection of details from encoding. Functional MRI data acquired during both the encoding and retrieval phases were used in conjunction with multi-voxel pattern-analysis (MVPA) to provide a measure of the degree to which encoding-related patterns of brain activity were later reactivated (reinstated) at the time of retrieval. Critically, the magnitude of reinstatement differed with respect to the encoding manipulation, such that reinstatement was stronger for items associated with the longer presentation duration. Together with duration-related differences in retrieval activity in left posterior parietal cortex, the results provide neural evidence for the reinstatement of different amounts of episodic information, consistent with the idea that recollection is based on a continuous neural signal.

This cross-sectional study examines the association of amount and different type of childhood maltreatment with responsiveness in regions of the brain implicated in emotional responding and response control in youths., Key Points Question Are the amount and type (abuse vs neglect) of childhood maltreatment differentially associated with the responsiveness of regions of the brain implicated in emotional responding and response control? Findings In this cross-sectional study including 116 youths aged 10 to 18 years, the amount of childhood maltreatment was inversely associated with the responsiveness of regions of the brain involved in response control and positively associated with emotional responding. This association was also found specifically for abuse but not for neglect. Meaning Different types of childhood maltreatment may have different associations with atypical neural responses; therefore, they may have different associations with different forms of psychiatric neurobiology., Importance Childhood maltreatment is associated with serious developmental consequences that may be different depending on the form of maltreatment. However, relatively little research has investigated this issue despite implications for understanding the development of psychiatric disorders after maltreatment. Objective To determine the association of childhood maltreatment and potential differential associations of childhood abuse or neglect with neural responsiveness within regions of the brain implicated in emotional responding and response control. Design, Setting, and Participants In this cross-sectional study, participants aged 10 to 18 years with varying levels of prior maltreatment as indexed by the Childhood Trauma Questionnaire (CTQ) were recruited from a residential care facility and the surrounding community. Blood oxygen level–dependent response data were analyzed via 2 analyses of covariance that examined 2 (sex) × 3 (task condition [view, congruent, incongruent]) × 3 (valence [negative, neutral, positive]) with Blom-transformed covariates: (1) total CTQ score; and (2) abuse and neglect subscores. Data were collected from April 1, 2016, to June 30, 2018. Data analyses occurred from June 10, 2018, to October 31, 2018. Main Outcomes and Measures Blood oxygenation level–dependent signals in response to an Affective Stroop task were measured via functional magnetic resonance imaging. Results The sample included 116 youths (mean [SD] age, 15.0 [2.2] years; 70 [60.3%] male). Fifteen participants reported no prior maltreatment. The remaining 101 participants (87.1%) reported at least some prior maltreatment, and 55 (54.5%) reported significant maltreatment, ie, total CTQ scores were greater than the validated CTQ score threshold of 40. There were significant total CTQ score × task condition associations within the bilateral postcentral gyrus, left precentral gyrus, midcingulate cortex, middle temporal gyrus, and superior temporal gyrus (left postcentral gyrus: F = 11.73; partial η2 = 0.14; right postcentral and precentral gyrus: F = 9.81; partial η2 = 0.10; midcingulate cortex: F = 12.76; partial η2 = 0.12; middle temporal gyrus: F = 13.24; partial η2 = 0.10; superior temporal gyrus: F = 10.33; partial η2 = 0.11). In all examined regions of the brain, increased maltreatment was associated with decreased differential responsiveness to incongruent task trials compared with view trials (left postcentral gyrus: r = −0.34; 95% CI, −0.17 to −0.51; right postcentral and precentral gyrus: r = −0.31; 95% CI, −0.14 to −0.49; midcingulate cortex: r = −0.36; 95% CI, −0.18 to −0.53; middle temporal gyrus: r = −0.35; 95% CI, −0.17 to −0.52; superior temporal gyrus: r = −0.37; 95% CI, −0.20 to −0.55). These interactions were particularly associated with level of abuse rather than neglect. A second analysis of covariance revealed significant abuse × task condition (but not neglect × task) interactions within the midcingulate cortex (F = 13.96; partial η2 = 0.11), right postcentral gyrus and inferior parietal lobule (F = 15.21; partial η2 = 0.12), left postcentral and precentral gyri (F = 11.16; partial η2 = 0.12), and rostromedial frontal cortex (F = 10.36; partial η2 = 0.08)). In all examined regions of the brain, increased abuse was associated with decreased differential responsiveness to incongruent task trials compared with view trials (midcingulate cortex: partial r = −0.33; P

In primates, neurons sensitive to figure–ground status are located in striate cortex (area V1) and extrastriate cortex (area V2). Although much is known about the anatomical structure and connectivity of the avian visual pathway, the functional organization of the avian brain remains largely unexplored. To pinpoint the areas associated with figure–ground segregation in the avian brain, we used a radioactively labeled glucose analog to compare differences in glucose uptake after figure–ground, color, and shape discriminations. We also included a control group that received food on a variable-interval schedule, but was not required to learn a visual discrimination. Although the discrimination task depended on group assignment, the stimulus displays were identical for all three experimental groups, ensuring that all animals were exposed to the same visual input. Our analysis concentrated on the primary thalamic nucleus associated with visual processing, the nucleus rotundus (Rt), and two nuclei providing regulatory feedback, the pretectum (PT) and the nucleus subpretectalis/interstitio-pretecto-subpretectalis complex (SP/IPS). We found that figure–ground discrimination was associated with strong and nonlateralized activity of Rt and SP/IPS, whereas color discrimination produced strong and lateralized activation in Rt alone. Shape discrimination was associated with lower activity of Rt than in the control group. Taken together, our results suggest that figure–ground discrimination is associated with Rt and that SP/IPS may be a main source of inhibitory control. Thus, figure–ground segregation in the avian brain may occur earlier than in the primate brain.

Neuroimaging studies of episodic memory have consistently demonstrated that memory retrieval involves reactivating patterns of neural activity that were present during encoding, and these effects are thought to reflect the qualitative retrieval (recollection) of information that is specific to the content of an episode. By contrast, recollection is also accompanied by other neural correlates that generalize across episodic content and are consequently referred to as the "core recollection network". The neural mechanism by which these specific and core effects interact to give rise to episodic memory retrieval is largely unknown. The current study addressed this issue by testing for correlations (connectivity) between pattern reactivation and activity in the core recollection network. Subjects encoded a series of words with different tasks and then completed a two-step source memory test, whereby they identified the task (source) previously associated with the word and the confidence of that judgment. Multivariate pattern analysis (MVPA) was used in combination with fMRI to first identify encoding-related neural patterns and then test for their reactivation during retrieval. Consistent with prior findings, the magnitude of reactivation increased with source-memory confidence. Moreover, individual-trial measures of reactivation exhibited positive correlations with activity in multiple regions of the core recollection network. Importantly, evidence of functional connectivity between pattern reactivation and a region of left posterior parietal cortex supports the role of this region in tracking the retrieval of episodic information in service of making subjective memory decisions.

Several fMRI studies have shown a correspondence between the brain regions activated during encoding and retrieval, consistent with the view that memory retrieval involves hippocampally-mediated reinstatement of cortical activity. With the limited temporal resolution of fMRI, the precise timing of such reactivation is unclear, calling into question the functional significance of these effects. Whereas reactivation influencing retrieval should emerge with neural correlates of retrieval success, that signifying post-retrieval monitoring would trail retrieval. The present study employed EEG to provide a temporal landmark of retrieval success from which we could investigate the sub-trial time course of reactivation. Pattern-classification analyses revealed that early-onsetting reactivation differentiated the outcome of recognition-memory judgments and was associated with individual differences in behavioral accuracy, while reactivation was also evident in a sustained form later in the trial. The EEG findings suggest that, whereas prior fMRI findings could be interpreted as reflecting the contribution of reinstatement to retrieval success, they could also indicate the maintenance of episodic information in service of post-retrieval evaluation.