Dynamic changes in large-scale functional network organization during autobiographical memory retrieval.

Autobiographical memory (AM), episodic memory for life events, involves the orchestration of multiple dynamic cognitive processes, including memory access and subsequent elaboration. Previous neuroimaging studies have contrasted memory access and elaboration processes in terms of regional brain activation and connectivity within large, multi-region networks. Although interactions between key memory-related regions such as the hippocampus and prefrontal cortex (PFC) have been shown to play an important role in AM retrieval, it remains unclear how such connectivity between specific, individual regions involved in AM retrieval changes dynamically across the retrieval process and how these changes relate to broader memory networks throughout the whole brain. The present functional magnetic resonance imaging (fMRI) study sought to assess the specific changes in interregional connectivity patterns across the AM retrieval processes to understand network level mechanisms of AM retrieval and further test current theoretical accounts of dynamic AM retrieval processes. We predicted that dynamic connections would reflect two hypothesized memory processes, with initial processes reflecting memory-access related connections between regions such as the anterior hippocampal and ventrolateral PFC regions, and later processes reflecting elaboration-related connections between dorsolateral frontal working memory regions and parietal-occipital visual imagery regions. One week prior to fMRI scanning, fifteen healthy adult participants generated AMs using personally selected cue words. During scanning, participants were cued to retrieve the AMs. We used a moving-window functional connectivity analysis and graph theoretic measures to examine dynamic changes in the strength and centrality of connectivity among regions involved in AM retrieval. Consistent with predictions, early, access-related processing primarily involved a ventral frontal to temporal-parietal network associated with strategic search and initial reactivation of specific episodic memory traces. In addition, neural network connectivity during later retrieval processes was associated with strong connections between occipital-parietal regions and dorsal fronto-parietal regions associated with mental imagery, reliving, and working memory processes. Taken together, these current findings help refine and extend dynamic neural processing models of AM retrieval by providing evidence of the specific connections throughout the brain that change in their synchrony with one another as processing progresses from access of specific event memories to elaborative reliving of the past event.

Association of Thalamic Dysconnectivity and Conversion to Psychosis in Youth and Young Adults at Elevated Clinical Risk.

IMPORTANCE: Severe neuropsychiatric conditions, such as schizophrenia, affect distributed neural computations. One candidate system profoundly altered in chronic schizophrenia involves the thalamocortical networks. It is widely acknowledged that schizophrenia is a neurodevelopmental disorder that likely affects the brain before onset of clinical symptoms. However, no investigation has tested whether thalamocortical connectivity is altered in individuals at risk for psychosis or whether this pattern is more severe in individuals who later develop full-blown illness. OBJECTIVES: To determine whether baseline thalamocortical connectivity differs between individuals at clinical high risk for psychosis and healthy controls, whether this pattern is more severe in those who later convert to full-blown illness, and whether magnitude of thalamocortical dysconnectivity is associated with baseline prodromal symptom severity. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, 2-year follow-up, case-control study, we examined 397 participants aged 12-35 years of age (243 individuals at clinical high risk of psychosis, of whom 21 converted to full-blown illness, and 154 healthy controls). The baseline scan dates were January 15, 2010, to April 30, 2012. MAIN OUTCOMES AND MEASURES: Whole-brain thalamic functional connectivity maps were generated using individuals' anatomically defined thalamic seeds, measured using resting-state functional connectivity magnetic resonance imaging. RESULTS: Using baseline magnetic resonance images, we identified thalamocortical dysconnectivity in the 243 individuals at clinical high risk for psychosis, which was particularly pronounced in the 21 participants who converted to full-blown illness. The pattern involved widespread hypoconnectivity between the thalamus and prefrontal and cerebellar areas, which was more prominent in those who converted to full-blown illness (t(173) = 3.77, P < .001, Hedge g = 0.88). Conversely, there was marked thalamic hyperconnectivity with sensory motor areas, again most pronounced in those who converted to full-blown illness (t(173) = 2.85, P < .001, Hedge g = 0.66). Both patterns were significantly correlated with concurrent prodromal symptom severity (r = 0.27, P < 3.6 × 10(-8), Spearman ρ = 0.27, P < 4.75 × 10(-5), 2-tailed). CONCLUSIONS AND RELEVANCE: Thalamic dysconnectivity, resembling that seen in schizophrenia, was evident in individuals at clinical high risk for psychosis and more prominently in those who later converted to psychosis. Dysconnectivity correlated with symptom severity, supporting the idea that thalamic connectivity may have prognostic implications for risk of conversion to full-blown illness.

Neural bases of motivated reasoning: an FMRI study of emotional constraints on partisan political judgment in the 2004 U.S. Presidential election.

Research on political judgment and decision-making has converged with decades of research in clinical and social psychology suggesting the ubiquity of emotion-biased motivated reasoning. Motivated reasoning is a form of implicit emotion regulation in which the brain converges on judgments that minimize negative and maximize positive affect states associated with threat to or attainment of motives. To what extent motivated reasoning engages neural circuits involved in "cold" reasoning and conscious emotion regulation (e.g., suppression) is, however, unknown. We used functional neuroimaging to study the neural responses of 30 committed partisans during the U.S. Presidential election of 2004. We presented subjects with reasoning tasks involving judgments about information threatening to their own candidate, the opposing candidate, or neutral control targets. Motivated reasoning was associated with activations of the ventromedial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, insular cortex, and lateral orbital cortex. As predicted, motivated reasoning was not associated with neural activity in regions previously linked to cold reasoning tasks and conscious (explicit) emotion regulation. The findings provide the first neuroimaging evidence for phenomena variously described as motivated reasoning, implicit emotion regulation, and psychological defense. They suggest that motivated reasoning is qualitatively distinct from reasoning when people do not have a strong emotional stake in the conclusions reached.

Attenuated brain response to auditory word stimulation with sevoflurane: a functional magnetic resonance imaging study in humans.

BACKGROUND: Functional magnetic resonance imaging offers a compelling, new perspective on altered brain function but is sparsely used in studies of anesthetic effect. To examine effects on verbal memory encoding, the authors imaged human brain response to auditory word stimulation using functional magnetic resonance imaging at different concentrations of an agent not previously studied, and tested memory after recovery. METHODS: Six male volunteers were studied breathing 0.0, 2.0, and 1.0% end-tidal sevoflurane (awake, deep, and light states, respectively) via laryngeal mask. In each condition, they heard 15 two-syllable English nouns via closed headphones. Each word was repeated 15 times (1/s), followed by 15 s of rest. Blood oxygenation level-dependent brain activations during blocks of stimulation versus rest were assessed with a 3-T Siemens Trio scanner and a 20-voxel spatial extent threshold. Memory was tested approximately 1.5 h after recovery with an auditory recognition task (chance performance = 33% correct). RESULTS: Scans showed widespread activations (P < 0.005, uncorrected) in the awake state, including bilateral superior temporal, frontal, and parietal cortex, right occipital cortex, bilateral thalamus, striatum, hippocampus, and cerebellum; more limited activations in the light state (bilateral superior temporal gyrus, right thalamus, bilateral parietal cortex, left frontal cortex, and right occipital cortex); and no significant auditory-related activation in the deep state. During recognition testing, subjects correctly selected 77 +/- 12% of words presented while they were awake as "old," versus 32 +/- 15 and 42 +/- 8% (P < 0.01) correct for the light and deep stages, respectively. CONCLUSIONS: Sevoflurane induces dose-dependent suppression of auditory blood oxygenation level-dependent signals, which likely limits the ability of words to be processed during anesthesia and compromises memory.

Men and women differ in amygdala response to visual sexual stimuli.

Men are generally more interested in and responsive to visual sexually arousing stimuli than are women. Here we used functional magnetic resonance imaging (fMRI) to show that the amygdala and hypothalamus are more strongly activated in men than in women when viewing identical sexual stimuli. This was true even when women reported greater arousal. Sex differences were specific to the sexual nature of the stimuli, were restricted primarily to limbic regions, and were larger in the left amygdala than the right amygdala. Men and women showed similar activation patterns across multiple brain regions, including ventral striatal regions involved in reward. Our findings indicate that the amygdala mediates sex differences in responsiveness to appetitive and biologically salient stimuli; the human amygdala may also mediate the reportedly greater role of visual stimuli in male sexual behavior, paralleling prior animal findings.