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Studies of autobiographical memory retrieval often use photographs to probe participants' memories for past events. Recent neuroimaging work has shown that viewing photographs depicting events from one's own life evokes a characteristic pattern of brain activity across a network of frontal, parietal, and medial temporal lobe regions that can be readily distinguished from brain activity associated with viewing photographs from someone else's life (Rissman, Chow, Reggente, and Wagner, 2016). However, it is unclear whether the neural signatures associated with remembering a personally experienced event are distinct from those associated with recognizing previously encountered photographs of an event. The present experiment used a novel functional magnetic resonance imaging (fMRI) paradigm to investigate putative differences in brain activity patterns associated with these distinct expressions of memory retrieval. Eighteen participants wore necklace-mounted digital cameras to capture events from their everyday lives over the course of three weeks. One week later, participants underwent fMRI scanning, where on each trial they viewed a sequence of photographs depicting either an event from their own life or from another participant's life and judged their memory for this event. Importantly, half of the trials featured photographic sequences that had been shown to participants during a laboratory session administered the previous day. Multi-voxel pattern analyses assessed the sensitivity of two brain networks of interest-as identified by a meta-analysis of prior autobiographical and laboratory-based memory retrieval studies-to the original source of the photographs (own life or other's life) and their experiential history as stimuli (previewed or non-previewed). The classification analyses revealed a striking dissociation: activity patterns within the autobiographical memory network were significantly more diagnostic than those within the laboratory-based network as to whether photographs depicted one's own personal experience (regardless of whether they had been previously seen), whereas activity patterns within the laboratory-based memory network were significantly more diagnostic than those within the autobiographical memory network as to whether photographs had been previewed (regardless of whether they were from the participant's own life). These results, also apparent in whole-brain searchlight classifications, provide evidence for dissociable patterns of activation across two putative memory networks as a function of whether real-world photographs trigger the retrieval of firsthand experiences or secondhand event knowledge.

Most complex cognitive tasks require the coordinated interplay of multiple brain networks, but the act of retrieving an episodic memory may place especially heavy demands for communication between the frontoparietal control network (FPCN) and the default mode network (DMN), two networks that do not strongly interact with one another in many task contexts. We applied graph theoretical analysis to task-related fMRI functional connectivity data from 20 human participants and found that global brain modularity—a measure of network segregation—is markedly reduced during episodic memory retrieval relative to closely matched analogical reasoning and visuospatial perception tasks. Individual differences in modularity were correlated with memory task performance, such that lower modularity levels were associated with a lower false alarm rate. Moreover, the FPCN and DMN showed significantly elevated coupling with each other during the memory task, which correlated with the global reduction in brain modularity. Both networks also strengthened their functional connectivity with the hippocampus during the memory task. Together, these results provide a novel demonstration that reduced modularity is conducive to effective episodic retrieval, which requires close collaboration between goal-directed control pro- cesses supported by the FPCN and internally oriented self-referential processing supported by the DMN.

The widely cited prefrontal dysfunction - excess subcortical dopamine model of schizophrenia posits that prefrontal deficits give rise to cognitive impairments and the disinhibition of subcortical dopamine release underlying psychosis. While this has been one of the most influential schizophrenia models, only a handful of studies have provided evidence supporting it directly in patients with schizophrenia. We previously demonstrated task-evoked substantia nigra hyperactivity in the context of prefrontal hypofunction and prefrontonigral functional disconnectivity. In addition, nigrostriatal functional connectivity was identified as a potential marker of psychosis. Because patients in this prior study had chronic schizophrenia and were treated with antipsychotics, in the present study we tested whether these findings were confounded by illness chronicity and medication effects by seeking to reproduce these findings in an independent sample of antipsychotic naïve, first episode (FE) patients. We compared event-related fMRI activations from 12 FE patients with 15 demographically matched healthy control subjects during cognitive testing. We found substantia nigra hyperactivity associated with prefrontal hypofunction and prefrontonigral functional disconnectivity, as well as the magnitude of nigrostriatal functional connectivity positively correlating with severity of psychosis. This study adds to the body of evidence supporting the prefrontal-dopamine model of schizophrenia and further validates nigrostriatal functional connectivity as a marker of psychosis.

While structural abnormalities of the dorsolateral prefrontal cortex (DLPFC) may pre-date and predict psychosis onset, the relationships between functional deficits, cognitive and psychosocial impairments has yet to be explored in the at-risk period. An established measure of cognitive control (AXCPT) was administered to demographically matched clinical-high-risk (CHR; n=25), first-episode schizophrenia (FE; n=35), and healthy control (HC; n=35) participants during functional magnetic resonance imaging (fMRI) to investigate these relationships. CHR and FE individuals demonstrated impaired context processing and reduced DLPFC activation relative to HC individuals during increased cognitive control demands. FE and CHR individuals' ability to increase DLPFC activity in response to cognitive control demands was associated with better task performance. Task performance was also associated with severity of disorganization and poverty symptoms in FE participants. These findings support more extensive studies using fMRI to examine the clinical significance of prefrontal cortical functioning in the earliest stages of psychosis.

Cognitive control deficits have been consistently documented in patients with schizophrenia. Recent work in cognitive neuroscience has hypothesized a distinction between two theoretically separable modes of cognitive control-reactive and proactive. However, it remains unclear the extent to which these processes are uniquely associated with dysfunctional neural recruitment in individuals with schizophrenia. This functional magnetic resonance imaging (fMRI) study utilized the color word Stroop task and AX Continuous Performance Task (AX-CPT) to tap reactive and proactive control processes, respectively, in a sample of 54 healthy controls and 43 patients with first episode schizophrenia. Healthy controls demonstrated robust dorsolateral prefrontal, anterior cingulate, and parietal cortex activity on both tasks. In contrast, patients with schizophrenia did not show any significant activation during proactive control, while showing activation similar to control subjects during reactive control. Critically, an interaction analysis showed that the degree to which prefrontal activity was reduced in patients versus controls depended on the type of control process engaged. Controls showed increased dorsolateral prefrontal cortex (DLPFC) and parietal activity in the proactive compared to the reactive control task, whereas patients with schizophrenia did not demonstrate this increase. Additionally, patients' DLPFC activity and performance during proactive control was associated with disorganization symptoms, while no reactive control measures showed this association. Proactive control processes and concomitant dysfunctional recruitment of DLPFC represent robust features of schizophrenia that are also directly associated with symptoms of disorganization.

Studies of autobiographical memory retrieval often use photographs to probe participants' memories for past events. Recent neuroimaging work has shown that viewing photographs depicting events from one's own life evokes a characteristic pattern of brain activity across a network of frontal, parietal, and medial temporal lobe regions that can be readily distinguished from brain activity associated with viewing photographs from someone else's life (Rissman, Chow, Reggente, and Wagner, 2016). However, it is unclear whether the neural signatures associated with remembering a personally experienced event are distinct from those associated with recognizing previously encountered photographs of an event. The present experiment used a novel functional magnetic resonance imaging (fMRI) paradigm to investigate putative differences in brain activity patterns associated with these distinct expressions of memory retrieval. Eighteen participants wore necklace-mounted digital cameras to capture events from their everyday lives over the course of three weeks. One week later, participants underwent fMRI scanning, where on each trial they viewed a sequence of photographs depicting either an event from their own life or from another participant's life and judged their memory for this event. Importantly, half of the trials featured photographic sequences that had been shown to participants during a laboratory session administered the previous day. Multi-voxel pattern analyses assessed the sensitivity of two brain networks of interest—as identified by a meta-analysis of prior autobiographical and laboratory-based memory retrieval studies—to the original source of the photographs (own life or other's life) and their experiential history as stimuli (previewed or non-previewed). The classification analyses revealed a striking dissociation: activity patterns within the autobiographical memory network were significantly more diagnostic than those within the laboratory-based network as to whether photographs depicted one's own personal experience (regardless of whether they had been previously seen), whereas activity patterns within the laboratory-based memory network were significantly more diagnostic than those within the autobiographical memory network as to whether photographs had been previewed (regardless of whether they were from the participant's own life). These results, also apparent in whole-brain searchlight classifications, provide evidence for dissociable patterns of activation across two putative memory networks as a function of whether real-world photographs trigger the retrieval of firsthand experiences or secondhand event knowledge. [ABSTRACT FROM AUTHOR]