The development of depressogenic self-schemas: Associations with children's regional grey matter volume in ventrolateral prefrontal cortex.

Cognitive theories of depression contend that biased cognitive information processing plays a causal role in the development of depression. Extensive research shows that deeper processing of negative and/or shallower processing of positive self-descriptors (i.e., negative and positive self-schemas) predicts current and future depression in adults and children. However, the neural correlates of the development of self-referent encoding are poorly understood. We examined children's self-referential processing using the self-referent encoding task (SRET) collected from 74 children at ages 6, 9, and 12; around age 10, these children also contributed structural magnetic resonance imaging data. From age 6 to age 12, both positive and negative self-referential processing showed mean-level growth, with positive self-schemas increasing relatively faster than negative ones. Further, voxel-based morphometry showed that slower growth in positive self-schemas was associated with lower regional gray matter volume (GMV) in ventrolateral prefrontal cortex (vlPFC). Our results suggest that smaller regional GMV within vlPFC, a critical region for regulatory control in affective processing and emotion development, may have implications for the development of depressogenic self-referential processing in mid-to-late childhood.

Topographic organization of the human caudate functional connectivity and age-related changes with resting-state fMRI.

The striatum is postulated to play a central role in gating cortical processing during goal-oriented behavior. While many human neuroimaging studies have treated the striatum as an undivided whole or several homogeneous compartments, some recent studies showed that its circuitry is topographically organized and has more complex relations with the cortical networks than previously assumed. Here, we took a gradient functional connectivity mapping approach that utilizes the entire anatomical space of the caudate nucleus to examine the organization of its functional relationship with the rest of the brain and how its topographic mapping changes with age. We defined the topography of the caudate functional connectivity using three publicly available resting-state fMRI datasets. We replicated and extended previous findings. First, we found two stable gradients of caudate connectivity patterns along its medial-lateral (M-L) and anterior-posterior (A-P) axes, supporting findings from previous tract-tracing studies of non-human primates that there are at least two main organizational principles within the caudate nucleus. Second, unlike previous emphasis of the A-P topology, we showed that the differential connectivity patterns along the M-L gradient of caudate are more clearly organized with the large-scale neural networks; such that brain networks associated with internal vs. external orienting behavior are respectively more closely linked to the medial vs. lateral extent of the caudate. Third, the caudate's M-L organization showed greater age-related reduction in integrity, which was further associated with age-related changes in behavioral measures of executive functions. In sum, our analysis confirmed a sometimes overlooked M-L functional connectivity gradient within the caudate nucleus, with its lateral longitudinal zone more closely linked to the frontoparietal cortical circuits and age-related changes in cognitive control. These findings provide a more precise mapping of the human caudate functional connectivity, both in terms of the gradient organization with cortical networks and age-related changes in such organization.

Longitudinal corpus callosum microstructural decline in early-stage Parkinson's disease in association with akinetic-rigid symptom severity.

Previous diffusion tensor imaging (DTI) studies of Parkinson's disease (PD) show reduced microstructural integrity of the corpus callosum (CC) relative to controls, although the characteristics of such callosal degradation remain poorly understood. Here, we utilized a longitudinal approach to identify microstructural decline in the entire volume of the CC and its functional subdivisions over 2 years and related the callosal changes to motor symptoms in early-stage PD. The study sample included 61 PD subjects (N = 61, aged 45-82, 38 M & 23 F, H&Y ≤ 2) from the Parkinson's Progressive Markers Initiative database (PPMI). Whole-brain voxel-wise results revealed significant fractional anisotropy (FA) and mean diffusivity (MD) changes in the CC, especially in the genu and splenium. Using individually drawn CC regions of interest (ROI), our analysis further revealed that almost all subdivisions of the CC show significant decline in FA to certain extents over the two-year timeframe. Additionally, FA seemed lower in the right hemisphere of the CC at both time-points, and callosal FA decline was associated with FA and MD decline in widespread cortical and subcortical areas. Notably, multiple regression analysis revealed that across-subject akinetic-rigid severity was negatively associated with callosal FA at baseline and 24 months follow-up, and the effect was strongest in the anterior portion of the CC. These results suggest that callosal microstructure alterations in the anterior CC may serve as a viable biomarker for akinetic-rigid symptomology and disease progression, even in early PD.

Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis.

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT).2 IT is a moderately heritable trait1 that can be measured in multiple species.3 In humans, levels of IT can be quantified from the first year of life through direct behavioral observations or reports by caregivers or teachers. Similar approaches as well as self-report questionnaires on current and/or retrospective levels of IT1 can be used later in life.

Errors in visuospatial working memory across space and time.

Visuospatial working memory (VSWM) involves cortical regions along the dorsal visual pathway, which are topographically organized with respect to the visual space. However, it remains unclear how such functional organization may constrain VSWM behavior across space and time. Here, we systematically mapped VSWM performance across the 2-dimensional (2D) space in various retention intervals in human subjects using the memory-guided and visually guided saccade tasks in two experiments. Relative to visually guided saccades, memory-guided saccades showed significant increases in unsystematic errors, or response variability, with increasing target eccentricity (3°-13° of visual angle). Unsystematic errors also increased with increasing delay (1.5-3 s, Experiment 1; 0.5-5 s, Experiment 2), while there was little or no interaction between delay and eccentricity. Continuous bump attractor modeling suggested neurophysiological and functional organization factors in the increasing unsystematic errors in VSWM across space and time. These findings indicate that: (1) VSWM representation may be limited by the functional topology of the visual pathway for the 2D space; (2) Unsystematic errors may reflect accumulated noise from memory maintenance while systematic errors may originate from non-mnemonic processes such as noisy sensorimotor transformation; (3) There may be independent mechanisms supporting the spatial and temporal processing of VSWM.

The Effects of Amyloid and Tau on Functional Network Connectivity in Older Populations.

Background: Neuroimaging studies suggest that aged brains show altered connectivity within and across functional networks. Similar changes in functional network integrity are also linked to the accumulation of pathological proteins in the brain, such as amyloid-beta plaques and neurofibrillary tau tangles seen in Alzheimer's disease. However, less is known about the specific impacts of amyloid and tau on functional network connectivity in cognitively normal older adults who harbor these proteins. Methods: We briefly summarize recent neuroimaging studies of aging and then thoroughly review positron emission tomography and functional magnetic resonance imaging studies measuring the relationship between amyloid-tau pathology and functional connectivity in cognitively normal older individuals. Results: The literature overall suggests that amyloid-positive older individuals show minor cognitive dysfunction and aberrant default mode network connectivity compared with amyloid-negative individuals. Tau, however, is more closely associated with network hypoconnectivity and poorer cognition. Those with substantial amyloid and tau experience even greater cognitive decline compared with those with primarily amyloid or tau, suggesting a potential interaction. Multimodal neuroimaging studies suggest that older adults with pathological protein deposits show amyloid-related hyperconnectivity and tau-related hypoconnectivity in multiple functional networks, including the default mode and frontoparietal networks. Discussion: We propose an updated model considering the effects of amyloid and tau on functional connectivity in older individuals. Large, longitudinal neuroimaging studies with multiple levels of analysis are required to obtain a deeper understanding of the dynamic relationship between pathological protein accumulation and functional connectivity changes, as amyloid- and tau-induced connectivity alterations may have critical and time-varying effects on neurodegeneration and cognitive decline. Impact statement Amyloid and tau accumulation have been linked with altered functional connectivity in cognitively normal older adults. This review synthesized recent functional imaging literatures in a discussion of how amyloid and tau can interactively affect functional connectivity in nonlinear ways, which can explain previous conflicting findings. Changes in connectivity strength may depend on the accumulation of both amyloid and tau, and their integrative effects seem to have critical consequences on cognition. Elucidating the effects of these pathological proteins on brain functioning is paramount to understand the etiology of Alzheimer's disease and the aging process overall.

Parkinson's Disease With Visual Hallucinations Is Associated With Epileptiform Activity on EEG.

Background: Visual hallucinations (VHs) in Parkinson's disease (PD) are the cardinal symptoms which declare the onset of PD psychosis (PDP). The anthropomorphic and zoomorphic VHs of PD resemble those of Charles Bonnet syndrome and temporal lobe epilepsy. In both of these disorders electroencephalography (EEG) abnormalities have been described. We therefore sought to examine whether VHs in PD were associated with similar EEG abnormalities. Methods: This retrospective observational study searched the medical records of 300 PD patients and filtered for those containing clinical 20-min scalp EEGs. Remaining records were separated into two groups: patients with reported VHs and those without. The prevalence of epileptiform discharges in the EEGs of both groups was identified. Results: Epileptiform discharges were present in 5 of 13 (38.5%) PD patients with VHs; all localized to the temporal lobe. No epileptiform discharges were observed in the EEGs of the 31 PD patients without VHs. Conclusion: The significantly high incidence of temporal lobe epileptiform discharges in PD patients with VHs as compared to those without VHs lends to the possibility of an association visual cortex epileptogenic focus. Accordingly, for treatment-refractory patients, antiepileptic drugs might be considered, as in the case of Charles Bonnet syndrome, temporal lobe epilepsy and migraine with visual aura. Future prospective studies involving larger samples and multi-center cohorts are required to validate these observational findings.

Functional neural network configuration in late childhood varies by age and cognitive state.

Late childhood and early adolescence is characterized by substantial brain maturation which contributes to both adult-like and age-dependent resting-state network connectivity patterns. However, it remains unclear whether these functional network characteristics in children are subject to differential modulation by distinct cognitive demands as previously found in adults. We conducted network analyses on fMRI data from 60 children (aged 9-12) during resting and during three distinct tasks involving decision making, visual perception, and spatial working memory. Graph measures of network architecture, functional integration, and flexibility were calculated for each of the four states. During resting state, the children's network architecture was similar to that in young adults (N = 60, aged 20-23) but the degree of similarity was age- and network-dependent. During the task states, the children's whole-brain network exhibited enhanced integration in response to increased cognitive demand. Additionally, the frontoparietal network showed flexibility in connectivity patterns across states while networks implicated in motor and visual processing remained relatively stable. Exploratory analyses suggest different relationships between behavioral performance and connectivity profiles for the working memory and perceptual tasks. Together, our findings demonstrate state- and age-dependent features in functional network connectivity during late childhood, potentially providing markers for brain and cognitive development.

Akinetic rigid symptoms are associated with decline in a cortical motor network in Parkinson's disease.

The akinetic/rigid (AR) motor subtype of Parkinson's Disease is associated with increased rates of motor and cognitive decline. Cross-sectional studies examining the neural correlates of AR have found abnormalities in both subcortical and cortical networks involved in motor planning and execution relative to controls. To better understand how these cross-sectional findings are implicated in the unique decline associated with the AR subtype, we examined whether baseline AR symptoms are associated with longitudinal decline of these networks, in contrast to other motor symptoms such as tremor. Using whole brain multiple regression analyses we found that worse AR symptoms at baseline were associated with greater gray matter loss over four years in superior parietal and paracentral lobules and motor cortex. These regions also showed altered connectivity patterns with posterior parietal, premotor, pre-supplementary motor area and dorsolateral prefrontal regions in association with AR symptoms across subjects. Thus, AR symptoms are related to gray matter decline and aberrant functional connectivity in a network of frontal-parietal regions critical for motor planning and execution. These structural and functional abnormalities may therefore be implicated in the more aggressive course of decline associated with the AR relative to tremor-dominant subtype.

Topographic Mapping as a Basic Principle of Functional Organization for Visual and Prefrontal Functional Connectivity.

The organization of region-to-region functional connectivity has major implications for understanding information transfer and transformation between brain regions. We extended connective field mapping methodology to 3-D anatomic space to derive estimates of corticocortical functional organization. Using multiple publicly available human (both male and female) resting-state fMRI data samples for model testing and replication analysis, we have three main findings. First, we found that the functional connectivity between early visual regions maintained a topographic relationship along the anterior-posterior dimension, which corroborates previous research. Higher order visual regions showed a pattern of connectivity that supports convergence and biased sampling, which has implications for their receptive field properties. Second, we demonstrated that topographic organization is a fundamental aspect of functional connectivity across the entire cortex, with higher topographic connectivity between regions within a functional network than across networks. The principle gradient of topographic connectivity across the cortex resembled whole-brain gradients found in previous work. Last but not least, we showed that the organization of higher order regions such as the lateral prefrontal cortex demonstrate functional gradients of topographic connectivity and convergence. These organizational features of the lateral prefrontal cortex predict task-based activation patterns, particularly visual specialization and higher order rules. In sum, these findings suggest that topographic input is a fundamental motif of functional connectivity between cortical regions for information processing and transfer, with maintenance of topography potentially important for preserving the integrity of information from one region to another.

Posterior parietal influences on visual network specialization during development: An fMRI study of functional connectivity in children ages 9 to 12.

Visual processing in the primate brain is highly organized along the ventral visual pathway, although it is still unclear how categorical selectivity emerges in this system. While many theories have attempted to explain the pattern of visual specialization within the ventral occipital and temporal areas, the biased connectivity hypothesis provides a framework which postulates extrinsic connectivity as a potential mechanism in shaping the development of category selectivity. As the posterior parietal cortex plays a central role in visual attention, we examined whether the pattern of parietal connectivity with the face and scene processing regions is closely linked with the functional properties of these two visually selective networks in a cohort of 60 children ages 9 to 12. Functionally localized face and scene selective regions were used in deriving each visual network's resting-state functional connectivity. The children's face and scene processing networks appeared to show a weak network segregation during resting state, which was confirmed when compared to that of a group of gender and handedness matched adults. Parietal regions of these children showed differential connectivity with the face and scene networks, and the extent of this differential parietal-visual connectivity predicted individual differences in the degree of segregation between the two visual networks, which in turn predicted individual differences in visual perception performance. Finally, the pattern of parietal connectivity with the face processing network also predicted the foci of face-related activation in the right fusiform gyrus across children. These findings provide evidence that extrinsic connectivity with regions such as the posterior parietal cortex may have important implications in the development of specialized visual processing networks.

Model testing for distinctive functional connectivity gradients with resting-state fMRI data.

In accordance with the concept of topographic organization of neuroanatomical structures, there is an increased interest in estimating and delineating continuous changes in the functional connectivity patterns across neighboring voxels within a region of interest using resting-state fMRI data. Fundamental to this functional connectivity gradient analysis is the assumption that the functional organization is stable and uniform across the region of interest. To evaluate this assumption, we developed a statistical model testing procedure to arbitrate between overlapping, shifted, or different topographic connectivity gradients across subdivisions of a structure. We tested the procedure using the striatum, a subcortical structure consisting of the caudate nucleus and putamen, in which an extensive literature, primarily from rodents and non-human primates, suggest to have a shared topographic organization of a single diagonal gradient. We found, across multiple resting state fMRI data samples of different spatial resolutions in humans, and one macaque resting state fMRI data sample, that the models with different functional connectivity gradients across the caudate and putamen was the preferred model. The model selection procedure was validated in control conditions of checkerboard subdivisions, demonstrating the expected overlapping gradient. More specifically, while we replicated the diagonal organization of the functional connectivity gradients in both the caudate and putamen, our analysis also revealed a medial-lateral organization within the caudate. Not surprisingly, performing the same analysis assuming a unitary gradient obfuscates the medial-lateral organization of the caudate, producing only a diagonal gradient. These findings demonstrate the importance of testing basic assumptions and evaluating interpretations across species. The significance of differential topographic gradients across the putamen and caudate and the medial-lateral gradient of the caudate in humans should be tested in future studies.

Levodopa improves response inhibition and enhances striatal activation in early-stage Parkinson's disease.

Dopaminergic medications improve the motor symptoms of Parkinson's disease (PD), but their effect on response inhibition, a critical executive function, remains unclear. Previous studies primarily enrolled patients in more advanced stages of PD, when dopaminergic medication loses efficacy, and patients were typically on multiple medications. Here, we recruited 21 patients in early-stage PD on levodopa monotherapy and 37 age-matched controls to perform the stop-signal task during functional magnetic resonance imaging. In contrast to previous studies reporting null effects in more advanced PD, levodopa significantly improved response inhibition performance in our sample. No significant group differences were found in brain activations to pure motor inhibition or error processing (stop success vs. error trials). However, relative to controls, the PD group showed weaker striatal activations to salient events (infrequent vs. frequent events: stop vs. go trials) and fronto-striatal task-residual functional connectivity; both were restored with levodopa. Thus, levodopa appears to improve an important executive function in early-stage PD via enhanced salient signal processing, shedding new light on the role of dopaminergic signaling in response inhibition.

Preschool negative emotionality predicts activity and connectivity of the fusiform face area and amygdala in later childhood.

Negative emotionality (NE) refers to individual differences in the propensity to experience and react with negative emotions and is associated with increased risk of psychological disorder. However, research on the neural bases of NE has focused almost exclusively on amygdala activity during emotional face processing. This study broadened this framework by examining the relationship between observed NE in early childhood and subsequent neural responses to emotional faces in both the amygdala and the fusiform face area (FFA) in a late childhood/early adolescent sample. Measures of NE were obtained from children at age 3 using laboratory observations, and functional magnetic resonance imaging (fMRI) data were collected when these children were between the ages of 9 and 12 while performing a visual stimulus identity matching task with houses and emotional faces as stimuli. Multiple regression analyses revealed that higher NE at age 3 is associated with significantly greater activation in the left amygdala and left FFA but lower functional connectivity between these two regions during the face conditions. These findings suggest that those with higher early NE have subsequent alterations in both activity and connectivity within an extended network during face processing.

Response inhibition in Parkinson's disease: a meta-analysis of dopaminergic medication and disease duration effects.

Parkinson's disease is a neurodegenerative disorder involving the basal ganglia that results in a host of motor and cognitive deficits. Dopamine-replacement therapy ameliorates some of the hallmark motor symptoms of Parkinson's disease, but whether these medications improve deficits in response inhibition, a critical executive function for behavioral control, has been questioned. Several studies of Parkinson's disease patients "on" and "off" (12-h withdrawal) dopaminergic medications suggested that dopamine-replacement therapy did not provide significant response inhibition benefits. However, these studies tended to include patients with moderate-to-advanced Parkinson's disease, when the efficacy of dopaminergic drugs is reduced compared to early-stage Parkinson's disease. In contrast, a few recent studies in early-stage Parkinson's disease report that dopaminergic drugs do improve response inhibition deficits. Based on these findings, we hypothesized that Parkinson's disease duration interacts with medication status to produce changes in cognitive function. To investigate this issue, we conducted a meta-analysis of studies comparing patients with Parkinson's disease and healthy controls on tests of response inhibition (50 comparisons from 42 studies). The findings supported the hypothesis; medication benefited response inhibition in patients with shorter disease duration, whereas "off" medication, moderate deficits were present that were relatively unaffected by disease duration. These findings support the role of dopamine in response inhibition and suggest the need to consider disease duration in research of the efficacy of dopamine-replacement therapy on cognitive function in Parkinson's disease.

Abnormal resting state effective connectivity within the default mode network in major depressive disorder: A spectral dynamic causal modeling study.

INTRODUCTION: Understanding the neural basis underlying major depressive disorder (MDD) is essential for the diagnosis and treatment of this mental disorder. Aberrant activation and functional connectivity of the default mode network (DMN) have been consistently found in patients with MDD. It is not known whether effective connectivity within the DMN is altered in MDD. OBJECTS: The primary object of this study is to investigate the effective connectivity within the DMN during resting state in MDD patients before and after eight weeks of antidepressant treatment. METHODS: We defined four regions of the DMN (medial frontal cortex, posterior cingulate cortex, left parietal cortex, and right parietal cortex) for each participant using a group independent component analysis. The coupling parameters reflecting the causal interactions among the DMN regions were estimated using spectral dynamic causal modeling (DCM). RESULTS: Twenty-seven MDD patients and 27 healthy controls were included in the statistical analysis. Our results showed declined influences from the left parietal cortex to other DMN regions in the pre-treatment patients as compared with healthy controls. After eight weeks of treatment, the influence from the right parietal cortex to the posterior cingulate cortex significantly decreased. CONCLUSION: These findings suggest that the reduced excitatory causal influence of the left parietal cortex is the key alteration of the DMN in patients with MDD, and the disrupted causal influences that parietal cortex exerts on the posterior cingulate cortex is responsive to antidepressant treatment.

Neural markers of emotional face perception across psychotic disorders and general population.

There is considerable variation in negative and positive symptoms of psychosis, global functioning, and emotional face perception (EFP), not only in schizophrenia but also in other psychotic disorders and healthy individuals. However, EFP impairment and its association with worse symptoms and global functioning have been examined largely in the domain of schizophrenia. The present study adopted a dimensional approach to examine the association of behavioral and neural measures of EFP with symptoms of psychosis and global functioning across individuals with schizophrenia spectrum (SZ; N = 28) and other psychotic (OP; N = 29) disorders, and never-psychotic participants (NP; N = 21). Behavioral and functional MRI data were recorded as participants matched emotional expressions of faces and geometrical shapes. Lower accuracy and increased activity in early visual regions, hippocampus, and amygdala during emotion versus shape matching were associated with higher negative, but not positive, symptoms and lower global functioning, across all participants. This association remained even after controlling for group-related (SZ, OP, and NP) variance, dysphoria, and antipsychotic medication status, except in amygdala. Furthermore, negative symptoms mediated the relationship between behavioral and brain EFP measures and global functioning. This study provides some of the first evidence supporting the specific relationship of EFP measures with negative symptoms and global functioning across psychotic and never-psychotic samples, and transdiagnostically across different psychotic disorders. Present findings help bridge the gap between basic EFP-related neuroscience research and clinical research in psychosis, and highlight EFP as a potential symptom-specific marker that tracks global functioning. (PsycINFO Database Record

Alterations in visual cortical activation and connectivity with prefrontal cortex during working memory updating in major depressive disorder.

The present study examined the impacts of major depressive disorder (MDD) on visual and prefrontal cortical activity as well as their connectivity during visual working memory updating and related them to the core clinical features of the disorder. Impairment in working memory updating is typically associated with the retention of irrelevant negative information which can lead to persistent depressive mood and abnormal affect. However, performance deficits have been observed in MDD on tasks involving little or no demand on emotion processing, suggesting dysfunctions may also occur at the more basic level of information processing. Yet, it is unclear how various regions in the visual working memory circuit contribute to behavioral changes in MDD. We acquired functional magnetic resonance imaging data from 18 unmedicated participants with MDD and 21 age-matched healthy controls (CTL) while they performed a visual delayed recognition task with neutral faces and scenes as task stimuli. Selective working memory updating was manipulated by inserting a cue in the delay period to indicate which one or both of the two memorized stimuli (a face and a scene) would remain relevant for the recognition test. Our results revealed several key findings. Relative to the CTL group, the MDD group showed weaker postcue activations in visual association areas during selective maintenance of face and scene working memory. Across the MDD subjects, greater rumination and depressive symptoms were associated with more persistent activation and connectivity related to no-longer-relevant task information. Classification of postcue spatial activation patterns of the scene-related areas was also less consistent in the MDD subjects compared to the healthy controls. Such abnormalities appeared to result from a lack of updating effects in postcue functional connectivity between prefrontal and scene-related areas in the MDD group. In sum, disrupted working memory updating in MDD was revealed by alterations in activity patterns of the visual association areas, their connectivity with the prefrontal cortex, and their relationship with core clinical characteristics. These results highlight the role of information updating deficits in the cognitive control and symptomatology of depression.

Hemispheric Lateralization of Resting-State Functional Connectivity of the Anterior Insula: Association with Age, Gender, and a Novelty-Seeking Trait.

Resting-state functional connectivity (rsFC) is widely used to examine cerebral functional organization. The imaging literature has described lateralization of insula activations during cognitive and affective processing. Evidence appears to support a role of the right-hemispheric insula in attentional orientation to salient stimulus, interoception, and physiological arousal, and a role of the left-hemispheric insula in cognitive and affective control, as well as perspective taking. In this study, in a large data set of healthy adults, we examined lateralization of the rsFC of the anterior insula (AI) by computing a laterality index (LI) of connectivity with 54 regions from the Automated Anatomic Labeling atlas. At a corrected threshold (p < 0.001), the AI is left lateralized in connectivity with the dorsomedial prefrontal cortex, superior frontal gyrus, inferior frontal cortex, and posterior orbital gyrus and right lateralized in connectivity with the postcentral gyrus, supramarginal gyrus, and superior parietal lobule. In gender differences, women, but not men, showed right-lateralized connectivity to the thalamus. Furthermore, in a subgroup of participants assessed by the tridimensional personality questionnaire, novelty seeking is correlated with the extent of left lateralization of AI connectivity to the pallidum and putamen in men and with the extent of right lateralization of AI connectivity to the parahippocampal gyrus in women. These findings support hemispheric functional differentiation of the AI.

Transdiagnostic neural markers of emotion-cognition interaction in psychotic disorders.

Deficits in working memory (WM) and emotion processing are prominent impairments in psychotic disorders, and have been linked to reduced quality of life and real-world functioning. Translation of knowledge regarding the neural circuitry implementing these deficits into improved diagnosis and targeted treatments has been slow, possibly because of categorical definitions of disorders. Using the dimensional Research Domain Criteria (RDoC) framework, we investigated the clinical and practical utility of transdiagnostic behavioral and neural measures of emotion-related WM disruption across psychotic disorders. Behavioral and functional MRI data were recorded while 53 participants with psychotic disorders and 29 participants with no history of psychosis performed a modified n-back task with fear and neutral distractors. Hierarchical regression analyses showed that psychotic symptoms entered after diagnosis accounted for unique variance in fear versus neutral accuracy and activation in the ventrolateral, dorsolateral, and dorsomedial prefrontal cortex, but diagnostic group entered after psychotic symptoms did not. These results remained even after controlling for negative symptoms, disorganized symptoms, and dysphoria. Finally, worse accuracy and greater prefrontal activity were associated with poorer social functioning and unemployment across diagnostic groups. Present results support the transdiagnostic nature of behavioral and neuroimaging measures of emotion-related WM disruption as they relate to psychotic symptoms, irrespective of diagnosis. They also provide support for the practical utility of these markers in explaining real-world functioning. Overall, these results elucidate key aspects of the RDoC construct of WM maintenance by clarifying its transdiagnostic importance and clinical utility in psychotic disorders. (PsycINFO Database Record