Schizophrenia Patients Show Largely Similar Salience Signaling Compared to Healthy Controls in an Observational Task Environment

Recent evidence suggests that the aberrant signaling of salience is associated with psychotic illness. Salience, however, can take many forms in task environments. For example, salience may refer to any of the following: (1) the valence of an outcome, (2) outcomes that are unexpected, called reward prediction errors (PEs), or (3) cues associated with uncertain outcomes. Here, we measure brain responses to different forms of salience in the context of a passive PE-signaling task, testing whether patients with schizophrenia (SZ) showed aberrant signaling of particular types of salience. We acquired event-related MRI data from 29 SZ patients and 23 controls during the performance of a passive outcome prediction task. Across groups, we found that the anterior insula and posterior parietal cortices were activated to multiple different types of salience, including PE magnitude and heightened levels of uncertainty. However, BOLD activation to salient events was not significantly different between patients and controls in many regions, including the insula, posterior parietal cortices, and default mode network nodes. Such results suggest that deficiencies in salience processing in SZ may not result from an impaired ability to signal salience per se, but instead the ability to use such signals to guide future actions. Notably, no between-group differences were observed in BOLD signal changes associated with PE-signaling in the striatum. However, positive symptom severity was found to significantly correlate with the magnitudes of salience contrasts in default mode network nodes. Our results suggest that, in an observational environment, SZ patients may show an intact ability to activate striatal and cortical regions to rewarding and non-rewarding salient events. Furthermore, reduced deactivation of a hypothesized default mode network node for SZ participants with high levels of positive symptoms, following salient events, point to abnormalities in interactions of the salience network with other brain networks, and their potential importance to positive symptoms.

Attention controls multisensory perception via 2 distinct mechanisms at different levels of the cortical hierarchy

To form a percept of the multisensory world, the brain needs to integrate signals from common sources weighted by their reliabilities and segregate those from independent sources. Previously, we have shown that anterior parietal cortices combine sensory signals into representations that take into account the signals’ causal structure (i.e., common versus independent sources) and their sensory reliabilities as predicted by Bayesian causal inference. The current study asks to what extent and how attentional mechanisms can actively control how sensory signals are combined for perceptual inference. In a pre- and postcueing paradigm, we presented observers with audiovisual signals at variable spatial disparities. Observers were precued to attend to auditory or visual modalities prior to stimulus presentation and postcued to report their perceived auditory or visual location. Combining psychophysics, functional magnetic resonance imaging (fMRI), and Bayesian modelling, we demonstrate that the brain moulds multisensory inference via 2 distinct mechanisms. Prestimulus attention to vision enhances the reliability and influence of visual inputs on spatial representations in visual and posterior parietal cortices. Poststimulus report determines how parietal cortices flexibly combine sensory estimates into spatial representations consistent with Bayesian causal inference. Our results show that distinct neural mechanisms control how signals are combined for perceptual inference at different levels of the cortical hierarchy.

Enhancement of Visuospatial Working Memory by Transcranial Direct Current Stimulation (tDCS) on Prefrontal and Parietal Cortices

Objective: Previous studies have reported dorsolateral prefrontal cortex (DLPFC) and posterior parietal (PPC) activation during the performance of spatial working memory (SWM), so we decided to investigate the comparison of Transcranial Direct current stimulation (tDCS) effect between these two areas. Methods: Fifty-four healthy right-handed students (27 female, 27 male; age= 24.3±.2 years) were randomly assigned to anodal (N=27) and sham group (N= 27), each of these groups was further divided into F4 (representing right DLPFC) or P4 (representing right PPC) subgroups, respectively. A Computerized Corsi Block Tapping task has then used to measure spatial working memory. The t-DCS intervention consisted of five daily sessions with a direct current of 1.5 mA for 15 minutes over the F4 or P4 area of the brain at 24-hour intervals. Results: Significant enhancement of the SWM span as well as a faster response were seen after anodal tDCS in both the forward and backward direction. Moreover, the right DLPFC stimulation induced a faster reaction time compared to the right PPC. Conclusions: Both DLPFC and PP cortices stimulation, as an element of the frontoparietal network, showed SWM enhancement, with the DLPFC being more effected. Our finding provides new evidence for the comparison of the effect of stimulation on the two main activated cortical areas during visuospatial WM.

Obesity status and obesity-associated gut dysbiosis effects on hypothalamic structural covariance

Background Functional connectivity alterations in the lateral and medial hypothalamic networks have been associated with the development and maintenance of obesity, but the possible impact on the structural properties of these networks remains largely unexplored. Also, obesity-related gut dysbiosis may delineate specific hypothalamic alterations within obese conditions. We aim to assess the effects of obesity, and obesity and gut-dysbiosis on the structural covariance differences in hypothalamic networks, executive functioning, and depressive symptoms. Methods Medial (MH) and lateral (LH) hypothalamic structural covariance alterations were identified in 57 subjects with obesity compared to 47 subjects without obesity. Gut dysbiosis in the subjects with obesity was defined by the presence of high (n = 28) and low (n = 29) values in a BMI-associated microbial signature, and posthoc comparisons between these groups were used as a proxy to explore the role of obesity-related gut dysbiosis on the hypothalamic measurements, executive function, and depressive symptoms. Results Structural covariance alterations between the MH and the striatum, lateral prefrontal, cingulate, insula, and temporal cortices are congruent with previously functional connectivity disruptions in obesity conditions. MH structural covariance decreases encompassed postcentral parietal cortices in the subjects with obesity and gut-dysbiosis, but increases with subcortical nuclei involved in the coding food-related hedonic information in the subjects with obesity without gut-dysbiosis. Alterations for the structural covariance of the LH in the subjects with obesity and gut-dysbiosis encompassed increases with frontolimbic networks, but decreases with the lateral orbitofrontal cortex in the subjects with obesity without gut-dysbiosis. Subjects with obesity and gut dysbiosis showed higher executive dysfunction and depressive symptoms. Conclusions Obesity-related gut dysbiosis is linked to specific structural covariance alterations in hypothalamic networks relevant to the integration of somatic-visceral information, and emotion regulation.

Reading Modality Modifies Reading Network: Insights from Neural basis of Braille in Proficient Blind Readers

The neural basis of reading is highly consistent across a variety of languages and visual scripts. An unanswered question is whether the sensory modality of symbols influences the neural basis of reading. According to the modality-invariant view, reading depends on the same neural mechanisms regardless of the sensory input modality. Consistent with this idea, previous studies find that the visual word form area (VWFA) within the ventral occipitotemporal cortex (vOTC) is active when blind individuals read Braille by touch. However, connectivity-based theories of brain function suggest that the neural entry point of written symbols (touch vs. vision) may influence the neural architecture of reading. We compared the neural basis of the visual print (sighted n=15) and tactile Braille (congenitally blind n=19) in proficient readers using analogous reading and listening tasks. Written stimuli varied in word-likeness from real words to consonant strings and non-letter shape strings. Auditory stimuli consisted of words and backward speech sounds. Consistent with prior work, vOTC was active during Braille and visual reading. However, in sighted readers, visual print elicited a posterior/anterior vOTC word-form gradient: anterior vOTC preferred larger orthographic units (words), middle vOTC preferring consonant strings, and posterior vOTC responded to shapes (i.e., lower-level physical features). No such gradient was observed in blind readers of Braille. Consistent with connectivity predictions, in blind Braille readers, posterior parietal cortices (PPC) and parieto-occipital areas were recruited to a greater degree and PPC contained word-preferring patches. Lateralization of Braille in blind readers was predicted by laterality of spoken language, as well as by reading hand. These results suggested that the neural basis of reading is influenced by symbol modality and support connectivity-based views of cortical function.

Distributed functions of prefrontal and parietal cortices during sequential categorical decisions

Comparing sequential stimuli is crucial for guiding complex behaviors. To understand mechanisms underlying sequential decisions, we compared neuronal responses in the prefrontal cortex (PFC), the lateral intraparietal (LIP), and medial intraparietal (MIP) areas in monkeys trained to decide whether sequentially presented stimuli were from matching (M) or nonmatching (NM) categories. We found that PFC leads M/NM decisions, whereas LIP and MIP appear more involved in stimulus evaluation and motor planning, respectively. Compared to LIP, PFC showed greater nonlinear integration of currently visible and remembered stimuli, which correlated with the monkeys’ M/NM decisions. Furthermore, multi-module recurrent networks trained on the same task exhibited key features of PFC and LIP encoding, including nonlinear integration in the PFC-like module, which was causally involved in the networks’ decisions. Network analysis found that nonlinear units have stronger and more widespread connections with input, output, and within-area units, indicating putative circuit-level mechanisms for sequential decisions.

Identifying the neural correlates of affective task-switching and asymmetric affective task switching costs

The control of emotions is of potentially great clinical relevance. Accordingly, there has been increasing interest in understanding the cognitive mechanisms underlying the ability to switch efficiently between the processing of affective and non-affective information. Reports of asymmetrically increased switch costs when switching towards the more salient emotion task indicate specific demands in the flexible control of emotion. The neural mechanisms underlying affective task switching, however, are so far not fully understood. Using functional MRI (N=60), we observed that affective task switching was accompanied by increased activity in domain-general fronto-parietal control systems. BOLD activity in medial frontal, anterolateral prefrontal, and inferior parietal cortices was directly related to affective switch costs, indicating that these regions play a particular role in individual differences in (affective) task-switching ability. Asymmetric switch costs were associated with increased activity in the left inferior frontal junction area, an area related to task set control, and the pre-supplementary motor area, which is critical for response inhibition, suggesting that asymmetric switch costs reflect higher demands on inhibitory control of the dominant emotion task. These results contribute to a refined understanding of brain systems for the flexible control of emotions, and thereby identify valuable target systems for future clinical research.

Brain Anatomical Mediators of GRIN2B Gene Association with Attention/Hyperactivity Problems: An Integrated Genetic-Neuroimaging Study

This study aims to investigate the genetic and neural determinants of attention and hyperactivity problems. Using a proof-of-concept imaging genetics mediation design, we explore the relationship between the glutamatergic GRIN2B gene variants and inattention/hyperactivity with neuroanatomical measures as intermediates. Fifty-eight children and adolescents were evaluated for behavioral problems at three time points over approximately 7 years. The final assessment included blood drawing for genetic analyses and 3T magnetic resonance imaging. Attention/hyperactivity problems based on the Child Behavior Checklist/6-18, six GRIN2B polymorphisms and regional cortical thickness, and surface area and volume were estimated. Using general linear model (GLM) and mediation analyses, we tested whether GRIN2B exerted an influence on stable inattention/hyperactivity over development, and to what extent this effect was mediated by brain morphology. GLM results enlightened the relation between GRIN2B rs5796555-/A, volume in the left cingulate isthmus and inferior parietal cortices and inattention/hyperactivity. The mediation results showed that rs5796555-/A effect on inattention/hyperactivity was partially mediated by volume in the left isthmus of the cingulate cortex, suggesting a key role of this region in translating glutamatergic GRIN2B variations to attention/hyperactivity problems. This evidence can have important implications in the management of neurodevelopmental and psychiatric disorders.