Assessing neural tuning for object perception in schizophrenia and bipolar disorder with multivariate pattern analysis of fMRI data.

IntroductionDeficits in visual perception are well-established in schizophrenia and are linked to abnormal activity in the lateral occipital complex (LOC). Related deficits may exist in bipolar disorder. LOC contains neurons tuned to object features. It is unknown whether neural tuning in LOC or other visual areas is abnormal in patients, contributing to abnormal perception during visual tasks. This study used multivariate pattern analysis (MVPA) to investigate perceptual tuning for objects in schizophrenia and bipolar disorder.MethodsFifty schizophrenia participants, 51 bipolar disorder participants, and 47 matched healthy controls completed five functional magnetic resonance imaging (fMRI) runs of a perceptual task in which they viewed pictures of four different objects and an outdoor scene. We performed classification analyses designed to assess the distinctiveness of activity corresponding to perception of each stimulus in LOC (a functionally localized region of interest). We also performed similar classification analyses throughout the brain using a searchlight technique. We compared classification accuracy and patterns of classification errors across groups.ResultsStimulus classification accuracy was significantly above chance in all groups in LOC and throughout visual cortex. Classification errors were mostly within-category confusions (e.g., misclassifying one chair as another chair). There were no group differences in classification accuracy or patterns of confusion.ConclusionsThe results show for the first time MVPA can be used successfully to classify individual perceptual stimuli in schizophrenia and bipolar disorder. However, the results do not provide evidence of abnormal neural tuning in schizophrenia and bipolar disorder

Reorganization of the Functional Connectome From Rest to a Visual Perception Task in Schizophrenia and Bipolar Disorder

Functional connectome organization is altered in schizophrenia (SZ) and bipolar disorder (BD). However, it remains unclear whether network reorganization during a task relative to rest is also altered in these disorders. This study examined connectome organization in patients with SZ (N = 43) and BD (N = 42) versus healthy controls (HC; N = 39) using fMRI data during a visual object-perception task and at rest. Graph analyses were conducted for the whole-brain network using indices selected a priori: three reflecting network segregation (clustering coefficient, local efficiency, modularity), two reflecting integration (characteristic path length, global efficiency). Group differences were limited to network segregation and were more evident in SZ (clustering coefficient, modularity) than in BD (clustering coefficient) compared to HC. State differences were found across groups for segregation (local efficiency) and integration (characteristic path length). There was no group-by-state interaction for any graph index. In summary, aberrant network organization compared to HC was confirmed, and was more evident in SZ than in BD. Yet, reorganization was largely intact in both disorders. These findings help to constrain models of dysconnection in SZ and BD, suggesting that the extent of functional dysconnectivity in these disorders tends to persist across changes in mental state

Efficacy of transoral fundoplication vs omeprazole for treatment of regurgitation in a randomized controlled trial.

Background The aim of this randomized, crossover study was to determine if transoral fundoplication (TF) could further improve clinical outcomes in partial responders to high-dose (HD) proton-pump inhibitor (PPI) therapy and to evaluate durability of TF. Methods In seven United States centers, patients with hiatal hernia ≤2 cm and abnormal esophageal acid exposure (EAE) were randomized to TF (n = 40) or HD PPIs (n = 23) group. At 6-month follow-up, PPI patients underwent crossover. We assessed clinical outcomes 6-month post TF in crossover patients (COP), as compared to 6-month of HD PPI therapy, and 12-month outcomes in patients initially randomized to TF. The primary outcome was symptom control evaluated by Reflux Disease Questionnaire and Reflux Symptom Index. Secondary outcomes included healing of esophagitis, normalization of EAE and PPI use after TF. We analyzed 21 COP and 39 TF patients. McNemar’s test or Fisher exact test was used to compare proportions. Results Of 63 randomized patients, 3 were lost to follow-up, leaving 39 TF and 21 COP for analyses. In the COP, TF further improved control of regurgitation and of atypical symptoms achieved after six months of HD PPIs. Of 20 patients with GERD symptoms after six months of high-dose PPI therapy, 65% (13/20) reported global elimination of troublesome regurgitation and atypical symptoms post TF off PPIs; 67% (6/9) reported no troublesome regurgitation. Esophagitis further healed in 75% (6/8) of patients. Seventy-one percent of COP patients were off PPIs six months following TF. Normalization of EAE decreased from 52% after HD PPIs (on PPIs) to 33% after TF (off PPIs), p =0.388. In the original TF group, 12-month post TF, 77% of patients achieved complete symptom control, 82% ceased PPI therapy, 100% healed esophagitis and 45% normalized EAE. Conclusions The results of this study indicate that in patients with incomplete symptom control on high-dose PPI therapy TF may provide further elimination of symptoms and esophagitis healing. In the original TF group, the clinical outcomes of TF remained stable between 6- and 12-month follow-up. Trial registration Clinicaltrials.gov: NCT01647958

From inefficient to pop-out visual search in one week

We investigated changes in brain activity while participants learned to perform a visual conjunction search task over eight successive days. In an eventrelated functional magnetic resonance imaging (fMRI) experiment, subjects searched for a red-green disk amongst many mirror-symmetric green-red distractors. Over sessions, accuracy increased and search-time decreased, indicative of perceptual learning and popout. This behavioral change was correlated with a decrease in neuronal activation in frontal and parietal cortex and an increase in activity in early visual areas during search. Training was specific to the targetdistractor stimuli and did not transfer to other configurations. Our findings suggest that difficult visual search can be learned within a few days and that the trained skill is associated with distinct changes in activation in occipital, parietal and frontal cortex

Evidence for intact stimulus-specific neural adaptation for visual objects in schizophrenia and bipolar disorder: An ERP study.

People with schizophrenia (SZ) or bipolar disorder (BD) experience dysfunction in visual processing. Dysfunctional neural tuning, in which neurons and neuronal populations are selectively activated by specific features of visual stimuli, may contribute to these deficits. Few studies have examined this possibility and there are inconsistent findings of tuning deficits in the literature. We utilized an event-related potential (ERP) paradigm to examine neural adaptation for visual objects, a measure of neural tuning whereby neurons respond less strongly to the repeated presentation of the same stimulus. Seventy-seven SZ, 53 BD, and 49 healthy comparison participants (HC) were examined. In three separate conditions, pictures of objects were presented repeatedly: the same object (SS), different objects from the same category (e.g., two different vases; SD), or different objects from different categories (e.g., a barrel and a clock, DD). Mass-univariate cluster-based permutation analyses identified electrodes and time-windows in which there were significant differences between the SS vs. DD and the SD vs. DD conditions. Mean ERP amplitudes were extracted from these clusters and analyzed for group differences. Results revealed a significant condition difference over parieto-occipital electrodes for the SS-DD comparison between 109-164 ms and for the SD-DD comparison between 78-203 ms, with larger amplitudes in the DD compared to either SS or SD condition. However, there were no significant differences in the pattern of results between groups. Thus, while we found neural adaptation effects using this ERP paradigm, we did not find evidence of group differences. Our results suggest that people with SZ or BD may not exhibit deficits in neural tuning for processing of visual objects using this EEG task with rapidly presented stimuli. However, the results are inconsistent with other studies using different methodologies (e.g., fMRI, behavioral tasks) that have found tuning deficits in people with schizophrenia

Neural correlates of context-dependent feature conjunction learning in visual search tasks

Many perceptual learning experiments show that repeated exposure to a basic visual feature such as a specific orientation or spatial frequency can modify perception of that feature, and that those perceptual changes are associated with changes in neural tuning early in visual processing. Such perceptual learning effects thus exert a bottom-up influence on subsequent stimulus processing, independent of task-demands or endogenous influences (e.g., volitional attention). However, it is unclear whether such bottom-up changes in perception can occur as more complex stimuli such as conjunctions of visual features are learned. It is not known whether changes in the efficiency with which people learn to process feature conjunctions in a task (e.g., visual search) reflect true bottom-up perceptual learning versus top-down, task-related learning (e.g., learning better control of endogenous attention). Here we show that feature conjunction learning in visual search leads to bottom-up changes in stimulus processing. First, using fMRI, we demonstrate that conjunction learning in visual search has a distinct neural signature: an increase in target-evoked activity relative to distractor-evoked activity (i.e., a relative increase in target salience). Second, we demonstrate that after learning, this neural signature is still evident even when participants passively view learned stimuli while performing an unrelated, attention-demanding task. This suggests that conjunction learning results in altered bottom-up perceptual processing of the learned conjunction stimuli (i.e., a perceptual change independent of the task). We further show that the acquired change in target-evoked activity is contextually dependent on the presence of distractors, suggesting that search array Gestalts are learned. (C) 2016 Wiley Periodicals, Inc