Impaired contour object perception in psychosis.

Contour integration, the process of joining spatially separated elements into a single unified line, has consistently been found to be impaired in schizophrenia. Recent work suggests that this deficit could be associated with psychotic symptomatology, rather than a specific diagnosis such as schizophrenia. Examining a transdiagnostic sample of participants with psychotic psychopathology, we obtained quantitative indices of contour perception in a psychophysical behavioral task. We found impaired contour discrimination performance among people with psychotic psychopathology (PwPP, n = 62) compared to healthy controls (n = 34) and biological relatives of PwPP (n = 44). Participants with schizophrenia (n = 31) showed impaired task performance compared to participants with bipolar disorder (n = 18). We also measured responses during an analogous task using ultra-high field (7T) functional MRI and found higher responses in the lateral occipital cortex of PwPP compared to controls. Using task-based functional connectivity analyses, we observed abnormal connectivity between visual brain areas during contour perception among PwPP. These connectivity differences only emerged when participants had to distinguish the contour object from background distractors, suggesting that a failure to suppress noise elements relative to contour elements may underlie impaired contour processing in PwPP. Our results are consistent with impaired contour integration in psychotic psychopathology, and especially schizophrenia, that is related to cognitive dysfunction, and may be linked to impaired functional connectivity across visual regions.

The psychosis human connectome project: Design and rationale for studies of visual neurophysiology.

Visual perception is abnormal in psychotic disorders such as schizophrenia. In addition to hallucinations, laboratory tests show differences in fundamental visual processes including contrast sensitivity, center-surround interactions, and perceptual organization. A number of hypotheses have been proposed to explain visual dysfunction in psychotic disorders, including an imbalance between excitation and inhibition. However, the precise neural basis of abnormal visual perception in people with psychotic psychopathology (PwPP) remains unknown. Here, we describe the behavioral and 7 tesla MRI methods we used to interrogate visual neurophysiology in PwPP as part of the Psychosis Human Connectome Project (HCP). In addition to PwPP (n = 66) and healthy controls (n = 43), we also recruited first-degree biological relatives (n = 44) in order to examine the role of genetic liability for psychosis in visual perception. Our visual tasks were designed to assess fundamental visual processes in PwPP, whereas MR spectroscopy enabled us to examine neurochemistry, including excitatory and inhibitory markers. We show that it is feasible to collect high-quality data across multiple psychophysical, functional MRI, and MR spectroscopy experiments with a sizable number of participants at a single research site. These data, in addition to those from our previously described 3 tesla experiments, will be made publicly available in order to facilitate further investigations by other research groups. By combining visual neuroscience techniques and HCP brain imaging methods, our experiments offer new opportunities to investigate the neural basis of abnormal visual perception in PwPP.

Tetrahydrocannabinol Reduces Hapten-Driven Mast Cell Accumulation and Persistent Tactile Sensitivity in Mouse Model of Allergen-Provoked Localized Vulvodynia.

Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. An increase in numbers of vulvar mast cells often accompanies a clinical diagnosis of vulvodynia and a history of allergies amplifies the risk of developing this condition. We previously showed that repeated exposures to oxazolone dissolved in ethanol on the labiar skin of mice led to persistent genital sensitivity to pressure and a sustained increase in labiar mast cells. Here we sensitized female mice to the hapten dinitrofluorobenzene (DNFB) dissolved in saline on their flanks, and subsequently challenged them with the same hapten or saline vehicle alone for ten consecutive days either on labiar skin or in the vaginal canal. We evaluated tactile ano-genital sensitivity, and tissue inflammation at serial timepoints. DNFB-challenged mice developed significant, persistent tactile sensitivity. Allergic sites showed mast cell accumulation, infiltration of resident memory CD8+CD103+ T cells, early, localized increases in eosinophils and neutrophils, and sustained elevation of serum Immunoglobulin E (IgE). Therapeutic intra-vaginal administration of Δ9-tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity. Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures.