Hippocampal temporal-parietal junction interaction in the production of psychotic symptoms: a framework for understanding the schizophrenic syndrome

A framework is described for understanding the schizophrenic syndrome at the brain systems level. It is hypothesized that over-activation of dynamic gesture and social perceptual processes in the temporal-parietal occipital junction (TPJ), posterior superior temporal sulcus (PSTS) and surrounding regions produce the syndrome (including positive and negative symptoms, their prevalence, prodromal signs, and cognitive deficits). Hippocampal system hyper-activity and atrophy have been consistently found in schizophrenia. Hippocampal activity is highly correlated with activity in the TPJ and may be a source of over-excitation of the TPJ and surrounding regions. Strong evidence for this comes from in-vivo recordings in humans during psychotic episodes. Many positive symptoms of schizophrenia can be reframed as the erroneous sense of a presence or other who is observing, acting, speaking, or controlling; these qualia are similar to those evoked during abnormal activation of the TPJ. The TPJ and PSTS play a key role in the perception (and production) of dynamic social, emotional, and attentional gestures for the self and others (e.g., body/face/eye gestures, audiovisual speech and prosody, and social attentional gestures such as eye gaze). The single cell representation of dynamic gestures is multimodal (auditory, visual, tactile), matching the predominant hallucinatory categories in schizophrenia. Inherent in the single cell perceptual signal of dynamic gesture representations is a computation of intention, agency, and anticipation or expectancy (for the self and others). Stimulation of the TPJ resulting in activation of the self representation has been shown to result a feeling of a presence or multiple presences (due to heautoscopy) and also bizarre tactile experiences. Neurons in the TPJ are also tuned, or biased to detect threat related emotions. Abnormal over-activation in this system could produce the conscious hallucination of a voice (audiovisual speech), a person or a touch. Over-activation could interfere with attentional/emotional gesture perception and production (negative symptoms). It could produce the unconscious feeling of being watched, followed, or of a social situation unfolding along with accompanying abnormal perception of intent and agency (delusions). Abnormal activity in the TPJ would also be predicted to create several cognitive disturbances that are characteristic of schizophrenia, including abnormalities in attention, predictive social processing, working memory, and a bias to erroneously perceive threat

From Tones in Tinnitus to Sensed Social Interaction in Schizophrenia: How Understanding Cortical Organization Can Inform the Study of Hallucinations and Psychosis

The content, modality, and perceptual attributes of hallucinations and other psychotic symptoms may be related to neural representation at a single cell and population level in the cerebral cortex. A brief survey of some principles and examples of cortical representation and organization will be presented together with evidence for a correspondence between the neurobiology of brain areas activated at the time of a hallucination and the content of the corresponding hallucinatory and psychotic experiences. Contrasting the hallucinations of schizophrenia with other conditions, we highlight phenomenological aspects of hallucinations that are ignored in clinical practice but carry potentially important information about the brain regions and dysfunctions underlying them. Knowledge of cortical representation and organization are being used to develop animal models of hallucination and to test treatments that are now beginning to translate to the clinical domain

The Function Biomedical Informatics Research Network Data Repository

The Function Biomedical Informatics Research Network (FBIRN) developed methods and tools for conducting multi-scanner functional magnetic resonance imaging (fMRI) studies. Method and tool development were based on two major goals: 1) to assess the major sources of variation in fMRI studies conducted across scanners, including instrumentation, acquisition protocols, challenge tasks, and analysis methods, and 2) to provide a distributed network infrastructure and an associated federated database to host and query large, multi-site, fMRI and clinical datasets. In the process of achieving these goals the FBIRN test bed generated several multi-scanner brain imaging data sets to be shared with the wider scientific community via the BIRN Data Repository (BDR). The FBIRN Phase 1 dataset consists of a traveling subject study of 5 healthy subjects, each scanned on 10 different 1.5 to 4 Tesla scanners. The FBIRN Phase 2 and Phase 3 datasets consist of subjects with schizophrenia or schizoaffective disorder along with healthy comparison subjects scanned at multiple sites. In this paper, we provide concise descriptions of FBIRN’s multi-scanner brain imaging data sets and details about the BIRN Data Repository instance of the Human Imaging Database (HID) used to publicly share the data

Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in Schizophrenia

The amplitude of low-frequency fluctuations (ALFF) in the blood oxygenation level-dependent (BOLD) signal during resting-state fMRI reflects the magnitude of local low-frequency BOLD oscillations, rather than interregional connectivity. ALFF is of interest to studies of cognition because fluctuations in spontaneous intrinsic brain activity relate to, and possibly even constrain, task-evoked brain responses in healthy people. Lower ALFF has been reported in schizophrenia, but the cognitive correlates of these reductions remain unknown. Here, we assess relationships between ALFF and attention and working memory in order to establish the functional relevance of intrinsic BOLD oscillatory power alterations with respect to specific cognitive impairments in schizophrenia. As part of the multisite FBIRN study, resting-state fMRI data were collected from schizophrenia subjects (SZ; n=168) and healthy controls (HC; n=166). Voxelwise fractional ALFF (fALFF), a normalized ALFF measure, was regressed on neuropsychological measures of sustained attention and working memory in SZ and HC to identify regions showing either common slopes across groups or slope differences between groups (all findings p<0.01 height, p<0.05 family-wise error cluster corrected). Poorer sustained attention was associated with smaller fALFF in the left superior frontal cortex and bilateral temporoparietal junction in both groups, with additional relationships in bilateral posterior parietal, posterior cingulate, dorsal anterior cingulate (ACC), and right dorsolateral prefrontal cortex (DLPFC) evident only in SZ. Poorer working memory was associated with smaller fALFF in bilateral ACC/mPFC, DLPFC, and posterior parietal cortex in both groups. Our findings indicate that smaller amplitudes of low-frequency BOLD oscillations during rest, measured by fALFF, were significantly associated with poorer cognitive performance, sometimes similarly in both groups and sometimes only in SZ, in regions known to subserve sustained attention and working memory. Taken together, these data suggest that the magnitude of resting-state BOLD oscillations shows promise as a biomarker of cognitive function in health and disease

Neural Correlates of Schizophrenia Negative Symptoms: Distinct Subtypes Impact Dissociable Brain Circuits.

BackgroundThe negative symptoms of schizophrenia include deficits in emotional expression and motivation. These deficits are stable over the course of illness and respond poorly to current medications. Previous studies have focused on negative symptoms as a single category; however, individual symptoms might be related to separate neurological disturbances. We analyzed data from the Functional Biomedical Informatics Research Network dataset to explore the relationship between individual negative symptoms and functional brain activity during an auditory oddball task.MethodsFunctional magnetic resonance imaging was conducted on 89 schizophrenia patients and 106 healthy controls during a two-tone auditory oddball task. Blood oxygenation level-dependent (BOLD) signal during the target tone was correlated with severity of five negative symptom domains from the Scale for the Assessment of Negative Symptoms.ResultsThe severity of alogia, avolition/apathy and anhedonia/asociality was negatively correlated with BOLD activity in distinct sets of brain regions associated with processing of the target tone, including basal ganglia, thalamus, insular cortex, prefrontal cortex, posterior cingulate and parietal cortex.ConclusionsIndividual symptoms were related to different patterns of functional activation during the oddball task, suggesting that individual symptoms might arise from distinct neural mechanisms. This work has potential to inform interventions that target these symptom-related neural disruptions