Beta-frequency electrophysiological bursts: BOLD correlates and relationships with psychotic illness

AIMS: To identify the BOLD (blood oxygenation level dependent) correlates of bursts of beta frequency band electrophysiological activity, and to compare BOLD responses between healthy controls and patients with psychotic illness. The post movement beta rebound (PMBR) is a transient increase in power in the beta frequency band (13-30 Hz), recorded with methods such as electroencephalography (EEG), following the completion of a movement. PMBR size is reduced in patients with schizophrenia and inversely correlated with severity of illness. PMBR size is inversely correlated with measures of schizotypy in non-clinical groups. Therefore, beta-band activity may reflect a fundamental neural process whose disruption plays an important role in the pathophysiology of schizophrenia. Recent work has found that changes in beta power reflect changes in the probability-of-occurrence of transient bursts of beta-frequency activity. Understanding the generators of beta bursts could help unravel the pathophysiology of psychotic illness and thus identify novel treatment targets. METHOD: EEG data were recorded simultaneously with BOLD data measured with 3T functional magnetic resonance imaging (fMRI), whilst participants performed an n-back working memory task. We included seventy-eight participants – 32 patients with schizophrenia, 16 with bipolar disorder and 30 healthy controls. Beta bursts were identified in the EEG data using a thresholding method and burst timings were used as markers in an event-related fMRI design convolved with a conventional haemodynamic response function. A region of interest analysis compared beta-event-related BOLD activity between patients and controls. RESULT: Beta bursts phasically activated brain regions implicated in coding task-relevant content (specifically, regions involved in the phonological representation of letter stimuli, as well as areas representing motor responses). Further, bursts were associated with suppression of tonically-active regions. In the EEG, PMBR was greater in controls than patients, and, in patients, PMBR size was positively correlated with Global Assessment of Functioning scores, and negatively correlated with persisting symptoms of disorganisation and performance on a digit symbol substition test. Despite this, patients showed greater, more extensive, burst-related BOLD activation than controls. CONCLUSION: Our findings are consistent with a recent model in which beta bursts serve to reactivate latently-maintained, task-relevant, sensorimotor information. The increased BOLD response associated with bursts in patients, despite reduced PMBR, could reflect inefficiency of burst-mediated cortical synchrony, or it may suggest that the sensorimotor information reactivated by beta bursts is less precisely specified in psychosis. We propose that dysfunction of the mechanisms by which beta bursts reactivate task-relevant content can manifest as disorganisation and working memory deficits, and may contribute to persisting symptoms and impairment in psychosis

Regional Brain Correlates of Beta Bursts in Health and Psychosis: A Concurrent Electroencephalography and Functional Magnetic Resonance Imaging Study

Background: There is emerging evidence for abnormal beta oscillations in psychosis. Beta-oscillations are likely to play a key role in the coordination of sensorimotor information, crucial to healthy mental function. Growing evidence suggests that beta oscillations typically manifest as transient “beta-bursts” that increase in probability following a motor response, observable as Post-Movement Beta Rebound (PMBR). Evidence indicates that PMBR is attenuated in psychosis, with greater attenuation associated with greater symptom severity and impairment. Delineating the functional role of beta-bursts may therefore be key to understanding the mechanisms underlying persistent psychotic illness.Methods: We used concurrent EEG and fMRI to identify BOLD correlates of beta-bursts during the N-back working memory task and intervening rest periods in healthy participants (N = 30) and patients with psychosis (N = 48). Results: During both task-blocks and intervening rest periods, beta-bursts phasically activated regions implicated in task-relevant content, while suppressing currently tonically active regions. Patients showed attenuated PMBR that was associated with persisting Disorganisation symptoms, as well as impairments in cognition and role function. Patients also showed greater task-related reductions in overall beta-burst rate, and greater, more extensive, beta-burst-related BOLD activation.Conclusions: Our evidence supports a model in which beta-bursts reactivate latently maintained sensorimotor information and are dysregulated and inefficient in psychosis. We propose that abnormalities in the mechanisms by which beta-bursts coordinate reactivation of contextually appropriate content can manifest as Disorganisation, working memory deficits and inaccurate forward models, and may underlie a “core deficit” associated with persisting symptoms and impairment

Glutathione and glutamate in schizophrenia: a 7T MRS study

In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate, and/or glutamine in the cerebral cortex, consistent with a post-inflammatory response, and that this reduction would be most marked in patients with “residual schizophrenia”, in whom an early stage with positive psychotic symptoms has progressed to a late stage characterized by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender, and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton magnetic resonance spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal components analysis (PCA) produced three clear components: an ACC glutathione–glutamate component; an insula-visual glutathione–glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione–glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excitotoxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness

Michigan Neural Distinctiveness (MiND) study protocol: investigating the scope, causes, and consequences of age-related neural dedifferentiation

Abstract Background Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). Methods The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. Discussion By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. Trial registration This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .https://deepblue.lib.umich.edu/bitstream/2027.42/148569/1/12883_2019_Article_1294.pd

Neural primacy of the salience processing system in schizophrenia

For effective information processing, two large-scale distributed neural networks appear to be critical: a multimodal executive system anchored on the dorsolateral prefrontal cortex (DLPFC) and a salience system anchored on the anterior insula. Aberrant interaction among distributed networks is a feature of psychiatric disorders such as schizophrenia. We used whole-brain Granger causal modeling using resting fMRI and observed a significant failure of both the feedforward and reciprocal influence between the insula and the DLPFC in schizophrenia. Further, a significant failure of directed influence from bilateral visual cortices to the insula was also seen in patients. These findings provide compelling evidence for a breakdown of the salience-execution loop in the clinical expression of psychosis. In addition, this offers a parsimonious explanation for the often-observed “frontal inefficiency,” the failure to recruit prefrontal system when salient or novel information becomes available in patients with schizophrenia

Glutathione and glutamate in schizophrenia: a 7T MRS study

In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate and/or glutamine in the cerebral cortex, consistent with a postinflammatory response, and that this reduction would be most marked in patients with residual schizophrenia an early stage with positive psychotic symptoms has progressed to a late stage characterised by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton Magnetic Resonance Spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal Components Analysis (PCA) produced three clear components: an ACC glutathione-glutamate component; an insula-visual glutathione-glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione-glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excito-toxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness

Brainhack: Developing a culture of open, inclusive, community-driven neuroscience

Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress