Infrequent stimulus deviations from repetitive sequences elicit mismatch negativity (MMN) even passively, making MMN practical for clinical applications. Auditory MMN is typically elicited by a change in one (or more) physical stimulus parameters (eg, pitch, duration). This lower-order simple MMN (sMMN) is impaired in long-term schizophrenia. However, sMMN contains activity from release from stimulus adaptation, clouding its face validity as purely deviance-related. More importantly, it is unreliably reduced in samples of first-episode psychosis, limiting its utility as a biomarker. Complex pattern-deviant MMN (cMMN) tasks, which elicit early and late responses, are based on higher-order abstractions and better isolate deviance detection. Their abstract nature may increase the sensitivity to processing deficits in early psychosis. However, both the early and late cMMNs are small, limiting separation between healthy and psychotic samples. In 29 healthy individuals, we tested a new dual-rule cMMN paradigm to assess additivity of deviance. Sounds alternated lateralization between left and right, and low and high pitches, creating a left-low, right-high alternating pattern. Deviants were a repeated left-low, violating lateralization and pitch patterns. Early and late cMMNs on the dual-rule task were significantly larger than those on the one-rule extra tone cMMN task (P < .05). Further, the dual-rule early cMMN was not significantly smaller than pitch or duration sMMNs (P > .48, .28, respectively). These results demonstrate additivity for cMMN pattern-violating rules. This increase in cMMN amplitude should increase group difference effect size, making it a prime candidate for a biomarker of disease presence at first psychotic episode, and perhaps even prior to the emergence of psychosis.
Alterations of mismatch responses (ie, neural activity evoked by unexpected stimuli) are often considered a potential biomarker of schizophrenia. Going beyond establishing the type of observed alterations found in diagnosed patients and related cohorts, computational methods can yield valuable insights into the underlying disruptions of neural mechanisms and cognitive function. Here, we adopt a typology of model-based approaches from computational cognitive neuroscience, providing an overview of the study of mismatch responses and their alterations in schizophrenia from four complementary perspectives: (a) connectivity models, (b) decoding models, (c) neural network models, and (d) cognitive models. Connectivity models aim at inferring the effective connectivity patterns between brain regions that may underlie mismatch responses measured at the sensor level. Decoding models use multivariate spatiotemporal mismatch response patterns to infer the type of sensory violations or to classify participants based on their diagnosis. Neural network models such as deep convolutional neural networks can be used for improved classification performance as well as for a systematic study of various aspects of empirical data. Finally, cognitive models quantify mismatch responses in terms of signaling and updating perceptual predictions over time. In addition to describing the available methodology and reviewing the results of recent computational psychiatry studies, we offer suggestions for future work applying model-based techniques to advance the study of mismatch responses in schizophrenia.
Background: People diagnosed with substance use disorders (SUDs) are at risk for impairment of brain function and structure. However, physicians still do not have any clinical biomarker of brain impairment that helps diagnose or treat these patients when needed. The most common method to study these patients is the classical electroencephalographic (EEG) analyses of absolute and relative powers, but this has limited individual clinical applicability. Other non-classical measures such as frequency band ratios and entropy show promise in these patients. Therefore, there is a need to expand the use of quantitative (q)EEG beyond classical measures in clinical populations. Our aim is to assess a group of classical and non-classical qEEG measures in a population with SUDs. Methods: We selected 56 non-medicated and drug-free adult patients (30 males) diagnosed with SUDs and admitted to Rehabilitation Clinics. According to qualitative EEG findings, patients were divided into four groups. We estimated the absolute and relative powers and calculated the entropy, and the alpha/(delta + theta) ratio. Results: Our findings showed a significant variability of absolute and relative powers among patients with SUDs. We also observed a decrease in the EEG-based entropy index and alpha/(theta + delta) ratio, mainly in posterior regions, in the patients with abnormal qualitative EEG. Conclusions: Our findings support the view that the power spectrum is not a reliable biomarker on an individual level. Thus, we suggest shifting the approach from the power spectrum toward other potential methods and designs that may offer greater clinical possibilities.
Mismatch negativity (MMN) to pitch (pMMN) and to duration (dMMN) deviant stimuli is significantly more attenuated in long-term psychotic illness compared to first-episode psychosis (FEP). It was recently shown that source-modeling of magnetically recorded MMN increases the detection of left auditory cortex MMN deficits in FEP, and that computational circuit modeling of electrically recorded MMN also reveals left-hemisphere auditory cortex abnormalities. Computational modeling using dynamic causal modeling (DCM) can also be used to infer synaptic activity from EEG-based scalp recordings. We measured pMMN and dMMN with EEG from 26 FEP and 26 matched healthy controls (HCs) and used a DCM conductance-based neural mass model including α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, N-methyl-D-Aspartate (NMDA), and Gamma-aminobutyric acid receptors to identify any changes in effective connectivity and receptor rate constants in FEP. We modeled MMN sources in bilateral A1, superior temporal gyrus, and inferior frontal gyrus (IFG). No model parameters distinguished groups for pMMN. For dMMN, reduced NMDA receptor activity in right IFG in FEP was detected. This finding is in line with literature of prefrontal NMDA receptor hypofunction in chronic schizophrenia and suggests impaired NMDA-induced synaptic plasticity may be present at psychosis onset where scalp dMMN is only moderately reduced. To the best of our knowledge, this is the first report of impaired NMDA receptor activity in FEP found through computational modeling of dMMN and shows the potential of DCM to non-invasively reveal synaptic-level abnormalities that underly subtle functional auditory processing deficits in early psychosis.
Objective: Post-stroke seizures (PSS) are one of the major stroke-related complications. Early therapeutic interventions are critical therefore using electroencephalography (EEG) as a predictive tool for future recurrence may be helpful. We aimed to assess frequencies of different EEG patterns in patients with PSS and their association with seizure recurrence and functional outcomes. Methods: All patients admitted with PSS were included and underwent interictal EEG recording during their admission and monitored for seizure recurrence for 24 months. Results: PSS was reported in 106 patients. Generalized slow wave activity (GSWA) was the most frequent EEG pattern observed (n = 62, 58.5%), followed by Focal sharp wave discharges (FSWDs) (n = 57, 55.8%), focal slow wave activity (FSWA) (n = 56, 52.8%), periodic discharges (PDs) (n = 13, 12.3%), and ictal epileptiform abnormalities (n = 6, 5.7%). FSWA and ictal EAs were positively associated with seizure recurrence (p < .001 and p = .015 respectively) and it remained significant even after adjusting for age, sex, stroke severity, stroke subtype, or use of anti-seizure medications (ASMs). Other positive associations were status epilepticus (SE) (p = .015), and use of older ASM (p < .001). FSWA and GSWA in EEG were positively associated with severe functional disability (p = .055, p = .015 respectively). Other associations were; Diabetes Mellitus (p = .034), Chronic Kidney Disease (p = .002), use of older ASMs (p = .037), presence of late PSS (p = .021), and those with Ischemic stroke (p = .010). Conclusions: Recognition and documentation of PSS-related EEG characteristics are important, as certain EEG patterns may help to identify the patients who are at risk of developing recurrence or worse functional outcomes.
Over the past decade, the Diagnostic and Statistical Manual's method of prescribing medications based on presenting symptoms has been challenged. The shift toward precision medicine began with the National Institute of Mental Health and culminated with the World Psychiatric Association's posit that a paradigm shift is needed. This study supports that shift by providing evidence explaining the high rate of psychiatric medication failure and suggests a possible first step toward precision medicine. A large psychiatric practice began collecting electroencephalograms (EEGs) for this study in 2012. The EEGs were analyzed by the same neurophysiologist (board certified in electroencephalography) on 1,233 patients. This study identified 4 EEG biomarkers accounting for medication failure in refractory patients: focal slowing, spindling excessive beta, encephalopathy, and isolated epileptiform discharges. Each EEG biomarker suggests underlying brain dysregulation, which may explain why prior medication attempts have failed. The EEG biomarkers cannot be identified based on current psychiatric assessment methods, and depending upon the localization, intensity, and duration, can all present as complex behavioral or psychiatric issues. The study highlights that the EEG biomarker identification approach can be a positive step toward personalized medicine in psychiatry, furthering the clinical thinking of "testing the organ we are trying to treat."
Objective. Neurophysiological tools remain indispensable instruments in the assessment of psychiatric disorders. These techniques are widely available, inexpensive and well tolerated, providing access to the assessment of brain functional alterations. In the clinical psychiatric context, electrophysiological techniques are required to provide important information on brain function. While there is an immediate benefit in the clinical application of these techniques in the daily routine (emergency assessments, exclusion of organic brain alterations), these tools are also useful in monitoring the progress of psychiatric disorders or the effects of therapy. There is increasing evidence and convincing literature to confirm that electroencephalography and related techniques can contribute to the diagnostic workup, to the identification of subgroups of disease categories, to the assessment of long-term causes and to facilitate response predictions. Methods and Results. In this report we focus on 3 different novel developments of the use of neurophysiological techniques in 3 highly prevalent psychiatric disorders: (1) the value of EEG recordings and machine learning analyses (deep learning) in order to improve the diagnosis of dementia subtypes; (2) the use of mismatch negativity in the early diagnosis of schizophrenia; and (3) the monitoring of addiction and the prevention of relapse using cognitive event-related potentials. Empirical evidence was presented. Conclusion. Such information emphasized the important role of neurophysiological tools in the identification of useful biological markers leading to a more efficient care management. The potential of the implementation of machine learning approaches together with the conduction of large cross-sectional and longitudinal studies was also discussed.