Background Electro- and magneto-encephalography (E/MEG) studies indicate among schizophrenia patients (SZ) abnormal, often reduced, entrained (steady-state; aSSR) and transient (N100/M100) neural responses to auditory stimuli. We complement this literature by focusing analyses on auditory cortices, assessing a wide range of stimulation frequencies with long driving periods, and evaluating relationships between aSSR and M100 reductions in SZ. Method Seventeen SZ and 17 healthy subjects (H) participated. Stimuli were 1500ms binaural broadband noise sequences modulated at 5, 20, 40, 80 or 160-Hz. MEG data were collected and co-registered with structural magnetic resonance images. aSSRs and M100s projected into brain space were analyzed as a function of hemisphere, stimulus density, and time. Results aSSR: At low (5-Hz) and high (80-Hz) modulation frequencies, SZ displayed weaker entrainment bilaterally. To 40-Hz stimuli, SZ showed weaker entrainment only in right auditory cortex. M100: While responses for H increased linearly with stimulus density, this effect was weaker or absent in SZ. Relationship: A principal components analysis of SZ deficits identified low (5-Hz entrainment and M100) and high (40–80-Hz entrainment) frequency components. Discriminant analysis indicated that the low frequency component uniquely differentiated SZ from H. The high frequency component correlated with negative symptoms among SZ. Conclusions SZ auditory cortices were unable to (i) generate healthy levels of theta- and high gamma-band (80Hz) entrainment (aSSR) and (ii) augment transient responses (M100s) to rapidly presented auditory information (an index of temporal integration). Only the latter was most apparent in left hemisphere, and may reflect a prominent neurophysiological deficit in schizophrenia.

P3 amplitude reduction (P3-AR) is associated with biological vulnerability to a spectrum of externalizing disorders, such as ADHD, conduct disorder, and substance use disorders. P3, however, is generally characterized as a broad activation involving multiple neurophysiological processes. One approach to separating P3-related processes is time-frequency (TF) analysis. The current study used a novel PCA-based TF analysis method to investigate relationships between P3, its associated TF components, and externalizing in a community-based sample of adolescent males. Results showed that 1) alone, P3 and each TF-PCA derived component could successfully discriminate diagnostic groups from controls, and 2) delta components in specific time ranges accounted for variance beyond that accounted for by P3. One delta component was associated with all diagnostic groups, suggesting it may represent a more parsimonious endophenotype for externalizing than P3-AR.

Individuals with schizophrenia (SZ) have deviations in auditory perception perhaps attributable to altered neural oscillatory response properties in thalamo-cortical and/or local cortico-cortical circuits. Previous EEG studies of auditory steady-state responses (aSSRs; a measure of sustained neuronal entrainment to repetitive stimulation) in SZ have indicated attenuated gamma range (≈40 Hz) neural entrainment. Stimuli in most such studies have been relatively brief (500–1000 ms) trains of 1 ms clicks or amplitude modulated pure tones (1000 Hz) with short, fixed interstimulus intervals (200–1000 ms). The current study used extended (1500 ms), more aurally dense broadband stimuli (500–4000 Hz noise; previously demonstrated to elicit larger aSSRs) with longer, variable interstimulus intervals (2700–3300 ms). Dense array EEG (256 sensor) was collected while 17 SZ and 16 healthy subjects passively listed to stimuli modulated at 15 different frequencies spanning beta and gamma ranges (16–44 Hz in 2 Hz steps). Results indicate that SZ have augmented aSSRs that were most extreme in the gamma range. Results also constructively replicate previous findings of attenuated low frequency auditory evoked responses (2–8 Hz) in SZ. These findings (i) highlight differential characteristics of low versus high frequency and induced versus entrained oscillatory auditory responses in both SZ and healthy stimulus processing, (ii) provide support for an NMDA-receptor hypofunction-based pharmacological model of SZ, and (iii) report a novel pattern of aSSR abnormalities suggesting that gamma band neural entrainment deviations among SZ may be more complex than previously supposed, including possibly being substantially influenced by physical stimulus properties.

Abnormalities in electrophysiological measures of stimulus-evoked brain activity (including the P3 event-related potential (ERP) and its associated delta and theta time-frequency (TF) components), and intrinsic, resting state brain activity (including EEG in the beta frequency band) have each been associated with biological vulnerability to a variety of externalizing (EXT) spectrum disorders, such as substance use disorders, conduct disorder, and antisocial behavior. While each of these individual measures has shown promise as an endophenotype for one or more aspects of EXT, we proposed that the power to identify EXT-related genes may be enhanced by using these measures collectively. Thus, we sought to explore a multivariate approach to identifying electrophysiological endophenotypes related to EXT, using measures identified in the literature as promising individual endophenotypes for EXT. Using data from our large twin sample (634 MZ and 335 DZ, male and female same-sex pairs), and fitting multivariate biometric Cholesky models, we found that these measures 1) were heritable, 2) showed significant phenotypic and genetic correlation with a general vulnerability to EXT (which is itself highly heritable), 3) showed modest phenotypic and genetic correlation with each other, and 4) were sensitive to genetic effects that differed as a function of gender. These relationships suggest that these endophenotypes are likely tapping into neurophysiological processes and genes that are both common across them and unique to each – all of which are relevant to a biological vulnerability to EXT psychopathology.

Theoretical models of addiction suggest that alterations in addiction domains including incentive salience, negative emotionality, and executive control lead to relapse in alcohol use disorder (AUD). To determine whether the functional organization of neural networks underlying these domains predict subsequent relapse, we generated theoretically defined addiction networks. We collected resting functional magnetic resonance imaging data from 45 individuals with AUD during early abstinence (number of days abstinent M = 25.40, SD = 16.51) and calculated the degree of resting-state functional connectivity (RSFC) within these networks. Regression analyses determined whether the RSFC strength in domain-defined addiction networks measured during early abstinence predicted subsequent relapse (dichotomous or continuous relapse metrics). RSFC within each addiction network measured during early abstinence was significantly lower in those that relapsed (vs. abstained) and predicted subsequent time to relapse. Lower incentive salience RSFC during early abstinence increased the odds of relapsing. Neither RSFC in a control network nor clinical self-report measures predicted relapse. The association between low incentive salience RSFC and faster relapse highlights the need to design timely interventions that enhance RSFC in AUD individuals at risk of relapsing faster.