Test-retest reliability of time-frequency measures of auditory steady-state responses in patients with schizophrenia and healthy controls.

BackgroundAuditory steady-state response (ASSR) paradigms have consistently demonstrated gamma band abnormalities in schizophrenia at a 40-Hz driving frequency with both electroencephalography (EEG) and magnetoencephalography (MEG). Various time-frequency measures have been used to assess the 40-Hz ASSR, including evoked power, single trial total power, phase-locking factor (PLF), and phase-locking angle (PLA). While both EEG and MEG studies have shown power and PLF ASSR measures to exhibit excellent test-retest reliability in healthy adults, the reliability of these measures in patients with schizophrenia has not been determined.MethodsASSRs were obtained by recording EEG data during presentation of repeated 20-Hz, 30-Hz and 40-Hz auditory click trains from nine schizophrenia patients (SZ) and nine healthy controls (HC) tested on two occasions. Similar ASSR data were collected from a separate group of 30 HC on two to three test occasions. A subset of these HC subjects had EEG recordings during two tasks, passively listening and actively attending to click train stimuli. Evoked power, total power, PLF, and PLA were calculated following Morlet wavelet time-frequency decomposition of EEG data and test-retest generalizability (G) coefficients were calculated for each ASSR condition, time-frequency measure, and subject group.ResultsG-coefficients ranged from good to excellent (> 0.6) for most 40-Hz time-frequency measures and participant groups, whereas 20-Hz G-coefficients were much more variable. Importantly, test-retest reliability was excellent for the various 40-Hz ASSR measures in SZ, similar to reliabilities in HC. Active attention to click train stimuli modestly reduced G-coefficients in HC relative to the passive listening condition.DiscussionThe excellent test-retest reliability of 40-Hz ASSR measures replicates previous EEG and MEG studies. PLA, a relatively new time-frequency measure, was shown for the first time to have excellent reliability, comparable to power and PLF measures. Excellent reliability of 40 Hz ASSR measures in SZ supports their use in clinical trials and longitudinal observational studies

Aberrant activity in conceptual networks underlies N400 deficits and unusual thoughts in schizophrenia.

BackgroundThe N400 event-related potential (ERP) is triggered by meaningful stimuli that are incongruous, or unmatched, with their semantic context. Functional magnetic resonance imaging (fMRI) studies have identified brain regions activated by semantic incongruity, but their precise links to the N400 ERP are unclear. In schizophrenia (SZ), N400 amplitude reduction is thought to reflect overly broad associations in semantic networks, but the abnormalities in brain networks underlying deficient N400 remain unknown. We utilized joint independent component analysis (JICA) to link temporal patterns in ERPs to neuroanatomical patterns from fMRI and investigate relationships between N400 amplitude and neuroanatomical activation in SZ patients and healthy controls (HC).MethodsSZ patients (n = 24) and HC participants (n = 25) performed a picture-word matching task, in which words were either matched (APPLE→apple) by preceding pictures, or were unmatched by semantically related (in-category; IC, APPLE→lemon) or unrelated (out of category; OC, APPLE→cow) pictures, in separate ERP and fMRI sessions. A JICA "data fusion" analysis was conducted to identify the fMRI brain regions specifically associated with the ERP N400 component. SZ and HC loading weights were compared and correlations with clinical symptoms were assessed.ResultsJICA identified an ERP-fMRI "fused" component that captured the N400, with loading weights that were reduced in SZ. The JICA map for the IC condition showed peaks of activation in the cingulate, precuneus, bilateral temporal poles and cerebellum, whereas the JICA map from the OC condition was linked primarily to visual cortical activation and the left temporal pole. Among SZ patients, fMRI activity from the IC condition was inversely correlated with unusual thought content.ConclusionsThe neural networks associated with the N400 ERP response to semantic violations depends on conceptual relatedness. These findings are consistent with a distributed network underlying neural responses to semantic incongruity including unimodal visual areas as well as integrative, transmodal areas. Unusual thoughts in SZ may reflect impaired processing in transmodal hub regions such as the precuneus, leading to overly broad semantic associations

Role of N-methyl-D-aspartate receptors in action-based predictive coding deficits in schizophrenia

Published in final edited form as:Biol Psychiatry. 2017 March 15; 81(6): 514–524. doi:10.1016/j.biopsych.2016.06.019.BACKGROUND: Recent theoretical models of schizophrenia posit that dysfunction of the neural mechanisms subserving predictive coding contributes to symptoms and cognitive deficits, and this dysfunction is further posited to result from N-methyl-D-aspartate glutamate receptor (NMDAR) hypofunction. Previously, by examining auditory cortical responses to self-generated speech sounds, we demonstrated that predictive coding during vocalization is disrupted in schizophrenia. To test the hypothesized contribution of NMDAR hypofunction to this disruption, we examined the effects of the NMDAR antagonist, ketamine, on predictive coding during vocalization in healthy volunteers and compared them with the effects of schizophrenia. METHODS: In two separate studies, the N1 component of the event-related potential elicited by speech sounds during vocalization (talk) and passive playback (listen) were compared to assess the degree of N1 suppression during vocalization, a putative measure of auditory predictive coding. In the crossover study, 31 healthy volunteers completed two randomly ordered test days, a saline day and a ketamine day. Event-related potentials during the talk/listen task were obtained before infusion and during infusion on both days, and N1 amplitudes were compared across days. In the case-control study, N1 amplitudes from 34 schizophrenia patients and 33 healthy control volunteers were compared. RESULTS: N1 suppression to self-produced vocalizations was significantly and similarly diminished by ketamine (Cohen’s d = 1.14) and schizophrenia (Cohen’s d = .85). CONCLUSIONS: Disruption of NMDARs causes dysfunction in predictive coding during vocalization in a manner similar to the dysfunction observed in schizophrenia patients, consistent with the theorized contribution of NMDAR hypofunction to predictive coding deficits in schizophrenia.This work was supported by AstraZeneca for an investigator-initiated study (DHM) and the National Institute of Mental Health Grant Nos. R01 MH-58262 (to JMF) and T32 MH089920 (to NSK). JHK was supported by the Yale Center for Clinical Investigation Grant No. UL1RR024139 and the US National Institute on Alcohol Abuse and Alcoholism Grant No. P50AA012879. (AstraZeneca for an investigator-initiated study (DHM); R01 MH-58262 - National Institute of Mental Health; T32 MH089920 - National Institute of Mental Health; UL1RR024139 - Yale Center for Clinical Investigation; P50AA012879 - US National Institute on Alcohol Abuse and Alcoholism)Accepted manuscrip

Initial 4D seismic results after CO 2 injection start-up at the Aquistore storage site

The first post-CO2-injection 3D time-lapse seismic survey was conducted at the Aquistore CO2 storage site in February 2016 using the same permanent array of buried geophones used for acquisition of three previous pre-CO2-injection surveys from March 2012 to November 2013. By February 2016, 36 kilotons of CO2 have been injected within the reservoir between 3170 and 3370 m depth. We have developed time-lapse results from analysis of the first post-CO2-injection data and three pre-CO2-injection data sets. The objective of our analysis was to evaluate the ability of the permanent array to detect the injected CO2. A “4D-friendly simultaneous” processing flow was applied to the data in an effort to maximize the repeatability between the pre- and post-CO2-injection volumes while optimizing the final subsurface image including the reservoir. Excellent repeatability was achieved among all surveys with global normalized root-mean-square (Gnrms) values of 1.13–1.19 for the raw prestack data relative to the baseline data, which decreased during processing to Gnrms values of approximately 0.10 for the final crossequalized migrated data volumes. A zone of high normalized root-mean-square (nrms) values (0.11–0.25 as compared with background values of 0.05–0.10) is identified within the upper Deadwood unit of the storage reservoir, which likely corresponds to approximately 18 kilotons of CO2. No significant nrms anomalies are observed within the other reservoir units due to a combination of reduced seismic sensitivity, higher background nrms values, and/or small quantities of CO2 residing within these zones

New Distribution Records for Amphibians and Reptiles in Connecticut, with Notes on the Status of an Introduced Species

Recent field work and a review of catalogued specimens in the herpetology collections at the Yale Peabody has yielded 170 new town records for amphibians and reptiles in Connecticut. These are reported here, along with observations on the status of the red-ear slider (Trachemys scripta) in Connecticut

Harvesting Intensity and Aridity Are More Important Than Climate Change in Affecting Future Carbon Stocks of Douglas-Fir Forests

Improved forest management may offer climate mitigation needed to hold warming to below 2°C. However, uncertainties persist about the effects of harvesting intensity on forest carbon sequestration, especially when considering interactions with regional climate and climate change. Here, we investigated the combined effects of harvesting intensity, climatic aridity, and climate change on carbon stocks in Douglas-fir [Pseudotsuga menziesii Mirb. (Franco)] stands. We used the Carbon Budget Model of the Canadian Forest Sector to simulate the harvest and regrowth of seven Douglas-fir stand types covering a 900 km-long climate gradient across British Columbia, Canada. In particular, we simulated stand growth under three regimes (+17%, −17% and historical growth increment) and used three temperature regimes [historical, representative concentration pathways (RCP) 2.6 and RCP 8.5]. Increasing harvesting intensity led to significant losses in total ecosystem carbon stocks 50 years post-harvest. Specifically, forests that underwent clearcutting were projected to stock about 36% less carbon by 2,069 than forests that were left untouched. Belowground carbon stocks 50 years into the future were less sensitive to harvesting intensity than aboveground carbon stocks and carbon losses were greater in arid interior Douglas-fir forests than in humid, more productive forests. In addition, growth multipliers and decay due to the RCP’s had little effect on total ecosystem carbon, but aboveground carbon declined by 7% (95% confidence interval [−10.98, −1.81]) in the high emissions (RCP8.5) scenario. We call attention to the implementation of low intensity harvesting systems to preserve aboveground forest carbon stocks until we have a more complete understanding of the impacts of climate change on British Columbia’s forests

Neurophysiological Distinction between Schizophrenia and Schizoaffective Disorder

Schizoaffective disorder (SA) is distinguished from schizophrenia (SZ) based on the presence of prominent mood symptoms over the illness course. Despite this clinical distinction, SA and SZ patients are often combined in research studies, in part because data supporting a distinct pathophysiological boundary between the disorders are lacking. Indeed, few studies have addressed whether neurobiological abnormalities associated with SZ, such as the widely replicated reduction and delay of the P300 event-related potential (ERP), are also present in SA. Scalp EEG was acquired from patients with DSM-IV SA (n = 15) or SZ (n = 22), as well as healthy controls (HC; n = 22) to assess the P300 elicited by infrequent target (15%) and task-irrelevant distractor (15%) stimuli in separate auditory and visual ”oddball” tasks. P300 amplitude was reduced and delayed in SZ, relative to HC, consistent with prior studies. These SZ abnormalities did not interact with stimulus type (target vs. task-irrelevant distractor) or modality (auditory vs. visual). Across sensory modality and stimulus type, SA patients exhibited normal P300 amplitudes (significantly larger than SZ patients and indistinguishable from HC). However, P300 latency and reaction time were both equivalently delayed in SZ and SA patients, relative to HC. P300 differences between SA and SZ patients could not be accounted for by variation in symptom severity, socio-economic status, education, or illness duration. Although both groups show similar deficits in processing speed, SA patients do not exhibit the P300 amplitude deficits evident in SZ, consistent with an underlying pathophysiological boundary between these disorders

Reward processing electrophysiology in schizophrenia : effects of age and illness phase

Background: Reward processing abnormalities may underlie characteristic pleasure and motivational impairments in schizophrenia. Some neural measures of reward processing show age-related modulation, highlighting the importance of considering age effects on reward sensitivity. We compared event-related potentials (ERPs) reflecting reward anticipation (stimulus-preceding negativity, SPN) and evaluation (reward positivity, RewP; late positive potential, LPP) across individuals with schizophrenia (SZ) and healthy controls (HC), with an emphasis on examining the effects of chronological age, brain age (i.e., predicted age based on neurobiological measures), and illness phase. Methods: Subjects underwent EEG while completing a slot-machine task for which rewards were not dependent on performance accuracy, speed, or response preparation. Slot-machine task EEG responses were compared between 54 SZ and 54 HC individuals, ages 19 to 65. Reward-related ERPs were analyzed with respect to chronological age, categorically-defined illness phase (early; ESZ versus chronic schizophrenia; CSZ), and were used to model brain age relative to chronological age. Results: Illness phase-focused analyses indicated there were no group differences in average SPN or RewP amplitudes. However, a group x reward outcome interaction revealed that ESZ differed from HC in later outcome processing, reflected by greater LPP responses following loss versus reward (a reversal of the HC pattern). While brain age estimates did not differ among groups, depressive symptoms in SZ were associated with older brain age estimates while controlling for negative symptoms. Conclusions: ESZ and CSZ did not differ from HC in reward anticipation or early outcome processing during a cognitively undemanding reward task, highlighting areas of preserved functioning. However, ESZ showed altered later reward outcome evaluation, pointing to selective reward deficits during the early illness phase of schizophrenia. Further, an association between ERP-derived brain age and depressive symptoms in SZ extends prior findings linking depression with reward-related ERP blunting. Taken together, both illness phase and age may impact reward processing among SZ, and brain aging may offer a promising, novel marker of reward dysfunction that warrants further study

Harvest intensity effects on carbon stocks and biodiversity are dependent on regional climate in Douglas-fir forests of British Columbia

Temperate forests provide crucial ecosystems services as living sinks for atmospheric carbon (C) and repositories of biodiversity. Applying harvesting at intensities that minimize losses offers one means for mitigating global change. However, little is known of overstory retention levels that best conserve ecosystem services in different regional climates, and likewise as climate changes. To quantify the effect of harvest intensity on C stocks and biodiversity, we compared five harvesting intensities (clearcutting,seedtree retention, 30% patch retention, 60% patch retention, and uncut controls) across a climatic aridity gradient that ranged from humid to semi-arid in the Douglas-fir (Pseudostuga menziesii) forests of British Columbia. We found that increased harvesting intensity reduced total ecosystem, aboveground, and live tree C stocks one year post-harvest, and the magnitude of these losses were negatively correlated with climatic aridity. In humid forests, total ecosystem C ranged from 50% loss following clearcut harvest, to 30% loss following large patch retention harvest. In arid forests this range was 60% to 8% loss, respectively. Where lower retention harvests are sought, the small patch retention treatment protected both C stocks and biodiversity in the arid forests, whereas the seedtree method performed as well or better in the humid forests. Belowground C stocks declined by an average of 29% after harvesting, with almost all of the loss from the forest floor and none from the mineral soil. Of the secondary pools, standing and coarse deadwood declined in all harvesting treatments regardless of cutting intensity or aridity, while C stocks in fine fuels and stumps increased. The understory plant C pool declined across all harvesting intensities in the humid forests, but increased in arid forests. Shannon’s diversity and richness of tree and bryoid species declined with harvesting intensity, where tree species losses were greatest in the humid forests and bryoid losses greatest in arid forests. Shrub and herb species were unaffected. This study showed that the highest retention level was best at reducing losses in C stocks and biodiversity, and clearcutting the poorest, and while partial retention of canopy trees can reduce losses in these ecosystem services, outcomes will vary with climatic aridity