Neural abnormalities of reward processing in adolescents with bipolar disorders: An ERP study.

Adolescent onset is common in bipolar disorders (BDs) and is associated with a worse illness course in adulthood. A model of BDs suggests that a dysregulated behavioral approach system (BAS), a neural system that mobilizes reward-seeking behavior, is at the root of BDs. Normative adolescence is often accompanied by dynamic changes to neural structures underlying the BAS and related cognitive processes. It is possible that adolescent-onset BDs is associated with abnormal BAS neurodevelopment. Consistently, the present study is the first to compare specific BAS-relevant anticipatory and consummatory reward processes as indexed by event-related potentials (ERPs) in adolescents with BDs and typically developing peers. Using a sample of 43 adolescents with BDs and 56 without psychopathology, we analyzed N1 and P3 responses to anticipatory cues and feedback-related negativity (FRN) and P3 responses to feedback stimuli during a monetary incentive delay (MID) task. Hierarchical linear models examined relationships between ERP amplitudes and diagnostic group, MID condition, sex, and age. During anticipation phase, adolescent boys with BDs exhibited significantly larger N1 amplitudes in loss than even or gain trials. During feedback phase, compared to their healthy peers, adolescents with BDs had smaller FRN amplitudes across all conditions. Additional effects involving age, sex and trial type were observed. The findings indicate subtle, non-ubiquitous BAS-relevant neural abnormalities involving early attentional processes during reward anticipation and reward learning following feedback in adolescents with BDs. Adolescents with BDs did not show overall hypersensitive neural responses to monetary reward anticipation or feedback observed in adults with BDs.

ETSNet: A deep neural network for EEG-based temporal-spatial pattern recognition in psychiatric disorder and emotional distress classification.

The use of EEG for evaluating and diagnosing neurological abnormalities related to psychiatric diseases and identifying human emotions has been improved by deep learning advancements. This research aims to categorize individuals with schizophrenia (SZ), their biological relatives (REL), and healthy controls (HC) using resting EEG brain source signal data defined by regions of interest (ROIs). The proposed solution is a deep neural network for the cortical source signals of the ROIs, incorporating a Squeeze-and-Excitation Block and multiple CNNs designed for eyes-open and closed resting states. The model, called EEG Temporal Spatial Network (ETSNet), has two variants: ETSNets and ETSNetf. Two evaluations were conducted to show the effectiveness of the proposed model. The average accuracy for the classification of SZ, REL, and HC using EEG resting data was 99.57% (ETSNetf), and the average accuracy for the classification of eyes-open (EO) and eyes-closed (EC) resting states was 93.15% (ETSNets). An ablation study was also conducted using two public datasets for intellectual and developmental disorders and emotional states, showing improved classification accuracy compared to advanced EEG classification algorithms when using ETSNets.

Intolerance of uncertainty and neural measures of anticipation and reactivity for affective stimuli.

Intolerance of uncertainty (IU) is a transdiagnostic construct referring to the aversive interpretation of contexts characterized by uncertainty. Indeed, there is a growing body of research examining individual differences in IU and how these are associated with emotional anticipation and reactivity during periods of certainty and uncertainty, however, how these associations are reflected via neurophysiological indices remain understudied and poorly understood. The present study examined the relationship between self-reported IU and neurophysiological measures of emotional anticipation and reactivity, namely stimulus preceding negativity (SPN) and late positive potential (LPP), and self-report measures of emotional experiences. These measures were captured during an S1-S2 picture viewing tasks in which participants were presented with cues (S1) that either indicated the affective valence of upcoming picture (S2) or provided no information about the valence. Findings here provide evidence for significant associations between SPN amplitude and IU scores during uncertain and certain-positive cueing conditions, and significant associations between LPP amplitude and IU scores during both certain- and uncertain-negative picture viewing conditions that appear driven by prospective IU sub-scores. These positive associations between IU and SPN amplitude are suggestive of heightened emotional anticipation following S1 cues, while positive associations between IU and LPP are suggestive of heightened emotional reactivity following S2 images. These findings are discussed in detail relative to existing IU literature, and potential implications of these findings.

AM-UNet: automated mini 3D end-to-end U-net based network for brain claustrum segmentation.

Recent advances in deep learning (DL) have provided promising solutions to medical image segmentation. Among existing segmentation approaches, the U-Net-based methods have been used widely. However, very few U-Net-based studies have been conducted on automatic segmentation of the human brain claustrum (CL). The CL segmentation is challenging due to its thin, sheet-like structure, heterogeneity of its image modalities and formats, imperfect labels, and data imbalance. We propose an automatic optimized U-Net-based 3D segmentation model, called AM-UNet, designed as an end-to-end process of the pre and post-process techniques and a U-Net model for CL segmentation. It is a lightweight and scalable solution which has achieved the state-of-the-art accuracy for automatic CL segmentation on 3D magnetic resonance images (MRI). On the T1/T2 combined MRI CL dataset, AM-UNet has obtained excellent results, including Dice, Intersection over Union (IoU), and Intraclass Correlation Coefficient (ICC) scores of 82%, 70%, and 90%, respectively. We have conducted the comparative evaluation of AM-UNet with other pre-existing models for segmentation on the MRI CL dataset. As a result, medical experts confirmed the superiority of the proposed AM-UNet model for automatic CL segmentation. The source code and model of the AM-UNet project is publicly available on GitHub: https://github.com/AhmedAlbishri/AM-UNET.

Interoception Underlies Therapeutic Effects of Mindfulness Meditation for Posttraumatic Stress Disorder: A Randomized Clinical Trial.

BACKGROUND: Mindfulness-based interventions have proven efficacy in treating posttraumatic stress disorder (PTSD), but the neurobiological mechanism underlying the therapeutic effects is unknown. As mindfulness meditation cultivates attention to the present moment and bodily sensations, neural functions related to interoception (i.e., central processes of bodily signals) might be such a mechanism. METHODS: We conducted a clinical trial in which veterans with PTSD were randomly assigned to receive an 8-week mindfulness-based stress reduction (MBSR) intervention (n = 47) or an active control intervention (present-centered group therapy; n = 51). We assessed pre- and postintervention PTSD symptoms and electroencephalography measures of neural outcomes, including spontaneous brain activity, cognitive task-related brain responses, and interoceptive brain responses (heartbeat-evoked brain responses). We conducted statistical causal mediation analyses using treatment type as a predictor, pre- and postintervention measures of symptom severity as treatment response, and the neural outcomes as mediators. RESULTS: Compared with the control group, the MBSR group had greater improvements in PTSD symptoms and increases in spontaneous alpha power (8-13 Hz), task-related frontal theta power (4-7 Hz in 140-220 ms after stimulus), and frontal theta heartbeat-evoked brain responses (3-5 Hz and 265-336 ms after R peak). The mediation analysis using latent difference score modeling revealed that only changes in frontal theta heartbeat-evoked brain responses mediated the MBSR treatment effect. CONCLUSIONS: Mindfulness meditation improves brain functions of attentional control and resting brain states reflective of internally oriented relaxation. However, interoceptive neural functions enhanced by MBSR seem to be a primary cerebral mechanism that improves symptoms of PTSD.

Self-reported perceptual aberrations in psychosis map to event-related potentials and semantic appraisals of objects.

Psychotic disorders have been associated with visual deficits and deviant semantic processing, making it unclear whether object detection abnormalities in psychosis originate from low-level or higher-order visual processes. The current study investigated how high-level visual processing is affected in psychosis by presenting object stimuli with equivalent low-level visual features. Outpatients with affective and nonaffective psychotic disorders, first-degree biological relatives, and psychiatrically unaffected individuals (N = 130) completed the Fragmented Ambiguous Object Task (FAOT) to assess recognition of objects in ambiguous stimuli. During the task, we recorded electroencephalography, quantified event-related potential (ERP) components (P1, N1, negative closure [NCL], N400), and derived four spatiotemporal event-related potential factors using principal components analysis (PCA). In addition to traditional diagnoses, psychosis was characterized using a dimensional measure of individual differences in self-reported sensory experiences (perceptual absorption) calculated from scales that tap the psychotic domain of the hierarchical structure of psychopathology. Rates of detecting objects within fragmented stimuli failed to differ across diagnostic groups or significantly predict perceptual absorption (p = .057). PCA factors that reflected smaller N1 and larger NCL amplitudes were associated with detecting objects. Exploratory analyses revealed that higher perceptual absorption was associated with reductions in the N400 and a late positive PCA factor. Although early and midlatency brain responses modulate during object detection, late brain responses tied to semantic appraisal of objects are related to perceptual aberrations often reported by individuals with severe psychopathology. Dimensional measures of personality appear sensitive to variation in biological systems relevant to psychotic symptomatology and object perception. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Posttraumatic stress symptom dimensions and brain responses to startling auditory stimuli in combat veterans.

Posttraumatic stress disorder (PTSD) is marked by alterations in emotional functioning, physiological reactivity, and attention. Neural reactivity to acoustic startle stimuli can be used to understand brain functions related to these alterations. Investigations of startle reactivity in PTSD have yielded inconsistent findings, which may reflect the heterogeneity of the disorder. Furthermore, little is known of how the common co-occurrence of mild traumatic brain injury (mTBI; i.e., concussion) may influence neural reactivity. We examined the event-related potentials (ERPs) of combat veterans (n = 102) to acoustic startle probes delivered during viewing of pleasant, neutral, unpleasant, and combat-related pictures. Interview-based assessments yielded dimensional characterizations of PTSD and mTBI. The P3 ERP response to startle probes was reduced during all affective relative to neutral pictures but failed to be associated with a PTSD diagnosis. However, two separable domains of PTSD symptomatology were associated with startle ERPs regardless of the picture conditions. Maladaptive avoidance was associated with smaller N1, P2, and P3 amplitudes, while intrusive reexperiencing was associated with larger P2 amplitudes. There were no main effects of mTBI. Findings suggest that level of symptomatology rather than a formal diagnosis of PTSD better explains alterations in neural reactivity after traumatic events, while mild brain injuries have little impact. Avoidance symptoms of PTSD may dampen neural functions that facilitate reorientation to threat while intrusive reexperiencing of traumatic events appears to heighten sensory reactivity. Considering specific aspects of symptomatology provides insight into the neural basis of trauma-related psychopathology and may help guide individualization of clinical interventions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Addressing measurement issues in electroencephalography studies of meditations as alternative interventions of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a debilitating mental disorder affecting numerous U.S. citizens, but conventional interventions have shown limited success in treating PTSD symptoms (e.g., high dropout rates). Various meditative techniques have been used as alternative interventions to treat PTSD, demonstrating that these interventions have strong potential to improve symptoms and quality of life in people with PTSD. Despite the initial promise, our limited understanding of the mechanisms of meditation has hindered the establishment of meditation as an evidence-based clinical intervention optimized for trauma survivors. Therefore, it is imperative to determine the neurobiological mechanism of meditation using rigorous functional outcome measures of the central nervous system. Electroencephalography (EEG) has been widely used as an ideal tool for mechanistic studies of meditation because it provides a sensitive functional neural measurement of synchronized brain networks that may reflect meditation-related trait and state changes in brain dynamics. However, recent meta-analyses of EEG meditation studies have provided mixed findings, with some consistencies across (e.g., enhanced theta and alpha frequency neural oscillations) as well as a number of inconsistent findings across studies. The present commentary addresses critical measurement issues in meditation EEG studies that are often disregarded and thus underlie the replication problems, which represent one of the major obstacles in mechanistic studies of meditation using EEG. In particular, the physiological artifact-related issues in time, frequency, and time-frequency measures and spatial-domain measurement problems inherent to EEG are reviewed, and standard methods of EEG processing and analysis are recommended to resolve the problems. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Abnormal neural functions associated with motor inhibition deficits in schizophrenia and bipolar disorder.

Deficits in response inhibition have been observed in schizophrenia and bipolar disorder; however, the neural origins of the abnormalities and their relevance to genetic liability for psychosis are unknown. We used a stop-signal task to examine motor inhibition and associated neural processes in schizophrenia patients (n = 57), bipolar disorder patients (n = 21), first-degree biological relatives of patients with schizophrenia (n = 34), and healthy controls (n = 56). Schizophrenia patients demonstrated motor control deficits reflected in longer stop-signal reaction times and elongated reaction times. With the possibility of needing to inhibit a button press, both schizophrenia and bipolar disorder patients showed diminished reductions of the P300 brain response and only the healthy controls demonstrated adjustments in response execution time, as measured by response-locked lateralized readiness potentials. Schizotypal traits in the biological relatives were associated with less P300 modulation consistent with the motor-related anomalies being associated with subtle schizophrenia-spectrum symptomatology in family members. The two patient groups had elongated response selection processes as manifest in the delayed onset of the stimulus-locked lateralized readiness potential. The bipolar disorder group was unique in showing significantly diminished neural responses to the stop-signal to inhibit a response. Antipsychotic medication dosage was related to worse motor inhibition, thus motor inhibition deficits in schizophrenia may be partially explained by the effect of pharmacological agents. Failed modulation of brain processes in relation to response inhibition probability and the lengthening of motor response selection appear to be transdiagnostic abnormalities spanning schizophrenia and bipolar disorder.

Dysfunctional Neural Processes Underlying Context Processing Deficits in Schizophrenia.

BACKGROUND: People with schizophrenia (PSZ) have profound deficits in context processing, an executive process that guides adaptive behaviors according to goals and stored contextual information. Although various neural processes are involved in context processing and are affected in PSZ, the core underlying neural dysfunction is unclear. METHODS: To determine the relative importance of neural dysfunctions within prefrontal cognitive control, sensory activity, and motor activity to context processing deficits in PSZ, we examined event-related potentials (ERPs) in 60 PSZ and 51 healthy control subjects during an optimal context processing task. We also analyzed the Ex-Gaussian reaction time distribution to examine abnormalities in motor control variability in PSZ. RESULTS: Compared with healthy control subjects, PSZ had lower response accuracy and greater variability in their normal reaction times during high context processing demands. Latencies of normal and slow responses were generally increased in PSZ. High context processing-related reductions in frontal ERPs were indicative of specific deficits in proactive and reactive cognitive controls in PSZ, while ERPs associated with visual and motor processes were reduced regardless of context processing demands, indicating generalized visuomotor deficits. In contrast to previous studies, we found that diminished frontal responses reflective of proactive control of the contextual cue, rather than visual responses of cue encoding, predicted response accuracy deficits in PSZ. In addition, probe-related ERP components of motor preparation, prefrontal reactive control, and frontomotor interaction predicted Ex-Gaussian indices of reaction time instability in PSZ. CONCLUSIONS: Prefrontal proactive and reactive control deficits associated with failures in using mental representation likely underlie context processing deficits in PSZ.

Neurophysiological correlates of cognitive control and approach motivation abnormalities in adolescent bipolar disorders.

Hypersensitivity to reward-relevant stimuli is theorized to be a core etiological factor in bipolar disorders (BDs). However, little is known about the role of cognitive control dysregulation within reward contexts in BDs, particularly during adolescence. Using electroencephalography (EEG), we explored alterations in cognitive control processes and approach motivation in 99 adolescents with (n=53) and without (n=46) BD during reward striving (target anticipation) and reward attainment (feedback) phases of a monetary incentive delay (MID) task. Time-frequency analysis yielded frontal theta and frontal alpha asymmetry as indices of cognitive control and approach motivation, respectively. Multilevel mixed models examined group differences, as well as age, sex, and other effects, on frontal theta and frontal alpha asymmetry during both phases of the task and on performance accuracy and reaction times. Healthy adolescent girls exhibited lower frontal theta than both adolescent girls with BD and adolescent boys with and without BD during reward anticipation and feedback. Across groups, adolescent boys displayed greater relative left frontal alpha activity than adolescent girls during reward anticipation and feedback. Behaviorally, adolescents with BD exhibited faster responses on both positively and negatively motivated trials versus neutral trials, whereas healthy adolescents had faster responses only on positively motivated trials; adolescents with BD were less accurate in responding to neutral trials compared to healthy controls. These findings shed light on normative and BD-specific involvement of approach motivation and cognitive control during different stages of reward processing in adolescence and, further, provide evidence of adolescent sex differences in these processes.

Preliminary Evidence for Limbic-Frontal Hyperexcitability in Psychogenic Nonepileptic Seizure Patients.

OBJECTIVES: The goal of the current pilot project was to probe the resting-state magnetoencephalography (MEG) in individuals with psychogenic nonepileptic seizures (PNES) and ascertain if there is evidence for frontal temporal cortical hyperexcitability, as evidenced by increased focal coherence in these regions. METHODS: Six patients with PNES and without any evidence of epilepsy were included. Nine healthy control (HC) subjects (age matched as a group) were also included. Subjects underwent 10 minutes of eyes open and 10 minutes of eyes closed MEG recording without any specific cognitive tasks (ie, resting state). RESULTS: Analysis shows posterior-occipital alpha power to be decreased but fronto-temporal delta/theta power increased in people with PNES compared with HC subjects. Analyses of mean interregional functional connectivity of 54 brain regions, patients with PNES tended to have reduced mean coherence in extra-fronto-temporal regions (ex-FTRs) while increased mean coherence in fronto-temporal regions (FTRs) compared with HC. Furthermore, all 6 patients with PNES had their highest coherence structure within the FTRs. This is in contrast to the HC subjects where only 3 of the 9 subjects had their highest coherence value structure in the FTRs (χ2 = 6.67, P = .010). CONCLUSIONS: The above findings are consistent with a disbalance between frontotemporal and posterior brain regions in this population with possible increased excitability in the FTRs. The data support the need for further investigations of the pathophysiology of PNES. The identification of a biomarker for PNES would not only provide for more informed therapeutic approaches, but it could also eliminate the stigma associated with the diagnosis of PNES.

Transcendental meditation for veterans with post-traumatic stress disorder.

OBJECTIVE: Transcendental Meditation (TM) is a mental technique using a mantra to facilitate meditation. TM has a potential for treating symptoms of posttraumatic stress disorder (PTSD), but its clinical efficacy remains to be clarified. This pilot study evaluated the acceptability, preliminary effectiveness, and neurophysiology of TM for veterans with PTSD. METHOD: Twenty-nine veterans (20.7% female) were recruited from a major medical center and enrolled in the study. TM instruction was provided by certified TM teachers from the Maharishi Foundation and consisted of 8 weeks of individual and group-based meditation instruction and practice. Outcomes were assessed at baseline, during treatment, posttreatment, and at 2-month follow-up, and included clinical interviews, self-report questionnaires, and electroencephalography (EEG) recorded during resting and meditation states. RESULTS: From baseline to posttreatment, participants reported reductions in PTSD symptoms, experiential avoidance, and depressive and somatic symptoms, as well as increases on measures of mindfulness and quality of life. Gains were either maintained or continued to improve through the 2-month follow-up. Compared to baseline, EEG spectral power increased in low-frequency bands (1-7 Hz) at posttreatment and follow-up and only during meditation states suggesting TM-specific changes in brain state associated with the intervention. CONCLUSIONS: TM appears to be an acceptable and effective treatment for veterans with PTSD that warrants further study regarding specific outcomes and beneficial changes in brain function. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A cyclical path to recovery: Calling into question the wisdom of incarceration after restoration.

Around 20-25% of the current offenders in Cook County Jail of Chicago Illinois are mentally ill. Each one of these offenders had to be named competent to stand trial when they were first being tried in court. The majority of these offenders that were considered incompetent to stand trial (IST) had to go through the competency restoration process where they were housed in a state hospital and received treatment until the court could deem them to be competent to stand trial. Many defendants with minor offenses that were eventually deemed competent to stand trial, stood trial and were found guilty and sent to jail. Given the quality of psychiatric care and the inherent stress of being incarcerated, our question was, "is it efficient to spend the time and tax dollars on providing necessary treatment to mentally ill with minor offenses so they can stand trial and be sent to jail verses placement in community-based treatment programs?" To answer this question we reviewed the US literature addressing the alternatives to incarceration (i.e., diversion programs), and the success rate of those programs to minimize re-arrests and future criminal behavior. The studies on the efficacy of diversion programs remain sparse. The limited available studies point to a higher success rate in the ability to treat mentally ill misdemeanor offenders as well as prevent future criminal behavior; however these programs must be utilized early. Our conclusions are that diversion programs have the potential to reduce recidivism for misdemeanor offendors but further research needs to be conducted to ascertain the specifics of best practices for implementation of such programs.

Brain Responses at Encoding Predict Limited Verbal Memory Retrieval by Persons with Schizophrenia.

OBJECTIVE: Special attention has been given to verbal memory deficits in schizophrenia because they are apparent in healthy biological relatives of affected individuals, indicating a link to genetic risk for the disorder. Despite a growing consensus that encoding abnormalities contribute to poor verbal memory in the disorder, few studies have directly examined how neural responses during encoding contribute to later memory performance. METHOD: We evaluated event-related potentials (ERPs) during encoding of verbal material by patients with schizophrenia, healthy first-degree biological relatives of patients, and healthy controls. The extent to which N1, N400, and anterior and parietal Late Positive Components (LPCs) explained encoding accuracy and later memory of material was investigated. RESULTS: Encoding accuracy was associated with asymmetry in anterior LPCs toward right frontal brain regions and was most evident in relatives. N1 was abnormal at encoding in schizophrenia and differentially accounted for later memory performance. In controls better recall of verbal material was predicted by a larger early occipital (N1) encoding response; however, in patients with schizophrenia smaller N1 encoding responses were related to better recall. Interestingly, better recognition of verbal material across groups was also predicted by smaller N1 amplitudes during encoding of word stimuli. CONCLUSION: Separable patterns of electrophysiological response during encoding appear to differentially support recall and recognition of material from memory. Similar patterns of electrophysiological response across patient and relative groups suggest that those who carry genetic liability for schizophrenia share deviations in the neural activity related to encoding of material into episodic memory.

Reduced P3b brain response during sustained visual attention is associated with remote blast mTBI and current PTSD in U.S. military veterans.

Approximately 275,000 American service members deployed to Iraq or Afghanistan have sustained a mild traumatic brain injury (mTBI), with 75% of these incidents involving an explosive blast. Combat-related mTBI is frequently associated with comorbid mental health disorders, especially posttraumatic stress disorder (PTSD). Attention problems, including sustained attention, are common cognitive complaints of veterans with TBI and PTSD. The present study sought to examine neural correlates of sustained attention in veterans with blast mTBI and/or current PTSD. In 124 veterans of Operations Enduring and Iraqi Freedom (OEF/OIF), we examined event-related potentials (ERPs) elicited by targets and non-targets during performance of a degraded-stimulus continuous performance task (DS-CPT). Four groups, consisting of veterans with blast-related mTBI only, current PTSD only, both blast mTBI and PTSD, and a control group, were studied. Compared to all other groups, blast mTBI only participants were more likely to respond regardless of stimulus type during the DS-CPT. During target detection, the three mTBI/PTSD groups showed reduced amplitude of the P3b (i.e., P300) ERP at Pz compared to the control group. P3b of the three affected groups did not differ from each other. These results suggest that parietal P3b amplitude reduction during target detection in the DS-CPT task may be an index of brain pathology after combat trauma, yet the diminished brain response fails to differentiate independent effects of blast-related mTBI or severity of PTSD symptomatology.

Abnormal cortical neural synchrony during working memory in schizophrenia.

OBJECTIVE: To better understand the origins of working memory (WM) impairment in schizophrenia we investigated cortical oscillatory activity in people with schizophrenia (PSZ) while they performed a WM task requiring encoding, maintenance, and retrieval/manipulation processes of spatial information. METHODS: We examined time-frequency synchronous energy of cortical source signals that were derived from magnetoencephalography (MEG) localized to cortical regions using WM-related hemodynamic responses and individualized structural head-models. RESULTS: Compared to thirteen healthy controls (HC), twelve PSZ showed performance deficits regardless of WM-load or duration. During encoding, PSZ had early theta and delta event-related synchrony (ERS) deficits in prefrontal and visual cortices which worsened with greater memory load and predicted WM performance. During prolonged maintenance of material, PSZ showed deficient beta event-related desynchrony (ERD) in dorsolateral prefrontal, posterior parietal, and visual cortices. In retrieval, PSZ showed reduced delta/theta ERS in the anterior prefrontal and ventral visual cortices and diminished gamma ERS in the premotor and posterior parietal cortices. CONCLUSIONS: Although beta/gamma cortical neural oscillatory deficits for maintenance/retrieval are evident during WM, the abnormal prefrontal theta-frequency ERS for encoding is most predictive of poor WM in schizophrenia. SIGNIFICANCE: Time-frequency-spatial analysis identified process- and frequency-specific neural synchrony abnormalities underlying WM deficits in schizophrenia.

A magnetoencephalography investigation of coherence source imaging in panic disorder.

Limbic and frontal structures are largely implicated in panic disorder (PD). Decreased coherence imaging values, as determined by magnetoencephalography (MEG), are suggestive of decreased or inefficient communication among these structures. We have previously demonstrated that coherence source imaging (CSI) values could be similar or higher in some PD patients. The purpose of the current investigation was to replicate these finding in a larger sample. Nine strictly diagnosed PD patients and nine age-matched and sex-matched healthy controls were examined. The CSI-MEG values of 26 frontotemporal regions (FTRs) and 28 extra-frontotemporal regions (ex-FTR; Brodmann areas) were determined for each participant. MEG scans were acquired using a 151-channel whole-head biomagnetometer system. Despite the relatively small sample size, CSI values were significantly lower in a number of FTRs in PD patients. In none of the ex-FTRs (i.e. posterior regions) were there differences between panic and control groups. The above data add to the complexity of understanding the nature of the pathophysiology of PD. Our finding of decreased focal coherence imaging values may reflect decreased excitability in these areas. The preliminary finding could be interpreted as an inhibitory process guarding against the spread of activity in closer hyperexcitable areas as seen in epilepsy. The current data provide evidence for dysfunctional communication within the frontotemporal structures. The findings have implications for the understanding of the neural circuitry underlying PD.

Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia.

Impaired retrieval processes evident during visual working memory in schizophrenia.

Prominent working memory (WM) deficits have been observed in people with schizophrenia (PSZ) across multiple sensory modalities, including the visuospatial realm. Electrophysiological abnormalities noted during early visual processing as well as later cognitive functions in PSZ may underlie deficiencies in WM ability, though the mechanisms linking behavior to neural responses are not well understood. WM dysfunction has also been observed in biological relatives of PSZ (REL) and therefore may be a manifestation of genetic liability for the disorder. We administered a delayed response visuospatial WM task to 23 PSZ, 30 of their REL, and 37 healthy controls (CTRL) to better understand the contributions of neural abnormalities to WM performance deficits associated with schizophrenia. PSZ performed more poorly on the WM task and failed to effectively process distractor stimuli as well as CTRL and REL. N1 electrophysiological responses to probes during retrieval differentiated the type and locations of stimuli presented during encoding in CTRL. Retrieval N1 responses in PSZ, however, failed to do so, while retrieval responses in REL showed more pronounced differentiation of stimulus features during encoding. Furthermore, neural responses during retrieval predicted behavioral performance in PSZ and REL, but not CTRL. These results suggest that retrieval processes are particularly important to efficient visuospatial WM function in PSZ and REL, and support further investigation of WM retrieval as a potential target for improving overall WM function through clinical intervention.