Thalamocortical dysrhythmia in patients with schizophrenia spectrum disorder and individuals at clinical high risk for psychosis.

Thalamocortical dysrhythmia (TCD) is a model characterized by abnormal resting-state thalamic oscillatory patterns where the alpha rhythm is replaced by cross-frequency coupling of low- and high-frequency rhythms. Although disrupted thalamic function is a suggested important pathophysiological mechanism underlying schizophrenia, knowledge regarding the TCD model in schizophrenia spectrum disorder (SSD) patients and individuals at clinical high risk (CHR) for psychosis is limited. A total of 169 SSD patients, 106 individuals at CHR for psychosis, and 105 healthy controls (HCs) underwent resting-state electroencephalography recordings. We performed mean global field power (MGFP) spectral analysis between 1 and 49 Hz as well as source-level theta phase-gamma amplitude coupling (TGC) analysis and compared resting-state oscillatory patterns across groups. Correlations between altered TGC values and psychotic symptom severity in the patient group were investigated. Spectral MGFP of low- and high-frequencies was larger in the SSD and CHR groups than in the HC group. The TGC of SSD patients was greater than that of HCs in the right frontal, right parietal, and left and right limbic lobes. Greater TGC in the right frontal and limbic lobes was associated with positive symptom severity in SSD patients. However, TGC in the CHR group was comparable to that in the HCs and was smaller than that in the SSD group in widespread cortical regions. The TCD pattern may be apparent after frank psychotic disorder onset in tandem with overt positive symptoms. A psychosis-risk state without overt psychotic symptoms could be characterized by abnormally increased low- and high-frequency activities with relatively preserved TGC.

Eye movement as a biomarker of impaired organizational strategies during visual memory encoding in obsessive-compulsive disorder.

The symptoms of obsessive-compulsive disorder (OCD) are largely related to impaired executive functioning due to frontostriatal dysfunction. To better treat OCD, the development of biomarkers to bridge the gap between the symptomatic-cognitive phenotype and brain abnormalities is warranted. Therefore, we aimed to identify biomarkers of impaired organizational strategies during visual encoding processes in OCD patients by developing an eye tracking-based Rey-Osterrieth complex figure test (RCFT). In 104 OCD patients and 114 healthy controls (HCs), eye movements were recorded during memorization of the RCFT figure, and organizational scores were evaluated. Kullback-Leibler divergence (KLD) scores were calculated to evaluate the distance between a participant's eye gaze distribution and a hypothetical uniform distribution within the RCFT figure. Narrower gaze distributions within the RCFT figure, which yielded higher KLD scores, indicated that the participant was more obsessed with detail and had less organizational strategy. The OCD patients showed lower organizational scores than the HCs. Although no group differences in KLD scores were noted, KLD scores were significantly associated with organization T scores in the OCD group. The current study findings suggest that eye tracking biomarkers of visual memory encoding provide a rapidly determined index of executive functioning, such as organizational strategies, in OCD patients.

Relationship between resting-state theta phase-gamma amplitude coupling and neurocognitive functioning in patients with first-episode psychosis.

BACKGROUND: Although cognitive dysfunction is a core element of schizophrenia, the neurobiological underpinnings of the pathophysiology are not yet sufficiently understood. Because the resting state is crucial for cognitive functioning and electroencephalography (EEG) can reflect instantaneous neural activity, we investigated theta phase-gamma amplitude coupling (TGC) of resting-state EEG and its relationship with cognitive function in patients with first-episode psychosis (FEP) to reveal the neural correlates of cognitive dysfunction. METHODS: A total of 59 FEP patients and 50 healthy controls (HCs) underwent resting-state, eyes-closed EEG recordings and performed the Trail Making Test Part A (TMT-A) and Part B (TMT-B) and California Verbal Learning Test (CVLT). TGC from the source signal of the resting-state EEG in default mode network (DMN)-related brain regions was compared between groups. Correlation analyses were performed between TGC and cognitive function test performance in FEP patients. RESULTS: Mean resting-state TGC was larger for the FEP patients than for the HCs. Patients with FEP showed increased TGC in the left posterior cingulate cortex, which was correlated with better performance on the TMT-A and TMT-B and on immediate and delayed recall in the CVLT. CONCLUSIONS: These results suggest that patients with FEP show compensatory hyperactivation of resting-state TGC in DMN-related brain regions, which may be related to the reallocation of cognitive resources to prepare for successful cognitive execution. This study not only highlights the neural underpinnings of cognitive dysfunction in FEP patients but also provides useful background to support the development of treatments for cognitive dysfunction in schizophrenia.

Auditory P300 as a Neurophysiological Correlate of Symptomatic Improvement by Transcranial Direct Current Stimulation in Patients With Schizophrenia: A Pilot Study.

Background. The reduced amplitude, prolonged latency, and increased intertrial variability of auditory P300 have been consistently reported in relation to the symptomatic severity of schizophrenia. This study investigated whether auditory P300 event-related potentials can be used as an objective indicator of symptomatic improvement by transcranial direct current stimulation (tDCS) in patients with schizophrenia. Methods. Ten patients with schizophrenia received 20 minutes of 2-mA tDCS twice a day for 5 consecutive weekdays. The anode was placed over the left dorsolateral prefrontal cortex, and the cathode was placed over the left temporo-parietal cortex. The Positive and Negative Syndrome Scale (PANSS) and the auditory P300 were measured for each participant at baseline and after the completion of the tDCS applications. Results. The participants showed significant improvement in the positive and negative symptoms as indexed by change in the PANSS scores by the tDCS. The P300 amplitude, latency, and intertrial variability did not statistically significantly differ after the tDCS application. However, a significant association was observed between the reduced P300 intertrial variability and improvement in the positive symptoms by tDCS. In addition, the changes in both the P300 latency and intertrial variability were significantly correlated with reduced negative symptoms after the tDCS application. Conclusions. Although this pilot study is limited by the small sample size and lack of a sham control, the results suggest that auditory P300 may be a putative marker reflecting the effect of tDCS on the positive and negative symptoms of schizophrenia.

Predicting Symptomatic and Functional Improvements over 1 Year in Patients with First-Episode Psychosis Using Resting-State Electroencephalography.

OBJECTIVE: Although early intervention from the beginning of a psychotic episode is essential for a better prognosis, biomarkers predictive of symptomatic and functional improvement in early psychotic disorders are lacking. This study aimed to investigate whether the spectral power of resting-state electroencephalography (EEG) can be used as a predictive marker of the 1-year prognosis in patients with first-episode psychosis (FEP). METHODS: Twenty-four patients with FEP and matched healthy control (HC) subjects were examined with resting-state EEG at baseline. The symptomatic severity and functional status of FEP patients were assessed at baseline and reassessed after 1 year of usual treatment. Repeated measures analysis of variance was conducted to compare EEG spectral powers across the groups. Multiple regression analysis revealed EEG spectral powers predictive of symptomatic and functional improvement in FEP patients at the 1-year follow-up. RESULTS: Delta band power in the frontal and posterior regions was significantly higher in patients with FEP than in HCs. Higher delta band power in the posterior region predicted later improvement of positive symptoms and general functional status. Lower delta band power in the frontal region predicted improvement of negative symptoms and general functioning after 1 year. CONCLUSION: These results suggest that increased delta absolute power is observed from the beginning of psychotic disorders. Furthermore, decreased delta power in the frontal region and increased delta power in the posterior region might be used as a predictive marker of a better prognosis of FEP, which would aid early intervention in clinical practice.

Dysfunctional attentional bias and inhibitory control during anti-saccade task in patients with internet gaming disorder: An eye tracking study.

BACKGROUND: Although internet gaming disorder (IGD) is considered an addictive disorder, evidence of the neurobiological underpinnings of IGD as an addictive disorder is currently lacking. We investigated whether attentional bias toward game-related stimuli was altered in IGD patients using an eye-tracking method during an anti-saccade task. METHODS: Twenty-three IGD patients and 27 healthy control (HC) subjects participated in the anti-saccade task with game-related, neutral, and scrambled images during eye tracking. Participants rated subjective scores of valence, arousal, and craving for each image stimulus after finishing eye tracking. Mixed design analysis of variance was performed to compare the differences between eye movement latency and error rate in the pro-saccade and anti-saccade conditions according to image type across the IGD and HC groups. RESULTS: In the anti-saccade task, the IGD group exhibited higher error rates in the case of game-related images than in neutral or scrambled images. However, ratings on valence, arousal, and craving did not vary among image types. The error rates of the HCs did not vary across image types, but higher arousal/craving and lower valence were reported with respect to the game-related images. CONCLUSIONS: Increased error rate during anti-saccade tasks with game-related stimuli in IGD may be due to disabilities in goal-directed behavior or inhibitory control, as observed in other addictive disorders. These findings suggest that attentional bias toward game-related stimuli can be a sensitive biological marker of IGD as an addictive disorder.

Predicting prognosis in patients with first-episode psychosis using auditory P300: A 1-year follow-up study.

OBJECTIVE: To clarify the role of auditory P300 in predicting prognosis in patients with first-episode psychosis (FEP) during a 1-year follow-up. METHODS: Auditory P300 of 24 patients with FEP and 24 matched healthy control (HC) participants were measured at baseline. The clinical status of the FEP patients was assessed at baseline and reassessed after 1 year. P300 amplitudes and latencies among the groups were analyzed using repeated measures analysis of variance. Multiple regression analysis was conducted to assess the predictive value of P300 in patients with FEP during the 1-year follow-up. RESULTS: Auditory P300 amplitudes were significantly smaller in FEP patients than HCs. Higher baseline P300 amplitudes at CPz significantly predicted better improvements in the Positive and Negative Syndrome Scale total, positive, and general scores, as well as in the Global Assessment of Functioning and Brief Psychiatric Rating Scale. CONCLUSIONS: P300 may predict improvements in symptoms, functional status, and overall psychiatric status in patients with FEP. SIGNIFICANCE: We first show that P300 amplitude at baseline predicts symptomatic and functional improvements after 1 year of treatment in patients with FEP. This finding may aid in effective interventions from the beginning of a psychotic episode to improve subsequent outcomes in clinical practice.

Altered Eye-Movement Patterns During Text Reading in Obsessive-Compulsive Disorder and Internet Gaming Disorder.

Obsessive-compulsive disorder (OCD) and internet gaming disorder (IGD), which are similar in that both involve repetitive behaviors and related with cognitive dysfunctions, frequently begin in early adolescence, which is a critical period for learning. Although the deterioration in cognitive functioning caused by these conditions may have adverse effects on information processing, such as text reading, there has been no comprehensive research on the objective indicators of altered reading patterns in these patients. Therefore, we evaluated eye-movement patterns during text reading in patients with OCD or IGD. In total, 20 patients with OCD, 28 patients with IGD and 24 healthy controls (HCs) participated in the reading task using an eye tracker. We compared the fixation durations (FDs), saccade amplitudes and eye-movement regressions of the three groups during reading. We explored relationships between the parameters reflecting altered reading patterns and those reflecting the severity of clinical symptoms. The average FDs and forward saccade amplitudes did not differ significantly among the groups. There were more eye-movement regressions in patients with OCD than in patients with IGD and HCs. No correlation was found between altered eye-movement patterns during reading and the severity of clinical symptoms in any of the patient groups. The significantly increased number of regressions (NRs) in the OCD group during reading may reflect these patients' difficulties with inferential information processing, whereas the reading pattern in the IGD group is relatively intact. These findings suggest that patients with OCD and patients with IGD have different eye-movement patterns during reading reflecting distinct cognitive impairments in the two patient groups.

Increased Attentional Bias Toward Visual Cues in Internet Gaming Disorder and Obsessive-Compulsive Disorder: An Event-Related Potential Study.

Internet gaming disorder (IGD) is a newly identified potential addiction disorder associated with compulsive internet-game playing behavior and attentional bias toward online gaming- related cues. Attentional bias toward addiction-related cues is the core feature of addiction that is associated with craving, but the pathophysiology of attentional bias in IGD is not well-understood, such as its relationship to compulsivity. In this study, we used the electrophysiological marker of late positive potential (LPP) to compare attentional bias in IGD and obsessive compulsive disorder (OCD). Twenty patients with IGD, 20 patients with OCD, and 23 healthy control (HC) subjects viewed a series of game-related, OCD-related, and neutral pictures while their event-related potentials (ERPs) were recorded. The game-related cues included in-game screen captures of popular internet games. The OCD-related cues included pictures which provokes obsessive and compulsive symptoms of contamination/washing or checking. LPPs were calculated as the mean value of amplitudes between 350 and 750 ms at the centro-parietal (CP1, CPz, CP2) and parietal (P1, Pz, P2) electrode sites. Higher LPP amplitudes were found for game-related cues in the IGD group than in the HCs, and higher LPP amplitudes were observed in the OCD group for OCD-related cues. The IGD group did not exhibit LPP changes in response to OCD-related cues. Subjective scales demonstrated increased arousal to game-related cues and OCD-related cues in both the IGD and OCD groups compared with the HC group. Increased LPPs in response to disorder-specific cues (game-related and OCD-related) were found in both IGD and OCD groups respectively, although the groups showed overlapping arousal on subjective scales. Our results indicate that LPP is a candidate neurophysiological marker for cue-related craving in IGD.

Predicting Remission in Subjects at Clinical High Risk for Psychosis Using Mismatch Negativity.

Background: The declining transition rate to psychotic disorder and the increasing rate of nonpsychotic poor outcomes among subjects at clinical high risk (CHR) for psychosis have increased the need for biomarkers to predict remission regardless of transition. This study investigated whether mismatch negativity (MMN) predicts the prognosis of CHR individuals during a 6-year follow-up period. Methods: A total of 47 healthy control (HC) subjects and 48 subjects at CHR for psychosis participated in the MMN assessment. The clinical statuses of the CHR subjects were examined at baseline and regularly for up to 6 years. The CHR subjects were divided into remitter and nonremitter groups, and the baseline MMN amplitudes and latencies were compared across the remitter, nonremitter, and HC groups. Regression analyses were performed to identify the predictive factors of remission, the improvement of attenuated positive symptoms, and functional recovery. Results: CHR nonremitters showed reduced MMN amplitudes at baseline compared to CHR remitters and HC subjects. A logistic regression analysis revealed that the baseline MMN amplitude at the frontal electrode site was the only significant predictor of remission. In a multiple regression analysis, the MMN amplitude, antipsychotic use, and years of education predicted an improvement in attenuated positive symptoms. The MMN amplitude at baseline predicted functional recovery. Conclusions: These results suggest that MMN is a putative predictor of prognosis regardless of the transition to psychotic disorder in subjects at CHR. Early prognosis prediction and the provision of appropriate interventions based on the initial CHR status might be aided using MMN.

Decomposing P300 into correlates of genetic risk and current symptoms in schizophrenia: An inter-trial variability analysis.

BACKGROUND: The P300 event-related potential (ERP) component, which reflects cognitive processing, is a candidate biomarker for schizophrenia. However, the role of P300 in the pathophysiology of schizophrenia remains unclear because averaged P300 amplitudes reflect both genetic predisposition and current clinical status. Thus, we sought to identify which aspects of P300 are associated with genetic risk versus symptomatic status via an inter-trial variability analysis. METHODS: Auditory P300, clinical symptoms, and neurocognitive function assessments were obtained from forty-five patients with schizophrenia, thirty-two subjects at genetic high risk (GHR), thirty-two subjects at clinical high risk (CHR), and fifty-two healthy control (HC) participants. Both conventional averaging and inter-trial variability analyses were conducted for P300, and results were compared across groups using analysis of variance (ANOVA). Pearson's correlation was utilized to determine associations among inter-trial variability for P300, current symptoms and neurocognitive status. RESULTS: Average P300 amplitude was reduced in the GHR, CHR, and schizophrenia groups compared with that in the HC group. P300 inter-trial variability was elevated in the CHR and schizophrenia groups but relatively normal in the GHR and HC groups. Furthermore, P300 inter-trial variability was significantly related to negative symptom severity and neurocognitive performance results in schizophrenia patients. CONCLUSIONS: These results suggest that P300 amplitude is an endophenotype for schizophrenia and that greater inter-trial variability of P300 is associated with more severe negative and cognitive symptoms in schizophrenia patients.

Neurophysiological correlates of altered response inhibition in internet gaming disorder and obsessive-compulsive disorder: Perspectives from impulsivity and compulsivity.

Although internet gaming disorder (IGD) and obsessive-compulsive disorder (OCD) represent opposite ends of the impulsivity and compulsivity dimensions, the two disorders share common neurocognitive deficits in response inhibition. However, the similarities and differences in neurophysiological features of altered response inhibition between IGD and OCD have not been investigated sufficiently. In total, 27 patients with IGD, 24 patients with OCD, and 26 healthy control (HC) subjects participated in a Go/NoGo task with electroencephalographic recordings. N2-P3 complexes elicited during Go and NoGo condition were analyzed separately and compared among conditions and groups. NoGo-N2 latency at the central electrode site was delayed in IGD group versus the HC group and correlated positively with the severity of internet game addiction and impulsivity. NoGo-N2 amplitude at the frontal electrode site was smaller in OCD patients than in IGD patients. These findings suggest that prolonged NoGo-N2 latency may serve as a marker of trait impulsivity in IGD and reduced NoGo-N2 amplitude may be a differential neurophysiological feature between OCD from IGD with regard to compulsivity. We report the first differential neurophysiological correlate of the altered response inhibition in IGD and OCD, which may be a candidate biomarker for impulsivity and compulsivity.

Development of a portable A-ABR screener using a microprocessor.

Hearing loss is one of the most common birth defects among infants. Most hearing-impaired children are not diagnosed until one to three years of age, which is too late to treat for normal speech and language development. If hearing impairment is identified and treated in its early stage, a child's speech and language skills could be comparable to his or her normal-hearing peers. Auditory brain-stem response (ABR) is nowadays one of the most reliable diagnostic tools in the early detection of hearing impairment. In this study, we applied the 'Fsp' method to distinguish between normal and impaired hearing. We have developed a battery-operated portable automated auditory brainstem response (A-ABR) system that automatically detects hearing impairment in neonates or infants. We partially validated the accuracy of this system in twenty normal-hearing adults.

A survival prediction model of hemorrhagic shock in rats using a logistic regression equation.

Hemorrhagic shock is a common cause of death in emergency rooms. Since the symptoms of hemorrhagic shock occur after shock has considerably progressed, it is difficult to diagnose shock early. The purpose of this study was to improve early diagnosis of hemorrhagic shock using a survival prediction model in rats. We measured ECG, blood pressure, respiration and temperature in 45 Sprague-Dawley rats, and then obtained a logistic regression equation predicting survival rates. Area under the ROC curves was 0.99. The Hosmer-Lemeshow goodness-of-fit chi-square was 0.86 (degree of freedom=8, p=0.999). Applying the determined optimal boundary value of 0.25, the accuracy of survival prediction was 94.7%.

Preliminary study on physiological changes of hemorrhagic shock in rats.

Hemorrhagic shock is a common cause of death in emergency rooms. The objective evaluation of hemorrhagic shock is very important for early diagnosis and treatment. The purpose of this study is to understand its mechanism by analyzing the changes of bio-signals in hemorrhagic shock using controlled hemorrhage of Sprague-Dawley rats. We constructed an integrated system to be able to control bleeding and to simultaneously measure bio-signals such as ECG, blood pressure, temperature, and respiration. In order to verify the system, we measured the bio-signals mentioned above while hemorrhagic shock was induced by withdrawing blood (2.5 ml / 100 g / 15 min) from a femoral vein for 10 rats.