An event-related potential study of prepotent motor activity and response inhibition deficits in schizophrenia.

Response inhibition deficits in schizophrenia (SZ) are accompanied by reduced neural activities using event-related potential (ERP) measurements. However, it remains unclear whether the reduction in inhibition-related ERPs in SZ is contingent upon prepotent motor tendencies. This study aimed to examine the relationship between ERP markers of prepotent motor activity (lateralised readiness potential, LRP) and response inhibition (P3) by collecting behavioural and EEG data from healthy control (HC) subjects and SZ patients during a modified Go/No-Go task. A trial-averaged analysis revealed that SZ patients made more commission errors in No-Go trials compared with HC subjects, although there was no significant difference in the inhibition-related P3 effect (i.e. larger P3 amplitudes in No-Go compared with Go trials) between the two groups. Subsequently, No-Go trials were sorted and median-split into bins of stronger and weaker motor tendencies. Both HC and SZ participants made more commission errors when faced with stronger motor tendencies. The LRP-sorted P3 data indicated that HC subjects exhibited larger P3 effects in response to stronger motor tendencies, whereas this trial-by-trial association between P3 and motor tendencies was absent in SZ patients. Furthermore, SZ patients displayed diminished P3 effects in No-Go trials with stronger motor tendencies but not in trials with weaker motor tendencies, relative to HC subjects. Taken together, these findings suggest that SZ patients are unable to dynamically adjust inhibition-related neural activities in response to changing inhibitory control demands and emphasise the importance of considering prepotent motor activity when investigating the neural mechanisms underlying response inhibition deficits in SZ.

Effects of polygenic risk of schizophrenia on interhemispheric callosal white matter integrity and frontotemporal functional connectivity in first-episode schizophrenia.

BACKGROUND: Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported. METHODS: Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts. RESULTS: Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)-left inferior temporal gyrus (ITG), right IFG-left ITG, right IFG-left middle frontal gyrus (MFG), and right IFG-right MFG in the FES group. CONCLUSION: Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.

Eye movement indices as predictors of conversion to psychosis in individuals at clinical high risk.

Eye movement abnormalities have been established as an "endophenotype" of schizophrenia. However, less is known about the possibility of these abnormalities as biomarkers for psychosis conversion among clinical high risk (CHR) populations. In the present study, 108 CHR individuals and 70 healthy controls (HC) underwent clinical assessments and eye-tracking tests, comprising fixation stability and free-viewing tasks. According to three-year follow-up outcomes, CHR participants were further stratified into CHR-converter (CHR-C; n = 21) and CHR-nonconverter (CHR-NC; n = 87) subgroups. Prediction models were constructed using Cox regression and logistic regression. The CHR-C group showed more saccades of the fixation stability test (no distractor) and a reduced saccade amplitude of the free-viewing test than HC. Moreover, the CHR-NC group exhibited excessive saccades and an increased saccade amplitude of the fixation stability test (no distractor; with distractor) compared with HC. Furthermore, two indices could effectively discriminate CHR-C from CHR-NC with an area under the receiver-operating characteristic (ROC) curve of 0.80, including the saccade number of the fixation stability test (no distractor) and the saccade amplitude of the free-viewing test. Combined with negative symptom scores of the Scale of Prodromal Symptoms, the area was 0.81. These findings support that eye movement alterations might emerge before the onset of clinically overt psychosis and could assist in predicting psychosis transition among CHR populations.

Functional near-infrared spectroscopy (fNIRS) as a tool to assist the diagnosis of major psychiatric disorders in a Chinese population.

Advances in neuroimaging have promised the development of specific and objective biomarkers for the diagnosis and treatment of psychiatric disorders. Recently, functional near-infrared spectroscopy (fNIRS) has been used during cognitive tasks to measure cortical dysfunction associated with mental illnesses such as Schizophrenia (SCH), Major-Depressive disorder (MD) and Bipolar Disorder (BD). We investigated the ability of fNIRS as a clinically viable tool to successfully distinguish healthy individuals from those with major psychiatric disorders. 316 patients with major psychiatric disorders (198 SCH/54 MD/64 BP) and 101 healthy controls were included in this study. Changes in oxygenated-hemoglobin during a Chinese language verbal fluency test were measured using a 52-channel fNIRS machine over the bilateral temporal and frontal lobe areas. We evaluated the ability of two task-evoked features selected from prior studies the Integral and Centroid values, to identify individuals with major diagnoses. Both the integral value of frontal and centroid value of temporal showed sensitivity in classifying individuals with mental disorders from healthy controls. However, using a combined index featuring both the integral value and centroid value to differentiate psychiatric disorders from healthy controls with an AUC of 0.913, differentiate individuals with mood disorders from healthy controls showed an AUC of 0.899, while for schizophrenia the AUC was 0.737. Our data suggest that fNIRS can be used as a candidate biomarker during differential diagnosis individuals with mood or psychosis disorders and offer a step towards individualization of treatment.

Relationship between duration of untreated prodromal symptoms and symptomatic and functional recovery.

Our previous study has found that a long duration of untreated prodromal symptoms (DUPrS) does not increase the conversion risk to psychosis in individuals with attenuated psychosis syndrome (APS). However, whether a long DUPrS will lead to other poor outcomes remains unknown. The purpose of this study was to analyse the association between the DUPrS and outcomes (symptomatic and functional recovery) in APS population. A post hoc analysis was performed in 391 individuals with APS as identified by the structured interview. APS subjects had follow-up interviews every 6 months for 2 years following diagnosis. Poor functional outcome was defined as a Global Assessment of Functioning (GAF) score less than 60 at the time of follow-up. Poor symptomatic outcome was defined as at least one of the positive symptoms rated scores of 3 or higher. A post hoc analysis was performed in 391 individuals with APS as identified by the structured interview. APS subjects had follow-up interviews every 6 months for 2 years following diagnosis. Poor functional outcome was defined as a Global Assessment of Functioning (GAF) score less than 60 at the time of follow-up. Poor symptomatic outcome was defined as at least one of the positive symptoms rated scores of 3 or higher. Of total 391 individuals, 334 were followed up for 2 years to assess clinical outcome, 82 (24.6%) had shown conversion to psychosis, 79 (23.7%) met the criteria of poor functioning outcome, and 145 (43.4%) met the criteria of poor symptomatic outcome. A significant correlation between GAF scores and DUPrS was observed in the non-converter group, but not in the converters. Individuals with APS who had a longer DUPrS were correlated with poorer functional outcome. However, it was not correlated with poorer symptomatic outcome. While a longer DUPrS was not related to poor symptomatic outcome, it was significantly related to poor functional outcome. Our findings highlight the importance of reducing DUPrS to decrease future functional impairment in populations at risk for psychosis.

Faux pas recognition performance in a help-seeking population at clinical high risk of psychosis.

There is a growing body of evidence suggesting that patients with psychosis show impaired theory of mind (ToM). However, much remains to be understood as to whether ToM deficits occur in the premorbid or post-onset period of psychosis. Our primary aim was to examine empirically impairment on ToM tasks in a group of individuals with clinical high risk (CHR) of psychosis. Fifty CHR participants identified through the Structured Interview for Prodromal Syndromes and 52 age-/education-matched controls were assessed with a complete standard neuropsychological battery (the MCCB, MATRICS Consensus Cognitive Battery) and a social cognition assessment (Faux Pas Test, FPT). We then examined the association of baseline FPT performance with conversion to psychosis at 12-month follow-up. Compared with controls, the CHR group showed significantly poorer performances on the FPT and most MCCB domains. Significant positive correlations were found between faux pas detection and the MCCB domains of Attention/Vigilance and Working Memory in CHR participants when controlling for age and years of education. Mean scores on the FPT in 14 converters who were diagnosed with full-blown psychosis within 12 months were significantly lower than they were for non-converters. Impairments in ToM ability are acquired earlier in the prodromal stage of psychosis, along with general cognition (such as memory function) deficits. Declines in ToM ability may overlap with the progress of psychosis (the gradual loss insight), sharing similar neural substrates, and reflected by impairments in basic cognitive function.

Direct and indirect effects of error monitoring on social functioning in a cohort with high-risk and first-episode psychosis.

Error monitoring plays a key role in people's adjustment to social life. This study aimed to examine the direct (DE) and indirect effects (IDE) of error monitoring, as indicated by error-related negativity (ERN), on social functioning in a clinical cohort from high-risk (APS) to first-episode psychosis (FEP). This study recruited 100 outpatients and 49 healthy controls (HC). ERN was recorded during a modified flanker task; social functioning was evaluated using the social scale of global functioning. The path analysis was executed using the "lavaan" package. When controlling for age and education, the clinical cohort had a smaller ERN than the HC group (F1, 145 = 19.58, p < 0.001, partial η2 = 0.12, 95%CI: 0.04-0.22). ERN demonstrated no substantial direct impact on current social functioning; however, it manifested indirect influences on social functioning via the disorganization factor of the Positive and Negative Syndrome Scale, both with (standardized IDE: -0.139, p = 0.009) and without (standardized IDE: -0.087, p = 0.018) accounting for the diagnosis, defined as a dummy variable (FEP = 1 and APS = 0) and included as a covariate. These findings suggest that error monitoring, as indicated by ERN, may serve as a potential prognostic indicator of social functioning in patients with psychosis.

Abnormal Scanning Patterns Based on Eye Movement Entropy in Early Psychosis.

BACKGROUND: Restricted scan path mode is hypothesized to explain abnormal scanning patterns in patients with schizophrenia. Here, we calculated entropy scores (drawing upon gaze data to measure the statistical randomness of eye movements) to quantify how strategical and random participants were to process image stimuli. METHODS: Eighty-six patients with first-episode schizophrenia (FES), 124 individuals at clinical high risk (CHR) for psychosis, and 115 healthy controls (HCs) completed an eye-tracking examination for freely viewing 35 static images (each presented 10s) and cognitive assessments. We compared the group differences in overall entropy score, as well as entropy scores under various conditions. Furthermore, we also investigated the correlation between entropy scores and symptoms along with cognitive function. RESULTS: Increased overall entropy scores were noted in FES and CHR groups relative to HCs, and these differences were already apparent within 0∼2.5s. In addition, the CHR group exhibited higher entropy when viewing low-meaning images compared to HCs. Moreover, the entropy within 0∼2.5s showed significant correlations with negative symptoms in the FES group, Attention/Vigilance scores in the CHR group, as well as Speed of processing and Attention/Vigilance scores across all three groups. CONCLUSIONS: The results indicate that FES and CHR individuals scan pictures more randomly and less strategically than HCs. These patterns also correlate with clinical symptoms and neurocognition. The present study highlights the potential of the eye movement entropy measure as a neurophysiological marker for early psychosis.

Eye Movement Characteristics for Predicting a Transition to Psychosis: Longitudinal Changes and Implications.

BACKGROUND AND HYPOTHESIS: Substantive inquiry into the predictive power of eye movement (EM) features for clinical high-risk (CHR) conversion and their longitudinal trajectories is currently sparse. This study aimed to investigate the efficiency of machine learning predictive models relying on EM indices and examine the longitudinal alterations of these indices across the temporal continuum. STUDY DESIGN: EM assessments (fixation stability, free-viewing, and smooth pursuit tasks) were performed on 140 CHR and 98 healthy control participants at baseline, followed by a 1-year longitudinal observational study. We adopted Cox regression analysis and constructed random forest prediction models. We also employed linear mixed-effects models (LMMs) to analyze longitudinal changes of indices while stratifying by group and time. STUDY RESULTS: Of the 123 CHR participants who underwent a 1-year clinical follow-up, 25 progressed to full-blown psychosis, while 98 remained non-converters. Compared with the non-converters, the converters exhibited prolonged fixation durations, decreased saccade amplitudes during the free-viewing task; larger saccades, and reduced velocity gain during the smooth pursuit task. Furthermore, based on 4 baseline EM measures, a random forest model classified converters and non-converters with an accuracy of 0.776 (95% CI: 0.633, 0.882). Finally, LMMs demonstrated no significant longitudinal alterations in the aforementioned indices among converters after 1 year. CONCLUSIONS: Aberrant EMs may precede psychosis onset and remain stable after 1 year, and applying eye-tracking technology combined with a modeling approach could potentially aid in predicting CHRs evolution into overt psychosis.

Impaired insight and error-monitoring deficits among outpatients with attenuated psychosis syndrome and first-episode psychosis.

We aimed to determine the relationship between electrophysiological signatures of error monitoring and clinical insight among outpatients with attenuated psychosis syndrome (APS) and first-episode psychosis (FEP). Error-related negativity (ERN), error positivity (Pe), and correct response negativity (CRN) were recorded during a modified flanker task for patients with FEP (n = 32), APS individuals (n = 58), and healthy controls (HC, n = 49). Clinical insight was measured using the Schedule of Assessment of Insight (SAI) and included awareness of illness (SAI-illness), relabeling of specific symptoms (SAI-symptoms), and treatment compliance (SAI-treatment). Compared with HC, patients with FEP showed smaller ERN (p < 0.001) and Pe (p = 0.011) amplitudes and individuals with APS showed smaller ERN amplitude (p = 0.009). No significant difference in CRN amplitude was observed among the groups. A smaller negative amplitude of ERN correlated with a lower score on SAI-symptoms (b = -0.032, 95% CI: 0.062 to -0.002, p = 0.035) and a decreased total score of SAI (b = -0.096, 95% CI: 0.182 to -0.010, p = 0.029). This links were adjusted for age, education, and diagnosis (a dummy variable with FEP = 1 and APS = 0), and was independent of positive symptoms. SAI-illness was predominantly influenced by diagnosis, whereas SAI-treatment was additionally affected by disorganized communications. Neither Pe nor CRN amplitude exhibited an association with clinical insight. Unconscious error detection, as indicated by ERN, may aid individuals at the preliminary stage of psychosis in recognizing the unusual symptoms.

TMS-EEG signatures of facilitated cognitive reappraisal in emotion regulation by left ventrolateral prefrontal cortex stimulation.

OBJECTIVE: Left ventrolateral prefrontal cortex (VLPFC) has been demonstrated to be a crucial region involved in the down-regulation of negative affect by cognitive reappraisal. However, the neural evidence of causality is still lacking. The current study was to investigate the contribution of left VLPFC in cognitive reappraisal by using single-pulse transcranial magnetic stimulation (spTMS) and electroencephalogram (EEG). METHODS: Fifteen participants repeated the cognitive reappraisal task at different TMS settings: no stimulation, spTMS applied at 300 ms after image onset to the left VLPFC, and to the vertex as a control site. EEG and behavioral data were concurrently recorded. TMS-evoked potential (TEP) and late positive potential (LPP) were investigated. RESULTS: In cognitive reappraisal, left VLPFC stimulation elicited stronger TEPs than vertex stimulation at 180 ms after TMS onset. Increased source activation of TEPs was identified in the precentral gyrus. Emotion regulation by reappraisal enlarged the trough of TEP at stimulation site. The left VLPFC stimulation led to enhanced LPP in cognitive reappraisal, which was negatively correlated with self-reported arousal. CONCLUSIONS: The TMS stimulation over left VLPFC influences the cognitive reappraisal process by potentiating the neural responses. Accordingly, the cortical region responsible for the execution of cognitive reappraisal is activated. The modulated neural activity is related to the behavioral response. The present study provided neural signatures for the facilitated execution of emotion regulation by left VLPFC stimulation, potentially contributing to the therapeutic protocols for mood disorders.

Reduced interpersonal neural synchronization in right inferior frontal gyrus during social interaction in participants with clinical high risk of psychosis: An fNIRS-based hyperscanning study.

BACKGROUND: Clinical high risk (CHR) of psychosis is characterized by cognitive impairment in social interaction. However, research investigating the neurobiological underpinnings of social interactions and interpersonal relationships in CHR participants is sparse. METHODS: 21 CHR and 54 healthy controls (HCs) participated in the study. Dyads were formed between one CHR, one sex-matched HC, and two sex-matched HCs comprising 19 CHR-HC dyads and 19 HC-HC dyads. The concentration changes of oxyhemoglobin and deoxyhemoglobin were examined during a two-block button-press "cooperation" and "competition" task using functional near-infrared spectroscopy(fNIRS) hyperscanning technology. CHR diagnosis and psychopathological assessments were performed by Structured Interview for Prodromal Syndromes (SIPS) and Scale of Prodromal Symptoms (SOPS). Neural synchronizations were compared between CHR-HC dyads and HC-HC dyads. Correlation analyses were performed to identify the relationship between neural synchronization, clinical syndrome and cognition. RESULTS: During the cooperation, but not the competition task, the CHR-HC dyads showed reduced inter-brain neural synchronization (INS) in the right inferior frontal gyrus (IFG) compared to the HC-HC dyads. INS also showed a positive correlation with the average cooperation rate. Moreover, the reduced INS in the CHR-HC group was significantly correlated with symptoms score of suspiciousness/persecutory ideas and movement disorders. CONCLUSIONS: The decreased INS in right IFG during cooperation could account for CHR's cognitive impairment of social interaction. Our findings provide evidence that inter-brain neural synchronization potentially represents a biomarker of social interaction deficits of CHR.

Visuospatial Learning Selectively Enhanced by Personalized Transcranial Magnetic Stimulation over Parieto-Hippocampal Network among Patients at Clinical High-Risk for Psychosis.

BACKGROUND AND HYPOTHESIS: Cognitive deficits in visuospatial learning (VSL) are highly associated with an increased risk of developing psychosis among populations with clinical high risk (CHR) for psychosis. Early interventions targeting VSL enhancement are warranted in CHR but remain rudimentary. We investigated whether personalized transcranial magnetic stimulation (TMS) over the left parieto-hippocampal network could improve VSL performance in CHR patients and if it could reduce the risk of psychosis conversion within 1 year. STUDY DESIGN: Sixty-five CHR patients were randomized to receive active or sham TMS treatments using an accelerated TMS protocol, consisting of 10 sessions of 20 Hz TMS treatments within 2 days. TMS target was defined by individual parieto-hippocampal functional connectivity and precisely localized by individual structural magnetic resonance imaging. VSL performance was measured using Brief Visuospatial Memory Test-Revised included in measurement and treatment research to improve cognition in schizophrenia consensus cognitive battery (MCCB). Fifty-eight CHR patients completed the TMS treatments and MCCB assessments and were included in the data analysis. STUDY RESULTS: We observed significant VSL improvements in the active TMS subgroup (Cohen's d = 0.71, P < .001) but not in the sham TMS subgroup (Cohen's d = 0.07, P = .70). In addition, active TMS improved the precision of VSL performance. At a 1-year follow-up, CHR patients who received active TMS showed a lower psychosis conversion rate than those who received sham TMS (6.7% vs 28.0%, χ2 = 4.45, P = .03). CONCLUSIONS: Our findings demonstrate that personalized TMS in the left parieto-hippocampal network may be a promising preventive intervention that improves VSL in CHR patients and reduces the risk of psychosis conversion at follow-up.

Comparing the efficacies of transcranial magnetic stimulation treatments using different targeting methods in major depressive disorder: protocol for a network meta-analysis.

INTRODUCTION: Transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (lDLPFC) has been widely used as a treatment for major depressive disorder (MDD) in the past two decades. Different methods for localising the lDLPFC target include the '5 cm' method, the F3 method and the neuro-navigational method. However, whether TMS efficacies differ between the three targeting methods remains unclear. We present a protocol for a systematic review and network meta-analysis (NMA) to compare the efficacies of TMS treatments using these three targeting methods in MDD. METHODS AND ANALYSIS: Relevant studies reported in English or Chinese and published up to May 2023 will be identified from searches of the following databases: PubMed, Cochrane Central Register of Controlled Trials, Embase, PsycINFO, China National Knowledge Infrastructure, Wan Fang Database, Chinese BioMedical Literature Database, and China Science and Technology Journal Database. We will include all randomised controlled trials assessing the efficacy of an active TMS treatment using any one of the three targeting methods compared with sham TMS treatment or comparing efficacies between active TMS treatments using different targeting methods. Interventions must include a minimum of 10 sessions of high-frequency TMS over the lDLPFC. The primary outcome is the reduction score of the 17-item Hamilton Depression Rating Scale, 24-item Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale. The dropout rate is a secondary outcome representing the TMS treatment's acceptability. Pairwise meta-analyses and a random-effects NMA will be conducted using Stata. We will use the surface under the cumulative ranking curve to rank the different targeting methods in terms of efficacy and acceptability. ETHICS AND DISSEMINATION: This systematic review and NMA does not require ethics approval. The results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023410273.

Increased theta-low gamma phase-amplitude coupling in resting electroencephalography after intermittent theta burst stimulation.

OBJECTIVE: Intermittent theta burst stimulation (iTBS) is based on the phase-amplitude coupling (PAC) pattern. We aimed to investigate the effect of iTBS on PAC in resting electroencephalography (EEG), which may provide insight into the underlying mechanism. METHODS: Twenty-one healthy volunteers were recruited and received both active and sham neuroimaging-guided iTBS on two separate days, which was precisely delivered to the right superior temporal gyrus. On each experimental day, resting EEG was recorded before and after stimulation for each participant. PACs across electrodes and frequency bands were calculated and compared to investigate the effect of iTBS. RESULTS: Theta (4-6 Hz) -low gamma (45-55 Hz) PAC over the stimulation site had a significant interaction effect, which increased after the active iTBS but did not differ after the sham iTBS. No significant interaction effect occurred in other cross-frequency couplings such as delta-low gamma, alpha-low gamma, delta-high gamma, theta-high gamma, or alpha-high gamma PAC in the region of interest. CONCLUSION: iTBS selectively modulated theta-low gamma PAC at the stimulation area, which exhibited both region- and frequency- specificity. This suggests that PAC may be a bridge connecting external neuromodulation to internal neuroplasticity.

The effect of initial antipsychotic treatment on hippocampal and amygdalar volume in first-episode schizophrenia is influenced by age.

BACKGROUND: Antipsychotic treatment has been shown to yield hippocampal and amygdalar volumetric changes in first-episode schizophrenia (FES). However, whether antipsychotic induced volumetric changes interact with age remains unclear. METHODS: The current study includes data from 120 medication naïve FES patients and 110 matched healthy controls (HC). Patients underwent MRI scans before (T1) and after (T2) antipsychotic treatment. HCs underwent MRI scans at baseline only. The hippocampus and amygdala were segmented via Freesurfer 7. General linear models were conducted to investigate the effect of age by diagnosis interaction on baseline volume. Linear mixed models (LMM) were used to detect the effect of age on volumetric changes from pre to post treatment in FES. RESULTS: GLM revealed a trending effect (F = 3.758, p = 0.054) of age by diagnosis interaction on the baseline volume of the left (whole) hippocampus, with older FES patients showing smaller hippocampal volumes, relative to HC, when controlled sex, education years, and ICV. LMM showed a significant age by time-point interaction effect (F = 4.194, estimate effect = -1.964, p = 0.043) on left hippocampal volume in all FES and significant time effect(F = 6.608,T1-T2(estimate effect) = 62.486, p = 0.011), whereby younger patients showed greater hippocampal volumetric decreases following treatment. At the subfield level, a significant time effect emerged in left molecular_layer_HP (F = 4.509,T1-T2(estimate effect) = 12.424, p = 0.032, FDR corrected) and left cornu ammonis(CA)4 (F = 4.800,T1-T2(estimate effect) = 7.527, p = 0.046, FDR corrected), implying volumetric reduction after treatment in these subfields. CONCLUSIONS: Our findings suggest that age plays an important role in the neuroplastic mechanisms of initial antipsychotics on the hippocampus and amygdala of schizophrenia.

Test-retest reliability of mismatch negativity and gamma-band auditory steady-state response in patients with schizophrenia.

Patients with schizophrenia show widespread impairments in clinical, cognitive and psychosocial functioning. Mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are two neurophysiological biomarkers widely used to inform diagnosis, guide treatments and track response to interventions in schizophrenia. However, evidence for the test-retest reliability of these indices across multiple sessions in schizophrenia patients remains scarce. In the present study, we included 34 schizophrenia patients (17 females) and obtained duration MMN (dMMN), frequency MMN (fMMN) and 40-Hz ASSR data across three sessions with intervals of 2 days. Event-related spectrum perturbation (ERSP) and inter-trial coherence (ITC) were calculated following Morlet wavelet time-frequency decomposition of ASSR data. The intra-class correlation coefficient (ICC) was used to quantify the reliability of MMN and ASSR measures among the three sessions. We found fair to good reliability for dMMN amplitudes but poor reliability for fMMN amplitudes. For the ASSR measures, ERSP showed good to excellent test-retest reliability while ITC had poor to fair test-retest reliability. In addition, the average of dMMN amplitudes was significantly correlated with that of ERSP across the three sessions. In summary, we established for the first time the short-term test-retest reliability of MMN and ASSR measures in schizophrenia patients. These findings demonstrate that dMMN amplitudes and ERSP of ASSR are reliable indices which may be used in longitudinal observational studies.

Neural indicator of positive reappraisal: A TMS-EEG study over the left VLPFC.

BACKGROUND: Positive reappraisal aims to reinterpret negative situations in a more positive light. Single-pulse transcranial magnetic stimulation (TMS) over the left ventrolateral prefrontal cortex (VLPFC) during positive reappraisal was suggested to improve emotion regulation capacity. However, it remains unclear whether the improvement of the capacity of emotion regulation was caused by the alterations of neural activity with TMS perturbation over the left VLPFC during positive reappraisal. METHODS: Single-pulse TMS was delivered among fifteen participants who engaged in positive reappraisal experiments with concurrent electroencephalogram (EEG) recordings. Participants repeated positive reappraisal experiments at three different stimulation settings: no stimulation, TMS pulses over the left VLPFC at 300 ms post-stimulus as the targeted stimulation and over the vertex as the control stimulation. RESULTS: TMS pulses over the left VLPFC at 300 ms post-stimuli increased late positive potential (LPP) amplitudes (300-800 ms) within the central-parietal and right prefrontal regions in response to the reappraisal stimuli compared with the negative stimuli. Moreover, changes in neural activity within the frontoparietal network contributed to the modulated LPP amplitudes of the reappraisal stimuli with the targeted stimulation. Importantly, the central-parietal LPP amplitudes of the reappraisal stimuli with the targeted stimulation was not only correlated with but also could predict the valence ratings using positive reappraisal. CONCLUSION: Our study demonstrated a causal role of the left VLPFC in positive reappraisal, and provided a neural indicator to indicate the degree to which single-pulse TMS modulated the emotional experience using positive reappraisal. It shows promise to apply in future closed-loop neuromodulation.

Reduced temporal activation during a verbal fluency test in clinical high risk of psychosis: a functional near-infrared spectroscopy-based study.

Background: Clinical high risk (CHR) of psychosis is a state in which positive symptoms cause the subjects distress but do not approach a severity level that fulfils the criteria for a psychotic episode. CHR exhibits cognitive deficits; however, the underlying neurobiological mechanisms remain unclear. This study aimed to investigate whether brain activation measured by the levels of oxygenated hemoglobin (oxy-Hb) in CHR subjects could be correlated with cognitive deficits. Methods: Fifty-eight CHR individuals who fulfilled the criteria for attenuated positive syndrome as specified in the Structured Interview for Prodromal Syndrome (SIPS) and the Scale of Prodromal Syndrome (SOPS) and 58 age- and sex-matched healthy participants were included in the study. All subjects completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) that includes tests measuring attention, verbal memory, verbal fluency, executive function, and general intelligence. Functional near-infrared spectroscopy (fNIRS) was used to measure the level of oxy-Hb in the dorsolateral prefrontal and frontotemporal cortices. Results: We observed significantly decreased oxy-Hb levels in channel 32 (located in the right superior temporal gyrus, rSTG)) within the CHR individuals compared with that in the healthy controls (HCs) (t=-3.44, Bonferroni-corrected p=0.002), indicating lower brain activity. A significant positive correlation was observed between task-related ß values and working memory in the CHR group (r=0.35, p=0.008). Conclusions: The brain activation of rSTG is abnormal among subjects at clinicial high risk for psychosis. This abnormality is probably associated with the neural mechanisms of deficits in the working memory during the early stage of psychosis.

Abnormal neural oscillations in clinical high risk for psychosis: a magnetoencephalography method study.

Background: Neural oscillations directly reflect the rhythmic changes of brain activities during the resting state or while performing specific tasks. Abnormal neural oscillations have been discovered in patients with schizophrenia. However, there is limited evidence available on abnormal spontaneous neural oscillations in clinical high risk for psychosis (CHR-P). The brain signals recorded by the magnetoencephalography (MEG) technique are not to be disrupted by the skull and scalp. Methods: In this study, we applied the MEG technique to record the resting-state neural activities in CHR-P. This was followed by a detailed MEG analysis method including three steps: (1) preprocessing, which was band-pass filtering based on the 0.5-60 Hz frequency range, removal of 50 Hz power frequency interference, and removal of electrocardiography (ECG) and electrooculography (EOG) artefacts by independent component analysis; (2) time-frequency analysis, a multitaper time-frequency transformation based on the Hanning window, and (3) source localisation, an exact low-resolution brain electromagnetic tomography. The method was verified by comparing a participant with CHR-P with a healthy control during the MEG recordings with an eyes-closed resting state. Results: Experimental results show that the neural oscillations in CHR-P were significantly abnormal in the theta frequency band (4-7 Hz) and the delta frequency band (1-3 Hz). Also, relevant brain regions were located in the left occipital lobe and left temporo-occipital junction for the theta band and in the right dorsolateral prefrontal lobe and near orbitofrontal gyrus for the delta band. Conclusions: Abnormal neural oscillations based on specific frequency bands and corresponding brain sources may become biomarkers for high-risk groups. Further work will validate these characteristics in CHR-P cohorts.