Mismatch Negativity as an Index of Auditory Short-Term Plasticity: Associations with Cortisol, Inflammation, and Gray Matter Volume in Youth at Clinical High Risk for Psychosis.

Mismatch negativity (MMN) event-related potential (ERP) component reduction, indexing N-methyl-D-aspartate receptor (NMDAR)-dependent auditory echoic memory and short-term plasticity, is a well-established biomarker of schizophrenia that is sensitive to psychosis risk among individuals at clinical high-risk (CHR-P). Based on the NMDAR-hypofunction model of schizophrenia, NMDAR-dependent plasticity is predicted to contribute to aberrant neurodevelopmental processes involved in the pathogenesis of schizophrenia during late adolescence or young adulthood, including gray matter loss. Moreover, stress and inflammation disrupt plasticity.

Targeting the superior temporal gyrus with real-time fMRI neurofeedback: A pilot study of the indirect effects on self-referential processes in schizophrenia.

Background: Individuals with schizophrenia (SZ) and auditory hallucinations (AHs) display a distorted sense of self and self-other boundaries. Alterations of activity in midline cortical structures such as the prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) during self-reference as well as in the superior temporal gyrus (STG) have been proposed as neuromarkers of SZ and AHs.

Methods: In this randomized, participant-blinded, sham-controlled trial, 22 adults (18 males) with SZ spectrum disorders (SZ or schizoaffective disorder) and frequent medication-resistant AHs received one session of real-time fMRI neurofeedback (NFB) either from the STG (n = 11; experimental group) or motor cortex (n = 11; control group).

Evaluation of Event-Related Potentials in Somatic Diseases - Systematic Review.

Many somatic illnesses (e.g. hypertension, diabetes, pulmonary and cardiac diseases, hepatitis C, kidney and heart failure, HIV infection, Sjogren's disease) may impact central nervous system functions resulting in emotional, sensory, cognitive or even personality impairments.

From communication dysfunction to treatment options in serious mental illness.

The Commentary covers research focused on language dysfunction in schizophrenia, and more broadly in communication dysfunction in this disorder, which I have examined with a variety of both behavioral and imaging methodologies. It briefly outlines how further progress can be achieved in pursuing the goal of a comprehensive understanding of its underlying causes. Possible therapeutic approaches are also briefly discussed.

Auditory N100 amplitude deficits predict conversion to psychosis in the North American Prodrome Longitudinal Study (NAPLS-2) cohort.

Background: The auditory N100 is an event related potential (ERP) that is reduced in schizophrenia, but its status in individuals at clinical high risk for psychosis (CHR) and its ability to predict conversion to psychosis remains unclear. We examined whether N100 amplitudes are reduced in CHR subjects relative to healthy controls (HC), and this reduction predicts conversion to psychosis in CHR.

Methods: Subjects included CHR individuals (n = 552) and demographically similar HC subjects (n = 236) from the North American Prodrome Longitudinal Study.

Mismatch Negativity in Response to Auditory Deviance and Risk for Future Psychosis in Youth at Clinical High Risk for Psychosis.

Importance: Although clinical criteria for identifying youth at risk for psychosis have been validated, they are not sufficiently accurate for predicting outcomes to inform major treatment decisions. The identification of biomarkers may improve outcome prediction among individuals at clinical high risk for psychosis (CHR-P).

Objective: To examine whether mismatch negativity (MMN) event-related potential amplitude, which is deficient in schizophrenia, is reduced in young people with the CHR-P syndrome and associated with outcomes, accounting for effects of antipsychotic medication use.

Abnormal Function in Dentate Nuclei Precedes the Onset of Psychosis: A Resting-State fMRI Study in High-Risk Individuals.

Objective: The cerebellum serves a wide range of functions and is suggested to be composed of discrete regions dedicated to unique functions. We recently developed a new parcellation of the dentate nuclei (DN), the major output nuclei of the cerebellum, which optimally divides the structure into 3 functional territories that contribute uniquely to default-mode, motor-salience, and visual processing networks as indexed by resting-state functional connectivity (RsFc). Here we test for the first time whether RsFc differences in the DN, precede the onset of psychosis in individuals at risk of developing schizophrenia.

Individualized risk components guiding antipsychotic delivery in patients with a clinical high risk of psychosis: application of a risk calculator.

Background: Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment.

Baseline Cortical Thickness Reductions in Clinical High Risk for Psychosis: Brain Regions Associated with Conversion to Psychosis Versus Non-Conversion as Assessed at One-Year Follow-Up in the Shanghai-At-Risk-for-Psychosis (SHARP) Study.

Objective: To assess cortical thickness (CT) and surface area (SA) of frontal, temporal, and parietal brain regions in a large clinical high risk for psychosis (CHR) sample, and to identify cortical brain abnormalities in CHR who convert to psychosis and in the whole CHR sample, compared with the healthy controls (HC).

Methods: Magnetic resonance imaging, clinical, and cognitive data were acquired at baseline in 92 HC, 130 non-converters, and 22 converters (conversion assessed at 1-year follow-up). CT and SA at baseline were calculated for frontal, temporal, and parietal subregions.

Longitudinal evaluation of visual P300 amplitude in clinical high-risk subjects: An event-related potential study.

Aim: We previously reported abnormal P300 and N200 in a visual oddball task, and progressive P300 amplitude reduction at 1-year follow-up in patients with first-episode schizophrenia. P300 reduction as well as intact P1/N1 were also observed in clinical high-risk subjects (CHR), but whether or not these components change over time is unknown. This study evaluates, longitudinally, the visual P300, as well as P1, N1, and N200, in CHR.

Neural characteristics of cognitive reappraisal success and failure: An ERP study.

Introduction: Cognitive reappraisal, an important strategy of emotion regulation, can change emotional experience and attention to emotional information. However, not all individuals can deploy reappraisal strategies successfully. In the current study, we investigated event-related potential (ERP) characteristics of reappraisal success and of reappraisal failure.

Real-time fMRI feedback impacts brain activation, results in auditory hallucinations reduction: Part 1: Superior temporal gyrus -Preliminary evidence.

Auditory hallucinations (AH) are one of the core symptoms of schizophrenia (SZ) and constitute a significant source of suffering and disability. One third of SZ patients experience pharmacology-resistant AH, so an alternative/complementary treatment strategy is needed to alleviate this debilitating condition. In this study, real-time functional Magnetic Resonance Imaging neurofeedback (rt-fMRI NFB), a non-invasive technique, was used to teach 10 SZ patients with pharmacology-resistant AH to modulate their brain activity in the superior temporal gyrus (STG), a key area in the neurophysiology of AH.

Real-time fMRI neurofeedback reduces auditory hallucinations and modulates resting state connectivity of involved brain regions: Part 2: Default mode network -preliminary evidence.

Auditory hallucinations (AHs) are one of the most distressing symptoms of schizophrenia (SZ) and are often resistant to medication. Imaging studies of individuals with SZ show hyperactivation of the default mode network (DMN) and the superior temporal gyrus (STG). Studies in SZ show DMN hyperconnectivity and reduced anticorrelation between DMN and the central executive network (CEN).

Altered P3a Modulations to Emotional Faces in Male Patients With Chronic Schizophrenia.

Existing evidence suggests that patients with schizophrenia may have a deficit in processing facial expressions. However, the neural basis of this processing deficit remains unclear. A total of 20 men diagnosed with chronic schizophrenia and 13 age- and sex-matched controls participated in the study.

Calculating individualized risk components using a mobile app-based risk calculator for clinical high risk of psychosis: findings from ShangHai At Risk for Psychosis (SHARP) program.

Background: Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program.

Abnormal Frequency Mismatch Negativity in Early Psychosis Outpatient Subjects.

. Abnormalities of mismatch negativity (MMN), an event-related potential, indexing preattentive mechanisms, are consistently reported in schizophrenia (SZ). MMN abnormalities elicited to different deviant types have been recently shown to distinguish among patients according to length of their illness as well as inpatient versus outpatient status, and to be modulated by premorbid IQ.

Brain functional connectivity data enhance prediction of clinical outcome in youth at risk for psychosis.

The first episode of psychosis is typically preceded by a prodromal phase with subthreshold symptoms and functional decline. Improved outcome prediction in this stage is needed to allow targeted early intervention. This study assesses a combined clinical and resting-state fMRI prediction model in 137 adolescents and young adults at Clinical High Risk (CHR) for psychosis from the Shanghai At Risk for Psychosis (SHARP) program.

Clinical subtypes that predict conversion to psychosis: A canonical correlation analysis study from the ShangHai At Risk for Psychosis program.

Objective: Since only 30% or fewer of individuals at clinical high risk convert to psychosis within 2 years, efforts are underway to refine risk identification strategies to increase their predictive power. The clinical high risk is a heterogeneous syndrome presenting with highly variable clinical symptoms and cognitive dysfunctions. This study investigated whether subtypes defined by baseline clinical and cognitive features improve the prediction of psychosis.

Association Between P300 Responses to Auditory Oddball Stimuli and Clinical Outcomes in the Psychosis Risk Syndrome.

Importance: In most patients, a prodromal period precedes the onset of schizophrenia. Although clinical criteria for identifying the psychosis risk syndrome (PRS) show promising predictive validity, assessment of neurophysiologic abnormalities in at-risk individuals may improve clinical prediction and clarify the pathogenesis of schizophrenia.

Objective: To determine whether P300 event-related potential amplitude, which is deficient in schizophrenia, is reduced in the PRS and associated with clinical outcomes.

Progressive reduction of auditory evoked gamma in first episode schizophrenia but not clinical high risk individuals.

The early auditory-evoked gamma band response (EAGBR) may serve as an index of the integrity of fast recurrent inhibition or synaptic connectivity in the auditory cortex, where abnormalities in individuals with schizophrenia have been consistently found. The EAGBR has been rarely investigated in first episode schizophrenia patients (FESZ) and individuals at clinical high risk (CHR) for schizophrenia, and never been compared directly between these populations nor evaluated longitudinally. Here we examined the EAGBR in FESZ, CHR, and matched healthy controls (HC) at baseline and 1-year follow-up assessments to determine whether the EAGBR was affected in these clinical groups, and whether any EAGBR abnormalities changed over time.

Neurobiological approaches to the study of clinical and genetic high risk for developing psychosis.

Research on neurobiological impairments in clinical and genetic high risk for developing psychosis individuals (CHR) has identified several brain abnormalities that impact both brain structure and function. The current review will discuss research examining brain abnormalities in clinical and genetic high risk for psychosis using magnetic resonance imaging (MRI) focusing on structural brain abnormalities, diffusion tensor imaging (DTI) focusing on the integrity of white matter tracks, functional MRI focusing on functional brain abnormalities, and EEG and event related potential (ERP) methodologies focusing on indices of cognitive dysfunction in CHR. Studies conducted across these different methodologies sought to identify brain regions and brain processes that would distinguish between those high risk individuals who converted to psychosis versus those who did not.

P300 as an index of transition to psychosis and of remission: Data from a clinical high risk for psychosis study and review of literature.

Auditory P300 oddball and novel components index working memory operations and salience processing, respectively, and are regarded as biomarkers of neurocognitive changes in both chronic and first-episode schizophrenia. Much less is known about whether P300 abnormalities exist in individuals at clinical high risk for psychosis (CHR) and if they are predictors of both transition to psychosis and remission from symptoms. One hundred and four CHR and 69 healthy control individuals (HC) completed P300 oddball paradigm, and 131 CHR and 69 HC subjects completed P300 novel paradigm.

Functional connectome organization predicts conversion to psychosis in clinical high-risk youth from the SHARP program.

The emergence of prodromal symptoms of schizophrenia and their evolution into overt psychosis may stem from an aberrant functional reorganization of the brain during adolescence. To examine whether abnormalities in connectome organization precede psychosis onset, we performed a functional connectome analysis in a large cohort of medication-naive youth at risk for psychosis from the Shanghai At Risk for Psychosis (SHARP) study. The SHARP program is a longitudinal study of adolescents and young adults at Clinical High Risk (CHR) for psychosis, conducted at the Shanghai Mental Health Center in collaboration with neuroimaging laboratories at Harvard and MIT.