Mismatch Negativity in Schizophrenia, Unaffected First-degree Relatives, and Healthy Controls.

BACKGROUND: Mismatch negativity (MMN) amplitude is attenuated in schizophrenia patients (SZ). However, variability in illness course among SZ samples and types of deviant stimuli used in MMN paradigms have contributed to inconsistent findings across studies. Though MMN is suggested to be impaired in schizotypy, the potential link between the two is yet to be systematically examined in unaffected first-degree relatives of schizophrenia patients (FDR). METHODS: The SZ sample had twenty-two drug-naïve or drug-free patients (dSZ) and thirty chronic/medicated patients (cSZ). dSZ and cSZ patients were compared with thirty-six unaffected FDR and thirty-two healthy controls (HC) using a two-tone passive auditory oddball MMN paradigm in an event-related potential experiment with two conditions (presented as separate blocks)-duration-deviant (duration-MMN) and frequency-deviant (frequency-MMN). Schizotypy scores and MMN indices were examined for correlation in FDR. RESULTS: Duration-MMN amplitude was significantly attenuated in both dSZ and cSZ compared to other groups. dSZ and cSZ did not differ on MMN indices. Psychopathology scores and features of illness (illness duration, medication dosage, etc.) did not correlate with MMN indices. In FDR, Schizotypal trait measures did not correlate with MMN indices. CONCLUSIONS: Duration-MMN emerged as a more robust indicator of prediction error signalling deficit in SZ. Frequency-MMN amplitude did not significantly differ among the groups, and MMN indices did not correlate with state and trait measures of schizophrenia-related psychopathology. These findings reiterates that auditory sensory processing captured by MMN is likely reflective of dynamic cognitive functions at the point of testing, and is unlikely to be an expression of enduring symptomatology.

Modulation of mind wandering using transcranial direct current stimulation: A meta-analysis based on electric field modeling.

Mind wandering (MW) is a heterogeneous construct involving task-unrelated thoughts. Recently, the interest in modulating MW propensity via non-invasive brain stimulation techniques has increased. Single-session transcranial direct current stimulation (tDCS) in healthy controls has led to mixed results in modulating MW propensity, possibly due to methodological heterogeneity. Therefore, our aim was to conduct a systematic meta-analysis to examine the influence of left dorsolateral prefrontal cortex (lDLPFC) and right inferior parietal lobule (rIPL) targeted tDCS on MW propensity. Importantly, by computational modeling of tDCS-induced electric fields, we accounted for differences in tDCS-dose across studies that varied strongly in their applied methodology. Fifteen single-session, sham-controlled tDCS studies published until October 2021 were included. All studies involved healthy adult participants and used cognitive tasks combined with MW thought-probes. Heterogeneity in tDCS electrode placement, stimulation polarity and intensity were controlled for by means of electric field simulations, while overall methodological quality was assessed via an extended risk of bias (RoB) assessment. We found that RoB was the strongest predictor of study outcomes. Moreover, the rIPL was the most promising cortical area for influencing MW, with stronger anodal electric fields in this region being negatively associated with MW propensity. Electric field strength in the lDLPFC was not related to MW propensity. We identified several severe methodological problems that could have contributed to overestimated effect sizes in this literature, an issue that needs urgent attention in future research in this area. Overall, there is no reliable evidence for tDCS influencing MW in the healthy. However, the analysis also revealed that increasing neural excitability in the rIPL via tDCS might be associated with reduced MW propensity. In an exploratory approach, we also found some indication that targeting prefrontal regions outside the lDLPFC with tDCS could lead to increased MW propensity.

Characterizing Heterogeneity in Neuroimaging, Cognition, Clinical Symptoms, and Genetics Among Patients With Late-Life Depression.

Importance: Late-life depression (LLD) is characterized by considerable heterogeneity in clinical manifestation. Unraveling such heterogeneity might aid in elucidating etiological mechanisms and support precision and individualized medicine. Objective: To cross-sectionally and longitudinally delineate disease-related heterogeneity in LLD associated with neuroanatomy, cognitive functioning, clinical symptoms, and genetic profiles. Design, Setting, and Participants: The Imaging-Based Coordinate System for Aging and Neurodegenerative Diseases (iSTAGING) study is an international multicenter consortium investigating brain aging in pooled and harmonized data from 13 studies with more than 35 000 participants, including a subset of individuals with major depressive disorder. Multimodal data from a multicenter sample (N = 996), including neuroimaging, neurocognitive assessments, and genetics, were analyzed in this study. A semisupervised clustering method (heterogeneity through discriminative analysis) was applied to regional gray matter (GM) brain volumes to derive dimensional representations. Data were collected from July 2017 to July 2020 and analyzed from July 2020 to December 2021. Main Outcomes and Measures: Two dimensions were identified to delineate LLD-associated heterogeneity in voxelwise GM maps, white matter (WM) fractional anisotropy, neurocognitive functioning, clinical phenotype, and genetics. Results: A total of 501 participants with LLD (mean [SD] age, 67.39 [5.56] years; 332 women) and 495 healthy control individuals (mean [SD] age, 66.53 [5.16] years; 333 women) were included. Patients in dimension 1 demonstrated relatively preserved brain anatomy without WM disruptions relative to healthy control individuals. In contrast, patients in dimension 2 showed widespread brain atrophy and WM integrity disruptions, along with cognitive impairment and higher depression severity. Moreover, 1 de novo independent genetic variant (rs13120336; chromosome: 4, 186387714; minor allele, G) was significantly associated with dimension 1 (odds ratio, 2.35; SE, 0.15; P = 3.14 ×108) but not with dimension 2. The 2 dimensions demonstrated significant single-nucleotide variant-based heritability of 18% to 27% within the general population (N = 12 518 in UK Biobank). In a subset of individuals having longitudinal measurements, those in dimension 2 experienced a more rapid longitudinal change in GM and brain age (Cohen f2 = 0.03; P = .02) and were more likely to progress to Alzheimer disease (Cohen f2 = 0.03; P = .03) compared with those in dimension 1 (N = 1431 participants and 7224 scans from the Alzheimer's Disease Neuroimaging Initiative [ADNI], Baltimore Longitudinal Study of Aging [BLSA], and Biomarkers for Older Controls at Risk for Dementia [BIOCARD] data sets). Conclusions and Relevance: This study characterized heterogeneity in LLD into 2 dimensions with distinct neuroanatomical, cognitive, clinical, and genetic profiles. This dimensional approach provides a potential mechanism for investigating the heterogeneity of LLD and the relevance of the latent dimensions to possible disease mechanisms, clinical outcomes, and responses to interventions.

Caregiver assisted home-based cognitive remediation for individuals diagnosed with schizophrenia: A pilot study.

Cognitive deficits in individuals diagnosed with schizophrenia are ubiquitous and, therefore, cognitive remediation is considered one of the prime targets of a comprehensive intervention program for schizophrenia. However, cognitive remediation is a resource consuming intervention and in lower and middle-income countries (LAMIC) such interventions are often neglected due to the resource constraints of the mental health services set-ups. Therefore, it is imperative to develop cognitive remediation programs that are less resource consuming for the mental health service delivery system. Keeping this in view, in the present pilot study, we tested the feasibility of a caregiver assisted home-based cognitive remediation program and compared its efficacy with a clinic-based cognitive remediation program. Findings show that it is feasible to conduct cognitive remediation program with the help of caregivers in patients' home settings and that the home-based cognitive remediation is as effective as the clinic-based cognitive remediation. The results of the study have been further discussed in the light of the practical implications, limitations and future research.

Online Theta Frequency Transcranial Alternating Current Stimulation for Cognitive Remediation in Schizophrenia: A Case Report and Review of Literature.

Transcranial alternating current stimulation (tACS), a noninvasive brain stimulation technique that uses low-intensity alternating current, has been postulated to be a potential therapeutic option in treating the cognitive deficits in schizophrenia. Transcranial alternating current stimulation synchronizes the neural oscillations to the applied stimulation frequency in the stimulated cortical regions. In this report, we have reviewed the literature pertinent to the clinical application of tACS in psychiatric disorders; in addition, we have described the clinical use of online theta tACS in a schizophrenia patient with cognitive deficits. Online theta tACS led to improvement in working memory, attention, processing speed, and emotional processing. The beneficial effect of tACS persisted during reassessment of the patient after 50 days. Transcranial alternating current stimulation, given its noninvasiveness, safety, and ease of administration, has the potential to ameliorate cognitive deficits in neuropsychiatric disorders like schizophrenia.

Enhanced error related negativity amplitude in medication-naïve, comorbidity-free obsessive compulsive disorder.

Error monitoring and response inhibition is a key cognitive deficit in obsessive-compulsive disorder (OCD). Frontal midline regions such as the cingulate cortex and pre-supplementary motor area are considered critical brain substrates of this deficit. Electrophysiological equivalent of the above dysfunction is a fronto-central event related potential (ERP) which occurs after an error called the error related negativity (ERN). In this study, we sought to compare the ERN parameters between medication-naïve, comorbidity-free subjects with OCD and healthy controls (HC). Age, sex and handedness matched subjects with medication-naïve, comorbidity-free OCD (N = 16) and Healthy Controls (N = 17) performed a modified version of the flanker task while EEG was acquired for ERN. EEG signals were recorded from the electrodes FCz and Cz. Clinical severity of OCD was assessed using the Yale Brown Obsessive Compulsive Scale. The subjects with OCD had significantly greater ERN amplitude at Cz and FCz. There were no significant correlations between ERN measures and illness severity measures. Overactive performance monitoring as evidenced by enhanced ERN amplitude could be considered as a biomarker for OCD.

Feasibility of Online Neuromodulation Using Transcranial Alternating Current Stimulation in Schizophrenia.

Abnormalities in resting and event-related brain oscillations are known to be associated with cognitive deficits in schizophrenia. Transcranial alternating current stimulation (tACS) modulates these rhythms across the neuronal circuits and could have a potential therapeutic role in psychiatric disorders. In this report, we describe, for the first time, application of online tACS in a schizophrenia patient with working memory deficits. This case report supports the feasibility and potential utility of online tACS in schizophrenia, which needs further systematic research.

Insight facilitation with add-on tDCS in schizophrenia.

Impaired insight in schizophrenia patients has been linked with prefrontal deficits. In this open-label study, we examined for potential insight facilitation effects of add-on tDCS (with anodal stimulation of left DLPFC and cathodal stimulation over left temporo-parietal junction) in schizophrenia patients (N=21) with persistent auditory hallucinations despite adequate antipsychotic treatment. Following tDCS, there was a significant improvement in insight with concurrent significant reduction in auditory hallucination severity. Improvement in insight correlated significantly with improvement in severity of auditory hallucinations. These findings suggest improvement of insight with add-on tDCS in schizophrenia with persistent auditory hallucinations.

Neural basis of tDCS effects on auditory verbal hallucinations in schizophrenia: a case report evidence for cortical neuroplasticity modulation.

Transcranial direct current stimulation (tDCS) has been reported to ameliorate auditory hallucinations that are nonresponsive/minimally responsive to antipsychotic treatment in schizophrenia. The neurobiological basis of the tDCS effects in ameliorating auditory hallucinations is yet to be explored. In this case report, for the first time, using the novel method for noninvasive assessment of cortical plasticity, we demonstrate potential neuroplasticity effect of tDCS in improving treatment-resistant auditory hallucinations in a schizophrenic patient.

Rapid improvement of auditory verbal hallucinations in schizophrenia after add-on treatment with transcranial direct-current stimulation.

Treatment of nonresponsive auditory hallucinations in schizophrenia have been reported to improve with transcranial direct-current stimulation. This case description illustrates the use of add-on transcranial direct-current stimulation for rapid amelioration of auditory hallucinations in schizophrenia during the acute phase. Because transcranial direct-current stimulation is safe, largely well tolerated, and relatively inexpensive, this add-on treatment option is worth exploring through further rigorous studies.

Transcranial direct current stimulation in schizophrenia.

Transcranial direct current stimulation (tDCS) is an upcoming treatment modality for patients with schizophrenia. A series of recent observations have demonstrated improvement in clinical status of schizophrenia patients with tDCS. This review summarizes the research work that has examined the effects of tDCS in schizophrenia patients with respect to symptom amelioration, cognitive enhancement and neuroplasticity evaluation. tDCS is emerging as a safe, rapid and effective treatment for various aspects of schizophrenia symptoms ranging from auditory hallucinations-for which the effect is most marked, to negative symptoms and cognitive symptoms as well. An interesting line of investigation involves using tDCS for altering and examining neuroplasticity in patients and healthy subjects and is likely to lead to new insights into the neurological aberrations and pathophysiology of schizophrenia. The mechanistic aspects of the technique are discussed in brief. Future work should focus on establishing the clinical efficacy of this novel technique and on evaluating this modality as an adjunct to cognitive enhancement protocols. Understanding the mechanism of action of tDCS as well as the determinants and neurobiological correlates of clinical response to tDCS remains an important goal, which will help us expand the clinical applications of tDCS for the treatment of patients with schizophrenia.