Modulating Inhibitory Control Processes Using Individualized High Definition Theta Transcranial Alternating Current Stimulation (HD θ-tACS) of the Anterior Cingulate and Medial Prefrontal Cortex.

Increased frontal midline theta activity generated by the anterior cingulate cortex (ACC) is induced by conflict processing in the medial frontal cortex (MFC). There is evidence that theta band transcranial alternating current stimulation (θ-tACS) modulates ACC function and alters inhibitory control performance during neuromodulation. Multi-electric (256 electrodes) high definition θ-tACS (HD θ-tACS) using computational modeling based on individual MRI allows precise neuromodulation targeting of the ACC via the medial prefrontal cortex (mPFC), and optimizes the required current density with a minimum impact on the rest of the brain. We therefore tested whether the individualized electrode montage of HD θ-tACS with the current flow targeted to the mPFC-ACC compared with a fixed montage (non-individualized) induces a higher post-modulatory effect on inhibitory control. Twenty healthy subjects were randomly assigned to a sequence of three HD θ-tACS conditions (individualized mPFC-ACC targeting; non-individualized MFC targeting; and a sham) in a double-blind cross-over study. Changes in the Visual Simon Task, Stop Signal Task, CPT III, and Stroop test were assessed before and after each session. Compared with non-individualized θ-tACS, the individualized HD θ-tACS significantly increased the number of interference words and the interference score in the Stroop test. The changes in the non-verbal cognitive tests did not induce a parallel effect. This is the first study to examine the influence of individualized HD θ-tACS targeted to the ACC on inhibitory control performance. The proposed algorithm represents a well-tolerated method that helps to improve the specificity of neuromodulation targeting of the ACC.

Cognitive profiles of healthy siblings of first-episode schizophrenia patients.

AIM: Cognitive deficit in psychotic illness is intensively studied, different cognitive subtypes have been suggested. In recent years, there has been an increase in the number of studies in patients with schizophrenia and their relatives searching for endophenotypes of the disease. The aim of our study was to investigate cognitive performance and cognitive subtypes in the siblings of the patients. METHODS: Four groups of subjects were included: patients with a first episode of psychotic illness, the siblings of these patients, and two control groups. All the study subjects (N = 84) had a battery of neuropsychological tests that measured basic cognitive domains - memory, executive functions, attention, visual-spatial skills, language skills and psychomotor speed - administered to them. The data were assessed with pairwise t-tests for group comparisons. The siblings were distributed into three groups according to their cognitive performance: non-deficit, partial deficit, and global deficit. Subsequently, the patients were assigned into three groups corresponding to their siblings' performance. RESULTS: Our results revealed attenuation of abstract thinking in the siblings compared to the controls. As expected, the patients showed impairment across all cognitive domains. The patients and siblings demonstrated similar profiles in each subtype, in the severity of their impairment, and in their patterns of cognitive performance. CONCLUSIONS: Our results suggest that the cognitive profile can be considered as an endophenotype of psychotic disorders.

Neuroactive Steroids and Cognitive Functions in First-Episode Psychosis Patients and Their Healthy Siblings.

Background: Neuroactive steroids (NAS) affect neurotransmitter systems and cognition; thus, they play role in etiopathogenesis of psychiatric disorders. Aims: The primary aim was to examine cognition and effects of NAS on cognitive functioning in first-episode psychosis patients and in their healthy siblings. The secondary aims were to verify whether cognitive deficit is an endophenotype of psychosis and whether higher NAS levels represent a high-risk factor for psychosis. Methods: Studied participants were 1) patients with first episode of psychosis, 2) healthy siblings of the patients, and 3) matching healthy controls. Study procedures included administration of a battery of neuropsychological tests assessing six cognitive domains and examination of NAS plasma levels [cortisol (CORT), 11-deoxycorticosterone (DOC), testosterone (TEST), dehydroepiandrostendione (DHEA), dihydrotestosterone (DHT), and progesterone (PROG)]. Results: A total of 67 subjects were analyzed (16 patients, 22 siblings, and 29 controls). Significant group differences were found in most of the cognitive domains; the patients had the lowest scores. The Kruskal-Wallis test revealed significant group differences in CORT levels (p < 0.01), TEST (p < 0.01), and DHT (p < 0.001); no difference was found in PROG, DHEA, and DOC. All cognitive domains, except for attention, were affected by the NAS levels. CORT levels of patients correlated with speed of processing (r = 0.55) and working memory (r = 0.52), while PROG levels correlated with abstraction (r = -0.63). In siblings, there was a negative correlation between TEST levels and verbal memory (r = -0.51) and PROG with attention (r = -0.47). Conclusions: Our results verified that individual domains of cognitive deficit (abstraction and verbal memory) can be considered as an endophenotype of psychosis. Higher levels of cortisol and testosterone in siblings are consistent with high-risk states for psychosis. Multiple interactions between NAS and cognitive functioning, particularly memory functions, were observed. Study limitations (small sample size and administration of antipsychotic medication) did not allow us to establish unequivocally NAS as an endophenotype.

Cognitive Profiles and Functional Connectivity in First-Episode Schizophrenia Spectrum Disorders - Linking Behavioral and Neuronal Data.

The character of cognitive deficit in schizophrenia is not clear due to the heterogeneity in research results. In heterogeneous conditions, the cluster solution allows the classification of individuals based on profiles. Our aim was to examine the cognitive profiles of first-episode schizophrenia spectrum disorder (FES) subjects based on cluster analysis, and to correlate these profiles with clinical variables and resting state brain connectivity, as measured with magnetic resonance imaging. A total of 67 FES subjects were assessed with a neuropsychological test battery and on clinical variables. The results of the cognitive domains were cluster analyzed. In addition, functional connectivity was calculated using ROI-to-ROI analysis with four groups: Three groups were defined based on the cluster analysis of cognitive performance and a control group with a normal cognitive performance. The connectivity was compared between the patient clusters and controls. We found different cognitive profiles based on three clusters: Cluster 1: decline in the attention, working memory/flexibility, and verbal memory domains. Cluster 2: decline in the verbal memory domain and above average performance in the attention domain. Cluster 3: generalized and severe deficit in all of the cognitive domains. FES diagnoses were distributed among all of the clusters. Cluster comparisons in neural connectivity also showed differences between the groups. Cluster 1 showed both hyperconnectivity between the cerebellum and precentral gyrus, the salience network (SN) (insula cortex), and fronto-parietal network (FPN) as well as between the PreCG and SN (insula cortex) and hypoconnectivity between the default mode network (DMN) and seeds of SN [insula and supramarginal gyrus (SMG)]; Cluster 2 showed hyperconnectivity between the DMN and cerebellum, SN (insula) and precentral gyrus, and FPN and IFG; Cluster 3 showed hypoconnectivity between the DMN and SN (insula) and SN (SMG) and pallidum. The cluster solution confirms the prevalence of a cognitive decline with different patterns of cognitive performance, and different levels of severity in FES. Moreover, separate behavioral cognitive subsets can be linked to patterns of brain functional connectivity.

Long-acting injectable antipsychotics for prevention and management of violent behaviour in psychotic patients.

BACKGROUND AND AIMS: It has been well established that long-term antipsychotic treatment prevents relapse, lowers number of rehospitalisations, and also effectively reduces violent behaviour. Although violent behaviour is not a typical manifestation of schizophrenia or other psychotic disorders, the diagnosis of psychosis increases the overall risk of violence. One of the few modifiable factors of violence risk is adherence with medication. In contrast, non-adherence with drug treatment and subsequent relapse increases risk of violent acts. Non-adherence can be addressed partially by long-acting injectable antipsychotics (LAI). The aim of our review was to examine the role of antipsychotic drugs, especially LAI, in prevention and management of violent behaviour in psychosis. METHODS: This is a non-systematic, narrative review of the data from open, naturalistic, retrospective, and population studies, case series, and post hoc analyses of randomised controlled trials. Search of electronic databases (PubMed, Embase) was performed to identify relevant papers. RESULTS: Nine published papers (3 cross-sectional chart reviews, 4 retrospective studies, 2 prospective, randomised trials) were found. The results indicated positive clinical and antiaggressive effects of LAI in psychotic patients with high risk of violent behaviour. DISCUSSION: Reviewed evidence suggests that secured drug treatment with LAI may have clinical benefit in schizophrenia patients with high risk of violent behaviour. LAI significantly reduced the severity of hostility, aggressivity, number of violent incidents, and criminal offences. These findings are supported further by the empirical evidence from clinical practice, high rates of prescribed LAI to schizophrenia patients in high-security and forensic psychiatric facilities. CONCLUSIONS: Available data encourage the use of LAI in forensic psychiatry, especially during court-ordered commitment treatment.

Case report: Is verbal cognitive performance in bilingual neuropsychiatric patients test-language dependent?

Bilingualism (BL) is increasing around the world. Although BL has been shown to have a broad impact-both positive and negative-on language and cognitive functioning, cognitive models and standards are mainly based on monolinguals. If we take cognitive performance of monolinguals as a standard, then the performance of bilinguals might not be accurately estimated. The assessment of cognitive functions is an important part of both the diagnostic process and further treatment in neurological and neuropsychiatric patients. In order to identify the presence or absence of cognitive deficit in bilingual patients, it will be important to determine the positive and/or negative impact of BL properties on measured cognitive performance. However, research of the impact of BL on cognitive performance in neuropsychiatric patients is limited. This article aims to compare the influence of the language (dominant-L1, second-L2) used for assessment of verbal cognitive performance in two cases of bilingual neuropsychiatric patients (English/Czech). Despite the fact that the two cases have different diagnoses, similarities in working memory and verbal learning profiles for L1 and L2 were present in both patients. We expected L1 to have higher performance in all measures when compared with L2. This assumption was partially confirmed. As expected, verbal working memory performance was better when assessed in L1. In contrast, verbal learning showed the same or better performance in L2 when compared with L1. Verbal fluency and immediate recall results were comparable in both languages. In conclusion, the language of administration partially influenced verbal performance of bilingual patients. Whether the language itself influenced low performance in a given language or it was a result of a deficit requires further research. According to our results, we suggest that an assessment in both languages needs to be a component of reasonable cognitive assessment of bilingual patients.