Directed brain interactions over time: A resting-state EEG comparison between schizophrenia and healthy individuals.

Understanding the neurophysiological mechanisms of schizophrenia (SZ) is one of the challenges of neuroscience. Many anatomical and functional studies have pointed to problems in brain connectivity in SZ individuals. However, little is known about the relationships between specific brain regions and impairments in brain connectivity in SZ individuals. Herein we propose a new approach using time-varying graphs and the motif synchronization method to build dynamic brain functional networks (BFNs). Dynamic BFNs were constructed from resting-state electroencephalography (rs-EEG) of 14 schizophrenia (SZ) individuals and 14 healthy controls (HCs). BFNs were evaluated based on the percentage of synchronization importance between a pair of regions (considering external and internal interactions) over time. We found differences in the directed interaction between brain regions in SZ individuals compared to the control group. Our method revealed low bilaterally directed interactions between the temporal lobes in SZ individuals compared to HCs, indicating a potential link between altered brain connectivity and the characteristic symptoms of schizophrenia. From a clinical perspective, these results shed light on developing new therapeutic approaches targeting these specific neural interactions that are altered in individuals with SZ. This knowledge allows the application of better interventions focused on restoring or compensating for interrupted connectivity patterns.

Ketamine in fibromyalgia: a systematic review.

OBJECTIVE: Fibromyalgia (FM) subjects are treated with antidepressant agents; in most cases, these drugs lose efficacy or have adverse effects. Ketamine is an anesthetic drug used in FM in some studies. This article aims to systematically review the safety and efficacy of ketamine in fibromyalgia (FM) patients. MATERIALS AND METHODS: We systematically searched articles on FM and ketamine published at Pubmed from 1966 to 2021. This study was registered at PROSPERO. RESULTS: There were only 6 articles published in this field, with a total of 115 patients. The female sex was predominant (88 to 100%). The age varied from 23 to 53 years old. Disease duration ranged from 1 month to 28 years. The dosage of ketamine changed from 0.1 mg/kg-0.3-0.5 mg/kg in intravenous infusion (4/5) and subcutaneous application (1/5). Regarding outcomes, the Visual analog scale (VAS) before ketamine was from 59 to 100 mm and after treatment from 2 to 95 mm. Most short-term studies had a good response. Only the study with 8 weeks of follow-up did not observe a good response. Side effects were common; all appeared during the infusion and disappeared after a few minutes of the ketamine injection. CONCLUSIONS: The present study demonstrates the effectiveness and safety of ketamine in FM patients in the short term. Although, more studies, including long-term follow-up studies, are still needed.

Analysis of functional connectivity using machine learning and deep learning in different data modalities from individuals with schizophrenia.

Objective. Schizophrenia(SCZ) is a severe mental disorder associated with persistent or recurrent psychosis, hallucinations, delusions, and thought disorders that affect approximately 26 million people worldwide, according to the World Health Organization. Several studies encompass machine learning (ML) and deep learning algorithms to automate the diagnosis of this mental disorder. Others study SCZ brain networks to get new insights into the dynamics of information processing in individuals suffering from the condition. In this paper, we offer a rigorous approach with ML and deep learning techniques for evaluating connectivity matrices and measures of complex networks to establish an automated diagnosis and comprehend the topology and dynamics of brain networks in SCZ individuals.Approach.For this purpose, we employed an functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) dataset. In addition, we combined EEG measures, i.e. Hjorth mobility and complexity, with complex network measurements to be analyzed in our model for the first time in the literature.Main results.When comparing the SCZ group to the control group, we found a high positive correlation between the left superior parietal lobe and the left motor cortex and a positive correlation between the left dorsal posterior cingulate cortex and the left primary motor. Regarding complex network measures, the diameter, which corresponds to the longest shortest path length in a network, may be regarded as a biomarker because it is the most crucial measure in different data modalities. Furthermore, the SCZ brain networks exhibit less segregation and a lower distribution of information. As a result, EEG measures outperformed complex networks in capturing the brain alterations associated with SCZ.Significance. Our model achieved an area under receiver operating characteristic curve (AUC) of 100% and an accuracy of 98.5% for the fMRI, an AUC of 95%, and an accuracy of 95.4% for the EEG data set. These are excellent classification results. Furthermore, we investigated the impact of specific brain connections and network measures on these results, which helped us better describe changes in the diseased brain.

Brain instability in dynamic functional connectivity in schizophrenia.

Schizophrenia is a severe psychiatric disorder associated with altered connectivity of brain functional networks (BFNs). Researchers have observed a profound disruption in prefrontal-temporal interactions, damage to hub regions in brain networks and modified topological organization of BFNs in schizophrenia (SCZ) individuals. Assessment of BFNs with dynamic approaches allow the characterization of new functional structures, such as topological stability patterns and temporal connectivity, which are not accessible through static methods. In this perspective, the present study investigated the physiological processes of brain connectivity in SCZ. A resting-state EEG dataset of 14 SCZ individuals and 14 healthy controls (HC) was obtained at a sampling rate of 250 Hz. Dynamic BFNs were constructed using time-varying graphs combined with the motifs' synchronization method and the indexes were evaluated in different scales: global averages, by hemispheres, by regions, and by electrodes for both groups. The SCZ group exhibited lower temporal connectivity, lesser hub probability, and fewer number of edges in right and left temporal lobes over time, besides increased temporal connectivity in the central-parietal region. Neither differences for the full synchronization time of BFNs were observed, nor for intra- and inter-hemispheric connections between groups. These results indicate that SCZ BFNs exhibit a dynamic fluctuation pattern with abrupt increases in connectivity over time for the regions studied. This elucidates an attempted interaction of the temporal area with other regions (frontal, central-parietal, and occipital) that is not sufficient to maintain a connectivity pattern in schizophrenia individuals similar to that of healthy subjects. Our results suggest that changes in interaction of dynamic BFNs connections in SCZ can be better approached by dynamic analyses that enable a thorough glance at brain changes over time.

Isotonic exercises and relaxing techniques in individuals with temporomandibular dysfunction.

Objective: The present study aimed to compare the clinical characteristics of volunteers with temporomandibular dysfunction before and after performing exercises with those of volunteers who only followed self-care guidelines.Methods: A parallel randomized controlled trial was performed. Individuals included underwent the intervention twice a week for one month, while the control group only followed self-care guidelines.Results: Twenty-three volunteers participated; however, during the study, four dropped out. At the end of the study, the degree of depression decreased in the volunteers in the intervention group.Conclusion: The level of pain decreased, but the improvement was not statistically significant and, therefore, could not be attributed to the intervention. It can be concluded that the strategies used to reduce pain in this study were not sufficient for clinical improvement in volunteers with temporomandibular dysfunction.

Brain Asymmetry in Pain Affective Modulation.

OBJECTIVE: The aim of this study was to characterize the dynamic brain networks underlying the affective modulation of pleasant, unpleasant, and neutral image perception due to painful stimulations in healthy subjects. METHODS: Forty volunteers, 20 men and 20 women, participated in this study. Brain activity was recorded by 64-channel electroencephalography. After data cleaning, brain functional networks were built through the use of the motif synchronization method. RESULTS: We found that increased cerebral connectivity in the left hemisphere under the pain condition broke the connection symmetry. Both women and men showed homophilic connections (intrahemispheric), but women were more homophilic than men. The pain condition increased homophily in the left hemisphere, and emotions could modulate pain. The frontal, central, and left temporal regions showed homophilic variation, depending on the emotional stimulus. CONCLUSIONS: Pain and emotions altered brain activity. There was increased connectivity and homophily in the left brain hemisphere for the painful experience. The emotions modulated brain activity in the pain condition. Overall, the brain presented homophilic characteristics; homophily changed, depending on emotion or pain. The left brain hemisphere seems to be related to pain processing.

Zinc supplementation combined with antidepressant drugs for treatment of patients with depression: a systematic review and meta-analysis.

CONTEXT: Zinc is an essential trace mineral required for the function of brain and neural structures. The role of zinc supplementation in the prevention and treatment of depression has been suggested in clinical studies that reported a reduction in depressive symptoms. OBJECTIVE: The aim of this review was to determine whether zinc supplementation vs placebo can prevent or improve depressive symptoms in children, adolescents, or adults. DATA SOURCES: Five electronic databases were searched, and studies published until September 2019 were included without language restriction. STUDY SELECTION: Randomized, controlled, crossover trials that evaluated the effect of zinc supplementation vs a comparator for prevention or improvement of depressive symptoms in children, adolescents, or adults were eligible for inclusion. DATA EXTRACTION: Two authors independently performed data extraction and risk-of-bias assessment. RESULTS: The initial search identified 12 322 studies, 5 of which were eligible for meta-analysis. The standardized mean difference (SMD) showed an average reduction of 0.36 point (95%CI, -0.67 to -0.04) in the intervention group compared with the placebo group. Forstudies in which the mean age of participants was ≥ 40 years, the SMD was reduced by 0.61 point (95%CI, -1.12 to -0.09) in the intervention group vs the placebo group. The meta-analysis by sample size (< 60 individuals and ≥ 60 individuals) did not show an effect of zinc supplementation in reducing depressive symptoms (SMD -0.28; 95%CI, -0.67 to -0.10; and SMD -0.52; 95%CI, -1.10 to 0.06). CONCLUSION: Zinc supplementation may reduce depressive symptoms in individuals treated with antidepressant drugs for clinical depression. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42018081691.

Analgesic effect of cathodal transcranial current stimulation over right dorsolateral prefrontal cortex in subjects with muscular temporomandibular disorders: study protocol for a randomized controlled trial.

BACKGROUND: Temporomandibular disorders are a group of orofacial pain conditions that are commonly identified in the general population. Like many other chronic pain conditions, they can be associated with anxiety/depression, which can be related to changes in the activity of the dorsolateral prefrontal cortex. Some studies have demonstrated clinical improvement in subjects with chronic pain who are given therapeutic neuromodulation. Transcranial direct current stimulation is a noninvasive brain stimulation technique that allows the modulation of neuronal membranes. This therapy can enhance or inhibit action potential generation in cortical neurons. In some instances, medications acting in the central nervous system may be helpful despite their adverse side effects. It is important to determine if cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex, an area that modulates emotion and motor cortex excitability, has an analgesic effect on chronic temporomandibular disorders pain. METHOD/DESIGN: The investigators will run a randomized, controlled crossover double blind study with 15 chronic muscular temporomandibular disorder subjects. Each subject will undergo active (1 mA and 2 mA) and sham transcranial direct current stimulation. Inclusion criteria will be determined by the Research Diagnostic Criteria for Temporomandibular Disorders questionnaire, with subjects who have a pain visual analogic scale score of greater than 4/10 and whose pain has been present for the previous 6 months, and with a State-Trait Anxiety Inventory score of more than 42. The influence of transcranial direct current stimulation will be assessed through a visual analogic scale, quantitative sensory testing, quantitative electroencephalogram, and the State-Trait Anxiety Inventory score. DISCUSSION: Some studies have demonstrated a strong association between anxiety/depression and chronic pain, where one may be the cause of the other. This is especially true in chronic temporomandibular disorders, and breaking this cycle may have an effect over the symptoms and associated dysfunction. We believe that by inhibiting activity of the dorsolateral prefrontal cortex though cathodal transcranial direct current stimulation, there may be a change in both anxiety/depression and pain level. Transcranial direct current stimulation may emerge as a new tool to be considered for managing these patients. We envision that the information obtained from this study will provide a better understanding of the management of chronic temporomandibular disorders. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov on 24 May 2014 (Identifier: NCT02152267 ).

Temporomandibular disorders in patients with schizophrenia using antipsychotic agents: a discussion paper.

Patients with psychiatric problems show a tendency to develop temporomandibular disorders (TMD). Particularly, patients with schizophrenia are quite likely to have signs and symptoms of TMD due to the impairment of their oral health, the use of antipsychotic drugs, and other general health problems. In nonschizophrenic populations, TMD have been considered as the main cause of nondental pain in the orofacial region, involving mechanisms associated with changes in masticatory activity at the cortical and neuromuscular levels. Individuals with schizophrenia do not usually complain of pain, and TMD is misdiagnosed in this population. In this paper, we aimed to review the clinical aspects of TMD in people with schizophrenia on antipsychotic drug therapy.

Sertindole in the management of schizophrenia.

Nowadays, new schizophrenia treatments are more ambitious than ever, aiming not only to improve psychotic symptoms, but also quality of life and social reinsertion. Our objective is to briefly but critically review the diagnosis of schizophrenia, the atypical antipsychotics sertindole's pharmacology, safety and status, and mainly evaluate the effects of sertindole compared with other second generation antipsychotics for people with schizophrenia and schizophrenia-like psychosis. In vitro studies showed that sertindole exerts a potent antagonism at serotonin 5-HT2A, 5-HT2C, dopamine D2, and αl adrenergic receptors. Sertindole offers an alternative treatment option for refractory patients given its good EPS profile, favorable metabolic profile, and comparable efficacy to risperidone. Due to cardiovascular safety concerns, sertindole is available as a second-line choice for patients intolerant to other antipsychotic agents. Further clinical studies, mainly comparisons with other second-generation antipsychotic agents, are needed to define the role of sertindole in the treatment of schizophrenia.

Aripiprazole for patients with schizophrenia and schizoaffective disorder: an open-label, randomized, study versus haloperidol.

INTRODUCTION: Aripiprazole, a dopamine D2 receptor partial agonist, has also partial agonist activity at serotonin (5-HT)1A receptors and antagonist activity at 5-HT2A receptors. METHODS: In this 8-week, multicenter, randomized, parallel-group, open-label, flexible-dose study, patients diagnosed with schizophrenia or schizoaffective disorder were randomized to aripiprazole 15-30 mg/day or haloperidol 10-15 mg/day. RESULTS: Patients treated with both aripiprazole and haloperidol improved from baseline in Positive and Negative Syndrome Scale total, positive, and negative scores as well as in Clinical Global Impressions scores (all P<.001). At the end of the study, the percentage of patients classified as responders--according to >or=40% reduction in the Positive and Negative Syndrome Scale negative subscale score--was significantly higher in the aripiprazole group (20%) than in the haloperidol group (0%) (P<.05). Additionally, a higher number of patients receiving haloperidol required more anticholinergic medications (P<.001) than aripiprazole-treated patients, whereas more aripiprazole (45.5%) than haloperidol-treated patients (12.9%) required benzodiazepines (P=.002). At endpoint, rates of preference of medication were higher in the aripiprazole group (63.2%) than in the haloperidol group (21.7%), as expressed by patients and caregivers (P=.001). CONCLUSION: Aripiprazole and haloperidol had similar efficacy in terms of reduction of overall psychopathology. Although aripiprazole has been demonstrated to be superior concerning negative symptoms and in terms of tolerability (extrapyramidal symptoms) and preferred by patients and caregivers than haloperidol, significantly more aripiprazole-treated patients required benzodiazepines.

Relapse in patients with schizophrenia: a comparison between risperidone and haloperidol.

OBJECTIVES: To compare rates of rehospitalization and time to relapse in risperidone vs. haloperidol-treated schizophrenic patients discharged from the hospital. METHODS: Randomized controlled trial comparing risperidone and haloperidol regarding relapse in patients with schizophrenia treated with flexible doses during one year. RESULTS: Twenty patients were assigned to risperidone and 13 to haloperidol. One patient from each group withdrew consent and one patient in the risperidone group was lost for follow-up. Six (30.0%) patients in the risperidone group and 3 (23.1%) in the haloperidol group relapsed (p=1.00). However, time to relapse was shorter in the later (logrank =4.2; p=.04). When rehospitalized, patients in the risperidone group stayed 34.5 days (median) at hospital as compared to the haloperidol group (median of 61 days) (p=.61). CONCLUSION: The proportion of schizophrenic patients who relapsed was similar in both groups; However, time to relapse was shorter in the haloperidol-treated patients.

[Diabetes mellitus and atypical antipsychotics]. / Diabetes mellitus e antipsicóticos atípicos.

Schizophrenic patients present a higher risk for the development of hyperglycemic disorder and the use of antipsychotic drugs seems to increase the risk of diabetes mellitus. The present review concerns the relation between atypical antipsychotic drugs and the risk of developing diabetes mellitus. A Medline and Webofscience search was performed by using the terms "Hyperglycemia", "Diabetes Mellitus" and "Antipsychotic Agents", to identify original papers and reviews published between 1997 and september 2002. It is concluded that there is a higher risk of glycemic disorders in the population of patients treated by antipsychotic drugs. Dietetic measures and attention to risk factors should be taken into account during the treatment of psychotic patients.