Spectroscopic abnormalities in the pregenual anterior cingulate cortex in obsessive-compulsive disorder using proton magnetic resonance spectroscopy: a controlled study.

BACKGROUND: The main aim of the present study is to determine the role of metabolites observed using proton magnetic resonance spectroscopy (1H-MRS) in obsessive-compulsive disorder (OCD). As the literature describing biochemical changes in OCD yields conflicting results, we focused on accurate metabolite quantification of total N-acetyl aspartate (tNAA), total creatine (tCr), total choline-containing compounds (tCh), and myo-inositol (mI) in the anterior cingulate cortex (ACC) to capture the small metabolic changes between OCD patients and controls and between OCD patients with and without medication. METHODS: In total 46 patients with OCD and 46 healthy controls (HC) matched for age and sex were included in the study. The severity of symptoms in the OCD was evaluated on the day of magnetic resonance imaging (MRI) using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Subjects underwent 1H-MRS from the pregenual ACC (pgACC) region to calculate concentrations of tNAA, tCr, tCho, and mI. Twenty-eight OCD and 28 HC subjects were included in the statistical analysis. We compared differences between groups for all selected metabolites and in OCD patients we analyzed the relationship between metabolite levels and symptom severity, medication status, age, and the duration of illness. RESULTS: Significant decreases in tCr (U = 253.00, p = 0.022) and mI (U = 197.00, p = 0.001) in the pgACC were observed in the OCD group. No statistically significant differences were found in tNAA and tCho levels; however, tCho revealed a trend towards lower concentrations in OCD patients (U = 278.00, p = 0.062). Metabolic concentrations showed no significant correlations with the age and duration of illness. The correlation statistics found a significant negative correlation between tCr levels and YBOCS compulsions subscale (cor = -0.380, p = 0.046). tCho and YBOCS compulsions subscale showed a trend towards a negative correlation (cor = -0.351, p = 0.067). Analysis of subgroups with or without medication showed no differences. CONCLUSIONS: Patients with OCD present metabolic disruption in the pgACC. The decrease in tCr shows an important relationship with OCD symptomatology. tCr as a marker of cerebral bioenergetics may also be considered as a biomarker of the severity of compulsions. The study failed to prove that metabolic changes correlate with the medication status or the duration of illness. It seems that a disruption in the balance between these metabolites and their transmission may play a role in the pathophysiology of OCD.

Electrophysiological correlates of suicidality.

Suicidal risk assessment is still a major challenge not only in psychiatric practice. Clinical investigation of suicidality can be significantly improved by using standardized scales for assessing suicide risk. The choice of a method for assessing suicidality also has significant implications for the search of valid available biomarker of suicidal behavior, where a less complex suicidality assessment procedure yields inaccurate results. This article offers an overview and analyzes in detail clinical studies of suicidality by electrophysiological methods since 2005 to 5/2020, especially in connection with presumed pathophysiological mechanism of the "suicidal brain" and the chosen method of sucidality assessment. Electrophysiological methods such as quantitative electroencephalography indicators, event-related potential, loudness dependence of the auditory evoked potential, polysomnography and heart rate variability offer a robust battery of easily available methods for assessing impaired emotional regulation. Nowadays it is unfortunately very difficult to point out the optimal electrophysiological examination of suicidal behaviour because of conflicting conclusion of presented studies which have been probably caused by various suicidal risk assessments, not always available data on affecting medication prior to testing and small samples of suicidal participants among studies. The most consistent and hopeful results are presented by evaluation of theta power by quantitative electroencephalography, although there are also few conflicting conclusions. The authors of this paper believe that this article could be good starting point for further research of electrophysiological methods in the field of suicidality.

Artifacts in Simultaneous hdEEG/fMRI Imaging: A Nonlinear Dimensionality Reduction Approach.

Simultaneous recordings of electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) are at the forefront of technologies of interest to physicians and scientists because they combine the benefits of both modalities-better time resolution (hdEEG) and space resolution (fMRI). However, EEG measurements in the scanner contain an electromagnetic field that is induced in leads as a result of gradient switching slight head movements and vibrations, and it is corrupted by changes in the measured potential because of the Hall phenomenon. The aim of this study is to design and test a methodology for inspecting hidden EEG structures with respect to artifacts. We propose a top-down strategy to obtain additional information that is not visible in a single recording. The time-domain independent component analysis algorithm was employed to obtain independent components and spatial weights. A nonlinear dimension reduction technique t-distributed stochastic neighbor embedding was used to create low-dimensional space, which was then partitioned using the density-based spatial clustering of applications with noise (DBSCAN). The relationships between the found data structure and the used criteria were investigated. As a result, we were able to extract information from the data structure regarding electrooculographic, electrocardiographic, electromyographic and gradient artifacts. This new methodology could facilitate the identification of artifacts and their residues from simultaneous EEG in fMRI.

Role of Glutamatergic System in Obsessive-Compulsive Disorder with Possible Therapeutic Implications.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric illness and 1 of the most common anxiety disorders with the prevalence of 3%. Although its pathogenesis remains unclear, the traditional model focused on alternations in the serotonin system. Selective serotonin reuptake inhibitors provide the most effective treatment; however, as much as 40-60% of patients do not respond to antidepressants therapy. Thus, attention has shifted towards other neurotransmitter systems and related neuroanatomical structures. Recently, there is extensive evidence showing a key role of glutamate pathways abnormalities within the cortico-striatal-thalamo-cortical circuitry and temporal lobes in OCD pathogenesis. In this review, we link together the existent neuroanatomical, neurophysiological, and neuropsychological evidence to argue for potential benefits of adjuvant treatment with glutamatergic agents, especially memantine. By a targeted de-excitation effect on the glutamatergic system in the temporal lobes and connected brain regions, memantine might further alleviate OCD symptoms. This effect should be even more pronounced in certain subtypes of patients with specific cognitive deficits and maladaptive compensatory memory processes (e.g., checkers).

The Comparison of Effectiveness of Various Potential Predictors of Response to Treatment With SSRIs in Patients With Depressive Disorder.

The substantial non-response rate in depressive patients indicates a continuing need to identify predictors of treatment outcome. The aim of this 6-week, open-label study was (1) to compare the efficacy of a priori defined predictors: ≥20% reduction in MADRS score at week 1, ≥20% reduction in MADRS score at week 2 (RM ≥ 20% W2), decrease of cordance (RC), and increase of serum and plasma level of brain-derived neurotrophic factor at week 1; and (2) to assess whether their combination yields higher efficacy in the prediction of response to selective serotonin re-uptake inhibitors (SSRIs) than when used singly. Twenty-one patients (55%) achieved a response to SSRIs. The RM ≥20% W2 (areas under curve-AUC = 0.83) showed better predictive efficacy compared to all other predictors with the exception of RC. The identified combined model (RM ≥ 20% W2 + RC), which predicted response with an 84% accuracy (AUC = 0.92), may be a useful tool in the prediction of response to SSRIs.

Sad mood induction has an opposite effect on amygdala response to emotional stimuli in euthymic patients with bipolar disorder and healthy controls.

BACKGROUND: Aberrant amygdala reactivity to affective stimuli represents a candidate factor predisposing patients with bipolar disorder (BD) to relapse, but it is unclear to what extent amygdala reactivity is state-dependent. We evaluated the modulatory influence of mood on amygdala reactivity and functional connectivity in patients with remitted BD and healthy controls. METHODS: Amygdala response to sad versus neutral faces was investigated using fMRI during periods of normal and sad mood induced by autobiographical scripts. We assessed the functional connectivity of the amygdala to characterize the influence of mood state on the network responsible for the amygdala response. RESULTS: We included 20 patients with remitted BD and 20 controls in our study. The sad and normal mood exerted opposite effects on the amygdala response to emotional faces in patients compared with controls (F1,38 = 5.85, p = 0.020). Sad mood amplified the amygdala response to sad facial stimuli in controls but attenuated the amygdala response in patients. The groups differed in functional connectivity between the amygdala and the inferior prefrontal gyrus (p ≤ 0.05, family-wise error-corrected) of ventrolateral prefrontal cortex (vlPFC) corresponding to Brodmann area 47. The sad mood challenge increased connectivity during the period of processing sad faces in patients but decreased connectivity in controls. LIMITATIONS: Limitations to our study included long-term medication use in the patient group and the fact that we mapped only depressive (not manic) reactivity. CONCLUSION: Our results support the role of the amygdala-vlPFC as the system of dysfunctional contextual affective processing in patients with BD. Opposite amygdala reactivity unmasked by the mood challenge paradigm could represent a trait marker of altered mood regulation in patients with BD.

The effectiveness of prefrontal theta cordance and early reduction of depressive symptoms in the prediction of antidepressant treatment outcome in patients with resistant depression: analysis of naturalistic data.

Current studies suggest that an early improvement of depressive symptoms and the reduction of prefrontal theta cordance value predict the subsequent response to antidepressants. The aim of our study was (1) to compare the predictive abilities of early clinical improvement defined as ≥ 20 % reduction in Montgomery and Åsberg Depression Rating Scale (MADRS) total score at week 1 and 2, and the decrease of prefrontal theta cordance at week 1 in resistant depressive patients and (2) to assess whether the combination of individual predictors yields more robust predictive power than either predictor alone. Eighty-seven subjects were treated (≥ 4 weeks) with various antidepressants chosen according to the judgment of attending psychiatrists. Areas under curve (AUC) were calculated to compare predictive effect of defined single predictors (≥ 20 % reduction in MADRS total score at week 1 and 2, and the decrease of cordance at week 1) and combined prediction models. AUCs of all three predictors were not statistically different (pair-wise comparison). The model combining all predictors yielded an AUC value 0.91 that was significantly higher than AUCs of each individual predictor. The results indicate that the combined predictor model may be a useful and clinically meaningful tool for the prediction of antidepressant response in patients with resistant depression.

EEG-vigilance regulation is associated with and predicts ketamine response in major depressive disorder.

Ketamine offers promising new therapeutic options for difficult-to-treat depression. The efficacy of treatment response, including ketamine, has been intricately linked to EEG measures of vigilance. This research investigated the interplay between intravenous ketamine and alterations in brain arousal, quantified through EEG vigilance assessments in two distinct cohorts of depressed patients (original dataset: n = 24; testing dataset: n = 24). Clinical response was defined as a decrease from baseline of >33% on the Montgomery-Åsberg Depression Rating Scale (MADRS) 24 h after infusion. EEG recordings were obtained pre-, start-, end- and 24 h post- infusion, and the resting EEG was automatically scored using the Vigilance Algorithm Leipzig (VIGALL). Relative to placebo (sodium chloride 0.9%), ketamine increased the amount of low-vigilance stage B1 at end-infusion. This increase in B1 was positively related to serum concentrations of ketamine, but not to norketamine, and was independent of clinical response. In contrast, treatment responders showed a distinct EEG pattern characterized by a decrease in high-vigilance stage A1 and an increase in low-vigilance B2/3, regardless of whether placebo or ketamine had been given. Furthermore, pretreatment EEG differed between responders and non-responders with responders showing a higher percentage of stage A1 (53% vs. 21%). The logistic regression fitted on the percent of A1 stages was able to predict treatment outcomes in the testing dataset with an area under the ROC curve of 0.7. Ketamine affects EEG vigilance in a distinct pattern observed only in responders. Consequently, the percentage of pretreatment stage A1 shows significant potential as a predictive biomarker of treatment response.Clinical Trials Registration: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000952-17/CZ Registration number: EudraCT Number: 2013-000952-17.

Prediction of treatment response and the effect of independent component neurofeedback in obsessive-compulsive disorder: a randomized, sham-controlled, double-blind study.

AIMS: The goal of this study was to assess the effect of independent component neurofeedback (NFB) on EEG and clinical symptoms in patients with obsessive-compulsive disorder (OCD). Subsequently, we explored predictors of treatment response and EEG correlates of clinical symptoms. METHODS: In a randomized, double-blind, parallel design, 20 inpatients with OCD underwent 25 sessions of NFB or sham feedback (SFB). NFB aimed at reducing EEG activity in an independent component previously reported abnormal in this diagnosis. Resting-state EEG recorded before and after the treatment was analyzed to assess its posttreatment changes, relationships with clinical symptoms and treatment response. RESULTS: Overall, clinical improvement in OCD patients was not accompanied by EEG change as assessed by standardized low-resolution electromagnetic tomography and normative independent component analysis. Pre- to posttreatment comparison of the trained component and frequency did not yield significant results; however, in the NFB group, the nominal values at the downtrained frequency were lower after treatment. The NFB group showed significantly higher percentage reduction of compulsions compared to the SFB group (p = 0.015). Pretreatment higher amount of delta (1-6 Hz) and low alpha oscillations as well as a lower amount of high beta activity predicted a worse treatment outcome. Source localization of these delta and high beta oscillations corresponded with previous EEG resting-state findings in OCD patients compared to healthy controls. CONCLUSION: Independent component NFB in OCD proved useful in percentage improvement of compulsions. Based on our correlation analyses, we hypothesize that we targeted a network related to treatment resistance.

Guidelines for the recording and evaluation of pharmaco-sleep studies in man: the International Pharmaco-EEG Society (IPEG).

The International Pharmaco-EEG Society (IPEG) presents guidelines summarising the requirements for the recording and computerised evaluation of pharmaco-sleep data in man. Over the past years, technical and data-processing methods have advanced steadily, thus enhancing data quality and expanding the palette of sleep assessment tools that can be used to investigate the activity of drugs on the central nervous system (CNS), determine the time course of effects and pharmacodynamic properties of novel therapeutics, hence enabling the study of the pharmacokinetic/pharmacodynamic relationship, and evaluate the CNS penetration or toxicity of compounds. However, despite the presence of robust guidelines on the scoring of polysomnography -recordings, a review of the literature reveals inconsistent -aspects in the operating procedures from one study to another. While this fact does not invalidate results, the lack of standardisation constitutes a regrettable shortcoming, especially in the context of drug development programmes. The present guidelines are intended to assist investigators, who are using pharmaco-sleep measures in clinical research, in an effort to provide clear and concise recommendations and thereby to standardise methodology and facilitate comparability of data across laboratories.

What are demographic and EEG differences between responding and non-responding panic disorder patients.

BACKGROUND: Standardized low-resolution electromagnetic tomography (sLORETA) is a new quantitative EEG method for determining distribution of neuronal electrical activity in the form of three-dimensional images of current density of the cerebral cortex. Unlike standard quantitative EEG, it allows noninvasive and detailed localization of neuronal generators responsible for surface EEG with zero localization error. The study aimed at finding electrotomographic differences between patients with panic disorder who respond well to cognitive behavioral therapy (CBT) and those with an inadequate response and to determine factors predicting a response to treatment. METHODS: The study comprised 24 patients diagnosed with panic disorder with or without agoraphobia (ICD-10 F41.0). The severity of symptoms was measured with the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Sheehan Anxiety Scale, subjective and objective Clinical Global Impression (CGI) and Dissociative Experiences Scale (DES). Additionally, quality of life was evaluated using the Q-LES-Q questionnaire. Based on final BAI score decreases by 25%, the patients were classified into two groups - responders and non-responders. 21-channel EEGs were recorded at baseline and after completion of therapy. Power spectra and intracortical tomography were computed by sLORETA in seven frequency bands and compared between (responders vs. non-responders) and within (pre- vs. post-treatment) groups. RESULTS: There were no differences between responders and non-responders with respect to age, gender and baseline disorder symptomatology. Statistical analysis of sLORETA values demonstrated no significant inter-group differences in the pretreatment current density distribution. After treatment, only responders showed a significant decrease of alpha-2 sources (p<0.05) in the occipital lobes and cuneus and a statistical trend for increased beta-3 sources (p<0.10) in the posterior cingulate. In non-responders, there were no statistically significant changes in sLORETA findings following therapy. CONCLUSIONS: The study failed to use pretreatment sLORETA in the prediction of therapeutic response in patients with panic disorder. However, we clearly demonstrated that only treatment response was associated with significant changes of electric neuronal activity. An analysis of demographic data suggested that duration of the disease, age, level of dissociation and employment may be considered as factors influencing the response.

Retrospective analysis of quantitative electroencephalography changes in a dissimulating patient after dying by suicide: A single case report.

We present the case of a 49-year-old man who was diagnosed with depressive disorder, with the first episode having a strong reactive factor. He was involuntarily admitted to a psychiatric hospital after a failed attempt at taking his own life, where he responded to psychotherapy and antidepressant therapy, as evidenced by a >60% reduction in his MADRS total score. He was discharged after 10 days of treatment, denied having suicidal ideations, and was motivated to follow the recommended outpatient care. The risk for suicide during hospitalization was also assessed using suicide risk assessment tools and psychological assessments, including projective tests. The patient underwent a follow-up examination with an outpatient psychiatrist on the 7th day after discharge, during which the suicide risk assessment tool was administered. The results indicated no acute suicide risk or worsening of depressive symptoms. On the 10th day after discharge, the patient took his own life by jumping out of the window of his flat. We believe that the patient had dissimulated his symptoms and possessed suicidal ideations, which were not detected despite repeated examinations specifically designed to assess suicidality and depression symptoms. We retrospectively analyzed his quantitative electroencephalography (QEEG) records to evaluate the change in prefrontal theta cordance as a potentially promising biomarker of suicidality, given the inconclusive results of studies published to date. An increase in prefrontal theta cordance value was found after the first week of antidepressant therapy and psychotherapy in contrast to the expected decrease due to the fading of depressive symptoms. As demonstrated by the provided case study, we hypothesized that prefrontal theta cordance may be an EEG indicator of a higher risk of non-responsive depression and suicidality despite therapeutic improvement.

The effect of low-frequency rTMS on auditory hallucinations, EEG source localization and functional connectivity in schizophrenia.

BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) diminishes auditory hallucinations (AHs). The aims of our study were a) to assess the efficacy of LF-rTMS in a randomized, sham-controlled double-blind alignment, b) to identify the electrophysiological changes accompanying the LF-rTMS, and c) to identify the influence of LF-rTMS on brain functional connectivity (FC). METHODS: Nineteen schizophrenia patients with antipsychotic-resistant AHs were randomized to either active (n = 10) or sham (n = 9) LF-rTMS administered over the left temporo-parietal region for ten days. The clinical effect was assessed by the Auditory Hallucination Rating Scale (AHRS). The localization of the differences in electrical activity was identified by standardized low resolution brain electromagnetic tomography (sLORETA) and FC was measured by lagged phase synchronization. RESULTS: AHRS scores were significantly improved for patients receiving active rTMS compared to the sham (median reduction: 40 % vs 12 %; p = 0.01). sLORETA revealed a decrease of alpha-2, beta-1,-2 bands in the left hemisphere in the active group. Active rTMS led to a decrease of the lagged phase connectivity in beta bands originating in areas close to the site of stimulation, and to a prevailing increase of alpha-2 FC. No significant differences in current density or FC were observed in the sham group. LIMITATIONS: Limitations to our study included the small group sizes, and the disability of LORETA to assess subcortical neuronal activity. CONCLUSIONS: LF-rTMS attenuated AHs and induced a decrease of higher frequency bands on the left hemisphere. The FC changes support the assumption that LF-rTMS is linked to the modulation of cortico-cortical coupling.

Glutamatergic abnormalities in the pregenual anterior cingulate cortex in obsessive-compulsive disorder using magnetic resonance spectroscopy: A controlled study.

In this study, we utilized proton magnetic resonance spectroscopy (MRS) to understand the role of glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) of OCD patients in the pregenual anterior cingulate cortex (pgACC). In total, 54 patients with OCD and 54 healthy controls (HC) matched for age and sex were included in the study. They underwent MRS in the pgACC region to calculate the concentrations of Glu, Gln, GABA, and Glu + Gln (Glx). After quality control of the MRS data, 21 OCD and 21 HC were statistically analyzed. The severity of symptoms were evaluated using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the statistical analysis, we compared differences between groups for the metabolites; in the OCD we analyzed the correlations with symptom severity, medication status, age, and duration of illness. A significant decrease in Glx, in Glu, and in Gln in the pgACC were observed in the OCD compared to HC. The correlation statistics showed a significant positive correlation between Glu levels and the YBOCS compulsions subscale. The results indicate that patients with OCD present a disturbance in glutamatergic metabolism in the pgACC. The results also demonstrate that these changes correlate with the severity of compulsions.

Psilocybin intoxication did not affect daytime or sleep-related declarative memory consolidation in a small sample exploratory analysis.

Psilocybin is investigated as a fast-acting antidepressant used in conjunction with psychotherapy. Intact cognitive functions, including memory, are one of the basic conditions of effective psychedelic-assisted therapy. While cognitive and memory processing is attenuated on various domains during psilocybin intoxication, the effect of psilocybin on the consolidation of memories learned outside of acute intoxication is not known. Thus the main aim of the current study was to test the effects of psilocybin on (A) memory consolidation of previously learned material just after the psilocybin session and (B) on overnight memory consolidation the night just after the psilocybin session. 20 healthy volunteers (10 M/10F) were enrolled in a placebo-controlled, double-blind, cross-over design. Effects on declarative memory consolidation in condition (A) The Groton Maze Learning Task and Rey Auditory Verbal Learning Test were used, and for (B) the Pair Associative Learning Test was used. We did not find psilocybin to improve memory consolidation. At the same time, we did not find psilocybin to negatively affect memory consolidation in any of the tests used. This evidence adds to the safety profile for the use of psilocybin.

Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats.

Introduction: Psilocybin is one of the most extensively studied psychedelic drugs with a broad therapeutic potential. Despite the fact that its psychoactivity is mainly attributed to the agonism at 5-HT2A receptors, it has high binding affinity also to 5-HT2C and 5-HT1A receptors and indirectly modulates the dopaminergic system. Psilocybin and its active metabolite psilocin, as well as other serotonergic psychedelics, induce broadband desynchronization and disconnection in EEG in humans as well as in animals. The contribution of serotonergic and dopaminergic mechanisms underlying these changes is not clear. The present study thus aims to elucidate the pharmacological mechanisms underlying psilocin-induced broadband desynchronization and disconnection in an animal model. Methods: Selective antagonists of serotonin receptors (5-HT1A WAY100635, 5-HT2A MDL100907, 5-HT2C SB242084) and antipsychotics haloperidol, a D2 antagonist, and clozapine, a mixed D2 and 5-HT receptor antagonist, were used in order to clarify the underlying pharmacology. Results: Psilocin-induced broadband decrease in the mean absolute EEG power was normalized by all antagonists and antipsychotics used within the frequency range 1-25 Hz; however, decreases in 25-40 Hz were influenced only by clozapine. Psilocin-induced decrease in global functional connectivity and, specifically, fronto-temporal disconnection were reversed by the 5-HT2A antagonist while other drugs had no effect. Discussion: These findings suggest the involvement of all three serotonergic receptors studied as well as the role of dopaminergic mechanisms in power spectra/current density with only the 5-HT2A receptor being effective in both studied metrics. This opens an important discussion on the role of other than 5-HT2A-dependent mechanisms underlying the neurobiology of psychedelics.

Frames of reference and their neural correlates within navigation in a 3D environment.

The goal of this study was an administration of the navigation task in a three-dimensional virtual environment to localize the electroencephalogram (EEG) features responsible for egocentric and allocentric reference frame processing in a horizontal and also in a vertical plane. We recorded the EEG signal of a traverse through a virtual tunnel to search for the best signal features that discriminate between specific strategies in particular plane. We identified intrahemispheric coherences in occipital-parietal and temporal-parietal areas as the most discriminative features. They have 10% lower error rate compared to single electrode features adopted in previous studies. The behavioral analysis revealed that 11% of participants switched from egocentric to allocentric strategy in a vertical plane, while 24% of participants consistently adopted egocentric strategy in both planes.

Guidelines for the recording and evaluation of pharmaco-EEG data in man: the International Pharmaco-EEG Society (IPEG).

The International Pharmaco-EEG Society (IPEG) presents updated guidelines summarising the requirements for the recording and computerised evaluation of pharmaco-EEG data in man. Since the publication of the first pharmaco-EEG guidelines in 1982, technical and data processing methods have advanced steadily, thus enhancing data quality and expanding the palette of tools available to investigate the action of drugs on the central nervous system (CNS), determine the pharmacokinetic and pharmacodynamic properties of novel therapeutics and evaluate the CNS penetration or toxicity of compounds. However, a review of the literature reveals inconsistent operating procedures from one study to another. While this fact does not invalidate results per se, the lack of standardisation constitutes a regrettable shortcoming, especially in the context of drug development programmes. Moreover, this shortcoming hampers reliable comparisons between outcomes of studies from different laboratories and hence also prevents pooling of data which is a requirement for sufficiently powering the validation of novel analytical algorithms and EEG-based biomarkers. The present updated guidelines reflect the consensus of a global panel of EEG experts and are intended to assist investigators using pharmaco-EEG in clinical research, by providing clear and concise recommendations and thereby enabling standardisation of methodology and facilitating comparability of data across laboratories.

Psychosocial Impact of Huntington's Disease and Incentives to Improve Care for Affected Families in the Underserved Region of the Slovak Republic.

INTRODUCTION: Huntington's disease (HD) is often on the margin of standard medical practice due to its low prevalence, the lack of causal treatment, and the typically long premanifest window prior to the onset of the symptoms, which contrasts with the long-lasting burden that the disease causes in affected families. METHODS: To capture these socio-psychological aspects of HD and map the experiences of affected individuals, persons at risk of HD, and caregivers, we created a questionnaire using a qualitative research approach. The questionnaire containing 16 questions was conducted online for a period of three months through patient associations in Slovakia and their infrastructures. RESULTS: In total, we received 30 responses. The survey results, in particular, indicate insufficient counselling by physicians with explicitly missing information about the possibility of preimplantation genetic diagnostic. There was also a necessity to improve comprehensive social and health care in the later stages of the disease, raise awareness of the disease in the general health community, and provide more information on ongoing clinical trials. CONCLUSION: The psychosocial effects, as well as the burden, can be mitigated by comprehensive genetic counselling as well as reproductive and financial guidelines and subsequent therapeutic programs to actively support patients, caregivers, children, and adolescents growing up in affected families, preferably with the help of local HD community association. LIMITATIONS: We have used online data collection to reach a wider HD community, but at the same time, we are aware that the quality of the data we would obtain through face-to-face interviews would be considerably better. Therefore, future studies need to be conducted to obtain more detailed information.