Serotonergic agonist psilocybin is a psychedelic with antidepressant potential. Sleep may interact with psilocybin's antidepressant properties like other antidepressant drugs via induction of neuroplasticity. The main aim of the study was to evaluate the effect of psilocybin on sleep architecture on the night after psilocybin administration. Regarding the potential antidepressant properties, we hypothesized that psilocybin, similar to other classical antidepressants, would reduce rapid eye movement (REM) sleep and prolong REM sleep latency. Moreover, we also hypothesized that psilocybin would promote slow-wave activity (SWA) expression in the first sleep cycle, a marker of sleep-related neuroplasticity. Twenty healthy volunteers (10 women, age 28-53) underwent two drug administration sessions, psilocybin or placebo, in a randomized, double-blinded design. Changes in sleep macrostructure, SWA during the first sleep cycle, whole night EEG spectral power across frequencies in non-rapid eye movement (NREM) and REM sleep, and changes in subjective sleep measures were analyzed. The results revealed prolonged REM sleep latency after psilocybin administration and a trend toward a decrease in overall REM sleep duration. No changes in NREM sleep were observed. Psilocybin did not affect EEG power spectra in NREM or REM sleep when examined across the whole night. However, psilocybin suppressed SWA in the first sleep cycle. No evidence was found for sleep-related neuroplasticity, however, a different dosage, timing, effect on homeostatic regulation of sleep, or other mechanisms related to antidepressant effects may play a role. Overall, this study suggests that potential antidepressant properties of psilocybin might be related to changes in sleep.
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Explainable artificial intelligence holds a great promise for neuroscience and plays an important role in the hypothesis generation process. We follow-up a recent machine learning-oriented study that constructed a deep convolutional neural network to automatically identify biological sex from EEG recordings in healthy individuals and highlighted the discriminative role of beta-band power. If generalizing, this finding would be relevant not only theoretically by pointing to some specific neurobiological sexual dimorphisms, but potentially also as a relevant confound in quantitative EEG diagnostic practice. To put this finding to test, we assess whether the automatic identification of biological sex generalizes to another dataset, particularly in the presence of a psychiatric disease, by testing the hypothesis of higher beta power in women compared to men on 134 patients suffering from Major Depressive Disorder. Moreover, we construct ROC curves and compare the performance of the classifiers in determining sex both before and after the antidepressant treatment. We replicate the observation of a significant difference in beta-band power between men and women, providing classification accuracy of nearly 77%. The difference was consistent across the majority of electrodes, however multivariate classification models did not generally improve the performance. Similar results were observed also after the antidepressant treatment (classification accuracy above 70%), further supporting the robustness of the initial finding.
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Introduction: Deficits in neurocognitive mechanisms such as inhibition control and cognitive flexibility have been suggested to mediate the symptoms in obsessive-compulsive disorder (OCD). These mechanisms are proposedly controlled by the "affective" and "executive" orbitofronto-striato-thalamo-cortical (CSTC) circuits with well-documented morphological and functional alterations in OCD that are associated with OCD symptoms. The precuneus region has been suggested in OCD as another key structure associated with the mechanism of "thought-action fusion." Our study aimed to elucidate the association of the altered functional coupling of the CSTC nodes (and precuneus), the OCD symptoms, and interference control/cognitive flexibility. Methods: In a group of 36 (17 medicated and 19 drug-free) OCD patients and matched healthy volunteers, we tested functional connectivity (FC) within the constituents of the dorsolateral prefrontal cortex "executive" CSTC, the orbitofrontal cortex/anterior cingulate "affective" CSTC, and precuneus. The functional connections showing the strongest effects were subsequently entered as explanatory variables to multiple regression analyses to identify possible associations between observed alterations of functional coupling and cognitive (Stroop test) and clinical measures (obsessions, compulsions, and anxiety level). Results: We observed increased FC (FWE p < 0.05 corr.) between CSTC seeds and regions of the parieto-occipital cortex, and between the precuneus and the angular gyrus and dorsolateral prefrontal cortex. Decreased FC was observed within the CSTC loop (caudate nucleus and thalamus) and between the anterior cingulate cortex and the limbic lobe. Linear regression identified a relationship between the altered functional coupling of thalamus with the right somatomotor parietal cortex and the Stroop color-word score. Similar association of thalamus FC has been identified also for obsessions severity. No association was observed for compulsions and anxiety. Conclusions: Our findings demonstrate altered FC in OCD patients with a prevailing increase in FC originating in CSTC regions toward other cortical areas, and a decrease in FC within the constituents of CSTC loops. Moreover, our results support the role of precuneus in OCD. The association of the cognitive and clinical symptoms with the FC between the thalamus and somatomotor cortex indicates that cognitive flexibility and inhibitory control are strongly linked and both mechanisms might contribute to the symptomatology of OCD.
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Depression is a mental health condition for which individuals commonly seek treatment. However, depressive episodes often resolve on their own, even without treatment. One evolutionary perspective, the analytical rumination hypothesis (ARH), suggests that depression occurs in response to complex problems. According to this perspective, depressive symptoms promote analytical rumination, i.e., distraction-resistant thoughts about the causes of problems [causal analysis (CA)] and how they can be solved [problem-solving analysis (PSA)]. By helping individuals solve complex problems, analytical rumination may contribute to remission from depression. The aim of this study was to investigate (1) whether clinically-depressed individuals have more complex problems and engage in more CA and PSA than non-depressed and (2) the effects of CA and PSA on decreases in problem complexity, depressive symptoms, and remission from the depression. Samples of 85 patients were treated for depression with antidepressants and psychotherapy, and 49 healthy subjects were assessed three times over a 4-month period (at Weeks 1, 5, and 16). At each assessment, they completed measures of depression, analytical rumination, and problem complexity. Depressed individuals reported having more complex problems and engaging in more CA than non-depressed participants. The two groups engaged in a similar degree of PSA. Findings from a multiple regression suggested that more PSA at Week 1 was related to a decrease in depressive symptoms at Week 5, even after controlling for baseline depression, problem number, and complexity. PSA at Week 1 did not predict the remission after hospitalization or at follow-up; however, having less complex problems at the baseline made it more likely that a patient would later remit. Engaging in more CA or PSA at Week 1 did not affect perceived problem complexity at Week 5 or at follow-up. However, these findings were not statistically significant when influential observations (or outliers) were included in the analysis. Our findings suggest that PSA may contribute to a decrease in symptoms of depression over time. However, alleviations in problem complexity and remission might only be achieved if problems are initially less complex. Future directions involve exploring how PSA might contribute to decreases in depressive symptoms and other mechanisms underlying remission from depression.
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Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depressive disorder, with outcomes approaching 45-55% response and 30-40% remission. Eligible predictors of treatment outcome, however, are still lacking. Few studies have investigated quantitative electroencephalography (QEEG) parameters as predictors of rTMS treatment outcome and none of them have addressed the source localization techniques to predict the response to low-frequency rTMS (LF rTMS). We investigated electrophysiological differences based on scalp EEG data and inverse solution method, exact low-resolution brain electromagnetic tomography (eLORETA), between responders and non-responders to LF rTMS in resting brain activity recorded prior to the treatment. Twenty-five unmedicated depressive patients (mean age of 45.7 years, 20 females) received a 4-week treatment of LF rTMS (1 Hz; 20 sessions per 600 pulses; 100% of the motor threshold) over the right dorsolateral prefrontal cortex. Comparisons between responders (≥50% reduction in Montgomery-Åsberg Depression Rating Scale score) and non-responders were made at baseline for measures of eLORETA current density, spectral absolute power, and inter-hemispheric and intra-hemispheric EEG asymmetry. Responders were found to have lower current source densities in the alpha-2 and beta-1 frequency bands bilaterally (with predominance on the left side) in the inferior, medial, and middle frontal gyrus, precentral gyrus, cingulate gyrus, anterior cingulate, and insula. The most pronounced difference was found in the left middle frontal gyrus for alpha-2 and beta-1 bands (p < 0.05). Using a spectral absolute power analysis, we found a negative correlation between the absolute power in beta and theta frequency bands on the left frontal electrode F7 and the change in depressive symptomatology. None of the selected asymmetries significantly differentiated responders from non-responders in any frequency band. Pre-treatment reduction of alpha-2 and beta-1 sources, but not QEEG asymmetry, was found in patients with major depressive disorder who responded to LF rTMS treatment. Prospective trials with larger groups of subjects are needed to further validate these findings.
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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.
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Memory decline associated with physiological aging and age-related neurological disorders has a direct impact on quality of life for seniors. With demographic aging, the assessment of cognitive functions is gaining importance, as early diagnosis can lead to more effective cognitive interventions. In comparison to classic paper-and-pencil approaches, virtual reality (VR) could offer an ecologically valid environment for assessment and remediation of cognitive deficits. Despite the rapid development and application of new technologies, the results of studies aimed at the role of VR immersion in assessing cognitive performance and the use of VR in aging populations are often ambiguous. VR can be presented in a less immersive form, with a desktop platform, or with more advanced technologies like head-mounted displays (HMDs). Both these VR platforms are associated with certain advantages and disadvantages. In this study, we investigated age-related differences related to the use of desktop and HMD platforms during memory assessment using an intra-subject design. Groups of seniors (N = 36) and young adults (N = 25) completed a virtual Supermarket Shopping task using desktop and HMD platforms in a counterbalanced order. Our results show that the senior performances were superior when using the non-immersive desktop platform. The ability to recall a shopping list in the young adult group remained stable regardless of the platform used. With the HMD platform, the performance of the subjects of both groups seemed to be more influenced by fatigue. The evaluated user experiences did not differ between the two platforms, and only minimal and rare side effects were reported by seniors. This implies that highly immersive technology has good acceptance among aging adults. These findings might have implications for the further use of HMD in cognitive assessment and remediation.
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Studies of consciousness have traditionally been based mainly upon the perceptual domains of consciousness. However, there is another side of consciousness, represented by various types of intrinsic conscious experiences. Even though intrinsic experiences can represent up to 50% of our conscious experiences, they are still largely neglected in conscious studies. We assume there are two reasons for this. First, the field of intrinsic conscious experiences is methodologically far more problematic than any other. Second, specific paradigms for capturing the correlates of intrinsic conscious experiences are almost nonexistent. Nevertheless, we expect the intrinsic side of consciousness to soon take its place in conscious studies, but first new experimental paradigms will have to be devised, which would be of a similar design to the paradigms used in studies of perceptual consciousness. In this hypothesis and theory article, we propose such a hypothetical paradigm, presenting the exploratory data of our proof-of-concept study, discussing its use, and addressing its shortcomings and their possible remediation.
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The elusive relationship between the mental domain and the physical brain, known as the mind-body problem, is still a hot topic of discussion among philosophers and neuroscientists. Rather than solving this problem, our pilot study addresses the question as to whether personality features could influence intuitions of the mind-body problem, or more precisely, whether it is possible to identify a person's intuitive inclinations toward dualism or materialism and their inclinations toward reduction of the mind to the brain. For the purposes of this pilot study, we developed a questionnaire, which employed several theories of analytic philosophy of the mind, in order to determine which category the participants would belong to. These main categories were dualism, non-reductive materialism and reductive materialism. To test whether personality features affect preferences for these categories, the participants were investigated by Cloninger's Temperament and Character Inventory (TCI). We found significant differences in the self-transcendence dimension of the TCI between participants who were evaluated as dualists and those who were assessed as reductive materialists. Our data show that the personality dimension of self-transcendence correlates with intuitive inclination toward reductive materialism or dualism. In addition, our results suggest that ideas, theories, and hypothetical solutions of the mind-body problem and possibly even conclusions, acceptance, and disputations of thought experiments of philosophy of the mind can be biased by personality traits. This fact should be taken into account in future discussions of the philosophy of the mind and may also be important for empirical research and an empirical understanding of the mind.
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In this review, we deal with two central questions of consciousness how and why, and we outline their possible future development. The question how refers to the empirical endeavor to reveal the neural correlates and mechanisms that form consciousness. On the other hand, the question why generally refers to the "hard problem" of consciousness, which claims that empirical science will always fail to provide a satisfactory answer to the question why is there conscious experience at all. Unfortunately, the hard problem of consciousness will probably never completely disappear because it will always have its most committed supporters. However, there is a good chance that its weight and importance will be highly reduced by empirically tackling consciousness in the near future. We expect that future empirical endeavor of consciousness will be based on a unifying brain theory and will answer the question as to what is the function of conscious experience, which will in turn replace the implications of the hard problem. The candidate of such a unifying brain theory is predictive coding, which will have to explain both perceptual consciousness and conscious mind-wandering in order to become the truly unifying theory of brain functioning.
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