Catatonia.

Catatonia is a neuropsychiatric disorder characterized by motor, affective and cognitive-behavioural signs, which lasts from hours to days. Intensive research over the past two decades has led to catatonia being recognized as an independent diagnosis in the International Classification of Diseases, 11th Revision (ICD-11) since 2022. Catatonia is found in 5-18% of inpatients on psychiatric units and 3.3% of inpatients on medical units. However, in an unknown number of patients, catatonia remains unrecognized and these patients are at risk of life-threatening complications. Hence, recognizing the symptoms of catatonia early is crucial to initiate appropriate treatment to achieve a favourable outcome. Benzodiazepines such as lorazepam and diazepam, electroconvulsive therapy, and N-methyl-D-aspartate antagonists such as amantadine and memantine, are the cornerstones of catatonia therapy. In addition, dopamine-modulating second-generation antipsychotics (for example, clozapine and aripiprazole) are effective in some patient populations. Early and appropriate treatment combined with new screening assessments has the potential to reduce the high morbidity and mortality associated with catatonia in psychiatric and non-psychiatric settings.

Is depression a global brain disorder with topographic dynamic reorganization?

Major depressive disorder (MDD) is characterized by a multitude of psychopathological symptoms including affective, cognitive, perceptual, sensorimotor, and social. The neuronal mechanisms underlying such co-occurrence of psychopathological symptoms remain yet unclear. Rather than linking and localizing single psychopathological symptoms to specific regions or networks, this perspective proposes a more global and dynamic topographic approach. We first review recent findings on global brain activity changes during both rest and task states in MDD showing topographic reorganization with a shift from unimodal to transmodal regions. Next, we single out two candidate mechanisms that may underlie and mediate such abnormal uni-/transmodal topography, namely dynamic shifts from shorter to longer timescales and abnormalities in the excitation-inhibition balance. Finally, we show how such topographic shift from unimodal to transmodal regions relates to the various psychopathological symptoms in MDD including their co-occurrence. This amounts to what we describe as 'Topographic dynamic reorganization' which extends our earlier 'Resting state hypothesis of depression' and complements other models of MDD.

Altered cardiac autonomic functioning associates with self-disorders in schizophrenia.

Elevated resting heart rate (RHR) and reduced heart rate variability (HRV) are signs of autonomic nervous system dysfunction identified in schizophrenia (SCZ). This dysfunction has been found to manifest prior to the onset of the clinical diagnosis. Yet whether such autonomic dysfunction is associated with vulnerability to schizophrenia remains unknown. This case-control study included recent onset SCZ patients (n = 35) and healthy controls (HC) (n = 33). Patients were scored for self-disorders (SD's) using the EASE manual and all participants underwent a 5-minute resting state electrocardiogram (ECG) recording. Patients were included from outpatient clinics in Denmark. The main measures comprised EASE total scores (SDs), RHR (beats per minute) and three standard HRV measures usually included in testing autonomic nervous system dysfunction: root mean squared of successive differences (RMSSD), standard deviation of normal-to-normal interval (SDNN) and high-frequency/ low frequency ratio (HF/LF). Pearson correlations and linear regression models adjusted for age, sex and medication were used in the SCZ group. The main finding was a positive moderate association between SDs and RHR (r = 0.463; p = 0.005) and a negative association between SDs and HRV (RMSSD) (r = -0.440; p = 0.008) in the SCZ group. Linear regression models found SDs to explain 22 % of the variance of RHR and 19 % in RMSSD. SDs correlated with LF/HF (r = 0.434; p = 0.009), but non-significantly with SDNN. The study provides evidence of an intriguing link between SDs as a susceptibility trait for schizophrenia spectrum disorders and altered cardiac autonomic functioning.

Arthur Schopenhauer: An underappreciated philosopher in psychiatry and his applied epistemology of body and self- experience.

BACKGROUND: Arthur Schopenhauer (1788-1860) was one of the most important thinkers of the 19th century. Although his writings have exerted great influence in many different disciplines, his epistemological concepts and analysis of the body and self-experience were rarely considered in the context of psychiatric research of schizophrenia spectrum disorders (SSD) and depression (MDD). METHODS: The method applied for the study of anomalous self and body-experience first consists in the close reading and analysis of Schopenhauer's most influential writings, namely his opus magnus "The World as Will and Representation" and his dissertation "On the Fourfold Root of the Principle of Sufficient Reason". Second, psychopathological and phenomenological aspects of the anomalous body and self, as well as altered space and time experience, are discussed by means of Schopenhauer's philosophy and four patient cases. RESULTS: Schopenhauer's insights contribute to contemporary psychiatry by (1) unifying materialistic (neurobiological) and idealistic (subjective) conceptions of psychiatric disorders and improving the awareness of methods in psychiatric research; (2) emphasizing the integral significance of the body as a gateway to the surrounding world and basal self-experience; (3) delineating subjective space and time-experience as crucial dimensions of the conditio humana in SSD and MDD; and (4) demonstrating the feasibility of transferring his theories directly to clinical case vignettes stemming from the daily clinical routine. CONCLUSION: Close reading of Schopenhauer's texts might help bridge the gap between different scientific methods in psychiatry and overcome the translational crisis of contemporary psychiatry by unifying neurobiological and subjective approaches to SSD and MDD.

Scale for time and space experience in anxiety (STEA): Phenomenology and its clinical relevance.

Anxiety is a pervasive emotional state where, phenomenologically, subjects often report changes in their experience of time and space. However, a systematic and quantified examination of time and space experience in terms of a self-report scale is still missing which eventually could also be used for clinical differential diagnosis. Based on historical phenomenological literature and patients' subjective reports, we here introduce, in a first step, the Scale for Time and Space Experience of Anxiety (STEA) in a smaller sample of 19 subjects with anxiety disorders and, in a second step, validate its shorter clinical version (cSTEA) in a larger sample of 48 anxiety subjects. The main findings are (i) high convergent and divergent validity of STEA with both Beck Anxiety Inventory (BAI) (r = 0.7325; p < 0.001) and Beck Depression Inventory (BDI) (r = 0.7749; p < 0.0001), as well as with spontaneous mind wandering (MWS) (r = 0.7343; p < 0.001) and deliberate mind wandering (MWD) (r = 0.1152; p > 0.05), (ii) statistical feature selection shows 8 key items for future clinical usage (cSTEA) focusing on the experience of temporal and spatial constriction, (iii) the effects of time and space experience (i.e., for both STEA and cSTEA scores) on the level of anxiety (BAI) are mediated by the degree of spontaneous mind wandering (MWS), (iv) cSTEA allows for differentiating high levels of anxiety from the severity of comorbid depressive symptoms, and (v) significant reduction in the cSTEA scores after a therapeutic intervention (breathing therapy). Together, our study introduces a novel fully quantified and highly valid self-report instrument, the STEA, for measuring time-space experiences in anxiety. Further we develop a shorter clinical version (cSTEA) which allows assessing time space experience in a valid, quick, and simple way for diagnosis, differential diagnosis, and therapeutic monitoring of anxiety.

Abnormal resting-state EEG phase dynamics distinguishes major depressive disorder and bipolar disorder.

Changes in EEG have been reported in both major depressive disorder (MDD) and bipolar disorder (BD). Specifically, power changes in EEG alpha and theta frequency bands during rest and task are known in both disorders. This leaves open whether there are changes in yet another component of the electrophysiological EEG signal, namely phase-related processes that may allow for distinguishing MDD and BD. For that purpose, we investigate EEG-based spontaneous phase in the resting state of MDD, BD and healthy controls. Our main findings show: (i) decreased spontaneous phase variability in frontal theta of both MDD and BD compared to HC; (ii) decreased spontaneous phase variability in central-parietal alpha in MDD compared to both BD and HC; (iii) increased delays or lags of alpha phase cycles in MDD (but not in BD), which (iv) correlate with the decreased phase variability in MDD. Together, we show similar (decreased frontal theta variability) and distinct (decreased central-parietal alpha variability with increased lags or delays) findings in the spontaneous phase dynamics of MDD and BD. This suggests potential relevance of theta and alpha phase dynamics in distinguishing MDD and BD in clinical differential-diagnosis.

Global neural self-disturbance in schizophrenia: A systematic fMRI review.

There is a general consensus that schizophrenia (SZ) is characterized by major changes in the sense of self. Phenomenological studies suggest that these changes in the sense of self stem from a basic disturbance, hence the term 'basic self-disturbance'. While imaging studies demonstrate changes in various regions during self-focused tasks, the exact neural correlates of such basic self-disturbances remain unclear. If the self-disturbance is indeed basic and thereby underlies all other symptoms, one would expect it to be related to more global rather than local changes in the brain. Testing this hypothesis, we conducted a systematic review of fMRI studies on self in SZ. Our main findings are 1. Abnormal activity related to the self can be observed in a variety of different regions ranging from higher-order transmodal to lower-order unimodal regions, 2. These findings hold true across different tasks including self-reflection, self-referentiality, and self-agency, and 3. The global neural abnormalities related to the self in SZ correspond to all layers of the self, predominantly the mental and exteroceptive self. Such global neural disturbance of self converges well with the basic self-disturbance as described in phenomenology.

Repertoire of timescales in uni - and transmodal regions mediate working memory capacity.

Working memory (WM) describes the dynamic process of maintenance and manipulation of information over a certain time delay. Neuronally, WM recruits a distributed network of cortical regions like the visual and dorsolateral prefrontal cortex as well as the subcortical hippocampus. How the input dynamics and subsequent neural dynamics impact WM remains unclear though. To answer this question, we combined the analysis of behavioral WM capacity with measuring neural dynamics through task-related power spectrum changes, e.g., median frequency (MF) in functional magnetic resonance imaging (fMRI). We show that the processing of the input dynamics, e.g., the task structure's specific timescale, leads to changes in the unimodal visual cortex's corresponding timescale which also relates to working memory capacity. While the more transmodal hippocampus relates to working memory capacity through its balance across multiple timescales or frequencies. In conclusion, we here show the relevance of both input dynamics and different neural timescales for WM capacity in uni - and transmodal regions like visual cortex and hippocampus for the subject's WM performance.

A measure centrality index for systematic empirical comparison of consciousness theories.

Consciousness science is marred by disparate constructs and methodologies, making it challenging to systematically compare theories. This foundational crisis casts doubts on the scientific character of the field itself. Addressing it, we propose a framework for systematically comparing consciousness theories by introducing a novel inter-theory classification interface, the Measure Centrality Index (MCI). Recognizing its gradient distribution, the MCI assesses the degree of importance a specific empirical measure has for a given consciousness theory. We apply the MCI to probe how the empirical measures of the Global Neuronal Workspace Theory (GNW), Integrated Information Theory (IIT), and Temporospatial Theory of Consciousness (TTC) would fare within the context of the other two. We demonstrate that direct comparison of IIT, GNW, and TTC is meaningful and valid for some measures like Lempel-Ziv Complexity (LZC), Autocorrelation Window (ACW), and possibly Mutual Information (MI). In contrast, it is problematic for others like the anatomical and physiological neural correlates of consciousness (NCC) due to their MCI-based differential weightings within the structure of the theories. In sum, we introduce and provide proof-of-principle of a novel systematic method for direct inter-theory empirical comparisons, thereby addressing isolated evolution of theories and confirmatory bias issues in the state-of-the-art neuroscience of consciousness.

Parkinsonism, Psychomotor Slowing, Negative and Depressive Symptoms in Schizophrenia Spectrum and Mood Disorders: Exploring Their Intricate Nexus Using a Network Analytic Approach.

BACKGROUND AND HYPOTHESIS: Parkinsonism, psychomotor slowing, negative and depressive symptoms show evident phenomenological similarities across different mental disorders. However, the extent to which they interact with each other is currently unclear. Here, we hypothesized that parkinsonism is an independent motor abnormality showing limited associations with psychomotor slowing, negative and depressive symptoms in schizophrenia spectrum (SSD), and mood disorders (MOD). STUDY DESIGN: We applied network analysis and community detection methods to examine the interplay and centrality (expected influence [EI] and strength) between parkinsonism, psychomotor slowing, negative and depressive symptoms in 245 SSD and 99 MOD patients. Parkinsonism was assessed with the Simpson-Angus Scale (SAS). We used the Positive and Negative Syndrome Scale (PANSS) to examine psychomotor slowing (item #G7), negative symptoms (PANSS-N), and depressive symptoms (item #G6). STUDY RESULTS: In SSD and MOD, PANSS item #G7 and PANSS-N showed the largest EI and strength as measures of centrality. Parkinsonism had small or no influence on psychomotor slowing, negative and depressive symptoms in SSD and MOD. In SSD and MOD, exploratory graph analysis identified one community, but parkinsonism showed a small influence on its occurrence. Network Comparison Test yielded no significant differences between the SSD and MOD networks (global strength p value: .396 and omnibus tests p value: .574). CONCLUSIONS: The relationships between the individual domains followed a similar pattern in both SSD and MOD highlighting their transdiagnostic relevance. Despite evident phenomenological similarities, our results suggested that parkinsonism is more independent of negative and depressive symptoms than psychomotor slowing in both SSD and MOD.

Where do the symptoms come from in depression? Topography and dynamics matter.

This scientific commentary refers to 'Brain dynamics predictive of response to psilocybin for treatment-resistant depression', by Vohryzek et al. (https://doi.org/10.1093/braincomms/fcae049).

The nested hierarchical model of self and its non-relational vs relational posttraumatic manifestation: an fMRI meta-analysis of emotional processing.

Different kinds of traumatic experiences like natural catastrophes vs. relational traumatic experiences (e.g., sex/physical abuse, interpersonal partner violence) are involved in the development of the self and PTSD psychopathological manifestations. Looking at a neuroscience approach, it has been proposed a nested hierarchical model of self, which identifies three neural-mental networks: (i) interoceptive; (ii) exteroceptive; (iii) mental. However, it is still unclear how the self and its related brain networks might be affected by non-relational vs relational traumatic experiences. Departing from this background, the current study aims at conducting a meta-analytic review of task-dependent fMRI studies (i.e., emotional processing task) among patients with PTSD due to non-relational (PTSD-NR) and relational (PTSD-R) traumatic experiences using two approaches: (i) a Bayesian network meta-analysis for a region-of-interest-based approach; (ii) a coordinated-based meta-analysis. Our findings suggested that the PTSD-NR mainly recruited areas ascribed to the mental self to process emotional stimuli. Whereas, the PTSD-R mainly activated regions associated with the intero-exteroceptive self. Accordingly, the PTSD-R compared to the PTSD-NR might not reach a higher symbolic capacity to process stimuli with an emotional valence. These results are also clinically relevant in support of the development of differential treatment approaches for non-relational vs. relational PTSD.

Deciphering the interplay between psychopathological symptoms, sensorimotor, cognitive and global functioning: a transdiagnostic network analysis.

BACKGROUND: Understanding the relationship between psychopathology and major domains of human neurobehavioral functioning may identify new transdiagnostic treatment targets. However, studies examining the interrelationship between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample are lacking. We hypothesized a close relationship between sensorimotor and cognitive functioning in a transdiagnostic patient sample. METHODS: We applied network analysis and community detection methods to examine the interplay and centrality [expected influence (EI) and strength] between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample consisting of 174 schizophrenia spectrum (SSD) and 38 mood disorder (MOD) patients. All patients (n = 212) were examined with the Positive and Negative Syndrome Scale (PANSS), the Heidelberg Neurological Soft Signs Scale (NSS), the Global Assessment of Functioning (GAF), and the Brief Cognitive Assessment Tool for Schizophrenia consisted of trail making test B (TMT-B), category fluency (CF) and digit symbol substitution test (DSST). RESULTS: NSS showed closer connections with TMT-B, CF, and DSST than with GAF and PANSS. DSST, PANSS general, and NSS motor coordination scores showed the highest EI. Sensory integration, DSST, and CF showed the highest strength. CONCLUSIONS: The close connection between sensorimotor and cognitive impairment as well as the high centrality of sensorimotor symptoms suggests that both domains share aspects of SSD and MOD pathophysiology. But, because the majority of the study population was diagnosed with SSD, the question as to whether sensorimotor symptoms are really a transdiagnostic therapeutic target needs to be examined in future studies including more balanced diagnostic groups.

Beyond task response-Pre-stimulus activity modulates contents of consciousness.

The current discussion on the neural correlates of the contents of consciousness (NCCc) focuses mainly on the post-stimulus period of task-related activity. This neglects the substantial impact of the spontaneous or ongoing activity of the brain as manifest in pre-stimulus activity. Does the interaction of pre- and post-stimulus activity shape the contents of consciousness? Addressing this gap in our knowledge, we review and converge two recent lines of findings, that is, pre-stimulus alpha power and pre- and post-stimulus alpha trial-to-trial variability (TTV). The data show that pre-stimulus alpha power modulates post-stimulus activity including specifically the subjective features of conscious contents like confidence and vividness. At the same time, alpha pre-stimulus variability shapes post-stimulus TTV reduction including the associated contents of consciousness. We propose that non-additive rather than merely additive interaction of the internal pre-stimulus activity with the external stimulus in the alpha band is key for contents to become conscious. This is mediated by mechanisms on different levels including neurophysiological, neurocomputational, neurodynamic, neuropsychological and neurophenomenal levels. Overall, considering the interplay of pre-stimulus intrinsic and post-stimulus extrinsic activity across wider timescales, not just evoked responses in the post-stimulus period, is critical for identifying neural correlates of consciousness. This is well in line with both processing and especially the Temporo-spatial theory of consciousness (TTC).

Stationary stable cross-correlation pattern and task specific deviations in unresponsive wakefulness syndrome as well as clinically healthy subjects.

Brain dynamics is highly non-stationary, permanently subject to ever-changing external conditions and continuously monitoring and adjusting internal control mechanisms. Finding stationary structures in this system, as has been done recently, is therefore of great importance for understanding fundamental dynamic trade relationships. Here we analyse electroencephalographic recordings (EEG) of 13 subjects with unresponsive wakefulness syndrome (UWS) during rest and while being influenced by different acoustic stimuli. We compare the results with a control group under the same experimental conditions and with clinically healthy subjects during overnight sleep. The main objective of this study is to investigate whether a stationary correlation pattern is also present in the UWS group, and if so, to what extent this structure resembles the one found in healthy subjects. Furthermore, we extract transient dynamical features via specific deviations from the stationary interrelation pattern. We find that (i) the UWS group is more heterogeneous than the two groups of healthy subjects, (ii) also the EEGs of the UWS group contain a stationary cross-correlation pattern, although it is less pronounced and shows less similarity to that found for healthy subjects and (iii) deviations from the stationary pattern are notably larger for the UWS than for the two groups of healthy subjects. The results suggest that the nervous system of subjects with UWS receive external stimuli but show an overreaching reaction to them, which may disturb opportune information processing.

Temporal imprecision of phase coherence in schizophrenia and psychosis-dynamic mechanisms and diagnostic marker.

Schizophrenia (SCZ) is a complex disorder in which various pathophysiological models have been postulated. Brain imaging studies using EEG/MEG and fMRI show altered amplitude and, more recently, decrease in phase coherence in response to external stimuli. What are the dynamic mechanisms of such phase incoherence, and can it serve as a differential-diagnostic marker? Addressing this gap in our knowledge, we uniquely combine a review of previous findings, novel empirical data, and computational-dynamic simulation. The main findings are: (i) the review shows decreased phase coherence in SCZ across a variety of different tasks and frequencies, e.g., task- and frequency-unspecific, which is further supported by our own novel data; (ii) our own data demonstrate diagnostic specificity of decreased phase coherence for SCZ as distinguished from major depressive disorder; (iii) simulation data exhibit increased phase offset in SCZ leading to a precision index, in the millisecond range, of the phase coherence relative to the timing of the external stimulus. Together, we demonstrate the key role of temporal imprecision in phase coherence of SCZ, including its mechanisms (phase offsets, precision index) on the basis of which we propose a phase-based temporal imprecision model of psychosis (PTP). The PTP targets a deeper dynamic layer of a basic disturbance. This converges well with other models of psychosis like the basic self-disturbance and time-space experience changes, as discussed in phenomenological and spatiotemporal psychopathology, as well as with the models of aberrant predictive coding and disconnection as in computational psychiatry. Finally, our results show that temporal imprecision as manifest in decreased phase coherence is a promising candidate biomarker for clinical differential diagnosis of SCZ, and more broadly, psychosis.

Distribution and frequency of clinical criteria and rating scales for diagnosis and assessment of catatonia in different study types.

BACKGROUND: A comprehensive assessment of catatonic symptoms is decisive for diagnosis, neuronal correlates, and evaluation of treatment response and prognosis of catatonia. Studies conducted so far used different cut-off criteria and clinical rating scales to assess catatonia. Therefore, the main aim of this study was to examine the frequency and distribution of diagnostic criteria and clinical rating scales for assessing catatonia that were used in scientific studies so far. METHODS: We conducted a systematic review using PubMed searching for articles using catatonia rating scales/criteria published from January 1st 1952 (introduction of catatonic schizophrenia to first edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM]) up to December 5th, 2022. RESULTS: 1928 articles were considered for analysis. 1762 (91,39 %) studies used one and 166 (8,61 %) used ≥2 definitions of catatonia. However, 979 (50,7 %) articles did not report any systematic assessment of catatonia. As for clinical criteria, DSM criteria were used by the majority of studies (n = 290; 14.0 %), followed by International Classification of Diseases (ICD) criteria (n = 61; 2.9 %). The Bush-Francis Catatonia Rating Scale (BFCRS) was found to be by far the most frequently utilized scale (n = 464; 22.4 % in the respective years), followed by Northoff Catatonia Rating Scale (NCRS) (n = 31; 1.5 % in the respective years). CONCLUSION: DSM and ICD criteria as well as BFCRS and NCRS were most frequently utilized and can therefore be recommended as valid instruments for the assessment of catatonia symptomatology.