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.

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.

Culture shapes spontaneous brain dynamics - Shared versus idiosyncratic neural features among Chinese versus Canadian subjects.

Environmental factors, such as culture, are known to shape individual variation in brain activity including spontaneous activity, but less is known about their population-level effects. Eastern and Western cultures differ strongly in their cultural norms about relationships between individuals. For example, the collectivism, interdependence and tightness of Eastern cultures relative to the individualism, independence and looseness of Western cultures, promote interpersonal connectedness and coordination. Do such cultural contexts therefore influence the group-level variability of their cultural members' spontaneous brain activity? Using novel methods adapted from studies of inter-subject neural synchrony, we compare the group-level variability of resting state EEG dynamics in Chinese and Canadian samples. We observe that Chinese subjects show significantly higher inter-subject correlation and lower inter-subject distance in their EEG power spectra than Canadian subjects, as well as lower variability in theta power and alpha peak frequency. We demonstrate, for the first time, different relationships among subjects' resting state brain dynamics in Chinese and Canadian samples. These results point to more idiosyncratic neural dynamics among Canadian participants, compared with more shared neural features in Chinese participants.

Increased noise relates to abnormal excitation-inhibition balance in schizophrenia: a combined empirical and computational study.

Electroencephalography studies link sensory processing issues in schizophrenia to increased noise level-noise here is background spontaneous activity-as measured by the signal-to-noise ratio. The mechanism, however, of such increased noise is unknown. We investigate if this relates to changes in cortical excitation-inhibition balance, which has been observed to be atypical in schizophrenia, by combining electroencephalography and computational modeling. Our electroencephalography task results, for which the local field potentials can be used as a proxy, show lower signal-to-noise ratio due to higher noise in schizophrenia. Both electroencephalography rest and task states exhibit higher levels of excitation in the functional excitation-inhibition (as a proxy of excitation-inhibition balance). This suggests a relationship between increased noise and atypical excitation in schizophrenia, which was addressed by using computational modeling. A Leaky Integrate-and-Fire model was used to simulate the effects of varying degrees of noise on excitation-inhibition balance, local field potential, NMDA current, and . Results show a noise-related increase in the local field potential, excitation in excitation-inhibition balance, pyramidal NMDA current, and spike rate. Mutual information and mediation analysis were used to explore a cross-level relationship, showing that the cortical local field potential plays a key role in transferring the effect of noise to the cellular population level of NMDA.

Intrinsic neural timescales mediate the cognitive bias of self - temporal integration as key mechanism.

Our perceptions and decisions are not always objectively correct as they are featured by a bias related to our self. What are the behavioral, neural, and computational mechanisms of such cognitive bias? Addressing this yet unresolved question, we here investigate whether the cognitive bias is related to temporal integration and segregation as mediated by the brain's Intrinsic neural timescales (INT). Using Signal Detection Theory (SDT), we operationalize the cognitive bias by the Criterion C as distinguished from the sensitivity index d'. This was probed in a self-task based on morphed self- and other faces. Behavioral data demonstrate clear cognitive bias, i.e., Criterion C. That was related to the EEG-based INT as measured by the autocorrelation window (ACW) in especially the transmodal regions dorsolateral prefrontal cortex (dlPFC) and default-mode network (DMN) as distinct from unimodal visual cortex. Finally, simulation of the same paradigm in a large-scale network model shows high degrees of temporal integration of temporally distinct inputs in CMS/DMN and dlPFC while temporal segregation predominates in visual cortex. Together, we demonstrate a key role of INT-based temporal integration in CMS/DMN and dlPFC including its relation to the brain's uni-transmodal topographical organization in mediating the cognitive bias of our self.

Temporal continuity of self: Long autocorrelation windows mediate self-specificity.

The self is characterized by an intrinsic temporal component consisting in continuity across time. On the neural level, this temporal continuity manifests in the brain's intrinsic neural timescales (INT) that can be measured by the autocorrelation window (ACW). Recent EEG studies reveal a relationship between resting state ACW and self-consciousness. However, it remains unclear whether ACW exhibits different degrees of task-related changes during self-specific compared to non-self-specific activities. To this end, participants in our study initially recorded an eight-minute autobiographical narrative. Following a resting-state session, participants were presented with their own narrative and the narrative of a stranger while undergoing concurrent EEG recording. Behaviorally, subjects evaluated both of the narratives and indicated their perceptions of positivity or negativity on a moment-to-moment basis by positioning a cursor relative to the center of the computer screen. Our results indicate: (a) greater spatial extension and velocity in the behavioral cursor movement during the self narrative assessment compared to the non-self narrative assessment; and (b) longer neural ACWs in response to the self- compared to the non-self narrative and rest. These findings demonstrate the importance of longer temporal windows in neural activity measured by ACW for self-specificity. More broadly, the results highlight the relevance of temporal continuity for the self on the neural level. Such temporal continuity may, correspondingly, also manifest on the psychological level as a "common currency" between brain and self.

Variability and task-responsiveness of electrophysiological dynamics: Scale-free stability and oscillatory flexibility.

Cortical oscillations and scale-free neural activity are thought to influence a variety of cognitive functions, but their differential relationships to neural stability and flexibility has never been investigated. Based on the existing literature, we hypothesize that scale-free and oscillatory processes in the brain exhibit different trade-offs between stability and flexibility; specifically, cortical oscillations may reflect variable, task-responsive aspects of brain activity, while scale-free activity is proposed to reflect a more stable and task-unresponsive aspect. We test this hypothesis using data from two large-scale MEG studies (HCP: n = 89; CamCAN: n = 195), operationalizing stability and flexibility by task-responsiveness and spontaneous intra-subject variability in resting state. We demonstrate that the power-law exponent of scale-free activity is a highly stable parameter, which responds little to external cognitive demands and shows minimal spontaneous fluctuations over time. In contrast, oscillatory power, particularly in the alpha range (8-13 Hz), responds strongly to tasks and exhibits comparatively large spontaneous fluctuations over time. In sum, our data support differential roles for oscillatory and scale-free activity in the brain with respect to neural stability and flexibility. This result carries implications for criticality-based theories of scale-free activity, state-trait models of variability, and homeostatic views of the brain with regulated variables vs. effectors.

Alpha and theta peak frequency track on- and off-thoughts.

Our thoughts are highly dynamic in their contents. At some points, our thoughts are related to external stimuli or tasks focusing on single content (on-single thoughts), While in other moments, they are drifting away with multiple simultaneous items as contents (off-multiple thoughts). Can such thought dynamics be tracked by corresponding neurodynamics? To address this question, here we track thought dynamics during post-stimulus periods by electroencephalogram (EEG) neurodynamics of alpha and theta peak frequency which, as based on the phase angle, must be distinguished from non-phase-based alpha and theta power. We show how, on the psychological level, on-off thoughts are highly predictive of single-multiple thought contents, respectively. Using EEG, on-single and off-multiple thoughts are mediated by opposite changes in the time courses of alpha (high in on-single but low in off-multiple thoughts) and theta (low in on-single but high in off-multiple thoughts) peak frequencies. In contrast, they cannot be distinguished by frequency power. Overall, these findings provide insight into how alpha and theta peak frequency with their phase-related processes track on- and off-thoughts dynamically. In short, neurodynamics track thought dynamics.

Intrinsic neural timescales: temporal integration and segregation.

We are continuously bombarded by external inputs of various timescales from the environment. How does the brain process this multitude of timescales? Recent resting state studies show a hierarchy of intrinsic neural timescales (INT) with a shorter duration in unimodal regions (e.g., visual cortex and auditory cortex) and a longer duration in transmodal regions (e.g., default mode network). This unimodal-transmodal hierarchy is present across acquisition modalities [electroencephalogram (EEG)/magnetoencephalogram (MEG) and fMRI] and can be found in different species and during a variety of different task states. Together, this suggests that the hierarchy of INT is central to the temporal integration (combining successive stimuli) and segregation (separating successive stimuli) of external inputs from the environment, leading to temporal segmentation and prediction in perception and cognition.

It's in the Timing: Reduced Temporal Precision in Neural Activity of Schizophrenia.

Studies of perception and cognition in schizophrenia (SCZ) show neuronal background noise (ongoing activity) to intermittently overwhelm the processing of external stimuli. This increased noise, relative to the activity evoked by the stimulus, results in temporal imprecision and higher variability of behavioral responses. What, however, are the neural correlates of temporal imprecision in SCZ behavior? We first report a decrease in electroencephalography signal-to-noise ratio (SNR) in two SCZ datasets and tasks in the broadband (1-80 Hz), theta (4-8 Hz), and alpha (8-13 Hz) bands. SCZ participants also show lower inter-trial phase coherence (ITPC)-consistency over trials in the phase of the signal-in theta. From these ITPC results, we varied phase offsets in a computational simulation, which illustrated phase-based temporal desynchronization. This modeling also provided a necessary link to our results and showed decreased neural synchrony in SCZ in both datasets and tasks when compared with healthy controls. Finally, we showed that reduced SNR and ITPC are related and showed a relationship to temporal precision on the behavioral level, namely reaction times. In conclusion, we demonstrate how temporal imprecision in SCZ neural activity-reduced relative signal strength and phase coherence-mediates temporal imprecision on the behavioral level.

Extending the "resting state hypothesis of depression" - dynamics and topography of abnormal rest-task modulation.

Major depressive disorder (MDD) is characterized by changes in both rest and task states as manifested in temporal dynamics (EEG) and spatial patterns (fMRI). Are rest and task changes related to each other? Extending the "Resting state hypothesis of depression" (RSHD) (Northoff et al., 2011), we, using multimodal imaging, take a tripartite approach: (i) we conduct a review of EEG studies in MDD combining both rest and task states; (ii) we present our own EEG data in MDD on brain dynamics, i.e., intrinsic neural timescales as measured by the autocorrelation window (ACW); and (iii) we review fMRI studies in MDD to probe whether different regions exhibit different rest-task modulation. Review of EEG data shows reduced rest-task change in MDD in different measures of temporal dynamics like peak frequency (and others). Notably, our own EEG data show decreased rest-task change as measured by ACW in frontal electrodes of MDD. The fMRI data reveal that different regions exhibit different rest-task relationships (normal rest-abnormal task, abnormal rest-normal task, abnormal rest-abnormal task) in MDD. Together, we demonstrate altered spatiotemporal dynamics of rest-task modulation in MDD; this further supports and extends the key role of the spontaneous activity in MDD as proposed by the RSHD.

The brain and its time: intrinsic neural timescales are key for input processing.

We process and integrate multiple timescales into one meaningful whole. Recent evidence suggests that the brain displays a complex multiscale temporal organization. Different regions exhibit different timescales as described by the concept of intrinsic neural timescales (INT); however, their function and neural mechanisms remains unclear. We review recent literature on INT and propose that they are key for input processing. Specifically, they are shared across different species, i.e., input sharing. This suggests a role of INT in encoding inputs through matching the inputs' stochastics with the ongoing temporal statistics of the brain's neural activity, i.e., input encoding. Following simulation and empirical data, we point out input integration versus segregation and input sampling as key temporal mechanisms of input processing. This deeply grounds the brain within its environmental and evolutionary context. It carries major implications in understanding mental features and psychiatric disorders, as well as going beyond the brain in integrating timescales into artificial intelligence.

Childhood trauma mediates repetitive transcranial magnetic stimulation efficacy in major depressive disorder.

Childhood trauma is one of the most prominent risk factors in developing major depressive disorder (MDD) and may lead to unfavorable outcomes of pharmacotherapy and psychotherapy in MDD. While how it modulates the treatment outcome of the repetitive transcranial magnetic stimulation (rTMS) and how sex difference may play a role in mediating this relationship remain unknown. To evaluate this question, 51 (37 women) MDD patients were treated with 10 Hz rTMS to the left dorsolateral prefrontal cortex (lDLPFC). The experience of childhood trauma was quantified by the Childhood Traumatic Questionnaire (CTQ). The depressive severity was assessed by Hamilton Depression Scale (HAMD) and Beck Depression Inventory (BDI) as the primary and secondary assessments. Beck Hopelessness Scale (BHS) and Hamilton Anxiety Scale (HAMA) were also assessed for further confirmation. Thirty-six (70.6%) participants showed a response including 17 (33.3%) achieving remission to the rTMS treatment. The alleviation of depressive symptoms was negatively correlated with the CTQ scores, specifically in women but not men, in subjective BDI and BHS, but not objective HAMD or HAMA. We demonstrate that childhood trauma negatively affects the subjective perception of rTMS-lDLPFC treatment outcomes in female MDD patients. This highlights the importance of measuring childhood trauma-related symptoms in routine clinical rTMS treatment, as they may impact perceived efficacy.

Dynamic relationships between spontaneous and evoked electrophysiological activity.

Spontaneous neural activity fluctuations have been shown to influence trial-by-trial variation in perceptual, cognitive, and behavioral outcomes. However, the complex electrophysiological mechanisms by which these fluctuations shape stimulus-evoked neural activity remain largely to be explored. Employing a large-scale magnetoencephalographic dataset and an electroencephalographic replication dataset, we investigate the relationship between spontaneous and evoked neural activity across a range of electrophysiological variables. We observe that for high-frequency activity, high pre-stimulus amplitudes lead to greater evoked desynchronization, while for low frequencies, high pre-stimulus amplitudes induce larger degrees of event-related synchronization. We further decompose electrophysiological power into oscillatory and scale-free components, demonstrating different patterns of spontaneous-evoked correlation for each component. Finally, we find correlations between spontaneous and evoked time-domain electrophysiological signals. Overall, we demonstrate that the dynamics of multiple electrophysiological variables exhibit distinct relationships between their spontaneous and evoked activity, a result which carries implications for experimental design and analysis in non-invasive electrophysiology.

Prestimulus dynamics blend with the stimulus in neural variability quenching.

Neural responses to the same stimulus show significant variability over trials, with this variability typically reduced (quenched) after a stimulus is presented. This trial-to-trial variability (TTV) has been much studied, however how this neural variability quenching is influenced by the ongoing dynamics of the prestimulus period is unknown. Utilizing a human intracranial stereo-electroencephalography (sEEG) data set, we investigate how prestimulus dynamics, as operationalized by standard deviation (SD), shapes poststimulus activity through trial-to-trial variability (TTV). We first observed greater poststimulus variability quenching in those real trials exhibiting high prestimulus variability as observed in all frequency bands. Next, we found that the relative effect of the stimulus was higher in the later (300-600ms) than the earlier (0-300ms) poststimulus period. Lastly, we replicate our findings in a separate EEG dataset and extend them by finding that trials with high prestimulus variability in the theta and alpha bands had faster reaction times. Together, our results demonstrate that stimulus-related activity, including its variability, is a blend of two factors: 1) the effects of the external stimulus itself, and 2) the effects of the ongoing dynamics spilling over from the prestimulus period - the state at stimulus onset - with the second dwarfing the influence of the first.

Temporal integration as "common currency" of brain and self-scale-free activity in resting-state EEG correlates with temporal delay effects on self-relatedness.

The self is a multifaceted phenomenon that integrates information and experience across multiple time scales. How temporal integration on the psychological level of the self is related to temporal integration on the neuronal level remains unclear. To investigate temporal integration on the psychological level, we modified a well-established self-matching paradigm by inserting temporal delays. On the neuronal level, we indexed temporal integration in resting-state EEG by two related measures of scale-free dynamics, the power law exponent and autocorrelation window. We hypothesized that the previously established self-prioritization effect, measured as decreased response times or increased accuracy for self-related stimuli, would change with the insertion of different temporal delays between the paired stimuli, and that these changes would be related to temporal integration on the neuronal level. We found a significant self-prioritization effect on accuracy in all conditions with delays, indicating stronger temporal integration of self-related stimuli. Further, we observed a relationship between temporal integration on psychological and neuronal levels: higher degrees of neuronal integration, that is, higher power-law exponent and longer autocorrelation window, during resting-state EEG were related to a stronger increase in the self-prioritization effect across longer temporal delays. We conclude that temporal integration on the neuronal level serves as a template for temporal integration of the self on the psychological level. Temporal integration can thus be conceived as the "common currency" of neuronal and psychological levels of self.

The self in art therapy - Brain-based assessment of the drawing process.

Art therapy plays important role in classical psychological assessment as it allows expressing the subject's sense of self. However, its effectiveness and validity could be impeded by lack of relationship to the patients' neuronal changes in their brain. The aim of our theoretical-empirical paper is to propose a novel brain-based quantitative objective measurement of the self and how it shapes the drawing process. We discuss recent data that how the autocorrelation window (ACW) is related to the temporal continuity of self in current neuroscience and further develop a method to use ACW to measure the temporal continuity of the drawing process, probing it in two case studies. As expected, the schizophrenic subject shows lower ACW values compared to the healthy subject and reflects the well-known deficit in the temporal continuity of the self in schizophrenia. We concluded that ACW and eventually other measures of the brain's spatiotemporal structure might be able to serve as objective markers of the self in the drawing process. As our approach connects brain, self, and drawing process, it provides the theoretical basis for the future development of a brain-based assessment of the self in the drawing process and art therapy.

From neuronal to psychological noise - Long-range temporal correlations in EEG intrinsic activity reduce noise in internally-guided decision making.

Our personal internal preferences while making decisions are usually consistent. Recent psychological studies, however, show observable variability of internal criteria occurs by random noise. The neural correlates of said random noise - an instance of 'psychological noise' - yet remain unclear. Combining simulation, behavioral, and neural approaches, our study investigated the psychological and neural correlates of such random noise in our internal criteria during decision making. We applied well-established decision-making tasks which relied on either internal criteria - occupation choice task as internally-guided decision making (IDM) - or external criteria - salary judgment task as externally-guided decision making (EDM). Subjects underwent EEG for resting state and task-evoked activity during IDM and EDM. We measured resting state long-range temporal correlation (LRTC) in the alpha frequency range as the index of neuronal noise. Based on our simulation, we identified a measure of psychological noise (as distinguished from true preference change) in IDM. The main finding shows that the indices for psychological noise are directly related to frontocentral LRTC in the alpha range. Higher degrees of frontocentral LRTC, which index lower neuronal noise, were related to lower degrees of psychological noise during IDM. This was not found during EDM. Resting state LRTC was also related to task-evoked activity, such as conflict-related negativity, during IDM only. Taken together, our data demonstrate, for the first time, the direct relationship between neuronal noise in the brain's intrinsic activity and psychological noise in the internal criteria of our decision making.

Neural variability quenching during decision-making: Neural individuality and its prestimulus complexity.

The spontaneous activity of the brain interacts with stimulus-induced activity which is manifested in event-related amplitude and its trial-to-trial variability (TTV). TTV describes the variability in the amplitude of the stimulus-evoked response across trials, and it is generally observed to be reduced, or quenched. While such TTV quenching has been observed on both the cellular and regional levels, its exact behavioral relevance and neuronal basis remains unclear. Applying a novel paradigm for testing neural markers of individuality in internally-guided decision-making, we here investigated whether TTV (i) represents an individually specific response by comparing individualized vs shared stimuli; and (ii) is mediated by the complexity of prestimulus activity as measured by the Lempel-Ziv Complexity index (LZC). We observed that TTV - and other electrophysiological markers such as ERP, ERSP, and ITC - showed first significant differences between individualized and shared stimuli (while controlling for task-related effects) specifically in the alpha and beta frequency bands, and secondly that TTV in the beta band correlated significantly with reaction time and eLORETA activity. Moreover, we demonstrate that the complexity (LZC) of neuronal activity is higher in the prestimulus period while it decreases during the poststimulus period, with the former also correlating specifically with poststimulus individualized TTV in alpha (but not with shared TTV). Together, our results show that the TTV represents a marker of 'neural individualization' which, being related to internal processes on both neural and psychological levels, is mediated by the information complexity of prestimulus activity. More generally, our results inform the pre-post-stimulus dynamics of rest-stimulus interaction, which is a basic and ubiquitous neural phenomenon in the brain and highly relevant for mental features including their individuality.