Flicker light stimulation enhances the emotional response to music: a comparison study to the effects of psychedelics.

Flicker light stimulation (FLS) is a non-pharmacological method of inducing altered states of consciousness (ASCs), producing hallucination-like phenomena as well as effects extending beyond the visual modality, including emotional effects. Research into the psychological and neural mechanisms of FLS is still in its infancy, but can be informed by research into other methods of inducing ASCs. For instance, research on classic psychedelics has reported enhancement of emotional responses to music. Here, we test to what degree FLS might also enhance the emotional response to music, using a study protocol designed to resemble a previous study on the effects of LSD as closely as possible, to allow for comparison of effect sizes across modalities and inform future research into FLS as an ASC-induction method. Twenty participants listened to emotionally evocative music in two conditions - with and without FLS - and reported on their emotional response to the music. FLS showed a significant enhancing effect on reported music-evoked emotion, especially emotions relating to "Joyful Activation"; additionally, we found that the experienced intensity of FLS correlated with reports of higher levels of emotional arousal. These findings motivate further research into FLS as a method for inducing ASCs and into the interactions between visual phenomena and music-evoked emotion.

A multimodal cortical network of sensory expectation violation revealed by fMRI.

The brain is subjected to multi-modal sensory information in an environment governed by statistical dependencies. Mismatch responses (MMRs), classically recorded with EEG, have provided valuable insights into the brain's processing of regularities and the generation of corresponding sensory predictions. Only few studies allow for comparisons of MMRs across multiple modalities in a simultaneous sensory stream and their corresponding cross-modal context sensitivity remains unknown. Here, we used a tri-modal version of the roving stimulus paradigm in fMRI to elicit MMRs in the auditory, somatosensory and visual modality. Participants (N = 29) were simultaneously presented with sequences of low and high intensity stimuli in each of the three senses while actively observing the tri-modal input stream and occasionally reporting the intensity of the previous stimulus in a prompted modality. The sequences were based on a probabilistic model, defining transition probabilities such that, for each modality, stimuli were more likely to repeat (p = .825) than change (p = .175) and stimulus intensities were equiprobable (p = .5). Moreover, each transition was conditional on the configuration of the other two modalities comprising global (cross-modal) predictive properties of the sequences. We identified a shared mismatch network of modality general inferior frontal and temporo-parietal areas as well as sensory areas, where the connectivity (psychophysiological interaction) between these regions was modulated during mismatch processing. Further, we found deviant responses within the network to be modulated by local stimulus repetition, which suggests highly comparable processing of expectation violation across modalities. Moreover, hierarchically higher regions of the mismatch network in the temporo-parietal area around the intraparietal sulcus were identified to signal cross-modal expectation violation. With the consistency of MMRs across audition, somatosensation and vision, our study provides insights into a shared cortical network of uni- and multi-modal expectation violation in response to sequence regularities.

The psychedelic afterglow phenomenon: a systematic review of subacute effects of classic serotonergic psychedelics.

Background: Classic serotonergic psychedelics have anecdotally been reported to show a characteristic pattern of subacute effects that persist after the acute effects of the substance have subsided. These transient effects, sometimes labeled as the 'psychedelic afterglow', have been suggested to be associated with enhanced effectiveness of psychotherapeutic interventions in the subacute period. Objectives: This systematic review provides an overview of subacute effects of psychedelics. Methods: Electronic databases (MEDLINE, Web of Science Core Collection) were searched for studies that assessed the effects of psychedelics (LSD, psilocybin, DMT, 5-MeO-DMT, mescaline, or ayahuasca) on psychological outcome measures and subacute adverse effects in human adults between 1950 and August 2021, occurring between 1 day and 1 month after drug use. Results: Forty-eight studies including a total number of 1,774 participants were eligible for review. Taken together, the following subacute effects were observed: reductions in different psychopathological symptoms; increases in wellbeing, mood, mindfulness, social measures, spirituality, and positive behavioral changes; mixed changes in personality/values/attitudes, and creativity/flexibility. Subacute adverse effects comprised a wide range of complaints, including headaches, sleep disturbances, and individual cases of increased psychological distress. Discussion: Results support narrative reports of a subacute psychedelic 'afterglow' phenomenon comprising potentially beneficial changes in the perception of self, others, and the environment. Subacute adverse events were mild to severe, and no serious adverse events were reported. Many studies, however, lacked a standardized assessment of adverse effects. Future studies are needed to investigate the role of possible moderator variables and to reveal if and how positive effects from the subacute window may consolidate into long-term mental health benefits.

Effect of frequency and rhythmicity on flicker light-induced hallucinatory phenomena.

Flicker light stimulation (FLS) uses stroboscopic light on closed eyes to induce transient visual hallucinatory phenomena, such as the perception of geometric patterns, motion, and colours. It remains an open question where the neural correlates of these hallucinatory experiences emerge along the visual pathway. To allow future testing of suggested underlying mechanisms (e.g., changes in functional connectivity, neural entrainment), we sought to systematically characterise the effects of frequency (3 Hz, 8 Hz, 10 Hz and 18 Hz) and rhythmicity (rhythmic and arrhythmic conditions) on flicker-induced subjective experiences. Using a novel questionnaire, we found that flicker frequency and rhythmicity significantly influenced the degree to which participants experienced simple visual hallucinations, particularly the perception of Klüver forms and dynamics (e.g., motion). Participants reported their experience of geometric patterns and dynamics was at highest intensity during 10 Hz rhythmic stimulation. Further, we found that frequency-matched arrhythmic FLS strongly reduced these subjective effects compared to equivalent rhythmic stimulation. Together, these results provide evidence that flicker rhythmicity critically contributes to the effects of FLS beyond the effects of frequency alone, indicating that neural entrainment may drive the induced phenomenal experience.

Differences in working memory coding of biological motion attributed to oneself and others.

The question how the brain distinguishes between information about self and others is of fundamental interest to both philosophy and neuroscience. In this functional magnetic resonance imaging (fMRI) study, we sought to distinguish the neural substrates of representing a full-body movement as one's movement and as someone else's movement. Participants performed a delayed match-to-sample working memory task where a retained full-body movement (displayed using point-light walkers) was arbitrarily labeled as one's own movement or as performed by someone else. By using arbitrary associations we aimed to address a limitation of previous studies, namely that our own movements are more familiar to us than movements of other people. A searchlight multivariate decoding analysis was used to test where information about types of movement and about self-association was coded. Movement specific activation patterns were found in a network of regions also involved in perceptual processing of movement stimuli, however not in early sensory regions. Information about whether a memorized movement was associated with the self or with another person was found to be coded by activity in the left middle frontal gyrus (MFG), left inferior frontal gyrus (IFG), bilateral supplementary motor area, and (at reduced threshold) in the left temporoparietal junction (TPJ). These areas are frequently reported as involved in action understanding (IFG, MFG) and domain-general self/other distinction (TPJ). Finally, in univariate analysis we found that selecting a self-associated movement for retention was related to increased activity in the ventral medial prefrontal cortex.

Enhanced processing of aversive stimuli on embodied artificial limbs by the human amygdala.

Body perception has been extensively investigated, with one particular focus being the integration of vision and touch within a neuronal body representation. Previous studies have implicated a distributed network comprising the extrastriate body area (EBA), posterior parietal cortex (PPC) and ventral premotor cortex (PMv) during illusory self-attribution of a rubber hand. Here, we set up an fMRI paradigm in virtual reality (VR) to study whether and how the self-attribution of (artificial) body parts is altered if these body parts are somehow threatened. Participants (N = 30) saw a spider (aversive stimulus) or a toy-car (neutral stimulus) moving along a 3D-rendered virtual forearm positioned like their real forearm, while tactile stimulation was applied on the real arm in the same (congruent) or opposite (incongruent) direction. We found that the PPC was more activated during congruent stimulation; higher visual areas and the anterior insula (aIns) showed increased activation during aversive stimulus presentation; and the amygdala was more strongly activated for aversive stimuli when there was stronger multisensory integration of body-related information (interaction of aversiveness and congruency). Together, these findings suggest an enhanced processing of aversive stimuli within the amygdala when they represent a bodily threat.

Phenomenological assessment of psychedelics induced experiences: Translation and validation of the German Challenging Experience Questionnaire (CEQ) and Ego-Dissolution Inventory (EDI).

Several measures have been designed to assess subjective experiences induced by psychedelic substances or other mind-altering drugs as well as non-pharmacological methods. Recently, two self-report questionnaires have been introduced to measure acute adverse effects following psilocybin ingestion and the phenomenon of ego-dissolution associated with the use of psychedelics, respectively. The 26-item Challenging Experience Questionnaire assesses multiple facets of psilocybin induced experiences on seven subscales, whereas the 8-item Ego-Dissolution Inventory consists of a unidimensional scale. In the present study, these questionnaires were translated into German and their psychometric properties then evaluated in an online survey on psychedelics induced experiences. Confirmatory factor analysis suggested an acceptable fit of the 7-factor structure of the German Challenging Experience Questionnaire with overall good internal consistency for all subscales. The factor structure did not differ based on gender or prior struggle with a psychiatric disorder, furthering the evidence of internal validity. Correlations with the State-Trait-Anxiety Inventory and the Altered States of Consciousness Rating Scale demonstrated convergent validity. Confirmatory factor analysis did not support the hypothesized single-factor structure of the German Ego-Dissolution Inventory and exploratory factor analysis suggested an alternative factor structure, where only five items loaded onto a common factor that was interpreted as ego-dissolution. Internal consistency of this 5-item measure was high and correlation with selected items of the Mystical Experience Questionnaire and Altered States of Consciousness Rating Scale supported convergent validity. Translation and validation of these questionnaires contribute to the advancement of common standards in the psychological and neuroscientific study of altered states of consciousness.

Altered states phenomena induced by visual flicker light stimulation.

Flicker light stimulation can induce short-term alterations in consciousness including hallucinatory color perception and geometric patterns. In the study at hand, the subjective experiences during 3 Hz and 10 Hz stroboscopic light stimulation of the closed eyes were assessed. In a within-subjects design (N = 24), we applied the Positive and Negative Affect Schedule (mood state), time perception ratings, the Altered State of Consciousness Rating Scale, and the Phenomenology of Consciousness Inventory. Furthermore, we tested for effects of personality traits (NEO Five-Factor Inventory-2 and Tellegen Absorption Scale) on subjective experiences. Such systematic quantification improves replicability, facilitates comparisons between pharmacological and non-pharmacological techniques to induce altered states of consciousness, and is the prerequisite to study their underlying neuronal mechanisms. The resulting data showed that flicker light stimulation-induced states were characterized by vivid visual hallucinations of simple types, with effects strongest in the 10 Hz condition. Additionally, participants' personality trait of Absorption scores highly correlated with the experienced alterations in consciousness. Our data demonstrate that flicker light stimulation is capable of inducing visual effects with an intensity rated to be similar in strength to effects induced by psychedelic substances and thereby support the investigation of potentially shared underlying neuronal mechanisms.

Representation of visual numerosity information during working memory in humans: An fMRI decoding study.

Both animal and human studies on numerosity have shown the importance of the parietal cortex for numerosity processing. However, most studies have focused on the perceptual processing of numerosity. Still, it is unclear how and where numerosity information is coded when this information is retained during a working memory delay phase. Such temporal storage could be realized by the same structures as perceptual processes, or be transformed to a more abstract representation, potentially involving prefrontal regions. FMRI decoding studies allow the identification of brain areas that exhibit multi-voxel activation patterns specific to the content of working memory. Here, we used an assumption-free searchlight-decoding approach to test where numerosity-specific codes can be found during a 12 s retention period. Participants (n = 24) performed a retro-cue delayed match-to-sample task, in which numerosity information was presented as visual dot arrays. We found mnemonic numerosity-specific activation in the right lateral portion of the intraparietal sulcus; an area well-known for perceptual processing of numerosity. The applied retro-cue design dissociated working memory delay activity from perceptual processes and showed that the intraparietal sulcus also maintained working memory representation independent of perception.

Rehearsal of tactile working memory: Premotor cortex recruits two dissociable neuronal content representations.

Recent working memory (WM) research has focused on identifying brain regions that retain different types of mental content. Only few neuroimaging studies have explored the mechanism of attention-based refreshing, which is a type of rehearsal and is thought to implement the dynamic components of WM allowing for update of WM contents. Here, we took advantage of the distinct coding properties of the superior parietal lobe (SPL), which retains spatial layout information, and the right inferior frontal gyrus (IFG), which retains frequency information of vibrotactile stimuli during tactile WM. In an fMRI delayed match-to-sample task, participants had to internally rehearse sequences of spatial layouts or vibratory frequencies. Our results replicate the dissociation of SPL and IFG for the retention of layout and frequency information in terms of activation differences between conditions. Additionally, we found strong premotor cortex (PMC) activation during rehearsal of either stimulus type. To explore interactions between these regions we used dynamic causal modeling and found that activation within the network was best explained by a model that allows the PMC to drive activity in the SPL and IFG during rehearsal. This effect was content-specific, meaning that the PMC showed stronger influence on the SPL during pattern rehearsal and stronger influence on the IFG during frequency rehearsal. In line with previously established PMC contributions to sequence processing, our results suggest that it acts as a content-independent area that flexibly recruits content-specific regions to bring a WM item into the focus of attention during the rehearsal of tactile stimulus sequences.

Acute and subacute psychoactive effects of Kambô, the secretion of the Amazonian Giant Maki Frog (Phyllomedusa bicolor): retrospective reports.

Kambô, the secretion of the Amazonian Giant Leaf Frog (Phyllomedusa bicolor) contains a plethora of bioactive peptides and was originally used by indigenous communities from the Amazon basin as medicine for improving hunting capacities. In the last 20 years, Kambô has spread to Western urban healing circles. To date it is still controversial whether the acute effects of Kambô include alterations of consciousness similar to known psychoactive substance like serotonergic psychedelics. Here we retrospectively assessed psychological effects of Kambô in a sample of anonymous users (n = 22, mean age: 39 years, ± 8.5; 45.5% female), administering standardized questionnaires for the assessment of altered states of consciousness (ASC), including the Altered States of Consciousness Rating Scale, the Phenomenology of Consciousness Inventory (PCI), the Mystical Experience Questionnaire (MEQ), the Challenging Experience Questionnaire (CEQ) for acute effects and the Persisting Effects Questionnaire (PEQ) and a scale assessing connectedness for subacute effects. The intensity of retrospectively reported acute psychological effects remained on a mild to moderate level, with no psychedelic-type distortions of perception or thinking. Conversely, persisting effects were predominantly described as positive and pleasant, revealing high scores on measures of personal and spiritual significance.

The multimodal Ganzfeld-induced altered state of consciousness induces decreased thalamo-cortical coupling.

Different pharmacologic agents have been used to investigate the neuronal underpinnings of alterations in consciousness states, such as psychedelic substances. Special attention has been drawn to the role of thalamic filtering of cortical input. Here, we investigate the neuronal mechanisms underlying an altered state of consciousness (ASC) induced by a non-pharmacological procedure. During fMRI scanning, N = 19 human participants were exposed to multimodal Ganzfeld stimulation, a technique of perceptual deprivation where participants are exposed to intense, unstructured, homogenous visual and auditory stimulation. Compared to pre- and post-resting-state scans, the Ganzfeld data displayed a progressive decoupling of the thalamus from the cortex. Furthermore, the Ganzfeld-induced ASC was characterized by increased eigenvector centrality in core regions of the default mode network (DMN). Together, these findings can be interpreted as an imbalance of sensory bottom-up signaling and internally-generated top-down signaling. This imbalance is antithetical to psychedelic-induced ASCs, where increased thalamo-cortical coupling and reduced DMN activity were observed.

Intraparietal sulcus maintains working memory representations of somatosensory categories in an adaptive, context-dependent manner.

Working memory (WM) representations are generally known to be influenced by task demands, but it is not clear whether this extends to the somatosensory domain. One way to investigate the influence of task demands is with categorization paradigms, wherein either a single stimulus or an associated category is maintained in WM. In the somatosensory modality, category representations have been identified in the premotor cortex (PMC) and the intraparietal sulcus (IPS). In this study we used multivariate-pattern-analysis with human fMRI data to investigate whether the WM representations in the PMC, IPS or other regions are influenced by changing task demands. We ensured the task-dependent, categorical WM information was decorrelated from stimulus features by (1) teaching participants arbitrary, non-rule based stimulus groupings and (2) contrasting identical pairs of stimuli across experimental conditions, where either a single stimulus or the associated group was maintained in WM. Importantly, we also decoupled the decision and motor output from the WM representations. With these experimental manipulations, we were able to pinpoint stimulus-specific WM information to the left frontal and parietal cortices and context-dependent, group-specific WM information to the left IPS. By showing that grouped stimuli are represented more similarly in the Group condition than in the Stimulus condition, free from stimulus and motor output confounds, we provide novel evidence for the adaptive nature of somatosensory WM representations in the IPS with changing task-demands.

Parametric Representation of Tactile Numerosity in Working Memory.

Estimated numerosity perception is processed in an approximate number system (ANS) that resembles the perception of a continuous magnitude. The ANS consists of a right lateralized frontoparietal network comprising the lateral prefrontal cortex (LPFC) and the intraparietal sulcus. Although the ANS has been extensively investigated, only a few studies have focused on the mental representation of retained numerosity estimates. Specifically, the underlying mechanisms of estimated numerosity working memory (WM) is unclear. Besides numerosities, as another form of abstract quantity, vibrotactile WM studies provide initial evidence that the right LPFC takes a central role in maintaining magnitudes. In the present fMRI multivariate pattern analysis study, we designed a delayed match-to-numerosity paradigm to test what brain regions retain approximate numerosity memoranda. In line with parametric WM results, our study found numerosity-specific WM representations in the right LPFC as well as in the supplementary motor area and the left premotor cortex extending into the superior frontal gyrus, thus bridging the gap in abstract quantity WM literature.

Neural basis of somatosensory target detection independent of uncertainty, relevance, and reports.

Research on somatosensory awareness has yielded highly diverse findings with putative neural correlates ranging from activity within somatosensory cortex to activation of widely distributed frontoparietal networks. Divergent results from previous studies may reside in cognitive processes that often coincide with stimulus awareness in experimental settings. To scrutinise the specific relevance of regions implied in the target detection network, we used functional magnetic resonance imaging (n = 27) on a novel somatosensory detection task that explicitly controls for stimulus uncertainty, behavioural relevance, overt reports, and motor responses. Using Bayesian Model Selection, we show that responses reflecting target detection are restricted to secondary somatosensory cortex, whereas activity in insular, cingulate, and motor regions is best explained in terms of stimulus uncertainty and overt reports. Our results emphasise the role of sensory-specific cortex for the emergence of perceptual awareness and dissect the contribution of the frontoparietal network to classical detection tasks.

The Somatotopy of Mental Tactile Imagery.

To what degree mental imagery (MI) bears on the same neuronal processes as perception has been a central question in the neurophysiological study of imagery. Sensory-recruitment models suggest that imagery of sensory material heavily relies on the involvement of sensory cortices. Empirical evidence mainly stems from the study of visual imagery and suggests that it depends on the mentally imagined material whether hierarchically lower regions are recruited. However, evidence from other modalities is necessary to infer generalized principles. In this fMRI study we used the somatotopic organization of the primary somatosensory cortex (SI) to test in how far MI of tactile sensations activates topographically sensory brain areas. Participants (N = 19) either perceived or imagined vibrotactile stimuli on their left or right thumbs or big toes. The direct comparison to a corresponding perception condition revealed that SI was somatotopically recruited during imagery. While stimulus driven bottom-up processing induced activity throughout all SI subareas, i.e., BA1, BA3a, BA3b, and BA2 defined by probabilistic cytoarchitectonic maps, top-down recruitment during imagery was limited to the hierarchically highest subarea BA2.

Neuronal correlates of label facilitated tactile perception.

It is a long-standing question in neurolinguistics, to what extent language can have a causal effect on perception. A recent behavioural study reported that participants improved their discrimination ability of Braille-like tactile stimuli after one week of implicit association training with language stimuli being co-presented redundantly with the tactile stimuli. In that experiment subjects were exposed twice a day for 1 h to the joint presentation of tactile stimuli presented to the fingertip and auditorily presented pseudowords. Their discrimination ability improved only for those tactile stimuli that were consistently paired with pseudowords, but not for those that were discordantly paired with different pseudowords. Thereby, a causal effect of verbal labels on tactile perception has been demonstrated under controlled laboratory conditions. This raises the question as to what the neuronal mechanisms underlying this implicit learning effect are. Here, we present fMRI data collected before and after the aforementioned behavioral learning to test for changes in brain connectivity as the underlying mechanism of the observed behavioral effects. The comparison of pre- and post-training revealed a language-driven increase in connectivity strength between auditory and secondary somatosensory cortex and the hippocampus as an association-learning related region.

Content-specific codes of parametric auditory working memory in humans.

Brain activity in frontal regions has been found to represent frequency information with a parametric code during working memory delay phases. The mental representation of frequencies has furthermore been shown to be modality independent in non-human primate electrophysiology and human EEG studies, suggesting frontal regions encoding quantitative information in a supramodal manner. A recent fMRI study using multivariate pattern analysis (MVPA) supports an overlapping multimodal network for the maintenance of visual and tactile frequency information over frontal and parietal brain regions. The present study extends the investigation of working memory representation of frequency information to the auditory domain. To this aim, we used MVPA on fMRI data recorded during an auditory frequency maintenance task. A support vector regression analysis revealed working memory information in auditory association areas and, consistent with earlier findings of parametric working memory, in a frontoparietal network. A direct comparison to an analogous dataset of vibrotactile parametric working memory revealed an overlap of information coding in prefrontal regions, particularly in the right inferior frontal gyrus. Therefore, our findings indicate that the prefrontal cortex represents frequency-specific working memory content irrespective of the modality as has been now also revealed for the auditory modality.

Brain regions that retain the spatial layout of tactile stimuli during working memory - A 'tactospatial sketchpad'?

Working memory (WM) studies have been essential for ascertaining how the brain flexibly handles mentally represented information in the absence of sensory stimulation. Most studies on the memory of sensory stimulus features have focused, however, on the visual domain. Here, we report a human WM study in the tactile modality where participants had to memorize the spatial layout of patterned Braille-like stimuli presented to the index finger. We used a whole-brain searchlight approach in combination with multi-voxel pattern analysis (MVPA) to investigate tactile WM representations without a priori assumptions about which brain regions code tactospatial information. Our analysis revealed that posterior and parietal cortices, as well as premotor regions, retained information across the twelve-second delay phase. Interestingly, parts of this brain network were previously shown to also contain information of visuospatial WM. Also, by specifically testing somatosensory regions for WM representations, we observed content-specific activation patterns in primary somatosensory cortex (SI). Our findings demonstrate that tactile WM depends on a distributed network of brain regions in analogy to the representation of visuospatial information.

Verbal labels facilitate tactile perception.

One of the key statements of linguistic relativity is that language has a causal effect on perception. Although much previous research has addressed such putative language perception causality, no firm proof is available thus far which demonstrates that verbal labels help or otherwise influence perceptual processes. Here, we tested the hypothesis of language perception causality by using novel, minimally-different tactile-patterned stimuli applied to the finger, which initially could not be discriminated by our participants. By combining novel verbal pseudoword- and novel tactile-patterned stimuli in an implicit learning experiment, we show a language-induced facilitation in tactile-patterned stimulus discrimination. After one week of intensive yet implicit learning of tactile stimuli in the presence of irrelevant consistent verbal labels, participants demonstrated significant discrimination improvement. In contrast, the same participants showed no improvement in discriminating tactile-patterned stimuli that had been learnt in the context of variable linguistic stimuli. These results show that specific mental links between verbal labels and perceptual information brought about by their correlated presentation enable one to better discriminate said sensory information (and build percepts).