Unravelling the multisensory learning advantage: Different patterns of within and across frequency-specific interactions drive uni- and multisensory neuroplasticity.

In the field of learning theory and practice, the superior efficacy of multisensory learning over uni-sensory is well-accepted. However, the underlying neural mechanisms at the macro-level of the human brain remain largely unexplored. This study addresses this gap by providing novel empirical evidence and a theoretical framework for understanding the superiority of multisensory learning. Through a cognitive, behavioral, and electroencephalographic assessment of carefully controlled uni-sensory and multisensory training interventions, our study uncovers a fundamental distinction in their neuroplastic patterns. A multilayered network analysis of pre- and post- training EEG data allowed us to model connectivity within and across different frequency bands at the cortical level. Pre-training EEG analysis unveils a complex network of distributed sources communicating through cross-frequency coupling, while comparison of pre- and post-training EEG data demonstrates significant differences in the reorganizational patterns of uni-sensory and multisensory learning. Uni-sensory training primarily modifies cross-frequency coupling between lower and higher frequencies, whereas multisensory training induces changes within the beta band in a more focused network, implying the development of a unified representation of audiovisual stimuli. In combination with behavioural and cognitive findings this suggests that, multisensory learning benefits from an automatic top-down transfer of training, while uni-sensory training relies mainly on limited bottom-up generalization. Our findings offer a compelling theoretical framework for understanding the advantage of multisensory learning.

Tinnitus and Multimodal Cortical Interaction. / Tinnitus und multimodale kortikale Interaktion.

The term of subjective tinnitus is used to describe a perceived noise without an external sound source. Therefore, it seems to be obvious that tinnitus can be understood as purely auditory, sensory problem. From a clinical point of view, however, this is a very inadequate description, as there are significant comorbidities associated with chronic tinnitus. Neurophysiological investigations with different imaging techniques give a very similar picture, because not only the auditory system is affected in chronic tinnitus patients, but also a widely ramified subcortical and cortical network. In addition to auditory processing systems, networks consisting of frontal and parietal regions are particularly disturbed. For this reason, some authors conceptualize tinnitus as a network disorder rather than a disorder of a circumscribed system. These findings and this concept suggest that tinnitus must be diagnosed and treated in a multidisciplinary and multimodal manner.

Aging Effects on the Neuroplastic Attributes of Multisensory Cortical Networks as Triggered by a Computerized Music Reading Training Intervention.

The constant increase in the graying population is the result of a great expansion of life expectancy. A smaller expansion of healthy cognitive and brain functioning diminishes the gains achieved by longevity. Music training, as a special case of multisensory learning, may induce restorative neuroplasticity in older ages. The current study aimed to explore aging effects on the cortical network supporting multisensory cognition and to define aging effects on the network's neuroplastic attributes. A computer-based music reading protocol was developed and evaluated via electroencephalography measurements pre- and post-training on young and older adults. Results revealed that multisensory integration is performed via diverse strategies in the two groups: Older adults employ higher-order supramodal areas to a greater extent than lower level perceptual regions, in contrast to younger adults, indicating an age-related shift in the weight of each processing strategy. Restorative neuroplasticity was revealed in the left inferior frontal gyrus and right medial temporal gyrus, as a result of the training, while task-related reorganization of cortical connectivity was obstructed in the group of older adults, probably due to systemic maturation mechanisms. On the contrary, younger adults significantly increased functional connectivity among the regions supporting multisensory integration.

Studying Physiological Synchrony in Couple Therapy through Partial Directed Coherence: Associations with the Therapeutic Alliance and Meaning Construction.

In line with the growing recognition of the role of embodiment, affect and implicit processes in psychotherapy, several recent studies examine the role of physiological synchrony in the process and outcome of psychotherapy. This study aims to introduce Partial Directed Coherence (PDC) as a novel approach to calculating psychophysiological synchrony and examine its potential to contribute to our understanding of the therapy process. The study adopts a single-case, mixed-method design and examines physiological synchrony in one-couple therapy in relation to the therapeutic alliance and a narrative analysis of meaning construction in the sessions. Interpersonal Physiological Synchrony (IPS) was calculated, via a windowed approach, through PDC of a Heart Rate Variability-derived physiological index, which was measured in the third and penultimate sessions. Our mixed-method analysis shows that PDC quantified significant moments of IPS within and across the sessions, modeling the characteristics of interpersonal interaction as well as the effects of therapy on the interactional dynamics. The findings of this study point to the complex interplay between explicit and implicit levels of interaction and the potential contribution of including physiological synchrony in the study of interactional processes in psychotherapy.

Statistical learning of multisensory regularities is enhanced in musicians: An MEG study.

The present study used magnetoencephalography (MEG) to identify the neural correlates of audiovisual statistical learning, while disentangling the differential contributions of uni- and multi-modal statistical mismatch responses in humans. The applied paradigm was based on a combination of a statistical learning paradigm and a multisensory oddball one, combining an audiovisual, an auditory and a visual stimulation stream, along with the corresponding deviances. Plasticity effects due to musical expertise were investigated by comparing the behavioral and MEG responses of musicians to non-musicians. The behavioral results indicated that the learning was successful for both musicians and non-musicians. The unimodal MEG responses are consistent with previous studies, revealing the contribution of Heschl's gyrus for the identification of auditory statistical mismatches and the contribution of medial temporal and visual association areas for the visual modality. The cortical network underlying audiovisual statistical learning was found to be partly common and partly distinct from the corresponding unimodal networks, comprising right temporal and left inferior frontal sources. Musicians showed enhanced activation in superior temporal and superior frontal gyrus. Connectivity and information processing flow amongst the sources comprising the cortical network of audiovisual statistical learning, as estimated by transfer entropy, was reorganized in musicians, indicating enhanced top-down processing. This neuroplastic effect showed a cross-modal stability between the auditory and audiovisual modalities.

Musical expertise is related to altered functional connectivity during audiovisual integration.

The present study investigated the cortical large-scale functional network underpinning audiovisual integration via magnetoencephalographic recordings. The reorganization of this network related to long-term musical training was investigated by comparing musicians to nonmusicians. Connectivity was calculated on the basis of the estimated mutual information of the sources' activity, and the corresponding networks were statistically compared. Nonmusicians' results indicated that the cortical network associated with audiovisual integration supports visuospatial processing and attentional shifting, whereas a sparser network, related to spatial awareness supports the identification of audiovisual incongruences. In contrast, musicians' results showed enhanced connectivity in regions related to the identification of auditory pattern violations. Hence, nonmusicians rely on the processing of visual clues for the integration of audiovisual information, whereas musicians rely mostly on the corresponding auditory information. The large-scale cortical network underpinning multisensory integration is reorganized due to expertise in a cognitive domain that largely involves audiovisual integration, indicating long-term training-related neuroplasticity.

Musical expertise is related to neuroplastic changes of multisensory nature within the auditory cortex.

Recent neuroscientific evidence indicates that multisensory integration does not only occur in higher level association areas of the cortex as the hierarchical models of sensory perception assumed, but also in regions traditionally thought of as unisensory, such as the auditory cortex. Nevertheless, it is not known whether expertise-induced neuroplasticity can alter the multisensory processing that occurs in these low-level regions. The present study used magnetoencephalography to investigate whether musical training may induce neuroplastic changes of multisensory processing within the human auditory cortex. Magnetoencephalography data of four different experiments were used to demonstrate the effect of long-term and short-term musical training on the integration of auditory, somatosensory and visual stimuli in the auditory cortex. The cross-sectional design of three of the experiments allowed us to infer that long-term musical training is related to a significantly different way of processing multisensory information within the auditory cortex, whereas the short-term training design of the fourth experiment allowed us to causally infer that multisensory music reading training affects the multimodal processing within the auditory cortex.

Neuroplastic effects of combined computerized physical and cognitive training in elderly individuals at risk for dementia: an eLORETA controlled study on resting states.

The present study investigates whether a combined cognitive and physical training may induce changes in the cortical activity as measured via electroencephalogram (EEG) and whether this change may index a deceleration of pathological processes of brain aging. Seventy seniors meeting the clinical criteria of mild cognitive impairment (MCI) were equally divided into 5 groups: 3 experimental groups engaged in eight-week cognitive and/or physical training and 2 control groups: active and passive. A 5-minute long resting state EEG was measured before and after the intervention. Cortical EEG sources were modelled by exact low resolution brain electromagnetic tomography (eLORETA). Cognitive function was assessed before and after intervention using a battery of neuropsychological tests including the minimental state examination (MMSE). A significant training effect was identified only after the combined training scheme: a decrease in the post- compared to pre-training activity of precuneus/posterior cingulate cortex in delta, theta, and beta bands. This effect was correlated to improvements in cognitive capacity as evaluated by MMSE scores. Our results indicate that combined physical and cognitive training shows indices of a positive neuroplastic effect in MCI patients and that EEG may serve as a potential index of gains versus cognitive declines and neurodegeneration. This trial is registered with ClinicalTrials.gov Identifier NCT02313935.

Multisensory integration during short-term music reading training enhances both uni- and multisensory cortical processing.

The human ability to integrate the input of several sensory systems is essential for building a meaningful interpretation out of the complexity of the environment. Training studies have shown that the involvement of multiple senses during training enhances neuroplasticity, but it is not clear to what extent integration of the senses during training is required for the observed effects. This study intended to elucidate the differential contributions of uni- and multisensory elements of music reading training in the resulting plasticity of abstract audiovisual incongruency identification. We used magnetoencephalography to measure the pre- and posttraining cortical responses of two randomly assigned groups of participants that followed either an audiovisual music reading training that required multisensory integration (AV-Int group) or a unisensory training that had separate auditory and visual elements (AV-Sep group). Results revealed a network of frontal generators for the abstract audiovisual incongruency response, confirming previous findings, and indicated the central role of anterior prefrontal cortex in this process. Differential neuroplastic effects of the two types of training in frontal and temporal regions point to the crucial role of multisensory integration occurring during training. Moreover, a comparison of the posttraining cortical responses of both groups to a group of musicians that were tested using the same paradigm revealed that long-term music training leads to significantly greater responses than the short-term training of the AV-Int group in anterior prefrontal regions as well as to significantly greater responses than both short-term training protocols in the left superior temporal gyrus (STG).

Mismatch negativity to acoustical illusion of beat: how and where the change detection takes place?

In case of binaural presentation of two tones with slightly different frequencies the structures of brainstem can no longer follow the interaural time differences (ITD) resulting in an illusionary perception of beat corresponding to frequency difference between the two prime tones. Hence, the beat-frequency does not exist in the prime tones presented to either ear. This study used binaural beats to explore the nature of acoustic deviance detection in humans by means of magnetoencephalography (MEG). Recent research suggests that the auditory change detection is a multistage process. To test this, we employed 26 Hz-binaural beats in a classical oddball paradigm. However, the prime tones (250 Hz and 276 Hz) were switched between the ears in the case of the deviant-beat. Consequently, when the deviant is presented, the cochleae and auditory nerves receive a "new afferent", although the standards and the deviants are heard identical (26 Hz-beats). This allowed us to explore the contribution of auditory periphery to change detection process, and furthermore, to evaluate its influence on beats-related auditory steady-state responses (ASSRs). LORETA-source current density estimates of the evoked fields in a typical mismatch negativity time-window (MMN) and the subsequent difference-ASSRs were determined and compared. The results revealed an MMN generated by a complex neural network including the right parietal lobe and the left middle frontal gyrus. Furthermore, difference-ASSR was generated in the paracentral gyrus. Additionally, psychophysical measures showed no perceptual difference between the standard- and deviant-beats when isolated by noise. These results suggest that the auditory periphery has an important contribution to novelty detection already at sub-cortical level. Overall, the present findings support the notion of hierarchically organized acoustic novelty detection system.

Tones and numbers: a combined EEG-MEG study on the effects of musical expertise in magnitude comparisons of audiovisual stimuli.

This study investigated the cortical responses underlying magnitude comparisons of multisensory stimuli and examined the effect that musical expertise has in this process. The comparative judgments were based on a newly learned rule binding the auditory and visual stimuli within the context of magnitude comparisons: "the higher the pitch of the tone, the larger the number presented." The cortical responses were measured by simultaneous MEG\EEG recordings and a combined source analysis with individualized realistic head models was performed. Musical expertise effects were investigated by comparing musicians to non-musicians. Congruent audiovisual stimuli, corresponding to the newly learned rule, elicited activity in frontotemporal and occipital areas. In contrast, incongruent stimuli activated temporal and parietal regions. Musicians when compared with nonmusicians showed increased differences between congruent and incongruent stimuli in a prefrontal region, thereby indicating that music expertise may affect multisensory comparative judgments within a generalized representation of analog magnitude.

Playing and listening to tailor-made notched music: cortical plasticity induced by unimodal and multimodal training in tinnitus patients.

BACKGROUND. The generation and maintenance of tinnitus are assumed to be based on maladaptive functional cortical reorganization. Listening to modified music, which contains no energy in the range of the individual tinnitus frequency, can inhibit the corresponding neuronal activity in the auditory cortex. Music making has been shown to be a powerful stimulator for brain plasticity, inducing changes in multiple sensory systems. Using magnetoencephalographic (MEG) and behavioral measurements we evaluated the cortical plasticity effects of two months of (a) active listening to (unisensory) versus (b) learning to play (multisensory) tailor-made notched music in nonmusician tinnitus patients. Taking into account the fact that uni- and multisensory trainings induce different patterns of cortical plasticity we hypothesized that these two protocols will have different affects. RESULTS. Only the active listening (unisensory) group showed significant reduction of tinnitus related activity of the middle temporal cortex and an increase in the activity of a tinnitus-coping related posterior parietal area. CONCLUSIONS. These findings indicate that active listening to tailor-made notched music induces greater neuroplastic changes in the maladaptively reorganized cortical network of tinnitus patients while additional integration of other sensory modalities during training reduces these neuroplastic effects.

Exploring the neurofunctional impairments and cognitive biases concerning food and body related stimuli in anorexia nervosa: An integrated EEG and eye-tracking study protocol.

BACKGROUND: Patients with Anorexia Nervosa (AN) exhibit significant cognitive and neural disturbances compared to healthy individuals when processing food and body-related stimuli. These disturbances not only contribute to the manifestation and chronification of their pathological eating behaviour but also underscore the complex interplay of cognitive, emotional, and neurobiological factors in AN. However, the precise underlying cognitive and neural mechanisms of these disturbances remain a compelling area of investigation. METHODS: This study presents a protocol developed for conducting a cross-sectional quasi-experimental study using a mixed model ANOVA approach with a crossover design. Our participants will consist of 20 patients with an active diagnosis of AN, 20 Overweight/obese individuals, and 20 Healthy Controls (HCs) with a normal BMI. An integrated eye-tracking and EEG methodology will be used in conjunction, with the primary aim of assessing participants' cognitive and neural processing towards high and low-calorie food stimuli. On an exploratory level, by utilizing the same methods, the present study will also investigate AN patients' responses towards high weight, normal weight, low weight, and self-body pictures, as well as towards images from the International Affective Picture System (IAPS) characterized by elevated valence and arousal levels. Additionally, behavioural methods such as yes or no questions, and self-reported questionnaires will be administered. The EEG and eye-tracking data will be analysed at early (50-300 ms) and late (350-500 ms) time intervals. DISCUSSION: The investigation of the underlying cognitive and neural processes employed by patients with AN during the processing of food and body-related stimuli can help us develop a better understanding of the cognitive and neural mechanisms that contribute to the manifestation and maintenance of the disorder and assist in the development of more effective screening methods. ETHICAL APPROVAL AND CONSENT TO PARTICIPATE: Ethical approval for the study has been obtained by the Cyprus National Bioethics Committee on 27.04.2023 (ΕΕΒΚ/ΕΠ/2023/19), and by the University of Cyprus (20.02.2023). Written informed consent will be obtained from all participants.

Musical expertise induces audiovisual integration of abstract congruency rules.

Perception of everyday life events relies mostly on multisensory integration. Hence, studying the neural correlates of the integration of multiple senses constitutes an important tool in understanding perception within an ecologically valid framework. The present study used magnetoencephalography in human subjects to identify the neural correlates of an audiovisual incongruency response, which is not generated due to incongruency of the unisensory physical characteristics of the stimulation but from the violation of an abstract congruency rule. The chosen rule-"the higher the pitch of the tone, the higher the position of the circle"-was comparable to musical reading. In parallel, plasticity effects due to long-term musical training on this response were investigated by comparing musicians to non-musicians. The applied paradigm was based on an appropriate modification of the multifeatured oddball paradigm incorporating, within one run, deviants based on a multisensory audiovisual incongruent condition and two unisensory mismatch conditions: an auditory and a visual one. Results indicated the presence of an audiovisual incongruency response, generated mainly in frontal regions, an auditory mismatch negativity, and a visual mismatch response. Moreover, results revealed that long-term musical training generates plastic changes in frontal, temporal, and occipital areas that affect this multisensory incongruency response as well as the unisensory auditory and visual mismatch responses.

Effects of musical training and event probabilities on encoding of complex tone patterns.

BACKGROUND: The human auditory cortex automatically encodes acoustic input from the environment and differentiates regular sound patterns from deviant ones in order to identify important, irregular events. The Mismatch Negativity (MMN) response is a neuronal marker for the detection of sounds that are unexpected, based on the encoded regularities. It is also elicited by violations of more complex regularities and musical expertise has been shown to have an effect on the processing of complex regularities. Using magnetoencephalography (MEG), we investigated the MMN response to salient or less salient deviants by varying the standard probability (70%, 50% and 35%) of a pattern oddball paradigm. To study the effects of musical expertise in the encoding of the patterns, we compared the responses of a group of non-musicians to those of musicians. RESULTS: We observed significant MMN in all conditions, including the least salient condition (35% standards), in response to violations of the predominant tone pattern for both groups. The amplitude of MMN from the right hemisphere was influenced by the standard probability. This effect was modulated by long-term musical training: standard probability changes influenced MMN amplitude in the group of non-musicians only. CONCLUSION: This study indicates that pattern violations are detected automatically, even if they are of very low salience, both in non-musicians and musicians, with salience having a stronger impact on processing in the right hemisphere of non-musicians. Long-term musical training influences this encoding, in that non-musicians benefit to a greater extent from a good signal-to-noise ratio (i.e. high probability of the standard pattern), while musicians are less dependent on the salience of an acoustic environment.

The relationship between musical training and the processing of audiovisual correspondences: Evidence from a reaction time task.

Numerous studies have reported both cortical and functional changes for visual, tactile, and auditory brain areas in musicians, which have been attributed to long-term training induced neuroplasticity. Previous investigations have reported advantages for musicians in multisensory processing at the behavioural level, however, multisensory integration with tasks requiring higher level cognitive processing has not yet been extensively studied. Here, we investigated the association between musical expertise and the processing of audiovisual crossmodal correspondences in a decision reaction-time task. The visual display varied in three dimensions (elevation, symbolic and non-symbolic magnitude), while the auditory stimulus varied in pitch. Congruency was based on a set of newly learned abstract rules: "The higher the spatial elevation, the higher the tone", "the more dots presented, the higher the tone", and "the higher the number presented, the higher the tone", and accuracy and reaction times were recorded. Musicians were significantly more accurate in their responses than non-musicians, suggesting an association between long-term musical training and audiovisual integration. Contrary to what was hypothesized, no differences in reaction times were found. The musicians' advantage on accuracy was also observed for rule-based congruency in seemingly unrelated stimuli (pitch-magnitude). These results suggest an interaction between implicit and explicit processing-as reflected on reaction times and accuracy, respectively. This advantage was generalised on congruency in otherwise unrelated stimuli (pitch-magnitude pairs), suggesting an advantage on processes requiring higher order cognitive functions. The results support the notion that accuracy and latency measures may reflect different processes.

Towards a Digital Twin in Human Brain: Brain Tumor Detection Using K-Means.

Digital Twins come to revolutionize the ongoing procedures of healthcare industry, with their ability to stimulate and predict patients' diagnosis and treatment. In this paper a K-means based brain tumor detection algorithm and its 3D modelling design, both derived from MRI scans, are presented towards to the creation of the digital twin.

Tinnitus-frequency specific activity and connectivity: A MEG study.

Tinnitus pathophysiology has been associated with an atypical cortical network that involves functional changes in auditory and non-auditory areas. Numerous resting-state studies have replicated a tinnitus brain network to be significantly different from healthy-controls. Yet it is still unknown whether the cortical reorganization is attributed to the tinnitus frequency specifically or if it is frequency-irrelevant. Employing magnetoencephalography (MEG), the current study aimed to identify frequency-specific activity patterns by using an individual tinnitus tone (TT) and a 500 Hz-control tone (CT) as auditory stimuli, across 54 tinnitus patients. MEG data were analyzed in a data-driven approach employing a whole-head model in source space and in sources' functional connectivity. Compared to the CT, the event related source space analysis revealed a statistically significant response to TT involving fronto-parietal regions. The CT mainly involved typical auditory activation-related regions. A comparison of the cortical responses to a healthy control group that underwent the same paradigm rejected the alternative interpretation that the frequency-specific activation differences were due to the higher frequency of the TT. Overall, the results suggest frequency-specificity of tinnitus-related cortical patterns. In line with previous studies, we demonstrated a tinnitus-frequency specific network comprising left fronto-temporal, fronto-parietal and tempo-parietal junctions.

Does combined training of biofeedback and neurofeedback affect smoking status, behavior, and longitudinal brain plasticity?

Introduction: Investigations of biofeedback (BF) and neurofeedback (NF) training for nicotine addiction have been long documented to lead to positive gains in smoking status, behavior and to changes in brain activity. We aimed to: (a) evaluate a multi-visit combined BF/NF intervention as an alternative smoking cessation approach, (b) validate training-induced feedback learning, and (c) document effects on resting-state functional connectivity networks (rsFCN); considering gender and degree of nicotine dependence in a longitudinal design. Methods: We analyzed clinical, behavioral, and electrophysiological data from 17 smokers who completed five BF and 20 NF sessions and three evaluation stages. Possible neuroplastic effects were explored comparing whole-brain rsFCN by phase-lag index (PLI) for different brain rhythms. PLI connections with significant change across time were investigated according to different resting-state networks (RSNs). Results: Improvements in smoking status were observed as exhaled carbon monoxide levels, Total Oxidative Stress, and Fageström scores decreased while Vitamin E levels increased across time. BF/NF promoted gains in anxiety, self-esteem, and several aspects of cognitive performance. BF learning in temperature enhancement was observed within sessions. NF learning in theta/alpha ratio increase was achieved across baselines and within sessions. PLI network connections significantly changed across time mainly between or within visual, default mode and frontoparietal networks in theta and alpha rhythms, while beta band RSNs mostly changed significantly after BF sessions. Discussion: Combined BF/NF training positively affects the clinical and behavioral status of smokers, displays benefit in smoking harm reduction, plays a neuroprotective role, leads to learning effects and to positive reorganization of RSNs across time. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02991781.

The impact of musical training in symbolic and non-symbolic audiovisual judgements of magnitude.

Quantity estimation can be represented in either an analog or symbolic manner and recent evidence now suggests that analog and symbolic representation of quantities interact. Nonetheless, those two representational forms of quantities may be enhanced by convergent multisensory information. Here, we elucidate those interactions using high-density electroencephalography (EEG) and an audiovisual oddball paradigm. Participants were presented simultaneous audiovisual tokens in which the co-varying pitch of tones was combined with the embedded cardinality of dot patterns. Incongruencies were elicited independently from symbolic and non-symbolic modality within the audio-visual percept, violating the newly acquired rule that "the higher the pitch of the tone, the larger the cardinality of the figure." The effect of neural plasticity in symbolic and non-symbolic numerical representations of quantities was investigated through a cross-sectional design, comparing musicians to musically naïve controls. Individual's cortical activity was reconstructed and statistically modeled for a predefined time-window of the evoked response (130-170 ms). To summarize, we show that symbolic and non-symbolic processing of magnitudes is re-organized in cortical space, with professional musicians showing altered activity in motor and temporal areas. Thus, we argue that the symbolic representation of quantities is altered through musical training.