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.

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.

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.

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.

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.

Putting music to trial: Consensus on key methodological challenges investigating music-based rehabilitation.

Major advances in music neuroscience have fueled a growing interest in music-based neurological rehabilitation among researchers and clinicians. Musical activities are excellently suited to be adapted for clinical practice because of their multisensory nature, their demands on cognitive, language, and motor functions, and music's ability to induce emotions and regulate mood. However, the overall quality of music-based rehabilitation research remains low to moderate for most populations and outcomes. In this consensus article, expert panelists who participated in the Neuroscience and Music VII conference in June 2021 address methodological challenges relevant to music-based rehabilitation research. The article aims to provide guidance on challenges related to treatment, outcomes, research designs, and implementation in music-based rehabilitation research. The article addresses how to define music-based rehabilitation, select appropriate control interventions and outcomes, incorporate technology, and consider individual differences, among other challenges. The article highlights the value of the framework for the development and evaluation of complex interventions for music-based rehabilitation research and the need for stronger methodological rigor to allow the widespread implementation of music-based rehabilitation into regular clinical practice.

Utilizing Co-Creative Principles to Develop an E-Learning Platform for Interprofessional Training on Tinnitus: The Erasmus+ Project Tin-TRAC.

Tinnitus treatment, diagnosis and management across Europe varies significantly. The lack of national clinical guidelines for tinnitus management in most European countries and the absence of a common language across all disciplines involved is reflected in the diversification of healthcare practices. Interprofessional Training for Tinnitus Researchers and Clinicians (Tin-TRAC) is an Erasmus+ project that aims to develop common educational ground in the form of an e-Learning platform, co-created by patients, researchers and clinicians, which is able to unify tinnitus diagnosis and treatment strategies across Europe. A pan-European thematic educational platform integrating the best practices and latest research achievements with regard to tinnitus diagnosis and management has the potential to act as a facilitator of the reduction of interdisciplinary and interregional practice diversification. A detailed analysis of the educational needs of clinicians and researchers across disciplines will be followed by the co-creative development of the curriculum. Reusable learning objects will incorporate the training contents and will be integrated in an open e-Learning platform. Tin-TRAC envisions that its output will answer the need to create a common language across the clinicians and researchers of different disciplines that are involved in tinnitus management, and reduce patients' prolonged suffering, non-adherence and endless referral trajectories.

Interaction within and between cortical networks subserving multisensory learning and its reorganization due to musical expertise.

Recent advancements in the field of network science allow us to quantify inter-network information exchange and model the interaction within and between task-defined states of large-scale networks. Here, we modeled the inter- and intra- network interactions related to multisensory statistical learning. To this aim, we implemented a multifeatured statistical learning paradigm and measured evoked magnetoencephalographic responses to estimate task-defined state of functional connectivity based on cortical phase interaction. Each network state represented the whole-brain network processing modality-specific (auditory, visual and audiovisual) statistical learning irregularities embedded within a multisensory stimulation stream. The way by which domain-specific expertise re-organizes the interaction between the networks was investigated by a comparison of musicians and non-musicians. Between the modality-specific network states, the estimated connectivity quantified the characteristics of a supramodal mechanism supporting the identification of statistical irregularities that are compartmentalized and applied in the identification of uni-modal irregularities embedded within multisensory stimuli. Expertise-related re-organization was expressed by an increase of intra- and a decrease of inter-network connectivity, showing increased compartmentalization.

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.

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.

Varenicline administration for smoking cessation may reduce apnea hypopnea index in sleep apnea patients.

OBJECTIVE/BACKGROUND: Varenicline (VAR) is used for smoking cessation as it inhibits nicotine for binding on its receptors reducing nicotine dependence. VAR administration has been reported to affect sleep. The aim of this study was to evaluate possible changes in polysomnography (PSG) during VAR treatment (SmokeFreeBrain) in healthy smokers and smokers with obstructive sleep apnea (OSA). PATIENTS/METHODS: Thirty smokers (21 men) with 15.3 ± 10.2 PY, aged 32.8 ± 4.5 years, with BMI 28.6 ± 4 kg/m2, 16 without and 14 with OSA (92% males) were studied with PSG (Embletta MPR-Master) before treatment with VAR while smoking and 20-30 days during VAR administration and smoking cessation for at least 5 days. RESULTS: No significant differences were observed in sleep macro architecture (N1, N2, N3, REM, Sleep Efficiency, Total Sleep Time) during VAR treatment apart from prolongation of sleep latency, N2 and N3 latency in both smokers with and without OSA. Apnea hypopnea index (AHI) was reduced in OSA smokers and especially during REM with a borderline increase of arousal index (ArI) and reduction of sleep efficiency (SE). CONCLUSION: VAR treatment worsened sleep quality as a prolongation of sleep latency, N2 and N3 latency was observed. A marginal reduction of AHI was found in OSA patients, more significantly during REM. Due to the small sample size, further studies are needed to distinguish between the adverse reactions of VAR treatment and smoking cessation effects and to evaluate whether VAR may play a role in OSA treatment.

Computerized Music-Reading Intervention Improves Resistance to Unisensory Distraction Within a Multisensory Task, in Young and Older Adults.

Incoming information from multiple sensory channels compete for attention. Processing the relevant ones and ignoring distractors, while at the same time monitoring the environment for potential threats, is crucial for survival, throughout the lifespan. However, sensory and cognitive mechanisms often decline in aging populations, making them more susceptible to distraction. Previous interventions in older adults have successfully improved resistance to distraction, but the inclusion of multisensory integration, with its unique properties in attentional capture, in the training protocol is underexplored. Here, we studied whether, and how, a 4-week intervention, which targets audiovisual integration, affects the ability to deal with task-irrelevant unisensory deviants within a multisensory task. Musically naïve participants engaged in a computerized music reading game and were asked to detect audiovisual incongruences between the pitch of a song's melody and the position of a disk on the screen, similar to a simplistic music staff. The effects of the intervention were evaluated via behavioral and EEG measurements in young and older adults. Behavioral findings include the absence of age-related differences in distraction and the indirect improvement of performance due to the intervention, seen as an amelioration of response bias. An asymmetry between the effects of auditory and visual deviants was identified and attributed to modality dominance. The electroencephalographic results showed that both groups shared an increase in activation strength after training, when processing auditory deviants, located in the left dorsolateral prefrontal cortex. A functional connectivity analysis revealed that only young adults improved flow of information, in a network comprised of a fronto-parietal subnetwork and a multisensory temporal area. Overall, both behavioral measures and neurophysiological findings suggest that the intervention was indirectly successful, driving a shift in response strategy in the cognitive domain and higher-level or multisensory brain areas, and leaving lower level unisensory processing unaffected.

Comparing pure tone and narrow band noise to measure tonal tinnitus pitch-match frequency.

Tinnitus assessment is a precursor for individualized treatment and outcome measurement. In the recent years, several studies proposed two-alternative forced choice (2AFC) recursive matching as a method to determine tinnitus pitch-match frequency in a standardized reliable manner. Currently, pure tones are used as comparison stimuli to assess pitch-match frequency. In this study, we investigated the psychometric quality of the method comparing different sound types. We measured 20 chronic tinnitus patients in 2 runs on 3 days. To assess pitch-match frequency, we used 2AFC recursive matching and compared results between pure tones and narrow band noise (NBN). Test-retest reliability between runs and across sound types was high (α>0.9) and increased across days. Perceived matching difficulty and time to completion decreased over repetitions. Importantly, the difference of matched frequencies (DMF) between runs was significantly less for NBN. When patients matched the spectral bandwidth of a test tone to their tinnitus, consistency was high (α=0.86) and no patient indicated continuously a pure tone. In conclusion, we recommend using NBN sounds in 2AFC recursive matching to assess pitch-match frequency as a standardized reliable method. Such a procedure could be offered as smartphone-based application to monitor tinnitus symptomatology for individualized assessment and treatment outcome.

Computerized physical and cognitive training improves the functional architecture of the brain in adults with Down syndrome: A network science EEG study.

Understanding the neuroplastic capacity of people with Down syndrome (PwDS) can potentially reveal the causal relationship between aberrant brain organization and phenotypic characteristics. We used resting-state EEG recordings to identify how a neuroplasticity-triggering training protocol relates to changes in the functional connectivity of the brain's intrinsic cortical networks. Brain activity of 12 PwDS before and after a 10-week protocol of combined physical and cognitive training was statistically compared to quantify changes in directed functional connectivity in conjunction with psychosomatometric assessments. PwDS showed increased connectivity within the left hemisphere and from left-to-right hemisphere, as well as increased physical and cognitive performance. Our findings reveal a strong adaptive neuroplastic reorganization as a result of the training that leads to a less-random network with a more pronounced hierarchical organization. Our results go beyond previous findings by indicating a transition to a healthier, more efficient, and flexible network architecture, with improved integration and segregation abilities in the brain of PwDS. Resting-state electrophysiological brain activity is used here for the first time to display meaningful relationships to underlying Down syndrome processes and outcomes of importance in a translational inquiry. This trial is registered with ClinicalTrials.gov Identifier NCT04390321.

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.

Reduced pain and analgesic use after acoustic binaural beats therapy in chronic pain - A double-blind randomized control cross-over trial.

BACKGROUND: Binaural Beats (BB) consist of two artificial acoustic stimuli with different frequency, presented simultaneously but independently to each ear. The human brain perceives and synchronizes to this frequency difference (entrainment). Aim of this study was to test the hypothesis that brain entrainment to a lower function rhythm, with BB application, can decrease pain perception and analgesic medication use, in chronic pain patients. METHODS: In a double blind, randomized, cross-over trial, BB at 5Hz (theta rhythm) were applied for 30 minutes, under simultaneous electroencephalogram recordings, followed by liberal, on demand use by chronic pain patients for a week, compared to sham stimulation (SS). Pain as the main outcome (numeric scale, NRS), stress (STAI) and medication usage (defined daily doses, DDD) were assessed at baseline, 30 minutes and week's end. RESULTS: Perceived pain (NRS) was significantly reduced in BB intervention (5.6±2.3 to 3.4±2.6, p<0.001), compared to SS (5.2±2.1 to 4.8±2.3, p=0.78), during the first 30-minute phase, as well as at the week's end (to 3.9±2.5 compared to 5.5±2.6 respectively, p<0.001). The mean EEG theta power at 5Hz was significantly increased only during BB application. Stress was significantly reduced at 30 minutes in both interventions but remained reduced only in the BB group at the week's end. Analgesic medication consumption (DDD, g) during the week was significantly less in the BB intervention (3.9±3.7 vs. 4.6±4.1, p<0.05), while reporting equal to SS mean levels of pain. CONCLUSIONS: Acoustic BB reduced pain intensity, stress and analgesic use, compared to SS, in chronic pain patients. SIGNIFICANCE: This study provides evidence that theta rhythm binaural beats can alleviate pain intensity, both after a brief 30 minute and a longer one week on-demand intervention. The subsequent significant reduction in analgesic medication consumption in chronic pain patients' daily living could offer a valuable tool, augmenting the effect of existing pain therapies.

Auditory Categorization of Man-Made Sounds Versus Natural Sounds by Means of MEG Functional Brain Connectivity.

Previous neuroimaging studies have shown that sounds can be discriminated due to living-related or man-made-related characteristics and involve different brain regions. However, these studies have mainly provided source space analyses, which offer simple maps of activated brain regions but do not explain how regions of a distributed system are functionally organized under a specific task. In the present study, we aimed to further examine the functional connectivity of the auditory processing pathway across different categories of non-speech sounds in healthy adults, by means of MEG. Our analyses demonstrated significant activation and interconnection differences between living and man-made object sounds, in the prefrontal areas, anterior-superior temporal gyrus (aSTG), posterior cingulate cortex (PCC), and supramarginal gyrus (SMG), occurring within 80-120 ms post-stimulus interval. Current findings replicated previous ones, in that other regions beyond the auditory cortex are involved during auditory processing. According to the functional connectivity analysis, differential brain networks across the categories exist, which proposes that sound category discrimination processing relies on distinct cortical networks, a notion that has been strongly argued in the literature also in relation to the visual system.

Maladaptive alterations of resting state cortical network in Tinnitus: A directed functional connectivity analysis of a larger MEG data set.

The present study used resting state MEG whole-head recordings to identify how chronic tonal tinnitus relates to altered functional connectivity of brain's intrinsic cortical networks. Resting state MEG activity of 40 chronic tinnitus patients and 40 matched human controls was compared identifying significant alterations in intrinsic networks of the tinnitus population. Directed functional connectivity of the resting brain, at a whole cortex level, was estimated by means of a statistical comparison of the estimated phase Transfer Entropy (pTE) between the time-series of cortical activations, as reconstructed by LORETA. As pTE identifies the direction of the information flow, a detailed analysis of the connectivity differences between tinnitus patients and controls was possible. Results indicate that the group of tinnitus patients show increased connectivity from right dorsal prefrontal to right medial temporal areas. Our results go beyond previous findings by indicating that the role of the left para-hippocampal area is dictated by a modulation from dmPFC; a region that is part of the dorsal attention network (DAN), as well as implicated in the regulation of emotional processing. Additionally, this whole cortex analysis showed a crucial role of the left inferior parietal cortex, which modulated the activity of the right superior temporal gyrus, providing new hypotheses for the role of this area within the context of current tinnitus models. Overall, these maladaptive alterations of the structure of intrinsic cortical networks show a decrease in efficiency and small worldness of the resting state network of tinnitus patients, which is correlated to tinnitus distress.