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On page 1 showing 1 ~ 20 papers out of 28 papers

Differences in Cortical Representation and Structural Connectivity of Hands and Feet between Professional Handball Players and Ballet Dancers.

  • Jessica Meier‎ et al.
  • Neural plasticity‎
  • 2016‎

It is known that intensive training and expertise are associated with functional and structural neuroadaptations. Most studies, however, compared experts with nonexperts; hence it is, specifically for sports, unclear whether the neuroplastic adaptations reported are sport-specific or sport-general. Here we aimed at investigating sport-specific adaptations in professional handball players and ballet dancers by focusing on the primary motor and somatosensory grey matter (GM) representation of hands and feet using voxel-based morphometry as well as on fractional anisotropy (FA) of the corticospinal tract by means of diffusion tensor imaging-based fibre tractography. As predicted, GM volume was increased in hand areas of handball players, whereas ballet dancers showed increased GM volume in foot areas. Compared to handball players, ballet dancers showed decreased FA in both fibres connecting the foot and hand areas, but they showed lower FA in fibres connecting the foot compared to their hand areas, whereas handball players showed lower FA in fibres connecting the hand compared to their foot areas. Our results suggest that structural adaptations are sport-specific and are manifested in brain regions associated with the neural processing of sport-specific skills. We believe this enriches the plasticity research in general and extends our knowledge of sport expertise in particular.


Connectomic and Surface-Based Morphometric Correlates of Acute Mild Traumatic Brain Injury.

  • Patrizia Dall'Acqua‎ et al.
  • Frontiers in human neuroscience‎
  • 2016‎

Reduced integrity of white matter (WM) pathways and subtle anomalies in gray matter (GM) morphology have been hypothesized as mechanisms in mild traumatic brain injury (mTBI). However, findings on structural brain changes in early stages after mTBI are inconsistent and findings related to early symptoms severity are rare. Fifty-one patients were assessed with multimodal neuroimaging and clinical methods exclusively within 7 days following mTBI and compared to 53 controls. Whole-brain connectivity based on diffusion tensor imaging was subjected to network-based statistics, whereas cortical surface area, thickness, and volume based on T1-weighted MRI scans were investigated using surface-based morphometric analysis. Reduced connectivity strength within a subnetwork of 59 edges located predominantly in bilateral frontal lobes was significantly associated with higher levels of self-reported symptoms. In addition, cortical surface area decreases were associated with stronger complaints in five clusters located in bilateral frontal and postcentral cortices, and in the right inferior temporal region. Alterations in WM and GM were localized in similar brain regions and moderately-to-strongly related to each other. Furthermore, the reduction of cortical surface area in the frontal regions was correlated with poorer attentive-executive performance in the mTBI group. Finally, group differences were detected in both the WM and GM, especially when focusing on a subgroup of patients with greater complaints, indicating the importance of classifying mTBI patients according to severity of symptoms. This study provides evidence that mTBI affects not only the integrity of WM networks by means of axonal damage but also the morphology of the cortex during the initial post-injury period. These anomalies might be greater in the acute period than previously believed and the involvement of frontal brain regions was consistently pronounced in both findings. The dysconnected subnetwork suggests that mTBI can be conceptualized as a dysconnection syndrome. It remains unclear whether reduced WM integrity is the trigger for changes in cortical surface area or whether tissue deformations are the direct result of mechanical forces acting on the brain. The findings suggest that rapid identification of high-risk patients with the use of clinical scales should be assessed acutely as part of the mTBI protocol.


The hypothesis of neuronal interconnectivity as a function of brain size-a general organization principle of the human connectome.

  • Jürgen Hänggi‎ et al.
  • Frontiers in human neuroscience‎
  • 2014‎

Twenty years ago, Ringo and colleagues proposed that maintaining absolute connectivity in larger compared with smaller brains is computationally inefficient due to increased conduction delays in transcallosal information transfer and expensive with respect to the brain mass needed to establish these additional connections. Therefore, they postulated that larger brains are relatively stronger connected intrahemispherically and smaller brains interhemispherically, resulting in stronger functional lateralization in larger brains. We investigated neuronal interconnections in 138 large and small human brains using diffusion tensor imaging-based fiber tractography. We found a significant interaction between brain size and the type of connectivity. Structural intrahemispheric connectivity is stronger in larger brains, whereas interhemispheric connectivity is only marginally increased in larger compared with smaller brains. Although brain size and gender are confounded, this effect is gender-independent. Additionally, the ratio of interhemispheric to intrahemispheric connectivity correlates inversely with brain size. The hypothesis of neuronal interconnectivity as a function of brain size might account for shorter and more symmetrical interhemispheric transfer times in women and for empirical evidence that visual and auditory processing are stronger lateralized in men. The hypothesis additionally shows that differences in interhemispheric and intrahemispheric connectivity are driven by brain size and not by gender, a finding contradicting a recently published study. Our findings are also compatible with the idea that the more asymmetric a region is, the smaller the density of interhemispheric connections, but the larger the density of intrahemispheric connections. The hypothesis represents an organization principle of the human connectome that might be applied also to non-human animals as suggested by our cross-species comparison.


Tracking the microstructural properties of the main white matter pathways underlying speech processing in simultaneous interpreters.

  • Stefan Elmer‎ et al.
  • NeuroImage‎
  • 2019‎

Due to the high linguistic and cognitive demands placed on real-time language translation, professional simultaneous interpreters (SIs) have previously been proposed to serve as a reasonable model for evaluating experience-dependent brain properties. However, currently it is still unknown whether intensive language training during adulthood might be reflected in microstructural changes in language-related white matter pathways contributing to sound-to-meaning mapping, auditory-motor integration, and verbal memory functions. Accordingly, we used a fully automated probabilistic tractography algorithm and compared the white matter microstructure of the bilateral inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF), and arcuate fasciculus (AF, long and anterior segments) between professional SIs and multilingual control participants. In addition, we classically re-evaluated the three constitutional elements of the AF (long, anterior, and posterior segments) using a deterministic manual dissection procedure. Automated probabilistic tractography demonstrated overall reduced mean fractional anisotropy (FA) and increased radial diffusivity (RD) in SIs in the fiber tracts of the left hemisphere (LH). Furthermore, SIs exhibited reduced mean FA in the bilateral AF. However, according to manual dissection, this effect was limited to the anterior AF segment and accompanied by increased mean RD. Deterministic AF reconstruction also uncovered increased mean FA in the right and RD in the left long AF segment in SIs compared to controls. These results point to a relationship between simultaneous interpreting and white matter organization of pathways underlying speech and language processing in the language-dominant LH as well as of the AF.


Increased cortical surface area of the left planum temporale in musicians facilitates the categorization of phonetic and temporal speech sounds.

  • Stefan Elmer‎ et al.
  • Cortex; a journal devoted to the study of the nervous system and behavior‎
  • 2013‎

We measured musicians and non-musicians by using structural magnetic resonance imaging to investigate relationships between cortical features of the left planum temporale (PT) and the categorization of consonant-vowel (CV) syllables and their reduced-spectrum analogues. The present work is based on previous functional studies consistently showing that the left PT is particularly responsive to transient acoustic features in CV syllables and their reduced-spectrum analogues, and on striking evidence pointing to structural alterations of the left PT as a function of musicianship. By combining these two observations, we hypothesized to find that differences in cortical surface area (SA) and cortical thickness (CT) of the left PT in musicians may facilitate the categorization of fast-changing phonetic cues. Behavioural results indicated that musicians and non-musicians achieved a comparable performance in the categorization of CV syllables, whereas the musicians performed significantly better than the controls in the more demanding reduced-spectrum condition. This better behavioural performance corresponds to an increased cortical SA of the left PT in musicians compared to non-musicians. No differences in CT of the left PT were found between groups. In line with our predictions, we revealed a positive correlation between cortical SA of the left PT in musicians and the behavioural performance during the acoustically more demanding reduced-spectrum condition. Hence, we provide first evidence for a relationship between musical expertise, cortical SA of the left PT, and the processing of fast-changing phonetic cues.


Volumetric associations between uncinate fasciculus, amygdala, and trait anxiety.

  • Volker Baur‎ et al.
  • BMC neuroscience‎
  • 2012‎

Recent investigations of white matter (WM) connectivity suggest an important role of the uncinate fasciculus (UF), connecting anterior temporal areas including the amygdala with prefrontal-/orbitofrontal cortices, for anxiety-related processes. Volume of the UF, however, has rarely been investigated, but may be an important measure of structural connectivity underlying limbic neuronal circuits associated with anxiety. Since UF volumetric measures are newly applied measures, it is necessary to cross-validate them using further neural and behavioral indicators of anxiety.


Brain activity elicited by viewing pictures of the own virtually amputated body predicts xenomelia.

  • Silvia Oddo-Sommerfeld‎ et al.
  • Neuropsychologia‎
  • 2018‎

Xenomelia is a rare condition characterized by the persistent desire for the amputation of physically healthy limbs. Prior studies highlighted the importance of superior and inferior parietal lobuli (SPL/IPL) and other sensorimotor regions as key brain structures associated with xenomelia. We expected activity differences in these areas in response to pictures showing the desired body state, i.e. that of an amputee in xenomelia.


Cortical thickness of left Heschl's gyrus correlates with hearing acuity in adults - A surface-based morphometry study.

  • Pia Neuschwander‎ et al.
  • Hearing research‎
  • 2019‎

To date, research examining the relationship between brain structure and hearing acuity is sparse, especially given the context of a broad age range. To investigate this relationship, we applied an automated surface-based morphometry (SBM) approach (FreeSurfer) in this study to re-examine a sample of normal-hearing (n = 17) and hearing-impaired (n = 17) age- and education-matched adults, aged between 20 and 63 years (Alfandari et al., 2018). The SBM approach allows the disentanglement of cortical surface area (CSA) from cortical thickness (CT), the 2 independent constituents of cortical volume (CV). We extend the findings of Alfandari and colleagues by showing several clusters in auditory-related areas as well as in the left and right angular gyrus that showed reduced CT, CSA and CV in hearing-impaired compared to normal-hearing listeners. Nevertheless, none of the clusters found correlated significantly with hearing acuity, measured by pure-tone thresholds, in the 2 groups. An additional vertex-wise correlation analysis between hearing acuity and morphometric parameters over all participants revealed a single significant cluster encompassing the left Heschl's gyrus. Higher hearing thresholds were associated with a thinner cortex within this cluster. Our results imply that hearing impairment is associated with reduced thickness in primary and secondary auditory cortex regions, those regions especially involved in perceiving and processing relevant speech cues. This decrease was observed not only in older but also in younger and middle-aged adults, independent of age-related decline in the cognitive domain and age-dependent whole-brain atrophy. Further, the results show the value added when considering CV, CT and CSA separately, relative to previous studies which have solely relied on voxel-based morphometry to investigate brain structure and hearing acuity across the lifespan.


Processing demands upon cognitive, linguistic, and articulatory functions promote grey matter plasticity in the adult multilingual brain: Insights from simultaneous interpreters.

  • Stefan Elmer‎ et al.
  • Cortex; a journal devoted to the study of the nervous system and behavior‎
  • 2014‎

Until now, considerable effort has been made to determine structural brain characteristics related to exceptional multilingual skills. However, at least one important question has not yet been satisfactorily addressed in the previous literature, namely whether and to which extent the processing demands upon cognitive, linguistic, and articulatory functions may promote grey matter plasticity in the adult multilingual brain. Based on the premise that simultaneous interpretation is a highly demanding linguistic task that places strong demands on executive and articulatory functions, here we compared grey matter volumes between professional simultaneous interpreters (SI) and multilingual control subjects. Thereby, we focused on a specific set of a-priori defined bilateral brain regions that have previously been shown to support neurocognitional aspects of language control and linguistic functions in the multilingual brain. These regions are the cingulate gyrus, caudate nucleus, frontal operculum (pars triangularis and opercularis), inferior parietal lobe (IPL) (supramarginal and angular gyrus), and the insula. As a main result, we found reduced grey matter volumes in professional SI, compared to multilingual controls, in the left middle-anterior cingulate gyrus, bilateral pars triangularis, left pars opercularis, bilateral middle part of the insula, and in the left supramarginal gyrus (SMG). Interestingly, grey matter volume in left pars triangularis, right pars opercularis, middle-anterior cingulate gyrus, and in the bilateral caudate nucleus was negatively correlated with the cumulative number of interpreting hours. Hence, we provide first evidence for an expertise-related grey matter architecture that may reflect a composite of brain characteristics that were still present before interpreting training and training-related changes.


The multiple synaesthete E.S.: neuroanatomical basis of interval-taste and tone-colour synaesthesia.

  • Jürgen Hänggi‎ et al.
  • NeuroImage‎
  • 2008‎

Synaesthesia is the involuntary physical experience of a crossmodal linkage such as when hearing a tone evokes the additional sensation of seeing a colour. We previously described a professional musician with absolute pitch perception who experiences both different tastes in response to hearing different tone intervals (e.g., major third and sweet) and the more common tone-colour synaesthesia in which each particular tone is linked to a specific colour (e.g., C and red). One of the current theories of synaesthesia proposes that local crossactivation or disinhibition of feedback occurs because of increased connectivity between relevant brain areas. Based on diffusion tensor and T1-weighted magnetic resonance imaging we performed fractional anisotropy (FA) analysis, probabilistic fibre tractography, and voxel-based morphometry in the synaesthete E.S. compared with 17 professional musicians and 20 normal control subjects using voxel-wise z-score transformations. We report increased FA and volumetric white (WM) and grey matter (GM) peculiarities in E.S.'s auditory and gustatory areas, hence explaining the interval-taste synaesthesia. Probabilistic fibre tractography revealed hyperconnectivity in bilateral perisylvian-insular regions in the synaesthete E.S. Differences in FA and volumetric WM and GM alterations in visual areas might represent the neuroarchitectural foundation of the tone-colour synaesthesia. Still unknown are the causes of the structural alterations, although an X-chromosomal linked dominant trait has been suggested. Whether hyperconnectivity occurs due to a failure in neural pruning or even synaptic sprouting remains to be shown. Our findings might have implications for the understanding of multimodal integration and may encourage similar research into dysfunctional perceptual phenomenon such as hallucinations in schizophrenics or in Charles Bonnet syndrome.


The architecture of the golfer's brain.

  • Lutz Jäncke‎ et al.
  • PloS one‎
  • 2009‎

Several recent studies have shown practice-dependent structural alterations in humans. Cross-sectional studies of intensive practice of specific tasks suggest associated long-term structural adaptations. Playing golf at a high level of performance is one of the most demanding sporting activities. In this study, we report the relationship between a particular level of proficiency in playing golf (indicated by golf handicap level) and specific neuroanatomical features.


Longitudinal changes in cocaine intake and cognition are linked to cortical thickness adaptations in cocaine users.

  • Sarah Hirsiger‎ et al.
  • NeuroImage. Clinical‎
  • 2019‎

Cocaine use has been consistently associated with decreased gray matter volumes in the prefrontal cortex. However, it is unclear if such neuroanatomical abnormalities depict either pre-existing vulnerability markers or drug-induced consequences. Thus, this longitudinal MRI study investigated neuroplasticity and cognitive changes in relation to altered cocaine intake.


Strength of Structural and Functional Frontostriatal Connectivity Predicts Self-Control in the Healthy Elderly.

  • Jürgen Hänggi‎ et al.
  • Frontiers in aging neuroscience‎
  • 2016‎

Self-regulation refers to the successful use of executive functions and initiation of top-down processes to control one's thoughts, behavior, and emotions, and it is crucial to perform self-control. Self-control is needed to overcome impulses and can be assessed by delay of gratification (DoG) and delay discounting (DD) paradigms. In children/adolescents, good DoG/DD ability depends on the maturity of frontostriatal connectivity, and its decline in strength with advancing age might adversely affect self-control because prefrontal brain regions are more prone to normal age-related atrophy than other regions. Here, we aimed at highlighting the relationship between frontostriatal connectivity strength and DoG performance in advanced age. We recruited 40 healthy elderly individuals (mean age 74.0 ± 7.7 years) and assessed the DoG ability using the German version of the DoG test for adults in addition to the delay discounting (DD) paradigm. Based on diffusion-weighted and resting-state functional magnetic resonance imaging data, respectively, the structural and functional whole-brain connectome were reconstructed based on 90 different brain regions of interest in addition to a 12-node frontostriatal DoG-specific network and the resulting connectivity matrices were subjected to network-based statistics. The 90-nodes whole-brain connectome analyses revealed subnetworks significantly associated with DoG and DD with a preponderance of frontostriatal nodes involved suggesting a high specificity of the findings. Structural and functional connectivity strengths between the putamen, caudate nucleus, and nucleus accumbens on the one hand and orbitofrontal, dorsal, and ventral lateral prefrontal cortices on the other hand showed strong positive correlations with DoG and negative correlations with DD corrected for age, sex, intracranial volume, and head motion parameters. These associations cannot be explained by differences in impulsivity and executive functioning. This pattern of correlations between structural or functional frontostriatal connectivity strength and self-control suggests that, in addition to the importance of the frontostriatal nodes itself, the structural and functional properties of different connections within the frontostriatal network are crucial for self-controlled behaviors in the healthy elderly. Because high DoG/low DD is a significant predictor of willpower and wellbeing in the elderly population, interventions aiming at strengthening frontostriatal connectivity to strengthen self-controlled behavior are needed in the future.


Takotsubo syndrome: How the broken heart deals with negative emotions.

  • Carina Klein‎ et al.
  • NeuroImage. Clinical‎
  • 2020‎

Patients suffering from Takotsubo syndrome have a higher prevalence of anxiety and depressive disorders compared to those with acute myocardial infarction and might thus show impaired regulation and processing of emotions.


Anterior cingulate volume predicts response to psychotherapy and functional connectivity with the inferior parietal cortex in major depressive disorder.

  • Fabio Sambataro‎ et al.
  • European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology‎
  • 2018‎

In major depressive disorder (MDD), the anterior cingulate cortex (ACC) has been associated with clinical outcome as well as with antidepressant treatment response. Nonetheless, the association between individual differences in ACC structure and function and the response to cognitive behavioral therapy (CBT) is still unexplored. For this aim, twenty-five unmedicated patients with MDD were scanned with structural and resting state functional magnetic resonance imaging before the beginning of CBT treatment. ACC morphometry was correlated with clinical changes following psychotherapy. Furthermore, whole-brain resting state functional connectivity with the ACC was correlated with clinical measures. Greater volume in the left subgenual (subACC), the right pregenual (preACC), and the bilateral supragenual (supACC) predicted depressive symptoms improvement after CBT. Greater subACC volume was related to stronger functional connectivity with the inferior parietal cortex and dorsolateral prefrontal cortex. Stronger subACC-inferior parietal cortex connectivity correlated with greater adaptive rumination. Greater preACC volume was associated with stronger functional connectivity with the inferior parietal cortex and ventrolateral prefrontal cortex. In contrast, greater right supACC volume was related to lower functional connectivity with the inferior parietal cortex. These results suggest that ACC volume and its functional connectivity with the fronto-parietal cortex are associated with CBT response in MDD, and this may be mediated by adaptive forms of rumination. Our findings support the role of the subACC as a potential predictor for CBT response.


Disrupted longitudinal restoration of brain connectivity during weight normalization in severe anorexia nervosa.

  • Lisa-Katrin Kaufmann‎ et al.
  • Translational psychiatry‎
  • 2023‎

Altered intrinsic brain connectivity of patients with anorexia nervosa has been observed in the acute phase of the disorder, but it remains unclear to what extent these alterations recover during weight normalization. In this study, we used functional imaging data from three time points to probe longitudinal changes in intrinsic connectivity patterns in patients with severe anorexia nervosa (BMI ≤ 15.5 kg/m2) over the course of weight normalization. At three distinct stages of inpatient treatment, we examined resting-state functional connectivity in 27 women with severe anorexia nervosa and 40 closely matched healthy controls. Using network-based statistics and graph-theoretic measures, we examined differences in global network strength, subnetworks with altered intrinsic connectivity, and global network topology. Patients with severe anorexia nervosa showed weakened intrinsic connectivity and altered network topology which did not recover during treatment. The persistent disruption of brain networks suggests sustained alterations of information processing in weight-recovered severe anorexia nervosa.


A CYP46 T/C SNP modulates parahippocampal and hippocampal morphology in young subjects.

  • Jürgen Hänggi‎ et al.
  • Neurobiology of aging‎
  • 2011‎

There is evidence that brain cholesterol metabolism modulates the vulnerability for Alzheimer's disease (AD). Previous data showed that brain β-amyloid load in elderly subjects with the CYP46 (cholesterol 24S-hydroxylase) TT-positive genotype was higher than in CYP46 TT-negative elderly subjects. We investigated effects of the CYP46 T/C polymorphism on parahippocampal and hippocampal grey matter (GM) morphology in 81 young subjects using structural magnetic resonance imaging based morphometry. We found that young TT-homozygotes exhibited smallest and CC-homozygotes largest parahippocampal and hippocampal GM volumes with the volumes of the CT-heterozygotes ranging in between. Parahippocampal and hippocampal volumes were positively correlated with delayed memory performance in C-carriers and negatively with immediate memory performance in TT-homozygotes. It has been shown that the brain cholesterol metabolism in general modulates dendrite outgrowth, synaptogenesis, and neuron survival, and it was suggested that CYP46 indirectly influences β-amyloid metabolism. CYP46 C-carriers are privileged both in terms of β-amyloid metabolism and in terms of brain reserve due to their larger parahippocampal and hippocampal structures. The exact cellular mechanisms that translate the CYP46 allelic variation into volumetric brain differences in the parahippocampal gyrus and hippocampus are still unknown and need to be further investigated.


Prion protein M129V polymorphism affects retrieval-related brain activity.

  • Andreas Buchmann‎ et al.
  • Neuropsychologia‎
  • 2008‎

The prion protein Met129Val polymorphism has recently been related to human long-term memory with carriers of either the 129MM or the 129MV genotype recalling 17% more words than 129(VV) carriers at 24h following learning. Here, we sampled genotype differences in retrieval-related brain activity at 30min and 24h following learning. Furthermore, genotype groups were compared regarding grey matter concentrations and cognitive profiles. We used event-related functional magnetic resonance imaging (fMRI) during a word recognition task on 12 Met/Met carriers, 12 Val/Met carriers, and 12 Val/Val carriers. These groups were matched for retrieval performance, gender, age, education, and other memory-related genetic polymorphisms. Although retrieval performance was matched, Val carriers exhibited enhanced retrieval-related brain activity at 30min and 24h following learning. At both time lags, correlations between retrieval-related brain activity and retrieval success were negative for Val homozygotes (the more activity, the worse retrieval success), while correlations showed no significance or were positive for Met homozygotes and heterozygotes. These results suggest a less economic use of retrieval-related neural resources in Val relative to Met carriers. Furthermore, Val carriers exhibited higher neocortical grey matter concentrations compared to Met carriers. When controlling for grey matter concentration, genotype effects in retrieval-related brain activity remained significant. Val and Met carriers yielded comparable brain activations for correct rejections of non-studied words and for working memory, which speaks to the specificity of the genotype effect. Findings suggest that the prion protein Met129Val polymorphism affects neural plasticity following learning at a time-scale of minutes to hours.


Identification of individual subjects on the basis of their brain anatomical features.

  • Seyed Abolfazl Valizadeh‎ et al.
  • Scientific reports‎
  • 2018‎

We examined whether it is possible to identify individual subjects on the basis of brain anatomical features. For this, we analyzed a dataset comprising 191 subjects who were scanned three times over a period of two years. Based on FreeSurfer routines, we generated three datasets covering 148 anatomical regions (cortical thickness, area, volume). These three datasets were also combined to a dataset containing all of these three measures. In addition, we used a dataset comprising 11 composite anatomical measures for which we used larger brain regions (11LBR). These datasets were subjected to a linear discriminant analysis (LDA) and a weighted K-nearest neighbors approach (WKNN) to identify single subjects. For this, we randomly chose a data subset (training set) with which we calculated the individual identification. The obtained results were applied to the remaining sample (test data). In general, we obtained excellent identification results (reasonably good results were obtained for 11LBR using WKNN). Using different data manipulation techniques (adding white Gaussian noise to the test data and changing sample sizes) still revealed very good identification results, particularly for the LDA technique. Interestingly, using the small 11LBR dataset also revealed very good results indicating that the human brain is highly individual.


Structural and functional hyperconnectivity within the sensorimotor system in xenomelia.

  • Jürgen Hänggi‎ et al.
  • Brain and behavior‎
  • 2017‎

Xenomelia is a rare condition characterized by the persistent and compulsive desire for the amputation of one or more physically healthy limbs. We highlight the neurological underpinnings of xenomelia by assessing structural and functional connectivity by means of whole-brain connectome and network analyses of regions previously implicated in empirical research in this condition.


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