Musicianship and Prominence of Interhemispheric Connectivity Determine Two Different Pathways to Atypical Language Dominance.

During infancy and adolescence, language develops from a predominantly interhemispheric control-through the corpus callosum (CC)-to a predominantly intrahemispheric control, mainly subserved by the left arcuate fasciculus (AF). Using multimodal neuroimaging, we demonstrate that human left-handers (both male and female) with an atypical language lateralization show a rightward participation of language areas from the auditory cortex to the inferior frontal cortex when contrasting speech to tone perception and an enhanced interhemispheric anatomical and functional connectivity. Crucially, musicianship determines two different structural pathways to this outcome. Nonmusicians present a relation between atypical lateralization and intrahemispheric underdevelopment across the anterior AF, hinting at a dysregulation of the ontogenetic shift from an interhemispheric to an intrahemispheric brain. Musicians reveal an alternative pathway related to interhemispheric overdevelopment across the posterior CC and the auditory cortex. We discuss the heterogeneity in reaching atypical language lateralization and the relevance of early musical training in altering the normal development of language cognitive functions.

Comparing human and chimpanzee temporal lobe neuroanatomy reveals modifications to human language hubs beyond the frontotemporal arcuate fasciculus.

The biological foundation for the language-ready brain in the human lineage remains a debated subject. In humans, the arcuate fasciculus (AF) white matter and the posterior portions of the middle temporal gyrus are crucial for language. Compared with other primates, the human AF has been shown to dramatically extend into the posterior temporal lobe, which forms the basis of a number of models of the structural connectivity basis of language. Recent advances in both language research and comparative neuroimaging invite a reassessment of the anatomical differences in language streams between humans and our closest relatives. Here, we show that posterior temporal connectivity via the AF in humans compared with chimpanzees is expanded in terms of its connectivity not just to the ventral frontal cortex but also to the parietal cortex. At the same time, posterior temporal regions connect more strongly to the ventral white matter in chimpanzees as opposed to humans. This pattern is present in both brain hemispheres. Additionally, we show that the anterior temporal lobe harbors a combination of connections present in both species through the inferior fronto-occipital fascicle and human-unique expansions through the uncinate and middle and inferior longitudinal fascicles. These findings elucidate structural changes that are unique to humans and may underlie the anatomical foundations for full-fledged language capacity.

Musical Sophistication and Multilingualism: Effects on Arcuate Fasciculus Characteristics.

The processing of auditory stimuli which are structured in time is thought to involve the arcuate fasciculus, the white matter tract which connects the temporal cortex and the inferior frontal gyrus. Research has indicated effects of both musical and language experience on the structural characteristics of the arcuate fasciculus. Here, we investigated in a sample of n = 84 young adults whether continuous conceptualizations of musical and multilingual experience related to structural characteristics of the arcuate fasciculus, measured using diffusion tensor imaging. Probabilistic tractography was used to identify the dorsal and ventral parts of the white matter tract. Linear regressions indicated that different aspects of musical sophistication related to the arcuate fasciculus' volume (emotional engagement with music), volumetric asymmetry (musical training and music perceptual abilities), and fractional anisotropy (music perceptual abilities). Our conceptualization of multilingual experience, accounting for participants' proficiency in reading, writing, understanding, and speaking different languages, was not related to the structural characteristics of the arcuate fasciculus. We discuss our results in the context of other research on hemispheric specializations and a dual-stream model of auditory processing.

Neuroanatomical correlates of musicianship in left-handers.

BACKGROUND: Left-handedness is a condition that reverses the typical left cerebral dominance of motor control to an atypical right dominance. The impact of this distinct control - and its associated neuroanatomical peculiarities - on other cognitive functions such as music processing or playing a musical instrument remains unexplored. Previous studies in right-handed population have linked musicianship to a larger volume in the (right) auditory cortex and a larger volume in the (right) arcuate fasciculus. RESULTS: In our study, we reveal that left-handed musicians (n = 55), in comparison to left-handed non-musicians (n = 75), exhibit a larger gray matter volume in both the left and right Heschl's gyrus, critical for auditory processing. They also present a higher number of streamlines across the anterior segment of the right arcuate fasciculus. Importantly, atypical hemispheric lateralization of speech (notably prevalent among left-handers) was associated to a rightward asymmetry of the AF, in contrast to the leftward asymmetry exhibited by the typically lateralized. CONCLUSIONS: These findings suggest that left-handed musicians share similar neuroanatomical characteristics with their right-handed counterparts. However, atypical lateralization of speech might potentiate the right audiomotor pathway, which has been associated with musicianship and better musical skills. This may help explain why musicians are more prevalent among left-handers and shed light on their cognitive advantages.

The importance of the dorsal branch of the arcuate fasciculus in phonological working memory.

Phonological working memory (PWM) is important for language learning and processing. The most studied language brain regions are the classical Broca's area on the inferior frontal gyrus and Wernicke's area on the posterior temporal region and their anatomical connection via the classic arcuate fasciculus (AF) referred to here as the ventral AF (AFv). However, areas on the middle frontal gyrus (MFG) are essential for PWM processes. There is also a dorsal branch of the AF (AFd) that specifically links the posterior temporal region with the MFG. Furthermore, there is the temporo-frontal extreme capsule fasciculus (TFexcF) that courses ventrally and links intermediate temporal areas with the lateral prefrontal cortex. The AFv, AFd and TFexcF were dissected virtually in the same participants who performed a PWM task in a functional magnetic resonance imaging study. The results showed that good performance on the PWM task was exclusively related to the properties of the left AFd, which specifically links area 8A (known to be involved in attentional aspects of executive control) with the posterior temporal region. The TFexcF, consistent with its known anatomical connection, was related to brain activation in area 9/46v of the MFG that is critical for monitoring the information in memory.

The cortical regions and white matter tracts underlying auditory comprehension in patients with primary brain tumor.

The comprehension of spoken language is one of the most essential language functions in humans. However, the neurological underpinnings of auditory comprehension remain under debate. Here we used multi-modal neuroimaging analyses on a group of patients with low-grade gliomas to localize cortical regions and white matter tracts responsible for auditory language comprehension. Region-of-interests and voxel-level whole-brain analyses showed that cortical areas in the posterior temporal lobe are crucial for language comprehension. The fiber integrity assessed with diffusion tensor imaging of the arcuate fasciculus and the inferior longitudinal fasciculus was strongly correlated with both auditory comprehension and the grey matter volume of the inferior temporal and middle temporal gyri. Together, our findings provide direct evidence for an integrated network of auditory comprehension whereby the superior temporal gyrus and sulcus, the posterior parts of the middle and inferior temporal gyri serve as auditory comprehension cortex, and the arcuate fasciculus and the inferior longitudinal fasciculus subserve as crucial structural connectivity. These findings provide critical evidence on the neural underpinnings of language comprehension.

The impact of patient factors and tumor characteristics on language neuroplasticity in left hemispheric diffuse gliomas prior to surgical resection.

PURPOSE: Language networks are reorganized during glioma growth, leading to varying language performance in patients with gliomas located in or around language-eloquent areas. Therefore, pre-treated language performance reflects the neuroplasticity potential. Different domains of language processing, such as speech expression, repetition, and comprehension, involving different neural networks. We analyzed the effects of patient factors and tumor characteristics on the pre-treated performance to investigate neuroplastic potential of different language domains. METHODS: Patient age, sex, education level, tumor grade, language pathway involvement, T1 contrast enhanced (C+), and FLAIR (T2) volume were selected as variables. The correlation with abnormal language performance was verified using univariate and multivariate logistic regression. RESULTS: In total, 104 left hemispheric glioma patients were enrolled in this study. 44% of patients had repetitive abnormalities, 34.9% had comprehensive abnormalities, and 32.1% had expressive abnormalities. The proportion of normal language performance was 60% in grade 2 and 3 gliomas and 16% in grade 4 gliomas. Tumor grade (p = 0.006) and T2 volume (p = 0.008) were associated with abnormal performance in the expressive domain, education level (p = 0.004) and T1 C+ volume (p = 0.049) in the repetitive domain, and education level (p = 0.013), T2 volume (p = 0.011), and tumor grade (p = 0.089) in the comprehensive domain. CONCLUSION: Different clinical and radiological factors affected the abnormal performance of the three language domains, indicating their functional connectivity and neuroplastic potential are inherently varied. The dynamic interactions between patient factors, tumor characteristics, and language processing should be considered when resecting left hemispheric gliomas.

Controversy over the temporal cortical terminations of the left arcuate fasciculus: a reappraisal.

The arcuate fasciculus has been considered a major dorsal fronto-temporal white matter pathway linking frontal language production regions with auditory perception in the superior temporal gyrus, the so-called Wernicke's area. In line with this tradition, both historical and contemporary models of language function have assigned primacy to superior temporal projections of the arcuate fasciculus. However, classical anatomical descriptions and emerging behavioural data are at odds with this assumption. On one hand, fronto-temporal projections to Wernicke's area may not be unique to the arcuate fasciculus. On the other hand, dorsal stream language deficits have been reported also for damage to middle, inferior and basal temporal gyri that may be linked to arcuate disconnection. These findings point to a reappraisal of arcuate projections in the temporal lobe. Here, we review anatomical and functional evidence regarding the temporal cortical terminations of the left arcuate fasciculus by incorporating dissection and tractography findings with stimulation data using cortico-cortical evoked potentials and direct electrical stimulation mapping in awake patients. First, we discuss the fibres of the arcuate fasciculus projecting to the superior temporal gyrus and the functional rostro-caudal gradient in this region where both phonological encoding and auditory-motor transformation may be performed. Caudal regions within the temporoparietal junction may be involved in articulation and associated with temporoparietal projections of the third branch of the superior longitudinal fasciculus, while more rostral regions may support encoding of acoustic phonetic features, supported by arcuate fibres. We then move to examine clinical data showing that multimodal phonological encoding is facilitated by projections of the arcuate fasciculus to superior, but also middle, inferior and basal temporal regions. Hence, we discuss how projections of the arcuate fasciculus may contribute to acoustic (middle-posterior superior and middle temporal gyri), visual (posterior inferior temporal/fusiform gyri comprising the visual word form area) and lexical (anterior-middle inferior temporal/fusiform gyri in the basal temporal language area) information in the temporal lobe to be processed, encoded and translated into a dorsal phonological route to the frontal lobe. Finally, we point out surgical implications for this model in terms of the prediction and avoidance of neurological deficit.

Lip movements enhance speech representations and effective connectivity in auditory dorsal stream.

Viewing speaker's lip movements facilitates speech perception, especially under adverse listening conditions, but the neural mechanisms of this perceptual benefit at the phonemic and feature levels remain unclear. This fMRI study addressed this question by quantifying regional multivariate representation and network organization underlying audiovisual speech-in-noise perception. Behaviorally, valid lip movements improved recognition of place of articulation to aid phoneme identification. Meanwhile, lip movements enhanced neural representations of phonemes in left auditory dorsal stream regions, including frontal speech motor areas and supramarginal gyrus (SMG). Moreover, neural representations of place of articulation and voicing features were promoted differentially by lip movements in these regions, with voicing enhanced in Broca's area while place of articulation better encoded in left ventral premotor cortex and SMG. Next, dynamic causal modeling (DCM) analysis showed that such local changes were accompanied by strengthened effective connectivity along the dorsal stream. Moreover, the neurite orientation dispersion of the left arcuate fasciculus, the bearing skeleton of auditory dorsal stream, predicted the visual enhancements of neural representations and effective connectivity. Our findings provide novel insight to speech science that lip movements promote both local phonemic and feature encoding and network connectivity in the dorsal pathway and the functional enhancement is mediated by the microstructural architecture of the circuit.

Damage to Broca's area does not contribute to long-term speech production outcome after stroke.

Broca's area in the posterior half of the left inferior frontal gyrus has long been thought to be critical for speech production. The current view is that long-term speech production outcome in patients with Broca's area damage is best explained by the combination of damage to Broca's area and neighbouring regions including the underlying white matter, which was also damaged in Paul Broca's two historic cases. Here, we dissociate the effect of damage to Broca's area from the effect of damage to surrounding areas by studying long-term speech production outcome in 134 stroke survivors with relatively circumscribed left frontal lobe lesions that spared posterior speech production areas in lateral inferior parietal and superior temporal association cortices. Collectively, these patients had varying degrees of damage to one or more of nine atlas-based grey or white matter regions: Brodmann areas 44 and 45 (together known as Broca's area), ventral premotor cortex, primary motor cortex, insula, putamen, the anterior segment of the arcuate fasciculus, uncinate fasciculus and frontal aslant tract. Spoken picture description scores from the Comprehensive Aphasia Test were used as the outcome measure. Multiple regression analyses allowed us to tease apart the contribution of other variables influencing speech production abilities such as total lesion volume and time post-stroke. We found that, in our sample of patients with left frontal damage, long-term speech production impairments (lasting beyond 3 months post-stroke) were solely predicted by the degree of damage to white matter, directly above the insula, in the vicinity of the anterior part of the arcuate fasciculus, with no contribution from the degree of damage to Broca's area (as confirmed with Bayesian statistics). The effect of white matter damage cannot be explained by a disconnection of Broca's area, because speech production scores were worse after damage to the anterior arcuate fasciculus with relative sparing of Broca's area than after damage to Broca's area with relative sparing of the anterior arcuate fasciculus. Our findings provide evidence for three novel conclusions: (i) Broca's area damage does not contribute to long-term speech production outcome after left frontal lobe strokes; (ii) persistent speech production impairments after damage to the anterior arcuate fasciculus cannot be explained by a disconnection of Broca's area; and (iii) the prior association between persistent speech production impairments and Broca's area damage can be explained by co-occurring white matter damage, above the insula, in the vicinity of the anterior part of the arcuate fasciculus.

The Microstructural Plasticity of the Arcuate Fasciculus Undergirds Improved Speech in Noise Perception in Musicians.

Musical training is thought to be related to improved language skills, for example, understanding speech in background noise. Although studies have found that musicians and nonmusicians differed in morphology of bilateral arcuate fasciculus (AF), none has associated such white matter features with speech-in-noise (SIN) perception. Here, we tested both SIN and the diffusivity of bilateral AF segments in musicians and nonmusicians using diffusion tensor imaging. Compared with nonmusicians, musicians had higher fractional anisotropy (FA) in the right direct AF and lower radial diffusivity in the left anterior AF, which correlated with SIN performance. The FA-based laterality index showed stronger right lateralization of the direct AF and stronger left lateralization of the posterior AF in musicians than nonmusicians, with the posterior AF laterality predicting SIN accuracy. Furthermore, hemodynamic activity in right superior temporal gyrus obtained during a SIN task played a full mediation role in explaining the contribution of the right direct AF diffusivity on SIN performance, which therefore links training-related white matter plasticity, brain hemodynamics, and speech perception ability. Our findings provide direct evidence that differential microstructural plasticity of bilateral AF segments may serve as a neural foundation of the cross-domain transfer effect of musical experience to speech perception amid competing noise.

Arcuate fasciculus architecture is associated with individual differences in pre-attentive detection of unpredicted music changes.

The mismatch negativity (MMN) is an event related brain potential (ERP) elicited by unpredicted sounds presented in a sequence of repeated auditory stimuli. The neural sources of the MMN have been previously attributed to a fronto-temporo-parietal network which crucially overlaps with the so-called auditory dorsal stream, involving inferior and middle frontal, inferior parietal, and superior and middle temporal regions. These cortical areas are structurally connected by the arcuate fasciculus (AF), a three-branch pathway supporting the feedback-feedforward loop involved in auditory-motor integration, auditory working memory, storage of acoustic templates, as well as comparison and update of those templates. Here, we characterized the individual differences in the white-matter macrostructural properties of the AF and explored their link to the electrophysiological marker of passive change detection gathered in a melodic multifeature MMN-EEG paradigm in 26 healthy young adults without musical training. Our results show that left fronto-temporal white-matter connectivity plays an important role in the pre-attentive detection of rhythm modulations within a melody. Previous studies have shown that this AF segment is also critical for language processing and learning. This strong coupling between structure and function in auditory change detection might be related to life-time linguistic (and possibly musical) exposure and experiences, as well as to timing processing specialization of the left auditory cortex. To the best of our knowledge, this is the first time in which the relationship between neurophysiological (EEG) and brain white-matter connectivity indexes using DTI-tractography are studied together. Thus, the present results, although still exploratory, add to the existing evidence on the importance of studying the constraints imposed on cognitive functions by the underlying structural connectivity.

Isolating the white matter circuitry of the dorsal language stream: Connectome-Symptom Mapping in stroke induced aphasia.

The application of ℓ1-regularized machine learning models to high-dimensional connectomes offers a promising methodology to assess clinical-anatomical correlations in humans. Here, we integrate the connectome-based lesion-symptom mapping framework with sparse partial least squares regression (sPLS-R) to isolate elements of the connectome associated with speech repetition deficits. By mapping over 2,500 connections of the structural connectome in a cohort of 71 stroke-induced cases of aphasia presenting with varying left-hemisphere lesions and repetition impairment, sPLS-R was trained on 50 subjects to algorithmically identify connectomic features on the basis of their predictive value. The highest ranking features were subsequently used to generate a parsimonious predictive model for speech repetition whose predictions were evaluated on a held-out set of 21 subjects. A set of 10 short- and long-range parieto-temporal connections were identified, collectively delineating the broader circuitry of the dorsal white matter network of the language system. The strongest contributing feature was a short-range connection in the supramarginal gyrus, approximating the cortical localization of area Spt, with parallel long-range pathways interconnecting posterior nodes in supramarginal and superior temporal cortex with anterior nodes in both ventral and-notably-in dorsal premotor cortex, respectively. The collective disruption of these pathways indexed repetition performance in the held-out set of participants, suggesting that these impairments might be characterized as a parietotemporal disconnection syndrome impacting cortical area Spt and its associated white matter circuits of the frontal lobe as opposed to being purely a disconnection of the arcuate fasciculus.

Delayed development of aphasia related to degeneration of the arcuate fasciculus in the dominant hemisphere nine years after the onset in a patient with intracerebral hemorrhage: a case report.

BACKGROUND: We report on a patient with an intracerebral hemorrhage (ICH), who showed delayed development of aphasia, which was demonstrated via follow up diffusion tensor tractography (DTT) to be related to neural degeneration of the arcuate fasciculus (AF). CASE PRESENTATION: A 51-year-old, right-handed male presented with right hemiparesis, which occurred at the onset of a spontaneous ICH in the left corona radiata and basal ganglia. Brain magnetic resonance images showed a hematoma in the left subcortical area at one month after onset and hemosiderin deposits in the left subcortical area at nine years after onset. At four weeks after onset, he exhibited severe aphasia, and Western Aphasia Battery (WAB) testing revealed an aphasia quotient in the 39.6 percentile (%ile). However, his aphasia improved to nearly a normal state, and at three months after onset, his aphasia quotient was in the 90.5 %ile. At approximately eight years after onset, he began to show aphasia, and his aphasia increased slowly with time resulting in a WAB aphasia quotient in the 12.5 %ile at nine years after onset. The integrity of the left AF over the hematoma was preserved on 1-month post-onset DTT. However, the middle portion of the left AF in the middle of the hemosiderin deposits showed discontinuation on 9-year post-onset DTT. The fractional anisotropy value of the left AF was higher on the 9-year post-onset DTT (0.48) than that on the 1-month post-onset DTT (0.35), whereas the mean diffusivity value was lower on the 9-year post-onset DTT (0.10) than that on the 1-month post-onset DTT (0.32). The fiber number of the left AF was decreased to 175 on the 9-year post-onset DTT from 239 on the 1-month post-onset DTT. CONCLUSIONS: We report on a patient with ICH who showed delayed development of aphasia, which appeared to be related to degeneration of the AF in the dominant hemisphere. Our results suggest that DTT would be useful in ruling out neural degeneration of the AF.

Relationships among language ability, the arcuate fasciculus and lesion volume in patients with putaminal hemorrhage: a diffusion tensor imaging study.

Relationships among language ability, arcuate fasciculus and lesion volume were investigated by use of diffusion tensor tractography in patients with putaminal hemorrhage. Thirty-three right-handed patients within six weeks of hemorrhage onset were recruited. Correlation of the aphasia quotient with subset (fluency, comprehension, repetition, naming) scores, diffusion tensor tractography parameters and lesion volume of patients, aphasia quotient (r = 0.446) with subset (naming: r = 0.489) score had moderate positive correlations with fractional anisotropy of the left arcuate fasciculus. The aphasia quotient subset (repetition) score had a strong positive correlation with fractional anisotropy of the left arcuate fasciculus (r = 0.520), whereas, aphasia quotient subset (fluency and comprehension) scores had no significant correlations with fractional anisotropy of the left arcuate fasciculus after Benjamini-Hochberg correction. Aphasia quotient (r = 0.668) with subset (fluency: r = 0.736, comprehension: r = 0.739, repetition: r = 0.649, naming: r = 0.766) scores had strong positive correlations with the tract volume of the left arcuate fasciculus and strong negative correlations with lesion volume (r = -0.521, fluency: r = -0.520, comprehension: r = -0.513, repetition: r = -0.518, naming: r = -0.562). Fractional anisotropy of the left arcuate fasciculus had a moderate negative correlation with lesion volume (r = -0.462), whereas the tract volume of the left arcuate fasciculus had a strong negative correlation with lesion volume (r = -0.700). According to the result of mediation analysis, tract volume of the left arcuate fasciculus fully mediated the effect of lesion volume on the aphasia quotient. Regarding the receiver operating characteristic curve, the lesion volume cut-off value was 29.17 cm3 and the area under the curve (0.74), sensitivity (0.77) and specificity (0.80) were higher than those of fractional anisotropy, tract volume and aphasia quotient cut-off values. It was found that level of language disability was related to lesion volume as well as to injury severity of arcuate fasciculus in the dominant hemisphere of patients with putaminal hemorrhage. In particular, the tract volume of the arcuate fasciculus in the dominant hemisphere fully mediated the effect of lesion volume on language ability. Additionally, a lesion volume of approximately 30 cm3 was helpful in discriminating arcuate fasciculus discontinuation in the dominant hemisphere.

What you learn & when you learn it: Impact of early bilingual & music experience on the structural characteristics of auditory-motor pathways.

Music and language engage the dorsal auditory pathway, linked by the arcuate fasciculus (AF). Sustained practice in these activities can modify brain structure, depending on length of experience but also age of onset (AoO). To study the impact of early experience on brain structure we manually dissected the AF in bilinguals with and without music training (MT) who differed in the AoO of their second language (L2), or MT. We found the usual left-greater-than-right asymmetry in the volume of the long segment (LS) of the AF across all groups. However, simultaneous exposure to two languages from birth enhanced this leftward asymmetry, while early start of MT (≤7) enhanced the right LS macrostructure, reducing the normative asymmetry. Thus, immersive exposure to an L2 in the first year of life can produce long-term plastic effects on the left LS, which is considered to be largely under genetic control, while deliberate music training in early childhood alters the right LS, whose structure appears more open to experience. These findings show that AoO of specific experience plays a key role in a complex gene-environment interaction model where normative brain maturation is differentially impacted by diverse intensive auditory-motor experiences at different points during development.

Intra- and interhemispheric white matter tract associations with auditory spatial processing: Distinct normative and aging effects.

Declining auditory spatial processing is hypothesized to contribute to the difficulty older adults have detecting, locating, and selecting a talker from among others in noisy listening environments. Though auditory spatial processing has been associated with several cortical structures, little is known regarding the underlying white matter architecture or how age-related changes in white matter microstructure may affect it. The arcuate fasciculus is a target for understanding age-related differences in auditory spatial attention based on normative spatial attention findings in humans. Similarly, animal and human clinical studies suggest that the corpus callosum plays a role in the cross-hemispheric integration of auditory spatial information important for spatial localization and attention. The current investigation used diffusion imaging to examine the extent to which age-group differences in the identification of spatially cued speech were accounted for by individual differences in the white matter microstructure of the right arcuate fasciculus and the corpus callosum. Higher right arcuate and callosal fractional anisotropy (FA) predicted better segregation and identification of spatially cued speech across younger and older listeners. Further, individual differences in callosal microstructure mediated age-group differences in auditory spatial processing. Follow-up analyses suggested that callosal tracts connecting left and right pre-frontal and posterior parietal cortex are particularly important for auditory spatial processing. The results are consistent with previous work in animals and clinical human samples and provide a cortical mechanism to account for age-related deficits in auditory spatial processing. Further, the results suggest that both intrahemispheric and interhemispheric mechanisms are involved in auditory spatial processing.

The ventral attention network: the mirror of the language network in the right brain hemisphere.

Resting-state functional MRI (RfMRI) analyses have identified two anatomically separable fronto-parietal attention networks in the human brain: a bilateral dorsal attention network and a right-lateralised ventral attention network (VAN). The VAN has been implicated in visuospatial cognition and, thus, potentially in the unilateral spatial neglect associated with right hemisphere lesions. Its parietal, frontal and temporal endpoints are thought to be structurally supported by undefined white matter tracts. We investigated the white matter tract connecting the VAN. We used three approaches to study the structural anatomy of the VAN: (a) independent component analysis on RfMRI (50 subjects), defining the endpoints of the VAN, (b) tractography in the same 50 healthy volunteers, with regions of interest defined by the MNI coordinates of cortical areas involved in the VAN used in a seed-based approach and (c) dissection, by Klingler's method, of 20 right hemispheres, for ex vivo studies of the fibre tracts connecting VAN endpoints. The VAN includes the temporoparietal junction and the ventral frontal cortex. The endpoints of the superior longitudinal fasciculus in its third portion (SLF III) and the arcuate fasciculus (AF) overlap with the VAN endpoints. The SLF III connects the supramarginal gyrus to the ventral portion of the precentral gyrus and the pars opercularis. The AF connects the middle and inferior temporal gyrus and the middle and inferior frontal gyrus. We reconstructed the structural connectivity of the VAN and considered it in the context if the pathophysiology of unilateral neglect and right hemisphere awake brain surgery.

Chronic disorders of consciousness: a case report with longitudinal evaluation of disease progression using 7 T magnetic resonance imaging.

BACKGROUND: Outcome prediction for patients with disorders of consciousness (DOC) is essential yet challenging. Evidence showed that patients with DOC lasting 1 year or longer after a brain injury were less likely to recover. However, the reasons why outcomes of DOC patients differ greatly remain unclear. With a variety of analytical methods and through quantitative behavioral assessments, we aimed to track the progression of a patient with severe brain injury, in order to advance our understanding of the underlying mechanisms of DOC. CASE PRESENTATION: We performed a longitudinal study for a 52-year-old male DOC patient who has remained in the state for 1.5 years with comprehensive rehabilitative therapies. The patient underwent 3 times of assessments of Coma Recovery Scale-Revised (CRS-R) and ultra-high-field 7 T magnetic resonance imaging (MRI). Both topologic properties and brain microstructure were analyzed to track disease progression. We observed dynamic increases of fiber densities with measurements at three time points (t1:1.5 M, t2:7.5 M t3:17.5 M). Specifically, fiber densities of the superior longitudinal fasciculus and arcuate fasciculus nerve fiber bundles improved mostly in the visual, verbal, and auditory subscales, which was consistent with the CRS-R scores. Moreover, the graph-theory analyses demonstrated that network topologic properties showed an improvement although the disease duration exceeded 1 year. CONCLUSIONS: DOC patients with a course longer than 1 year remain possible to improve, and including evaluation methods such as WM connectome analysis and graph theory could be potentially valuable for a more precise assessment of patients with a longer course of DOC.

Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics.

Ninety per cent of the human population has been right-handed since the Paleolithic, yet the brain signature and genetic basis of handedness remain poorly characterized. Here, we correlated brain imaging phenotypes from ∼9000 UK Biobank participants with handedness, and with loci found significantly associated with handedness after we performed genome-wide association studies (GWAS) in ∼400 000 of these participants. Our imaging-handedness analysis revealed an increase in functional connectivity between left and right language networks in left-handers. GWAS of handedness uncovered four significant loci (rs199512, rs45608532, rs13017199, and rs3094128), three of which are in-or expression quantitative trait loci of-genes encoding proteins involved in brain development and patterning. These included microtubule-related MAP2 and MAPT, as well as WNT3 and MICB, all implicated in the pathogenesis of diseases such as Parkinson's, Alzheimer's and schizophrenia. In particular, with rs199512, we identified a common genetic influence on handedness, psychiatric phenotypes, Parkinson's disease, and the integrity of white matter tracts connecting the same language-related regions identified in the handedness-imaging analysis. This study has identified in the general population genome-wide significant loci for human handedness in, and expression quantitative trait loci of, genes associated with brain development, microtubules and patterning. We suggest that these genetic variants contribute to neurodevelopmental lateralization of brain organization, which in turn influences both the handedness phenotype and the predisposition to develop certain neurological and psychiatric diseases.