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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.

Background and Purpose: Brain tumors can result in displacement or destruction of important white matter tracts such as the inferior fronto-occipital fascicle (IFOF). Diffusion tensor imaging (DTI) can assess the extent of this effect and potentially provide neurosurgeons with an accurate map to guide tumor resection; analyze IFOF displacement patterns in temporoinsular gliomas based on tumor grading and topography in the temporal lobe; and assess whether these patterns follow a predictable pattern, to assist in maximal tumor resection while preserving IFOF function., Methods: Thirty-four patients with temporal gliomas and available presurgical MRI were recruited. Twenty-two had insula infiltration. DTI deterministic region of interest (ROI)-based tractography was performed using commercial software. Tumor topographic imaging characteristics analyzed were as follows: location in the temporal lobe and extent of extratemporal involvement. Qualitative tractographic data obtained from directional DTI color maps included type of involvement (displaced/edematous-infiltrated/destroyed) and displacement direction. Quantitative tractographic data of ipsi- and contralateral IFOF included whole tract volume, fractional anisotropy, and fractional anisotropy of a 2-dimensional coronal ROI on the tract at the point of maximum tumor involvement., Results: The most common tract involvement pattern was edematous/infiltrative displacement. Displacement patterns depended on main tumor location in the temporal lobe and presence of insular involvement. All tumors showed superior displacement pattern. In lateral tumors, displacement tendency was medial. In medial tumors, displacement tendency was lateral. When we add insular involvement, the tendency was more medial displacement. A qualitative and quantitative assessment supported these results., Conclusions: IFOF displacement patterns are reproducible and suitable for temporoinsular gliomas presurgical planning., (© 2022 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

The presence of white matter lesions in patients with cerebral small vessel disease (SVD) is among the main causes of cognitive decline. We investigated the relation between white matter hyperintensity (WMH) locations and executive and language abilities in 442 SVD patients without dementia with varying burden of WMH. We used Stroop Word Reading, Stroop Color Naming, Stroop Color-Word Naming, and Category Fluency as language measures with varying degrees of executive demands. The Symbol Digit Modalities Test (SDMT) was used as a control task, as it measures processing speed without requiring language use or verbal output. A voxel-based lesion-symptom mapping (VLSM) approach was used, corrected for age, sex, education, and lesion volume. VLSM analyses revealed statistically significant clusters for tests requiring language use, but not for SDMT. Worse scores on all tests were associated with WMH in forceps minor, thalamic radiations and caudate nuclei. In conclusion, an association was found between WMH in a core frontostriatal network and executive-verbal abilities in SVD, independent of lesion volume and processing speed. This circuitry underlying executive-language functioning might be of potential clinical importance for elderly with SVD. More detailed language testing is required in future research to elucidate the nature of language production difficulties in SVD., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Primary progressive aphasia (PPA) is a clinical neurodegenerative syndrome with word finding problems as a core clinical symptom. Many aspects of word finding have been clarified in psycholinguistics using picture naming and a picture-word interference (PWI) paradigm, which emulates naming under contextual noise. However, little is known about how word finding depends on white-matter tract integrity, in particular, the atrophy of tracts located ventrally to the Sylvian fissure. To elucidate this question, we examined word finding in individuals with PPA and healthy controls employing PWI, tractography, and computer simulations using the WEAVER++ model of word finding. Twenty-three individuals with PPA and twenty healthy controls named pictures in two noise conditions. Mixed-effects modelling was performed on naming accuracy and reaction time (RT) and fixel-based tractography analyses were conducted to assess the relation between ventral white-matter integrity and naming performance. Naming RTs were longer for individuals with PPA compared to controls and, critically, individuals with PPA showed a larger noise effect compared to controls. Moreover, this difference in noise effect was differentially related to tract integrity. Whereas the noise effect did not depend much on tract integrity in controls, a lower tract integrity was related to a smaller noise effect in individuals with PPA. Computer simulations supported an explanation of this paradoxical finding in terms of reduced propagation of noise when tract integrity is low. By using multimodal analyses, our study indicates the significance of the ventral pathway for naming and the importance of RT measurement in the clinical assessment of PPA., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Apathy is the neuropsychiatric syndrome that correlates most highly with Huntington's disease progression, and, like early patterns of neurodegeneration, is associated with lesions to cortico-striatal connections. However, due to its multidimensional nature and elusive etiology, treatment options are limited., Objectives: To disentangle underlying white matter microstructural correlates across the apathy spectrum in Huntington's disease., Methods: Forty-six Huntington's disease individuals (premanifest (N = 22) and manifest (N = 24)) and 35 healthy controls were scanned at 3-tesla and underwent apathy evaluation using the short-Problem Behavior Assessment and short-Lille Apathy Rating Scale, with the latter being characterized into three apathy domains, namely emotional, cognitive, and auto-activation deficit. Diffusion tensor imaging was used to study whether individual differences in specific cortico-striatal tracts predicted global apathy and its subdomains., Results: We elucidate that apathy profiles may develop along differential timelines, with the auto-activation deficit domain manifesting prior to motor onset. Furthermore, diffusion tensor imaging revealed that inter-individual variability in the disruption of discrete cortico-striatal tracts might explain the heterogeneous severity of apathy profiles. Specifically, higher levels of auto-activation deficit symptoms significantly correlated with increased mean diffusivity in the right uncinate fasciculus. Conversely, those with severe cognitive apathy demonstrated increased mean diffusivity in the right frontostriatal tract and left dorsolateral prefrontal cortex to caudate nucleus tract., Conclusions: The current study provides evidence that white matter correlates associated with emotional, cognitive, and auto-activation subtypes may elucidate the heterogeneous nature of apathy in Huntington's disease, as such opening a door for individualized pharmacological management of apathy as a multidimensional syndrome in other neurodegenerative disorders., (Copyright © 2019. Published by Elsevier Inc.)

In the present study, we aimed to test the association between the correct function of the left ventral white matter pathways and semantic processing (dual stream models for language processing, Hickok & Poeppel, 2004), using a new set of language tasks during intraoperative electrical stimulation at white matter level. Additionally, we evaluated brain regions needed for correct performance on the different semantic tasks using lesion-symptom analyses (voxel lesion-symptom mapping and track-wise lesion analysis) in a sample of 62 candidates for the awake brain surgery. We found that electrical stimulation in the vicinity of the inferior longitudinal and inferior fronto-occipital fasciculi disturbed performance on semantic processing tasks. Individuals presented with significantly more semantic paraphasias during brain tumor resection than during the electrical stimulation at the cortex level. Track-wise analyses confirmed the role of these left ventral pathways in semantic processing: a significant relationship was observed between the probability of inferior fronto-occipital fasciculus disconnection/damage and the semantic matching tasks, as well as the number of semantic paraphasias in naming. Importantly, the same analyses for the total score of the Boston Naming Test confirmed significant relationships between this test score and the integrity of the inferior fronto-occipital, inferior longitudinal and uncinate fasciculi. This was further supported by the results of VLSM analyses showing a significant relationship between BNT and the presence of lesion within left middle and inferior temporal gyri. The present findings provide new intraoperative evidence for the role of the white-matter ventral pathways in semantic processing, while at the same time emphasizing the need to include a broader assessment of semantic-conceptual aspects during the awake neurosurgical intervention. This approach will ensure better preservation of functional tissue in the tumoral vicinity and therefore substantially diminish post-surgical language impairments., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

OBJECTIVE Subcortical electrical stimulation during brain surgery may allow localization of functionally crucial white matter fibers and thus tailoring of the tumor resection according to its functional limits. The arcuate fasciculus (AF) is a white matter bundle connecting frontal, temporal, and parietal cortical areas that is often disrupted by left brain lesions. It plays a critical role in several cognitive functions related to phonological processing, but current intraoperative monitoring methods do not yet allow mapping of this tract with sufficient precision. In the present study the authors aimed to test a new paradigm for the intraoperative monitoring of the AF. METHODS In this report, the authors studied 12 patients undergoing awake brain surgery for tumor resection with a related risk of AF damage. To preserve AF integrity and the cognitive processes sustained by this tract in the intraoperative context, the authors used real word repetition (WR) and nonword repetition (NWR) tasks as complements to standard picture naming. RESULTS Compared with the errors identified by WR or picture naming, the NWR task allowed the detection of subtle errors possibly related to AF alterations. Moreover, only 3 patients demonstrated phonological paraphasias in standard picture naming, and in 2 of these patients the paraphasias co-occurred with the total loss of WR and NWR ability. Before surgery, lesion volume predicted a patient's NWR performance. CONCLUSIONS The authors suggest that monitoring NWR intraoperatively may complement the standard naming tasks and could permit better preservation of the important language production functions subserved by the AF.

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. The most frequent pathologic finding in this condition is hippocampal sclerosis (HS). In addition, in a small proportion (14-23%) of refractory TLE patients, the presence of HS is bilateral. TLE involves grey matter (GM) and white matter (WM) abnormalities in a wide cortico-subcortical network. However, the impact of neuronal loss on specific WM fiber pathways and associated functional systems as well as seizure propagation pathways remains unclear. There is still much controversy regarding the role of the commissures (corpus callosum, hippocampal commissure and anterior commissure) in interhemispheric seizure propagation. This study aimed to investigate the integrity of WM interhemispheric connectivity in a singular sample of patients with TLE and bilateral HS using structural magnetic resonance imaging (MRI). We performed multimodal structural MRI [high resolution T1-weighted and diffusion tensor imaging (DTI)] analyses of seven patients with medically refractory TLE with bilateral HS, fourteen unilateral left TLE patients and fifteen matched healthy individuals. Whole-brain voxel-wise analysis techniques were used. These patients evidenced WM derangement [reduced fractional anisotropy (FA), increased mean diffusivity (MD) or reduced WM volume] in temporal and extratemporal tracks, but also in commissural pathways, compared to the unilateral left TLE patients and the control group. Presence of reduced FA or increased MD in the fornix, cingulum and uncinate fasciculus in addition to reduced WM volume in the fornix was also encountered. Neuropsychological assessment was performed without significant correlations with structural data. The current results support the idea that commissural pathways play a contributory role in interhemispheric TLE seizure propagation in bilateral HS and offer new perspectives about the long-term effects on interhemispheric connectivity associated with seizure propagation patterns in TLE patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The frontal aslant tract (FAT) is a recently described major connection between the preSMA and Broca's area, whose functional role remains undefined. In this study we examined a patient presenting a morphological overregularization strategy in a verb generation task during awake surgery. This specific language deficit coincided with brain tumor resection at the level of the left FAT. During the task execution the patient formed the non-existent verbs by applying a morphological derivation rule to the given nouns, instead of retrieving the appropriate verbs. DTI results confirmed left FAT damage. Neuropsychological follow-up showed that this morphological derivation impairment partially persisted after surgery, whereas the results on a wide spectrum of other language-related tasks remained satisfactory. Additionally, we compared the pre- and the post-operational fMRI activation maps for the same verb generation task. We discuss the potential role of the left FAT in the morphological derivation process and in lexical retrieval., (Copyright © 2015 Elsevier Inc. All rights reserved.)