Inferior Longitudinal Fascicle Research Articles

Amyloid and tau pathology are associated with white matter properties in cognitively unimpaired older adults at risk of AD dementia

AbstractBackgroundWhite matter changes are hypothesized to be among the earliest changes occurring in the course of Alzheimer’s disease (AD). We investigated associations between AD pathology, namely amyloid and tau, and white matter microstructural changes in cognitively unimpaired individuals at risk of AD dementia. We expected higher levels of pathology to be related to lower free‐water‐corrected fractional anisotropy.MethodWe studied 223 cognitively normal older adults with PET and multi‐shell diffusion MRI from the PREVENT‐AD cohort. We first measured standardized uptake value ratios (SUVRs) in 40 brain regions for amyloid‐ß (Aß, i.e., lateral and medial prefrontal, parietal, lateral temporal, and cingulate cortical regions in both hemispheres) and 26 brain regions for tau (i.e., Braak stages I, III, and IV). We then used TractSeg, a deep learning framework, to segment 49 well‐established white matter bundles. We mapped free‐water‐corrected fractional anisotropy (FAT) in those bundles. Lastly, to explore the relationships between AD pathology and white matter microstructure across bundles, we applied two separate partial least squares analyses: one for Aß pathology and one for tau (Figure 1).ResultWe found one significant latent variable relating Aß pathology to FAT. Specifically, higher levels of Aß pathology were associated with the combination of higher levels of FAT within the rostral body of the uncinate fascicle and superior longitudinal fascicle (Figure 2A). We found two significant latent variables relating tau pathology to FAT for which higher levels of tau pathology were associated with elevated FAT within the uncinate fascicle, thalamo‐occipital bundle, optic radiation, inferior occipitofrontal fascicle, inferior longitudinal fascicle, middle longitudinal fascicle, etc. (Figure 2B).ConclusionIn cognitively unimpaired individuals at risk of AD, increased Aß and tau pathology were associated with higher levels of FAT in AD‐related bundles. These unexpected findings may suggest an inverted U‐shape pattern between AD pathology and FAT in the preclinical phase of AD for which FAT values would start by increasing before decreasing later in the course of the disease. This first increase might be a marker of early pathological processes such as neuroinflammation or swelling.

Language deficits in primary lateral sclerosis: cortical atrophy, white matter degeneration and functional disconnection between cerebral regions.

Primary lateral sclerosis (PLS) is traditionally regarded as a pure upper motor neuron disorder, but recent cases series have highlighted cognitive deficits in executive and language domains. A single-centre, prospective neuroimaging study was conducted with comprehensive clinical and genetic profiling. The structural and functional integrity of language-associated brain regions and networks were systematically evaluated in 40 patients with PLS in comparison to 111 healthy controls. The structural integrity of the arcuate fascicle, frontal aslant tract, inferior occipito-frontal fascicle, inferior longitudinal fascicle, superior longitudinal fascicle and uncinate fascicle was evaluated. Functional connectivity between the supplementary motor region and the inferior frontal gyrus and connectivitybetween Wernicke's and Broca's areas was also assessed. Cortical thickness reductions were observed in both Wernicke's and Broca's areas. Fractional anisotropy reduction was noted in the aslant tract and increased radical diffusivity (RD) identifiedin the aslanttract, arcuate fascicle and superior longitudinal fascicle in the left hemisphere. Functional connectivity was reduced along the aslant track, i.e. between the supplementary motor region and the inferior frontal gyrus, but unaffected between Wernicke's and Broca's areas. Cortical thickness alterations, structural and functional connectivity changes were also noted in the right hemisphere. Disease-burden in PLS is not confined to motor regions, but there is also a marked involvement of language-associated tracts, networks and cortical regions. Given the considerably longer survival in PLS compared to ALS, the impact of language impairment on the management of PLS needs to be carefully considered.

The involvement of language-associated networks, tracts, and cortical regions in frontotemporal dementia and amyotrophic lateral sclerosis: Structural and functional alterations.

Language deficits are cardinal manifestations of some frontotemporal dementia (FTD) phenotypes and also increasingly recognized in sporadic and familial amyotrophic lateral sclerosis (ALS). They have considerable social and quality-of-life implications, and adaptive strategies are challenging to implement. While the neuropsychological profiles of ALS-FTD phenotypes are well characterized, the neuronal underpinnings of language deficits are less well studied. A multiparametric, quantitative neuroimaging study was conducted to characterize the involvement of language-associated networks, tracts, and cortical regions with a panel of structural, diffusivity, and functional magnetic resonance imaging (MRI) metrics. Seven study groups were evaluated along the ALS-FTD spectrum: healthy controls (HC), individuals with ALS without cognitive impairment (ALSnci), C9orf72-negative ALS-FTD, C9orf72-positive ALS-FTD, behavioral-variant FTD (bvFTD), nonfluent variant primary progressive aphasia (nfvPPA), and semantic variant PPA (svPPA). The integrity of the Broca's area, Wernicke's area, frontal aslant tract (FAT), arcuate fascicle (AF), inferior occipitofrontal fascicle (IFO), inferior longitudinal fascicle (ILF), superior longitudinal fascicle (SLF), and uncinate fascicle (UF) was quantitatively evaluated. The functional connectivity (FC) between Broca's and Wernicke' areas and FC along the FAT was also specifically assessed. Patients with nfvPPA and svPPA exhibit distinctive patterns of gray and white matter degeneration in language-associated brain regions. Individuals with bvFTD exhibit Broca's area, right FAT, right IFO, and UF degeneration. The ALSnci group exhibits Broca's area atrophy and decreased FC along the FAT. Both ALS-FTD cohorts, irrespective of C9orf72 status, show bilateral FAT, AF, and IFO pathology. Interestingly, only C9orf72-negative ALS-FTD patients exhibit bilateral uncinate and right ILF involvement, while C9orf72-positive ALS-FTD patients do not. Language-associated tracts and networks are not only affected in language-variant FTD phenotypes but also in ALS and bvFTD. Language domains should be routinely assessed in ALS irrespective of the genotype.

Preoperative language tract integrity is a limiting factor in recovery from aphasia after glioma surgery

Aphasia can occur in a broad range of pathological conditions that affect cortical or subcortical structures. Here we test the hypothesis that white matter integrity of language pathways assessed by preoperative diffusion tensor imaging (DTI) is associated with language performance and its recovery after glioma resection. 27 patients with preoperative DTI were included. Segmentation of the arcuate fascicle (AF), the inferior fronto-occipital fascicle (IFOF), the inferior longitudinal fascicle (ILF), the superior longitudinal fascicle (SLF), and the uncinate fascicle (UF) was performed with a fully-connected neural network (FCNN, TractSeg). Median fractional anisotropy (FA) was extracted from the resulting volumes as surrogate marker for white matter integrity and tested for correlation with clinical parameters. After correction for demographic data and multiple testing, preoperative white matter integrity of the IFOF, the ILF, and the UF in the left hemisphere were independently and significantly associated with aphasia three months after surgery. Comparison between patients with and without aphasia three months after surgery revealed significant differences in preoperative white matter integrity of the left AF (p = 0.021), left IFOF (p = 0.015), left ILF (p = 0.003), left SLF (p = 0.001, p = 0.021, p = 0.043 for respective sub-bundles 1–3), left UF (p = 0.041) and the right AF (p = 0.027). Preoperative assessment of white matter integrity of the language network by time-efficient MRI protocols and FCNN-driven segmentation may assist in the evaluation of postoperative rehabilitation potential in glioma patients.

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.

Dimensions of Formal Thought Disorder and Their Relation to Gray- and White Matter Brain Structure in Affective and Psychotic Disorders.

Factorial dimensions and neurobiological underpinnings of formal thought disorders (FTD) have been extensively investigated in schizophrenia spectrum disorders (SSD). However, FTD are also highly prevalent in other disorders. Still, there is a lack of knowledge about transdiagnostic, structural brain correlates of FTD. In N = 1071 patients suffering from DSM-IV major depressive disorder, bipolar disorder, or SSD, we calculated a psychopathological factor model of FTD based on the SAPS and SANS scales. We tested the association of FTD dimensions with 3 T MRI measured gray matter volume (GMV) and white matter fractional anisotropy (FA) using regression and interaction models in SPM12. We performed post hoc confirmatory analyses in diagnostically equally distributed, age- and sex-matched sub-samples to test whether results were driven by diagnostic categories. Cross-validation (explorative and confirmatory) factor analyses revealed three psychopathological FTD factors: disorganization, emptiness, and incoherence. Disorganization was negatively correlated with a GMV cluster comprising parts of the middle occipital and angular gyri and positively with FA in the right posterior cingulum bundle and inferior longitudinal fascicle. Emptiness was negatively associated with left hippocampus and thalamus GMV. Incoherence was negatively associated with FA in bilateral anterior thalamic radiation, and positively with the hippocampal part of the right cingulum bundle. None of the gray or white matter associations interacted with diagnosis. Our results provide a refined mapping of cross-disorder FTD phenotype dimensions. For the first time, we demonstrated that their neuroanatomical signatures are associated with language-related gray and white matter structures independent of diagnosis.

Two different subcortical language networks supporting distinct Japanese orthographies: morphograms and phonograms.

Language systems worldwide are based on either morphograms or phonograms, but Japanese is unique in that uses a complicated combination of kanji (morphogram) and kana (phonogram) characters. The white matter networks associated with reading have been investigated previously but remain incompletely understood. In this study, we performed intraoperative language mapping under local anesthesia and postoperative language assessments of 53 consecutive patients who underwent awake craniotomy for surgical resection of cerebral glioma within the dominant temporal or parietal lobe. Six cases showing intraoperative dyslexia elicited by direct electrical stimulation (DES) were examined, and all cases showed transient symptoms of kanji or kana dyslexia during DES. We investigated the intraoperative positive mapping points localized near four white matter bundles: the arcuate fascicle, posterior superior longitudinal fascicle, inferior fronto-occipital longitudinal fascicle, and inferior longitudinal fascicle (ILF). The intraoperative DES distributions for kanji dyslexia were especially associated with the anterior-inferior side of the ILF. On the other hand, the DES points associated with kana dyslexia were localized on the posterior-superior side of the complex composed of these four tracts. These results suggest the presence of specific non-interfering networks that subserve the processes of reading morphograms and phonograms.

Blood pressure variability and brain neuroimaging in patients with type 2 diabetes

To analyse a role of BP (blood pressure) variability in shaping neuroplasticity in patients with type 2 diabetes mellitus (DM). The study enrolled 100 patients with type 2 DM divided according to the presence of cognitive impairment (CI) and 25 control subjects. Biochemical blood count, plasma osteopontin, 24-hour self-blood pressure monitoring (SBPM) and brain MRI were assessed. Patients with type 2 DM and CI had higher body mass index as well as glycated hemoglobin (HbA1c), glucose, alanine aminotransferase, osteopontin and hyperlipidemia (p≤0.05). There was a significant difference in all standard indices, patients with type 2 DM were classified as «non-dipper», and there were significantly higher values of the index of time and area of stay in the state of suprathreshold BP and BP variability at night, as well as the risk of latent arterial hypertension in CI. Neuroimaging assessment revealed decreased blood flow according to contrast and non-contrast perfusion in all parameters in cortical (especially the frontal lobe) and subcortical structures (predominantly in the shell region), and was associated with SMAD parameters. Mean systolic and diastolic BP during the day and night, as well as the variability index, also influenced the integrity between cortico-spinal tract, hook, inferior longitudinal and arcuate fascicles. The same parameters altered hippocampal metabolism in terms of N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr), Cho/Cr ratios. In patients with type 2 DM, BP variability contributes to CI through a proinflammatory mechanism (osteopontin) leading to brain neuroimaging abnormalities.

Deep brain stimulation in Parkinson's disease: analysis of brain fractional anisotropy differences in operated patients.

Deep brain stimulation (DBS) of the subthalamic nucleus is currently an evidence-based therapeutic option for motor symptoms in patients with Parkinson's disease (PD), although other non-motor symptoms can be affected by stimulation. Our objective is to evaluate the global changes in the connectivity of the large-scale structural network in PD patients that have obtained a benefit from subthalamic DBS. Retrospective study of 31 subjects: 7 PD patients with subthalamic DBS (group A), 12 age and gender-matched non-operated PD (B) and 12 healthy controls (C). All subjects had undergone a 1.5 T brain MRI with DTI. DICOM images were processed with the FSL5.0 software and TBSS tool. The study group comprised 23 men and 8 women. No statistically significant differences in age, gender, scores on the HandY scale and mean follow-up between group A and B were found, and in age and gender between groups A and C. Statistical analysis revealed differences in the fractional anisotropy of the different groups in certain areas: bilateral corticospinal tract, anterior thalamic radiations, bilateral fronto-occipital fascicle, both superior longitudinal fascicles, and left inferior longitudinal fascicle. In our series, PD patients treated with bilateral subthalamic DBS showed a significantly higher fractional anisotropy in widespread areas of the cerebral white matter; suggesting that neuromodulation produces connectivity changes in different neural networks.

Impairment and Plasticity of Language-Related White Matter in Patients With Brain Arteriovenous Malformations

Language dysfunction is rarely seen in patients with unruptured brain arteriovenous malformation (AVM) albeit the AVM nidus involving language areas, which provides a unique disease model to study language reorganization. The objective of this study was to investigate the impairment and reorganization patterns and characteristics of language-related white matter in AVMs located at different brain areas. Thirty-three patients with AVMs involving language areas were prospectively enrolled. Patients were categorized into 3 groups according to the lesion locations: the frontal (14 patients), temporal (15 patients), and parietal groups (4 patients). Thirty age- and sex-matched healthy controls were enrolled as comparison. All participants underwent diffusion tensor imaging scans, and automated fiber quantification method was applied to quantitatively study the difference of segmented language-related white matter connectivity between 3 AVM groups and control group. Language functions were normal in all subjects according to Western Aphasia Battery test. In the frontal group, fractional anisotropy (FA) value decreased in the left arcuate fascicle and increased in left superior longitudinal fasciculus and uncinate fascicle; in the temporal group, FA values decreased in left inferior fronto-occipital fascicle and inferior longitudinal fascicle and increased in right anterior thalamic radiation and uncinate fascicle; in the parietal group, FA values decreased in left arcuate fascicle and inferior longitudinal fascicle and increased in bilateral anterior thalamic radiations and uncinate fascicles and right inferior fronto-occipital fascicle. In fascicles with decreased FA values, the increase of radial diffusivity was common, and fascicles with increased FA values usually presented along with increased axial diffusivity values. Remodeling of language-related white matter occurs when traditional language areas are involved by AVM nidus, and its reorganization patterns vary with locations of AVM nidus. Fascicle impairment is mainly caused by the myelin deficits, and its plasticity may be dominated by the axon remodeling procedure.

Inferior Longitudinal Fascicle and Reading: Exploring Their Relationship Through a Brain Stimulation Case Study

Awake brain surgery allows for maximal tumor resection, while minimizing postoperative deficits, even when the tumor is located within eloquent brain regions. In the current study, we present the case of a patient who underwent awake craniotomy to remove a space-occupying lesion located at the left (dominant) temporal lobe. During subcortical mapping, electrical stimulation of the inferior longitudinal fasciculus caused severe errors (paralexias) on a semantic odd-word out task but not on other tasks that use different input routes and processes. The cognitive neuropsychological model for single word processing assisted us to associate a specific structure (inferior longitudinal fascicle [ILF]) with a specific cognitive process (i.e., access to the semantic system). Our results highlight the importance of subcortical fascicles in reading and agree with previous studies regarding the critical role of ILF in reading comprehension.

Benefit of Action Naming Over Object Naming for Visualization of Subcortical Language Pathways in Navigated Transcranial Magnetic Stimulation-Based Diffusion Tensor Imaging-Fiber Tracking.

Visualization of functionally significant subcortical white matter fibers is needed in neurosurgical procedures in order to avoid damage to the language network during resection. In an effort to achieve this, positive cortical points revealed during preoperative language mapping with navigated transcranial magnetic stimulation (nTMS) can be employed as regions of interest (ROIs) for diffusion tensor imaging (DTI) fiber tracking. However, the effect that the use of different language tasks has on nTMS mapping and subsequent DTI-fiber tracking remains unexplored. The visualization of ventral stream tracts with an assumed lexico-semantic role may especially benefit from ROIs delivered by the lexico-semantically demanding verb task, Action Naming. In a first step, bihemispheric nTMS language mapping was administered in 18 healthy participants using the standard task Object Naming and the novel task Action Naming to trigger verbs in a small sentence context. Cortical areas in which nTMS induced language errors were identified as language-positive cortical sites. In a second step, nTMS-based DTI-fiber tracking was conducted using solely these language-positive points as ROIs. The ability of the two tasks’ ROIs to visualize the dorsal tracts Arcuate Fascicle and Superior Longitudinal Fascicle, the ventral tracts Inferior Longitudinal Fascicle, Uncinate Fascicle, and Inferior Fronto-Occipital Fascicle, the speech-articulatory Cortico-Nuclear Tract, and interhemispheric commissural fibers was compared in both hemispheres. In the left hemisphere, ROIs of Action Naming led to a significantly higher fraction of overall visualized tracts, specifically in the ventral stream’s Inferior Fronto-Occipital and Inferior Longitudinal Fascicle. No difference was found between tracking with Action Naming vs. Object Naming seeds for dorsal stream tracts, neither for the speech-articulatory tract nor the inter-hemispheric connections. While the two tasks appeared equally demanding for phonological-articulatory processes, ROI seeding through the task Action Naming seemed to better visualize lexico-semantic tracts in the ventral stream. This distinction was not evident in the right hemisphere. However, the distribution of tracts exposed was, overall, mirrored relative to those in the left hemisphere network. In presurgical practice, mapping and tracking of language pathways may profit from these findings and should consider inclusion of the Action Naming task, particularly for lesions in ventral subcortical regions.

Lesion-symptom mapping of language impairments in patients suffering from left perisylvian gliomas

Brain tumors cause local structural impairments of the cerebral network. Moreover, brain tumors can also affect functional brain networks more distant from the lesion. In this study, we analyzed the impact of glioma WHO grade II-IV tumors on grey and white matter in relation to impaired language function. In a retrospective analysis of 60 patients, 14 aphasic and 46 non-aphasic, voxel-based lesion-symptom mapping (VLSM) was used to identify tumor induced lesions in grey (GM) and white matter (WM) related to patients’ performance in subtests of the Aachen Aphasia Test (AAT). Significant clusters were analyzed for atlas-based grey and white matter involvements in relation to different linguistic modalities.VLSM analysis indicated significant contribution of a posterior perisylvian cluster covering WM and GM to AAT performance averaged across subtests. When considering individual AAT subtests, a substantial overlap between significant clusters for analysis of the token test, picture naming and language comprehension results could be observed.The WM-cluster intersections reflect the overall importance of the perisylvian area in language function, similarly to GM participations. Especially the constant high percentages of Heschl's gyrus, superior temporal gyrus, inferior longitudinal and middle longitudinal fascicles, but also arcuate and inferior fronto-occipital fascicles highlight the importance of the posterior perisylvian area for language function.

Anatomy of nerve fiber bundles at micrometer-resolution in the vervet monkey visual system.

Although the primate visual system has been extensively studied, detailed spatial organization of white matter fiber tracts carrying visual information between areas has not been fully established. This is mainly due to the large gap between tracer studies and diffusion-weighted MRI studies, which focus on specific axonal connections and macroscale organization of fiber tracts, respectively. Here we used 3D polarization light imaging (3D-PLI), which enables direct visualization of fiber tracts at micrometer resolution, to identify and visualize fiber tracts of the visual system, such as stratum sagittale, inferior longitudinal fascicle, vertical occipital fascicle, tapetum and dorsal occipital bundle in vervet monkey brains. Moreover, 3D-PLI data provide detailed information on cortical projections of these tracts, distinction between neighboring tracts, and novel short-range pathways. This work provides essential information for interpretation of functional and diffusion-weighted MRI data, as well as revision of wiring diagrams based upon observations in the vervet visual system.

Altered diffusion in motor white matter tracts in psychosis patients with catatonia

Catatonia is a complex psychomotor symptom frequently observed in schizophrenia. Neural activity within the motor system is altered in catatonia. Likewise, white matter (WM) is also expected to be abnormal. The aim of this study was to test, if schizophrenia patients with catatonia show specific WM alterations. Forty-eight patients with schizophrenia and 43 healthy controls were included. Catatonia was currently present in 13 patients with schizophrenia. Tract-Based Spatial Statistics was used to test for differences in fractional anisotropy (FA) in the whole brain between the three groups. We detected a group effect (F-test) of WM within the corpus callosum (CC). In the t-test, patients with catatonia showed higher FA in many left lateralized WM clusters involved in motor behaviour compared to patients without catatonia, including the CC, internal and external capsule, superior longitudinal fascicle (SLF) and corticospinal tract (CST). Similarly, patients with catatonia showed also higher FA in the left internal capsule and left CST compared to healthy controls. In contrast, the group comparison between patients without catatonia and healthy controls revealed lower FA in many right lateralized clusters, comprising the CC, internal capsule, SLF, and inferior longitudinal fascicle in patients without catatonia. Our results are in line with the notion of an altered motor system in catatonia. Thus, our study provides evidence for increased WM connectivity, especially in motor tracts in schizophrenia patients with catatonia.

Prediction of Memory Impairment in Epilepsy Surgery by White Matter Diffusion

To analyze the relationship between cognitive performance and white matter integrity in patients with temporal lobe epilepsy (TLE) to establish radiologic criteria to help with patient selection for surgery. The study included 19 adults with temporal lobe epilepsy. A tractography analysis of fractional anisotropy and mean diffusivity (MD) of the following fascicles was performed: arcuate fascicle, cingulum, fornix, inferior fronto-occipital fascicle, inferior longitudinal fascicle, parahippocampal fibers of the cingulum, and uncinate fascicle. The Wechsler Memory Scale-Third Edition neuropsychological test was performed to evaluate short- and long-term verbal (Logical Memory I and II subtests) and nonverbal (Visual Reproduction I and II subtests) memory. Relationships between memory scores and diffusion were calculated. Lower Logical Memory I subtest scores were correlated with lower MD of the right inferior fronto-occipital fascicle, while lower Logical Memory II subtest scores were related to higher values of fractional anisotropy in bilateral cingulum, right uncinate, and right parahippocampal fibers of the cingulum and lower MD in left cingulum fascicle. Finally, lower values in Visual Reproduction I subtest scores were associated with lower values in MD in right cingulum and inferior fronto-occipital fascicles. Structural changes of some white matter tracts were associated with deterioration of both short- and long-term memory. These alterations were more associated with verbal memory than with nonverbal memory. These changes mainly consist of an increase in fractional anisotropy and a decrease in MD, which could be interpreted as reorganization phenomena. Diffusion tensor imaging could be a useful tool for cognitive assessment in surgical candidates with temporal lobe epilepsy who are not suitable for neuropsychological testing or in whom their results do not lead to definitive conclusions.

Microsurgical anatomy of the sagittal stratum.

The sagittal stratum (SS) is a critical neural crossroad traversed by several white matter tracts that connect multiple areas of the ipsilateral hemisphere. Scant information about the anatomical organization of this structure is available in literature. The goal of this study was to provide a detailed anatomical description of the SS and to discuss the functional implications of the findings when a surgical approach through this structure is planned. Five formalin-fixed human brains were dissected under the operating microscope by using the fiber dissection technique originally described by Ludwig and Klingler. The SS is a polygonal crossroad of associational fibers situated deep on the lateral surface of the hemisphere, medial to the arcuate/superior longitudinal fascicle complex, and laterally to the tapetal fibers of the atrium. It is organized in three layers: a superficial layer formed by the middle and inferior longitudinal fascicles, a middle layer corresponding to the inferior fronto-occipital fascicle, and a deep layer formed by the optic radiation, intermingled with fibers of the anterior commissure. It originates posteroinferiorly to the inferior limiting sulcus of the insula, contiguous with the fibers of the temporal stem, and ends into the posterior temporo-occipito-parietal cortex. The white matter fiber dissection reveals the tridimensional architecture of the SS and the relationship between its fibers. A detailed understanding of the anatomy of the SS is essential to decrease the operative risks when a surgical approach within this area is undertaken.

Associations between clinical outcome and tractography based on navigated transcranial magnetic stimulation in patients with language-eloquent brain lesions.

Navigated transcranial magnetic stimulation (nTMS) in combination with diffusion tensor imaging fiber tracking (DTI FT) is increasingly used to locate subcortical language-related pathways. The aim of this study was to establish nTMS-based DTI FT for preoperative risk stratification by evaluating associations between lesion-to-tract distances (LTDs) and aphasia and by determining a cut-off LTD value to prevent surgery-related permanent aphasia. Fifty patients with left-hemispheric, language-eloquent brain tumors underwent preoperative nTMS language mapping and nTMS-based DTI FT, followed by tumor resection. nTMS-based DTI FT was performed with a predefined fractional anisotropy (FA) of 0.10, 0.15, 50% of the individual FA threshold (FAT), and 75% FAT (minimum fiber length [FL]: 100 mm). The arcuate fascicle (AF), superior longitudinal fascicle (SLF), inferior longitudinal fascicle (ILF), uncinate fascicle (UC), and frontooccipital fascicle (FoF) were identified in nTMS-based tractography, and minimum LTDs were measured between the lesion and the AF and between the lesion and the closest other subcortical language-related pathway (SLF, ILF, UC, or FoF). LTDs were then associated with the level of aphasia (no/transient or permanent surgery-related aphasia, according to follow-up examinations). A significant difference in LTDs was observed between patients with no or only surgery-related transient impairment and those who developed surgery-related permanent aphasia with regard to the AF (FA = 0.10, p = 0.0321; FA = 0.15, p = 0.0143; FA = 50% FAT, p = 0.0106) as well as the closest other subcortical language-related pathway (FA = 0.10, p = 0.0182; FA = 0.15, p = 0.0200; FA = 50% FAT, p = 0.0077). Patients with surgery-related permanent aphasia showed the lowest LTDs in relation to these tracts. Thus, LTDs of ≥ 8 mm (AF) and ≥ 11 mm (SLF, ILF, UC, or FoF) were determined as cut-off values for surgery-related permanent aphasia. nTMS-based DTI FT of subcortical language-related pathways seems suitable for risk stratification and prediction in patients suffering from language-eloquent brain tumors. Thus, the current role of nTMS-based DTI FT might be expanded, going beyond the level of being a mere tool for surgical planning and resection guidance.

Uncovering the inferior fronto-occipital fascicle and its topological organization in non-human primates: the missing connection for language evolution.

Whether brain networks underlying the multimodal processing of language in humans are present in non-human primates is an unresolved question in primate evolution. Conceptual awareness in humans, which is the backbone of verbal and non-verbal semantic elaboration, involves intracerebral connectivity via the inferior fronto-occipital fascicle (IFOF). While non-human primates can communicate through visual information channels, there has been no formal demonstration that they possess a functional homologue of the human IFOF. Therefore, we undertook a post-mortem diffusion MRI tractography study in conjunction with Klingler micro-dissection to search for IFOF fiber tracts in brain of Old-World (vervet) monkeys. We found clear and concordant evidence from both techniques for the existence of bilateral fiber tracts connecting the frontal and occipital lobes. These tracts closely resembled the human IFOF with respect to trajectory, topological organization, and cortical terminal fields. Moreover, these fibers are clearly distinct from other bundles previously described in this region of monkey brain, i.e., the inferior longitudinal and uncinate fascicles, and the external and extreme capsules. This demonstration of an IFOF in brain of a species that diverged from the human lineage some 22millions years ago enhances our comprehension about the evolution of language and social behavior.

Relevance of brain lesion location for cognition in vascular mild cognitive impairment.

BackgroundVascular mild cognitive impairment (VMCI) is a potentially transitional state between normal aging and vascular dementia. The presence of macroscopic white matter lesions (WML) of moderate or severe extension on brain MRI is the hallmark of the VMCI.ObjectiveTo assess the clinical relevance of the frequency of WML in patients with VMCI independently of total lesion volume (LV).MethodsIn this multicenter study, we included 110 patients with VMCI (age: 74.3 ± 6.6 years; sex: 60 women). Cognitive assessment was performed with the VMCI-Tuscany Neuropsychological Battery, which allowed to identify four VMCI groups: amnestic single (n = 9) and multi-domain (n = 76), non-amnestic single- (n = 10) and multi-domain (n = 15). Distribution and frequency of WML on MRI FLAIR images were evaluated with lesion probability map (LPM). Voxelwise statistics was performed with nonparametric permutation tests, controlling for age, sex, slice thickness, center, magnetic field strength, total LV and head size (p < .01, family-wise error-corrected for multiple comparisons across space).ResultsLPM of the WML had a fairly symmetric and widespread distribution across brain. A higher frequency of WML along association tracts of the WM such as inferior longitudinal fascicle, inferior fronto-occipital fascicle and superior longitudinal fascicle, was correlated with worst cognitive scores at the Trail Making Test Part A and Copy of the Rey–Osterrieth Complex Figure. The non-amnestic groups showed a higher frequency of WML in the anterior cingulum and superior longitudinal fascicle close to the frontal gyrus.ConclusionsOur study showed that in patients with VMCI, independently of total LV, the higher frequency of lesions along association tracts of the WM, which mediate intrahemispheric long-range connectivity, is related with psychomotor speed and constructional praxis. Moreover, a prevalence of lesions in the frontal WM seems to characterize VMCI patients with involvement of non-amnestic domains.