Arcuate Fasciculus Research Articles

Lesion-symptom mapping of language impairments in people with brain tumours: The influence of linguistic stimuli.

People with tumours in specific brain sites might face difficulties in tasks with different linguistic material. Previous lesion-symptom mapping studies (VLSM) demonstrated that people with tumours in posterior temporal regions have more severe linguistic impairments. However, to the best of our knowledge, preoperative performance and lesion location on tasks with different linguistic stimuli have not been examined. In the present study, we performed VLSM on 52 people with left gliomas to examine whether tumour distribution differs depending on the tasks of the Aachen Aphasia Test. The VLSM analysis revealed that single-word production (e.g. object naming) was associated with the inferior parietal lobe and that compound and sentence production were additionally associated with posterior temporal gyri. Word repetition was affected in people with tumours in inferior parietal areas, whereas sentence repetition was the only task to be associated with frontal regions. Subcortically, word and sentence production were found to be affected in people with tumours reaching the arcuate fasciculus, and compound production was primarily associated with tumours affecting the inferior longitudinal and inferior fronto-occipital fasciculus. Our work shows that tasks with linguistic stimuli other than single-word naming (e.g. compound and sentence production) relate to additional cortical and subcortical brain areas. At a clinical level, we show that tasks that target the same processes (e.g. repetition) can have different neural correlates depending on the linguistic stimuli used. Also, we highlight the importance of left temporoparietal areas.

Segmental Abnormalities of White Matter Microstructure in Primary Hypothyroidism Identified by Automated Fiber Quantification

Introduction: Hypothyroidism leads to impaired white matter (WM) integrity, associated with cognitive/neuropsychiatric dysfunction. However, the specific segmental abnormalities of the fibers remain unexplored. Therefore, this study aimed to investigate whether the damage of the WM is limited to a specific segment or the entire bundle via diffusion metrics using automated fiber quantification. Methods: A cross-sectional study was conducted on 31 hypothyroid patients and 28 healthy controls. Thyroid-related hormone levels, cognitive/neuropsychiatric function, and diffusion tensor image data were collected and analyzed. Correlation and random forest analyses were also performed. Results: The mean fractional anisotropy (FA) values were reduced at the fiber tract level. The mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were increased in several fiber tracts, i.e., cingulum cingulate (CC), anterior forceps of corpus callosum (CCF_A). Significant correlations were found between cognitive function and diffusion indicators such as the FA value of the left corticospinal tract and arcuate fasciculus (AF), the MD value of left CC, the RD value of left AF, the AD value of left CC, and CCF_A. The widespread microstructure disruption was spread on multiple specific segments of different tracts at the point-wise level. The random forest revealed that the accuracy of recognizing hypothyroid patients was 82.5%, with the anterior component of CCF_A having the most significant contribution. Conclusion: WM microstructural integrity impairments were found in multi-segments of the multiple fiber bundles in hypothyroidism, which might be a potential mechanism of the underlying neurocognitive decline and cerebral impairment. The CCF_A might serve as a neuro biomarker for early warning of cerebral impairment in hypothyroidism.

Arcuate Fasciculus Microstructure Predicts Alcohol Dependence Risk through Higher IQ.

IQ has been found to correlate with alcohol consumption, with a higher IQ being a risk for alcohol misuse. Furthermore, recent research has shown that the microstructure of the arcuate fasciculus is associated with IQ. This study therefore aimed to examine the association between the arcuate fasciculus microstructure, IQ, and alcohol dependence risk. In this study, we performed probabilistic tractography between Wernicke's and Broca's areas in the left and right hemispheres to examine the association of the arcuate fasciculus's integrity with IQ and alcohol dependence risk, using DTI data from 344 individuals. Data regarding IQ were obtained from the Wechsler Abbreviated Scale of Intelligence (WASI-II). Alcohol substance involvement (SI) score was derived using the National Institute on Drug Abuse (NIDA) Quick Screen and was used as an index for alcohol dependence risk. Both the left arcuate fasciculus and IQ were found to have a significant association with alcohol dependence risk. A mediation analysis revealed that this association between the left arcuate fasciculus microstructure and an alcohol dependence risk was mediated by IQ. It is suggested that the left arcuate fasciculus microstructure is associated with IQ which is associated with alcohol dependence risk. While alcohol consumption is known to be robustly toxic to the brain, the left arcuate fasciculus shows exceptional characteristics in which its microstructure integrity is positively associated with an alcohol dependence risk through higher IQ. Clinical implications are discussed.

Applicability of automated tractography during acute care stroke rehabilitation.

[Purpose] To assess the clinical applicability of a novel automated tractography tool named XTRACT during acute stroke rehabilitation. [Participants and Methods] Three patients with left hemisphere stroke were sampled. Diffusion tensor images were acquired on the second week, and automated tractography was then applied. Tractography images and fractional anisotropy (FA) values in the corticospinal tract (CST) and arcuate fasciculus (AF) were assessed in relation to hemiparesis and aphasia. [Results] Patient 1 was nearly asymptomatic; FA in the left CST was 0.610 and that in the AF was 0.509. Patient 2 had severe hemiparesis and mild motor aphasia. Tractography images of the CST and AF were blurred; FA in the left CST was 0.295 and that in the AF was 0.304. Patient 3 showed no hemiparesis or aphasia at initial assessment. Tractography image of the CST was intact but that of the AF was less clear; FA in the left CST was 0.586 and that in the AF was 0.338. Considering the less clear images of the AF and lower FA value in Patients 2 and 3, further examinations for aphasia were performed, which revealed agraphia. [Conclusion] Visualization and quantification of neural fibers using automated tractography promoted planning acute care rehabilitative treatment in patients with stroke.

Do naps benefit novel word learning? Developmental differences and white matter correlates.

Memory representations of newly learned words undergo changes during nocturnal sleep, as evidenced by improvements in explicit recall and lexical integration (i.e., after sleep, novel words compete with existing words during online word recognition). Some studies have revealed larger sleep-benefits in children relative to adults. However, whether daytime naps play a similar facilitatory role is unclear. We investigated the effect of a daytime nap (relative to wake) on explicit memory (recall/recognition) and lexical integration (lexical competition) of newly learned novel words in young adults and children aged 10-12 years, also exploring white matter correlates of the pre- and post-nap effects of word learning in the child group with diffusion weighted MRI. In both age groups, a nap maintained explicit memory of novel words and wake led to forgetting. However, there was an age group interaction when comparing change in recall over the nap: children showed a slight improvement whereas adults showed a slight decline. There was no evidence of lexical integration at any point. Although children spent proportionally more time in slow-wave sleep (SWS) than adults, neither SWS nor spindle parameters correlated with over-nap changes in word learning. For children, increased fractional anisotropy (FA) in the uncinate fasciculus and arcuate fasciculus were associated with the recognition of novel words immediately after learning, and FA in the right arcuate fasciculus was further associated with changes in recall of novel words over a nap, supporting the importance of these tracts in the word learning and consolidation process. These findings point to a protective role of naps in word learning (at least under the present conditions), and emphasize the need to better understand both the active and passive roles that sleep plays in supporting vocabulary consolidation over development.

Atypical development in white matter microstructures in ADHD: A longitudinal diffusion imaging study.

In cross-sectional studies, alterations in white matter microstructure are evident in children with attention-deficit/hyperactivity disorder (ADHD) but not so prominent in adults with ADHD compared to typically-developing controls (TDC). Moreover, the developmental trajectories of white matter microstructures in ADHD are unclear, given the limited longitudinal imaging studies that characterize developmental changes in ADHD vs. TDC. This longitudinal study acquired diffusion spectrum imaging (DSI) at two time points. The sample included 55 participants with ADHD and 61 TDC. The enrollment/first DSI age ranged from 7 to 18 years, with a five-year mean follow-up time. We examined time-by-diagnosis interaction on the generalized fractional anisotropy (GFA) of 45 white matter tracts, adjusting for confounding factors and correcting for multiple comparisons. We also tested whether the longitudinal changes of microstructures were associated with ADHD symptoms and attention performance in a computerized continuous performance test. Participants with ADHD showed more rapid development of GFA in the arcuate fasciculus, superior longitudinal fasciculus, frontal aslant tract, cingulum, inferior fronto-occipital fasciculus (IFOF), frontostriatal tract connecting the prefrontal cortex (FS-PFC), thalamic radiation, corticospinal tract, and corpus callosum. Within participants with ADHD, more rapid GFA increases in cingulum and FS-PFC were associated with slower decreases in inattention symptoms. In addition, in all participants, more rapid GFA increases in cingulum and IFOF were associated with greater improvement in attention performance. Our findings suggest atypical developmental trajectories of white matter tracts in ADHD, characterized by normalization and possible compensatory neuroplastic processes with age from childhood to early adulthood.

Neural correlates of verbal fluency revealed by longitudinal T1, T2 and FLAIR imaging in stroke

Diffusion-weighted imaging has been widely used in the research on post-stroke verbal fluency but acquiring diffusion data is not always clinically feasible. Achieving comparable reliability for detecting brain variables associated with verbal fluency impairments, based on more readily available anatomical, non-diffusion images (T1, T2 and FLAIR), enables clinical practitioners to have complementary neurophysiological information at hand to facilitate diagnosis and treatment of language impairment. Meanwhile, although the predominant focus in the stroke recovery literature has been on cortical contributions to verbal fluency, it remains unclear how subcortical regions and white matter disconnection are related to verbal fluency. Our study thus utilized anatomical scans of ischaemic stroke survivors (n = 121) to identify longitudinal relationships between subcortical volume, white matter tract disconnection, and verbal fluency performance at 3- and 12-months post-stroke. Subcortical grey matter volume was derived from FreeSurfer. We used an indirect probabilistic approach to quantify white matter disconnection in terms of disconnection severity, the proportion of lesioned voxel volume to the total volume of a tract, and disconnection probability, the probability of the overlap between the stroke lesion and a tract. These disconnection variables of each subject were identified based on the disconnectome map of the BCBToolkit. Using a linear mixed multiple regression method with 5-fold cross-validations, we correlated the semantic and phonemic fluency scores with longitudinal measurements of subcortical grey matter volume and 22 bilateral white matter tracts, while controlling for demographic variables (age, sex, handedness and education), total brain volume, lesion volume, and cortical thickness. The results showed that the right subcortical grey matter volume was positively correlated with phonemic fluency averaged over 3 months and 12 months. The finding generalized well on the test data. The disconnection probability of left superior longitudinal fasciculus II and left posterior arcuate fasciculus was negatively associated with semantic fluency only on the training data, but the result aligned with our previous study using diffusion scans in the same clinical population. In sum, our results presented evidence that routinely acquired anatomical scans can serve as a reliable source for deriving neural variables of post-stroke verbal fluency performance. The use of this method might provide an ecologically valid and more readily implementable analysis tool.

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.

Repetitive transcranial magnetic stimulation for hypokinetic dysarthria in Parkinson's disease enhances white matter integrity of the auditory-motor loop.

In our previous study, repeated sessions of repetitive transcranial magnetic stimulation (rTMS) over the auditory feedback area were shown to improve hypokinetic dysarthria (HD) in Parkinson's disease (PD) and led to changes in functional connectivity within the left-sided articulatory networks. We analyzed data from this previous study and assessed the effects of rTMS for HD in PD on the diffusion parameters of the left anterior arcuate fasciculus (AAF), which connects the auditory feedback area with motor regions involved in articulation. Patients were assigned to 10 sessions of real or sham 1-Hz stimulation over the right posterior superior temporal gyrus. Stimulation effects were evaluated using magnetic resonance diffusion tensor imaging and by a speech therapist using a validated tool (Phonetics score of the Dysarthric Profile) at baseline, immediately after 2 weeks of stimulation, and at follow-up visits at Weeks 6 and 10 after the baseline. Altogether, data from 33 patients were analyzed. A linear mixed model revealed significant time-by-group interaction (p= 0.006) for the relative changes of fractional anisotropy of the AAF; the value increases were associated with the temporal evolution of the Phonetics score (R= 0.367, p= 0.028) in the real stimulation group. Real rTMS treatment for HD in PD as compared to sham stimulation led to increases of white matter integrity of the auditory-motor loop during the 2-month follow-up period. The changes were related to motor speech improvements.

Speaking in gestures: Left dorsal and ventral frontotemporal brain systems underlie communication in conducting.

Conducting constitutes a well-structured system of signs anticipating information concerning the rhythm and dynamic of a musical piece. Conductors communicate the musical tempo to the orchestra, unifying the individual instrumental voices to form an expressive musical Gestalt. In a functional magnetic resonance imaging (fMRI) experiment, 12 professional conductors and 16 instrumentalists conducted real-time novel pieces with diverse complexity in orchestration and rhythm. For control, participants either listened to the stimuli or performed beat patterns, setting the time of a metronome or complex rhythms played by a drum. Activation of the left superior temporal gyrus (STG), supplementary and premotor cortex and Broca's pars opercularis (F3op) was shared in both musician groups and separated conducting from the other conditions. Compared to instrumentalists, conductors activated Broca's pars triangularis (F3tri) and the STG, which differentiated conducting from time beating and reflected the increase in complexity during conducting. In comparison to conductors, instrumentalists activated F3op and F3tri when distinguishing complex rhythm processing from simple rhythm processing. Fibre selection from a normative human connectome database, constructed using a global tractography approach, showed that the F3op and STG are connected via the arcuate fasciculus, whereas the F3tri and STG are connected via the extreme capsule. Like language, the anatomical framework characterising conducting gestures is located in the left dorsal system centred on F3op. This system reflected the sensorimotor mapping for structuring gestures to musical tempo. The ventral system centred on F3Tri may reflect the art of conductors to set this musical tempo to the individual orchestra's voices in a global, holistic way.

Dissociations in white matter tracts and neuropsychological findings in a 17 years old patient with Subacute sclerosing panencephalitis

The present multimodal diffusion tensor imaging and neuropsychological study investigated the integrity of the white matter fascicles in a 17 years-old patient diagnosed with subacute sclerosing panencephalitis (SSPE).A brief neuropsychological testing showed that word and pseudoword repetition, naming, semantic and phonological fluency, long-term memory, working memory were impaired.A review of the literature on Diffusion weighted imaging (DWI) and Diffusion Tensor Imaging (DTI) evidenced that, studies investigating the integrity of white matter in this condition being a rare disease, are very few. Significant differences (p < 0.05) were found between the fractional anisotropy (FA) values of the controls and the patient in the Superior Longitudinal fasciculus, the Inferior Longitudinal Fasciculus, the Inferior Fronto-Occipital Fasciculus, the Uncinate Fasciculus, and the Arcuate Fasciculus with lower values in the patient. No differences were found for the corticospinal tract. The number of streamlines was significantly lower in the patient, compared to controls, for the left Superior Longitudinal fasciculus, and for the left Uncinate fasciculus while for all the other fascicles, the number did not significantly differ from controls. DTI results were consistent with the patient’s cognitive profile showing impairments at repetition, at tasks tapping lexical-semantics and long-term memory / retrieval. Diffusion tensor imaging results indicate that there were diffuse alterations of the degree of anisotropic diffusion along the white matter tracts distributed in posterior-anterior direction. Differently, a selective sparing of this measure was observed along the white matter tract distributed in inferior-superior direction (the corticospinal fascicle).

White Matter Correlates of Domain-Specific Working Memory.

Prior evidence suggests domain-specific working memory (WM) buffers for maintaining phonological (i.e., speech sound) and semantic (i.e., meaning) information. The phonological WM buffer's proposed location is in the left supramarginal gyrus (SMG), whereas semantic WM has been related to the left inferior frontal gyrus (IFG), the middle frontal gyrus (MFG), and the angular gyrus (AG). However, less is known about the white matter correlates of phonological and semantic WM. We tested 45 individuals with left hemisphere brain damage on single word processing, phonological WM, and semantic WM tasks and obtained T1 and diffusion weighted neuroimaging. Virtual dissections were performed for each participants' arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), middle longitudinal fasciculus (MLF), and uncinate fasciculus (UF), which connect the proposed domain-specific WM buffers with perceptual or processing regions. The results showed that the left ILF, MLF, IFOF, and the direct segment of the AF were related to semantic WM performance. Phonological WM was related to both the left ILF and the MLF. This work informs our understanding of the white matter correlates of WM, especially semantic WM, which has not previously been investigated. In addition, this work helps to adjudicate between theories of verbal WM, providing some evidence for separate pathways supporting phonological and semantic WM.

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.

Tractography-based navigated TMS language mapping protocol.

This study explores the feasibility of implementing a tractography-based navigated transcranial magnetic stimulation (nTMS) language mapping protocol targeting cortical terminations of the arcuate fasciculus (AF). We compared the results and distribution of errors from the new protocol to an established perisylvian nTMS protocol that stimulated without any specific targeting over the entire perisylvian cortex. Sixty right-handed patients with language-eloquent brain tumors were examined in this study with one half of the cohort receiving the tractographybased protocol and the other half receiving the perisylvian protocol. Probabilistic tractography using MRtrix3 was performed for patients in the tractography-based group to identify the AF's cortical endpoints. nTMS mappings were performed and resulting language errors were classified into five psycholinguistic groups. Tractography and nTMS were successfully performed in all patients. The tractogram-based group showed a significantly higher median overall ER than the perisylvian group (3.8% vs. 2.9% p <.05). The median ER without hesitation errors in the tractogram-based group was also significantly higher than the perisylvian group (2.0% vs. 1.4%, p <.05). The ERs by error type showed no significant differences between protocols except in the no response ER, with a higher median ER in the tractogram-based group (0.4% vs. 0%, p <.05). Analysis of ERs based on the Corina cortical parcellation system showed especially high nTMS ERs over the posterior middle temporal gyrus (pMTG) in the perisylvian protocol and high ERs over the middle and ventral postcentral gyrus (vPoG), the opercular inferior frontal gyrus (opIFG) and the ventral precentral gyrus (vPrG) in the tractography-based protocol. By considering the white matter anatomy and performing nTMS on the cortical endpoints of the AF, the efficacy of nTMS in disrupting patients' object naming abilities was increased. The newly introduced method showed proof of concept and resulted in AF-specific ERs and noninvasive cortical language maps, which could be applied to additional fiber bundles related to the language network in future nTMS studies.

Altered diffusion tensor imaging (DTI) parameters in brain parenchyma after traumatic brain injury

Aim of studyTo evaluate the role of diffuse tensor imaging (DTI) in detecting structural alterations following TBI with persistent symptoms without findings on conventional structural imaging.MethodsThis was a prospective study that enrolled a total of 30 individuals (12 females and 18 males), 6 control with no history of trauma and 24 with previous history of trauma. All subjects underwent conventional brain MRI and DTI. The eigenvalues of the genue and splenium of corpus callosum (CC), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), corticospinal tract (CS), arcuate fasciculus (AF) were measured bilaterally in all cases using suitable region of interest and the fraction anisotropy (FA), mean diffusivity (MD), were calculated. FA and MD values were compared between patients and control subjects. Diagnostic accuracy was calculated for FA, MD and combined. Sensitivity and Specificity were determined from the curve and PPV, NPV and accuracy underwent calculation through cross-tabulation.ResultAs compared with controls, FA was significantly decreased and MD was significantly increased in genue and splenium of CC and CS. For the Combined FA & MD in differentiating cases with trauma there was statistically significant difference in SLF, AF, genue, splenium, ILF and CS as p value < 0.05.ConclusionsDTI parameters is a promising tool in the detection of subtle brain parenchymal changes in patients with TBI who have persistent symptoms and no evident abnormalities on conventional MRI. Furthermore combined use of FA and MD shows better diagnostic accuracy in differentiation between control and trauma patient.

Beyond the Dorsal Column Medial Lemniscus in Proprioception and Stroke: A White Matter Investigation.

Proprioceptive deficits are common following stroke, yet the white matter involved in proprioception is poorly understood. Evidence suggests that multiple cortical regions are involved in proprioception, each connected by major white matter tracts, namely: Superior Longitudinal Fasciculus (branches I, II and III), Arcuate Fasciculus and Middle Longitudinal Fasciculus (SLF I, SLF II, SLF III, AF and MdLF respectively). However, direct evidence on the involvement of these tracts in proprioception is lacking. Diffusion imaging was used to investigate the proprioceptive role of the SLF I, SLF II, SLF III, AF and MdLF in 26 participants with stroke, and seven control participants without stroke. Proprioception was assessed using a robotic Arm Position Matching (APM) task, performed in a Kinarm Exoskeleton robotic device. Lesions impacting each tract resulted in worse APM task performance. Lower Fractional Anisotropy (FA) was also associated with poorer APM task performance for the SLF II, III, AF and MdLF. Finally, connectivity data surrounding the cortical regions connected by each tract accurately predicted APM task impairments post-stroke. This study highlights the importance of major cortico-cortical white matter tracts, particularly the SLF III and AF, for accurate proprioception after stroke. It advances our understanding of the white matter tracts responsible for proprioception.

Predicting Post-Stroke Cognitive Impairment Using Lesion Location

<h3>Research Objectives</h3> To develop a model to predict specific cognitive impairments following stroke based on the lesion's white matter edge density and location with respect to the left posterior arcuate fasciculus. <h3>Design</h3> Retrospective observational cohort study. <h3>Setting</h3> University medical center, inpatient and outpatient. <h3>Participants</h3> 149 adults (> 18 years old at time of stroke) from the Iowa Lesion Patient Registry. Participants must have had a stroke, an MRI or CT with visible focal brain lesion, and a neuropsychological assessment completed at the medical center. The cohort was 50% female, predominantly White (83%), upper middle-aged (mean age of 59 years old), and had an average of 13 years of education. <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> Cognitive impairment was quantified using z-scores for the following neuropsychological assessments, selected based on completion by >50% of participants Trail Making Test B, five subtests of the Wechsler Adult Intelligence Scale-IV, Benton Visual Retention Test, Rey Auditory Verbal Learning Test, Complex Figure Test, and two subtests of the Boston Diagnostic Aphasia Examination. The proportion of impaired tests per participant was also calculated. Lesion overlap with the left posterior arcuate fasciculus (LPAF) and lesion edge density were determined by summation of voxels. <h3>Results</h3> There was a significant though small positive correlation between the proportion of impaired z-scores and lesion overlap with the LPAF (r = 0.33, p <.001), indicating that greater lesion overlap corresponds to impairment on a greater number of neuropsychological test scores. The correlation between edge density and proportion of impaired scores was small and borderline significant (r=0.17, p=0.05). For individual neuropsychological tests, participants with lesion overlap to the LPAF had significantly lower scores than non-overlap participants on the majority (10 of 16) of assessed scores, and edge density was significantly negatively correlated to 7 of the 16 test scores. <h3>Conclusions</h3> Lesion overlap with the left posterior arcuate fasciculus has the potential to be used as a predictive marker of cognitive impairment in a post-stroke cohort and may be a stronger measure of cognitive impairment than edge density. <h3>Author(s) Disclosures</h3> No disclosures.

Mechanisms of Cognitive Decline due to White Matter Lesions in Cognitively Intact Older Adults

AbstractBackgroundWhite matter hyperintensities (WMH) on FLAIR MRI are highly prevalent in older adults and are linked to cognitive deficits as well as dementia. Likely mechanisms underlying associations between WMH and cognitive deficits include widespread partial disconnection due to the diffuse nature of progressive WMH and/or tract‐specific disconnection syndromes. We used a virtual lesion approach to evaluate cognitive deficits in domains associated with three tracts: left arcuate fasciculus (LAF; verbal working memory), inferior longitudinal fasciculus (ILF; visual processing), and fornix (memory).MethodWMH were semi‐automatically segmented from FLAIR MRI data in 481 ADNI controls and applied as regions of avoidance for probabilistic fiber tracking on DTI data in 46 healthy older subjects from the Human Connectome Lifespan database. Correlations between overall WMH burden or individual tract disruption and global or tract‐domain‐specific cognitive tests were assessed. Tract disconnection was also compared in subgroups with enriched disruption of specific tracts with respect to global WMH burden, Amyloid beta deposition status, and best (&gt;Mean+1SD) versus worst (&lt;Mean‐1SD) test performance.ResultAll three tracts showed disconnections due to WMH and the mean tract disconnection increased significantly with overall WMH burden (ILF; p&lt;0.001, LAF: p&lt;0.001, Fornix; p=0.025) (Figure 1A). Also, both overall WMH burden and percent disconnection in ILF were associated with prolonged Trail A and Trail B times after correction for age and education (Table 1). In subgroup analyses, Amyloid beta positive status significantly moderated correlation of Trail B times with overall WMH burden (p=0.007) and ILF disconnection (p=0.020) (Figure 2). Subjects with enriched ILF disconnection (Figure 1B) also had prolonged Trail A times than the average group (34.3 vs 30.2, p=0.003). Based on cognitive tests performance, subjects with better scores on verbal category fluency or verbal logical memory tests had lower LAF (p=0.035) and fornix (Test I; p=0.003, Test II; 0.025) disconnection.ConclusionWhile overall WMH burden correlates with cognitive deficits in ADNI controls, significant correlations between specific tract disconnection and tract‐domain‐specific cognitive tests are also observed. Both mechanisms likely contribute to age‐associated cognitive decline. Furthermore, amyloid beta accumulation strengthens these relationships.

Language input in late infancy scaffolds emergent literacy skills and predicts reading related white matter development.

Longitudinal studies provide the unique opportunity to test whether early language provides a scaffolding for the acquisition of the ability to read. This study tests the hypothesis that parental language input during the first 2 years of life predicts emergent literacy skills at 5 years of age, and that white matter development observed early in the 3rd year (at 26 months) may help to account for these effects. We collected naturalistic recordings of parent and child language at 6, 10, 14, 18, and 24 months using the Language ENvironment Analysis system (LENA) in a group of typically developing infants. We then examined the relationship between language measures during infancy and follow-up measures of reading related skills at age 5 years, in the same group of participants (N = 53). A subset of these children also completed diffusion and quantitative MRI scans at age 2 years (N = 20). Within this subgroup, diffusion tractography was used to identify white matter pathways that are considered critical to language and reading development, namely, the arcuate fasciculus (AF), superior and inferior longitudinal fasciculi, and inferior occipital-frontal fasciculus. Quantitative macromolecular proton fraction (MPF) mapping was used to characterize myelin density within these separately defined regions of interest. The longitudinal data were then used to test correlations between early language input and output, white matter measures at age 2 years, and pre-literacy skills at age 5 years. Parental language input, child speech output, and parent-child conversational turns correlated with pre-literacy skills, as well as myelin density estimates within the left arcuate and superior longitudinal fasciculus. Mediation analyses indicated that the left AF accounted for longitudinal relationships between infant home language measures and 5-year letter identification and letter-sound knowledge, suggesting that the left AF myelination at 2 years may serve as a mechanism by which early language experience supports emergent literacy.

Brain microstructural changes and fatigue after COVID-19.

Fatigue and cognitive complaints are the most frequent persistent symptoms in patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to assess fatigue and neuropsychological performance and investigate changes in the thickness and volume of gray matter (GM) and microstructural abnormalities in the white matter (WM) in a group of patients with mild-to-moderate coronavirus disease 2019 (COVID-19). We studied 56 COVID-19 patients and 37 matched controls using magnetic resonance imaging (MRI). Cognition was assessed using Montreal Cognitive Assessment and Cambridge Neuropsychological Test Automated Battery, and fatigue was assessed using Chalder Fatigue Scale (CFQ-11). T1-weighted MRI was used to assess GM thickness and volume. Fiber-specific apparent fiber density (FD), free water index, and diffusion tensor imaging data were extracted using diffusion-weighted MRI (d-MRI). d-MRI data were correlated with clinical and cognitive measures using partial correlations and general linear modeling. COVID-19 patients had mild-to-moderate acute illness (95% non-hospitalized). The average period between real-time quantitative reverse transcription polymerase chain reaction-based diagnosis and clinical/MRI assessments was 93.3 (±26.4) days. The COVID-19 group had higher total CFQ-11 scores than the control group (p < 0.001). There were no differences in neuropsychological performance between groups. The COVID-19 group had lower FD in the association, projection, and commissural tracts, but no change in GM. The corona radiata, corticospinal tract, corpus callosum, arcuate fasciculus, cingulate, fornix, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus were involved. CFQ-11 scores, performance in reaction time, and visual memory tests correlated with microstructural changes in patients with COVID-19. Quantitative d-MRI detected changes in the WM microstructure of patients recovering from COVID-19. This study suggests a possible brain substrate underlying the symptoms caused by SARS-CoV-2 during medium- to long-term recovery.