Vestibular Agnosia is linked to abnormal functional brain networks

Activation of the peripheral vestibular apparatus simultaneously elicits a reflex vestibular nystagmus and the vestibular perception of self-motion (vestibular-motion perception) or vertigo. In a newly characterised condition called Vestibular Agnosia found in conditions with disrupted brain network connectivity, e.g. traumatic brain injury (TBI) or neurodegeneration (Parkinson’s Disease), the link between vestibular reflex and perception is uncoupled, such that, peripheral vestibular activation elicits a vestibular ocular reflex nystagmus but without vertigo. Using structural brain imaging in acute traumatic brain injury, we recently linked vestibular agnosia to postural imbalance via disrupted right temporal white-matter circuits (inferior longitudinal fasciculus), however no white-matter tracts were specifically linked to vestibular agnosia. Given the relative difficulty in localizing the neuroanatomical correlates of vestibular-motion perception, and compatible with current theories of human consciousness (viz. the Global Neuronal Workspace Theory), we postulate that vestibular-motion perception (vertigo) is mediated by the coordinated interplay between fronto-parietal circuits linked to whole-brain broadcasting of the vestibular signal of self-motion. We thus used resting state functional MRI (rsfMRI) to map functional brain networks and hence test our postulate of an anterior-posterior cortical network mediating vestibular agnosia. Whole-brain rsfMRI was acquired from 39 prospectively recruited acute TBI patients (and 37 matched controls) with preserved peripheral and reflex vestibular function, along with self-motion perceptual thresholds during passive yaw rotations in the dark, and posturography. Following quality control of the brain imaging, 25 TBI patients’ images were analyzed. We classified 11 TBI patients with vestibular agnosia and 14 without vestibular agnosia based on laboratory testing of self-motion perception. Using independent component analysis, we found altered functional connectivity within posterior (right superior longitudinal fasciculus) and anterior networks (left rostral prefrontal cortex) in vestibular agnosia. Regions of interest analyses showed both inter-hemispheric and intra-hemispheric (left anterior-posterior) network disruption in vestibular agnosia. Assessing the brain regions linked via right inferior longitudinal fasciculus, a tract linked to vestibular agnosia in unbalanced patients (but now controlled for postural imbalance), seed-based analyses showed altered connectivity between higher order visual cortices involved in motion perception and mid-temporal regions. In conclusion, vestibular agnosia in our patient group is mediated by multiple brain network dysfunction, involving primarily left frontal and bilateral posterior networks. Understanding the brain mechanisms of vestibular agnosia provide both an insight into the physiological mechanisms of vestibular perception as well as an opportunity to diagnose and monitor vestibular cognitive deficits in brain disease such as TBI and neurodegeneration linked to imbalance and spatial disorientation.

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.

Disrupted White Matter Integrity and Cognitive Functions in Amyloid-β Positive Alzheimer’s Disease with Concomitant Lobar Cerebral Microbleeds

Background: Lobar cerebral microbleeds (CMBs), which can impair white matter (WM), are often concomitant with definite Alzheimer’s disease (AD). Objective: To explore the features of cognitive impairments and WM disruptions due to lobar CMBs in patients with AD. Methods: There were 310 participants who underwent Florbetapir F18 (AV45) amyloid PET and susceptibility-weighted imaging. Participants with cognitive impairment and amyloid-β positive (ADCI) were included into three groups: ADCI without CMBs, with strictly lobar CMBs (SL-CMBs), and with mixed CMBs (M-CMBs). Tract-based spatial statistics were performed to detect the group differences in WM integrity. Results: There were 82 patients and 29 healthy controls finally included. A decreasing tendency in memory and executive performance can be found among HCs > no CMBs (n = 16) >SL-CMBs (n = 41) >M-CMBs (n = 25) group. Compared to no CMBs, M-CMBs group had significantly decreased fractional anisotropy in left anterior thalamic radiation (ATR), forceps major, forceps minor and inferior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus (IFOF), and superior longitudinal fasciculus. M-CMBs group also had lower fractional anisotropy in left ATR, IFOF, uncinate fasciculus, and forceps minor compared with SL-CMBs. Furthermore, analysis of Pearson correlation indicated damages in discrepant WMs were positively associated with impairment of memory, executive function, and attention. Conclusion: This study showed lobar CMBs had intensively aggravated cognitive impairments associated with extensive WM damages in definite AD. These findings highlight that lobar CMBs play an important role in AD progression and need to be taken into consideration for the early detection of AD.

Sleep and White Matter in Adults with Down Syndrome

Adults with Down syndrome are at a high risk for disordered sleep. These sleep problems could have marked effects on aging and Alzheimer’s disease, potentially altering white matter integrity. This study examined the associations between disordered sleep assessed via an actigraph accelerometer worn on 7 consecutive nights, presence of diagnosis of obstructive sleep apnea, and diffusion tensor imaging indices of white matter integrity in 29 non-demented adults with Down Syndrome (48% female, aged 33–54 years). Average total sleep time was associated with lower mean diffusivity in the left superior longitudinal fasciculus (r = −0.398, p = 0.040). Average sleep efficiency, length of awakenings, and movement index were related to fractional anisotropy in the right inferior longitudinal fasciculus (r = −0.614 to 0.387, p ≤ 0.050). Diagnosis of obstructive sleep apnea was associated with fractional anisotropy in the right inferior longitudinal fasciculus (r = −0.373 p = 0.050). Findings suggest that more disrupted sleep is associated with lower white matter integrity in the major association tracts in middle-aged adults with Down syndrome. Longitudinal work is needed to confirm the directionally of associations. Sleep interventions could be an important component for promoting optimal brain aging in the Down syndrome population.

Prosopagnosia associated with brain metastasis near the inferior longitudinal fasciculus in the nondominant temporal lobe: illustrative case

BACKGROUND Disruptions of the inferior longitudinal fasciculus (ILF) in the nondominant temporal lobe can lead to the rare but significant higher visual-processing disturbance of prosopagnosia. Here, the authors describe a 57-year-old right hand-dominant female with a large breast cancer brain metastasis in the right temporal lobe who underwent resection and subsequent Gamma Knife radiosurgery. She presented with difficulty with facial recognition, but following surgical intervention, the prosopagnosia became more profound. OBSERVATIONS Even in nondominant cortex, significant deficits can arise when operating near higher visual-processing centers, including the ILF. LESSONS This case highlights the utility of imaging-based tractography obtained from preoperative imaging for resective surgical planning even when operating in areas that do not involve what is traditionally considered elegant areas of the brain. To optimize neurological outcomes in metastatic tumor resection, awareness and diffusion tensor imaging of neighboring, displaced white matter tracts may prevent permanent deficits in higher visual processing.

Prosopagnosia following nonlanguage dominant inferior temporal lobe low-grade glioma resection in which the inferior longitudinal fasciculus was disrupted preoperatively: illustrative case

BACKGROUND Prosopagnosia is a rare neurological condition characterized by the impairment of face perception with preserved visual processing and cognitive functioning and is associated with injury to the fusiform gyrus and inferior longitudinal fasciculus (ILF). Reports of this clinical impairment following resection of right temporal lobe diffuse gliomas in the absence of contralateral injury are exceedingly scarce and not expected as a complication of surgery. OBSERVATIONS The authors describe the case of a young female patient found to have an incidental diffuse glioma in the right inferior temporal lobe despite evidence of preoperative ILF disruption by the tumor. Following resection of the lesion, despite the preoperative disruption to the ILF by the tumor, the patient developed prosopagnosia. There was no evidence of contralateral, left-sided ILF injury. LESSONS Given the significant functional impairment associated with prosopagnosia, neurosurgeons should be aware of the exceedingly rare possibility of a visual-processing deficit following unilateral and, in this case, right-sided inferior temporal lobe glioma resections. More investigation is needed to determine whether preoperative testing can determine dominance of facial-processing networks for patients with lesions in the right inferior posterior temporooccipital lobe and whether intraoperative mapping could help prevent this complication.

Microstructural Measures of the Inferior Longitudinal Fasciculus Predict Later Cognitive and Language Development in Infants Born With Extremely Low Birth Weight

Objective: Extremely preterm children are at high risk for adverse neurodevelopmental outcomes. Identifying predictors of discrete developmental outcomes early in life would allow for targeted neuroprotective therapies when neuroplasticity is at its peak. Our goal was to examine whether diffusion magnetic resonance imaging (MRI) metrics of the inferior longitudinal and uncinate fasciculi early in life could predict later cognitive and language outcomes. Study Design: In this pilot study, 43 extremely low-birth-weight preterm infants were scanned using diffusion MRI at term-equivalent age. White matter tracts were assessed via diffusion tensor imaging metrics of fractional anisotropy and mean diffusivity. The Language and Cognitive subscale scores of the Bayley Scales of Infant & Toddler Development-III at 18-22 months corrected age were our outcomes of interest. Multiple linear regression models were created to assess diffusion metrics of the inferior longitudinal and uncinate fasciculi as predictors of Bayley scores. We controlled for brain injury score on structural MRI, maternal education, birth weight, and age at MRI scan. Results: Of the 43 infants, 36 infants had high-quality diffusion tensor imaging and returned for developmental testing. The fractional anisotropy of the inferior longitudinal fasciculus was associated with Bayley-III scores in univariate analyses and was an independent predictor of Bayley-III cognitive and language development over and above known predictors in multivariable analyses. Conclusions: Incorporating new biomarkers such as the fractional anisotropy of the inferior longitudinal fasciculus with structural MRI findings could enhance accuracy of neurodevelopment predictive models. Additional research is needed to validate our findings in a larger cohort.

White Matter Abnormalities Associated With Prolonged Recovery in Adolescents Following Concussion

Background: Concussion symptoms in adolescents typically resolve within 4 weeks. However, 20 – 30% of adolescents experience a prolonged recovery. Abnormalities in tracts implicated in visuospatial attention and emotional regulation (i.e., inferior longitudinal fasciculus, ILF; inferior fronto-occipital fasciculus, IFOF; uncinate fasciculus; UF) have been consistently reported in concussion; yet, to date, there are no objective markers of prolonged recovery in adolescents. Here, we evaluated the utility of diffusion MRI in outcome prediction. Forty-two adolescents (12.1 – 17.9 years; female: 44.0%) underwent a diffusion Magnetic Resonance Imaging (dMRI) protocol within the first 10 days of concussion. Based on days of injury until medical clearance, adolescents were then categorized into SHORT (<28 days; N = 21) or LONG (>28 days; N = 21) recovery time. Fractional anisotropy (FA) in the ILF, IFOF, UF, and/or concussion symptoms were used as predictors of recovery time (SHORT, LONG). Forty-two age- and sex-matched healthy controls served as reference. Higher FA in the ILF (left: adjusted odds ratio; AOR = 0.36, 95% CI = 0.15 – 0.91, P = 0.030; right: AOR = 0.28, 95% CI = 0.10 – 0.83, P = 0.021), IFOF (left: AOR = 0.21, 95% CI = 0.07 – 0.66, P = 0.008; right: AOR = 0.30, 95% CI = 0.11 – 0.83, P = 0.020), and UF (left: AOR = 0.26, 95% CI = 0.09 – 0.74, P = 0.011; right: AOR = 0.28, 95% CI = 0.10 – 0.73, P = 0.010) was associated with SHORT recovery. In additional analyses, while adolescents with SHORT recovery did not differ from HC, those with LONG recovery showed lower FA in the ILF and IFOF (P < 0.014). Notably, inclusion of dMRI findings increased the sensitivity and specificity (AUC = 0.93) of a prediction model including clinical variables only (AUC = 0.75). Our findings indicate that higher FA in long associative tracts (especially ILF) might inform a more objective and accurate prognosis for recovery time in adolescents following concussion.

Disturbances in White Matter Integrity in the Ultra-High-Risk Psychosis State—A Systematic Review

Schizophrenia is a severe and disabling mental illness whose etiology still remains unclear. The available literature indicates that there exist white matter (WM) abnormalities in people with schizophrenia spectrum disorders. Recent developments in modern neuroimaging methods have enabled the identification of the structure, morphology, and function of the underlying WM fibers in vivo. The purpose of this paper is to review the existing evidence about WM abnormalities in individuals at ultra-high risk of psychosis (UHR) with the use of diffusion tensor imaging (DTI) available from the National Center for Biotechnology Information PubMed (Medline) and Health Source: Nursing/Academic Edition databases. Of 358 relevant articles identified, 25 papers published in the years 2008–2020 were ultimately included in the review. Most of them supported the presence of subtle aberrations in WM in UHR individuals, especially in the superior longitudinal fasciculus (SLF), the inferior longitudinal fasciculus (ILF), and the inferior fronto-occipital fasciculus (IFOF). These alterations may therefore be considered a promising neurobiological marker for the risk of psychosis. However, due to methodological discrepancies and the relative scarcity of evidence, further investigation is called for, especially into connectome analysis in UHR patients.

Working Memory Training Effects on White Matter Integrity in Young and Older Adults

ObjectivesWorking memory is essential for daily life skills like reading comprehension, reasoning, and problem-solving. Healthy aging of the brain goes along with working memory decline that can affect older people’s independence in everyday life. Interventions in the form of cognitive training are a promising tool for delaying age-related working memory decline, yet the underlying structural plasticity of white matter is hardly studied.MethodsWe conducted a longitudinal diffusion tensor imaging study to investigate the effects of an intensive four-week adaptive working memory training on white matter integrity quantified by global and tract-wise mean diffusivity. We compared diffusivity measures of fiber tracts that are associated with working memory of 32 young and 20 older participants that were randomly assigned to a working memory training group or an active control group.ResultsThe behavioral analysis showed an increase in working memory performance after the four-week adaptive working memory training. The neuroanatomical analysis revealed a decrease in mean diffusivity in the working memory training group after the training intervention in the right inferior longitudinal fasciculus for the older adults. There was also a decrease in mean diffusivity in the working memory training group in the right superior longitudinal fasciculus for the older and young participants after the intervention.ConclusionThis study shows that older people can benefit from working memory training by improving their working memory performance that is also reflected in terms of improved white matter integrity in the superior longitudinal fasciculus and the inferior longitudinal fasciculus, where the first is an essential component of the frontoparietal network known to be essential in working memory.