Microscopic fractional anisotropy outperforms multiple sclerosis lesion assessment and clinical outcome associations over standard fractional anisotropy tensor.

We aimed to compare the ability of diffusion tensor imaging and multi-compartment spherical mean technique to detect focal tissue damage and in distinguishing between different connectivity patterns associated with varying clinical outcomes in multiple sclerosis (MS). Seventy-six people diagnosed with MS were scanned using a SIEMENS Prisma Fit 3T magnetic resonance imaging (MRI), employing both conventional (T1w and fluid-attenuated inversion recovery) and advanced diffusion MRI sequences from which fractional anisotropy (FA) and microscopic FA (µFA) maps were generated. Using automated fiber quantification (AFQ), we assessed diffusion profiles across multiple white matter (WM) pathways to measure the sensitivity of anisotropy diffusion metrics in detecting localized tissue damage. In parallel, we analyzed structural brain connectivity in a specific patient cohort to fully grasp its relationships with cognitive and physical clinical outcomes. This evaluation comprehensively considered different patient categories, including cognitively preserved (CP), mild cognitive deficits (MCD), and cognitively impaired (CI) for cognitive assessment, as well as groups distinguished by physical impact: those with mild disability (Expanded Disability Status Scale [EDSS] <=3) and those with moderate-severe disability (EDSS >3). In our initial objective, we employed Ridge regression to forecast the presence of focal MS lesions, comparing the performance of µFA and FA. µFA exhibited a stronger association with tissue damage and a higher predictive precision for focal MS lesions across the tracts, achieving an R-squared value of .57, significantly outperforming the R-squared value of .24 for FA (p-value <.001). In structural connectivity, µFA exhibited more pronounced differences than FA in response to alteration in both cognitive and physical clinical scores in terms of effect size and number of connections. Regarding cognitive groups, FA differences between CP and MCD groups were limited to 0.5% of connections, mainly around the thalamus, while µFA revealed changes in 2.5% of connections. In the CP and CI group comparison, which have noticeable cognitive differences, the disparity was 5.6% for FA values and 32.5% for µFA. Similarly, µFA outperformed FA in detecting WM changes between the MCD and CI groups, with 5% versus 0.3% of connections, respectively. When analyzing structural connectivity between physical disability groups, µFA still demonstrated superior performance over FA, disclosing a 2.1% difference in connectivity between regions closely associated with physical disability in MS. In contrast, FA spotted a few regions, comprising only 0.6% of total connections. In summary, µFA emerged as a more effective tool than FA in predicting MS lesions and identifying structural changes across patients with different degrees of cognitive and global disability, offering deeper insights into the complexities of MS-related impairments.

Midbrain and pons MRI shape analysis and its clinical and CSF correlates in degenerative parkinsonisms: a pilot study.

OBJECTIVES: To conduct brainstem MRI shape analysis across neurodegenerative parkinsonisms and control subjects (CS), along with its association with clinical and cerebrospinal fluid (CSF) correlates. METHODOLOGY: We collected demographic and clinical variables, performed planimetric and shape MRI analyses, and determined CSF neurofilament-light chain (NfL) levels in 84 participants: 11 CS, 12 with Parkinson's disease (PD), 26 with multiple system atrophy (MSA), 21 with progressive supranuclear palsy (PSP), and 14 with corticobasal degeneration (CBD). RESULTS: MSA featured the most extensive and significant brainstem shape narrowing (that is, atrophy), mostly in the pons. CBD presented local atrophy in several small areas in the pons and midbrain compared to PD and CS. PSP presented local atrophy in small areas in the posterior and upper midbrain as well as the rostral pons compared to MSA. Our findings of planimetric MRI measurements and CSF NfL levels replicated those from previous literature. Brainstem shape atrophy correlated with worse motor state in all parkinsonisms and with higher NfL levels in MSA, PSP, and PD. CONCLUSION: Atypical parkinsonisms present different brainstem shape patterns which correlate with clinical severity and neuronal degeneration. In MSA, shape analysis could be further explored as a potential diagnostic biomarker. By contrast, shape analysis appears to have a rather limited discriminant value in PSP. KEY POINTS: • Atypical parkinsonisms present different brainstem shape patterns. • Shape patterns correlate with clinical severity and neuronal degeneration. • In MSA, shape analysis could be further explored as a potential diagnostic biomarker.

The cerebellum and psychological trauma: A systematic review of neuroimaging studies.

Psychological trauma is highly prevalent among psychiatric disorders, however, the relationship between trauma, neurobiology and psychopathology is not yet fully understood. The cerebellum has been recognized as a crucial structure for cognition and emotion, however, it has been relatively ignored in the literature of psychological trauma, as it is not considered as part of the traditional fear neuro-circuitry. The aim of this review is to investigate how psychological trauma affects the cerebellum and to make conclusive remarks on whether the cerebellum forms part of the trauma-affected brain circuitry. A total of 267 unique records were screened and 39 studies were included in the review. Structural cerebellar alterations and aberrant cerebellar activity and connectivity in trauma-exposed individuals were consistently reported across studies. Early-onset of adverse experiences was associated with cerebellar alterations in trauma-exposed individuals. Several studies reported alterations in connectivity between the cerebellum and nodes of large-brain networks, which are implicated in several psychiatric disorders, including the default mode network, the salience network and the central executive network. Also, trauma-exposed individuals showed altered resting state and task based cerebellar connectivity with cortical and subcortical structures that are involved in emotion and fear regulation. Our preferred interpretation of the results is through the lens of the Universal Cerebellar Transform, the hypothesis that the cerebellum, given its homogeneous cytoarchitecture, performs a common computation for motor, cognitive and emotional functions. Therefore, trauma-induced alterations in this computation might set the ground for a variety of psychiatric symptoms.

Testing an Adapted Auditory Verbal Learning Test Paradigm for fMRI to Lateralize Verbal Memory in Patients with Epilepsy.

BACKGROUND AND PURPOSE: fMRI is a noninvasive tool for predicting postsurgical deficits in candidates with pharmacoresistant temporal lobe epilepsy. We aimed to test an adapted paradigm of the Rey Auditory Verbal Learning Test to evaluate differences in memory laterality indexes between patients and healthy controls and its association with neuropsychological scores. MATERIALS AND METHODS: We performed a prospective study of 50 patients with temporal lobe epilepsy and 22 healthy controls. Participants underwent a block design language and memory fMRI. Laterality indexes and the hippocampal anterior-posterior index were calculated. Language and memory lateralization was organized into typical and atypical on the basis of laterality indexes. A neuropsychological assessment was performed with a median time from fMRI of 8 months and was compared with fMRI performance. RESULTS: We studied 40 patients with left temporal lobe epilepsy and 10 with right temporal lobe epilepsy. Typical language occurred in 65.3% of patients and 90.9% of healthy controls (P = .04). The memory fMRI laterality index was obtained in all healthy controls and 92% of patients. The verbal memory laterality index was bilateral (24.3%) more frequently than the language laterality index (7.69%) in patients with left temporal lobe epilepsy. Atypical verbal memory was greater in patients with left temporal lobe epilepsy (56.8%) than in healthy controls (36.4%), and the proportion of bilateral laterality indexes (53.3%) was larger than right laterality indexes (46.7%). Atypical verbal memory might be associated with higher cognitive scores in patients. No relevant differences were seen in the hippocampal anterior-posterior index according to memory impairment. CONCLUSIONS: The adapted Rey Auditory Verbal Learning Test paradigm fMRI might support verbal memory lateralization. Temporal lobe epilepsy laterality influences hippocampal memory laterality indexes. Left temporal lobe epilepsy has shown a higher proportion of atypical verbal memory compared with language, potentially to memory functional reorganization.