Cerebellar and basal ganglia structural connections in humans: Effect of aging and relation with memory and learning

IntroductionThe cerebellum and basal ganglia were initially considered anatomically distinct regions, each connected via thalamic relays which project to the same cerebral cortical targets, such as the motor cortex. In the last two decades, transneuronal viral transport studies in non-human primates showed bidirectional connections between the cerebellum and basal ganglia at the subcortical level, without involving the cerebral cortical motor areas. These findings have significant implications for our understanding of neurodevelopmental and neurodegenerative diseases. While these subcortical connections were established in smaller studies on humans, their evolution with natural aging is less understood.MethodsIn this study, we validated and expanded the previous findings of the structural connectivity within the cerebellum-basal ganglia subcortical network, in a larger dataset of 64 subjects, across different age ranges. Tractography and fixel-based analysis were performed on the 3 T diffusion-weighted dataset using Mrtrix3 software, considering fiber density and cross-section as indicators of axonal integrity. Tractography of the well-established cerebello-thalamo-cortical tract was conducted as a control. We tested the relationship between the structural white matter integrity of these connections with aging and with the performance in different domains of Addenbrooke’s Cognitive Examination.ResultsTractography analysis isolated connections from the dentate nucleus to the contralateral putamen via the thalamus, and reciprocal tracts from the subthalamic nucleus to the contralateral cerebellar cortex via the pontine nuclei. Control tracts of cerebello-thalamo-cortical tracts were also isolated, including associative cerebello-prefrontal tracts. A negative linear relationship was found between the fiber density of both the ascending and descending cerebellum-basal ganglia tracts and age. Considering the cognitive assessments, the fiber density values of cerebello-thalamo-putaminal tracts correlated with the registration/learning domain scores. In addition, the fiber density values of cerebello-frontal and subthalamo-cerebellar (Crus II) tracts correlated with the cognitive assessment scores from the memory domain.ConclusionWe validated the structural connectivity within the cerebellum-basal ganglia reciprocal network, in a larger dataset of human subjects, across wider age range. The structural features of the subcortical cerebello-basal ganglia tracts in human subjects display age-related neurodegeneration. Individual morphological variability of cerebellar tracts to the striatum and prefrontal cortex was associated with different cognitive functions, suggesting a functional contribution of cerebellar tracts to cognitive decline with aging. This study offers new perspectives to consider the functional role of these pathways in motor learning and the pathophysiology of movement disorders involving the cerebellum and striatum

Novel Face-Name Paired Associate Learning and Famous Face Recognition in Mild Cognitive Impairment: A Neuropsychological and Brain Volumetric Study

Purpose: To assess visual associative learning and famous face recognition ability among subjects with stable amnestic mild cognitive impairment (MCI) relative to early stage dementia due to Alzheimer’s disease (AD) and cognitively normal healthy controls (NC) and to correlate these differences with volumetric changes on MRI. Methods: A hospital-based cross-sectional observational study was conducted on 61 participants. The subjects underwent neuropsychological evaluation, including validated newly designed tests for novel face-name paired association learning recall and famous face recognition. MRI volumetry was done on a subset of patients to ascertain the topographical patterns of volume loss. Results: There were significant differences in performance on free recall for face-name paired associate learning in MCI (n = 22) compared to NC (n = 20) (p < 0.001) and MCI compared to AD (n = 19; p < 0.001). Significant differences were also noted in scores on the famous personalities test between MCI and NC (p = 0.007), and MCI and AD (p = 0.032). The free recall component of face-name pair associative learning significantly correlated with left cuneus (p = 0.005; r = 0.833) and right cuneus (p = 0.003; r = 0.861) volume in AD with no significant correlation among MCI and NC cohorts. Conclusions: Novel and semantically familiar face-name associative recalls are significantly impaired in MCI, and these potentially predate the MRI volumetric changes in MCI. Our findings expand the spectrum of recall deficits in MCI

Region of Interest focused MRI to Synthetic CT Translation using Regression and Classification Multi-task Network

In this work, we present a method for synthetic CT (sCT) generation from zero-echo-time (ZTE) MRI aimed at structural and quantitative accuracies of the image, with a particular focus on the accurate bone density value prediction. We propose a loss function that favors a spatially sparse region in the image. We harness the ability of a multi-task network to produce correlated outputs as a framework to enable localisation of region of interest (RoI) via classification, emphasize regression of values within RoI and still retain the overall accuracy via global regression. The network is optimized by a composite loss function that combines a dedicated loss from each task. We demonstrate how the multi-task network with RoI focused loss offers an advantage over other configurations of the network to achieve higher accuracy of performance. This is relevant to sCT where failure to accurately estimate high Hounsfield Unit values of bone could lead to impaired accuracy in clinical applications. We compare the dose calculation maps from the proposed sCT and the real CT in a radiation therapy treatment planning setup

Clinical applications of functional MRI in epilepsy

The role of functional MRI (fMRI) in the presurgical evaluation of patients with intractable epilepsy is being increasingly recognized. Real-time fMRI is an easily performable diagnostic technique in the clinical setting. It has become a noninvasive alternative to intraoperative cortical stimulation and the Wada test for eloquent cortex mapping and language lateralization, respectively. Its role in predicting postsurgical memory outcome and in localizing the ictal activity is being recognized. This review article describes the biophysical basis of blood-oxygen-level-dependent (BOLD) fMRI and the methodology adopted, including the design, paradigms, the fMRI setup, and data analysis. Illustrative cases have been discussed, wherein the fMRI results influenced the seizure team's decisions with regard to diagnosis and therapy. Finally, the special issues involved in fMRI of epilepsy patients and the various challenges of clinical fMRI are detailed

Functional magnetic resonance imaging of the brain: A quick review

Ability to non-invasively map the hemodynamic changes occurring focally in areas of brain involved in various motor, sensory and cognitive functions by functional magnetic resonance imaging (fMRI) has revolutionized research in neuroscience in the last two decades. This technique has already gained clinical use especially in pre-surgical evaluation of epilepsy and neurosurgical planning of resection of mass lesions adjacent to eloquent cortex. In this review we attempt to illustrate basic principles and techniques of fMRI, its applications, practical points to consider while performing and evaluating clinical fMRI and its limitations

Structural and functional neuroimaging in intractable epilepsy

Medical management remains unsatisfactory in about a third of patients with epilepsy and some of them are candidates for resective epilepsy surgery. Structural and functional neuroimaging plays an important role in the identification of the precise cortical region responsible for seizures and is very crucial for a good surgical outcome. Furthermore, identification of eloquent cortical areas near the region to be resected is essential to avoid postoperative neurologic deficit. The magnetic resonance imaging (MRI) protocol for epilepsy can be individually tailored depending on the seizure semiology and possibly electroencephalography. New MRI techniques demonstrate the structure of the brain in fine detail, help in understanding the underlying pathology, and demonstrate functional activity of the brain with high spatial and temporal resolution. Metabolic imaging techniques, such as positron emission tomography (PET) and single photon emission tomography (SPECT) visualize metabolic alterations of the brain in the ictal and interictal states. In MR-negative epilepsy patients, these techniques may have localizing value. The proper use and interpretation of the findings provided by these new technologies is crucial. In this review article, we discuss various conventional and advanced MRI techniques, interpretation of various findings, and the role of functional imaging modalities, such as functional MRI, PET, and SPECT in the localization of epileptogenic substrate as well as for understanding the pathophysiology, propagation, and neurochemical correlates of epilepsy