Exploring Structural And Functional Disruptions In Mci Using Multimodal Neuroimaging Techniques

Mild cognitive impairment(MCI)is known to be a preclinical stage of dementia.MCI associated with small-vessel disease(sv MCI)might be a forme fruste of subcortical vascular dementia(SVa D),which is a subtype of Vascular Dementia and the most prevalent dementia in the Asian population.Studies have shown that the basal ganglia nucleus,specifically the striatum might be the most vulnerable structure in sv MCI.In this study,we used multimodal MRI techniques including structural MRI and resting-state f MRI to explore structural and functional alternations of striatal regions in sv MCI patients.We investigated their relationships to cognitive dysfunctions.These experiments were further extended to animal models to corroborate the human findings.Cerebral small vessel diseases play a crucial role in both vascular and nonvascular dementias.The location of white matter hyperintensities(WMHs),a neuroimaging marker of cerebral small vessel disease,has been found to vary between different types of dementias,with those in basal ganglia have been particularly associated with subcortical vascular cognitive impairment(SVCI).However,few studies have investigated the anatomical variation of WMHs across different basal ganglia nuclei and its effect on brain network derogation in patients with SVCI.The first study sought to examine WMHs and functional connectivity changes in basal ganglia circuits in patients at a prodromal stage of Alzheimer’s disease(amnestic mild cognitive impairment,a MCI,n =40)and SVCI(subcortical mild cognitive impairment,sv MCI,n =40).As there has been renewed focus highlighting the potential role of the basal ganglia circuit in episodic learning and memory,we hypothesized that structural and functional disruption of basal ganglia in sv MCI would be associated with memory abnormalities,as reflected in auditory-verbal learning performance.We found that WMHs in both sv MCI and a MCI groups were distributed heterogeneously across different basal ganglia nuclei,with the dorsal and ventral caudate showing the most WMHs.Importantly,such anatomical heterogeneity in white matter impairments across basal ganglia regions was associated with changes in their functional connectivity only in patients with sv MCI.Specifically,while increased WMHs in dorsal caudate was predictive of its reduced functional connectivity with regions in the executive control network,in ventral caudate,WM impairments were associated with increased functional connectivity with default mode regions.Furthermore,in sv MCI patients,both WMH and functional connectivity alterations in the dorsal caudate were reflective of immediate verbal recall performance,while changes in the ventral caudate correlated with delayed verbal recall performance.In contrast,in a MCI patients,basal ganglia WMHs were not correlated with their changes in functional connectivity changes,which decreased significantly with almost all basal ganglia structures,rather than restricting to specific basal ganglia subdivisions as observed in the sv MCI group.Our findings demonstrate that heterogeneously distributed basal ganglia WMHs are associated with changes in functional network interactions and verbal episodic memory performance only in sv MCI patients,which may reflect a differential role of the cerebrovascular pathology in disrupting network-level communications and cognition between Alzheimer’s and subcortical vascular dementia,and provide new insights in developing novel biomarkers that improve our ability to discriminate between these two memory disorders.Alzheimer’s pathology and dementia are mostly studied in cortical regions.In all major neurodegenerative diseases,aberrant functional connectivity in major brain networks are observed and while recent studies have shown that these cerebral intrinsic connectivity networks can be mapped in a similar fashion onto the cerebellum,and also the existence of Cortico-basal gangliacerebellar circuit has been suggested by various studies,research in these areas is primarily focused on the Cerebral cortex and Cerebellar connections in neurodegenerative diseases are rarely studied.The second experiment was performed to expand on the idea that the functional and structural changes observed in cortical and subcortical structures in neurodegenerative disorders could extend to the cerebellum.Voxel-Based Morphometry Analysis was performed to analyze Grey matter atrophy pattern,and basal ganglia functional connectivity changes were observed in the control group(N=40),and sv MCI group(N=40)across both cerebral and cerebellar,and subcortical structures.The study showed that the amount of cerebellar atrophy observed within a network correlated with its counterpart in the cerebral cortex.Also,key regions of the cerebellum,which are reported to have a role in cognitive function,and working memory and are known to be the functional link to the hippocampus showed both anatomical atrophy and decreased functional connectivity with the striatum.These atrophy patterns in the cerebellum also correlated with memory performances.These findings demonstrate that there are coupled changes in cerebral and cerebellar circuits and these changes along with basal ganglia connectivity reflect that degeneration patterns in sv MCI are not limited to the cerebral cortex but similarly extend to the cerebellum,and the cortico-basal ganglia-cerebellar circuit seems to play an important role in the pathology of this disease.The third study was done using a rodent model of vascular dementia and was aimed to expand upon the previous human study.Unlike human experiments,animal models present a multitude of options while designing experiments as per specific requirements.These models can be applied to conduct connectivity analyses using various disease models and other treatments.rsf MRI studies on animals can provide a better understanding of the undergoing phenomenon.In this study,a rodent model of vascular dementia was used and functional connectivity of the striatum across the rodent brain was studied.The striatum is the site of input from the granular cortex,parietal association area,and visual cortex,which are the reasons involved in spatial memory.In this study,rsf MRI of 2-VO rats along with healthy rats were done and functional connectivity of the striatum was studied.Behavior experiments were performed using the Morris Water Maze task to test spatial and working memory.The results showed decreased functional connectivity of the striatum along regions such as the diencephalon and hippocampus suggesting a disruption in cortico-subcortical circuits in the rates,and thereby a loss of spatial memory as these areas are known to be involved in spatial navigation.