Interhemispheric Functional and Structural Disconnection in Alzheimer’s Disease: A Combined Resting-State fMRI and DTI Study

Abstract

Neuroimaging studies have demonstrated that patients with Alzheimer’s disease presented disconnection syndrome. However, little is known about the alterations of interhemispheric functional interactions and underlying structural connectivity in the AD patients. In this study, we combined resting-state functional MRI and diffusion tensor imaging (DTI) to investigate interhemispheric functional and structural connectivity in 16 AD, 16 mild cognitive impairment (MCI), as well as 16 cognitive normal healthy subjects (CN). The pattern of the resting state interhemispheric functional connectivity was measured with a voxel-mirrored homotopic connectivity (VMHC) method. Decreased VMHC was observed in AD and MCI subjects in anterior brain regions including the prefrontal cortices and subcortical regions with a pattern of AD<MCI<CN. Increased VMHC was observed in MCI subjects in posterior brain regions with patterns of AD/CN < MCI (sensorimotor cortex) and AD < CN/MCI (occipital gyrus). DTI analysis showed the most significant difference among the three cohorts was the fractional anisotropy in the genu of corpus callosum, which was positively associated with the VMHC of prefrontal and subcortical regions. Across all the three cohorts, the diffusion parameters in the genu of corpus callosum and VMHC in the above brain regions had significant correlation with the cognitive performance. These results demonstrate that there are specific patterns of interhemispheric functional connectivity changes in the AD and MCI, which can be significantly correlated with the integrity changes in the midline white matter structures. These results suggest that VMHC can be used as a biomarker for the degeneration of the interhemispheric connectivity in AD.

Long-term dynamics of aberrant neuronal activity in Alzheimer’s disease

“…The observed increase in correlated spontaneous activity in our data thus might result from aberrant correlated synaptic excitatory inputs, which could result from structural remodelling known to accompany for instance amyloid plaque pathology 12,40 . In line with this idea are also findings reporting increased local connectivity and synchronization in AD, while inter-regional connectivity was strongly decreased 41,42 . In conclusion, the network mechanisms underlying neural synchronization in AD under different conditions remains elusive thus far and warrants further scrutiny.…”

Extreme male developmental trajectories of homotopic brain connectivity in autism

“…Specifically, we focused on interhemispheric homotopic connectivity, and investigated voxel‐mirrored homotopic connectivity (VMHC) which reflects the similarity between fMRI time series of two symmetrical voxels in the right and left hemispheres. This measure previously was shown to have a potential to distinguish various neurological and neuropsychiatric populations, including ASD (Anderson et al, ; Hahamy, Behrmann, & Malach, ), schizophrenia (Lang et al, ), depression (Hou et al, ), Parkinson's disease (Zhu et al, ), Alzheimer's disease (Wang et al, ), amyotrophic lateral sclerosis (Zhang et al, ), and stroke (Yang et al, ). In addition, it has been reported to change throughout the lifespan in typical brains (Zuo et al, ).…”

Inter-hemispheric functional dysconnectivity mediates the association of corpus callosum degeneration with memory impairment in AD and amnestic MCI

“…Using a modular analysis method of graph theory, one study found the insula module, the largest homotopic module in the control group, had lost symmetric functional connection properties in the AD group28. More recently, a decreased inter-hemispheric functional connectivity mainly in the anterior brain regions has been reported29.…”