Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment.

Abnormalities of functional connectivity in the default mode network (DMN) recently have been reported in patients with amnestic mild cognitive impairment (aMCI), Alzheimer's disease (AD) or other psychiatric diseases. As such, these abnormalities may be epiphenomena instead of playing a causal role in AD progression. To date, few studies have investigated specific brain networks, which extend beyond the DMN involved in the early AD stages, especially in aMCI. The insula is one site affected by early pathological changes in AD and is a crucial hub of the human brain networks. Currently, we explored the contribution of the insula networks to cognitive performance in aMCI patients. Thirty aMCI and 26 cognitively normal (CN) subjects participated in this study. Intrinsic connectivity of the insula networks was measured, using the resting-state functional connectivity fMRI approach. We examined the differential connectivity of insula networks between groups, and the neural correlation between the altered insula networks connectivity and the cognitive performance in aMCI patients and CN subjects, respectively. Insula subregional volumes were also investigated. AMCI subjects, when compared to CN subjects, showed significantly reduced right posterior insula volumes, cognitive deficits and disrupted intrinsic connectivity of the insula networks. Specifically, decreased intrinsic connectivity was primarily located in the frontal-parietal network and the cingulo-opercular network, including the anterior prefrontal cortex (aPFC), anterior cingulate cortex, operculum, inferior parietal cortex and precuneus. Increased intrinsic connectivity was primarily situated in the visual-auditory pathway, which included the posterior superior temporal gyrus and middle occipital gyrus. Conjunction analysis was performed; and significantly decreased intrinsic connectivity in the overlapping regions of the anterior and posterior insula networks, including the bilateral aPFC, left dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, and anterior temporal pole was found. Furthermore, the disrupted intrinsic connectivity was associated with episodic memory (EM) deficits in the aMCI patients and not in the CN subjects. These findings demonstrated that the functional integration of the insula networks plays an important role in the EM process. They provided new insight into the neural mechanism underlying the memory deficits in aMCI patients.

Xie C ，Bai F ，Yu H ，Shi Y ，Yuan Y ，Chen G ，Li W ，Chen G ，Zhang Z ，Li SJ ... -  《-》

Aberrant default mode network in subjects with amnestic mild cognitive impairment using resting-state functional MRI.

Amnestic mild cognitive impairment (aMCI) is a syndrome associated with faster memory decline than normal aging and frequently represents the prodromal phase of Alzheimer's disease. When a person is not actively engaged in a goal-directed task, spontaneous functional magnetic resonance imaging (fMRI) signals can reveal functionally connected brain networks, including the so-called default mode network (DMN). To date, only a few studies have investigated DMN functions in aMCI populations. In this study, group-independent component analysis was conducted for resting-state fMRI data, with slices acquired perpendicular to the long axis of the hippocampus, from eight subjects with aMCI and eight normal control subjects. Subjects with aMCI showed an increased DMN activity in middle cingulate cortex, medial prefrontal cortex and left inferior parietal cortex compared to the normal control group. Decreased DMN activity for the aMCI group compared to the normal control group was noted in lateral prefrontal cortex, left medial temporal lobe (MTL), left medial temporal gyrus, posterior cingulate cortex/retrosplenial cortex/precuneus and right angular gyrus. Although MTL volume difference between the two groups was not statistically significant, a decreased activity in left MTL was observed for the aMCI group. Positive correlations between the DMN activity and memory scores were noted for left lateral prefrontal cortex, left medial temporal gyrus and right angular gyrus. These findings support the premise that alterations of the DMN occur in aMCI and may indicate deficiencies in functional, intrinsic brain architecture that correlate with memory function, even before significant MTL atrophy is detectable by structural MRI.

Jin M ，Pelak VS ，Cordes D 《-》

Deficits in episodic memory retrieval reveal impaired default mode network connectivity in amnestic mild cognitive impairment.

Dunn CJ ，Duffy SL ，Hickie IB ，Lagopoulos J ，Lewis SJ ，Naismith SL ，Shine JM ... -  《NeuroImage-Clinical》

Convergent and divergent intranetwork and internetwork connectivity patterns in patients with remitted late-life depression and amnestic mild cognitive impairment.

Both remitted late-life depression (rLLD) and amnesiac mild cognitive impairment (aMCI) alter brain functions in specific regions of the brain. They are also disconnection syndromes that are associated with a high risk of developing Alzheimer's disease (AD). Resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) was performed to define the shared and distinct aberrant patterns in intranetwork and internetwork connectivity between rLLD and aMCI and to determine how knowledge of these differences might contribute to our essential understanding of the altered sequences involved in functional systems both inside and outside of resting-state networks. We used rs-fcMRI to investigate in five functionally well-defined brain networks in two large cohorts of subjects at high risk for AD (55 rLLD and 87 aMCI) and 114 healthy controls (HC). A reduced degree of functional connectivity was observed in the bilateral inferior temporal cortex and supplemental motor area, and reduced correlations were observed within the sensory-motor network (SMN) and in the default mode network (DMN)-control network (CON) pair in the rLLD group than the HC group. The aMCI group showed only focal functional changes in regions of interest pairs, a trend toward increased correlations within the salience network and SMN, and a trend toward a reduced correlation in the DMN-CON pair. Furthermore, the rLLD group exhibited more severely altered functional connectivity than the aMCI group. Interestingly, these altered connectivities were associated with specific multi-domain cognitive and behavioral functions in both rLLD and aMCI. The degree of functional connectivity in the right primary auditory areas was negatively correlated with Hamilton Depression Scale scores in rLLD. Notably, altered connectivity between the right middle temporal cortex and the posterior cerebellum was negatively correlated with Mattis Dementia Rating Scale scores in both rLLD and aMCI. These results demonstrate that rLLD and aMCI may share convergent and divergent aberrant intranetwork and internetwork connectivity patterns as a potential continuous spectrum of the same disease. They further suggest that dysfunctions in the right specific temporal-cerebellum neural circuit may contribute to the similarities observed in rLLD and aMCI conversion to AD.

Chen J ，Shu H ，Wang Z ，Zhan Y ，Liu D ，Liao W ，Xu L ，Liu Y ，Zhang Z ... -  《-》

State-based functional connectivity changes associate with cognitive decline in amnestic mild cognitive impairment subjects.

Episodic memory (EM) dysfunction is a central characteristic of amnestic mild cognitive impairment (aMCI) subjects, and has a high risk of converting to Alzheimer's disease (AD). However, it is unknown how the EM network is modulated when a situation is switched. Twenty-six aMCI and twenty-two cognitively normal (CN) subjects were enrolled in this study. All of the subjects completed multi-dimensional neuropsychological tests and underwent functional magnetic resonance imaging scans during a resting-state and an episodic memory retrieval task state. The EM network was constructed using a seed-based functional connectivity (FC) approach. AMCI subjects showed poorer cognitive performances in the episodic memory and executive function. We demonstrated that connectivity of the left posterior parahippocampal gyrus (LpPHG) connected to the left ventral medial prefrontal cortex and the right postcentral gyrus (RPCG) was significantly decreased in aMCI subjects compared to CN subjects. Meanwhile, there was increased connectivity of the LpPHG to the right dorsal medial prefrontal cortex (RDMPFC), RPCG, left inferior parietal cortex, and bilateral superior parietal lobe in all of the subjects that changed from a resting-state to a task-state. Interestingly, the changed LpPHG-RDMPFC connectivity strength was significantly correlated with EM scores and executive function in the aMCI subjects. As a result, general brain regions are functionally organized and integrated into the EM network, and this strongly suggests that more cognitive resources are mobilized to meet the challenge of cognitive demand in the task state. These findings extend our understanding of the underlying mechanisms of EM deficits in aMCI subjects.

Yue C ，Wu D ，Bai F ，Shi Y ，Yu H ，Xie C ，Zhang Z ... -  《-》