Peipeng Liang

Functional disconnection and compensation in mild cognitive impairment: evidence from DLPFC connectivity using resting-state fMRI.

The known regional abnormality of the dorsolateral prefrontal cortex (DLPFC) and its role in various neural circuits in mild cognitive impairment (MCI) has given prominence to its importance in studies on the disconnection associated with MCI. The purpose of the current study was to examine the DLPFC functional connectivity patterns during rest in MCI patients and the impact of regional grey matter (GM) atrophy on the functional results. Structural and functional MRI data were collected from 14 MCI patients and 14 age, gender-matched healthy controls. We found that both the bilateral DLPFC showed reduced functional connectivity with the inferior parietal lobule (IPL), superior/medial frontal gyrus and sub-cortical regions (e.g., thalamus, putamen) in MCI patients when compared with healthy controls. Moreover, the DLPFC connectivity with the IPL and thalamus significantly correlated with the cognitive performance of patients as measured by mini-mental state examination (MMSE), clock drawing test (CDT), and California verbal learning test (CVLT) scores. When taking GM atrophy as covariates, these results were approximately consistent with those without correction, although there may be a decrease in the statistical power. These results suggest that the DLPFC disconnections may be the substrates of cognitive impairments in MCI patients. In addition, we also found enhanced functional connectivity between the left DLPFC and the right prefrontal cortex in MCI patients. This is consistent with previous findings of MCI-related increased activation during cognitive tasks, and may represent a compensatory mechanism in MCI patients. Together, the present study demonstrated the coexistence of functional disconnection and compensation in MCI patients using DLPFC functional connectivity analysis, and thus might provide insights into biological mechanism of the disease.

Abnormal amygdala connectivity in patients with primary insomnia: Evidence from resting state fMRI

BACKGROUND Neurobiological mechanisms underlying insomnia are poorly understood. Previous findings indicated that dysfunction of the emotional circuit might contribute to the neurobiological mechanisms underlying insomnia. The present study will test this hypothesis by examining alterations in functional connectivity of the amygdala in patients with primary insomnia (PI). METHODS Resting-state functional connectivity analysis was used to examine the temporal correlation between the amygdala and whole-brain regions in 10 medication-naive PI patients and 10 age- and sex-matched healthy controls. Additionally, the relationship between the abnormal functional connectivity and insomnia severity was investigated. RESULTS We found decreased functional connectivity mainly between the amygdala and insula, striatum and thalamus, and increased functional connectivity mainly between the amygdala and premotor cortex, sensorimotor cortex in PI patients as compared to healthy controls. The connectivity of the amygdala with the premotor cortex in PI patients showed significant positive correlation with the total score of the Pittsburgh Sleep Quality Index (PSQI). CONCLUSIONS The decreased functional connectivity between the amygdala and insula, striatum, and thalamus suggests that dysfunction in the emotional circuit might contribute to the neurobiological mechanisms underlying PI. The increased functional connectivity of the amygdala with the premotor and sensorimotor cortex demonstrates a compensatory mechanism to overcome the negative effects of sleep deficits and maintain the psychomotor performances in PI patients.

Comparison of grey matter atrophy between patients with neuromyelitis optica and multiple sclerosis: a voxel-based morphometry study.

PURPOSE Previous studies have established regional grey matter (GM) loss in multiple sclerosis (MS). However, whether there is any regional GM atrophy in neuromyelitis optica (NMO) and the difference between NMO and MS is unclear. The present study addresses this issue by voxel-based morphometry (VBM). METHODS Conventional magnetic resonance imaging (MRI) and T1-weighted three-dimensional MRI were obtained from 26 NMO patients, 26 relapsing-remitting MS (RRMS) patients, and 26 normal controls. An analysis of covariance model assessed with cluster size inference was used to compare GM volume among three groups. The correlations of GM volume changes with disease duration, expanded disability status scale (EDSS) and brain T2 lesion volume (LV) were analyzed. RESULTS GM atrophy was found in NMO patients in several regions of frontal, temporal, parietal lobes and insula (uncorrected, p < 0.001). While extensive GM atrophy was found in RRMS patients, including most cortical regions and the deep grey matter (corrected for multiple comparisons, p < 0.01). Compared with NMO, those with RRMS had significant GM loss in bilateral thalami, caudate, left parahippocampal gyrus, right hippocampus and insula (corrected, p < 0.01). In RRMS group, regional GM loss in right caudate and bilateral thalami were strongly correlated with brain T2LV. CONCLUSIONS Our study found the difference of GM atrophy between NMO and RRMS patients mainly in deep grey matter. The correlational results suggested axonal degeneration from lesions on T2WI may be a key pathogenesis of atrophy in deep grey matter in RRMS.

Changes in thalamus connectivity in mild cognitive impairment: Evidence from resting state fMRI

PURPOSE The subcortical region such as thalamus was believed to have close relationship with many cerebral cortexes which made it especially interesting in the study of functional connectivity. Here, we used resting state functional MRI (fMRI) to examine changes in thalamus connectivity in mild cognitive impairment (MCI), which presented a neuro-disconnection syndrome. MATERIALS AND METHODS Data from 14 patients and 14 healthy age-matched controls were analyzed. Thalamus connectivity was investigated by examination of the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions. RESULTS We found that functional connectivity between the left thalamus and a set of regions was decreased in MCI; these regions are: bilateral cuneus, middle occipital gyrus (MOG), superior frontal gyrus (SFG), medial prefrontal cortex (MPFC), precuneus, inferior frontal gyrus (IFG) and precentral gyrus (PreCG). There are also some regions showed reduced connectivity to right thalamus; these regions are bilateral cuneus, MOG, fusiform gyrus (FG), MPFC, paracentral lobe (PCL), precuneus, superior parietal lobe (SPL) and IFG. We also found increased functional connectivity between the left thalamus and the right thalamus in MCI. CONCLUSION The decreased connectivity between the thalamus and the other brain regions might indicate reduced integrity of thalamus-related cortical networks in MCI. Furthermore, the increased connectivity between the left and right thalamus suggest compensation for the loss of cognitive function. Briefly, impairment and compensation of thalamus connectivity coexist in the MCI patients.

Abnormal baseline brain activity in patients with neuromyelitis optica: a resting-state fMRI study.

PURPOSE Recent immunopathologic and MRI findings suggest that tissue damage in neuromyelitis optica (NMO) is not limited to spinal cord and optic nerve, but also in brain. Baseline brain activity can reveal the brain functional changes to the tissue damages and give clues to the pathophysiology of NMO, however, it has never been explored by resting-state functional MRI (fMRI). We used regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI to investigate how baseline brain activity changes in patients with NMO. METHODS Resting-state fMRIs collected from seventeen NMO patients and seventeen age- and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration were further explored. RESULTS Our results showed that NMO patients had significantly decreased ALFF in precuneus, posterior cingulate cortex (PCC) and lingual gyrus; and increased ALFF in middle frontal gyrus, caudate nucleus and thalamus, compared to normal controls. Moderate negative correlations were found between the EDSS and ALFF in the left middle frontal gyrus (r=-0.436, p=0.040) and the left caudate (r=-0.542, p=0.012). CONCLUSION The abnormal baseline brain activity shown by resting-state fMRI in NMO is relevant to cognition, visual and motor systems. It implicates a complex baseline brain status of both functional impairments and adaptations caused by tissue damages in these systems, which gives clues to the pathophysiology of NMO.

Baseline and longitudinal patterns of hippocampal connectivity in mild cognitive impairment: Evidence from resting state fMRI

The hippocampus is believed to have close relationship with many cerebral cortexes and constitute memory network to modulate and facilitate communication, which makes it especially interesting and meaningful in the study of functional connectivity in mild cognitive impairment (MCI). However, functional connectivity between the hippocampus and other brain regions remains unclear in MCI. Furthermore, the longitudinal changes of the hippocampal connectivity have not been reported. In the study, resting state functional MRI (fMRI) was used to examine changes in hippocampal connectivity comparing 14 patients and 14 healthy age-matched controls. We found that functional connectivity between the hippocampus and a set of regions was disrupted in MCI, these regions are: the right frontal lobe, the bilateral temporal lobe and the right insular. While, the left posterior cingulate cortex, precuneus, hippocampus, caudate and right occipital gyrus showed increased connectivity to the hippocampus in MCI. Additionally, we traced the seven MCI patients and compared the hippocampal connectivity in initial stage and 3 years later stage. Several regions presented decreased connectivity to the hippocampus after 3 years. Finally, the hippocampal connectivity with some regions showed significant correlation with the cognitive performance of patients. Based on these findings, the decreased hippocampal connectivity might indicate reduced integrity of hippocampal cortical memory network in MCI. In addition, the increased hippocampal connectivity suggested compensation for the loss of memory function. With the development of the disease, the hippocampal connectivity may lose some compensation and add some more disruption due to the pathological changes.

The baseline and longitudinal changes of PCC connectivity in mild cognitive impairment: a combined structure and resting-state fMRI study.

The baseline and longitudinal changes of the posterior cingulate cortex (PCC) connectivity were assessed in order to clarify the neural mechanism of mild cognitive impairment (MCI). Twenty-eight right-handed subjects (14 MCI patients and 14 healthy elders) participated in this study. Clinical and neuropsychological examinations were performed on all the subjects. PCC functional connectivity was studied by examining the correlation between low frequency fMRI signal fluctuations in the PCC and those in all the other brain regions. Additionally, we traced all the MCI patients and compared their PCC connectivity in the initial stage and that in 3 years later. We also explored the relationship between the PCC functional connectivity strength and cognitive performances. Our results are as follows: Functional connectivity between the PCC and a set of regions is decreased in MCI patients. Most of these regions are within the default mode network (DMN). Three years later, the regions of superior frontal gyrus (SFG) and middle frontal gyrus (MFG) presented further decreased connectivity to the PCC in MCI. In addition, we also find enhanced functional connectivity between PCC and medial prefrontal cortex (MPFC), PCC and anterior cingulate cortex (ACC) in MCI patients. At last, our research also shows that the PCC connectivity with some regions significantly correlates with the cognitive performances of patients as measured by mini-mental state examination (MMSE), and California verbal learning test (CVLT) scores. The baseline and longitudinal changes of the PCC connectivity in our study suggest that impairment and compensation coexist in the disease progress of MCI patients.

Regional homogeneity changes in patients with neuromyelitis optica revealed by resting-state functional MRI

OBJECTIVE Resting-state brain activity in neuromyelitis optica (NMO) patients can give clues to the pathophysiology of the disorder, and may be helpful in diagnosis; however, it has been less explored using functional MRI (fMRI). In the current study, we used a regional homogeneity (ReHo) method to investigate NMO-related modulations of neural activity in the resting state. METHODS Resting-state fMRIs acquired in 17 NMO patients as well as in 17 age- and sex-matched normal controls were compared. Kendalls coefficient of concordance was used to measure the regional homogeneity. Correlative analyses were performed to explore the relationship between the expanded disability status scale (EDSS), disease duration and ReHo in regions with significant group differences. RESULTS Comparing the NMO group with the healthy controls, we found ReHo decreased in extensive brain regions, including the left anterior cingulate, left medial frontal gyrus, left posterior cingulate, right precuneus and right middle temporal gyrus; and increased in the right inferior frontal gyrus. CONCLUSIONS These results demonstrate that neural activity in the resting state is changed in patients with NMO. SIGNIFICANCE The present study reveals clear abnormalities of NMO patients in the baseline activities that have not been well detected, and further improves our understanding of the neural substrates of cognitive impairment in NMO patients.

Common and dissociable neural correlates associated with component processes of inductive reasoning

The ability to draw numerical inductive reasoning requires two key cognitive processes, identification and extrapolation. This study aimed to identify the neural correlates of both component processes of numerical inductive reasoning using event-related fMRI. Three kinds of tasks: rule induction (RI), rule induction and application (RIA), and perceptual judgment (Jud) were solved by twenty right-handed adults. Our results found that the left superior parietal lobule (SPL) extending into the precuneus and left dorsolateral prefrontal cortex (DLPFC) were commonly recruited in the two components. It was also observed that the fronto-parietal network was more specific to identification, whereas the striatal-thalamic network was more specific to extrapolation. The findings suggest that numerical inductive reasoning is mediated by the coordination of multiple brain areas including the prefrontal, parietal, and subcortical regions, of which some are more specific to demands on only one of these two component processes, whereas others are sensitive to both.

Three Subsystems of the Inferior Parietal Cortex Are Differently Affected in Mild Cognitive Impairment

The Inferior parietal cortex (IPC), including the intraparietal sulcus (IPS), angular gyrus (AG), and supramarginal gyrus (SG), plays an important role in episodic memory, and is considered to be one of the specific neuroimaging markers in predicting the conversion of mild cognitive impairment (MCI) to Alzheimers disease (AD). However, it is still unclear whether the connectivity of the IPC is impaired in MCI patients. In the present study, we used resting state fMRI to examine the functional connectivity of the three subdivisions of the IPC in MCI patients after controlling the impact of regional grey matter atrophy. It was found that, using IPS, AG, and SG as seeds of functional connectivity, three canonical functional networks could be correspondingly traced, i.e., executive control network (ECN), default mode network (DMN), and salience network (SN), and the three networks are differently altered in MCI patients. In contrast to the healthy controls, it was found that in MCI patients: 1) AG connectivity was significantly reduced within the DMN; 2) IPS showed decreased connectivity with the right inferior frontal gyrus while showing increased connectivity with the left frontal regions within the ECN; and 3) SG displayed decreased connectivity with a distribution of regions including the frontal and parietal regions, and increased connectivity with some sub-cortical areas within the SN. Moreover, the connectivity within the three networks was correlated with episodic memory and general cognitive impairment in MCI patients. These results extend well beyond the DMN, and further suggest that MCI is associated with alteration of large-scale functional brain networks.