Structural and Functional Changes in Subcortical Vascular Mild Cognitive Impairment: A Combined Voxel-Based Morphometry and Resting-State fMRI Study

The present study aimed to investigate changes in structural gray matter (GM) volume and functional amplitude of spontaneous low-frequency oscillations (LFO) and functional connectivity density in patients with subcortical vascular mild cognitive impairment (svMCI). Structural MRI and resting-sate functional MRI data were collected from 26 svMCI patients and 28 age- and gender-matched healthy controls. Structurally, widespread GM atrophy was found in the svMCI patients that resided primarily in frontal (e.g., the superior and middle frontal gyri and medial prefrontal cortex) and temporal (the superior and inferior temporal gyri) brain regions as well as several subcortical brain sites (e.g., the thalamus and the caudate). Functionally, svMCI-related changes were predominantly found in the default mode network (DMN). Compared with the healthy controls, the svMCI patients exhibited decreased LFO amplitudes in the anterior part of the DMN (e.g., the medial prefrontal cortex), whereas increased LFO amplitudes in the posterior part of the DMN (e.g., the posterior cingulate/precuneus). As for functional connectivity density, the DMN regions (e.g., the posterior cingulate/precuneus, the medial prefrontal cortex and the middle temporal gyrus) consistently exhibited decreased functional connectivity. Finally, the overall patterns of functional alterations in LFO amplitudes and functional connectivity density remained little changed after controlling for structural GM volume losses, which suggests that functional abnormalities can be only partly explained by morphological GM volume changes. Together, our results indicate that svMCI patients exhibit widespread abnormalities in both structural GM volume and functional intrinsic brain activity, which have important implications in understanding the pathophysiological mechanism of svMCI.     

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

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.     

The role of the DLPFC in inductive reasoning of MCI patients and normal agings: An fMRI study

Previous studies of young people have revealed that the left dorsolateral prefrontal cortex (DLPFC) plays an important role in inductive reasoning. An fMRI experiment was performed in this study to examine whether the left DLPFC was involved in inductive reasoning of MCI patients and normal agings, and whether the activation pattern of this region was different between MCI patients and normal agings. The fMRI results indicated that MCI patients had no difference from normal agings in behavior per-formance (reaction time and accuracy) and the activation pattern of DLPFC. However, the BOLD re-sponse of the DLPFC region for MCI patients was weaker than that for normal agings, and the func-tional connectivity between the bilateral DLPFC regions for MCI patients was significantly higher than for normal agings. Taken together, these results indicated that DLPFC plays an important role in inductive reasoning of agings, and the functional abnormity of DLPFC may be an earlier marker of MCI before structural alterations.     

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.     

MRI Markers for Mild Cognitive Impairment: Comparisons between White Matter Integrity and Gray Matter Volume Measurements

The aim of the study was to evaluate the value of assessing white matter integrity using diffusion tensor imaging (DTI) for classification of mild cognitive impairment (MCI) and prediction of cognitive impairments in comparison to brain atrophy measurements using structural MRI. Fifty-one patients with MCI and 66 cognitive normal controls (CN) underwent DTI and T1-weighted structural MRI. DTI measures included fractional anisotropy (FA) and radial diffusivity (DR) from 20 predetermined regions-of-interest (ROIs) in the commissural, limbic and association tracts, which are thought to be involved in Alzheimer''s disease; measures of regional gray matter (GM) volume included 21 ROIs in medial temporal lobe, parietal cortex, and subcortical regions. Significant group differences between MCI and CN were detected by each MRI modality: In particular, reduced FA was found in splenium, left isthmus cingulum and fornix; increased DR was found in splenium, left isthmus cingulum and bilateral uncinate fasciculi; reduced GM volume was found in bilateral hippocampi, left entorhinal cortex, right amygdala and bilateral thalamus; and thinner cortex was found in the left entorhinal cortex. Group classifications based on FA or DR was significant and better than classifications based on GM volume. Using either DR or FA together with GM volume improved classification accuracy. Furthermore, all three measures, FA, DR and GM volume were similarly accurate in predicting cognitive performance in MCI patients. Taken together, the results imply that DTI measures are as accurate as measures of GM volume in detecting brain alterations that are associated with cognitive impairment. Furthermore, a combination of DTI and structural MRI measurements improves classification accuracy.     

Default Mode Network Connectivity as a Function of Familial and Environmental Risk for Psychotic Disorder

Background

Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.

Methods

Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology.

Results

There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity.

Discussion

Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network “connectivity at rest” intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.     

Investigation of brain functional connectivity in patients with mild cognitive impairment: A functional near‐infrared spectroscopy (fNIRS) study

This study examines brain functional connectivity in both cognitively normal seniors and patients with mild cognitive impairment (MCI) to elucidate prospective markers of MCI. A homemade four‐channel functional near‐infrared spectroscopy (fNIRS) system was employed to measure hemodynamic responses in the subjects' prefrontal cortex during a resting state, an oddball task, a 1‐back task, and a verbal fluency task. Brain functional connectivity was calculated as the Pearson correlation coefficients between fNIRS channels. The results show that during the verbal fluency task, while the healthy control (HC) group presents a significantly stronger inter‐hemispheric connectivity compared to intra‐hemispheric connectivity, there is no difference between the inter‐ and intra‐hemispheric connectivity in the MCI group. In addition, a comparison between the MCI and HC connectivity reveals that the MCI group has a statistically higher right and inter‐hemispheric connectivity during the resting state, but a significantly lower left and inter‐hemispheric connectivity during the verbal fluency test. These findings demonstrate the potential of fNIRS to study brain functional connectivity in neurodegenerative diseases.     

Altered Resting-State Functional Connectivity of the Frontal-Striatal Reward System in Social Anxiety Disorder

We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions.     

Altered cerebellar-cerebral functional connectivity in geriatric depression

Although volumetric and activation changes in the cerebellum have frequently been reported in studies on major depression, its role in the neural mechanism of depression remains unclear. To understand how the cerebellum may relate to affective and cognitive dysfunction in depression, we investigated the resting-state functional connectivity between cerebellar regions and the cerebral cortex in samples of patients with geriatric depression (n = 11) and healthy controls (n = 18). Seed-based connectivity analyses were conducted using seeds from cerebellum regions previously identified as being involved in the executive, default-mode, affective-limbic, and motor networks. The results revealed that, compared with controls, individuals with depression show reduced functional connectivity between several cerebellum seed regions, specifically those in the executive and affective-limbic networks with the ventromedial prefrontal cortex (vmPFC) and increased functional connectivity between the motor-related cerebellum seed regions with the putamen and motor cortex. We further investigated whether the altered functional connectivity in depressed patients was associated with cognitive function and severity of depression. A positive correlation was found between the Crus II–vmPFC connectivity and performance on the Hopkins Verbal Learning Test-Revised delayed memory recall. Additionally, the vermis–posterior cinglate cortex (PCC) connectivity was positively correlated with depression severity. Our results suggest that cerebellum–vmPFC coupling may be related to cognitive function whereas cerebellum–PCC coupling may be related to emotion processing in geriatric depression.     

Default-Mode Network Changes in Huntington’s Disease: An Integrated MRI Study of Functional Connectivity and Morphometry

Previous MRI studies of functional connectivity in pre-symptomatic mutation carriers of Huntington’s disease (HD) have shown dysfunction of the Default-Mode Network (DMN). No data however are currently available on the DMN alterations in the symptomatic stages of the disease, which are characterized by cortical atrophy involving several DMN nodes. We assessed DMN integrity and its possible correlations with motor and cognitive symptoms in 26 symptomatic HD patients as compared to 22 normal volunteers, by analyzing resting state functional MRI data, using the Precuneal Cortex/Posterior Cingulate Cortices (PC/PCC) as seed, controlling at voxel level for the effect of atrophy by co-varying for gray matter volume. Direct correlation with PC/PCC was decreased, without correlation with atrophy, in the ventral medial prefrontal cortex (including anterior cingulate and subgenual cortex), right dorso-medial prefrontal cortex, and in the right inferior parietal cortex (mainly involving the angular gyrus). Negative correlations with PC/PCC were decreased bilaterally in the inferior parietal cortices, while a cluster in the right middle occipital gyrus presented increased correlation with PC/PCC. DMN changes in the ventral medial prefrontal cortex significantly correlated with the performance at the Stroop test (p = .0002). Widespread DMN changes, not correlating with the atrophy of the involved nodes, are present in symptomatic HD patients, and correlate with cognitive disturbances.     

Anatomical and functional deficits in patients with amnestic mild cognitive impairment

Background

Anatomical and functional deficits have been studied in patients with amnestic mild cognitive impairment (MCI). However, it is unclear whether and how the anatomical deficits are related to the functional alterations. Present study aims to characterize the association between anatomical and functional deficits in MCI patients.

Methods

Seventeen amnestic MCI patients and 18 healthy aging controls were scanned using a T1 Weighted MPRAGE sequence and a gradient-echo echo-planar imaging sequence. Clinical severity of MCI patients was evaluated by using Clinical Dementia Rating, Mini Mental State Examination (MMSE), Clock Drawing Test, Auditory Verbal Learning Test and Activities of Daily Living. VBM with DARTEL was used to characterize the gray matter deficits in MCI. Regional amplitude of low-frequency (0.01–0.08 Hz) fluctuations (ALFF) was used to evaluate regional functional alteration in MCI and fractional ALFF(fALFF) in slow 4 (0.027–0.073 Hz) and slow 5 (0.01–0.027 Hz) were also calculated.

Results

Significantly decreased gray matter volume (GMV) was observed in amnestic MCI group mainly in bilateral prefrontal, left temporal and posterior cingulate cortex. Significant positive correlation was observed between the GMV in left inferior frontal gyrus and MMSE scores. Interestingly, decreased ALFF/fALFF was revealed in MCI group compared to controls mainly in prefrontal, left parietal regions and right fusiform gyrus, while the increased ALFF/fALFF was found in limbic and midbrain. Furthermore, the changes of fALFF in MCI in the slow-5 band were greater than those in the slow-4. No significant correlation was found between the morphometric and functional results.

Conclusions

Findings from the study document that wide spread brain volume reduction accompanied with decreased and increased regional function in MCI, while the anatomical and functional changes were independently. Therefore, the combination of structural and functional MRI methods would provide complementary information and together advance our understanding of the pathophysiology underlying the symptoms of MCI.     

Regional Brain Atrophy and Functional Connectivity Changes Related to Fatigue in Multiple Sclerosis

Fatigue is one of the most frequent symptoms in multiple sclerosis (MS), and recent studies have described a relationship between the sensorimotor cortex and its afferent and efferent pathways as a substrate of fatigue. The objectives of this study were to assess the neural correlates of fatigue in MS through gray matter (GM) and white matter (WM) atrophy, and resting state functional connectivity (rs-FC) of the sensorimotor network (SMN). Eighteen healthy controls (HCs) and 60 relapsing-remitting patients were assessed with the Fatigue Severity Scale (FSS). Patients were classified as fatigued (F) or nonfatigued (NF). We investigated GM and WM atrophy using voxel-based morphometry, and rs-FC changes with a seed-based method and independent component analysis (ICA). F patients showed extended GM and WM atrophy focused on areas related to the SMN. High FSS scores were associated with reductions of WM in the supplementary motor area. Seed analysis of GM atrophy in the SMN showed that HCs presented increased rs-FC between the primary motor and somatosensory cortices while patients with high FSS scores were associated with decreased rs-FC between the supplementary motor area and associative somatosensory cortex. ICA results showed that NF patients presented higher rs-FC in the primary motor cortex compared to HCs and in the premotor cortex compared to F patients. Atrophy reduced functional connectivity in SMN pathways and MS patients consequently experienced high levels of fatigue. On the contrary, NF patients experienced high synchronization in this network that could be interpreted as a compensatory mechanism to reduce fatigue sensation.     

Frequency-Dependent Changes of Local Resting Oscillations in Sleep-Deprived Brain

Sleep deprivation (SD) adversely affects brain function and is accompanied by frequency dependent changes in EEG. Recent studies have suggested that BOLD fluctuations pertain to a spatiotemporal organization with different frequencies. The present study aimed to investigate the frequency-dependent SD-related brain oscillatory activity by using the amplitude of low-frequency fluctuation (ALFF) analysis. The ALFF changes were measured across different frequencies (Slow-4: 0.027–0.073 Hz; Slow-5: 0.01–0.027 Hz; and Typical band: 0.01–0.08 Hz) in 24 h SD as compared to rested wakeful during resting-state fMRI. Sixteen volunteers underwent two fMRI sessions, once during rested wakefulness and once after 24 h of SD. SD showed prominently decreased ALFF in the right inferior parietal lobule (IPL), bilateral orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC), while increased ALFF in the visual cortex, left sensorimotor cortex and fusiform gyrus. Across the Slow-4 and Slow-5, results differed significantly in the OFC, DLPFC, thalamus and caudate in comparison to typical frequency band; and Slow-4 showed greater differences. In addition, negative correlations of behavior performance and ALFF patterns were found mainly in the right IPL across the typical frequency band. These observations provided novel insights about the physiological responses of SD, identified how it disturbs the brain rhythms, and linked SD with frequency-dependent alterations in amplitude patterns.     

Cerebral Correlates of Abnormal Emotion Conflict Processing in Euthymic Bipolar Patients: A Functional MRI Study

Background

Patients with bipolar disorder experience cognitive and emotional impairment that may persist even during the euthymic state of the disease. These persistent symptoms in bipolar patients (BP) may be characterized by disturbances of emotion regulation and related fronto-limbic brain circuitry. The present study aims to investigate the modulation of fronto-limbic activity and connectivity in BP by the processing of emotional conflict.

Methods

Fourteen euthymic BP and 13 matched healthy subjects (HS) underwent functional magnetic resonance imaging (fMRI) while performing a word-face emotional Stroop task designed to dissociate the monitoring/generation of emotional conflict from its resolution. Functional connectivity was determined by means of psychophysiological interaction (PPI) approach.

Results

Relative to HS, BP were slower to process incongruent stimuli, reflecting higher amount of behavioral interference during emotional Stroop. Furthermore, BP showed decreased activation of the right dorsolateral prefrontal cortex (DLPFC) during the monitoring and a lack of bilateral amygdala deactivation during the resolution of the emotional conflict. In addition, during conflict monitoring, BP showed abnormal positive connectivity between the right DLPFC and several regions of the default mode network.

Conclusions

Overall, our results highlighted dysfunctional processing of the emotion conflict in euthymic BP that may be subtended by abnormal activity and connectivity of the DLPFC during the conflict monitoring, which, in turn, leads to failure of amygdala deactivation during the resolution of the conflict. Emotional dysregulation in BP may be underpinned by a lack of top-down cognitive control and a difficulty to focus on the task due to persistent self-oriented attention.     

Analysis of grey matter in thalamus and basal ganglia based on EEG α3/α2 frequency ratio reveals specific changes in subjects with mild cognitive impairment

GM (grey matter) changes of thalamus and basal ganglia have been demonstrated to be involved in AD (Alzheimer''s disease). Moreover, the increase of a specific EEG (electroencephalogram) marker, α3/α2, have been associated with AD-converters subjects with MCI (mild cognitive impairment). To study the association of prognostic EEG markers with specific GM changes of thalamus and basal ganglia in subjects with MCI to detect biomarkers (morpho-physiological) early predictive of AD and non-AD dementia. Seventy-four adult subjects with MCI underwent EEG recording and high-resolution 3D MRI (three-dimensional magnetic resonance imaging). The α3/α2 ratio was computed for each subject. Three groups were obtained according to increasing tertile values of α3/α2 ratio. GM density differences between groups were investigated using a VBM (voxel-based morphometry) technique. Subjects with higher α3/α2 ratios when compared with subjects with lower and middle α3/α2 ratios showed minor atrophy in the ventral stream of basal ganglia (head of caudate nuclei and accumbens nuclei bilaterally) and of the pulvinar nuclei in the thalamus; The integrated analysis of EEG and morpho-structural markers could be useful in the comprehension of anatomo-physiological underpinning of the MCI entity.     

The Selective Impairment of Resting-State Functional Connectivity of the Lateral Subregion of the Frontal Pole in Schizophrenia

Objective

Although extensive resting-state functional connectivity (rsFC) changes have been reported in schizophrenia, rsFC changes of the frontal pole (FP) remain unclear. The FP contains several subregions with different connection patterns; however, it is unknown whether the FP subregions are differentially affected in schizophrenia. To explore this possibility, we compared rsFC differences of the FP subregions between schizophrenia patients and healthy controls.

Method

One hundred healthy controls and 91 patients with schizophrenia underwent resting-state functional MRI with a sensitivity-encoded spiral-in (SENSE-SPIRAL) imaging sequence to reduced susceptibility-induced signal loss and distortion. The FP was subdivided into the orbital (FPo), medial (FPm), and lateral (FPl) subregions. Mean fMRI time series were extracted for each FP subregion and entered into a seed-based rsFC analysis.

Results

The FP subregions exhibited differential rsFC patterns in both healthy controls and schizophrenia patients. Direct comparison between groups revealed reduced rsFCs between the bilateral FPl and several cognitive-related regions, including the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex/precuneus, temporal cortex and inferior parietal lobule in schizophrenia. Although the FPl exhibited obvious atrophy, rsFC changes were unrelated to volumetric atrophy in the FPl, to duration of illness, and to antipsychotic medication dosage. No significant differences were observed in the rsFCs of other FP subregions.

Conclusion

These findings suggest a selective (the lateral subregion) functional disconnection of the FP subregions in schizophrenia.     

Decreased Thalamocortical Functional Connectivity after 36 Hours of Total Sleep Deprivation: Evidence from Resting State fMRI

Objectives

The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections, which hold a key function in segregating internally and externally directed awareness information. Previous task-related studies have revealed altered activities of the thalamus after total sleep deprivation (TSD). However, it is still unclear how TSD impacts on the communication between the thalamus and cerebral cortex. In this study, we examined changes of thalamocortical functional connectivity after 36 hours of total sleep deprivation by using resting state function MRI (fMRI).

Materials and Methods

Fourteen healthy volunteers were recruited and performed fMRI scans before and after 36 hours of TSD. Seed-based functional connectivity analysis was employed and differences of thalamocortical functional connectivity were tested between the rested wakefulness (RW) and TSD conditions.

Results

We found that the right thalamus showed decreased functional connectivity with the right parahippocampal gyrus, right middle temporal gyrus and right superior frontal gyrus in the resting brain after TSD when compared with that after normal sleep. As to the left thalamus, decreased connectivity was found with the right medial frontal gyrus, bilateral middle temporal gyri and left superior frontal gyrus.

Conclusion

These findings suggest disruptive changes of the thalamocortical functional connectivity after TSD, which may lead to the decline of the arousal level and information integration, and subsequently, influence the human cognitive functions.     

Aging alters the multichemical networking profile of the human brain: an in vivo (1)H-MRS study of young versus middle-aged subjects

In our most recent study of normal aging, we found decreased concentration of multiple chemicals in the brain of middle-aged subjects, as compared with younger subjects using in vivo proton magnetic resonance spectroscopy ((1)H-MRS). We hypothesized that these age-dependent differences in brain chemistry changes might be a reflection of the multichemical-networking-profile (MCNP) changes during aging. Using (1)H-MRS and correlation analysis, we examined the patterns of regional chemical levels and MCNP within and across multiple brain regions for all nine chemicals of (1)H-MR spectra. The brain chemistry changes and MCNP patterns were compared between 21 young (19--31-year-old) and 31 middle-aged (40--52-year-old) normal volunteers. Middle-aged subjects demonstrated a significant decrease of chemical levels in the prefrontal cortex and sensorimotor cortex (SMC), as compared with the young age group. Of these, neurotransmitters GABA and glutamate in the dorsolateral prefrontal cortex (DLPFC) were altered the most. We also found a significant increase of overall chemical correlation strength in MCNP within and across all studied brain regions with increased age. These changes were caused by alterations in the pattern of negative chemical connectivity across brain regions, which become weaker (less negative) in middle-aged subjects. The interregional chemical connectivity for the cingulate cortex, SMC and the thalamus was changed the most with increased age. Increased levels of chemical correlation strength across brain regions in aging were found for most chemicals studied (including neurotransmitters GABA and glutamate), and not for N-acetyl aspartate. These age-related differences in the connectivity of neurotransmitters were not region dependent. The results suggest that aging is associated with changes of the regional brain chemistry and the brain MCNP. The latter process may reflect an adaptive or compensatory response (possibly related to the elongation of dendrites with aging) to reduced levels of regional brain chemicals. The (1)H-MRS approach proposed here can be used as a valuable tool in the study of the brain chemistry, MCNP and their relationships in normal and abnormal aging.     

Altered Oscillation and Synchronization of Default-Mode Network Activity in Mild Alzheimer’s Disease Compared to Mild Cognitive Impairment: An Electrophysiological Study

Some researchers have suggested that the default mode network (DMN) plays an important role in the pathological mechanisms of Alzheimer’s disease (AD). To examine whether the cortical activities in DMN regions show significant difference between mild AD from mild cognitive impairment (MCI), electrophysiological responses were analyzed from 21 mild Alzheimer’s disease (AD) and 21 mild cognitive impairment (MCI) patients during an eyes closed, resting-state condition. The spectral power and functional connectivity of the DMN were estimated using a minimum norm estimate (MNE) combined with fast Fourier transform and imaginary coherence analysis. Our results indicated that source-based EEG maps of resting-state activity showed alterations of cortical spectral power in mild AD when compared to MCI. These alterations are characteristic of attenuated alpha or beta activities in the DMN, as are enhanced delta or theta activities in the medial temporal, inferior parietal, posterior cingulate cortex and precuneus. With regard to altered synchronization in AD, altered functional interconnections were observed as specific connectivity patterns of connection hubs in the precuneus, posterior cingulate cortex, anterior cingulate cortex and medial temporal regions. Moreover, posterior theta and alpha power and altered connectivity in the medial temporal lobe correlated significantly with scores obtained on the Mini-Mental State Examination (MMSE). In conclusion, EEG is a useful tool for investigating the DMN in the brain and differentiating early stage AD and MCI patients. This is a promising finding; however, further large-scale studies are needed.