Binbin Nie

Cerebral and cerebellar gray matter reduction in first-episode patients with major depressive disorder: A voxel-based morphometry study

PURPOSE To investigate cerebral and cerebellar gray matter abnormalities in patients with first-episode major depressive disorder (MDD). MATERIALS AND METHODS We examined the structural difference in regional gray matter density (GMD) between 22 first-episode MDD patients and 30 age-, gender- and education-matched healthy controls by optimized voxel-based morphometry (VBM) based on magnetic resonance imaging. RESULTS Compared with healthy controls, MDD patients showed decreased GMD in the right medial and left lateral orbitofrontal cortex, right dorsolateral prefrontal cortex (DLPFC), bilateral temporal pole, right superior temporal gyrus, bilateral anterior insular cortex, left parahippocampal gyrus, and left cerebellum. In addition, in MDD patients, there was a negative correlation between GMD values of the right DLPFC and the score of the depression rating scale. CONCLUSIONS Our findings provided additional support for the involvement of limbic-cortical circuits in the pathophysiology of MDD and preliminary evidence that a defect involving the cerebellum may also be implicated.

Altered functional connectivity of the dorsolateral prefrontal cortex in first-episode patients with major depressive disorder

BACKGROUND The aim of this study was to investigate resting-state functional connectivity alteration of the right dorsolateral prefrontal cortex (DLPFC) in patients with first-episode major depressive disorder (MDD). METHODS Twenty-two first-episode MDD patients and thirty age-, gender- and education-matched healthy control subjects were enrolled. Rest state functional magnetic resonance images and structure magnetic resonance images were scanned. The functional connectivity analysis was done based on the result of voxel-based morphometry (VBM). And the right DLPFC was chosen as the seed region of interests (ROI), as its gray matter density (GMD) decreased in the MDD patients compared with controls and its GMD values were negative correlation with the Hamilton Depression Rating Scale (HDRS) scores. RESULTS Compared to healthy controls, the MDD patients showed increased functional connectivity with right the DLPFC in the left dorsal anterior cingulate cortex (ACC), left parahippocampal gyrus (PHG), thalamus and precentral gyrus. In contrast, there were decreased functional connectivity between the right DLPFC and right parietal lobe. CONCLUSIONS By applying the VBM results to the functional connectivity analysis, the study suggested that abnormality of GMD in right DLPFC might be related to the functional connectivity alteration in the pathophysiology of MDD, which might be useful in further characterizing structure-function relations in this disorder.

Hippocampal neurochemistry is involved in the behavioural effects of neonatal maternal separation and their reversal by post-weaning environmental enrichment: A magnetic resonance study

Exposure to early life stress results in behavioural changes, and these dysfunctions may persist throughout adulthood. In this study, we investigated whether hippocampus volume and neurochemical changes were involved in the appearance of these effects in the maternal separation (MS) animal model using the noninvasive techniques of structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Sprague-Dawley rats exposed to MS for 180 min from postnatal days (PND) 2-14 demonstrated decreased sucrose preference, increased immobility in the forced swimming test (FST), and impaired memory in the Morris water maze in adulthood. Environmental enrichment (EE) (PND 21-60) could ameliorate the effects of MS on sucrose preference and learning and memory but not on immobility in the FST. In addition, EE significantly increased N-acetylaspartate (NAA) of MS animals. However, we did not find an effect of MS or EE on hippocampal volume. These results indicate the involvement of hippocampal neurochemistry in the behavioural changes that result from early stressful life events and their modification by post-weaning EE. Thus changes in NAA, as a measure of neuronal integrity, appear to be a sensitive correlate of these behavioural effects.

A rat brain MRI template with digital stereotaxic atlas of fine anatomical delineations in paxinos space and its automated application in voxel-wise analysis

This study constructs a rat brain T2‐weighted magnetic resonance imaging template including olfactory bulb and a compatible digital atlas. The atlas contains 624 carefully delineated brain structures based on the newest (2005) edition of rat brain atlas by Paxinos and Watson. An automated procedure, as an SPM toolbox, was introduced for spatially normalizing individual rat brains, conducting statistical analysis and visually localizing the results in the Atlas coordinate space. The brain template/atlas and the procedure were evaluated using functional images between rats with the right side middle cerebral artery occlusion (MCAO) and normal controls. The result shows that the brain region with significant signal decline in the MCAO rats was consistent with the occlusion position. Hum Brain Mapp, 2013.

Effect of acupuncture in mild cognitive impairment and Alzheimer disease: a functional MRI study.

We aim to clarify the mechanisms of acupuncture in treating mild cognitive impairment (MCI) and Alzheimer disease (AD) by using functional magnetic resonance imaging (fMRI). Thirty-six right-handed subjects (8 MCI patients, 14 AD patients, and 14 healthy elders) participated in this study. Clinical and neuropsychological examinations were performed on all the subjects. MRI data acquisition was performed on a SIEMENS verio 3-Tesla scanner. The fMRI study used a single block experimental design. We first acquired the baseline resting state data in the initial 3 minutes; we then acquired the fMRI data during the procession of acupuncture stimulation on the acupoints of Tai chong and Hegu for the following 3 minutes. Last, we acquired fMRI data for another 10 minutes after the needle was withdrawn. The preprocessing and data analysis were performed using the statistical parametric mapping (SPM8) software. Then the two-sample t-tests were performed between each two groups of different states. We found that during the resting state, brain activities in AD and MCI patients were different from those of control subjects. During the acupuncture and the second resting state after acupuncture, when comparing to resting state, there are several regions showing increased or decreased activities in MCI, AD subjects compared to normal subjects. Most of the regions were involved in the temporal lobe and the frontal lobe, which were closely related to the memory and cognition. In conclusion, we investigated the effect of acupuncture in AD and MCI patients by combing fMRI and traditional acupuncture. Our fMRI study confirmed that acupuncture at Tai chong (Liv3) and He gu (LI4) can activate certain cognitive-related regions in AD and MCI patients.

Learning and Memory Alterations Are Associated with Hippocampal N-acetylaspartate in a Rat Model of Depression as Measured by 1H-MRS

It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS), to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA) in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume.

Abnormal Resting-State Activities and Functional Connectivities of the Anterior and the Posterior Cortexes in Medication-Naïve Patients with Obsessive-Compulsive Disorder

Background Obsessive-compulsive disorder (OCD) is a mental illness characterized by the loss of control. Because the cingulate cortex is believed to be important in executive functions, such as inhibition, we used functional magnetic resonance imaging (fMRI) techniques to examine whether and how activity and functional connectivity (FC) of the cingulate cortex were altered in drug-naïve OCD patients. Methods Twenty-three medication-naïve OCD patients and 23 well-matched healthy controls received fMRI scans in a resting state. Functional connectivities of the anterior cingulate (ACC) and the posterior cingulate (PCC) to the whole brain were analyzed using correlation analyses based on regions of interest (ROI) identified by the fractional amplitude of low-frequency fluctuation (fALFF). Independent Component Analysis (ICA) was used to identify the resting-state sub-networks. Results fALFF analysis found that regional activity was increased in the ACC and decreased in the PCC in OCD patients when compared to controls. FC of the ACC and the PCC also showed different patterns. The ACC and the PCC were found to belong to different resting-state sub-networks in ICA analysis and showed abnormal FC, as well as contrasting correlations with the severity of OCD symptoms. Conclusions Activity of the ACC and the PCC were increased and decreased, respectively, in the medication-naïve OCD patients compared to controls. Different patterns in FC were also found between the ACC and the PCC with respect to these two groups. These findings implied that the cardinal feature of OCD, the loss of control, may be attributed to abnormal activities and FC of the ACC and the PCC.

Adolescent escitalopram administration modifies neurochemical alterations in the hippocampus of maternally separated rats.

Early life stress is a potential precursor of eventual neuropsychiatric diseases and may result in altered neurodevelopment and function of the hippocampus, which thus provides a site at which potential interventions to modify the effects of early life stress may act. In this study, Sprague-Dawley rat pups comprising male and female animals underwent maternal separation (MS) for 180 min from postnatal days (PND) 2 to 14, or were left with their dams. They subsequently received daily administration of saline (0.9%), escitalopram (10 mg/kg), or no treatment during adolescence (PND 43-60). All adult animals underwent brain magnetic resonance imaging (MRI) and bilateral hippocampal proton magnetic resonance spectroscopy ((1)H-MRS). Neither MS nor escitalopram treatment had a significant effect on hippocampal volume. Adult rats that experienced MS displayed significantly increased choline-containing compounds (Cho) and decreased N-acetylaspartate (NAA), glutamate (Glu) and Myo-inositol (MI) relative to the stable neurometabolite creatine (Cr) in hippocampus. Administration of escitalopram during adolescence could modify the alterations of NAA/Cr, Glu/Cr and MI/Cr. The effects of MS on hippocampal neurochemistry were most significant in the right hippocampus. These results indicate that MS in rats has long-term consequences on hippocampal neurochemistry reflective of neural density/functional integrity, especially on the right hippocampus, and adolescent administration with escitalopram can at least partially ameliorate these neurochemical alterations. Furthermore, these metabolite changes seem to be more sensitive indicators of the results from early life stress than volume changes.

Delineation of Early and Later Adult Onset Depression by Diffusion Tensor Imaging

Background Due to a lack of evidence, there is no consistent age of onset to define early onset (EO) versus later onset (LO) major depressive disorder (MDD). Fractional anisotropy (FA), derived from diffusion tensor imaging (DTI), has been widely used to study neuropsychiatric disorders by providing information about the brain circuitry, abnormalities of which might facilitate the delineation of EO versus LO MDD. Method In this study, 61 pairs of untreated, non-elderly, first-episode MDD patients and healthy controls (HCs) aged 18–45 years old received DTI scans. The voxel-based analysis method (VBM), classification analysis, using the Statistical Package for the Social Sciences (SPSS), and regression analyses were used to determine abnormal FA clusters and their correlations with age of onset and clinical symptoms. Results Classification analysis suggested in the best model that there were two subgroups of MDD patients, delineated by an age of onset of 30 years old, by which MDD patients could be divided into EO (18–29 years old) and LO (30–45 years old) groups. LO MDD was characterized by decreased FA, especially in the white matter (WM) of the fronto-occipital fasciculus and posterior limb of internal capsule, with a negative correlation with the severity of depressive symptoms; in marked contrast, EO MDD showed increased FA, especially in the WM of the corpus callosum, corticospinal midbrain and inferior fronto-occipital fasciculus, while FA of the WM near the midbrain had a positive correlation with the severity of depressive symptoms. Conclusion Specific abnormalities of the brain circuitry in EO vs. LO MDD were delineated by an age of onset of 30 years old, as demonstrated by distinct abnormal FA clusters with opposite correlations with clinical symptoms. This DTI study supported the evidence of an exact age for the delineation of MDD, which could have broad multidisciplinary importance. Trial Registration ClinicalTrials.gov NCT00703742

fMRI Evidence of Acupoints Specificity in Two Adjacent Acupoints

Objectives. Acupoint specificity is the foundation of acupuncture treatment. The aim of this study is to investigate whether the acupoint specificity exists in two adjacent acupoints. Design and Setting. Two adjacent real acupoints, LR3 (Taichong) and ST44 (Neiting), and a nearby nonacupoint were selected. Thirty-three health volunteers were divided into three groups in random order, and each group only received acupuncture at one of the three points. While they received acupuncture, fMRI scan was performed. Results. The common cerebral activated areas responding to LR3 and ST44 included the contralateral primary somatosensory area (SI) and ipsilateral cerebellum. Acupuncture at LR3 specifically activated contralateral middle occipital gyrus, ipsilateral medial frontal gyrus, superior parietal lobe, middle temporal gyrus, rostral anterior cingulate cortex (rACC), lentiform nucleus, insula, and contralateral thalamus. Stimulation at ST44 selectively activated ipsilateral secondary somatosensory area (SII), contralateral middle frontal gyrus, inferior frontal gyrus, lingual gyrus, lentiform nucleus, and bilateral posterior cingulate cortex (PCC). Conclusions. Acupuncture at adjacent acupoints elicits distinct cerebral activation patterns, and those specific patterns might be involved in the mechanism of the specific therapeutic effects of different acupoints.