Investigation of anterior cingulate cortex gamma-aminobutyric acid and glutamate-glutamine levels in obsessive-compulsive disorder using magnetic resonance spectroscopy.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a relatively common and disabling psychiatric disorder whose pathophysiology is incompletely understood. In this study, we utilized magnetic resonance spectroscopy (MRS) in an effort to provide a better understanding of the role of brain gamma-aminobutyric acid (GABA) and glutamate in the pathophysiology of OCD. We hypothesized that beyond the separate effects of these neurotransmitter systems, a disruption in the balance between GABA and glutamate could be particularly relevant to OCD. METHODS: We obtained MRS measures of GABA and glutamate concentrations in the anterior cingulate cortex from 23 adult patients with OCD and 20 sex- and age-matched healthy community volunteers. Established clinical rating scales were used to assess the severities of OCD, anxiety, and depression symptoms. Statistical analysis involved the assessment of patient-control group differences in the individual measures of GABA and glutamate, as well as in the ratio of the GABA to glutamate measures. Additionally, we explored whether differences in the MRS measures existed between two subgroups of patients formed according to the severity of their OCD symptoms. Finally, we assessed the relations of demographic and clinical variables to the MRS measures. RESULTS: Patients with OCD displayed a higher estimated GABA level and a higher GABA to glutamate ratio than healthy participants, but no significant group differences were observed in the measure of glutamate. The MRS measures did not vary by subgroup and showed no correlations with demographic and clinical variables. CONCLUSIONS: These results indicate that GABA abnormalities within the anterior cingulate cortex contribute to the pathophysiology of OCD. The results fail to provide evidence that glutamate abnormalities alone are involved in adult OCD. Yet, it seems that a disruption in the balance between glutamate and GABA neurotransmission may have a particularly important role to play in OCD pathophysiology

Abnormal Voxel-Wise Degree Centrality in Patients With Late-Life Depression: A Resting-State Functional Magnetic Resonance Imaging Study.

Objectives:Late-life depression (LLD) has negative impacts on somatic, emotional and cognitive domains of the lives of patients. Elucidating the abnormality in the brain networks of LLD patients could help to strengthen the understanding of LLD pathophysiology, however, the studies exploring the spontaneous brain activity in LLD during the resting state remain limited. This study aimed at identifying the voxel-level whole-brain functional connectivity changes in LLD patients. Methods:Fifty patients with late-life depression (LLD) and 33 healthy controls were recruited. All participants underwent a resting-state functional magnetic resonance imaging scan to assess the voxel-wise degree centrality (DC) changes in the patients. Furthermore, DC was compared between two patient subgroups, the late-onset depression (LOD) and the early-onset depression (EOD). Results:Compared with the healthy controls, LLD patients showed increased DC in the inferior parietal lobule, parahippocampal gyrus, brainstem and cerebellum (p < 0.05, AlphaSim-corrected). LLD patients also showed decreased DC in the somatosensory and motor cortices and cerebellum (p < 0.05, AlphaSim-corrected). Compared with EOD patients, LOD patients showed increased centrality in the superior and middle temporal gyrus and decreased centrality in the occipital region (p < 0.05, AlphaSim-corrected). No significant correlation was found between the DC value and the symptom severity or disease duration in the patients after the correction for multiple comparisons. Conclusions:These findings indicate that the intrinsic abnormality of network centrality exists in a wide range of brain areas in LLD patients. LOD patients differ with EOD patients in cortical network centrality. Our study might help to strengthen the understanding of the pathophysiology of LLD and the potential neural substrates underlie related emotional and cognitive impairments observed in the patients

Abnormal Dynamic Functional Connectivity Associated With Subcortical Networks in Parkinson’s Disease: A Temporal Variability Perspective

Parkinson’s disease (PD) is a neurodegenerative disease characterized by dysfunction in distributed functional brain networks. Previous studies have reported abnormal changes in static functional connectivity using resting-state functional magnetic resonance imaging (fMRI). However, the dynamic characteristics of brain networks in PD is still poorly understood. This study aimed to quantify the characteristics of dynamic functional connectivity in PD patients at nodal, intra- and inter-subnetwork levels. Resting-state fMRI data of a total of 42 PD patients and 40 normal controls (NCs) were investigated from the perspective of the temporal variability on the connectivity profiles across sliding windows. The results revealed that PD patients had greater nodal variability in precentral and postcentral area (in sensorimotor network, SMN), middle occipital gyrus (in visual network), putamen (in subcortical network) and cerebellum, compared with NCs. Furthermore, at the subnetwork level, PD patients had greater intra-network variability for the subcortical network, salience network and visual network, and distributed changes of inter-network variability across several subnetwork pairs. Specifically, the temporal variability within and between subcortical network and other cortical subnetworks involving SMN, visual, ventral and dorsal attention networks as well as cerebellum was positively associated with the severity of clinical symptoms in PD patients. Additionally, the increased inter-network variability of cerebellum-auditory pair was also correlated with clinical severity of symptoms in PD patients. These observations indicate that temporal variability can detect the distributed abnormalities of dynamic functional network of PD patients at nodal, intra- and inter-subnetwork scales, and may provide new insights into understanding PD

Regional High Iron in the Substantia Nigra Differentiates Parkinson’s Disease Patients From Healthy Controls

Background: Iron is important in the pathophysiology of Parkinson’s disease (PD) specifically related to degeneration of the substantia nigra (SN). Magnetic resonance imaging (MRI) can be used to measure brain iron in the entire structure but this approach is insensitive to regional changes in iron content.Objective: The goal of this work was to use quantitative susceptibility mapping (QSM) and R2∗ to quantify both global and regional brain iron in PD patients and healthy controls (HC) to ascertain if regional changes correlate with clinical conditions and can be used to discriminate patients from controls.Methods: Susceptibility and R2∗ maps of 25 PD and 24 HC subjects were reconstructed from data collected on a 3T GE scanner. For the susceptibility maps, three-dimensional regions-of-interest (ROIs) were traced on eight deep gray matter (DGM) structures and an age-based threshold was applied to define regions of high iron content. The same multi-slice ROIs were duplicated on the R2∗ maps as well. Mean susceptibility values of both global and regional high iron (RII) content along with global R2∗ values were measured and compared not only between the two cohorts, but also to susceptibility and R2∗ baselines as a function of age. Finally, clinical features were compared for those PD patients lying above and below the upper 95% regional susceptibility-age prediction intervals.Results: The SN was the only structure showing significantly higher susceptibility in PD patients compared to controls globally (p &lt; 0.01) and regionally (p &lt; 0.001). The R2∗ values were also higher only in the SN of PD patients compared to the healthy cohort (p &lt; 0.05). Furthermore, those patients with abnormal susceptibility values lying above the upper 95% prediction intervals had significantly higher united Parkinson’s diagnostic rating scores. R2∗ values had larger errors and showed larger dispersion as a function of age than QSM data for global analysis while the dispersion was significantly less for QSM using the RII iron content.Conclusion: Abnormal iron deposition in the SN, especially in RII areas, could serve as a biomarker to distinguish PD patients from HC and to assess disease severity

Application of Neuromelanin MR Imaging in Parkinson Disease

MRI has been used to develop biomarkers for movement disorders such as Parkinson disease (PD) and other neurodegenerative disorders with parkinsonism such as progressive supranuclear palsy and multiple system atrophy. One of these imaging biomarkers is neuromelanin (NM), whose integrity can be assessed from its contrast and volume. NM is found mainly in certain brain stem structures, namely, the substantia nigra pars compacta (SNpc), the ventral tegmental area, and the locus coeruleus. Another major biomarker is brain iron, which often increases in concert with NM degeneration. These biomarkers have the potential to improve diagnostic certainty in differentiating between PD and other neurodegenerative disorders similar to PD, as well as provide a better understanding of pathophysiology. Mapping NM in vivo has clinical importance for gauging the premotor phase of PD when there is a greater than 50% loss of dopaminergic SNpc melanized neurons. As a metal ion chelator, NM can absorb iron. When NM is released from neurons, it deposits iron into the intracellular tissues of the SNpc; the result is iron that can be imaged and measured using quantitative susceptibility mapping. An increase of iron also leads to the disappearance of the nigrosome-1 sign, another neuroimage biomarker for PD. Therefore, mapping NM and iron changes in the SNpc are a practical means for improving early diagnosis of PD and in monitoring disease progression. In this review, we discuss the functions and location of NM, how NM-MRI is performed, the automatic mapping of NM and iron content, how NM-related imaging biomarkers can be used to enhance PD diagnosis and differentiate it from other neurodegenerative disorders, and potential advances in NM imaging methods. With major advances currently evolving for rapid imaging and artificial intelligence, NM-related biomarkers are likely to have increasingly important roles for enhancing diagnostic capabilities in PD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2

Longitudinal data for magnetic susceptibility of normative human brain development and aging over the lifespan.

The data presented in this article accompany the research article entitled "Longitudinal Atlas for Normative Human Brain Development and Aging over the Lifespan using Quantitative Susceptibility Mapping" (Zhang et al., 2018) [1]. The longitudinal evolution of magnetic susceptibility in human brain indicates critical characteristics of normal brain development and aging. In the corresponding research article, we build longitudinal QSM atlases over various age intervals using 166 healthy subjects (83F/69M) with an age range of 1-83 years old. Based on the newly built atlases, we investigate the regional evolutions of magnetic susceptibility in the brain. In this article, we report anatomical evolutions of the age-specific QSM atlases in deep gray matter nuclei and in two selected white matter fiber bundles. In addition to iron-rich brain nuclei, the evolution patterns of the magnetic susceptibility in the amygdala and hippocampus are also presented

Longitudinal data for magnetic susceptibility of normative human brain development and aging over the lifespan

The data presented in this article accompany the research article entitled “Longitudinal Atlas for Normative Human Brain Development and Aging over the Lifespan using Quantitative Susceptibility Mapping” (Zhang et al., 2018) [1]. The longitudinal evolution of magnetic susceptibility in human brain indicates critical characteristics of normal brain development and aging. In the corresponding research article, we build longitudinal QSM atlases over various age intervals using 166 healthy subjects (83F/69M) with an age range of 1–83 years old. Based on the newly built atlases, we investigate the regional evolutions of magnetic susceptibility in the brain. In this article, we report anatomical evolutions of the age-specific QSM atlases in deep gray matter nuclei and in two selected white matter fiber bundles. In addition to iron-rich brain nuclei, the evolution patterns of the magnetic susceptibility in the amygdala and hippocampus are also presented