Brain Metabolite Levels Research Articles

Acupuncture therapy in treating migraine: results of a magnetic resonance spectroscopy imaging study.

BackgroundAcupuncture has been proven to be effective as an alternative therapy in treating migraine, but the pathophysiological mechanisms of the treatment remain unclear. This study investigated possible neurochemical responses to acupuncture treatment.Patients and methodsProton magnetic resonance spectroscopy imaging was used to investigate biochemical levels pre- and post-acupuncture treatment. Participants (N=45) included subjects diagnosed with: 1) migraine without aura; 2) cervicogenic headache; and 3) healthy controls. Participants in the two patient groups received verum acupuncture using acupoints that target migraine without aura but not cervicogenic headache, while the healthy controls received a sham treatment. All participants had magnetic resonance spectroscopy scans before and after the acupuncture therapy. Levels of brain metabolites were examined in relation to clinical headache assessment scores.ResultsA significant increase in N-acetylaspartate/creatine was observed in bilateral thalamus in migraine without aura after the acupuncture treatment, which was significantly correlated with the headache intensity score.ConclusionThe data demonstrate brain biochemical changes underlying the effect of acupuncture treatment of migraine.

S172. BRAIN METABOLITES AND THE RELATION WITH COGNITION AND PSYCHOTIC SYMPTOMS IN MEDICATION-FREE PSYCHOSIS AND CONTROLS: A PHARMACOLOGICAL MAGNETIC RESONANCE SPECTROSCOPY STUDY

BackgroundPsychotic disorders are complex neuropsychiatric disorders characterized by positive, negative and cognitive symptoms. Over the recent years, several neurotransmitter systems and neurometabolites have been related to psychotic disorders but the exact underlying neurobiological mechanisms are still not well understood. One neurotransmitter system that has been increasingly related to psychosis is the cholinergic muscarinic system. Increased choline concentrations and reduced muscarinic M1 receptor expression have been reported in schizophrenia. Therefore, the present study investigated brain metabolite concentrations, their responsivity to M1 receptor blockage, and their relation to cognitive, positive and negative symptoms in psychosis.Methods31 medication-free subjects with a psychotic disorder (mean age 27 years) and 31 gender, age and IQ-matched healthy control subjects (mean age 25 years) were enrolled in the study. 1H-proton magnetic resonance spectroscopy (1H-MRS, PRESS) was used to measure brain metabolites in the anterior cingulate cortex (ACC) and striatum. Metabolites measured included choline (Cho), glutamate (Glu), glutamine (Gln), GLX, myoinositol (MI), N-acetylaspartate (NAA) and gluthatione (GSH) (metabolite to creatine ratios were analyzed). All subjects were measured twice: once after placebo and once after a pharmacological challenge (4 mg. biperiden, a M1 receptor antagonist). The order of drug – challenge was counterbalanced. In addition, cognitive function was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and psychotic symptom severity was assessed with the Positive and Negative Syndrome Scale (PANSS) to examine the relation between brain metabolites and cognition and psychosis symptoms.ResultsNo significant differences were found in both ACC and striatal brain metabolite levels between subjects with a psychotic disorder and controls after placebo. Moreover, M1 blockade did not significantly affect brain metabolite levels in these regions and no group x challenge interaction effects were found. In addition, in both groups, no correlation was found between cognitive functioning and any of the brain metabolites. In subjects with a psychotic disorder, a positive correlation was found between striatal choline levels (after placebo) and negative symptom severity (p = 0.024).DiscussionThese results suggest that there are no differences in ACC and striatal brain metabolites between medication-free subjects with a psychotic disorder and healthy controls and that these metabolites are not influences by acute muscarinic M1 receptor antagonism. The significant correlation between striatal choline and negative symptom severity in the psychosis group could indicate that the cholinergic system is involved in negative symptom pathology. This is the first study that examined the influence of M1 receptor blockade on brain metabolites and therefore these results warrant replication.

The long-term effect of erythropoiesis stimulating agents given to preterm infants: a proton magnetic resonance spectroscopy study on neurometabolites in early childhood.

Erythropoiesis stimulating agents (ESAs) are neuroprotective in cell and animal models of preterm birth. Prematurity has been shown to alter neurometabolite levels in children in studies using proton magnetic resonance spectroscopy (1H-MRS). We hypothesized that ESA treatment in premature infants would tend to normalize neurometabolites by 4-6years of age. Children in a longitudinal study of neurodevelopment underwent MRI and 1H-MRS at approximately 4years and 6years of age. Prematurely born children (500-1,250g birth weight) received ESAs (erythropoietin or darbepoetin) or placebo during their neonatal hospitalization, and these groups were compared to healthy term controls. 1H-MRS spectra were obtained from the anterior cingulate (gray matter) and frontal lobe white matter, assessing combined N-acetylaspartate and N-acetylaspartylglutamate (tNAA), myo-inositol, choline compounds (Cho), combined creatine and phosphocreatine, and combined glutamate and glutamine. No significant (P≤0.5) group differences were observed for any metabolite level. Significant age-related increases in white-matter tNAA and Cho were observed, as well as a trend for increased gray-matter tNAA. Neither prematurity nor neonatal ESA treatment was associated with differences in brain metabolite levels in the children of this study at a significance level of 0.05. These findings suggest that earlier differences that might have existed had normalized by 4-6years of age or were too small to be statistically significant in the current sample.

Metabolic Changes Associated with a Rat Model of Diabetic Depression Detected by Ex Vivo 1H Nuclear Magnetic Resonance Spectroscopy in the Prefrontal Cortex, Hippocampus, and Hypothalamus.

Diabetic patients often present with comorbid depression. However, the pathogenetic mechanisms underlying diabetic depression (DD) remain unclear. To explore the mechanisms underpinning the pathogenesis of the disease, we used ex vivo 1H nuclear magnetic resonance spectroscopy and immunohistochemistry to investigate the main metabolic and pathological changes in various rat brain areas in an animal model of DD. Compared with the control group, rats in the DD group showed significant decreases in neurotransmitter concentrations of glutamate (Glu) and glutamine (Gln) in the prefrontal cortex (PFC), hippocampus, and hypothalamus and aspartate and glycine in the PFC and hypothalamus. Gamma-aminobutyric acid (GABA) was decreased only in the hypothalamus. Levels of the energy product, lactate, were higher in the PFC, hippocampus, and hypothalamus of rats with DD than those in control rats, while creatine was lower in the PFC and hippocampus, and alanine was lower in the hypothalamus. The levels of other brain metabolites were altered, including N-acetyl aspartate, taurine, and choline. Immunohistochemistry analysis revealed that expressions of both glutamine synthetase and glutaminase were decreased in the PFC, hippocampus, and hypothalamus of rats with DD. The metabolic changes in levels of Glu, Gln, and GABA indicate an imbalance of the Glu-Gln metabolic cycle between astrocytes and neurons. Our results suggest that the development of DD in rats may be linked to brain metabolic changes, including inhibition of the Glu-Gln cycle, increases in anaerobic glycolysis, and disturbances in the lactate-alanine shuttle, and associated with dysfunction of neurons and astrocytes.

Online effects of transcranial direct current stimulation on prefrontal metabolites in gambling disorder

Gambling disorder is characterized by persistent maladaptive gambling behaviors and is now considered among substance-related and addictive disorders. There is still unmet therapeutic need for these clinical populations, however recent advances indicate that interventions targeting the Glutamatergic/GABAergic system hold promise in reducing symptoms in substance-related and addictive disorders, including gambling disorder. There is some data indicating that transcranial direct current stimulation may hold clinical benefits in substance use disorders and modulate levels of brain metabolites including glutamate and GABA. The goal of the present work was to test whether this non-invasive neurostimulation method modulates key metabolites in gambling disorder. We conducted a sham-controlled, crossover, randomized study, blinded at two levels in order to characterize the effects of transcranial direct current stimulation over the dorsolateral prefrontal cortex on neural metabolites levels in sixteen patients with gambling disorder. Metabolite levels were measured with magnetic resonance spectroscopy from the right dorsolateral prefrontal cortex and the right striatum during active and sham stimulation. Active as compared to sham stimulation elevated prefrontal GABA levels. There were no significant changes between stimulation conditions in prefrontal glutamate + glutamine and N-acetyl Aspartate, or in striatal metabolite levels. Results also indicated positive correlations between metabolite levels during active, but not sham, stimulation and levels of risk taking, impulsivity and craving. Our findings suggest that transcranial direct current stimulation can modulate GABA levels in patients with gambling disorder which may represent an interesting future therapeutic avenue.

Relationships between brain metabolite levels, functional connectivity, and negative mood in urologic chronic pelvic pain syndrome patients compared to controls: A MAPP research network study.

Until recently, the predominant pathology of chronic pelvic pain conditions was thought to reside in the peripheral tissues. However, mounting evidence from neuroimaging studies suggests an important role of the central nervous system in the pathogenesis of these conditions. In the present cross-sectional study, proton magnetic resonance spectroscopy (1H-MRS) of the brain was conducted in female patients with urologic chronic pelvic pain syndrome (UCPPS) to determine if they exhibit abnormal concentrations of brain metabolites (e.g. those indicative of heightened excitatory tone) in regions involved in the processing and modulation of pain, including the anterior cingulate cortex (ACC) and the anterior and posterior insular cortices. Compared to a group of age-matched healthy subjects, there were significantly higher levels of choline (p = 0.006, uncorrected) in the ACC of UCPPS patients. ACC choline levels were therefore compared with the region's resting functional connectivity to the rest of the brain. Higher choline was associated with greater ACC-to-limbic system connectivity in UCPPS patients, contrasted with lower connectivity in controls (i.e. an interaction). In patients, ACC choline levels were also positively correlated with negative mood. ACC γ-aminobutyric acid (GABA) levels were lower in UCPPS patients compared with controls (p = 0.02, uncorrected), but this did not meet statistical correction for the 4 separate regional comparisons of metabolites. These results are the first to uncover abnormal GABA and choline levels in the brain of UCPPS patients compared to controls. Low GABA levels have been identified in other pain syndromes and might contribute to CNS hyper-excitability in these conditions. The relationships between increased ACC choline levels, ACC-to-limbic connectivity, and negative mood in UCPPS patients suggest that this metabolite could be related to the affective symptomatology of this syndrome.

Longitudinal increases of brain metabolite levels in 5-10 year old children.

Longitudinal magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies reveal significant changes in brain structure and structural networks that occur together with cognitive and behavioral maturation in childhood. However, the underlying cellular changes accompanying brain maturation are less understood. Examining regional age-related changes in metabolite levels provides insight into the physiology of neurodevelopment. Magnetic resonance spectroscopy (MRS) measures localize brain metabolism. The majority of neuroimaging studies of healthy development are from the developed world. In a longitudinal MRS study of 64 South African children aged 5 to 10 years old (29 female; 29 HIV exposed, uninfected), we examined the age-related trajectories of creatine (Cr+PCr), N-acetyl-aspartate (NAA), the combined NAA+N-acetyl-aspartyl-glutamate (NAAG), choline (GPC+PCh), glutamate (Glu) and the combined Glu+glutamine (Glu+Gln) in voxels within gray and white matter, as well as subcortically in the basal ganglia (BG). In frontal gray matter, we found age-related increases in Cr+PCr, NAA, NAA+NAAG and Glu+Gln levels pointing to synaptic activity likely related to learning. In the BG we observed increased levels of Glu, Glu+Gln and NAA+NAAG with age that point to subcortical synaptic reorganization. In white matter, we found increased levels of Cr+PCr, NAA, NAA+NAAG, Glu and Glu+Gln with age, implicating these metabolites in ongoing myelination. We observed no sex-age or HIV exposure-age interactions, indicating that physiological changes are independent of sex during this time period. The metabolite trajectories presented, therefore, provide a critical benchmark of normal cellular growth for a low socioeconomic pediatric population in the developing world against which pathology and abnormal development may be compared.

Specialized Information Processing Deficits and Distinct Metabolomic Profiles Following TM-Domain Disruption of Nrg1.

Although there is considerable genetic and pathologic evidence for an association between neuregulin 1 (NRG1) dysregulation and schizophrenia, the underlying molecular and cellular mechanisms remain unclear. Mutant mice containing disruption of the transmembrane (TM) domain of the NRG1 gene constitute a heuristic model for dysregulation of NRG1-ErbB4 signaling in schizophrenia. The present study focused on hitherto uncharacterized information processing phenotypes in this mutant line. Using a mass spectrometry-based metabolomics approach, we also quantified levels of unique metabolites in brain. Across 2 different sites and protocols, Nrg1 mutants demonstrated deficits in prepulse inhibition, a measure of sensorimotor gating, that is, disrupted in schizophrenia; these deficits were partially reversed by acute treatment with second, but not first-, generation antipsychotic drugs. However, Nrg1 mutants did not show a specific deficit in latent inhibition, a measure of selective attention that is also disrupted in schizophrenia. In contrast, in a “what–where–when” object recognition memory task, Nrg1 mutants displayed sex-specific (males only) disruption of “what–when” performance, indicative of impaired temporal aspects of episodic memory. Differential metabolomic profiling revealed that these behavioral phenotypes were accompanied, most prominently, by alterations in lipid metabolism pathways. This study is the first to associate these novel physiological mechanisms, previously independently identified as being abnormal in schizophrenia, with disruption of NRG1 function. These data suggest novel mechanisms by which compromised neuregulin function from birth might lead to schizophrenia-relevant behavioral changes in adulthood.

脑卒中肌张力增高与多巴胺神经递质水平关系的研究

目的：探究分析脑卒中患者出现肌张力障碍后，体内多巴胺递质水平的变化以及两者之间的相关性。方法：选取2015年1月至2016年1月期间在我院收治的脑卒中后肌张力障碍在II级以上患者59例作为观察组，59例脑卒中后肌张力在II级以下患者作为对照组，并对两组患者进行康复治疗。使用头颅磁共振波谱分析对研究对象神经递质多巴胺(DA)、乙酰胆碱(Cho)以及脑部代谢产物如N-乙酰天门冬氨酸(NAA)、乳酸(Lac)等指标进行检测，分析观察其指标变化水平。结果：观察组DA的含量与对照组相比显著升高，Cho、NAA的峰值显著降低，Lac的含量显著升高，且两组之间的差异有统计学意义(P < 0.05)。结论：肌张力障碍患者脑部的神经递质水平和代谢产物存在失衡，提示其与肌张力障碍有一定的相关性，可为临床脑卒中患者的治疗及预后提供重要的临床研究基础。 Objective: To explore and analyze the changes of dopamine level after stroke patients presenting dystonia and the correlation between them. Methods: 59 stroke patients with dystonia of level II or above who were treated in our hospital from January 2015 to January 2016 were included in observation group, and 59 stroke patients with dystonia below level II were included in control group, and both of the two groups of patients were treated for rehabilitation. Head magnetic resonance-spectroscopy was used to examine the neurotransmitters like dopamine (DA) and acetylcholine (Cho) and the brain metabolites like N-acetyl aspartic acid (NAA), lactic acid (Lac) and the changes of these indicators were observed and analyzed. Results: Compared to the control group, the content of DA in the observation group was significantly increased, and the peak values of Cho and NAA were significantly decreased and the content of Lac was significantly increased; there was statistical significance in the difference between the two groups (P < 0.05). Conclusion: The levels of neurotransmitter and brain metabolites of dystonia patients were imbalanced, which suggested that there was certain correlation with dystonia, providing an important basis for clinical research on the treatment and prognosis of stroke patients.

The positive effects of high-frequency right dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation on memory, correlated with increases in brain metabolites detected by proton magnetic resonance spectroscopy in recently detoxified alcohol-dependent patients.

ObjectiveTo explore the effect of right dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) on memory, and its correlation with levels of hippocampal brain metabolites detected by proton magnetic resonance spectroscopy (1H-MRS) in recently detoxified alcohol-dependent patients.Materials and methodsIn this randomized, double-blind sham-controlled trial, alcohol-dependent patients were enrolled and randomized into two groups: the experimental group (rTMS, 10 Hz, on right DLPFC, 20 sessions) and the control group (sham stimulation). Memory function was assessed using Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) before and after treatment. 1H-MRS was used to detect the levels of N-acetyl aspartic acid (NAA), choline (Cho), and creatine (Cr) in bilateral hippocampi before and after treatment.ResultsThirty-eight patients (18 in the experimental group and 20 in the control group) were included in the analyses. The experimental group showed significantly greater changes in HVLT-R, BVMT-R, NAA/Cr, and Cho/Cr after rTMS from baseline than the control group. The percentage change in BVMT-R and HVLT-R correlated with the percentage change in NAA/Cr and Cho/Cr in the right brain.ConclusionHigh-frequency right DLPFC rTMS was associated with improvement in memory dysfunction, which is correlated with levels of hippocampal brain metabolites detected by 1H-MRS in recently detoxified alcohol-dependent patients.

Brain metabolite levels and language abilities in preschool children

IntroductionLanguage acquisition occurs rapidly during early childhood and lays the foundation for future reading success. However, little is known about the brain–language relationships in young children. The goal of this study was to investigate relationships between brain metabolites and prereading language abilities in healthy preschool‐aged children.MethodsParticipants were 67 healthy children aged 3.0–5.4 years scanned on a 3T GE MR750w MRI scanner using short echo proton spectroscopy with a voxel placed in the anterior cingulate gyrus (n = 56) and/or near the left angular gyrus (n = 45). Children completed the NEPSY‐II Phonological Processing and Speeded Naming subtests at the same time as their MRI scan. We calculated glutamate, glutamine, creatine/phosphocreatine, choline, inositol, and NAA concentrations, and correlated these with language skills.ResultsIn the anterior cingulate, Phonological Processing Scaled Scores were significantly correlated with glutamate, creatine, and inositol concentrations. In the left angular gyrus, Speeded Naming Combined Scaled Scores showed trend correlations with choline and glutamine concentrations.ConclusionsFor the first time, we demonstrate relationships between brain metabolites and prereading language abilities in young children. Our results show relationships between language and inositol and glutamate that may reflect glial differences underlying language function, and a relationship of language with creatine. The trend between Speeded Naming and choline is consistent with previous research in older children and adults; however, larger sample sizes are needed to confirm whether this relationship is indeed significant in young children. These findings help understand the brain basis of language, and may ultimately lead to earlier and more effective interventions for reading disabilities.

Chronic psychosocial stress in mice leads to changes in brain functional connectivity and metabolite levels comparable to human depression

Human depression, for which chronic psychosocial stress is a major risk factor, is characterized by consistent alterations in neurocircuitry. For example, there is increased functional connectivity (FC) within and between regions comprising the default mode network (DMN) including prefrontal cortex and cingulate cortex. Alterations in network FC are associated with specific aspects of psychopathology. In mice, chronic psychosocial stress (CPS) leads to depression-relevant behavior, including increased fear learning, learned helplessness, fatigue and decreased motivation for reward. Using multimodal in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS), we investigated CPS effects on function and structure in the mouse brain under light anesthesia. Mice underwent a baseline MRI/MRS session, followed by 15-day CPS (n=26) or control handling (n=27), and a post-treatment MRI/MRS session. In BOLD fMRI, relative to controls, CPS mice exhibited robust, reproducible increases in FC within 8 of 9 identified cortical networks, including the prefrontal and cingulate cortices that contribute to the “mouse DMN”. CPS mice exhibited increases in between-network FC, including amygdala - prefrontal cortex and amygdala - cingulate cortex. MRS identified metabolic alterations in CPS mice as increased inositol levels in amygdala and increased glycerophosphorylcholine levels in prefrontal cortex. Diffusion-weighted MRI detected increased fractional anisotropic values in the cingulum. This study demonstrates that chronic psychosocial stress induces FC states in the mouse brain analogous to those observed in depression, as well as cerebral metabolism and white matter pathway alterations that contribute to understanding of pathological processes. It also demonstrates the importance of brain imaging to the establishment of valid animal models in translational psychiatry.

HIV-associated CD4+/CD8+ depletion in infancy is associated with neurometabolic reductions in the basal ganglia at age 5 years despite early antiretroviral therapy.

Investigating consequences of early or late antiretroviral therapy (ART) initiation in infancy on young brain development using magnetic resonance spectroscopy. Most pediatric HIV/ART-related neurological studies are from neuropsychological/clinical perspectives. Magnetic resonance spectroscopy can elucidate the mechanisms underpinning neurocognitive outcomes by quantifying the brain's chemical condition through localized metabolism to provide insights into health and development. Basal ganglia metabolite concentrations were assessed in thirty-eight 5-year-old HIV-infected children previously participating in a randomized trial comparing early limited ART to deferred continuous ART, as well as 15 uninfected controls (12 HIV exposed). Metabolite levels were compared between 26 infected children who initiated ART at/before 12 weeks and 12 who initiated afterward, and were correlated with clinical HIV and treatment-related measures. HIV-infected children initiating ART after 12 weeks had lower creatine, choline and glutamate (P < 0.05) than those initiating ART at/before 12 weeks. The CD4/CD8 ratio at baseline correlated with N-acetyl-aspartate (r = 0.56, P = 0.003) and choline (r = 0.36, P = 0.03) at 5 years, irrespective of treatment regimen and ART interruption. In comparison with uninfected controls, 80% of whom were HIV-exposed in utero, children on early treatment had higher N-acetyl-aspartate (P = 0.006) and choline (P = 0.03). Despite early ART (<12 weeks), low baseline CD4/CD8 predicts brain metabolite levels in later childhood. Also, HIV exposure and antiretroviral exposure for preventing vertical HIV transmission may hinder metabolite health, but needs further investigation.

Longitudinal Metabolite Profiling of Cerebrospinal Fluid in Normal Pressure Hydrocephalus Links Brain Metabolism with Exercise-Induced VEGF Production and Clinical Outcome.

Idiopathic normal pressure hydrocephalus is a neurological disease caused by abnormal cerebrospinal fluid flow and presents with symptoms such as dementia. Current therapy involves the removal of excess cerebrospinal fluid by shunting. Not all patients respond to this therapy and biomarkers are needed that could facilitate the characterization of patients likely to benefit from this treatment. Here, we measure brain metabolism in normal pressure hydrocephalus patients by performing a novel longitudinal metabolomic profiling study of cerebrospinal fluid. We find that the levels of brain metabolites correlate with clinical parameters, the amount of vascular endothelial growth factor in the cerebrospinal fluid, and environmental stimuli such as exercise. Metabolomic analysis of normal pressure hydrocephalus patients provides insight into changes in brain metabolism that accompany cerebrospinal fluid disorders and may facilitate the development of new biomarkers for this condition.

Impact of Single or Repeated Dose Intranasal Zinc-free Insulin in Young and Aged F344 Rats on Cognition, Signaling, and Brain Metabolism.

Novel therapies have turned to delivering compounds to the brain using nasal sprays, bypassing the blood brain barrier, and enriching treatment options for brain aging and/or Alzheimer's disease. We conducted a series of in vivo experiments to test the impact of intranasal Apidra, a zinc-free insulin formulation, on the brain of young and aged F344 rats. Both single acute and repeated daily doses were compared to test the hypothesis that insulin could improve memory recall in aged memory-deficient animals. We quantified insulin signaling in different brain regions and at different times following delivery. We measured cerebral blood flow (CBF) using MRI and also characterized several brain metabolite levels using MR spectroscopy. We show that neither acute nor chronic Apidra improved memory or recall in young or aged animals. Within 2 hours of a single dose, increased insulin signaling was seen in ventral areas of the aged brains only. Although chronic Apidra was able to offset reduced CBF with aging, it also caused significant reductions in markers of neuronal integrity. Our data suggest that this zinc-free insulin formulation may actually hasten cognitive decline with age when used chronically.

Brain metabolite levels in recently sober individuals with alcohol use disorder: Relation to drinking variables and relapse

Magnetic resonance spectroscopy (MRS) studies in alcohol use disorder (AUD) typically report lower levels of N-acetylaspartate (NAA) and choline-containing compounds (Cho) in several brain regions. Metabolite levels, however, are labile and can be affected by several competing factors, some related to drinking variables.. This in vivo MRS study included 20 recently sober (19.6±12.6 days) individuals with AUD and 15 controls. MRS was performed in single voxels placed in frontal white matter and thalamic regions using Constant-Time Point Resolved Spectroscopy (CT-PRESS) for absolute quantification of NAA, Cho, total creatine (tCr), and glutamate (Glu). A trend toward a thalamic NAA deficit in the total AUD group compared with controls was attributable to the subgroup of alcoholics who relapsed 3 or so months after scanning. In the total AUD group, frontal and thalamic NAA and Cho levels were lower with more recent drinking; frontal and thalamic Cho levels were also lower in AUD individuals with past stimulant abuse. Thalamic Cho levels were higher in binge-drinking AUD individuals and in those with longer length of alcohol dependence. MRS-visible metabolite peaks appear to be modulated by variables related to drinking behaviors, suggesting a sensitivity of MRS in tracking and predicting the dynamic course of alcoholism.

A Longitudinal (6-week) 3T 1H-MRS Study on the Effects of Lithium Treatment on Anterior Cingulate Cortex Metabolites in Bipolar Depression

The anterior cingulate cortex (ACC) is a key area in mood regulation. To date, no longitudinal study has specifically evaluated lithium׳s effects on ACC metabolites using 1H-MRS, as well as its association with clinical improvement in bipolar depression. This 1H-MRS (TE=35ms) study evaluated 24 drug-free BD patients during depressive episodes and after lithium treatment at therapeutic levels. Brain metabolite levels (N-acetyl aspartate (NAA), creatine (tCr), choline, myo-inositol, and glutamate levels) were measured in the ACC at baseline (week 0) and after lithium monotherapy (week 6). The present investigation showed that ACC glutamate (Glu/tCr) and glutamate+glutamine (Glx/tCr) significantly increased after six weeks of lithium therapy. Regarding the association with clinical improvement, remitters showed an increase in myoinositol levels (mI/tCr) after lithium treatment compared to non-remitters. The present findings reinforce a role for ACC glutamate-glutamine cycling and myoinositol pathway as key targets for lithium׳s therapeutic effects in BD.

Association of adult attention deficit hyperactivity disorder subtypes and response to methylphenidate HCL treatment: A magnetic resonance spectroscopy study

The effects of methylphenidate (MPH) treatment on N-acetyl aspartate (NAA), choline and creatine are being examined in individuals with different subtypes of attention deficit hyperactivity disorder (ADHD). Sixty ADHD subjects were included into the study aging between 18 and 60 years. Levels of NAA, creatine and choline in anterior cingulate cortex, cerebellum, striatum and dorsolateral prefrontal cortex were measured with magnetic resonance spectroscopy. Then, 10mg oral MPH was given to the subjects and the same metabolite levels were measured after an interval of 30min. Distribution of the patients according to the ADHD subtypes was as follows: 21 of them (35.0%) were in the inattentive type, 11 of them (18.3%) were in the hyperactive type and 28 of them were (46.7%) in the combined type. Changes of brain metabolite levels after MPH were found not to be statistically significantly different between the subtypes. The increase of choline levels after MPH compared to the levels of choline before MPH in striatum in the combined type patients were statistically significant. No clear association was found between ADHD subtypes and changes of brain metabolites with use of MPH in adult ADHD.

Evaluation of disease progression in INCL by MR spectroscopy.

ObjectiveInfantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase-1 deficiency, which impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury. As part of a pilot study to evaluate treatment benefits of cysteamine bitartrate and N-acetylcysteine, we quantitatively measured brain metabolite levels using magnetic resonance spectroscopy (MRS).MethodsA subset of two patients from a larger treatment and follow-up study underwent serial quantitative single-voxel MRS examinations of five anatomical sites. Three echo times were acquired in order to estimate metabolite T2. Measured metabolite levels included correction for partial volume of cerebrospinal fluid. Comparison of INCL patients was made to a reference group composed of asymptomatic and minimally symptomatic Niemann-Pick disease type C patients.ResultsIn INCL patients, N-acetylaspartate (NAA) was abnormally low at all locations upon initial measurement, and further declined throughout the follow-up period. In the cerebrum (affected early in the disease course), choline and myo-inositol were initially elevated and fell during the follow-up period, whereas in the cerebellum and brainstem (affected later), choline and myo-inositol were initially normal and rose subsequently.InterpretationCholine and myo-inositol levels in our patients are consistent with patterns of neuroinflammation observed in two INCL mouse models. Low, persistently declining NAA was expected based on the progressive, irreversible nature of the disease. Progression of metabolite levels in INCL has not been previously quantified; therefore the results of this study serve as a reference for quantitative evaluation of future therapeutic interventions.

Magnetic Resonance Spectroscopy in Alzheimer's Disease: Systematic Review and Meta-Analysis.

The application of non-invasive proton magnetic resonance spectroscopy (1H-MRS) could potentially identify changes in cerebral metabolites in the patients with Alzheimer's disease (AD). However, whether these metabolites can serve as biomarkers for the diagnosis of AD remains unclear. Using meta-analysis, we aimed to investigate the patterns of cerebral metabolite changes in several cerebral regions that are strongly associated with cognitive decline in AD patients. Using Hedges' g effect size, a systematic search was performed in PubMed, Cochrane Library, Ovid, Embase, and EBSCO, and 38 studies were integrated into the final meta-analysis. According to the observational studies, N-acetyl aspartate (NAA) in AD patients was significantly reduced in the posterior cingulate (PC) (effect size (ES) =-0.924, p < 0.005) and bilateral hippocampus (left hippocampus: ES =-1.329, p < 0.005; right hippocampus: ES =-1.287, p < 0.005). NAA/Cr (creatine) ratio decreased markedly in the PC (ES =-1.052, p < 0.005). Simultaneously, significant elevated myo-inositol (mI)/Cr ratio was found not only in the PC but also in the parietal gray matter. For lack of sufficient data, we failed to elucidate the efficacy of pharmacological interventions with the metabolites changes. The available data indicates that NAA, mI, and the NAA/Cr ratio might be potential biomarkers of brain dysfunction in AD subjects. Choline (Cho)/Cr and mI/NAA changes might also contribute toward the diagnostic process. Thus, large, well-designed studies correlated with cerebral metabolism are needed to better estimate the cerebral extent of alterations in brain metabolite levels in AD patients.