Decrease In N-acetylaspartate Research Articles

Perturbed neurochemical and microstructural organization in a mouse model of prenatal opioid exposure: A multi-modal magnetic resonance study.

Methadone-based treatment for pregnant women with opioid use disorder is quite prevalent in the clinical environment. A number of clinical and animal model-based studies have reported cognitive deficits in infants prenatally exposed to methadone-based opioid treatments. However, the long-term impact of prenatal opioid exposure (POE) on pathophysiological mechanisms that govern neurodevelopmental impairment is not well understood. Using a translationally relevant mouse model of prenatal methadone exposure (PME), the aim of this study is to investigate the role of cerebral biochemistry and its possible association with regional microstructural organization in PME offspring. To understand these effects, 8-week-old male offspring with PME (n = 7) and prenatal saline exposure (PSE) (n = 7) were scanned in vivo on 9.4 Tesla small animal scanner. Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed in the right dorsal striatum (RDS) region using a short echo time (TE) Stimulated Echo Acquisition Method (STEAM) sequence. Neurometabolite spectra from the RDS was first corrected for tissue T1 relaxation and then absolute quantification was performed using the unsuppressed water spectra. High-resolution in vivo diffusion MRI (dMRI) for region of interest (ROI) based microstructural quantification was also performed using a multi-shell dMRI sequence. Cerebral microstructure was characterized using diffusion tensor imaging (DTI) and Bingham-neurite orientation dispersion and density imaging (Bingham-NODDI). MRS results in the RDS showed significant decrease in N-acetyl aspartate (NAA), taurine (tau), glutathione (GSH), total creatine (tCr) and glutamate (Glu) concentration levels in PME, compared to PSE group. In the same RDS region, mean orientation dispersion index (ODI) and intracellular volume fraction (VFIC) demonstrated positive associations with tCr in PME group. ODI also exhibited significant positive association with Glu levels in PME offspring. Significant reduction in major neurotransmitter metabolites and energy metabolism along with strong association between the neurometabolites and perturbed regional microstructural complexity suggest a possible impaired neuroadaptation trajectory in PME offspring which could be persistent even into late adolescence and early adulthood.

Electroconvulsive therapy triggers a reversible decrease in brain N-acetylaspartate.

Based on previous research on electroconvulsive therapy (ECT) we have proposed a model where disruption, potentiation, and rewiring of brain networks occur in sequence and serve as the underlying therapeutic mechanism of ECT. This model implies that a temporary disturbance of neuronal networks (disruption) is followed by a trophic effect (potentiation), which enables the rewiring of neuronal circuits to a more euthymic functioning brain. We hypothesized that disruption of neuronal networks could trigger biochemical alterations leading to a temporary decrease in N-acetylaspartate (tNAA, considered a marker of neuronal integrity), while choline (a membrane component), myo-Inositol (mI, astroglia marker), and glutamate/glutamine (Glx, excitatory neurotransmitter) were postulated to increase. Previous magnetic resonance spectroscopy studies, reporting diverse findings, have used two different referencing methods - creatine ratios and tissue corrected values referenced to water - for the quantification of brain metabolites. Changes in creatine during ECT have also been reported, which may confound estimates adopting this as an internal reference. Using MR spectroscopy, we investigated 31 moderately to severely depressed patients and 19 healthy controls before, during, and after ECT or at similar time points (for controls). We tested whether biochemical alterations in tNAA, choline, mI, and Glx lend support to the disrupt, potentiate, and rewire hypothesis. We used both creatine ratios and water-scaled values for the quantification of brain metabolites to validate the results across referencing methods. Levels of tNAA in the anterior cingulate cortex decreased after an ECT treatment series (average 10.6 sessions) by 6% (p = 0.007, creatine ratio) and 3% (p = 0.02, water referenced) but returned to baseline 6 months after ECT. Compared to after treatment series tNAA levels at 6-month follow-up had increased in both creatine ratio (+6%, p < 0.001) and water referenced data (+7%, p < 0.001). Findings for other brain metabolites varied and could not be validated across referencing methods. Our findings suggest that prior research must be interpreted with care, as several referencing and processing methods have been used in the past. Yet, the results for tNAA were robust across quantification methods and concur with relevant parts of the disrupt, potentiate, and rewire model.

Whole-Brain Magnetic Resonance Spectroscopy Reveals Distinct Alterations in Neurometabolic Profile in Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is an atypical Parkinsonian syndrome characterized by supranuclear gaze palsy, early postural instability, and a frontal dysexecutive syndrome. Contrary to normal brain magnetic resonance imaging in Parkinson's disease (PD), PSP shows specific cerebral atrophy patterns and alterations, but these findings are not present in every patient, and it is still unclear if these signs are also detectable in early disease stages. The aim of the present study was to analyze the metabolic profile of patients with clinically diagnosed PSP in comparison with matched healthy volunteers and PD patients using whole-brain magnetic resonance spectroscopicimaging (wbMRSI). Thirty-nine healthy controls (HCs), 29 PD, and 22 PSP patients underwent wbMRSI. PSP and PD patients were matched for age and handedness with HCs. Clinical characterization was performed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, PSP rating scale, and DemTect (test for cognitive assessment). In PSP patients a significant reduction in N-acetyl-aspartate (NAA) was detected in all brain lobes. Fractional volume of the cerebrospinal fluid significantly increased in PSP patients compared to PD and healthy volunteers. In PSP much more neuronal degeneration and cerebral atrophy have been detected compared with PD. The most relevant alteration is the decrease in NAA in all lobes of the brain, which also showed a partial correlation with clinical symptoms. However, more studies are needed to confirm the additional value of wbMRSI in clinical practice. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

172. Decrease in N-Acetylaspartate in the Anterior Cingulate Cortex After Electroconvulsive Therapy is Reversible

172. Decrease in N-Acetylaspartate in the Anterior Cingulate Cortex After Electroconvulsive Therapy is Reversible

Predicting the Onset of Ischemic Stroke With Fast High-Resolution 3D MR Spectroscopic Imaging.

Neurometabolite concentrations provide a direct index of infarction progression in stroke. However, their relationship with stroke onset time remains unclear. To assess the temporal dynamics of N-acetylaspartate (NAA), creatine, choline, and lactate and estimate their value in predicting early (<6 hours) vs. late (6-24hours) hyperacute stroke groups. Cross-sectional cohort. A total of 73 ischemic stroke patients scanned at 1.8-302.5 hours after symptom onset, including 25 patients with follow-up scans. A 3 T/magnetization-prepared rapid acquisition gradient echo sequence for anatomical imaging, diffusion-weighted imaging and fluid-attenuated inversion recovery imaging for lesion delineation, and 3D MR spectroscopic imaging (MRSI) for neurometabolic mapping. Patients were divided into hyperacute (0-24hours), acute (24hours to 1 week), and subacute (1-2 weeks) groups, and into early (<6 hours) and late (6-24hours) hyperacute groups. Bayesian logistic regression was used to compare classification performance between early and late hyperacute groups by using different combinations of neurometabolites as inputs. Linear mixed effects modeling was applied for group-wise comparisons between NAA, creatine, choline, and lactate. Pearson's correlation analysis was used for neurometabolites vs. time. P < 0.05 was considered statistically significant. Lesional NAA and creatine were significantly lower in subacute than in acute stroke. The main effects of time were shown on NAA (F=14.321) and creatine (F= 12.261). NAA was significantly lower in late than early hyperacute patients, and was inversely related to time from symptom onset across both groups (r=-0.440). The decrease of NAA and increase of lactate were correlated with lesion volume (NAA: r=-0.472; lactate: r=0.366) in hyperacute stroke. Discrimination was improved by combining NAA, creatine, and choline signals (area under the curve [AUC]=0.90). High-resolution 3D MRSI effectively assessed the neurometabolite changes and discriminated early and late hyperacute stroke lesions. 1. Stage 2.

MR Perfusion Imaging as a Problem- Solving Tool for Differentiating High-grade Glioma and Tumefactive Demyelination: A Report of Two Cases

Clinically, it is nearly impossible to differentiate between high-grade glioma, specifically Glioblastoma Multiforme (GBM), and Tumefactive Demyelination (TMD). Radiologically, distinguishing between GBM and TMD is challenging since they show similar findings on Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). To avoid invasive procedures that may increase patient morbidity, the use of MR perfusion imaging is highlighted in these case reports. We present two cases of young adult females with neurological deficits. The first case involves an 18-year-old female who presented with a dull, intermittent, holocephalic headache for eight months, along with heaviness and recent onset of pain in the right upper limb. MR spectroscopy revealed an increased choline/creatinine ratio at the margins of the lesion, measuring approximately 2.4, with a decrease in N-Acetylaspartate (NAA) and NAA/Creatinine. Based on these findings, the possibility of either high-grade glioma or TMD was considered. Further evaluation using perfusion imaging showed a substantial increase in the mean relative Cerebral Blood Volume (rCBV) within the lesion, suggesting a higher likelihood of high-grade glioma rather than TMD. Biopsy confirmed the diagnosis as high-grade glioma (GBM), revealing marked mitotic changes with nuclear pleomorphism and multinucleated cells. The second case involves a 22-year- old female who presented with left upper limb and lower limb weakness for 10 days. MR spectroscopy showed reduced NAA values and an elevated choline peak with small lactate at a few places. A choline/creatine ratio of 1.9 was obtained. On perfusion imaging, the observed mean rCBV values were substantially low (rCBV measuring approximately 1.07). Consequently, a final radiological diagnosis of TMD was considered. A biopsy confirmed the presence of inflammatory demyelination.

Evaluation of suprachiasmatic nucleus in Alzheimer’s disease with non-invasive magnetic resonance methods

Evaluation of suprachiasmatic nucleus in Alzheimer’s disease with non-invasive magnetic resonance methods

Magnetic resonance imaging and spectroscopy in late-onset GM2-gangliosidosis

ObjectiveOur study aimed to quantify structural changes in relation to metabolic abnormalities in the cerebellum, thalamus, and parietal cortex of patients with late-onset GM2-gangliosidosis (LOGG), which encompasses late-onset Tay-Sachs disease (LOTS) and Sandhoff disease (LOSD). MethodsWe enrolled 10 patients with LOGG (7 LOTS, 3 LOSD) who underwent a neurological assessment battery and 7 age-matched controls. Structural MRI and MRS were performed on a 3 T scanner. Structural volumes were obtained from FreeSurfer and normalized by total intracranial volume. Quantified metabolites included N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), and combined glutamate-glutamine (Glx). Metabolic concentrations were corrected for partial volume effects. ResultsStructural analyses revealed significant cerebellar atrophy in the LOGG cohort, which was primarily driven by LOTS patients. NAA was lower and mI higher in LOGG, but this was also significantly driven by the LOTS patients. Clinical ataxia deficits (via the Scale for the Assessment and Rating of Ataxia) were associated with neuronal injury (via NAA), neuroinflammation (via mI), and volumetric atrophy in the cerebellum. InterpretationThe decrease of NAA in the cerebellum suggests that, in addition to cerebellar atrophy, there is ongoing impaired neuronal function and/or loss, while an increase in mI indicates possible neuroinflammation in LOGG (more so within the LOTS subvariant). Quantifying cerebellar atrophy in relation to neurometabolic differences in LOGG may lead to improvements in assessing disease severity, progression, and pharmacological efficacy. Lastly, additional neuroimaging studies in LOGG are required to contrast LOTS and LOSD more accurately.

Usefulness of magnetic resonance spectroscopy in mesial temporal sclerosis: a systematic review.

Magnetic resonance spectroscopy (MRS) provides non-invasive information about metabolic features in different regions of the brain affected by mesial temporal sclerosis (MTS). To review articles analyzing the most common alterations in biochemical parameters in MTS and the applications of MRS in presurgical assessment. We undertook a systematic literature search for MRS in MTS in PubMed, SCOPUS, and Cochrane based on the MESH terms ""Magnetic Resonance Spectroscopy", "Proton Magnetic Resonance Spectroscopy", "Carbon-13 Magnetic Resonance Spectroscopy", "1H-MRS", "31P-MRS", "mesial temporal sclerosis", "hippocampal sclerosis", "mesial temporal seizure", and "mesial temporal epilepsy". Of the initial 134 articles found, 30 were selected after the exclusion process. Of these, 13 detected a decrease in N-acetylaspartate (NAA), 9 showed a decreased in the ratio NAA/Cho+Cr, and 8 demonstrated a decreased in the ratio NAA/Cr, all of them in the ipsilateral hippocampus. Nine studies also found reduced NAA levels in extrahippocampal regions. The main findings were a decrease in NAA in the ipsilateral hippocampus. In addition, NAA levels were low outside the hippocampus so MTS could be a more extensive disease. Patients without MTS also presented a decrease in NAA in the ipsilateral hippocampus although NAA was even lower in the MTS patients. Thus, MRS could be useful in the presurgical evaluation to locate the epileptogenic focus, but not specific for the diagnosis of MTS.

Neurometabolic patterns of an “at risk for mental disorders” syndrome involve abnormalities in the thalamus and anterior midcingulate cortex

BackgroundThe ultra-high risk (UHR) paradigm allows the investigation of individuals at increased risk of developing psychotic or other mental disorders with the aim of making prevention and early intervention as specific as possible in terms of the individual outcome. MethodsSingle-session 1H-/31P-Chemical Shift Imaging of thalamus, prefrontal (DLPFC) and anterior midcingulate (aMCC) cortices was applied to 69 UHR patients for psychosis and 61 matched healthy controls. N-acetylaspartate (NAA), glutamate/glutamine complex (Glx), energy (PCr, ATP) and phospholipid metabolites were assessed, analysed by ANOVA (or ANCOVA [with covariates]) and correlated with symptomatology (SCL-90R). ResultsThe thalamus showed decreased NAA, inversely correlated with self-rated aggressiveness, as well as increased PCr, and altered phospholipid breakdown. While the aMCC showed a pattern of NAA decrease and PCr increase, the DLPFC showed PCr increase only in the close-to-psychosis patient subgroup. There were no specific findings in transition patients. ConclusionThe results do not support the notion of a specific pre-psychotic neurometabolic pattern, but likely reflect correlates of an “at risk for mental disorders syndrome”. This includes disturbed neuronal (mitochondrial) metabolism in the thalamus and aMCC, with emphasis on left-sided structures, and altered PL remodeling across structures.

Altered neurometabolism in major depressive disorder: A whole brain 1H-magnetic resonance spectroscopic imaging study at 3T

IntroductionMajor depressive disorder (MDD) is a severe mental disorder with a neurobiological basis that is poorly understood. Several studies demonstrated widespread, functional and neurometabolic alterations in MDD. However, little is known about whole brain neurometabolic alterations in MDD. MethodThirty-two patients with MDD and 32 paired on a one-to-one basis healthy controls (CTRL) underwent 1H-whole brain spectroscopic (1H-WBS) imaging. Lobar and cerebellar metabolite concentrations of brain N-acetylaspartate (NAA), total choline (tCho), total creatine (tCr), glutamine (Gln), glutamate (Glu), and myo-Inositol (mI) were assessed in patients and controls. ResultsDecreased NAA, tCho, and tCr were found in the right frontal and right parietal lobe in MDD compared to CTRL, and to a lesser extent in the left frontal lobe. Furthermore, in MDD increased glutamine was observed in the right frontal lobe and bitemporal lobes, and increased glutamate in the cerebellum. ConclusionAltered global neurometabolism examined using 1H-WBS imaging in MDD may be interpreted as signs of neuronal dysfunction, altered energy metabolism, and oligodendrocyte dysfunction. In particular, the parallel decrease in NAA, tCr and tCho in the same brain regions may be indicative of neuronal dysfunction that may be counterbalanced by an increase of the neuroprotective metabolite glutamine. Future prospective investigations are warranted to study the functional importance of these findings.

High-resolution metabolic imaging of high-grade gliomas using 7T-CRT-FID-MRSI

ObjectivesSuccessful neurosurgical intervention in gliomas depends on the precision of the preoperative definition of the tumor and its margins since a safe maximum resection translates into a better patient outcome. Metabolic high-resolution imaging might result in improved presurgical tumor characterization, and thus optimized glioma resection. To this end, we validated the performance of a fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in a patient cohort of 23 high-grade gliomas (HGG). Materials and methodsWe preoperatively measured 23 patients with histologically verified HGGs (17 male, 8 female, age 53 ± 15) with an MRSI sequence based on concentric ring trajectories with a 64 × 64 × 39 measurement matrix, and a 3.4 × 3.4 × 3.4 mm3 nominal voxel volume in 15 min. Quantification used a basis-set of 17 components including N-acetyl-aspartate (NAA), total choline (tCho), total creatine (tCr), glutamate (Glu), glutamine (Gln), glycine (Gly) and 2-hydroxyglutarate (2HG). The resultant metabolic images were evaluated for their reliability as well as their quality and compared to spatially segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast enhanced + edema, peritumoral) based on clinical data and also compared to histopathology (e.g., grade, IDH-status). ResultsEighteen of the patient measurements were considered usable. In these patients, ten metabolites were quantified with acceptable quality. Gln, Gly, and tCho were increased and NAA and tCr decreased in nearly all tumor regions, with other metabolites such as serine, showing mixed trends. Overall, there was a reliable characterization of metabolic tumor areas. We also found heterogeneity in the metabolic images often continued into the peritumoral region. While 2HG could not be satisfyingly quantified, we found an increase of Glu in the contrast-enhancing region of IDH-wildtype HGGs and a decrease of Glu in IDH1-mutant HGGs. ConclusionsWe successfully demonstrated high-resolution 7T 3D-MRSI in HGG patients, showing metabolic differences between tumor regions and peritumoral tissue for multiple metabolites. Increases of tCho, Gln (related to tumor metabolism), Gly (related to tumor proliferation), as well as decreases in NAA, tCr, and others, corresponded very well to clinical tumor segmentation, but were more heterogeneous and often extended into the peritumoral region.

N-Acetylaspartate Levels in Elderly Patients with Depression during Treatment with Antidepressants and Actovegin

Objectives. To study the N-acetylaspartate (NAA) content in the plasma of elderly patients with depression during treatment with antidepressants combined with Actovegin. Materials and methods. Nineteen patients – seven men, 12 women, age 70.5 ± 5.8 years – were treated in hospital conditions. Patients underwent clinical psychiatric evaluation using a series of psychometric scales, along with computerized tomography (CT) and biochemical assay of NAA. Patients received antidepressants (venlafaxine and fluvoxamine at therapeutic doses) and Actovegin for 28 days and were investigated before and after treatment (day 28). Results and conclusions. Decreases in blood NAA were found in pretreatment patients as compared with healthy subjects, with increases after treatment, which corresponded to a significant improvement in patients’ status both clinically and on psychometric scales. Heterogeneity was found in the cohort of patients in relation to the nature of changes in contents (increases or decreases) of NAA, which was not linked with treatment efficacy but correlated with the burden of comorbid somatic diseases, especially vascular, and some CT features (leukoaraiosis). The authors emphasize the preliminary nature of the results.

Motor cortex metabolite alterations in amyotrophic lateral sclerosis assessed in vivo using edited and non-edited magnetic resonance spectroscopy

Previous MRI and proton spectroscopy (1H-MRS) studies have revealed impaired neuronal integrity and altered neurometabolite concentrations in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). Here, we aim to use MRI with conventional and novel MRS sequences to further investigate neurometabolic changes in the motor cortex of ALS patients and their relation to clinical parameters. We utilized the novel HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy) MRS sequence to simultaneously quantify the inhibitory neurotransmitter GABA and antioxidant glutathione in ALS patients (n = 7) and healthy controls (n = 7). In addition, we have also quantified other MRS observable neurometabolites using a conventional point-resolved MR spectroscopy (PRESS) sequence in ALS patients (n = 20) and healthy controls (n = 20). We observed a trend towards decreasing glutathione concentrations in the motor cortex of ALS patients (p = 0.0842). In addition, we detected a 11% decrease in N-acetylaspartate (NAA) (p = 0.025), a 15% increase in glutamate + glutamine (Glx) (p = 0.0084) and a 21% increase in myo-inositol (mIns) (p = 0.0051) concentrations for ALS patients compared to healthy controls. Furthermore, significant positive correlations were found between GABA-NAA (p = 0.0480; Rρ = 0.7875) and NAA-mIns (p = 0.0448; Rρ = −0.4651) levels among the patients. NAA levels in the bulbar-onset patient group were found to be significantly (p = 0.0097) lower compared to the limb-onset group. A strong correlation (p < 0.0001; Rρ = −0,8801) for mIns and a weak correlation (p = 0.0066; Rρ = −0,6673) for Glx was found for the disease progression, measured by declining of the ALS Functional Rating Scale-Revised criteria (ALSFRS-R). Concentrations of mIns and Glx also correlated with disease severity measured by forced vital capacity (FVC). Results suggest that mean neurometabolite concentrations detected in the motor cortex may indicate clinical and pathological changes in ALS.

Brain magnetic resonance spectroscopy (MRS) as a diagnostic tool for detecting early neurological changes in children with Wilson’s disease

PurposeAlthough brain magnetic resonance spectroscopy (MRS) imaging findings in adult Wilson disease (WD) have been explained in extensive details, a paucity of information currently exists regarding brain MRS imaging findings in pediatric WD. The purpose of this study was to clarify the role of brain MRS in detecting early metabolite abnormalities in children with WD. Patient and methodsA case-controlled prospective study included 26 children with WD and 26 healthy controls. All children were subjected to examination on a 1.5 T MRI scanner. The spectra of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr), as well as the metabolite ratios of NAA/Cho, NAA/Cr, and Cho/Cr, were measured and compared between two groups. ResultsEight patients revealed increased signal intensity in the basal ganglia at T1-weighted images. When compared with healthy controls, WD patients showed a significant decrease (p < 0.05) in NAA (63.8 ± 9.6 vs 97.6 ± 3.8), Cho (46.7 ± 8.9 vs 87.3 ± 4.7), Cr (44 ± 10.1 vs 81.9 ± 4.05), NAA/Cho (1.92 ± 1.2 vs 3.34 ± 0.55), NAA/Cr (1.29 ± 0.7 vs 2.46 ± 0.34), and Cho/Cr (0.78 ± 0.4 vs 2 ± 0.13). Patients complicated with liver cell failure showed a significant decrease in all previous parameters (p < 0.05) than patients without complications. Patients with mixed neurological and hepatic diseases showed a severe reduction in NAA, NAA/Cr, and NAA/Cho compared with patients with hepatic disease only. ConclusionMRS in pediatric WD detects early neurological changes even with normal MRI.

Quantitative analysis of neurometabolites in adolescents with persistent symptoms following concussion using magnetic resonance spectroscopy

There is great interest in developing physiologic markers of persistent concussion symptoms (PCS) that can occur following mild traumatic brain injury (mTBI). Magnetic resonance spectroscopy (MRS) can non-invasively measure changes in brain metabolism and is directly translatable to clinical application. Previous studies have shown that mTBI is associated with decreases in N-acetylaspartate (NAA), though most prior work has focused on adults. In this pilot project, we hypothesized that adolescents with PCS would have decreased NAA in frontal white matter (FWM) and the anterior cingulate cortex (ACC) relative to adolescents without PCS. Twenty-two patients (14–18 years old) with persistent symptoms following sport or recreation-related concussion (PCS+) were recruited from a concussion clinic and assessed at least 4-week post-injury. Twenty-one adolescents with varying concussion history but without PCS served as controls (PCS−). Exclusion criteria included current or prior moderate/severe TBI, neurodevelopmental disorder, or psychiatric disorder unrelated to current injury. Participants completed a clinical assessment battery that included self-reported concussion and psychiatric symptoms and neurocognitive testing. MRS was performed in the ACC and right FWM using a PRESS sequence on a GE 3T scanner. Spectra were analyzed using LCModel to calculate metabolite levels. Independent samples t -tests were used to compare groups, with apriori analyses focused on NAA, NAA plus N-acetylaspartylglutamic acid (total NAA), and combined glutamate and glutamine (Glx). PCS+ showed significant elevations in concussion and psychiatric symptoms as well as decreased neurocognitive performance compared to controls ( p = 0.05). In addition, PCS+ had a significant decrease in total NAA ( p = 0.012) and a non-significant decrease in NAA ( p = 0.057) in the FWM when compared to PCS−. No differences between groups were seen in the ACC ( p = 0.1). Our results suggest a relationship between PCS in adolescents and decreased total NAA in frontal white matter. Additional analyses investigating the relationship between neuro metabolites and clinical measures are underway.

Choline and N-acetyl aspartate levels in the dorsolateral prefrontal cortex at the beginning of the recovery phase as markers of increased risk for depressive episode recurrence under different duration of maintenance therapy and after it: a retrospective cohort study

AimTo evaluate the relationship between the dynamics of proton magnetic resonance spectroscopy (1H-MRS) brain metabolite levels at the beginning of the recovery phase of the index depressive episode and the time to the recurrence of depression.MethodsThis retrospective cohort study analyzed the changes in N-acetyl aspartate (NAA), choline (Cho), and glutamate-glutamine in 48 patients with recurrent depression treated with maintenance antidepressant monotherapy at a stable dose. 1H-MRS was performed at the start of the recovery phase and 6 months later. 1H-MRS parameters, index episode descriptors, and depressive disorder course were analyzed by Cox proportional hazards model.ResultsNAA and Cho decrease six months after the beginning of the recovery period were time-independent risk factors for depressive episode recurrence. Hazard ratio associated with NAA decrease was 2.02 (95% confidence interval 1.06-3.84) and that associated with Cho decrease was 2.06 (95% confidence interval 1.02-4.17). These changes were not related to symptoms severity, as Montgomery-Asberg Depression Scale score remained generally unchanged (mean -0.01; standard deviation 1.6) over the first 6 months of recovery.ConclusionPatients receiving maintenance antidepressant therapy after recovery who experience a decrease in NAA or Cho levels early in the recovery phase have a double risk of depressive episode recurrence. Sustained NAA and Cho levels at the beginning of the recovery phase may indicate increased brain resilience conferred by antidepressant therapy, while NAA and Cho decrease may indicate only the trait-related temporal effect of therapy in another stratum of patients.

Neuro-Metabolite Changes in a Single Season of University Ice Hockey Using Magnetic Resonance Spectroscopy

Background: Previous research has shown evidence for transient neuronal loss after repetitive head impacts (RHI) as demonstrated by a decrease in N-acetylaspartate (NAA). However, few studies have investigated other neuro-metabolites that may be altered in the presence of RHI; furthermore, the relationship of neuro-metabolite changes to neurocognitive outcome and potential sex differences remain largely unknown.Objective: The aim of this study was to identify alterations in brain metabolites and their potential association with neurocognitive performance over time as well as to characterize sex-specific differences in response to RHI.Methods: 33 collegiate ice hockey players (17 males and 16 females) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011–2012. The MRS voxel was placed in the corpus callosum. Pre- and postseason neurocognitive performances were assessed using the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). Absolute neuro-metabolite concentrations were then compared between pre- and postseason MRS were (level of statistical significance after correction for multiple comparisons: p < 0.007) and correlated to ImPACT scores for both sexes.Results: A significant decrease in NAA was observed from preseason to postseason (p = 0.001). Furthermore, a trend toward a decrease in total choline (Cho) was observed (p = 0.044). Although no overall effect was observed for glutamate (Glu) over the season, a difference was observed with females showing a decrease in Glu and males showing an increase in Glu, though this was not statistically significant (p = 0.039). In both males and females, a negative correlation was observed between changes in Glu and changes in verbal memory (p = 0.008).Conclusion: The results of this study demonstrate changes in absolute concentrations of neuro-metabolites following exposure to RHI. Results suggest that changes in Glu are correlated with changes in verbal memory. Future studies need to investigate further the association between brain metabolites and clinical outcome as well as sex-specific differences in the brain's response to RHI.

Neurobiological Effects of Binge Drinking Help in Its Detection and Differential Diagnosis from Alcohol Dependence.

The prevalence of binge drinking in the general population is 3-4 times higher than that of alcohol dependence. Neuroimaging studies show that binge drinking in adolescence impairs brain development and white matter integrity. Regions with reduced functional activity include the limbic system, ventral diencephalon, frontal lobe, and middle and inferior temporal lobes, whereas the right superior frontal and parietal lobes are typically hyperactivated. The observed activation of the frontoparietal areas might reflect the alternative memory system operating, whereas the reduced occipito-hippocampal response is associated with impaired visual and linguistic processing/learning. Some other findings from literature research include a decrease of N-acetylaspartate (NAA) in the frontal lobe and its increase in the parietal lobes, as well as the reduced components of event-related potentials, reflecting deficit in attention, working memory, inhibition, and executive functioning. Animal studies show that even a single day of binge drinking results in a neurodegeneration and reactive gliosis in the limbic cortex as well as in gene expression dysregulation and histone acetylation. Another biological evidence on binge drinking effect include inflammatory response, oxidative stress, formation of toxic ceramides, activation of caspase 3, and secretion of corticoliberin. Some of the binge drinking-induced cognitive abnormalities can be reversible after three weeks of abstinence. Although binge drinkers have a similar pattern of neuropsychological deficits with chronic alcohol consumers (mainly memory deficits), binge drinkers have prominent impairment of inhibitory control, which may be a marker of binge pattern of alcohol drinking. The optimal therapeutic strategies should target the inhibitory control processes to facilitate discontinuation of alcohol consumption and to block its possible progression to the alcohol dependence syndrome.

MAGNETIC RESONANCE SPECTROSCOPY OF NORMAL APPEARING WHITE MATTER IN EARLY RELAPSING-REMITTING MULTIPLE SCLEROSIS

Back ground: Multiple sclerosis (MS) is an inflammatory disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged .MS is a chronic disease of the central nervous system characterised by multicentral inflammation and myelin destruction . Magnetic resonance imaging (MRI) is now widely used for diagnosing MS and detecting clinically silent lesions. However, correlations found between conventional techniques, such as T2-weighted lesion load, and disability, are weak or absent and therefore, neither the magnetic resonance techniques nor clinical measurements are gold standard to assess disease or disability.Alteration of NAWM is of great importance because its true patho-physiological significance is not completely understood. Decrease in N-Acetyl Aspartate (NAA) has been used as an marker of axonal damage or loss that presumably appears secondary to inflammation or demyelination ,although primary axonal damage is not excluded . Objectives : Demonstrate the limitation of convenential magnetic resonance techniques. Observation the pathological processes in NAWM by MRS. Correlation between the results of MRS and the physical disability of the patients using EDSS . Subjects and methods: This study was carried out on 23 patients with clinically definite multiple sclerosis patients, who met the criteria of clinically definite MS according to McDonald criteria 2010, selected from Neurology Department, Zagazig University Hospitals ]10[. Results: We found that the mean value of NAA and the mean ratios of NAA/CR and NAA/ CHO were significant lower in the Cases but the mean values of MI and GLX are significant higher. . Also there was significant negative correlation between the mean value of NAA in MS plaque by MRS and EDSS score as a measure of disability. There was significant negative correlation between the mean value of NAA in NAWM and EDSS score . Discussion: We have clearly demonstrated a correlation between an MRS measure and EDSS. EDSS seems to reflect the existence of irreversible disability probably related to axonal degeneration. Key wards Multiple sclerosis; Magnetic resonance imaging;Normal appearing white mater;Proton magnetic resonance spectroscopy;Expanded Disability Status Scale