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OBJECTIVES: The role played by medial prefrontal cortex (MPFC) glutamate (Glu) and gamma-aminobutyric acid (GABA) in the pathophysiology and the treatment of major depression (MD) is increasingly recognized. Although measurements of MPFC GABA and Glu have been shown to be sensitive to physiological fluctuations of female hormones, none of the magnetic resonance spectroscopy (MRS) investigations of MPFC Glu and GABA in MD have controlled for possible bias effect of the reproductive stage of the women included. METHODS: MPFC Glu and GABA+ (which include homocarnosine and macromolecules) referenced to creatine and phosphocreatine, were measured via magnetic resonance spectroscopy (MRS) using a 3-Tesla magnet in 24 women with MD and 24 healthy women paired for reproductive status. All participants were unmedicated. RESULTS: There were no statistical differences in either MPFC Glu [95 % CI: (-0.025, 0.034)] or MPFC GABA+ [95 % CI: (-0.005, 0.017)] between women with MD and healthy controls. CONCLUSIONS: Our investigation does not support abnormalities in measurement of MPFC Glu and GABA in MD women when stringent control for reproductive status is performed. As a result of the inherent limitations of MRS methodology, our results do not preclude glutamatergic and GABAergic dysregulations in the MPFC of women with MD.
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Trastorno Depresivo Mayor , Ácido Glutámico , Femenino , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Depresión , Corteza Prefrontal/diagnóstico por imagen , Ácido gamma-AminobutíricoRESUMEN
BACKGROUND: It has been suggested that the dorsolateral prefrontal cortex (DLPFC), especially the left DLPFC, has an important role in the pathophysiology and the treatment of major depressive disorder (MDD); furthermore, the contributory and antidepressant role of γ-aminobutyric acid (GABA) is increasingly recognized. Given that most female patients with MDD are of reproductive age, we sought to assess in vivo baseline GABA levels in the left DLPFC among unmedicated females of reproductive age with depression. METHODS: We compared healthy females and females with MDD. Both groups were of reproductive age. We confirmed absence of current or past psychiatric diagnosis among healthy controls or a current diagnosis of MDD via a structured interview. We measured GABA+ (including homocarnosine and macromolecules), referenced to creatine and phosphocreatine, via magnetic resonance spectroscopy using a 3 Tesla magnet. RESULTS: We included 20 healthy controls and 13 participants with MDD. All participants were unmedicated at the time of the study. All females were scanned during the early follicular phase of the menstrual cycle. Levels of GABA+ in the left DLPFC were significantly lower among participants with MDD (median 0.08) than healthy controls (median 0.10; U = 66.0, p = 0.02, r = 0.41). LIMITATIONS: When we adjusted for fit error as a covariate, we lost statistical significance for left DLPFC GABA+. However, when we adjusted for signal-to-noise ratio, statistical significance was maintained. CONCLUSION: Our results suggest that GABA+ levels in the left DLPFC may vary by depression status and should be examined as a possible treatment target.
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Creatina , Trastorno Depresivo Mayor , Humanos , Femenino , Fosfocreatina , Trastorno Depresivo Mayor/diagnóstico por imagen , Corteza Prefontal Dorsolateral , DepresiónRESUMEN
OBJECTIVE: Perimenopause is associated with an increased risk of developing a major depressive (MD) episode. A significant number of women develop their first MD episode during perimenopause, suggesting a unique pathophysiology of perimenopausal (PM) depression. Previous research has shown that depression is associated with decreased gamma-aminobutyric acid (GABA) levels in the medial prefrontal cortex (MPFC) of MD patients. The objective of this study was to compare MPFC GABA+ levels in healthy reproductive-aged (RD) and PM women. METHODS: A total of 18 healthy PM and 20 RD women were included in the study. MPFC GABA+ levels, which include homocarnosine and macromolecules, were measured via magnetic resonance spectroscopy using a 3 Tesla magnet. MPFC GABA+ levels were referenced to creatine + phosphocreatine (Cr+PCr). Absence of current or past psychiatric diagnosis was confirmed via a structured interview. RD participants were scanned during the early follicular phase of the menstrual cycle. PM women were scanned outside of ovulatory cycles. RESULTS: Mean MPFC GABA+ concentrations (relative to Cr+PCr) were decreased in the PM group compared with the RD group (PM mean = 0.08 ± 0.02, RD mean = 0.09 ± 0.02, t = -2.03, df = 36, P = .05) even after correcting for in percentage in gray matter (GM). Because PM women were inherently older than RD women (aged 48.8 ± 3.55 and 31.5 ± 9.66 years, respectively), the age difference between the 2 groups was statistically significant (P < .001). When age was treated as an independent covariate and included in the model, the difference in GABA+ between PM and RD women was no longer significant (P = .092). CONCLUSION: Perimenopause is associated with decreased MPFC GABA+/Cr+PCr levels, which may contribute to the increased risk of experiencing a MD episode during PM.
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Trastorno Depresivo Mayor , Perimenopausia , Humanos , Femenino , Adulto , Trastorno Depresivo Mayor/diagnóstico por imagen , Espectroscopía de Resonancia Magnética/métodos , Corteza Prefrontal/diagnóstico por imagen , Creatina , Ácido gamma-AminobutíricoRESUMEN
Objective: The perimenopause is associated with an increased risk of developing a major depressive (MD) episode. The biological changes occurring during perimenopause responsible for this increased risk of depression remain to be elucidated. Postmortem and magnetic resonance spectroscopy (MRS) studies have revealed decreased gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in the dorsolateral prefrontal cortex (DLPFC) of MD patients. The objective of this study was to compare LDLPFC GABA+ and Glu ratios (referenced to creatine and phosphocreatine) in healthy reproductive-aged (RD) and perimenopausal (PM) women. Materials and methods: Eighteen healthy PM and 20 RD women were included in the study. Our dependent variables, LDLPFC Glu and GABA+ ratios which include homocarnosine and macromolecules, were measured via MRS, using a 3 Tesla magnet. Absence of current or past psychiatric diagnosis was confirmed via a structured interview. RD participants were scanned during the early follicular phase of the menstrual cycle (MC). PM women were scanned outside of ovulatory cycles. Results: Mean LDLPFC GABA+ and Glu ratios were not statistically different between the PM group and RD group (PM mean = 0.10 ± 0.06, RD mean = 0.11 ± 0.04, t = -0.383, df = 36, d = -0.13, p = 0.70) (PM mean = 0.56 ± 0.06, RD mean = 0.57 ± 0.05, t = -0.794, df = 36, d = -0.26, p = 0.43), respectively. The perimenopause demarcates the end of the reproductive life. Unsurprisingly PM women were older than RD women (PM women: 48.8 ± 3.55 years, range 41-53 years old; RD women: 31.5 ± 9.66 years, range 18-47 years old) (p < 0.001). This inherent entanglement of group and age is a limitation of our study. Conclusion: Contrary to our previous findings of decreased GABA+ and Glu in the medial prefrontal cortex in perimenopausal women, the perimenopause is not associated with decreased GABA+ or Glu ratios in the LDLPFC. This suggests that brain areas playing a role in MD display different sensitivity to the female hormones fluctuations associated with perimenopause.
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Objective: There is an increased risk of experiencing depression during perimenopause (PM), a period of rapidly changing female hormone concentrations. Women at particular risk of developing major depression (MD) during PM are those with history of mood sensitivity to female hormone fluctuations i.e., women with a history of premenstrual dysphoric disorder (PMDD) and/or post-partum depression (PPD). Depressive symptomology has been associated with fluctuations of glutamate (Glu) levels in the medial prefrontal cortex (MPFC) in MD patients as well as PMDD and PPD patients. The objective of the study was to compare MPFC Glu levels in healthy perimenopausal and reproductive-aged (RD) women. Methods: Medial prefrontal cortex Glu levels in healthy perimenopausal (n = 15) and healthy RD women (n = 16) were compared via Magnetic Resonance Spectroscopy (MRS) scan using a 3 Tesla (T) magnet. Absence of depressive symptomology and psychiatric comorbidity was confirmed via semi-structured interview. Participants were scanned during the early follicular phase (FP) of the menstrual cycle (MC). Results: Mean MPFC Glu concentrations were decreased in the PM group compared to RD group (PM mean = 0.57 ± 0.03, RD mean = 0.63 ± 0.06, t = -3.84, df = 23.97, p = 0.001). Conclusion: Perimenopause is associated with decreases in MPFC Glu levels. This decrease may be contributing to the increased risk of experiencing depression during PM. Further research should assess MPFC Glu levels in perimenopausal women suffering from MD.
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BACKGROUND: There is a paucity of data connecting the metabolic and cognitive functioning of abstinent cocaine users. This is a pressing public health concern as approximately 1% of the Canadian population and 0.4% of the global population is estimated to have used cocaine in the past year. METHODS: Our clinical study compared the in vivo neurochemical profiles in the prefrontal cortex to cognitive tests associated with the same region in 21 moderate term abstinent cocaine users (average 187days abstinent, range 15-1432days), and 30 healthy controls using 3T 1H MRS. RESULTS: The abstinent cocaine users exhibited a 10% decrease in N-acetylaspartate (NAA) relative to healthy control subjects (p<0.01, Cohen's d=1.15). When subdivided by method of administration, a significant decrease in glutamate levels in former crack smokers compared to healthy controls (p<0.05) was observed, this decrease was not present in powder users. Abstinent users were significantly worse than healthy controls on the Trail Making Test B (p<0.05), and performance on this task was inversely related to NAA levels (p<0.05). Abstinent cocaine users showed deficits in the Wisconsin card sorting test with failures to maintain set (p<0.01). CONCLUSIONS: Our work suggests that there are subtle but important changes in the brain that remain even with the moderate term cessation of cocaine use.
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Ácido Aspártico/análogos & derivados , Encéfalo/fisiopatología , Trastornos Relacionados con Cocaína/psicología , Función Ejecutiva/fisiología , Corteza Prefrontal/fisiología , Ácido Aspártico/química , Canadá , Trastornos Relacionados con Cocaína/fisiopatología , Cognición , Humanos , Pruebas Neuropsicológicas/normasRESUMEN
OBJECTIVE: Young adults with early phase schizophrenia often report a past or current pattern of illicit substance use and/or alcohol misuse. Still, little is known about the cumulative and separate effects of each stressor on white matter tissue, at this vulnerable period of brain development. METHODS: Participants involved 24 healthy controls with a past or current history of sustained illicit drug use and/or alcohol misuse (users), 23 healthy controls without such history (normative data), and 27 users with early phase schizophrenia. (1)H-MRS data were acquired from a large frontal volume encompassing 95% of white matter, using a 4Tesla scanner (LASER sequence, TR/TE 3200/46ms). RESULTS: Reduced levels of choline-containing compounds (Cho) were specific to the effect of illness (Cohen's d=0.68), with 22% of the variance in Cho levels accounted for by duration of illness. Reduced levels of myoInositol (d=1.10) and creatine plus phosphocreatine (d=1.07) were specific to the effects of illness plus substance use. Effect of substance use on its own was revealed by reductions in levels of glutamate plus glutamine (d=0.83) in control users relative to normative data. CONCLUSIONS: The specific effect of illness on white matter might indicate a decreased synthesis of membrane phospholipids or alternatively, reduced membrane cellular density. In terms of limitations, this study did not include patients without a lifetime history of substance use (non-users), and the specific effect of each substance used could not be studied separately.
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Lóbulo Frontal/metabolismo , Esquizofrenia/metabolismo , Trastornos Relacionados con Sustancias/metabolismo , Sustancia Blanca/metabolismo , Adulto , Femenino , Lóbulo Frontal/diagnóstico por imagen , Humanos , Masculino , Análisis Multivariante , Fosfolípidos/metabolismo , Espectroscopía de Protones por Resonancia Magnética , Escalas de Valoración Psiquiátrica , Esquizofrenia/diagnóstico por imagen , Trastornos Relacionados con Sustancias/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
Acute symptoms of methamphetamine-induced psychosis are similar to those of primary schizophrenia. Understanding similarities or differences in the biological substrate of these psychoses could lead to early differentiation of these two clinical conditions resulting in more efficient treatment strategies. Proton magnetic resonance spectroscopy was acquired from the medial prefrontal cortex in 29 unmedicated patients with first episode of psychosis (FEP), 29 abstinent methamphetamine-addicted people (METH) and 45 healthy controls (HCs) (age range 17.3 to 29.9years old). The METH group displayed robust reductions in concentration levels of glutamate (Glu) relative to FEP (Cohen's d=1.20) and HC (d=0.87). The METH group also displayed reduced levels of N-acetylaspartate (NAA) relative to FEP (d=0.53) and HC (d=0.76). The HC group displayed a positive association between levels of Glu and NAA, r(45)=0.52, p<0.001, while the two clinical groups failed to show this normal association. This suggests that the cellular metabolism is altered in both conditions. These data support the assumption that cellular abnormalities differ between primary schizophrenia and methamphetamine addiction despite the overlap in clinical presentation.
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Trastornos Relacionados con Anfetaminas/metabolismo , Ácido Glutámico/metabolismo , Corteza Prefrontal/metabolismo , Trastornos Psicóticos/metabolismo , Esquizofrenia/metabolismo , Adolescente , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Humanos , Espectroscopía de Protones por Resonancia Magnética , Escalas de Valoración Psiquiátrica , Adulto JovenRESUMEN
BACKGROUND: This research is a one-site neuroimaging component of a two-site genetic study involving patients with schizophrenia at early and later stages of illness. Studies support a role for the neuronal Per-Arnt-Sim 3 (NPAS3) gene in processes that are essential for normal brain development. Specific NPAS3 variants have been observed at an increased frequency in schizophrenia. In humans, NPAS3 protein was detected in the hippocampus from the first trimester of gestation. In addition, NPAS3 protein levels were reduced in the dorsolateral prefrontal cortex of some patients with schizophrenia. Npas3 knockout mice display behavioural, neuroanatomical and structural changes with associated severe reductions in neural precursor cell proliferation in the hippocampal dentate gyrus. This study will evaluate the hypothesis that the severe reductions in neural precursor cell proliferation in the dentate gyrus will be present to some degree in patients carrying schizophrenia-associated NPAS3 variants and less so in other patients. METHODS/DESIGN: Patients enrolled in the larger genetic study (n = 150) will be invited to participate in this neuroimaging arm. The genetic data will be used to ensure a sample size of 45 participants in each genetic subgroup of patients (with and without NPAS3 variants). In addition, we will recruit 60 healthy controls for acquisition of normative data. The following neuroimaging measures will be acquired from the medial temporal region: a) an index of the microcellular environment; b) a macro-structural volumetric measure of the hippocampus; and c) concentration levels of N-acetylaspartate, a marker of neuronal health. DISCUSSION: This study will help to establish the contribution of the NPAS3 gene and its variants to brain tissue abnormalities in schizophrenia. Given the genetic and phenotypic heterogeneity of the disorder and the large variation in outcomes, the identification of biological subgroups may in future support tailoring of treatment approaches in order to optimize recovery.
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Proteínas del Tejido Nervioso/genética , Esquizofrenia/genética , Lóbulo Temporal/fisiopatología , Factores de Transcripción/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Análisis Mutacional de ADN , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Estudios Multicéntricos como Asunto , Neuroimagen , Esquizofrenia/fisiopatologíaRESUMEN
BACKGROUND: A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. METHODS/DESIGN: Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. DISCUSSION: We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use.
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Lóbulo Frontal/fisiopatología , Fumar Marihuana/fisiopatología , Imagen Multimodal , Neuroimagen , Esquizofrenia/fisiopatología , Sustancia Blanca/fisiopatología , Adolescente , Adulto , Cannabis , Imagen de Difusión Tensora , Femenino , Lóbulo Frontal/patología , Humanos , Masculino , Fumar Marihuana/patología , Red Nerviosa/patología , Red Nerviosa/fisiopatología , Proyectos de Investigación , Esquizofrenia/diagnóstico , Esquizofrenia/patología , Sustancia Blanca/patología , Adulto JovenRESUMEN
Different lines of evidence suggest an abnormal cerebral energy metabolism as being critical to the pathophysiology of schizophrenia. However, it is unknown as to whether levels of creatine (Cr) would be involved in these anomalies. The study involved 33 unmedicated first episode psychosis patients and 41 healthy controls. Proton magnetic resonance spectroscopy ((1) H-MRS) was performed at 3 T using a long TE (TE/TM/TR of 240/27/3000 ms) such that within the total phosphocreatine (PCr) plus Cr signal (tCr(240)), mainly Cr was detectable. The target region was an 18 cm(3) prefrontal volume. A negative association was found between age of patients and tCr(240) levels referenced to internal water, with 20% of the variance in tCr(240) accounted for by Age. A secondary finding revealed 16% reduction of tCr(240) levels in patients, solely when comparing participants older than the median age of patients. No association existed between tCr(240) levels and clinical variables. These findings support previous data reporting abnormalities in brain creatine kinase isoenzymes involved with the maintenance of energy pools in schizophrenia. The implications of using a long TE are discussed in terms of the relative proportions of Cr and PCr within the tCr(240) signal, and of potential group differences in T(2) times.
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Encéfalo/metabolismo , Creatina/análisis , Espectroscopía de Resonancia Magnética/métodos , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/metabolismo , Adolescente , Adulto , Antipsicóticos/uso terapéutico , Biomarcadores/análisis , Femenino , Humanos , Masculino , Protones , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
The medial prefrontal cortex (MPFC) is a key brain area in depressive symptomatology; specifically, glutamate (Glu) has been reported to play a significant role in major depression (MD) in this area. MPFC Glu levels are sensitive to ovarian hormone fluctuations and pregnancy and the postpartum period are associated with the most substantial physiological alterations of female hormones. It is therefore logical to measure MPFC Glu levels in women with postpartum depression (PPD). Using in vivo magnetic resonance spectroscopy (MRS) at a field strength of 3 T, we acquired single-voxel spectra from the MPFC of 12 women with PPD and 12 healthy controls (HCs) matched for postpartum scan timing. Water-referenced MPFC Glu levels were measured using a MRS technique that allowed us to be specific for Glu with very little glutamine contamination. The concentrations of other water-quantified brain metabolites such as glycerophosphorylcholine plus phosphorylcholine, N-acetylaspartate (NAA), and creatine plus phosphocreatine were measured in the same MR spectra. MPFC Glu levels were higher in women with PPD (7.21±1.20) compared to matched HCs (6.04±1.21). There were no differences between groups for other brain metabolites measured. These findings suggest an association between Glu dysregulation in the MPFC and PPD. Whether the pathophysiology of PPD differs from the pathophysiology of MD remains to be determined. Further investigations are needed to determine the chronological associations between the occurrence of symptoms of PPD and the onset of changes in MPFC Glu levels.
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Depresión Posparto/patología , Ácido Glutámico/metabolismo , Corteza Prefrontal/metabolismo , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Estudios de Casos y Controles , Creatina/metabolismo , Femenino , Glicerilfosforilcolina/metabolismo , Humanos , Espectroscopía de Resonancia Magnética , Fosforilcolina/metabolismo , Embarazo , Factores de Tiempo , Adulto JovenRESUMEN
Although motor symptoms of Parkinson's disease (PD) are initially responsive to dopamine replacement therapy, nonresponsive features develop over time, suggesting that impaired dopaminergic function alone may not be wholly responsible for all the motor features of the disease. Previous studies suggest impaired function in the presupplementary motor area (pre-SMA) in PD. Our objective was to determine whether pre-SMA abnormalities are present in untreated patients with early disease. We measured N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in pre-SMA in 26 untreated patients with early PD (disease duration 3.0 +/- 2.0 yr) and 15 control subjects with single voxel magnetic resonance spectroscopy. Neither NAA/Cr nor Cho/Cr ratios differed significantly between groups. These observations suggest that, although pre-SMA function is impaired in moderately advanced PD, it is relatively spared in early disease. We suggest that pre-SMA dysfunction is in part responsible for the dopamine nonresponsive features associated with disease progression.
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Corteza Motora/fisiopatología , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Anciano , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análisis , Estudios de Casos y Controles , Colina/análisis , Creatina/análisis , Femenino , Humanos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Corteza Motora/metabolismoRESUMEN
Glutamate was quantified by proton magnetic resonance spectroscopy ((1)H-MRS) in the medial frontal lobes of 15 adult siblings of individuals with schizophrenia (HR) and 14 healthy volunteers (HV), all of whom also completed a Continuous Performance Test (CPT). Subjects were free of psychopathology but the HR group showed greater variability in glutamate levels. After median stratification, the high glutamate group contained a larger proportion of HR than HV subjects and scored lower on the CPT. Elevated glutamate may relate to poor sustained attention and elevated risk of schizophrenia, suggesting a potential role for glutamate in an endophenotype for schizophrenia.
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Atención/fisiología , Trastornos del Conocimiento/genética , Discriminación en Psicología/fisiología , Lóbulo Frontal/fisiopatología , Ácido Glutámico/metabolismo , Espectroscopía de Resonancia Magnética , Pruebas Neuropsicológicas , Reconocimiento Visual de Modelos/fisiología , Desempeño Psicomotor/fisiología , Esquizofrenia/genética , Psicología del Esquizofrénico , Adulto , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/fisiopatología , Creatina/metabolismo , Femenino , Predisposición Genética a la Enfermedad/genética , Predisposición Genética a la Enfermedad/psicología , Humanos , Inhibición Psicológica , Masculino , Persona de Mediana Edad , Tiempo de Reacción/fisiología , Riesgo , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatología , Trastorno de la Personalidad Esquizotípica/diagnóstico , Trastorno de la Personalidad Esquizotípica/genética , Trastorno de la Personalidad Esquizotípica/fisiopatología , HermanosRESUMEN
The hippocampus (HC) and amygdala (AG) decrease in volume with age and in Parkinson's disease (PD) with (PDD) and without dementia. We compared 44 PD to 44 age, sex and education-matched subjects without PD (non-PD) and 13 PDD subjects. T1-weighted MR images were used to manually segment the head, body and tail of the HC and the AG. HC volumes, corrected to intracranial volume, were smaller in PDD than non-PD (p=0.04), reflected predominantly by head atrophy. Right AG volumes were smaller in PD compared to non-PD (p=0.03). HC volumes in older (>70), but not younger, non-demented PD differed from non-PD (HC, p=0.02; head, p=0.03). Age correlated negatively with overall HC (r=-0.43, p=0.004) and head (r=-0.48, p=0.001) in PD, but not in non-PD. In PD, left HC head volumes correlated with recall, but not recognition scores on the CVLT-II (r=0.35, p=0.02) and BVMT-R (r=0.35, p=0.02); AG volumes correlated with CVLT-II recall (r=0.35, p=0.02). No correlations were found in non-PD (p>0.4). In conclusion, functionally meaningful age-associated hippocampal and amygdala atrophy occurs in PD.
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Envejecimiento/patología , Amígdala del Cerebelo/patología , Demencia/patología , Hipocampo/patología , Imagen por Resonancia Magnética/métodos , Enfermedad de Parkinson/patología , Anciano , Anciano de 80 o más Años , Atrofia/patología , Demencia/complicaciones , Femenino , Humanos , Masculino , Enfermedad de Parkinson/complicacionesRESUMEN
Impaired brain energy metabolism with increased regional brain lactate may play a role in the pathogenesis of Huntington's disease (HD). Magnetic resonance spectroscopy (MRS) has provided conflicting evidence, however, regarding metabolic changes. Our objective was to evaluate the potential contribution of CSF lactate to the changes observed with MRS in HD. We performed single voxel MRS at 3 T in 23 patients with HD and 28 age-matched control subjects using a method to segment voxels into grey matter, white matter, and CSF, and to extrapolate regional lactate content to a hypothetical voxel containing 100% brain in order to control for differences in CSF lactate. Lactate/creatine and lactate/N-acetyl aspartate (Lac/NAA) ratios were significantly increased in parieto-occipital (p<0.05) and cerebellar (p<0.01) voxels in HD patients. After extrapolating group Lac/NAA results to a theoretical voxel containing 100% brain, this ratio was greater in the HD group than the control group, suggesting possibly increased lactate in this predicted voxel, although the difference between groups did not reach statistical significance. These results suggest an increase in brain lactate content in manifest HD, in a regionally non-specific fashion, although the possibility of a CSF contribution to this increase cannot be ruled out. Regardless, this supports the possibility of impaired mitochondrial function resulting in abnormal brain energy metabolism in HD.
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Encéfalo/metabolismo , Enfermedad de Huntington/patología , Ácido Láctico/metabolismo , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Estudios de Casos y Controles , Colina/metabolismo , Creatina/metabolismo , Femenino , Humanos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
The anterior cingulate (AC) gyrus and the presupplementary motor area (pre-SMA) show pathological changes in Parkinson's disease (PD). We examined if PD patients show magnetic resonance spectroscopy (MRS) changes in NAA/Cr in the AC, pre-SMA, or posterior cingulate (PC). Forty-four (27 male, 17 female) healthy nondemented PD patients and 38 controls (18 male, 20 female) 65 years of age and older were examined using the Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental State Examination, Frontal Assessment Battery, and Geriatric Depression Scale. MRS was performed at 1.5 T. Voxels (8 cc; PRESS; TE = 80; TR = 1,600 ms) were placed mid-sagittally. Gray matter and white matter volumes were measured within voxels using SPM2. Spectra were analyzed using LC model to yield NAA/Cr and Cho/Cr. Demographic and cognitive measures did not differ between groups. Motor UPDRS was 17.7 +/- 8.8 for PD. Pre-SMA NAA/Cr was lower in PD (PD: 1.39 +/- 0.17; control: 1.47 +/- 0.16; P = 0.045) and correlated negatively with age (r = 0.39; P = 0.01), but not with UPDRS, disease duration, or dopamine equivalents. AC and PC NAA/Cr and Cho/Cr in any region did not differ (P > 0.05). In conclusion, pre-SMA NAA/Cr was selectively decreased in PD, consistent with neuronal dysfunction. This should be further examined as a biomarker of disease in PD.
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Espectroscopía de Resonancia Magnética , Corteza Motora/patología , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
BACKGROUND: Clinical assessment is insensitive to the degree of cerebral involvement in amyotrophic lateral sclerosis (ALS). Regional brain concentrations N-acetylaspartylglutamate (NAA) plus myo-inositol (Ins), as measured by magnetic resonance spectroscopy, are respectively decreased and increased, suggesting that these compounds may provide a biomarker of the degree of cerebral involvement in ALS. OBJECTIVE: To test the hypothesis that the NAA/Ins ratio may provide an index of cerebral involvement in patients with ALS. DESIGN: High-field (3.0-T) magnetic resonance spectroscopy was performed to determine the NAA/creatine plus phosphocreatine (NAA/Cr), NAA/choline (NAA/Cho), Ins/Cr, and NAA/Ins ratios in the motor cortex. PARTICIPANTS: Seventeen patients with ALS and 15 healthy control subjects were studied. RESULTS: In patients with ALS, the greatest abnormality was a 22% decrease in NAA/Ins (71% sensitivity and 93% specificity, P = .001); Ins/Cr was increased 18% (88% sensitivity and 53% specificity, P = .04), NAA/Cr was decreased 10% (88% sensitivity and 47% specificity, P = .04), and NAA/Cho was decreased 14% (53% sensitivity and 87% specificity, P = .047). Correlation of the ALS Functional Rating Scale with NAA/Ins approached statistical significance (R = 0.43, P = .07). CONCLUSION: The NAA/Ins ratio may provide a meaningful biomarker in ALS given its optimal sensitivity and specificity profile.
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Esclerosis Amiotrófica Lateral/patología , Espectroscopía de Resonancia Magnética/métodos , Corteza Motora/patología , Adulto , Anciano , Esclerosis Amiotrófica Lateral/metabolismo , Dipéptidos/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/metabolismoRESUMEN
An optimized single-shot proton double-quantum (DQ) filter for the quantification of gamma-aminobutyric acid (GABA) levels in human brain is reported. It is demonstrated that creation of DQ coherences following dual-resonance-selective refocusing gives a theoretical editing efficiency of 50% for the detection of the GABA resonance at 3.01 ppm. The sequence times are optimized with both numerical and experimental analyses of the editing performance, giving an experimental editing efficiency of 42%. It is acknowledged that homocarnosine is partially coedited, leading to a 20% contribution to the edited signal; however, macromolecule contamination is negligible in vivo under these experimental conditions. The GABA concentration in human prefrontal cortex is estimated to be 0.8 +/- 0.1 micromol/g (mean +/- SD, n = 6), with reference to the internal standard creatine at 9 micromol/g.
Asunto(s)
Química Encefálica , Espectroscopía de Resonancia Magnética/métodos , Ácido gamma-Aminobutírico/metabolismo , Adulto , Humanos , Sustancias Macromoleculares/metabolismoRESUMEN
Using as an example the myo-inositol (mI) band at approximately 3.6 ppm in the proton spectrum from brain, an evaluation is presented that highlights the difficulties of quantifying metabolites with strongly coupled spins with either STEAM or PRESS and demonstrates some advantages of prospective sequence analysis when measuring their concentrations. The analysis emphasizes the variation in coupled-spin signal yield and lineshape, compared with that of uncoupled singlets such as N-acetylaspartate, a variation that differs from one metabolite spin system to another. This difference in variation between a target metabolite (e.g., mI) and its contaminating background metabolites (e.g., glutamate and taurine, etc.) is shown to provide in certain circumstances a substantial reduction in background contamination (both metabolite and macromolecule) while maintaining sufficient signal-to-noise ratio for precise quantification. For example, sequence times are demonstrated, both for STEAM and for PRESS, that, relative to the short echo-time sequences typical in the literature, enhance the signal to metabolite background of the 3.6-ppm band of mI by factors of 1.7 and 1.3, respectively, essentially eliminate the macromolecular baseline, and yet in vivo retain an S/N approximately 10 in both cases.