Biomedical subjects

Gregory J Moore

Publications and source records attributed to Gregory J Moore.

10 recordsLinked to original sources

PubMed2003

Proton echo-planar spectroscopic imaging with highly effective outer volume suppression using combined presaturation and spatially selective echo dephasing.

A highly effective outer volume suppression (OVS) technique, termed spatially selective echo dephasing (SSED), which employs gradient dephasing of spatially selective spin echoes, is introduced. SSED, which is relatively insensitive to T(1) dispersion among lipid signals and B(1) inhomogeneity, was integrated with very high spatial resolution 2D proton echo-planar spectroscopic imaging (PEPSI) to assess residual lipid bleeding into cortical regions in the human brain. The method was optimized to minimize signal refocusing of secondary spin-echoes in areas of overlapping suppression slices. A comparison of spatial presaturation with single or double SSED, and with combined presaturation and SSED shows that the latter method has superior performance with spatially uniform lipid suppression factors in excess of 70. Metabolite mapping (choline, creatine, and NAA) with a 64 x 64 spatial matrix and 0.3 cm(3) voxels in close proximity to peripheral lipid regions was demonstrated at 1.5 T with a scan time of 32 min using the standard head coil.

Brain↗

PubMed2003

Real-time fMRI of temporolimbic regions detects amygdala activation during single-trial self-induced sadness.

Temporolimbic circuits play a crucial role in the regulation of human emotion. A highly sensitive single-shot multiecho functional magnetic resonance imaging (fMRI) technique with gradient compensation of local magnetic field inhomogeneities and real-time data analysis were used to measure increases in amygdala activation during single 60-s trials of self-induced sadness. Six healthy male and female subjects performed a validated mood induction paradigm with randomized presentation of sad or neutral faces in 10 trials per scan. Subjects reported the intensity of experienced sadness after each trial. Immediate feedback of amygdala activation was given to the subjects during the ongoing scan to reinforce mood induction. Correspondence between increased intensity of predominantly left sided amygdala activation and self-rating of sadness was found in 78% of 120 sad trials, in contrast to only 14% of neutral trials. Amygdala activation was reproducible during repeated scanning sessions and displayed the strongest correlation with self-rating among all regions. These results suggest that amygdala activation may be closely associated with self-induced sadness. This novel real-time fMRI technology is applicable to a wide range of neuroscience studies, particularly those of the limbic system, and to neuropsychiatric conditions, such as depression, in which pathology of the amygdala has been implicated.

Adult↗

PubMed2003

Increased amygdala: hippocampal volume ratios associated with severity of anxiety in pediatric major depression.

BACKGROUND: Neurobiologic abnormalities in the temporal lobe, particularly medial temporolimbic circuits, have been implicated in the pathogenesis of major depressive disorder (MDD). Although MDD commonly emerges during childhood and adolescence, to our knowledge, no prior study has examined temporal lobe anatomy in pediatric patients with MDD near the onset of illness before treatment. METHODS: Volumetric magnetic resonance imaging scans were conducted in 23 psychotropic drug-naïve pediatric patients with MDD, aged 8-17 years, and 23 case-matched healthy comparison subjects. RESULTS: Pediatric patients with MDD had significantly larger left (14%) and right (11%) amygdala:hippocampal volume ratios than controls. Increased left and right amygdala:hippocampal volume ratios were associated with increased severity of anxiety but not increased severity of depression or duration of illness. CONCLUSION: These results suggest that alterations in amygdala:hippocampal volume ratios in pediatric MDD may more reflect severity of associated anxiety than depression. These results underscore the importance of assessment for comorbidity in the study of MDD.

Adolescent↗

PubMed2003

Localized functional neurochemical marker abnormalities in dorsolateral prefrontal cortex in pediatric obsessive-compulsive disorder.

BACKGROUND: Neurobiological abnormalities in the prefrontal cortex have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Although OCD commonly arises during childhood and adolescence, to our knowledge, no prior study has examined prefrontal cortex neurochemistry in pediatric patients with OCD. METHODS: A multislice spectroscopic imaging sequence with validated phantom replacement methodology was used to measure N-acetyl-aspartate (NAA), a putative neuronal marker; choline compounds (Cho); and creatine/phosphocreatine (Cr) in right and left dorsolateral prefrontal cortex (DLPFC) of 15 treatment-naïve OCD patients, 8-15 years of age, and 15 case-matched healthy comparison subjects. RESULTS: A significant increase (21% higher) in NAA was observed in left but not right DLPFC in OCD patients versus control subjects. No significant differences in Cho or Cr were observed between groups in left or right DLPFC. CONCLUSIONS: These results provide new evidence of localized functional neurochemical marker alterations in left DLPFC in pediatric OCD. Increased left DLPFC NAA may represent neuronal hypertrophy or hyperplasia, glial hypoplasia, and/or abnormal pruning of neural brain elements in DLPFC.

Adolescent↗

PubMed2003

The use of mood stabilizers as plasticity enhancers in the treatment of neuropsychiatric disorders.

Mood disorders have traditionally been conceptualized as neurochemical disorders, but there is now evidence from a variety of sources demonstrating regional reductions in central nervous system (CNS) volume, as well as reductions in the numbers and/or sizes of glia and neurons in discrete brain areas. Although the precise cellular mechanisms underlying these morphometric changes remain to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. It is thus noteworthy that lithium and valproate have recently been demonstrated to robustly increase the expression of the cytoprotective protein bcl-2 (an abbreviation for the B-cell lymphoma/leukemia-2 gene) in the CNS in vivo and in cells of human neuronal origin. Lithium and valproate also robustly activate a signaling cascade utilized by endogenous growth factors-the extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathway. Complementary human studies have shown that chronic lithium administration significantly increases gray matter content in a regionally selective manner, suggesting a reversal of illness-related atrophy and an increase in the volume of the neuropil. These unique and unexpected properties of lithium and valproate suggest that they may have broader utility as adjunctive agents in the treatment of a variety of neuropsychiatric disorders associated with cell atrophy or loss. The adjunctive use of these agents-at low doses-may provide the trophic support necessary to restore, enhance, and maintain normal synaptic connectivity, thereby allowing the chemical signal to reinstate the optimal functioning of critical circuits necessary for normal functioning.

Anticonvulsants↗

PubMed2002

Proton magnetic resonance spectroscopic imaging in pediatric major depression.

BACKGROUND: Neurobiologic abnormalities in dorsolateral prefrontal cortex (DLPFC) are believed to be involved in the pathophysiology of major depressive disorder (MDD). Although MDD commonly emerges during childhood and adolescence, to our knowledge, no prior study has examined the DLPFC in pediatric patients with MDD. METHODS: In this study, choline compounds (Cho), N-acetylaspartate (NAA), and creatine/phosphocreatine (Cr) were measured in left and right DLPFC using a multislice proton magnetic resonance spectroscopic imaging sequence with validated phantom replacement methodology in 11 treatment-naïve MDD patients, 10-16 years of age, and 11 case-matched healthy control subjects. RESULTS: A significant increase in Cho was observed in left but not right DLPFC in MDD patients versus control subjects (32.5% higher). No significant differences in NAA or Cr were observed between case-control pairs. CONCLUSIONS: These results provide new evidence of localized functional neurochemical marker alterations in left DLPFC in pediatric MDD. Our results must be considered preliminary, however, given the small sample size.

Adolescent↗

PubMed2002

Prefrontal cortical volume in childhood-onset major depression: preliminary findings.

BACKGROUND: Abnormalities in the prefrontal cortex have been implicated in the pathogenesis of major depressive disorder (MDD). To our knowledge, no prior study has examined prefrontal cortical anatomy in pediatric patients with MDD near the onset of illness before receiving treatment. METHODS: Volumetric magnetic resonance imaging studies were conducted in 22 psychotropic-naive patients with MDD, aged 9 to 17 years (10 males and 12 females), and 22 case-matched healthy comparison control subjects. Twelve of the 22 patients with MDD had at least 1 first-degree relative with MDD (familial MDD), whereas 10 had no clear family history of MDD (nonfamilial MDD). RESULTS: Patients with nonfamilial MDD had significantly larger left-sided but not right-sided prefrontal cortical volumes than patients with familial MDD (17% larger) and controls (11% larger). Left-sided and right-sided prefrontal cortical volumes did not differ significantly between patients with familial MDD and controls. CONCLUSIONS: These results provide new evidence of prefrontal cortical alterations in pediatric MDD that may differ in familial and nonfamilial subtypes of MDD. Our findings must be considered preliminary, however, in view of the small sample size.

Adolescent↗

PubMed2002

Mood disorders: treatment-induced changes in brain neurochemistry and structure.

Continuing advances in neuroimaging technology as well as postmortem examinations have enabled researchers to begin to accumulate substantial evidence suggesting that chronic mood disorders may be associated with actual structural and neurochemical changes within the brain. There is emerging evidence to suggest that various treatment modalities may also induce measurable changes within the brain detectable with specialized neuroimaging techniques, which may be responsible for their clinical therapeutic effects. One such specialized neuroimaging technique, magnetic resonance spectroscopy (MRS), is briefly reviewed. Included is an overview of basic MRS technology and a review of its application in the study of chronic mood disorders to date. We review our recent studies investigating neurochemical changes induced by the mood stabilizer, lithium, in the treatment of bipolar disorder (BPD). Finally, in view of accumulating evidence suggesting a neuronal atrophy and cell death hypothesis for depression, we discuss the potential use of MRS to evaluate pharmacologic interventions for important potential neurotrophic and neuroprotective effects on the adult human brain.

Brain↗

PubMed2002

Patients lacking the major CNS myelin protein, proteolipid protein 1, develop length-dependent axonal degeneration in the absence of demyelination and inflammation.

Axonal degeneration contributes to clinical disability in the acquired demyelinating disease multiple sclerosis. Axonal degeneration occurs during acute attacks, associated with inflammation, and during the chronic progressive phase of the disease in which inflammation is not prominent. To explore the importance of interactions between oligodendrocytes and axons in the CNS, we analysed the brains of rodents and humans with a null mutation in the gene encoding the major CNS myelin protein, proteolipid protein (PLP1, previously PLP). Histological analyses of the CNS of Plp1 null mice and of autopsy material from patients with null PLP1 mutations were performed to evaluate axonal and myelin integrity. In vivo proton magnetic resonance spectroscopy (MRS) of PLP1 null patients was conducted to measure levels of N-acetyl aspartate (NAA), a marker of axonal integrity. Length-dependent axonal degeneration without demyelination was identified in the CNS of Plp1 null mice. Proton MRS of PLP1-deficient patients showed reduced NAA levels, consistent with axonal loss. Analysis of patients' brain tissue also demonstrated a length-dependent pattern of axonal loss without significant demyelination. Therefore, axonal degeneration occurs in humans as well as mice lacking the major myelin protein PLP1. This degeneration is length-dependent, similar to that found in the PNS of patients with the inherited demyelinating neuropathy, CMT1A, but is not associated with significant demyelination. Disruption of PLP1-mediated axonal--glial interactions thus probably causes this axonal degeneration. A similar mechanism may be responsible for axonal degeneration and clinical disability that occur in patients with multiple sclerosis.

Adult↗

PubMed2002

Magnetic resonance spectroscopy: neurochemistry and treatment effects in affective disorders.

Recent developments in the clinical capabilities of magnetic resonance spectroscopy (MRS) have provided researchers with considerable insight into potential neurochemical alterations associated with the pathology and treatment of affective disorders. This review focuses on the clinical application of MRS to the study of affective disorders, discusses the major MRS visible neurochemicals, and addresses some essential principles of MRS methodology, such as pulse sequences and neurochemical quantitation. Additionally, some of the more recent key findings in the area of mood disorders and their treatment are highlighted, including pharmacological effects and mechanisms. For example, several independent groups have reported alterations in levels of choline, myoinositol, N-acetylaspartate, and gamma-aminobutyric acid in the central nervous systems of patients with major depression, bipolar disorder, panic disorder, or obsessive-compulsive disorder. Finally, the current direction of advances and areas of further investigation are discussed. This review will afford the reader a fundamental foundation in the applications of MRS in mood disorders and an update on some of the current findings in this rapidly developing discipline.

Animals↗