[show abstract][hide abstract] ABSTRACT: Children with dyslexia have difficulty learning to recognize written words owing to subtle deficits in oral language related to processing sounds and accessing words automatically. The purpose of this study was to compare regional changes in brain lactate between dyslexic children and control subjects during oral language activation.
Brain lactate metabolism was measured during four different cognitive tasks (three language tasks and one nonlanguage task) in six dyslexic boys and in seven control subjects (age- and IQ-matched right-handed boys who are good readers) using a fast MR spectroscopic imaging technique called proton echo-planar spectroscopic imaging (1-cm3 voxel resolution). The area under the N-acetylaspartate (NAA) and lactate peaks was measured to calculate the lactate/NAA ratio in each voxel.
Dyslexic boys showed a greater area of brain lactate elevation (2.33+/-SE 0.843 voxels) as compared with the control group (0.57+/-SE 0.30 voxels) during a phonological task in the left anterior quadrant. No significant differences were observed in the nonlanguage tasks.
Dyslexic and control children differ in brain lactate metabolism when performing language tasks, but do not differ in nonlanguage auditory tasks.
American Journal of Neuroradiology 10/1999; 20(8):1393-8. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Since there is limited information concerning caffeine's metabolic effects on the human brain, the authors applied a rapid proton echo-planar spectroscopic imaging technique to dynamically measure regional brain metabolic responses to caffeine ingestion. They specifically measured changes in brain lactate due to the combined effects of caffeine's stimulation of glycolysis and reduction of cerebral blood flow.
Nine heavy caffeine users and nine caffeine-intolerant individuals, who had previously discontinued or substantially curtailed use of caffeinated products because of associated anxiety and discomforting physiological arousal, were studied at baseline and then during 1 hour following ingestion of caffeine citrate (10 mg/kg). To assess state-trait contributions and the effects of caffeine tolerance, five of the caffeine users were restudied after a 1- to 2-month caffeine holiday.
The caffeine-intolerant individuals, but not the regular caffeine users, experienced substantial psychological and physiological distress in response to caffeine ingestion. Significant increases in global and regionally specific brain lactate were observed only among the caffeine-intolerant subjects. Reexposure of the regular caffeine users to caffeine after a caffeine holiday resulted in little or no adverse clinical reaction but significant rises in brain lactate which were of a magnitude similar to that observed for the caffeine-intolerant group.
These results provide direct evidence for the loss of caffeine tolerance in the human brain subsequent to caffeine discontinuation and suggest mechanisms for the phenomenon of caffeine intolerance other than its metabolic effects on elevating brain lactate.
American Journal of Psychiatry 03/1999; 156(2):229-37. · 14.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: A fast, proton echo-planar spectroscopic imaging (PEPSI) technique, capable of simultaneously measuring metabolites from multiple brain regions, was used to investigate the anatomical distribution and magnitude of brain lactate responses to intravenous lactate infusion among subjects with panic disorder and control subjects.
Fifteen subjects with panic disorder and 10 control subjects were studied. All subjects were medication free and met DSM-IV criteria for panic disorder, or, for controls, no Axis I psychiatric disorder. Two-dimensional axial metabolite images having 1-cm3 spatial resolution were acquired at 61/2-minute intervals during 3 conditions: a 20-minute baseline, 20-minute 0.5-mol/L sodium lactate infusion, and 15-minute postinfusion period.
Intravenous lactate infusion increased brain lactate levels throughout the axial brain section studied in all subjects. Panic-disordered subjects had significantly greater global brain lactate increases in response to lactate infusion. Lateralization of brain lactate response did not occur, nor were discrete regional loci of elevated lactate observed. Cerebrospinal fluid lactate changes corresponded to lactate changes in brain tissue. Severity of symptoms provoked by lactate infusion did not directly correlate with brain lactate response.
Greater overall rises in brain lactate among subjects with panic disorder compared with controls occurred in response to lactate infusion. We were unable to detect a distinct regional pattern for magnitude differences in brain lactate rise by which to identify a specific neuroanatomical substrate underlying a lactate-induced panic response. The wide anatomical distribution of these brain lactate increases suggest metabolic and/or neurovascular mechanisms for the abnormal rise in subjects with panic disorder.
Archives of General Psychiatry 02/1999; 56(1):70-7. · 13.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: The current state-of-the-art imaging technique in multiple sclerosis (MS) is magnetic resonance (MR) imaging. With improved imaging technology, MR spectroscopy offers the capacity to identify those chemical changes associated with MS and promises to enhance our ability to understand this disease. Physiologic function in the central nervous system can be measured using evoked potentials. This article analyzes the correlation between these two techniques.
Physical Medicine and Rehabilitation Clinics of North America 09/1998; 9(3):561-7, vi. · 1.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: We performed a double-blind study to measure the clinical and subclinical effects of an alternative medicine magnetic device on disease activity in multiple sclerosis (MS). The MS patients were exposed to a magnetic pulsing device (Enermed) where the frequency of the magnetic pulse was in the 4-13 Hz range (50-100 milliGauss). A total of 30 MS patients wore the device on preselected sites between 10 and 24 hours a day for 2 months. Half of the patients (15) randomly received an Enermed device that was magnetically inactive and the other half received an active device. Each MS patient received a set of tests to evaluate MS disease status before and after wearing the Enermed device. The tests included (1) a clinical rating (Kurtzke, EDSS), (2) patient-reported performance scales, and (3) quantitative electroencephalography (QEEG) during a language task. Although there was no significant change between pretreatment and posttreatment in the EDSS scale, there was a significant improvement in the performance scale (PS) combined rating for bladder control, cognitive function, fatigue level, mobility, spasticity, and vision (active group -3.83 +/- 1.08, p < 0.005; placebo group -0.17 +/- 1.07, change in PS scale). There was also a significant change between pretreatment and posttreatment in alpha EEG magnitude during the language task recorded at various electrode sites on the left side. In this double-blind, placebo-controlled study, we have demonstrated a statistically significant effect of the Enermed magnetic pulsing device on patient performance scales and on alpha EEG magnitude during a language task.
The Journal of Alternative and Complementary Medicine 02/1997; 3(1):21-9. · 1.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diffusion imaging and T2-weighted magnetic resonance imaging were performed on 16 monkeys with experimental allergic encephalomyelitis (EAE), a model of the human demyelinating disease MS. The purpose of this study was to determine whether local changes in diffusion image intensity could be correlated with the formation of acute and chronic demyelinating lesions. Diffusion image analysis was restricted to the internal capsule of the brain because of its anatomic orientation of fiber pathways. Acute inflammatory EAE lesions were large and monophasic, as visualized by T2-weighted MRI, and were accompanied by a decrease in the diffusion MR image signal with the diffusion-sensitizing gradient in all three orthogonal directions (n = 27 brain regions, P < 0.005). Chronic demyelinating lesions were preceded by multiple inflammatory attacks, as visualized by MRI, and by a decrease in diffusion MR image signal with the diffusion-sensitizing gradient in the two orthogonal directions perpendicular to the fibers of the internal capsule (n = 18 brain regions, P < 0.005). However, for the chronic group, there was no significant change in the diffusion MR image signal with diffusion-sensitizing gradient parallel to the fibers of the internal capsule at the terminal scan, suggesting little change in the water diffusion within the nerve fibers. These results suggest that diffusion imaging holds promise for measuring subtle changes in water diffusion due to different types of brain damage.
[show abstract][hide abstract] ABSTRACT: Volume-localized proton spectroscopy and T2-weighted MRI were performed on 23 monkeys with experimental allergic encephalomyelitis (EAE). The purpose of this study was to determine the relationships between temporal changes in lesion activity (measured on T2-weighted MRI), MRS [N-acetyl aspartate (NAA), creatine (CR), choline (CHO)], and the histologic definition of disease determined post-mortem. Animals were scanned in the same areas of the brain once a week before and after sensitization to myelin basic protein (BP). Histologic lesion types were predicted by a combination of preceding MRI and MRS measurements. Acutely fatal EAE lesions were large and monophasic as visualized by MRI, and increased CHO (p < 0.02, n = 16) and CHO/CR ratio (p < 0.001, n = 16) were detected by MRS at disease onset. Chronic EAE lesions were preceded by multiple inflammatory attacks as visualized by MRI and consistently low levels of NAA (p < 0.02, n = 13) and NAA/CR (p < 0.01, n = 13) which occurred after the initial attack. MRI negative brain regions (from animals that were sensitized to BP) were associated with low CHO/CR (p < 0.1, n = 5). The temporal correlation of MRI lesion activity and absolute MRS proton metabolites shows promise for predicting the subsequent duration and histologic type of lesions in EAE in non-human primates.
NMR in Biomedicine 05/1995; 8(2):49-58. · 3.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: A clear understanding of choline metabolism is important in our goal to modify demyelination and remyelination in multiple sclerosis. To develop a technique capable of measuring metabolic changes in the brain, we have studied the incorporation of a phosphonium analogue of choline (P-choline) in tissue extracts of rats. After feeding adult rats a choline-deficient diet supplemented with P-choline, the analogue was not detectable by in vivo volume-localized 1H spectroscopy. However, in vitro 31P measurements of brain extracts revealed an 11% incorporation of P-choline into phosphatidylcholine. We report that P-choline incorporates preferentially into the lipid pool over the lipid precursor pool and we provide evidence that the choline peak resolved by in vivo 1H spectroscopy is only composed of small molecular weight choline-containing compounds.
Magnetic Resonance in Medicine 04/1995; 33(3):285-92. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diffusion-weighted magnetic resonance imaging (MRI) was compared with T2-weighted MRI in longitudinal studies of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, in five monkeys (Macaca fascicularis). In a region of the brain that had highly directional myelinated fibers (internal capsule) sequential changes were identified on diffusion-weighted images on and before the day these changes were detected on conventional T2-weighted images. Changes were also identified on diffusion-weighted images in brain areas that did not develop T2-weighted abnormalities. This result suggests that diffusion-weighted image intensities are sensitive to pathologic conditions of the brain that can not be seen on T2-weighted images.
Magnetic Resonance in Medicine 05/1993; 29(4):478-84. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Our purpose was to compare cerebral proton MR metabolite changes in patients with multiple sclerosis (MS) and abnormal visual evoked potentials (VEPs) with those in MS patients with normal VEPs.
Seventeen subjects with clinically definite MS were studied with VEPs and MR spectroscopic imaging. Proton MR metabolites were measured using a fast spectroscopic imaging technique called proton echo-planar spectroscopic imaging (PEPSI). Kurtzke's Expanded Disability Status Scale (EDSS) score was also ascertained for each subject to obtain a clinical rating. Twelve regions of interest within the visual pathway of the cerebrum were evaluated for levels of N-acetylaspartate (NAA), choline, creatine, and the presence or absence of MR-detectable lesions.
PEPSI NAA values (water-normalized, CSF-corrected) were significantly lower in MS subjects with abnormal VEPs than in subjects with normal VEPs. MR-detectable lesion fractions and EDSS scores were also significantly different between the two VEP groups, but NAA comparison had a P value 100 times less than either of these measures.
In patients with MS, NAA measurements in the optic pathways of the brain were sensitive to VEP abnormalities. NAA was more sensitive to VEP changes than were choline, creatine, MR-detectable lesions, and EDSS score.
American Journal of Neuroradiology 19(6):1047-54. · 3.17 Impact Factor