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Biomedical subjects

William M Brooks

Publications and source records attributed to William M Brooks.

At least 19 recordsLinked to original sources
PubMed2006

A mouse model of sensorimotor controlled cortical impact: characterization using longitudinal magnetic resonance imaging, behavioral assessments and histology.

The present study establishes a new mouse model for traumatic brain injury (TBI), using an electromechanically driven linear motor impactor device to deliver a lateral controlled cortical impact (CCI) injury to the sensorimotor cortex. Lesion cavity size was measured, and inter-animal consistency demonstrated, at 14 days post injury. Qualitative information regarding damage progression over time was obtained by scanning with high field magnetic resonance imaging (MRI) at five time points following injury. Functional impairment and recovery were measured with the Rotarod, gridwalk and cylinder tests, and lesion cavity volume was measured post mortem with thionin-stained tissue sections. The study establishes the reliability of a linear-motor based device for producing repeatable damage in a CCI model, demonstrates the power of longitudinal MRI in studying damage evolution, and confirms that a simple battery of functional tests record sensorimotor impairment and recovery.

Animals↗
PubMed2006

Neural mechanisms underlying hyperphagia in Prader-Willi syndrome.

OBJECTIVE: Prader-Willi syndrome (PWS) is a genetic disorder associated with developmental delay, obesity, and obsessive behavior related to food consumption. The most striking symptom of PWS is hyperphagia; as such, PWS may provide important insights into factors leading to overeating and obesity in the general population. We used functional magnetic resonance imaging to study the neural mechanisms underlying responses to visual food stimuli, before and after eating, in individuals with PWS and a healthy weight control (HWC) group. RESEARCH METHODS AND PROCEDURES: Participants were scanned once before (pre-meal) and once after (post-meal) eating a standardized meal. Pictures of food, animals, and blurred control images were presented in a block design format during acquisition of functional magnetic resonance imaging data. RESULTS: Statistical contrasts in the HWC group showed greater activation to food pictures in the pre-meal condition compared with the post-meal condition in the amygdala, orbitofrontal cortex, medial prefrontal cortex (medial PFC), and frontal operculum. In comparison, the PWS group exhibited greater activation to food pictures in the post-meal condition compared with the pre-meal condition in the orbitofrontal cortex, medial PFC, insula, hippocampus, and parahippocampal gyrus. Between-group contrasts in the pre- and post-meal conditions confirmed group differences, with the PWS group showing greater activation than the HWC group after the meal in food motivation networks. DISCUSSION: Results point to distinct neural mechanisms associated with hyperphagia in PWS. After eating a meal, the PWS group showed hyperfunction in limbic and paralimbic regions that drive eating behavior (e.g., the amygdala) and in regions that suppress food intake (e.g., the medial PFC).

Adolescent↗
PubMed2006

Magnetic resonance spectroscopy detects brain injury and predicts cognitive functioning in children with brain injuries.

Proton magnetic resonance spectroscopy (1H-MRS) and neuropsychological assessment were utilized in a longitudinal investigation of traumatic brain injury (TBI) in children. A spectroscopic imaging protocol was implemented, and neurometabolite ratios of NAA/Cre and Cho/Cre were calculated for anterior and posterior halves of a supraventricular slab of brain tissue. NAA/Cre was reduced and Cho/Cre increased in TBI patients as compared to controls, for both brain regions. Each ratio predicted aspects of neuropsychological performance, though the specific relationships varied somewhat by region and function. Anterior NAA/Cre increased and anterior Cho/Cre decreased from 3 to 21 weeks post-injury, suggesting neurometabolic recovery.

Adolescent↗
PubMed2005

Sex differences in N-acetylaspartate correlates of general intelligence: an 1H-MRS study of normal human brain.

Researchers have long attempted to determine brain correlates of intelligence using available neuroimaging technology including CT, MRI, PET, and fMRI. Although structural and functional imaging techniques are well suited to assess gross cortical regions associated with intelligence, the integrity and functioning of underlying white matter networks critical to coordinated cortical integration remain comparatively understudied. A relatively recent neuroimaging advance is magnetic resonance spectroscopy (MRS) which allows for interrogation of biochemical substrates of brain structure and function in vivo. In this study, we examined twenty-seven normal control subjects (17 male, 10 female) to determine whether N-acetylaspartate (NAA), a metabolite found primarily within neurons, is related to intelligence as assessed by the Wechsler Adult Intelligence Scale-III. Of the three white matter regions studied (i.e., left frontal, right frontal, left occipito-parietal), we found that a model including only left occipito-parietal white matter predicted intellectual performance [F(1,25) = 8.65, P = .007; r2 = .26], providing regional specificity to our previous findings of NAA-IQ relationships. Moreover, we found that a complex combination of left frontal and left occipito-parietal NAA strongly predicted performance in women, but not men [F(2,7) = 21.84, P < .001; adjusted r2 = .82]. Our results highlight a biochemical substrate of normal intellectual performance, mediated by sex, within white matter association fibers linking posterior to frontal brain regions.

Adolescent↗
PubMed2005

Virtual navigation in humans: the impact of age, sex, and hormones on place learning.

Certain cognitive processes, including spatial ability, decline with normal aging. Spatial ability is also a cognitive domain with robust sex differences typically favoring males. However, tests of spatial ability do not seem to measure a homogeneous class of processes. For many, mentally matching rotated three-dimensional images is the gold standard for measuring spatial cognition in humans, while the Morris water task (MWT) is a preferred method in the domain of nonhuman animal research. The MWT is sensitive to hippocampal damage, a structure critical for normal learning and memory and often implicated in age-related cognitive decline. A computerized (virtual) version of the MWT (VMWT) appears to require and engage human hippocampal circuitry, and has proven useful in studying sex differences and testing spatial learning theories. In Experiment 1, we tested participants (20-90 years of age) in the VMWT and compared their performance to that on the Vandenberg Mental Rotation Test. We report an age-related deficit in performance on both tasks. In Experiment 2, we tested young (age 20-39) and elderly (age >60) participants in the VMWT and correlated their performance to the circulating levels of testosterone and cortisol. Our findings indicate that the persistence of male spatial advantage may be related to circulating testosterone, but not cortisol levels, and independent of generalized age-related cognitive decline.

Adult↗
PubMed2005

Microneurography of human median nerve.

PURPOSE: To examine the possibility of performing high-resolution MRI (microneurography) on peripheral nerves. MATERIALS AND METHODS: A specific radio frequency (RF) coil was developed to probe the human median nerve at a magnetic field strength of 9.4 T and tested on three excised samples by acquiring microneurograms. RESULTS: The microneurograms revealed neuronal tissue constituents at subfascicular level. The contrast features on proton-density and T1- and T2-weighted images were described and compared. The microscopic water movement was quantified using diffusion weighting parallel and orthogonal to the neuronal fiber orientation. The characteristics of anisotropic diffusion in the median nerve were comparable to those reported from other biological tissues (white matter and kidney). CONCLUSION: The results overall suggest that microneurography might provide new noninvasive insights into microscopic gross anatomy of the peripheral nerve, injury evaluation, and efficacy of repair, although the feasibility at current clinically relevant field strengths is yet to be determined.

Cadaver↗
PubMed2005

Magnetic resonance angiography of rat spinal cord at 9.4 T: a feasibility study.

In this study we investigated the feasibility of performing 3D time-of-flight magnetic resonance angiography to remotely image the arteries of rat spinal cord. Using a custom-designed implantable radiofrequency coil, we acquired angiograms from normal and injured cords. The potential of the approach was evaluated in terms of longitudinally monitoring the vascular reorganization of spinal cord following an injury.

Animals↗
PubMed2005

Neural mechanisms underlying food motivation in children and adolescents.

Dramatic increases in childhood obesity necessitate a more complete understanding of neural mechanisms of hunger and satiation in pediatric populations. In this study, normal weight children and adolescents underwent functional magnetic resonance imaging (fMRI) scanning before and after eating a meal. Participants showed increased activation to visual food stimuli in the amygdala, medial frontal/orbitofrontal cortex, and insula in the pre-meal condition; no regions of interest responded in the post-meal condition. These results closely parallel previous findings in adults. In addition, we found evidence for habituation to food stimuli in the amygdala within the pre-meal session. These findings provide evidence that normal patterns of neural activity related to food motivation begin in childhood. Results have implications for obese children and adults, who may have abnormal hunger and satiation mechanisms.

Adolescent↗
PubMed2005

Effects of ketamine on anterior cingulate glutamate metabolism in healthy humans: a 4-T proton MRS study.

OBJECTIVE: The authors' goal was to test in humans the hypothesis that N-methyl-d-aspartate receptor (NMDAR) antagonism results in increased cortical glutamate activity, as proposed by the NMDAR hypofunction model of schizophrenia. METHOD: 4-T 1H proton magnetic resonance spectroscopy (1H-MRS) was used to acquire in vivo spectra from the bilateral anterior cingulate of 10 healthy subjects while they received a subanesthetic dose of either placebo or ketamine, an NMDAR antagonist. Assessments given before and after ketamine or placebo administration included the Brief Rating Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, the Clinician-Administered Dissociative States Scale, and the Stroop task. RESULTS: As predicted, there was a significant increase in anterior cingulate glutamine, a putative marker of glutamate neurotransmitter release, with ketamine administration. This increase was not related to schizophrenia-like positive or negative symptoms but was marginally related to Stroop performance. CONCLUSIONS: In humans as in animals, an acute hypofunctional NMDAR state is associated with increased glutamatergic activity in the anterior cingulate.

Adult↗
PubMed2005

Late proton MR spectroscopy in children after traumatic brain injury: correlation with cognitive outcomes.

BACKGROUND AND PURPOSE: Proton MR spectroscopy has demonstrated reduced levels of N-acetylaspartate (NAA) in normal-appearing occipital and frontal regions of patients with acute nonpenetrating traumatic brain injury (TBI). We studied the relationship of frontoparietal NAA, choline (Cho), and creatine (Cr) to test the hypothesis that reduction in NAA is predictive of cognitive outcome. METHODS: Proton spectra were collected by using conventional 2D chemical shift imaging in five healthy children and seven children (6 weeks to 3 years) with severe (n=4), moderate (n=2), or mild (n=1) TBI. Spectra in the anterior and posterior regions of the left and right frontoparietal areas were averaged for analysis by using LCModel, with a phantom-established basis function, for quantification of NAA, Cho, and Cr concentrations. Intellectual function, expressive language, and arithmetic capability were measured within 4 months of imaging. RESULTS: NAA/Cho concentration was lower in TBI patients than in control subjects, but no group differences were present for Cho or Cr. Hemispheric levels for NAA, Cho, and Cr were higher on the left than on the right, but we found no effect of region and no interactions. Cognition was lower in the TBI group than the control group and correlated with NAA levels. Left frontal Cho was also correlated with arithmetic scores, whereas Cr was not significantly correlated. CONCLUSION: NAA levels remain low after TBI and are related to cognitive function. Neurometabolite values are greater in the left frontoparietal region than in the right, and the left frontal Cho level is related to arithmetic ability.

Adolescent↗
PubMed2004

Reduced area of the corpus callosum in posttraumatic stress disorder.

Magnetic resonance imaging (MRI) studies have revealed decreases in the mid-sagittal area of the corpus callosum (CC) in pediatric posttraumatic stress disorder (PTSD), but at present no data are available in adult PTSD patients. We have previously reported decreased whole-brain white matter (WM) volume in adults with PTSD and now report corpus callosum area from the same sample. MRI was used to obtain whole-brain images in 12 adult patients with PTSD and 10 matched controls. Total parenchyma (white matter plus gray matter [GM]) volume, mid-sagittal area of the CC and seven sub-regions of this structure were calculated. In PTSD patients, the total CC area, absolute and normalized to total brain parenchyma, was smaller compared with control values. Several absolute and normalized CC sub-regions were also smaller in PTSD patients: genu (region 2), mid-body (region 5) and isthmus (region 6). There was also a trend for the anterior mid-body (area 4) to be smaller in PTSD patients. No differences were found in the rostrum (region 1), rostral body (region 3) or splenium (region 7). Adult patients with PTSD had decreased CC area after correcting for total brain tissue, indicating that these differences are not attributable to generalized white matter atrophy. These findings are similar to previous results in children with PTSD and suggest specific changes in the CC.

Adult↗
PubMed2004

Multisequence magnetic resonance imaging study of neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To investigate the relationship between magnetization transfer imaging (MTI), diffusion-weighted imaging (DWI), proton magnetic resonance spectroscopy (H-MRS), and T2 relaxometry findings in patients with primary neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: The study group consisted of 24 female patients (mean age 36 years [range 23-65]) who had had a variety of neuropsychiatric symptoms that were judged to be due to NPSLE according to the criteria of the American College of Rheumatology. Patients with current active disease were excluded from participation. Quantitative MTI, DWI, H-MRS, and T2 relaxometry data were acquired in all patients, and the correlation coefficients were calculated. RESULTS: MTI results reflecting a decrease in homogeneity of cerebral parenchyma correlated significantly with H-MRS results representing axonal damage. MTI results also correlated significantly with DWI results reflecting increased diffusivity in the cerebral parenchyma. Finally, MTI results reflecting decreased cerebral homogeneity correlated significantly with increased T2 relaxation time, associated with either edema or gliosis. Increased T2 relaxation time correlated significantly with DWI results reflecting increased diffusivity. With the exception of the correlation between H-MRS and MTI findings, there was no significant correlation between H-MRS results and any other parameter. CONCLUSION: The selected study parameters represent different biologic features in the human brain and can be informative with regard to different pathologic processes in NPSLE. The demonstrated associations between MTI, DWI, H-MRS, and T2 data in patients with a history of NPSLE suggest that there is one pathogenesis and/or common neuropathologic outcome in NPSLE despite differences in clinical presentation.

Adult↗
PubMed2003

Reproducibility of 1H-MRS measurements in schizophrenic patients.

The reproducibility of single-voxel spectroscopic measures in a stable schizophrenic patient population is reported. Spectra acquired 1 week apart, in the left frontal white matter and left caudate nucleus of 12 patients, were analyzed using both frequency and time-domain techniques. No significant change in mean concentrations for N-acetylaspartate (NAA), choline (Cho), and creatine (Cre) were found between sessions. Variation from scan to scan was low for the left frontal white matter, with coefficients of variation (CV) < 5% for all three metabolites. NAA measures from the left caudate nucleus had similar reproducibility (CV = 5%), but Cho and Cre were poorer by comparison (CV = 16-18%). The two methods used for spectral analyses produced similar results, indicating that both techniques are appropriate. These results extend previous studies of healthy, normal subjects, and establish that it is possible to obtain reliable measures of brain metabolites in clinical populations.

Adult↗
PubMed2003

Effects of intermittent cycle exercise on intramyocellular lipid use and recovery.

The purpose of this investigation was to compare intramyocellular lipid (IMCL) changes in skeletal muscle in nine moderately trained subjects after 45 min of interval cycling and through 1 h of recovery. The exercise session was continuous with alternating cycling intensity achieving 50 (3 min) and 110% (2 min) of ventilatory threshold. Spectra from the vastus lateralis were acquired before, immediately after, and 60 min following exercise using a 1.5 T Signa whole-body magnet (point-resolved spectroscopy sequence, echo time 60 ms, transverse relaxation time 2000 ms, 128 acquisitions, and 20 mm3 voxel). Immediately following exercise, IMCL concentration decreased 38% compared to pre-exercise levels (P < 0.05). Fitness level and baseline IMCL were not correlated with changes in IMCL following exercise (P > 0.05). In the 60-min recovery, IMCL was reduced 30% compared to baseline (P < 0.05) and did not recover. In contrast, a nonexercising control group showed no change in IMCL. Our results suggest that IMCL decreased significantly following 45 min of interval cycling, with little recovery in the hour following.

Adult↗
PubMed2003

Skeletal muscle mitochondrial function and lean body mass in healthy exercising elderly.

BACKGROUND: The decline in muscle mass (sarcopenia) with aging may be related to a decline in mitochondrial function. However, investigators have yet to reach a consensus as to whether a decline in mitochondrial function can be attenuated by physical activity has yet to reach a consensus. METHODS: Using dynamic 31PMRS to measure mitochondrial function, we measured baseline Phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiester (PDE), [ADP], pH and recovery times (t(1/2)) for PCr and [ADP] following exercise, in 45 older (73+/-4 years, SD), and 20 younger subjects (25+/-4 years, SD) who were matched for body mass across high and low activity levels and within age and sex groupings. RESULTS: Baseline PCr, and Pi, were lower, and PDE higher in the older subjects compared to younger subjects (all P<0.01). The t(1/2)(ADP) was longer in older subjects (P<0.001) controlling for age and sex in the low activity group (P=0.02). In the older low activity groups, t(1/2)(PCr) was longer than high activity groups. Higher PDE levels were positively correlated with longer t(1/2)(PCr) in the older low activity females (both P<0.05). CONCLUSIONS: Our data suggests that mitochondrial function declines with age in healthy, exercising elderly adults and that the decline appears to be influenced by the level of physical activity.

Adenosine Diphosphate↗
PubMed2003

The aging hippocampus: cognitive, biochemical and structural findings.

Aging is often accompanied by learning and memory problems, many of which resemble deficits associated with hippocampal damage. Studies of aging in nonhuman animals have demonstrated hippocampus-related memory decline, and point to a possible locus for impairments associated with normal and pathological aging in humans. Two well-characterized hippocampus-dependent tasks in nonhuman animal literature are the Morris water task (MWT) and the transverse patterning discrimination task (TPDT). We employed the virtual MWT and the TPDT to assess hippocampus-dependent cognition in humans. Magnetic resonance imaging and proton magnetic resonance spectroscopy were employed to measure hippocampal volume and neurochemistry respectively. Age-related deficits were observed in performance on both hippocampus-dependent tasks. This pattern of impairment was accompanied by decreased hippocampal NAA/Cre ratios and volume, both of which imply neuronal loss and/or decrease in neuronal density. Collectively, our results suggest that hippocampus undergoes structural and biochemical changes with normal aging and that these changes may represent an important component of age-related deterioration in hippocampus-dependent cognition.

Adult↗
PubMed2003

Proton magnetic resonance spectroscopy investigation of the right frontal lobe in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: To investigate neurometabolite concentrations in right prefrontal white matter in children with attention-deficit/hyperactivity disorder (ADHD) and relations of neurometabolites with attention skill and frontal anatomy. METHOD: Single voxel proton magnetic resonance spectroscopy ( H-MRS), quantitative morphometric analysis of left and right dorsolateral frontal volumes, and assessment of attentional problems with the Conners Continuous Performance Test were undertaken in 23 children (17 male) with ADHD (with no comorbid learning disabilities) and 24 matched controls (16 male). RESULTS: No overall group differences were found for any neurometabolite. However, a group by sex interaction was noted for -acetylaspartate, such that girls with ADHD had especially low concentrations. Morphological analyses revealed smaller right (but not left) dorsolateral volumes in children with ADHD, and in the ADHD group this volume correlated with neurometabolite concentrations. In the ADHD group Continuous Performance Test performance was related to both dorsolateral volume and the creatine-phosphocreatine peak from H-MRS. CONCLUSIONS: These results add to a growing body of evidence suggesting sex-specific neurobiological differences in ADHD and draw attention to relationships between neurochemistry, neuroanatomy, and performance in children with ADHD. Study limitations include small sample size and clinical heterogeneity among the children with ADHD.

Aspartic Acid↗