Biomedical subjects

Perry F Renshaw

Publications and source records attributed to Perry F Renshaw.

At least 19 recordsLinked to original sources

PubMed2007

Asymmetrically altered integrity of cingulum bundle in posttraumatic stress disorder.

Previously, our group reported the altered white matter tract integrity of the left anterior cingulate in posttraumatic stress disorder (PTSD) in whole-brain exploration. Current study intended to explore whether the alteration was more prominent in any specific regions of the cingulum bundle. Diffusion tensor images of 21 PTSD subjects and 21 healthy comparison subjects were acquired. Eight isocubic regions of interest (ROIs), i.e. bilateral rostral, subgenual, dorsal, and upper cingulum bundle, were selected. Fractional anisotropy values in each ROI, which indicate the white matter tract integrity, were measured and compared between groups. Relative to comparison subjects, PTSD subjects had significantly smaller fractional anisotropy values in the left side of rostral, subgenual and dorsal cingulum bundle (26.7, 25.0, 22.2% decrease, respectively), but not in the right side ROIs. We report an asymmetrical alteration of the cingulum bundle in PTSD.

Adult↗

PubMed2006

Decreased frontal white-matter integrity in abstinent methamphetamine abusers.

This study explored differences in frontal white-matter (WM) integrity between methamphetamine (MA) abusers and healthy comparison subjects using diffusion tensor imaging (DTI). Fractional anisotropy (FA) values, which indicate WM integrity, were calculated for regions-of-interest in frontal WM on diffusion tensor images of 32 MA abusers and 30 healthy comparison subjects. Frontal executive functions were also assessed by the Wisconsin Card Sorting test (WCST). MA abusers had significantly lower FA values in bilateral frontal WM at the anterior commissure-posterior commissure (AC-PC) plane and the right frontal WM 5 mm above the AC-PC plane relative to healthy comparison subjects. MA abusers had more total, perseveration and non-perseveration errors in the WCST relative to healthy comparison subjects. FA values of the right frontal WM 5 mm above the AC-PC plane negatively correlated with the number of total and non-perseveration errors in the WCST in MA abusers. In the sub-analysis for gender differences, lower FA values in frontal WM and more errors in the WCST were found only in male MA abusers, not in female MA abusers, relative to comparison subjects of the respective gender. We report that frontal WM integrity of MA abusers is compromised. This finding may also be related to impairment in frontal executive function. In addition, the neurotoxic effect of MA on frontal WM may be less prominent in women than in men, possibly due to oestrogen's neuroprotective effect.

Adult↗

PubMed2006

Relationship between N-acetyl-aspartate in gray and white matter of abstinent methamphetamine abusers and their history of drug abuse: a proton magnetic resonance spectroscopy study.

OBJECTIVE: Altered concentrations of the brain metabolites, including N-acetyl-aspartate (NAA) and myo-inositol (MI), may indicate neurotoxicity associated with drug abuse. In this study, the authors explored differences in brain metabolites between abstinent methamphetamine (MA) abusers and healthy comparison subjects and the associations between metabolite concentrations and clinical characteristics. METHOD: Proton magnetic resonance spectroscopy (MRS) was performed on 30 abstinent MA abusers and 20 healthy comparison subjects. Two sets of MA user subgroups were defined depending on abstinence duration (greater or less than 6 months) or the total cumulative MA dose (greater or less than 100 g lifetime). NAA and other metabolites were measured in the frontal gray and white matter and compared between MA abuser groups and healthy comparison subjects. RESULTS: MI concentrations were higher for the MA abusers relative to healthy comparison subjects. NAA concentration was lower in frontal white matter of MA abusers with a 'large' cumulative dose relative to those with a 'small' cumulative dose and to healthy comparison subjects. Additionally, in MA abusers NAA concentrations in frontal white matter correlated inversely with the cumulative MA dose. In contrast, there was no significant difference in frontal gray matter NAA concentration among the three groups. However, frontal gray matter NAA concentrations for MA abusers correlated negatively with the total cumulative MA dose and positively with the duration of abstinence. There were no differences between the different MA user groups for MI. CONCLUSIONS: The current findings suggest that MA-induced metabolic alterations of frontal gray and white matter are dose-dependent, for primarily male subjects. Additionally, these findings potentially suggest that the MA-related abnormalities may, in part, recover with abstinence in gray matter, but not in the white matter regions.

Adult↗

PubMed2006

Mania, glutamate/glutamine and risperidone in pediatric bipolar disorder: a proton magnetic resonance spectroscopy study of the anterior cingulate cortex.

BACKGROUND: The purpose of this study was to investigate the anterior cingulate cortex (ACC) glutamate/glutamine (Glx) to creatine ratio (Glx/Cr) in two groups of children with Bipolar Disorder (BPD): those exhibiting manic symptoms requiring treatment and those being stably treated with the atypical antipsychotic risperidone. Atypical antipsychotics have been shown to increase serum glutamate levels and ACC Glx/Cr in subjects with schizophrenia. In this study, we hypothesized that the children with BPD in need of treatment would have lower Glx/Cr compared with the children with BPD being stably treated with risperidone. METHODS: Proton MR spectra were acquired, at 1.5 T, from the ACC of eighteen subjects with a DSM-IV diagnosis of BPD: ten (11.10+/-3.48 years; five female) were manic and not medicated with any antipsychotic and eight (10.88+/-2.99 years; one female) were medicated with the atypical antipsychotic risperidone. RESULTS: Children with BPD exhibiting manic symptoms requiring treatment had lower Glx/Cr than children with BPD being stably treated with the atypical antipsychotic risperidone. The children treated with risperidone also had significantly lower YMRS and CGI-Mania scores than the children not treated with risperidone. Both YMRS and CGI-Mania scores correlated negatively with ACC Glx/Cr levels. LIMITATIONS: The cross-sectional design, small sample size, the use of Glx rather than glutamate or glutamine and the use of Cr ratios rather than absolute concentrations are limitations of this study. CONCLUSIONS: Children with mania have lower Glx/Cr levels than children with BPD being stably treated with the atypical antipsychotic risperidone. Mania may be associated with reduced glutamate/glutamine levels in the ACC: other imaging studies have shown mania associated with hypometabolism in the ACC. These reductions in glutamate/glutamine may be increased following successful treatment with glutamatergic agents.

Adolescent↗

PubMed2006

Topiramate raises anterior cingulate cortex glutamine levels in healthy men; a 4.0 T magnetic resonance spectroscopy study.

RATIONALE: Potential mechanisms of action of topiramate include alterations of glutamatergic and GABAergic systems. In particular, topiramate has been shown to increase occipital cortex GABA levels, as measured using proton magnetic resonance spectroscopy (MRS). OBJECTIVES: The purpose of this study was to measure the effect of acute oral topiramate on the GABA precursors glutamate and glutamine in the anterior cingulate cortex (ACC) and occipital lobe (OL) using high-field (4.0 T) proton MRS (1H MRS). METHODS: Proton MR spectra were acquired from healthy men at three times: at baseline and 2 and 6 h after ingesting 50 (N=5) or 100 mg (N=5) of topiramate. Blood samples were acquired prior to each scan for the purpose of obtaining serum topiramate levels. RESULTS: A 100-mg dose of topiramate significantly increased ACC glutamine levels within 2 h of ingestion and OL glutamine levels within 6 h of ingestion. There were no measured significant effects of topiramate on ACC or OL glutamate levels. CONCLUSIONS: A 100-mg dose of oral topiramate increased serum topiramate and ACC glutamine levels within 2 h. OL glutamine levels increased within 6 h. Increased brain glutamine levels may be a consequence of topiramate positively modulating GABAA receptors. This result is of interest given the possible role for topiramate in the treatment of epilepsy, migraine headache, bipolar disorder, eating disorders, and alcohol dependence.

Adolescent↗

PubMed2006

Spatially weighted BOLD signal for comparison of functional magnetic resonance imaging and near-infrared imaging of the brain.

We introduce a weighted spatial average of the functional magnetic resonance imaging (fMRI) BOLD signal (blood oxygen level-dependent) that is appropriate for comparison with the changes in oxy- and deoxy-hemoglobin concentrations measured with near-infrared spectroscopy (NIRS) during brain activation. Because the BOLD signal shows a spatial dependence (both in shape and amplitude) within the region of activation, the location of the optical probe with respect to the region of BOLD activation should be taken into account for comparison of the BOLD and NIRS signals. Our new method is based on combining weighted contributions of the BOLD signal from each activated voxel, with a weight given by a hitting density function for photons migrating between a given pair of illumination and collection points. We present a case study where we have found that the new spatially weighted BOLD signal shows a high spatial and temporal correlation with the oxy- and deoxy-hemoglobin concentration changes measured with NIRS during a hand-tapping protocol. These findings reinforce the idea that fMRI and NIRS are sensitive to similar underlying hemodynamic changes, and indicate that the proposed weighted BOLD signal is needed for a quantitative comparison of BOLD and NIRS signals.

Brain↗

PubMed2006

Brain changes to hypocapnia using rapidly interleaved phosphorus-proton magnetic resonance spectroscopy at 4 T.

Substantial controversy persists in the literature concerning the physiologic consequences hypocapnia, or low partial pressure of carbon dioxide (PaCO(2)). Invasive animal studies have demonstrated large pH increases (>0.25 U), phosphocreatine (PCr) decreases (>30%), and adenosine triphosphate (ATP) decreases (>10%) after hyperventilation (HV) (20 mm Hg PaCO(2)). However, using magnetic resonance spectroscopy, HV studies in awake humans have demonstrated only small pH changes ( approximately 0.05 U) and no changes in PCr or ATP. It remains important to ascertain whether this failure to detect PCr changes in human studies reflects a true absence of changes, or a limitation in data fidelity. The present study used a rapidly interleaved phosphorus-proton spectroscopy acquisition from large samples at high magnetic field (4 T), to measure pH, PCr, inorganic phosphate, beta-ATP, and lactate changes with high temporal and signal sensitivity. Five of six subjects had usable data. During 20 mins HV, PaCO(2) reached a minimum at 16 mins (17 mm Hg); however, the maximum pH change (+0.047) peaked earlier (14 mins). Maximal lactate increases were measured at 15 mins. By 10 mins, maximum changes were observed for PCr (-3.4%) and inorganic phosphate (+6.4%). No changes in beta-ATP were observed. The peak in pH, despite continued decreases in PaCO(2), suggests active buffering during HV. These data, and the small magnitude of early PCr and inorganic phosphate changes, do not support substantial energy compromise during HV. Other mitigating factors, such as anesthesia-induced deregulation of the cerebrovasculature, might have contributed to the exaggerated metabolic changes observed in previous animal investigations.

Adenosine Triphosphate↗

PubMed2006

Emotional task-dependent low-frequency fluctuations and methylphenidate: Wavelet scaling analysis of 1/f-type fluctuations in fMRI of the cerebellar vermis.

UNLABELLED: Ion channel currents, neural firing patterns, and brain BOLD signals display 1/f-type fluctuations or fractal properties in time. By design, fMRI methods attempt to minimize the contribution of variance from low-frequency physiological 1/f-noise. New fMRI methods are described to visualize and measure 1/f-type BOLD fluctuations in volunteers recalling affectively neutral or emotional memories or meditating (i.e., attending to breathing) then retrospectively rating emotional content. A wavelet scaling exponent (alpha) was used to characterize signals from 0.015625 to 0.5Hz in cerebellar lobules VIII to X of the vermis (posterior inferior vermis; PIV), a region coordinating balance, eye tracking, locomotion, and vascular tone, and a possible site of pathology in attention deficit hyperactivity disorder (ADHD). RESULTS: Changes in alpha and emotional measures were correlated in PIV voxels (r = 0.622, d.f .= 14, P < 0.0005), but not other regions examined. In contrast, conventional means and standard deviations of PIV voxels were unchanged. Methylphenidate, shown to decrease slow oscillations in rodent basal ganglia [Ruskin DN, Bergstrom DA, Shenker A, Freeman LE, Baek D, Walters JR. Drugs used in the treatment of attention-deficit/hyperactivity disorder affect postsynaptic firing rate and oscillation without preferential dopamine autoreceptor action. Biol Psychiatry 2001;49:340-50.], abolished task-dependent alpha changes in the PIV of an adult with ADHD. Wavelet analysis of long BOLD time series appears well suited to fractal physiology and studies of pharmacologically modulated cerebellar-thalamic-cortical function in ADHD or other psychiatric disorders.

Adult↗

PubMed2006

Proton and sodium MRI assessment of fluid level in calf tissue.

PURPOSE: To investigate the feasibility of using (1)H and (23)Na MRI to detect fluid levels in the lower leg muscle. MATERIALS AND METHODS: Proton and sodium MRI was applied to detect body fluid levels in the lower leg muscles of 18 healthy young male subjects at 3T and 4T. The paradigms under investigation were a postural change from sitting upright to lying supine, and saline infusion. RESULTS: We found that the average proton MR signal in gastrocnemius and soleus muscles were reduced following the postural change by 3.5% +/- 1.4% (P < 0.05) and rose following saline infusion by 3.7% +/- 0.9% (P < 0.01). More dramatically, the sodium MR signal decreased by 7.1% +/- 1.2% (P < 0.01) following the postural change and increased following saline infusion by 12% +/- 3.8% (P < 0.05). The ratio of intra- to extracellular fluid levels was 1.6 +/- 0.5 for the subjects based on the acquired proton and sodium data. CONCLUSION: Our results indicate that proton and sodium MRI can be used to assess fluid levels in the lower extremities, and this technique may be applied to evaluate fluid retention.

Adolescent↗

PubMed2006

In vivo detection of brain glycine with echo-time-averaged (1)H magnetic resonance spectroscopy at 4.0 T.

A single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) method is described that enables the in vivo measurement of endogenous brain glycine (Gly) levels in human subjects. At 4.0 T, TE-averaging (1)H-MRS dramatically attenuates the overlapping myo-inositol (mI) resonances at 3.52 ppm, permitting a more reliable measure of the Gly singlet peak. This methodology initially is described and tested in phantoms. The phantom data infers that the 3.55-ppm peak predominantly is Gly with a smaller contribution from mI. The composite resonance thus is differentiated from pure Gly and mI and is labeled Gly*. The mI contribution was calculated as <2% of the total Gly* signal for a 1:1 mI/Gly mixture. The technique subsequently was used to acquire TE-averaged (1)H-MRS data from the occipital cortex of healthy control subjects. The resultant spectra closely resembled experimental phantom data. LC-model analysis provided a means for quantifying TE-averaged (1)H-MRS spectra and a mean test-retest variability measure of 15% was established for brain Gly* levels in studies of six healthy subjects.

Adult↗

PubMed2006

Advances in magnetic resonance imaging methods for the evaluation of bipolar disorder.

This article reviews the current state of magnetic resonance imaging techniques as applied to bipolar disorder. Addressed are conventional methods of structural neuroimaging and recently developed techniques. This latter group comprises volumetric analysis, voxel-based morphometry, the assessment of T2 white matter hyperintensities, shape analysis, cortical surface-based analysis, and diffusion tensor imaging. Structural analysis methods used in magnetic resonance imaging develop exponentially, and now present opportunities to identify disease-specific neuroanatomic alterations. Greater acuity and complementarity in measuring these alterations has led to the generation of further hypotheses regarding the pathophysiology of bipolar disorder. Included in the summary of findings is consideration of a resulting neuroanatomic model. Integrative issues and future directions in this relatively young field, including multi-modal approaches enabling us to produce more comprehensive results, are discussed.

Bipolar Disorder↗

PubMed2006

Methadone maintenance improves cognitive performance after two months of treatment.

Methadone maintenance (MM) has received little scientific attention regarding neurocognitive effects. The present study examined cognitive function in 17 opiate-dependent subjects at baseline and after 2 months of MM treatment. Subjects demonstrated significant improvements from baseline on measures of verbal learning and memory, visuospatial memory, and psychomotor speed and reduced frequency of drug use (Addiction Severity Index) relative to baseline, although the total percentage of urine samples positive for additional illicit substances was slightly increased. No effect of illicit drug use was observed when the sample was stratified by urine toxicology results, suggesting that improvements in cognition were not associated with additional illicit drug use. Results suggest that opiate-dependent subjects exhibit significant improvement in cognitive function after MM treatment. Future investigations are needed to confirm these findings.

Adult↗

PubMed2006

Cerebellar vermis involvement in cocaine-related behaviors.

Although the cerebellum is increasingly being viewed as a brain area involved in cognition, it typically is excluded from circuitry considered to mediate stimulant-associated behaviors since it is low in dopamine. Yet, the primate cerebellar vermis (lobules II-III and VIII-IX) has been reported to contain axonal dopamine transporter immunoreactivity (DAT-IR). We hypothesized that DAT-IR-containing vermis areas would be activated in cocaine abusers by cocaine-related cues and, in healthy humans, would accumulate DAT-selective ligands. We used BOLD fMRI to determine whether cocaine-related cues activated DAT-IR-enriched vermis regions in cocaine abusers and positron emission tomography imaging of healthy humans to determine whether the DAT-selective ligand [11C]altropane accumulated in those vermis regions. Cocaine-related cues selectively induced BOLD activation in lobules II-III and VIII-IX in cocaine users, and, at early time points after ligand administration, we found appreciable [11C]altropane accumulation in lobules VIII-IX, possibly indicating DAT presence in this region. These data suggest that parts of cerebellar vermis mediate cocaine's persisting and acute effects. In light of prior findings illustrating vermis connections to midbrain dopamine cell body regions, established roles for the vermis as a locus of sensorimotor integration and motor planning, and findings of increased vermis activation in substance abusers during reward-related and other cognitive tasks, we propose that the vermis be considered one of the structures involved in cocaine- and other incentive-related behaviors.

Adult↗

PubMed2006

Regional cerebral cortical thinning in bipolar disorder.

OBJECTIVE: This study was conducted to explore differences in cortical thickness between subjects with bipolar disorder and healthy comparison subjects using cortical surface-based analysis. METHODS: Brain magnetic resonance images were acquired from 25 subjects with bipolar disorder and 21 healthy comparison subjects. Cortical surface-based analysis was conducted using the Freesurfer application. Group differences in cortical thickness, defined by the distance from gray/white boundary to the pial surface, were assessed using statistical difference maps. RESULTS: Subjects with bipolar disorder exhibited significantly decreased cortical thickness in left cingulate cortex, left middle frontal cortex, left middle occipital cortex, right medial frontal cortex, right angular cortex, right fusiform cortex and bilateral postcentral cortices, relative to healthy comparison subjects (all p < 0.001). Duration of illness in bipolar subjects was inversely correlated with the cortical thickness of the left middle frontal cortex. CONCLUSIONS: Cortical thinning was present in multiple prefrontal cortices in bipolar disorder. There was also cortical thinning in sensory and sensory association cortices, which has not been reported in previous studies using region-of-interest or voxel-based morphometry methods. Cortical thinning observed in the current study may be related to impairment of emotional, cognitive, and sensory processing in bipolar disorder but longitudinal studies will be necessary to test this hypothesis.

Adult↗

PubMed2006

Hippocampal volume, PTSD, and alcoholism in combat veterans.

Studies imposing rigorous control over lifetime alcohol intake have usually not found smaller hippocampal volumes in persons with posttraumatic stress disorder. Because the majority of negative studies have used adolescent samples, it has been suggested that chronicity is a necessary condition for such findings. To test the hypothesis that a smaller hippocampus in PTSD is unrelated to comorbid alcoholism or to chronicity, this study estimated hippocampal volume in a relatively large group (N=99) of combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed. In subjects with histories of alcoholism, unadjusted hippocampal volume was 9% smaller in persons with PTSD than in those without PTSD. In nonalcoholic subjects, the PTSD-related difference in hippocampal volume was 3%. The failure to observe a strong association between PTSD and hippocampal volume in nonalcoholic subjects was not ascribable to younger age, reduced PTSD chronicity, or lower PTSD symptom severity. The possibility that smaller hippocampal volume is limited to groups in which PTSD is compounded by comorbid alcoholism is not necessarily incompatible with results suggesting a smaller hippocampus is predispositional to PTSD. Further examination of the role of alcoholism and other comorbid conditions in studies of brain structure and function in PTSD appears warranted.

Adult↗

PubMed2006

Basal ganglia shape alterations in bipolar disorder.

OBJECTIVE: Shape differences in the caudate heads and putamen were compared between drug-naive and drug-treated patients with bipolar disorder and healthy comparison subjects by using spherical harmonic (SPHARM) techniques. On the basis of previous studies, the authors hypothesized that the drug-naive patients would exhibit shape differences of the caudate heads and putamen, especially on the right side, relative to the healthy comparison subjects, and that shape differences, relative to healthy comparison subjects, would differ between drug-naive and drug-treated patients. METHOD: Brain magnetic resonance images were acquired from 49 bipolar disorder patients (21 drug-naive and 28 drug-treated patients) and 37 healthy comparison subjects. Volumetric measurements were obtained, and SPHARM descriptions were used to measure between-group radius differences in the surfaces of the caudate heads and putamen. RESULTS: Although no significant between-group volume differences were found in the striatal structures, significant shape differences in the anterior and ventral surfaces of the striatum were observed. Specifically, shape differences, more prominent for the right side, were found for drug-naive bipolar disorder patients, relative to the healthy comparison subjects, but not for drug-treated bipolar disorder subjects. CONCLUSIONS: The findings suggest that drug-naive bipolar disorder patients have shape differences of the striatum, relative to healthy comparison subjects, and that these differences may be modulated by treatment. The findings more generally demonstrate the sensitivity of the SPHARM analytic technique for detecting subtle anatomical shape differences in small brain regions in the absence of volume differences.

Adult↗

PubMed2006

Differences in brain chemistry in children and adolescents with attention deficit hyperactivity disorder with and without comorbid bipolar disorder: a proton magnetic resonance spectroscopy study.

OBJECTIVE: The authors' goal was to investigate phosphatidylinositol and glutamatergic metabolism in the anterior cingulate cortex of children and adolescents with attention deficit hyperactivity disorder (ADHD) alone, children with ADHD plus bipolar disorder, and children with no axis I diagnosis. METHOD: Proton spectra were acquired from a 4.8-ml voxel placed in the anterior cingulate cortex of 30 subjects who were 6 to 13 years old. Fifteen subjects had ADHD and no comorbid disorder, eight had ADHD plus bipolar disorder, and seven were healthy comparison subjects. RESULTS: Children with ADHD had a significantly higher ratio of glutamate plus glutamine to myo-inositol-containing compounds than children with ADHD plus bipolar disorder and healthy children. CONCLUSIONS: myo-Inositol-containing compounds may provide information on the action of antimanic treatments such as lithium, valproate, and carbamazepine. Glutamate and glutamine are measures of glutamatergic neurotransmission and thus may also reflect changes in serotonin and dopamine pathways.

Adolescent↗

PubMed2006

Increased medial thalamic creatine-phosphocreatine found by proton magnetic resonance spectroscopy in children with obsessive-compulsive disorder versus major depression and healthy controls.

Altered brain creatine-phosphocreatine levels might reflect changes in brain energy use and have been implicated in the pathogenesis of obsessive-compulsive disorder and major depressive disorder. We used proton magnetic resonance spectroscopy to measure absolute concentrations of creatine-phosphocreatine in the right and left medial thalami in 18 pediatric patients with major depressive disorder 9 to 17 years of age, 18 case-matched healthy controls, and 27 patients with obsessive-compulsive disorder 7 to 16 years old. The two patient groups were psychotropic drug naive and were not comorbid for the diagnosis of the comparison group. We found significantly increased left and right medial thalamic creatine-phosphocreatine concentrations in patients with obsessive-compulsive disorder compared with both healthy controls and patients with major depression. Creatine-phosphocreatine concentrations did not differ significantly between patients with major depression and healthy controls. Our data suggest that increased medial thalamic creatine-phosphocreatine concentrations in patients with untreated obsessive-compulsive disorder reflect altered energy use in the medial thalamus and might differentiate patients with obsessive-compulsive disorder from healthy controls and patients with major depression. Although these results must be considered preliminary, further study of the diagnostic specificity of creatine-phosphocreatine in obsessive-compulsive disorder is indicated.

Adolescent↗