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Biomedical subjects

Peter C Williamson

Publications and source records attributed to Peter C Williamson.

At least 19 recordsLinked to original sources
PubMed2006

Detection and mapping of hippocampal abnormalities in autism.

Brain imaging studies of the hippocampus in autism have yielded inconsistent results. In this study, a computational mapping strategy was used to examine the three-dimensional profile of hippocampal abnormalities in autism. Twenty-one males with autism (age: 9.5+/-3.3 years) and 24 male controls (age: 10.3+/-2.4 years) underwent a volumetric magnetic resonance imaging scan at 3 Tesla. The hippocampus was delineated, using an anatomical protocol, and hippocampal volumes were compared between the two groups. Hippocampal traces were also converted into three-dimensional parametric surface meshes, and statistical brain maps were created to visualize morphological differences in the shape and thickness of the hippocampus between groups. Parametric surface meshes and shape analysis revealed subtle differences between patients and controls, particularly in the right posterior hippocampus. These deficits were significant even though the groups did not differ significantly with traditional measures of hippocampal volume. These results suggest that autism may be associated with subtle regional reductions in the size of the hippocampus. The increased statistical and spatial power of computational mapping methods provided the ability to detect these differences, which were not found with traditional volumetric methods.

Adolescent↗
PubMed2006

Grey and white matter differences in brain energy metabolism in first episode schizophrenia: 31P-MRS chemical shift imaging at 4 Tesla.

Altered high energy and membrane metabolism, measured with phosphorus magnetic resonance spectroscopy (31P-MRS), has been inconsistently reported in schizophrenic patients in several anatomical brain regions implicated in the pathophysiology of this illness, with little attention to the effects of brain tissue type on the results. Tissue regression analysis correlates brain tissue type to measured metabolite levels, allowing for the extraction of "pure" estimated grey and white matter compartment metabolite levels. We use this tissue analysis technique on a clinical dataset of first episode schizophrenic patients and matched controls to investigate the effect of brain tissue specificity on altered energy and membrane metabolism. In vivo brain spectra from two regions, (a) the fronto-temporal-striatal region and (b) the frontal-lobes, were analyzed from 12 first episode schizophrenic patients and 11 matched controls from a (31)P chemical shift imaging (CSI) study at 4 Tesla (T) field strength. Tissue regression analyses using voxels from each region were performed relating metabolite levels to tissue content, examining phosphorus metabolite levels in grey and white matter compartments. Compared with controls, the first episode schizophrenic patient group showed significantly increased adenosine triphosphate levels (B-ATP) in white matter and decreased B-ATP levels in grey matter in the fronto-temporal-striatal region. No significant metabolite level differences were found in grey or white matter compartments in the frontal cortex. Tissue regression analysis reveals grey and white matter specific aberrations in high-energy phosphates in first episode schizophrenia. Although past studies report inconsistent regional differences in high-energy phosphate levels in schizophrenia, the present analysis suggests more widespread differences that seem to be strongly related to tissue type. Our data suggest that differences in grey and white matter tissue content between past studies may account for some of the variance in the literature.

Adult↗
PubMed2006

Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity.

BACKGROUND: Volumetric studies have reported reductions in the size of the corpus callosum (CC) in autism, but the callosal regions contributing to this deficit have differed among studies. In this study, a computational method was used to detect and map the spatial pattern of CC abnormalities in male patients with autism. METHODS: Twenty-four boys with autism (aged 10.0 +/- 3.3 years) and 26 control boys (aged 11.0 +/- 2.5 years) underwent a magnetic resonance imaging (MRI) scan at 3 Tesla. Total and regional areas of the CC were determined using traditional morphometric methods. Three-dimensional (3D) surface models of the CC were also created from the MRI scans. Statistical maps were created to visualize morphologic variability of the CC and to localize regions of callosal thinning in autism. RESULTS: Traditional morphometric methods detected a significant reduction in the total callosal area and in the anterior third of the CC in patients with autism; however, 3D maps revealed significant reductions in both the splenium and genu of the CC in patients. CONCLUSIONS: Statistical maps of the CC revealed callosal deficits in autism with greater precision than traditional morphometric methods. These abnormalities suggest aberrant connections between cortical regions, which is consistent with the hypothesis of abnormal cortical connectivity in autism.

Adolescent↗
PubMed2005

White matter abnormalities in autism detected through transverse relaxation time imaging.

While neuroimaging studies have reported neurobiological abnormalities in autism, the underlying tissue abnormalities remain unclear. Quantitative transverse relaxation time (T2) imaging permits the examination of tissue abnormalities in vivo, with increased T2 largely reflecting increased tissue water. Blood flow and the presence of tissue iron may also affect T2. In this study, we used voxel-based relaxometry of the cerebrum and global averages to examine T2 abnormalities in autism. Nineteen males with autism (age: 9.2 +/- 3.0 years) and 20 male controls (age: 10.7 +/- 2.9 years) underwent magnetic resonance imaging at 3.0 T. Quantitative T2 maps, generated through gradient echo sampling of the free induction decay and echo, were segmented into gray matter, white matter, and cerebrospinal fluid. Average cerebral gray and white matter T2 were determined and compared between groups. To assess localized T2 differences, the quantitative T2 maps were warped to a template created for this study, smoothed, and compared using statistical parametric mapping. Patients with autism had an increase in average cerebral white matter T2, although no group differences were seen in average cerebral gray matter T2. Patients with autism also had bilateral regional T2 increases in the gray matter and associated white matter of the parietal lobes (primary sensory association areas) and occipital lobes (visual association areas) and in the white matter within the supplementary motor areas in the frontal lobes. The regional and global elevations in white matter T2 suggest abnormalities of white matter tissue water content in autism, which may represent a neurobiological basis for the aberrant cortical connectivity hypothesized to underlie the disorder.

Adolescent↗
PubMed2005

Functional connectivity of dissociative responses in posttraumatic stress disorder: a functional magnetic resonance imaging investigation.

BACKGROUND: The purpose of this study was to assess interregional brain activity covariations during traumatic script-driven imagery in subjects with posttraumatic stress disorder (PTSD). METHODS: Functional magnetic resonance imaging and functional connectivity analyses were used to assess interregional brain activity covariations during script-driven imagery in PTSD subjects with a dissociative response, PTSD subjects with a flashback response, and healthy control subjects. RESULTS: Significant between-group differences in functional connectivity were found. Comparing dissociated PTSD patients and control subjects' connectivity maps in the left ventrolateral thalamus (VLT) [-14, -16, 4] revealed that control subjects had higher covariations between activations in VLT and in the left superior frontal gyrus (Brodmann's area [BA] 10), right parahippocampal gyrus (BA 30), and right superior occipital gyrus (BA 19, 39), whereas greater covariation with VLT in dissociated PTSD subjects occurred in the right insula (BA 13, 34), left parietal lobe (BA 7), right middle frontal gyrus (BA 8), superior temporal gyrus (BA 38, 34), and right cuneus (BA 19). Comparing dissociated PTSD and flashback PTSD connectivity maps in the right cingulate gyrus [3, 16, 30] revealed that dissociated PTSD subjects had higher covariations between activations in this region and the left inferior frontal gyrus (BA 47). CONCLUSIONS: Greater activation of neural networks involved in representing bodily states was seen in dissociated PTSD subjects than in non-PTSD control subjects. These findings might illuminate the mechanisms underlying distorted body perceptions often observed clinically during dissociative episodes.

Accidents, Traffic↗
PubMed2005

Implementation issues of multivoxel STEAM-localized 1H spectroscopy.

Single-voxel STEAM-localized spectroscopy studies of neuropsychiatric patients yield high-quality data at short echo times, but are often limited to only a few regions of interest due to the linear increase of acquisition time with the number of regions examined. A multivoxel STEAM approach increases the number of regions of interest examined with a less than linear increase in acquisition time. Several implementation issues were considered, especially the signal contribution of outer voxel stimulated echoes (OVSE), which can lead to systematic errors in the quantification of relative metabolite concentrations. The relative signal contribution of OVSEs was found to be as great as 30% in phantoms. Gradient polarity switching completely canceled the contribution of OVSEs. A two-voxel STEAM approach produces phantom and in vivo data quality comparable to single-voxel STEAM in practically half the time. Quantification precision and accuracy are preserved in phantoms and in vivo.

Analysis of Variance↗
PubMed2005

Brain magnetic resonance spectroscopy in Tourette's disorder.

OBJECTIVE: Although abnormalities of neural circuits involving the cortex, striatum, and thalamus are hypothesized to underlie Tourette's disorder, the neuronal abnormalities within components of these circuits are unknown. The purpose of this study was to examine the cellular neurochemistry within these circuits in Tourette's disorder using proton magnetic resonance spectroscopy, a method that has not previously been used in neurobiological investigations of the disorder. METHOD: Proton magnetic resonance spectroscopic imaging examinations were conducted in 25 males with Tourette's disorder (age 10.9 +/- 2.0 years) and 32 male comparison subjects (age 11.5 +/- 2.7 years). Spectra from frontal cortex, caudate nucleus, putamen, and thalamus were analyzed, and N-acetylaspartate, creatine, choline, myoinositol, and glutamate + glutamine were quantified and compared between the groups. RESULTS: Patients with Tourette's disorder demonstrated a reduction in N-acetylaspartate and choline in the left putamen, along with reduced levels of creatine bilaterally in the putamen. In the frontal cortex, patients had significantly lower concentrations of N-acetylaspartate bilaterally, lower levels of creatine on the right side, and reduced myoinositol on the left side. CONCLUSIONS: The results of this study suggest compromised neuronal integrity and deficits in density of neuronal and nonneuronal cells in components of the neural circuits implicated in Tourette's disorder.

Adolescent↗
PubMed2004

Comparative study of proton and phosphorus magnetic resonance spectroscopy in schizophrenia at 4 Tesla.

This study used high-field magnetic resonance spectroscopy to examine the correlation of 1H and 31P metabolite levels in patients with schizophrenia and normal controls. 1H and 31P in vivo spectra were acquired successively from the left anterior cingulate and left thalamus of nine chronic schizophrenic patients and eight comparable healthy controls. A significant positive correlation between glutamine (Gln) and phosphoethanolamine (PEtn) was found in the left anterior cingulate of patients. In the left thalamus of patients, a significant negative correlation between N-acetylaspartate (NAA) and glycerophosphocholine (GroPCho) was found. No significant correlations were found in controls. The correlation between glutamine and phosphoethanolamine may reflect a link between neurotransmission alterations and membrane phospholipid metabolism alterations. The negative correlation between N-acetylaspartate and glycerophosphocholine may reflect the presence of neurodegeneration.

Adult↗
PubMed2004

Duration of untreated psychosis vs. N-acetylaspartate and choline in first episode schizophrenia: a 1H magnetic resonance spectroscopy study at 4.0 Tesla.

N-acetylaspartate (NAA) has been associated with neuronal integrity and function, and choline-containing compounds have been linked to neuronal membrane integrity. This study examined the influence of the duration of untreated psychosis, duration of prodromal symptoms and total length of untreated illness on these markers of neuronal loss or damage. In vivo 1H magnetic resonance spectroscopy data were acquired from 1.5-cc volumes in the left anterior cingulate and left thalamus of 19 never-treated first episode schizophrenic subjects using STEAM20 at 4.0 Tesla. Duration of untreated psychosis, prodrome and total length of untreated illness were correlated with levels of NAA and choline. No significant correlation was observed between NAA and duration of untreated psychosis and untreated illness in both regions examined. Thalamic NAA negatively correlated with duration of prodromal symptoms. A positive correlation between choline and duration of untreated psychosis was identified in both regions studied. Delays in treatment of psychotic symptoms of schizophrenia were not associated with a reduction in markers of neuronal integrity or function in contrast to longer prodromal periods, which were associated with lower NAA. Neuronal damage, potentially detectable via lower NAA, may be occurring before the onset of psychosis. Increased choline is associated with longer duration of untreated psychosis and could indicate that psychosis-related membrane alterations precede the appearance of NAA reductions observed by studies of chronic schizophrenia.

Adolescent↗
PubMed2004

The nature of traumatic memories: a 4-T FMRI functional connectivity analysis.

OBJECTIVE: This study used functional connectivity analyses to assess interregional brain activity correlations during the recall of traumatic memories in traumatized subjects with and without posttraumatic stress disorder (PTSD). METHOD: Both 4-T functional magnetic resonance imaging (fMRI) and functional connectivity analyses were used to assess interregional brain activity correlations during script-driven symptom provocation in traumatized subjects with (N=11) and without (N=13) PTSD. Functional connectivity analyses were carried out by using data for brain regions activated in both the PTSD group and the comparison group. The use of functional connectivity analyses in addition to subtraction analyses allowed assessment of specific brain regions involved in the recall of traumatic events and of the neuronal networks underlying the recall of such events. RESULTS: Significant between-group differences in functional connectivity were found. Comparison of connectivity maps at coordinates x=2, y=20, z=36 (right anterior cingulate gyrus) for the two groups showed that the subjects without PTSD had greater correlation than the PTSD subjects in the left superior frontal gyrus (Brodmann's area 9), left anterior cingulate gyrus (Brodmann's area 32), left striatum (caudate), left parietal lobe (Brodmann's areas 40 and 43), and left insula (Brodmann's area 13). In contrast, the PTSD subjects showed greater correlation than the subjects without PTSD in the right posterior cingulate gyrus (Brodmann's area 29), right caudate, right parietal lobe (Brodmann's areas 7 and 40), and right occipital lobe (Brodmann's area 19). CONCLUSIONS: The differences in brain connectivity between PTSD and comparison subjects may account for the nonverbal nature of traumatic memory recall in PTSD subjects, compared to a more verbal pattern of traumatic memory recall in comparison subjects.

Brain↗
PubMed2004

Focal changes in brain energy and phospholipid metabolism in first-episode schizophrenia: 31P-MRS chemical shift imaging study at 4 Tesla.

BACKGROUND: Membrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy ((31)P-MRS) have been reported in patients with schizophrenia in several brain regions. AIMS: Using improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T (31)P-MRS. METHOD: Brain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm(3) effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex. RESULTS: People with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group. CONCLUSIONS: The increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.

Adult↗
PubMed2003

Recall of emotional states in posttraumatic stress disorder: an fMRI investigation.

BACKGROUND: The goal of this study was to examine the neuronal circuitry underlying different emotional states (neutral, sad, anxious, and traumatic) in posttraumatic stress disorder (PTSD) in traumatized subjects versus traumatized subjects without PTSD. METHODS: Traumatized subjects with (n = 10) and without (n = 10) PTSD were studied using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging (fMRI) at a 4 Tesla field strength. RESULTS: Compared to the trauma-exposed comparison group, PTSD subjects showed significantly less activation of the thalamus and the anterior cingulate gyrus (area 32) in all three emotional states (sad, anxious, and traumatic). CONCLUSION: These findings suggest thalamic and anterior cingulate dysfunction in the recollection of traumatic as well as other negative events. Thalamic and anterior cingulate dysfunction may underlie emotion dysregulation often observed clinically in PTSD.

Adult↗
PubMed2003

An MRI study of subgenual prefrontal cortex in patients with familial and non-familial bipolar I disorder.

BACKGROUND: Over the past few years there has been an interest in the use of magnetic resonance imaging (MRI) to study specific brain regions in bipolar disorder. The present study compared the grey matter volume in the subgenual prefrontal cortex in patients with familial and non-familial bipolar disorder and normal control subjects. METHODS: MRI brain scans were performed on 12 patients with bipolar I disorder including six patients with a positive family history of bipolar disorder as well as eight control subjects. RESULTS: There was a significant reduction in the grey matter volume in the right subgenual prefrontal cortex, but not in the left subgenual prefrontal cortex. A family history x sex interaction with right prefrontal cortex volume was also observed as a trend. For females, a positive family history was associated with reduced right prefrontal cortex volumes; for males, a positive family history was associated with increased right prefrontal cortex volumes. LIMITATIONS: Small sample size, reduced statistical power. CONCLUSION: These data add to the emerging literature on structural changes in the subgenual prefrontal cortex in bipolar disorder, especially in patients with a positive family history.

Adult↗
PubMed2003

Glutamate and glutamine in the anterior cingulate and thalamus of medicated patients with chronic schizophrenia and healthy comparison subjects measured with 4.0-T proton MRS.

OBJECTIVE: This in vivo (1)H magnetic resonance spectroscopy study examined levels of glutamate, glutamine, and N-acetylaspartate in medicated patients with chronic schizophrenia. METHOD: Localized in vivo (1)H spectra were acquired at 4.0 T from the left anterior cingulate and thalamus of 21 patients with schizophrenia and 21 comparable healthy volunteers. RESULTS: Significantly lower levels of glutamine and glutamate were found in the left anterior cingulate cortex of patients with schizophrenia than in the healthy volunteers. For the schizophrenia patients, the glutamine level in the left thalamus was found to be higher than normal, and there was a significant negative correlation between N-acetylaspartate level and duration of positive symptoms. CONCLUSIONS: Since previous studies have found higher than normal levels of glutamine in the left anterior cingulate of never-treated patients, decreased levels of these metabolites in chronic patients could be related to neurodegeneration or the effects of chronic medication.

Adult↗
PubMed2002

Brain activation during script-driven imagery induced dissociative responses in PTSD: a functional magnetic resonance imaging investigation.

BACKGROUND: The goal of this study was to examine the neuronal circuitry underlying dissociative responses to traumatic script-driven imagery in sexual-abuse-related posttraumatic stress disorder (PTSD). Pilot studies in our laboratory have shown that PTSD patients had very different responses to traumatic script-driven imagery. Approximately 70% of patients relived their traumatic experience and showed an increase in heart rate while recalling the traumatic memory. The other 30% of patients had a dissociative response with no concomitant increase in heart rate. This article focuses on the latter group. METHODS: The neuronal circuitry underlying dissociative responses in PTSD was studied using the traumatic script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging (fMRI) at a 4 Tesla field strength in 7 subjects with sexual-abuse-related PTSD and 10 control subjects. RESULTS: Compared with control subjects, PTSD patients in a dissociative state showed more activation in the superior and middle temporal gyri (BA 38), the inferior frontal gyrus (BA 47), the occipital lobe (BA 19), the parietal lobe (BA 7), the medial frontal gyrus (BA 10), the medial cortex (BA 9), and the anterior cingulate gyrus (BA 24 and 32). CONCLUSIONS: These findings suggest that prefrontal and limbic structures underlie dissociative responses in PTSD. Differences observed clinically, psychophysiologically, and neurobiologically between patients who respond to traumatic script-driven imagery with dissociative versus nondissociative responses may suggest different neuronal mechanisms underlying these two distinct reactions.

Adult↗
PubMed2002

In vivo brain (31)P-MRS: measuring the phospholipid resonances at 4 Tesla from small voxels.

An optimized phosphorous ((31)P) three-dimensional chemical-shift imaging (3D-CSI) protocol was developed at 4 T to study the phospholipid metabolism from discrete regions in the human brain without the need for (1)H-decoupling or nuclear Overhauser enhancement (NOE). In this study, a spherically bound, weighted average, random point omission 3D-CSI technique was developed and tested, based on methods proposed in the literature. The technique yields a significant (p < 0.001, two-tailed, 5% confidence level) increase in signal-to-noise (SNR) efficiency over conventional 3D-CSI (phantom 32%), without an increase in voxel bleedthrough. An automated time-domain fitting procedure utilizing prior spectral knowledge quantified the individual brain phospholipid metabolites from 15 cm(3) effective (8.0 cm(3) nominal) volumes from the left/right-parieto-occipital cortex and left/right thalamus in 10 normal volunteers. Individual constituents from the phosphomonoester (PME) region; phosphoethanolamine (PEth), phosphocholine (PCh) and the phosphodiester (PDE) region; glycerophosphoethanolamine (GPEth), glycerophosphocholine (GPCh) and membrane phospholipids (MP) were separately quantified to assess the precision of our method at 4 T against previous (1)H-decoupled (31)P-MRS brain studies at lower fields and much larger voxels. Derived concentrations (mM/l tissue) for PEth, PCh, GPEth, GPCh and MP in the left-parieto-occipital cortex were 0.81 +/- 0.21, 0.46 +/- 0.14, 0.74 +/- 0.30, 1.15 +/- 0.43 and 1.54 +/- 0.95 mM, respectively, and 0.94 +/- 0.16, 0.46 +/- 0.17, 0.83 +/- 0.22, 1.14 +/- 0.40 and 1.26 +/- 0.78 mM for the right parieto-occipital cortex. Derived concentrations (mM/l tissue) for PEth, PCh, GPEth, GPCh and MP in the left-thalamus were 0.69 +/- 0.18, 0.42 +/- 0.16, 0.63 +/- 0.20, 1.05 +/- 0.42 and 0.93 +/- 0.56 mM, respectively, and 0.68 +/- 0.24, 0.34 +/- 0.18, 0.60 +/- 0.23, 1.09 +/- 0.36 and 0.74 +/- 0.48 mM for the right-thalamus. This is the first study to our knowledge that has been able to quantify each of these individual phospholipid metabolites from such small voxels in the brain within a clinically reasonable scan time and without (1)H-decoupling or NOE.

Adult↗
PubMed2002

Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers.

OBJECTIVE: This in vivo (1)H magnetic resonance spectroscopy study examined levels of glutamate, glutamine, and N-acetylaspartate in patients experiencing their first episode of schizophrenia. METHOD: Localized in vivo (1)H spectra were acquired at 4.0 T from the left anterior cingulate and thalamus of 21 never-treated patients with schizophrenia and 21 comparable healthy volunteers. RESULTS: The level of glutamine was significantly higher in the left anterior cingulate cortex and thalamus of the patients with schizophrenia than in the healthy subjects. No differences were found between groups in the levels of other metabolites in the anterior cingulate or thalamus. CONCLUSIONS: Higher than normal glutamine levels in the left anterior cingulate and thalamus provide in vivo evidence of greater than normal glutamatergic activity proposed by glutamatergic models of schizophrenia. In contrast to other studies in chronically ill patients, no differences were seen in the levels of N-acetylaspartate in either location, suggesting that the findings in patients with chronic schizophrenia may be related to the effect of medication or the progression of the illness.

Adult↗