Biomedical subjects

Maria Densmore

Publications and source records attributed to Maria Densmore.

15 recordsLinked to original sources

PubMed2025

A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group. METHODS: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9). RESULTS: PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges' g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges' g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p corrected  = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p corrected  = .001). CONCLUSIONS: PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Humans↗

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↗

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↗

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

A 4.0-T fMRI study of brain connectivity during word fluency in first-episode schizophrenia.

OBJECTIVE: To use functional magnetic resonance imaging (fMRI) to investigate functional connectivity, and hence, underlying neural networks, in never-treated, first-episode patients with schizophrenia using a word fluency paradigm known to activate prefrontal, anterior cingulate, and thalamic regions. Abnormal connectivity between the prefrontal cortex (PFC) and other brain regions has been demonstrated in chronic, medicated patients in previous positron emission tomography (PET) studies, but has not to our knowledge, previously been demonstrated using both first-episode, drug-naïve patients and fMRI technology. METHODS: A 4.0-Tesla (T) fMRI was used to examine activation and functional connectivity [psychophysiological interactions (PPIs)] during a word fluency task compared to silent reading in 10 never-treated, first-episode patients with schizophrenia and 10 healthy volunteers of comparable age, sex, handedness, and parental education. RESULTS: Compared to healthy volunteers, the schizophrenia patient group exhibited less activation during the word fluency task, mostly in the right anterior cingulate and prefrontal regions. Psychophysiological interactions between right anterior cingulate and other parts of the brain revealed a localized interaction with the left temporal lobe in healthy volunteers during the task and a widespread unfocussed interaction in patients. CONCLUSION: These findings suggest anterior cingulate involvement in the neuronal circuitry underlying schizophrenia.

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

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↗

PubMed2002

Region-specific changes in phospholipid metabolism in chronic, medicated schizophrenia: (31)P-MRS study at 4.0 Tesla.

BACKGROUND: Membrane phospholipid abnormalities in people with schizophrenia, measured with (31)P magnetic resonance spectroscopy ((31)P-MRS), have been previously reported in brain regions involved in this disorder. AIMS: In this 4.0 Tesla (31)P-MRS study of people with schizophrenia, membrane phospholipid metabolism was examined in brain regions previously inaccessible due to their small volumes. METHOD: Three-dimensional chemical-shift imaging (3D-CSI) examined 15 cc volumes in 12 brain regions in 11 people with chronic schizophrenia and 11 healthy control volunteers. RESULTS: Glycerophosphoethanolamine was decreased in the anterior cingulate, right prefrontal cortex and left thalamus, but increased in the left hippocampus and cerebellum in those with schizophrenia. Phosphoethanolamine and glycerophosphocholine were decreased in the right prefrontal region and phosphocholine was decreased in the anterior cingulate. No significant difference in membrane phospholipid levels existed between groups in the parieto-occipital and posterior cingulate regions. CONCLUSIONS: Altered membrane phospholipid metabolism was demonstrated in all regions implicated in schizophrenia.

Adult↗