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Ruth O'Gorman

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Prof. Saeid Eslamian

Isfahan University of Technology

Juan Carlos Moreno Garcia

Centre National de la Recherche Scientifique / French National Centre for Scientific Research

Francesca Stavrakopoulou

University of Exeter

Tehran University of Medical Sciences

Saint-Petersburg Stieglitz State Academy of Art and Design

John Christopher Examen

Chinese General Hospital Colleges

Andrea Semplicini

Università degli Studi di Padova

Andrea Fiorillo

Università della Campania Luigi Vanvitelli

Charles Nemeroff

University of Miami

Arthur Reingold

University of California, Berkeley

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Papers by Ruth O'Gorman

MRI magnetic susceptibility mapping of target structures for deep brain stimulation (DBS)

by Ruth O'Gorman and Karin Shmueli

Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study

by Ruth O'Gorman and J. Horder

Translational psychiatry, 2014

There is increasing evidence that abnormalities in glutamate signalling may contribute to the pat... more There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo. However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine (Glu+Gln; abbreviated as Glx) along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD-the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)-and one 'control' region-the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy con...

INTERACTION BETWEEN HIPPOCAMPAL GLUTAMATE AND STRIATAL DOPAMINE – RELATIONSHIP TO SUBSEQUENT ONSET OF PSYCHOSIS

Acute effects of single-dose aripiprazole and haloperidol on resting cerebral blood flow (rCBF) in the human brain

Antipsychotic drugs act on the dopaminergic system (first-generation antipsychotics, FGA), but so... more Antipsychotic drugs act on the dopaminergic system (first-generation antipsychotics, FGA), but some also directly affect serotonergic function (second-generation antipsychotics, SGA) in the brain. Short and long-term effects of these drugs on brain physiology remain poorly understood. Moreover, it remains unclear whether any physiological effect in the brain may be different for FGAs and SGAs. Immediate (þ3.30 h) and different effects of single-dose FGA (haloperidol, 3 mg) and a SGA (aripiprazole, 10 mg) on resting cerebral blood flow (rCBF) were explored in the same 20 healthy volunteers using a pulsed continuous arterial spin labeling (pCASL) sequence (1.5T) in a placebocontrolled, repeated measures design. Both antipsychotics increased striatal rCBF but the effect was greater after haloperidol. Both decreased frontal rCBF, and opposite effects of the drugs were observed in the temporal cortex (haloperidol decreased, aripiprazole increased rCBF) and in the posterior cingulate (haloperidol increased, aripiprazole decreased rCBF). Further increases were evident in the insula, hippocampus, and anterior cingulate after both antipsychotics, in the motor cortex following haloperidol and in the occipital lobe the claustrum and the cerebellum after aripiprazole. Further decreases were observed in the parietal and occipital cortices after aripiprazole. This study suggests that early and different rCBF changes are evident following a single-dose of FGA and SGA. The effects occur in healthy volunteers, thus may be independent from any underlying pathology, and in the same regions identified as structurally and functionally altered in schizophrenia, suggesting a possible relationship between antipsychotic-induced rCBF changes and brain alterations in schizophrenia. Hum Brain Mapp 00:000-000, 2012. V C 2012 Wiley Periodicals, Inc.

Reduced subcortical glutamate/glutamine in adults with autism spectrum disorders: a [(1)H]MRS study

by Ruth O'Gorman and J. Horder

Translational psychiatry, 2014

Dysfunctional glutamatergic neurotransmission has been implicated in autism spectrum disorder (AS... more Dysfunctional glutamatergic neurotransmission has been implicated in autism spectrum disorder (ASD). However, relatively few studies have directly measured brain glutamate in ASD adults, or related variation in glutamate to clinical phenotype. We therefore set out to investigate brain glutamate levels in adults with an ASD, comparing these to healthy controls and also comparing results between individuals at different points on the spectrum of symptom severity. We recruited 28 adults with ASD and 14 matched healthy controls. Of those with ASD, 15 fulfilled the 'narrowly' defined criteria for typical autism, whereas 13 met the 'broader phenotype'. We measured the concentration of the combined glutamate and glutamine signal (Glx), and other important metabolites, using proton magnetic resonance spectroscopy in two brain regions implicated in ASD-the basal ganglia (including the head of caudate and the anterior putamen) and the dorsolateral prefrontal cortex-as well as in a parietal cortex 'control' region. Individuals with ASD had a significant decrease (Po0.001) in concentration of Glx in the basal ganglia, and this was true in both the 'narrow' and 'broader' phenotype. Also, within the ASD sample, reduced basal ganglia Glx was significantly correlated with increased impairment in social communication (P ¼ 0.013). In addition, there was a significant reduction in the concentration of other metabolites such as choline, creatine (Cr) and N-acetylaspartate (NAA) in the basal ganglia. In the dorsolateral prefrontal cortex, Cr and NAA were reduced (Po0.05), although Glx was not. There were no detectable differences in Glx, or any other metabolite, in the parietal lobe control region. There were no significant between-group differences in age, gender, IQ, voxel composition or data quality. In conclusion, individuals across the spectrum of ASD have regionally specific abnormalities in subcortical glutamatergic neurotransmission that are associated with variation in social development.

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound

by Ruth O'Gorman and Ernst Martin

Journal of therapeutic ultrasound, 2014

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation... more Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation of target tissues. While this emerging modality is increasingly used for the treatment of various types of extracranial soft tissue tumors, it has only recently been acknowledged as a modality for noninvasive neurosurgery. MRgFUS has been particularly successful for functional neurosurgery, whereas its clinical application for tumor neurosurgery has been delayed for various technical and procedural reasons. Here, we report the case of a 63-year-old patient presenting with a centrally located recurrent glioblastoma who was included in our ongoing clinical phase I study aimed at evaluating the feasibility and safety of transcranial MRgFUS for brain tumor ablation. Applying 25 high-power sonications under MR imaging guidance, partial tumor ablation could be achieved without provoking neurological deficits or other adverse effects in the patient. This proves, for the first time, the feasibi...

Relationship between brain glutamate levels and clinical outcome in individuals at ultra high risk of psychosis

by Ruth O'Gorman and James Stone

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014

Alterations in brain glutamate levels may be associated with psychosis risk, but the relationship... more Alterations in brain glutamate levels may be associated with psychosis risk, but the relationship to clinical outcome in at-risk individuals is unknown. Glutamate concentration was measured in the left thalamus and anterior cingulate cortex (ACC) using 3-Tesla proton magnetic resonance spectroscopy in 75 participants at ultra high risk (UHR) of psychosis and 56 healthy controls. The severity of attenuated positive symptoms and overall functioning were assessed. Measures were repeated in 51 UHR and 33 Control subjects after a mean of 18 months. UHR subjects were allocated to either remission (no longer meeting UHR criteria) or non-remission (meeting UHR or psychosis criteria) status on follow-up assessment. Thalamic glutamate levels at presentation were lower in the UHR non-remission (N=29) compared with the remission group (N=22) (t(49)=3.03; P=0.004), and were associated with an increase in the severity of total positive symptoms over time (r=-0.33; df=47; P=0.02), most notably abn...

Abstracts of Presentations at the International Conference on Basic and Clinical Multimodal Imaging (BaCI), a Joint Conference of the International Society for Neuroimaging in Psychiatry (ISNIP), the International Society for Functional Source Imaging (ISFSI), the International Society for Bioele...

by Ruth O'Gorman, Renata Smieskova, L. Spinelli, and Anna Prinster

Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS)

Does elevated cortical glutamate release drive loss of grey matter in psychosis?

Early Intervention in Psychiatry

Thalamic glutamate and the transition to psychosis

Posterior cingulate γ-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype

by Ruth O'Gorman, Lars Michels, Spyros Kollias, and Roger Luechinger

Neurobiology of Aging, 2015

The biomarker potential of the inhibitory neurotransmitter g-aminobutyric acid (GABA) for the in ... more The biomarker potential of the inhibitory neurotransmitter g-aminobutyric acid (GABA) for the in vivo characterization of preclinical stages in Alzheimer's disease has not yet been explored. We measured GABA, glutamate þ glutamine (Glx), and N-acetyl-aspartate (NAA) levels by single-voxel MEGA-PRESS magnetic resonance spectroscopy in the posterior cingulate cortex of 21 elderly subjects and 15 patients with amnestic mild cognitive impairment. Participants underwent Pittsburgh Compound B positron emission tomography, apolipoprotein E (APOE) genotyping, and neuropsychological examination. GABA, Glx, and NAA levels were significantly lower in patients. NAA was lower in Pittsburgh Compound Bpositive subjects and APOE ε4 allele carriers. GABA, Glx, and NAA levels were positively correlated to CERAD word learning scores. Reductions in GABA, Glx, and NAA levels may serve as metabolic biomarkers for cognitive impairment in amnestic mild cognitive impairment. Because GABA and Glx do not seem to reflect amyloid b deposition or APOE genotype, they are less likely biomarker candidates for preclinical Alzheimer's disease.

Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: Preliminary findings

by Ruth O'Gorman and Lars Michels

Psychiatry Research: Neuroimaging, 2014

Increased cerebral perfusion in adult attention deficit hyperactivity disorder is normalised by stimulant treatment: A non-invasive MRI pilot study

Neuroimage, 2008

The neurobiological basis for attention deficit hyperactivity disorder (ADHD) has not yet been fu... more The neurobiological basis for attention deficit hyperactivity disorder (ADHD) has not yet been fully established, although there is a growing body of evidence pointing to functional and structural abnormalities involving the basal ganglia, cerebellum, and regions of frontal grey matter. The purpose of this study was to investigate regional cerebral perfusion in adults with ADHD and age-matched control subjects, and to assess the perfusion response to stimulant treatment in the ADHD group using a non-invasive magnetic resonance perfusion imaging technique. Whole-brain cerebral perfusion images were acquired from nine right-handed male patients with ADHD and eleven age-matched control subjects using a continuous arterial spin labelling (CASL) technique. The ADHD group was assessed once on their normal treatment and once after withdrawing from treatment for at least one week. An automated voxel-based analysis was used to identify regions where the cerebral perfusion differed significantly between the ADHD and control groups, and where the perfusion altered significantly with stimulant treatment. Regional cerebral perfusion was increased in the ADHD group in the left caudate nucleus, frontal and parietal regions. Psychomotor stimulant treatment acted to normalise perfusion in frontal cortex and the caudate nucleus with additional decreases in parietal and parahippocampal regions. These findings highlight the potential sensitivity of non-invasive perfusion MRI techniques like CASL in the evaluation of perfusion differences due to illness and medication treatment, and provide further evidence that persistence of ADHD symptomatology into adulthood is accompanied by abnormalities in frontal and striatal brain regions.

Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA

NeuroImage, 2013

There is increasing interest in the use of edited proton magnetic resonance spectroscopy for the ... more There is increasing interest in the use of edited proton magnetic resonance spectroscopy for the detection of GABA in the human brain. At a recent meeting held at Cardiff University, a number of spectroscopy groups met to discuss the acquisition, analysis and interpretation of GABA-edited MR spectra. This paper aims to set out the issues discussed at this meeting, reporting areas of consensus around parameters and procedures in the field and highlighting those areas where differences remain. It is hoped that this paper can fulfill two needs, providing a summary of the current &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;state-of-the-art&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; in the field of GABA-edited MRS at 3T using MEGA-PRESS and a basic guide to help researchers new to the field to avoid some of the pitfalls inherent in the acquisition and processing of edited MRS for GABA.

INTERACTION BETWEEN HIPPOCAMPAL GLUTAMATE AND STRIATAL DOPAMINE – RELATIONSHIP TO SUBSEQUENT ONSET OF PSYCHOSIS

Schizophrenia Research, 2010

Abstracts of Presentations at the International Conference

by Ruth O'Gorman, Renata Smieskova, umberto volpe, L. Spinelli, and Anna Prinster

200 – Brain glutamate and grey matter volume in the early phase of psychosis

Schizophrenia Research, 2008

Cortical and cerebellar modulation of autonomic responses to loud sounds

Psychophysiology, 2014

Detecting unexpected environmental change causes modulation of autonomic activity essential for s... more Detecting unexpected environmental change causes modulation of autonomic activity essential for survival. Understanding the neural mechanisms associated with responses to loud sounds may provide insights into the pathophysiology of posttraumatic stress disorder (PTSD), since individuals with PTSD exhibit heightened autonomic responses to unexpected loud sounds. We combined fMRI with autonomic psychophysiological assessment to investigate central and peripheral reactivity to loud tones in 20 healthy participants. Activity in anterior insula, pregenual anterior cingulate cortex, anterior midcingulate cortex, supplementary motor area, supramarginal gyrus, and cerebellar lobules VIII-IX was associated with both tones and concomitant skin conductance responses. Since regions signaling unexpected external events modulate autonomic activity, heightened loud tone autonomic responses in PTSD may reflect sensitization of this "salience" network.

Frontal GABA Levels Change during Working Memory

by Lars Michels, Ruth O'Gorman, and Peter Klaver

PLoS ONE, 2012

Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but chan... more Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing.

In vivo detection of GABA and glutamate with MEGA-PRESS: Reproducibility and gender effects

by Ruth O'Gorman and Ernst Martin

Journal of Magnetic Resonance Imaging, 2011

Purpose-To evaluate the reproducibility of γ-aminobutyric acid (GABA) and glutamate concentration... more

MRI magnetic susceptibility mapping of target structures for deep brain stimulation (DBS)

by Ruth O'Gorman and Karin Shmueli

Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study

by Ruth O'Gorman and J. Horder

Translational psychiatry, 2014

There is increasing evidence that abnormalities in glutamate signalling may contribute to the pat... more There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo. However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine (Glu+Gln; abbreviated as Glx) along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD-the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)-and one 'control' region-the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy con...

INTERACTION BETWEEN HIPPOCAMPAL GLUTAMATE AND STRIATAL DOPAMINE – RELATIONSHIP TO SUBSEQUENT ONSET OF PSYCHOSIS

Acute effects of single-dose aripiprazole and haloperidol on resting cerebral blood flow (rCBF) in the human brain

Antipsychotic drugs act on the dopaminergic system (first-generation antipsychotics, FGA), but so... more Antipsychotic drugs act on the dopaminergic system (first-generation antipsychotics, FGA), but some also directly affect serotonergic function (second-generation antipsychotics, SGA) in the brain. Short and long-term effects of these drugs on brain physiology remain poorly understood. Moreover, it remains unclear whether any physiological effect in the brain may be different for FGAs and SGAs. Immediate (þ3.30 h) and different effects of single-dose FGA (haloperidol, 3 mg) and a SGA (aripiprazole, 10 mg) on resting cerebral blood flow (rCBF) were explored in the same 20 healthy volunteers using a pulsed continuous arterial spin labeling (pCASL) sequence (1.5T) in a placebocontrolled, repeated measures design. Both antipsychotics increased striatal rCBF but the effect was greater after haloperidol. Both decreased frontal rCBF, and opposite effects of the drugs were observed in the temporal cortex (haloperidol decreased, aripiprazole increased rCBF) and in the posterior cingulate (haloperidol increased, aripiprazole decreased rCBF). Further increases were evident in the insula, hippocampus, and anterior cingulate after both antipsychotics, in the motor cortex following haloperidol and in the occipital lobe the claustrum and the cerebellum after aripiprazole. Further decreases were observed in the parietal and occipital cortices after aripiprazole. This study suggests that early and different rCBF changes are evident following a single-dose of FGA and SGA. The effects occur in healthy volunteers, thus may be independent from any underlying pathology, and in the same regions identified as structurally and functionally altered in schizophrenia, suggesting a possible relationship between antipsychotic-induced rCBF changes and brain alterations in schizophrenia. Hum Brain Mapp 00:000-000, 2012. V C 2012 Wiley Periodicals, Inc.

Reduced subcortical glutamate/glutamine in adults with autism spectrum disorders: a [(1)H]MRS study

by Ruth O'Gorman and J. Horder

Translational psychiatry, 2014

Dysfunctional glutamatergic neurotransmission has been implicated in autism spectrum disorder (AS... more Dysfunctional glutamatergic neurotransmission has been implicated in autism spectrum disorder (ASD). However, relatively few studies have directly measured brain glutamate in ASD adults, or related variation in glutamate to clinical phenotype. We therefore set out to investigate brain glutamate levels in adults with an ASD, comparing these to healthy controls and also comparing results between individuals at different points on the spectrum of symptom severity. We recruited 28 adults with ASD and 14 matched healthy controls. Of those with ASD, 15 fulfilled the 'narrowly' defined criteria for typical autism, whereas 13 met the 'broader phenotype'. We measured the concentration of the combined glutamate and glutamine signal (Glx), and other important metabolites, using proton magnetic resonance spectroscopy in two brain regions implicated in ASD-the basal ganglia (including the head of caudate and the anterior putamen) and the dorsolateral prefrontal cortex-as well as in a parietal cortex 'control' region. Individuals with ASD had a significant decrease (Po0.001) in concentration of Glx in the basal ganglia, and this was true in both the 'narrow' and 'broader' phenotype. Also, within the ASD sample, reduced basal ganglia Glx was significantly correlated with increased impairment in social communication (P ¼ 0.013). In addition, there was a significant reduction in the concentration of other metabolites such as choline, creatine (Cr) and N-acetylaspartate (NAA) in the basal ganglia. In the dorsolateral prefrontal cortex, Cr and NAA were reduced (Po0.05), although Glx was not. There were no detectable differences in Glx, or any other metabolite, in the parietal lobe control region. There were no significant between-group differences in age, gender, IQ, voxel composition or data quality. In conclusion, individuals across the spectrum of ASD have regionally specific abnormalities in subcortical glutamatergic neurotransmission that are associated with variation in social development.

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound

by Ruth O'Gorman and Ernst Martin

Journal of therapeutic ultrasound, 2014

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation... more Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation of target tissues. While this emerging modality is increasingly used for the treatment of various types of extracranial soft tissue tumors, it has only recently been acknowledged as a modality for noninvasive neurosurgery. MRgFUS has been particularly successful for functional neurosurgery, whereas its clinical application for tumor neurosurgery has been delayed for various technical and procedural reasons. Here, we report the case of a 63-year-old patient presenting with a centrally located recurrent glioblastoma who was included in our ongoing clinical phase I study aimed at evaluating the feasibility and safety of transcranial MRgFUS for brain tumor ablation. Applying 25 high-power sonications under MR imaging guidance, partial tumor ablation could be achieved without provoking neurological deficits or other adverse effects in the patient. This proves, for the first time, the feasibi...

Relationship between brain glutamate levels and clinical outcome in individuals at ultra high risk of psychosis

by Ruth O'Gorman and James Stone

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014

Alterations in brain glutamate levels may be associated with psychosis risk, but the relationship... more Alterations in brain glutamate levels may be associated with psychosis risk, but the relationship to clinical outcome in at-risk individuals is unknown. Glutamate concentration was measured in the left thalamus and anterior cingulate cortex (ACC) using 3-Tesla proton magnetic resonance spectroscopy in 75 participants at ultra high risk (UHR) of psychosis and 56 healthy controls. The severity of attenuated positive symptoms and overall functioning were assessed. Measures were repeated in 51 UHR and 33 Control subjects after a mean of 18 months. UHR subjects were allocated to either remission (no longer meeting UHR criteria) or non-remission (meeting UHR or psychosis criteria) status on follow-up assessment. Thalamic glutamate levels at presentation were lower in the UHR non-remission (N=29) compared with the remission group (N=22) (t(49)=3.03; P=0.004), and were associated with an increase in the severity of total positive symptoms over time (r=-0.33; df=47; P=0.02), most notably abn...

Abstracts of Presentations at the International Conference on Basic and Clinical Multimodal Imaging (BaCI), a Joint Conference of the International Society for Neuroimaging in Psychiatry (ISNIP), the International Society for Functional Source Imaging (ISFSI), the International Society for Bioele...

by Ruth O'Gorman, Renata Smieskova, L. Spinelli, and Anna Prinster

Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS)

Does elevated cortical glutamate release drive loss of grey matter in psychosis?

Early Intervention in Psychiatry

Thalamic glutamate and the transition to psychosis

Posterior cingulate γ-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype

by Ruth O'Gorman, Lars Michels, Spyros Kollias, and Roger Luechinger

Neurobiology of Aging, 2015

The biomarker potential of the inhibitory neurotransmitter g-aminobutyric acid (GABA) for the in ... more The biomarker potential of the inhibitory neurotransmitter g-aminobutyric acid (GABA) for the in vivo characterization of preclinical stages in Alzheimer's disease has not yet been explored. We measured GABA, glutamate þ glutamine (Glx), and N-acetyl-aspartate (NAA) levels by single-voxel MEGA-PRESS magnetic resonance spectroscopy in the posterior cingulate cortex of 21 elderly subjects and 15 patients with amnestic mild cognitive impairment. Participants underwent Pittsburgh Compound B positron emission tomography, apolipoprotein E (APOE) genotyping, and neuropsychological examination. GABA, Glx, and NAA levels were significantly lower in patients. NAA was lower in Pittsburgh Compound Bpositive subjects and APOE ε4 allele carriers. GABA, Glx, and NAA levels were positively correlated to CERAD word learning scores. Reductions in GABA, Glx, and NAA levels may serve as metabolic biomarkers for cognitive impairment in amnestic mild cognitive impairment. Because GABA and Glx do not seem to reflect amyloid b deposition or APOE genotype, they are less likely biomarker candidates for preclinical Alzheimer's disease.

Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: Preliminary findings

by Ruth O'Gorman and Lars Michels

Psychiatry Research: Neuroimaging, 2014

Increased cerebral perfusion in adult attention deficit hyperactivity disorder is normalised by stimulant treatment: A non-invasive MRI pilot study

Neuroimage, 2008

The neurobiological basis for attention deficit hyperactivity disorder (ADHD) has not yet been fu... more The neurobiological basis for attention deficit hyperactivity disorder (ADHD) has not yet been fully established, although there is a growing body of evidence pointing to functional and structural abnormalities involving the basal ganglia, cerebellum, and regions of frontal grey matter. The purpose of this study was to investigate regional cerebral perfusion in adults with ADHD and age-matched control subjects, and to assess the perfusion response to stimulant treatment in the ADHD group using a non-invasive magnetic resonance perfusion imaging technique. Whole-brain cerebral perfusion images were acquired from nine right-handed male patients with ADHD and eleven age-matched control subjects using a continuous arterial spin labelling (CASL) technique. The ADHD group was assessed once on their normal treatment and once after withdrawing from treatment for at least one week. An automated voxel-based analysis was used to identify regions where the cerebral perfusion differed significantly between the ADHD and control groups, and where the perfusion altered significantly with stimulant treatment. Regional cerebral perfusion was increased in the ADHD group in the left caudate nucleus, frontal and parietal regions. Psychomotor stimulant treatment acted to normalise perfusion in frontal cortex and the caudate nucleus with additional decreases in parietal and parahippocampal regions. These findings highlight the potential sensitivity of non-invasive perfusion MRI techniques like CASL in the evaluation of perfusion differences due to illness and medication treatment, and provide further evidence that persistence of ADHD symptomatology into adulthood is accompanied by abnormalities in frontal and striatal brain regions.

Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA

NeuroImage, 2013

There is increasing interest in the use of edited proton magnetic resonance spectroscopy for the ... more There is increasing interest in the use of edited proton magnetic resonance spectroscopy for the detection of GABA in the human brain. At a recent meeting held at Cardiff University, a number of spectroscopy groups met to discuss the acquisition, analysis and interpretation of GABA-edited MR spectra. This paper aims to set out the issues discussed at this meeting, reporting areas of consensus around parameters and procedures in the field and highlighting those areas where differences remain. It is hoped that this paper can fulfill two needs, providing a summary of the current &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;state-of-the-art&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; in the field of GABA-edited MRS at 3T using MEGA-PRESS and a basic guide to help researchers new to the field to avoid some of the pitfalls inherent in the acquisition and processing of edited MRS for GABA.

INTERACTION BETWEEN HIPPOCAMPAL GLUTAMATE AND STRIATAL DOPAMINE – RELATIONSHIP TO SUBSEQUENT ONSET OF PSYCHOSIS

Schizophrenia Research, 2010

Abstracts of Presentations at the International Conference

by Ruth O'Gorman, Renata Smieskova, umberto volpe, L. Spinelli, and Anna Prinster

200 – Brain glutamate and grey matter volume in the early phase of psychosis

Schizophrenia Research, 2008

Cortical and cerebellar modulation of autonomic responses to loud sounds

Psychophysiology, 2014

Detecting unexpected environmental change causes modulation of autonomic activity essential for s... more Detecting unexpected environmental change causes modulation of autonomic activity essential for survival. Understanding the neural mechanisms associated with responses to loud sounds may provide insights into the pathophysiology of posttraumatic stress disorder (PTSD), since individuals with PTSD exhibit heightened autonomic responses to unexpected loud sounds. We combined fMRI with autonomic psychophysiological assessment to investigate central and peripheral reactivity to loud tones in 20 healthy participants. Activity in anterior insula, pregenual anterior cingulate cortex, anterior midcingulate cortex, supplementary motor area, supramarginal gyrus, and cerebellar lobules VIII-IX was associated with both tones and concomitant skin conductance responses. Since regions signaling unexpected external events modulate autonomic activity, heightened loud tone autonomic responses in PTSD may reflect sensitization of this "salience" network.

Frontal GABA Levels Change during Working Memory

by Lars Michels, Ruth O'Gorman, and Peter Klaver

PLoS ONE, 2012

Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but chan... more Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task. Further, only GABA increased significantly during the first working memory run and then decreased continuously across subsequent task runs. The decrease of GABA over time was paralleled by a trend towards decreased reaction times and higher task accuracy. These results demonstrate a link between neurotransmitter dynamics and hemodynamic activity during working memory, indicating that functional neuroimaging metrics depend on the balance of excitation and inhibition required for cognitive processing.

In vivo detection of GABA and glutamate with MEGA-PRESS: Reproducibility and gender effects

by Ruth O'Gorman and Ernst Martin

Journal of Magnetic Resonance Imaging, 2011

Purpose-To evaluate the reproducibility of γ-aminobutyric acid (GABA) and glutamate concentration... more