Posterior cingulate cortex targeted real-time fMRI neurofeedback recalibrates functional connectivity with the amygdala, posterior insula, and default-mode network in PTSD.

BACKGROUND: Alterations within large-scale brain networks-namely, the default mode (DMN) and salience networks (SN)-are present among individuals with posttraumatic stress disorder (PTSD). Previous real-time functional magnetic resonance imaging (fMRI) and electroencephalography neurofeedback studies suggest that regulating posterior cingulate cortex (PCC; the primary hub of the posterior DMN) activity may reduce PTSD symptoms and recalibrate altered network dynamics. However, PCC connectivity to the DMN and SN during PCC-targeted fMRI neurofeedback remains unexamined and may help to elucidate neurophysiological mechanisms through which these symptom improvements may occur. METHODS: Using a trauma/emotion provocation paradigm, we investigated psychophysiological interactions over a single session of neurofeedback among PTSD (n = 14) and healthy control (n = 15) participants. We compared PCC functional connectivity between regulate (in which participants downregulated PCC activity) and view (in which participants did not exert regulatory control) conditions across the whole-brain as well as in a priori specified regions-of-interest. RESULTS: During regulate as compared to view conditions, only the PTSD group showed significant PCC connectivity with anterior DMN (dmPFC, vmPFC) and SN (posterior insula) regions, whereas both groups displayed PCC connectivity with other posterior DMN areas (precuneus/cuneus). Additionally, as compared with controls, the PTSD group showed significantly greater PCC connectivity with the SN (amygdala) during regulate as compared to view conditions. Moreover, linear regression analyses revealed that during regulate as compared to view conditions, PCC connectivity to DMN and SN regions was positively correlated to psychiatric symptoms across all participants. CONCLUSION: In summary, observations of PCC connectivity to the DMN and SN provide emerging evidence of neural mechanisms underlying PCC-targeted fMRI neurofeedback among individuals with PTSD. This supports the use of PCC-targeted neurofeedback as a means by which to recalibrate PTSD-associated alterations in neural connectivity within the DMN and SN, which together, may help to facilitate improved emotion regulation abilities in PTSD.

Increased top-down control of emotions during symptom provocation working memory tasks following a RCT of alpha-down neurofeedback in PTSD.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been found to be associated with emotion under-modulation from the prefrontal cortex and a breakdown of the top-down control of cognition and emotion. Novel adjunct therapies such as neurofeedback (NFB) have been shown to normalize aberrant neural circuits that underlie PTSD psychopathology at rest. However, little evidence exists for NFB-linked neural improvements under emotionally relevant cognitive load. The current study sought to address this gap by examining the effects of alpha-down NFB in the context of an emotional n-back task. METHODS: We conducted a 20-week double-blind randomized, sham-controlled trial of alpha-down NFB and collected neuroimaging data before and after the NFB protocol. Participants performed an emotional 1-back and 2-back working memory task, with interleaved trauma-neutral and trauma-relevant cues in the fMRI scanner. Data from 35 participants with a primary diagnosis of PTSD were analyzed in this study (n = 18 in the experimental group undergoing alpha-down NFB, n = 17 in the sham-control group). RESULTS: Firstly, within-group analyses showed clinically significant reductions in PTSD symptom severity scores at the post-intervention timepoint and 3-month follow-up for the experimental group, and not for the sham-control group. The neuroimaging analyses revealed that alpha-down NFB enhanced engagement of top-down cognitive and emotional control centers, such as the dorsolateral prefrontal cortex (dlPFC), and improved integration of the anterior and posterior parts of the default mode network (DMN). Finally, our results also indicate that increased alpha-down NFB performance correlated with increased activity in brain regions involved in top-down control and bodily consciousness/embodied processing of self (TPJ and posterior insula). CONCLUSION: This is the first study to provide mechanistic insights into how NFB may normalize dysfunctional brain activity and connectivity in PTSD under cognitive load with simultaneous symptom provocation, adding to a growing body of evidence supporting the therapeutic neuromodulatory effects of NFB. This preliminary study highlights the benefits of alpha-down NFB training as an adjunctive therapy for PTSD and warrants further investigation into its therapeutic effects on cognitive and emotion control in those with PTSD.

Differential mechanisms of posterior cingulate cortex downregulation and symptom decreases in posttraumatic stress disorder and healthy individuals using real-time fMRI neurofeedback.

BACKGROUND: Intrinsic connectivity networks, including the default mode network (DMN), are frequently disrupted in individuals with posttraumatic stress disorder (PTSD). The posterior cingulate cortex (PCC) is the main hub of the posterior DMN, where the therapeutic regulation of this region with real-time fMRI neurofeedback (NFB) has yet to be explored. METHODS: We investigated PCC downregulation while processing trauma/stressful words over 3 NFB training runs and a transfer run without NFB (total n = 29, PTSD n = 14, healthy controls n = 15). We also examined the predictive accuracy of machine learning models in classifying PTSD versus healthy controls during NFB training. RESULTS: Both the PTSD and healthy control groups demonstrated reduced reliving symptoms in response to trauma/stressful stimuli, where the PTSD group additionally showed reduced symptoms of distress. We found that both groups were able to downregulate the PCC with similar success over NFB training and in the transfer run, although downregulation was associated with unique within-group decreases in activation within the bilateral dmPFC, bilateral postcentral gyrus, right amygdala/hippocampus, cingulate cortex, and bilateral temporal pole/gyri. By contrast, downregulation was associated with increased activation in the right dlPFC among healthy controls as compared to PTSD. During PCC downregulation, right dlPFC activation was negatively correlated to PTSD symptom severity scores and difficulties in emotion regulation. Finally, machine learning algorithms were able to classify PTSD versus healthy participants based on brain activation during NFB training with 80% accuracy. CONCLUSIONS: This is the first study to investigate PCC downregulation with real-time fMRI NFB in both PTSD and healthy controls. Our results reveal acute decreases in symptoms over training and provide converging evidence for EEG-NFB targeting brain networks linked to the PCC.

A randomized, controlled trial of alpha-rhythm EEG neurofeedback in posttraumatic stress disorder: A preliminary investigation showing evidence of decreased PTSD symptoms and restored default mode and salience network connectivity using fMRI.

OBJECTIVE: The default-mode network (DMN) and salience network (SN) have been shown to display altered connectivity in posttraumatic stress disorder (PTSD). Restoring aberrant connectivity within these networks with electroencephalogram neurofeedback (EEG-NFB) has been shown previously to be associated with acute decreases in symptoms. Here, we conducted a double-blind, sham-controlled randomized trial of alpha-rhythm EEG-NFB in participants with PTSD (n = 36) over 20-weeks. Our aim was to provide mechanistic evidence underlying clinical improvements by examining changes in network connectivity via fMRI. METHODS: We randomly assigned participants with a primary diagnosis of PTSD to either the experimental group (n = 18) or sham-control group (n = 18). We collected resting-state fMRI scans pre- and post-NFB intervention, for both the experimental and sham-control PTSD groups. We further compared baseline brain connectivity measures pre-NFB to age-matched healthy controls (n = 36). RESULTS: With regard to the primary outcome measure of PTSD severity, we found a significant main effect of time in the absence of a group × time interaction. Nevertheless, we found significantly decreased PTSD severity scores in the experimental NFB group only, when comparing post-NFB (dz = 0.71) and 3-month follow-up scores (dz = 0.77) to baseline measures. Interestingly, we found evidence to suggest a shift towards normalization of DMN and SN connectivity post-NFB in the experimental group only. Both decreases in PTSD severity and NFB performance were correlated to DMN and SN connectivity post-NFB in the experimental group. Critically, remission rates of PTSD were significant higher in the experimental group (61.1%) as compared to the sham-control group (33.3%). CONCLUSION: The current study shows mechanistic evidence for therapeutic changes in DMN and SN connectivity that are known to be associated with PTSD psychopathology with no patient dropouts. This preliminary investigation merits further research to demonstrate fully the clinical efficacy of EEG-NFB as an adjunctive therapy for PTSD.

Sahaj Samadhi meditation vs a Health Enhancement Program in improving late-life depression severity and executive function: study protocol for a two-site, randomized controlled trial.

BACKGROUND: Recent estimates suggest an 11% prevalence of current late-life depression (LLD) and a lifetime prevalence of 16-20%. LLD leads to cognitive disturbance as well as a nearly two to three times increased risk of dementia. We conducted a recent randomized controlled trial (RCT) which demonstrated that Sahaj Samadhi meditation (SSM), an easy-to-implement, meditation-based augmentation strategy, led to higher rates of symptom remission when compared to treatment as usual (40.0 vs 16.3%; odds ratio, 3.36; 95% CI 1.06-10.64; p = 0.040). Here we present a protocol describing a two-site, blinded, RCT, comparing an SSM arm to an active-control arm - a Health Enhancement Program (HEP) intervention - in their ability to reduce depressive symptoms and improve executive functioning, among several other exploratory outcomes. METHODS/DESIGN: One hundred and ninety-two (n = 192) participants with LLD will be recruited at two sites (London, ON, Canada, and Montreal, QC, Canada). Participants will undergo stratified randomization with regards to site and the presence of treatment-resistant-LLD (TR-LLD) or not, to either SSM or HEP. We will assess change in (1) depression severity using the Hamilton Depression Rating Scale (HAM-D), (2) executive functioning, and (3) other exploratory physiological and mood-based measures, at baseline (0 weeks), post intervention (12 weeks), and 26 weeks after baseline. Raters, clinicians, and care providers will be blinded to group allocation while participants will be blinded to the study hypotheses. DISCUSSION: This study should more definitively assess whether SSM can be used as an augmentation strategy in routine clinical care for patients suffering from LLD and TR-LLD. If the effects of SSM are significantly better than HEP, it will offer support for the routine use of this intervention to manage LLD/TR-LLD and comorbid declines in executive dysfunction. The results of this study could also inform whether SSM can improve/prevent cognitive decline in LLD. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03564041 . Registered on 20 June 2018.

Overlapping frontoparietal networks in response to oculomotion and traumatic autobiographical memory retrieval: implications for eye movement desensitization and reprocessing.

Background: Oculomotor movements have been shown to aid in the retrieval of episodic memories, serving as sensory cues that engage frontoparietal brain regions to reconstruct visuospatial details of a memory. Frontoparietal brain regions not only are involved in oculomotion, but also mediate, in part, the retrieval of autobiographical episodic memories and assist in emotion regulation. Objective: We sought to investigate how oculomotion influences retrieval of traumatic memories by examining patterns of frontoparietal brain activation during autobiographical memory retrieval in post-traumatic stress disorder (PTSD) and in healthy controls. Method: Thirty-nine participants (controls, n = 19; PTSD, n = 20) recollected both neutral and traumatic/stressful autobiographical memories while cued simultaneously by horizontal and vertical oculomotor stimuli. The frontal (FEF) and supplementary (SEF) eye fields were used as seed regions for psychophysiological interaction analyses in SPM12. Results: As compared to controls, upon retrieval of a traumatic/stressful memory while also performing simultaneous horizontal eye movements, PTSD showed: i) increased SEF and FEF connectivity with the right dorsolateral prefrontal cortex, ii) increased SEF connectivity with the right dorsomedial prefrontal cortex, and iii) increased SEF connectivity with the right anterior insula. By contrast, as compared to PTSD, upon retrieval of a traumatic/stressful memory while also performing simultaneous horizontal eye movements, controls showed: i) increased FEF connectivity with the right posterior insula and ii) increased SEF connectivity with the precuneus. Conclusions: These findings provide a neurobiological account for how oculomotion may influence the frontoparietal cortical representation of traumatic memories. Implications for eye movement desensitization and reprocessing are discussed.

Antecedentes: Se ha visto que los movimientos óculomotores ayudan a la recuperación de memorias episódicas, sirviendo como señales sensoriales que envuelven las regiones cerebrales frontoparietales para reconstruir detalles visuoespaciales. Las regiones cerebrales frontoparietales no solo están involucradas críticamente en el movimiento ocular, pero ellos también median, en parte, la recuperación de la memoria episódica autobiográfica y ayudan en la regulación emocional.Objetivo: Buscamos investigar cómo el movimiento ocular influye en la recuperación de la memoria traumática al examinar patrones de activación cerebral frontoparietales durante la recuperación de la memoria autobiográfica en trastorno de estrés postraumático (TEPT) y controles sanos.Método: Se recolectaron en treinta y nueve participantes (controles, n= 19; TEPT, n=20): (i) neutral; y (ii) memorias autobiográficas traumáticas/estresantes mientras se señalaba simultáneamente por estímulos oculomotores horizontales y verticales. Se usaron los campos oculares frontal (FEF por sus siglas en inglés) y suplementario (SEF por sus siglas en inglés) como regiones bases para el análisis de interacción psico fisiológica en SPM12.Resultados: En comparación con los controles, al recuperar una memoria traumática/estresante mientras se realizan simultáneamente movimientos oculares horizontales, el TEPT mostró: (i) SEF aumentado y conectividad FEF con la corteza prefrontal dorsolateral derecha, (ii) conectividad SEF aumentada con la corteza prefrontal dorsomedial derecha y (iii) conectividad SEF aumentada con la ínsula anterior derecha. En contraste, al compararlo con TEPT, al recuperar una memoria traumática/estresante mientras se realizan simultáneamente movimientos oculares horizontales, los controles mostraron: (i) conectividad FEF aumentada con la región posterior derecha de la ínsula y (ii) conectividad SEF aumentada con el precuneoConclusiones: Estos hallazgos proveen un base neurobiológica de cómo los movimientos oculares pueden influir en la representación cortical frontoparietal de las memorias traumáticas. Se discuten las implicaciones del reprocesamiento y desensibilización por movimientos oculares.

Intrinsic connectivity network dynamics in PTSD during amygdala downregulation using real-time fMRI neurofeedback: A preliminary analysis.

Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real-time fMRI neurofeedback (rt-fMRI-NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala-a key region-of-interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt-fMRI-NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task-negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt-fMRI-NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.

Glutamatergic metabolite correlations with neuropsychological tests in first episode schizophrenia.

Increased glutamatergic metabolites have been found in first episode schizophrenia. Although abnormal neuropsychological functioning has been demonstrated to be a core feature of schizophrenia, no studies have examined glutamatergic metabolites and neuropsychological function in drug-naïve patients. The present study addressed whether higher levels of glutamatergic metabolites would be associated with poorer neuropsychological performance and social functioning in first episode patients. Glutamatergic concentration estimates were obtained from the left anterior cingulate cortex (ACC) and thalamus at baseline and 10 months after treatment in 16 patients with psychosis using 4.0 T (1)H magnetic resonance spectroscopy. A neuropsychological test battery was administered at baseline and 1 year. In the ACC, baseline glutamine was associated with performance on the Paced Auditory Serial Addition Task (PASAT). Glutamate at 10 months was associated with Wisconsin Card Sorting Test (WCST) errors and Trail-Making Test-B duration. Glutamine at 10 months was positively associated with WCST errors and negatively associated with WCST categories completed. In the thalamus, baseline glutamine was negatively associated with performance on the PASAT. Thalamic glutamate at baseline showed a trend towards a negative association with social functioning at 5 years. Glutamatergic metabolites were associated with neuropsychological test deficits and impaired social functioning at 5-year follow-up in patients with first episode psychosis, findings suggestive of an association between glutamatergic alterations on neurotoxicity early in the course of schizophrenia.

Effect of direct eye contact in women with PTSD related to interpersonal trauma: Psychophysiological interaction analysis of connectivity of an innate alarm system.

In healthy individuals, direct eye contact is thought to modulate a cortical route eliciting social cognitive processes via activation of a fast subcortical pathway. This study aimed to examine functional brain connectivity during direct eye contact in women with posttraumatic stress disorder (PTSD) related to childhood abuse as compared with healthy controls. We conducted psychophysiological interaction (PPI) analyses in Statistical Parametric Mapping-8 (SPM8) using the superior colliculus (SC) and locus coeruleus (LC) as seed regions while 16 healthy subjects and 16 patients with a primary diagnosis of PTSD related to childhood maltreatment viewed a functional magnetic resonance imaging (fMRI) paradigm involving direct (D) versus averted (A) gaze (happy, sad, neutral). The PTSD group showed a significantly enhanced connectivity between the SC and the anterior cingulate, and between the LC and the thalamus, caudate, putamen, insula, cingulate gyrus, and amygdala, as compared with healthy individuals. Symptom severity scores on the Clinician-Administered PTSD Scale (CAPS) showed significant positive correlations with superior colliculus connectivity with the perigenual and posterior cingulate, insula, and sublenticular extended amygdala. Functional connectivity data suggest increased recruitment of brain regions involved in emotion processing during direct gaze in PTSD in association with the fast subcortical pathway. The interpretation of eye contact as a signal of threat may require more emotion regulatory capacities in patients with PTSD.

Mind over chatter: plastic up-regulation of the fMRI salience network directly after EEG neurofeedback.

Neurofeedback (NFB) involves a brain-computer interface that allows users to learn to voluntarily control their cortical oscillations, reflected in the electroencephalogram (EEG). Although NFB is being pioneered as a noninvasive tool for treating brain disorders, there is insufficient evidence on the mechanism of its impact on brain function. Furthermore, the dominant rhythm of the human brain is the alpha oscillation (8-12 Hz), yet its behavioral significance remains multifaceted and largely correlative. In this study with 34 healthy participants, we examined whether during the performance of an attentional task, the functional connectivity of distinct fMRI networks would be plastically altered after a 30-min session of voluntary reduction of alpha rhythm (n=17) versus a sham-feedback condition (n=17). We reveal that compared to sham-feedback, NFB induced an increase of connectivity within regions of the salience network involved in intrinsic alertness (dorsal anterior cingulate), which was detectable 30 min after termination of training. The increase in salience network (default-mode network) connectivity was negatively (positively) correlated with changes in 'on task' mind-wandering as well as resting state alpha rhythm. Crucially, we observed a causal dependence between alpha rhythm synchronization during NFB and its subsequent change at resting state, not exhibited by the SHAM group. Our findings provide neurobehavioral evidence for the brain's exquisite functional plasticity, and for a temporally direct impact of NFB on a key cognitive control network, suggesting a promising basis for its use to treat cognitive disorders under physiological conditions.

Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia.

BACKGROUND: Thalamic glutamine loss and grey matter reduction suggest neurodegeneration in first-episode schizophrenia, but the duration is unknown. AIMS: To observe glutamine and glutamate levels, grey matter volumes and social functioning in patients with schizophrenia followed to 80 months after diagnosis. METHOD: Grey matter volumes and proton magnetic resonance spectroscopy metabolites in left anterior cingulate and left thalamus were measured in 17 patients with schizophrenia before medication and 10 and 80 months after diagnosis. Social functioning was assessed with the Life Skills Profile Rating Scale (LSPRS) at 80 months. RESULTS: The sum of thalamic glutamate and glutamine levels decreased over 80 months, and correlated inversely with the LSPRS. Thalamic glutamine and grey matter loss were significantly correlated in frontal, parietal, temporal and limbic regions. CONCLUSIONS: Brain metabolite loss is correlated with deteriorated social functioning and grey matter losses in schizophrenia, consistent with neurodegeneration.

Regional brain activation during hypoglycemia in type 1 diabetes.

CONTEXT: Mechanisms underlying the brain response to hypoglycemia are not well understood. OBJECTIVE: Our objective was to determine the blood glucose level at which the hypothalamus and other brain regions are activated in response to hypoglycemia in type 1 diabetic patients and control subjects. DESIGN: This was a cross-sectional study evaluating brain activity using functional magnetic resonance imaging in conjunction with a hyperinsulinemic hypoglycemic clamp to lower glucose from euglycemia (90 mg/dl) to hypoglycemia (50 mg/dl). SETTING: The study was performed at the Brain Imaging Center in the McLean Hospital. STUDY PARTICIPANTS: Seven type 1 diabetic patients between 18 and 50 yr old and six matched control subjects were included in the study. INTERVENTION: Hyperinsulinemic hypoglycemic clamp was performed. MAIN OUTCOME MEASURES: Blood glucose level at peak hypothalamic activation, amount of regional brain activity during hypoglycemia in both groups, and difference in regional brain activation between groups were calculated. RESULTS: The hypothalamic region activates at 68 +/- 9 mg/dl in control subjects and 76 +/- 8 mg/dl in diabetic patients during hypoglycemia induction. Brainstem, anterior cingulate cortex, uncus, and putamen were activated in both groups (P < 0.001). Each group also activated unique brain areas not active in the other group. CONCLUSIONS: This application of functional magnetic resonance imaging can be used to identify the glucose level at which the hypothalamus is triggered in response to hypoglycemia and whether this threshold differs across patient populations. This study suggests that a core network of brain regions is recruited during hypoglycemia in both diabetic patients and control subjects.

Longitudinal grey-matter and glutamatergic losses in first-episode schizophrenia.

BACKGROUND: Progressive volumetric changes in the brains of people with schizophrenia have been attributed to a number of factors. AIMS: To determine whether glutamatergic changes in patients with schizophrenia correlated with grey-matter losses during the first years of illness. METHOD: Left anterior cingulate and thalamic glutamatergic metabolite levels and grey-matter volumes were examined in 16 patients with first-episode schizophrenia before and after 10 months and 30 months of antipsychotic treatment and in 16 healthy participants on two occasions 30 months apart. RESULTS: Higher than normal glutamine levels were found in the anterior cingulate and thalamus of never-treated patients. Thalamic levels of glutamine were significantly reduced after 30 months. Limited grey-matter reductions were seen in patients at 10 months followed by widespread grey-matter loss at 30 months. Parietal and temporal lobe grey-matter loss was correlated with thalamic glutamine loss. CONCLUSIONS: Elevated glutamine levels in never-treated patients followed by decreased thalamic glutamine and grey-matter loss in connected regions could indicate either neurodegeneration or a plastic response to reduced subcortical activity.

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.

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.

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.

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.