Metabolism In Cingulate Cortex Research Articles

Brain metabolic changes and clinical response to superolateral medial forebrain bundle deep brain stimulation for treatment-resistant depression.

Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle is an efficacious therapy for treatment-resistant depression, providing rapid antidepressant effects. In this study, we use 18F-fluorodeoxyglucose-positron emission tomography (PET) to identify brain metabolic changes over 12 months post-DBS implantation in ten of our patients, compared to baseline. The primary outcome measure was a 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score, which was interpreted as a response. Deterministic fiber tracking was used to individually map the target area; probabilistic tractography was used to identify modulated fiber tracts modeled using the cathodal contacts. Eight of the ten patients included in this study were responders. PET imaging revealed significant decreases in bilateral caudate, mediodorsal thalamus, and dorsal anterior cingulate cortex metabolism that was evident at 6 months and continued to 12 months post surgery. At 12 months post-surgery, significant left ventral prefrontal cortical metabolic decreases were also observed. Right caudate metabolic decrease at 12 months was significantly correlated with mean MADRS reduction. Probabilistic tractography modeling revealed that such metabolic changes lay along cortico-limbic nodes structurally connected to the DBS target site. Such observed metabolic changes following DBS correlated with clinical response provide insights into how future studies can elaborate such data to create biomarkers to predict response, the development of which likely will require multimodal imaging analysis.

Hypoxia alters posterior cingulate cortex metabolism during a memory task: A 1H fMRS study

Environmental hypoxia (fraction of inspired oxygen (FIO2) ∼ 0.120) is known to trigger a global increase in cerebral blood flow (CBF). However, regionally, a heterogeneous response is reported, particularly within the posterior cingulate cortex (PCC) where decreased CBF is found after two hours of hypoxic exposure. Furthermore, hypoxia reverses task-evoked BOLD signals within the PCC, and other regions of the default mode network, suggesting a reversal of neurovascular coupling. An alternative explanation is that the neural architecture supporting cognitive tasks is reorganised. Therefore, to confirm if this previous result is neural or vascular in origin, a measure of neural activity that is not haemodynamic-dependant is required.To achieve this, we utilised functional magnetic resonance spectroscopy to probe the glutamate response to memory recall in the PCC during normoxia (FIO2 = 0.209) and after two hours of poikilocapnic hypoxia (FIO2 = 0.120). We also acquired ASL-based measures of CBF to confirm previous findings of reduced CBF within the PCC in hypoxia.Consistent with previous findings, hypoxia induced a reduction in CBF within the PCC and other regions of the default mode network. Under normoxic conditions, memory recall was associated with an 8% increase in PCC glutamate compared to rest (P = 0.019); a change which was not observed during hypoxia. However, exploratory analysis of other neurometabolites showed that PCC glucose was reduced during hypoxia compared to normoxia both at rest (P = 0.039) and during the task (P = 0.046).We conclude that hypoxia alters the activity-induced increase in glutamate, which may reflect a reduction in oxidative metabolism within the PCC. The reduction in glucose in hypoxia reflects continued metabolism, presumably by non-oxidative means, without replacement of glucose due to reduced CBF.

Diagnostic imaging of dementia with Lewy bodies, frontotemporal lobar degeneration, and normal pressure hydrocephalus.

Neuroimaging can provide important biomarkers and is very useful for supporting dementia diagnosis. This review summarizes the neuroimaging findings of dementia with Lewy bodies (DLB), frontotemporal lobar degeneration (FTLD), and normal pressure hydrocephalus (NPH). In DLB, medial temporal atrophy is milder than that of Alzheimer's disease. 2-fluoro-2-deoxy-D-glucose-positron emission tomography and brain perfusion single-photon emission computed tomography demonstrate hypometabolism and hypoperfusion in the occipital lobe, in addition to decreased metabolism and perfusion in the parietotemporal, posterior cingulate, precuneus, and frontal association cortices. The cingulate island sign, which shows relatively spared middle-to-posterior cingulate cortex metabolism compared with precuneus hypometabolism, is proposed to detect DLB in 2-fluoro-2-deoxy-D-glucose-positron emission tomography imaging. Reduced uptake in dopamine transporter imaging and reduced myocardial uptake in iodine-123 metaiodobenzylguanidine cardiac scintigraphy are indicative biomarkers for DLB diagnosis. Characteristic findings of FTLD include dominant frontotemporal atrophy, hypometabolism, and hypoperfusion. Most idiopathic NPH cases demonstrate disproportionally enlarged subarachnoid space hydrocephalus findings, including dilated ventricular systems, enlarged Sylvian fissures, tight sulci in the midline, and a high convexity.

The Cingulate Island Sign on FDG-PET vs. IMP-SPECT to Assess Mild Cognitive Impairment in Alzheimer's Disease vs. Dementia with Lewy Bodies.

The cingulate island sign (CIS) on 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET); ie, the relative preservation of mid-posterior cingulate cortex metabolism, is a supportive biomarker in the diagnostic criteria for dementia with Lewy bodies (DLB). However, limited information is currently available on the diagnostic value of the CIS on FDG-PET or 123 I-iodoamphetamine single-photon emission computed tomography (IMP-SPECT) for differentiating between mild cognitive impairment (MCI) due to Alzheimer's disease (AD) (MCI-AD) and MCI due to DLB (MCI-DLB). We examined the CIS ratio in 9 AD patients, 9 DLB patients, 8 patients with MCI-AD, and 9 patients with MCI-DLB using FDG-PET and IMP-SPECT. The CIS ratio was calculated using NEUROSTAT software. In the dementia groups, a receiver operating characteristic analysis of the CIS ratio showed significant accuracy for differentiating between AD and DLB on FDG-PET and IMP-SPECT. In the MCI groups, only the FDG-PET derived CIS ratio displayed significant accuracy for differentiating between AD and DLB. The FDG-PET and IMP-SPECT derived CIS ratios are both useful for differentiating between AD and DLB. The FDG-PET derived CIS ratio is more valuable than the IMP-SPECT derived CIS ratio for differential diagnosis in patients with MCI. A larger study is needed to confirm these results.

RETRACTED: The cingulate island sign in patients with dementia with Lewy bodies or Alzheimer's disease: A direct comparison between 18F-FDG PET and 123I-IMP SPECT

The cingulate island sign (CIS) on 18F-fluorodeoxyglucose positron emission tomography (FDG PET); i.e., the relative preservation of mid-posterior cingulate cortex metabolism, is a supportive biomarker in the diagnostic criteria for dementia with Lewy bodies (DLB). Information is lacking, however, regarding the diagnostic value of the CIS on FDG PET or 123I-iodoamphetamine single-photon emission computed tomography (IMP SPECT) for differentiating between mild cognitive impairment (MCI) due to Alzheimer's disease (AD) (MCI-AD) and MCI due to DLB (MCI-DLB). We examined the CIS ratio for nine AD patients, nine DLB patients, eight patients with MCI-AD, and nine patients with MCI-DLB using FDG PET and IMP SPECT. The CIS ratio was calculated as the total count density for the mid-posterior cingulate cortex divided by the total count density for the precuneus and cuneus using the stereotactic extraction estimation method. In the dementia groups, receiver operating characteristic analysis of the CIS ratio showed significant accuracy for differentiating between AD and DLB on both FDG PET and IMP SPECT. In the MCI groups, only the FDG PET-derived CIS ratio displayed significant accuracy for differentiating between AD and DLB. A larger study is needed to replicate these findings.

Proton MR Spectroscopy in Patients With Sleep-Related Hypermotor Epilepsy (SHE): Evidence of Altered Cingulate Cortex Metabolism.

To identify structural and/or metabolic alterations in patients with sleep-related hypermotor epilepsy (SHE) using magnetic resonance imaging (MRI) and proton MR spectroscopy (1H-MRS). Nineteen SHE patients (seven males; 34.7 ± 9.7 years, mean age ± standard deviation) and 17 matched healthy volunteers (seven males; 34.0 ± 8.9 years) were included in the study. In all patients, the diagnosis of SHE was confirmed by video-polysomnographic recording of seizures. Semiology, seizure frequency, and therapy were assessed for all patients. For each recruited participant, structural MRI and 1H-MRS sequences were acquired. 1H-MRS was performed on two regions of interest: the medial thalamus and the anterior cingulate gyrus. At examination, five patients were seizure free. In the remainder, seizure frequency ranged from yearly to multiple episodes per night. Brain MRI was normal in all patients but one. The ratio of N-acetyl-aspartate/Creatine (NAA/Cr) was significantly reduced in the anterior cingulate cortex in patients compared to controls (p < .05). Thalamic NAA/Cr showed no differences between patients and controls. Regression analysis showed that NAA/Cr in the anterior cingulate gyrus correlated with seizure frequency (p < .05), being lower in patients with higher seizure frequency. Given the absence of structural MR changes, our 1H-MRS data point to a functional NAA reduction in the cingulate cortex of SHE patients, more severe in those patients with higher seizure frequency and thus supporting the involvement of the anterior mesial structures in the pathophysiology of SHE.

Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using 18FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic efficacy, whereas these posttreatment sex differences contribute to clinical treatment failure more commonly experienced by the former.

ASSOCIATION OF HIPPOCAMPAL VOLUME AND POSTERIOR CINGULATE CORTEX METABOLISM MODULATED BY WHITE MATTER CONNECTIVITY

ASSOCIATION OF HIPPOCAMPAL VOLUME AND POSTERIOR CINGULATE CORTEX METABOLISM MODULATED BY WHITE MATTER CONNECTIVITY

Nociception Coma Scale-Revised total scores correlate with anterior cingulate cortex as measured by FDG-PET in patients with disorders of consciousness

Event Abstract Back to Event Nociception Coma Scale-Revised total scores correlate with anterior cingulate cortex as measured by FDG-PET in patients with disorders of consciousness Camille Chatelle1*, Aurore Thibaut1, Marie-Aurélie Bruno1, Melanie Boly1, Claire Bernard2, Roland Hustinx2, Caroline Schnakers1 and Steven Laureys1 1 University of Liège, Cyclotron Research Centre, Belgium 2 University Hospital of Liège, Nuclear Medicine Dept, Belgium Introduction. The Nociception Coma Scale-Revised was recently validated to assess possible pain perception in patients with disorders of consciousness (i.e., vegetative state/unresponsive wakefulness syndrome and minimally conscious state [1,2,3]). We here aim to identify correlations between cerebral glucose metabolism and Nociception Coma Scale-Revised total scores in disorders of consciousness. Methods. [18F]-fluorodeoxyglucose-PET was performed in 42 patients with disorders of consciousness (29 males, aged 42±17 years; 26 minimally conscious state; 19 post-traumatic; 22 in the acute/subacute setting (i.e., < 1 year post insult). All patients had Coma Recovery Scale-Revised [4] and Nociception Coma Scale-Revised assessment on the day of PET imaging. Data preprocessing and analyses employed statistical parametric mapping (SPM8) and results were considered significant at small-volume corrected p<0.05 for a priori identified coordinates of the pain matrix (Boly et al., 2008 [5]) (i.e., thalamus, primary and secondary somatosensory cortex, insula and anterior cingulate cortex). Results. Anterior cingulate cortex metabolism showed a positive linear correlation with Nociception Coma Scale-Revised total scores and not with Coma Recovery Scale-Revised total scores (corrected p= 0.018; x=20, y=16, z=36). The observed effect showed no significant difference depending on etiology or duration. Conclusions. Nociception Coma Scale-Revised scores (and not Coma Recovery Scale-Revised scores) correlated with metabolic activity of anterior cingulate cortex, known to be involved in the affective emotional component of pain perception. Our data support the hypothesis that Nociception Coma Scale-Revised assessment in non-communicative patients with disorders of consciousness indeed reflects possible pain perception, permitting clinicians to treat adequately and optimize the clinical management of this challenging patient population [6]. Figure 1 Acknowledgements CC is Research Fellow; MAB, MB and CS are Postdoctoral Researcher and SL is Research Director at the Fonds National de la Recherche Scientifique de Belgique (FNRS). This research was supported by FNRS, University and University Hospital of Liège, European Commission, James S. McDonnell Foundation, Mind Science Foundation, Concerted Research Action and Fondation Léon Frédéricq.

Correlation of Glutamate Levels in the Anterior Cingulate Cortex With Self-reported Impulsivity in Patients With Borderline Personality Disorder and Healthy Controls

Dysfunction and deficits in the structure of the anterior cingulate cortex have been reported in borderline personality disorder (BPD). To our knowledge, there is only 1 published study to date investigating anterior cingulate cortex metabolism in subjects with BPD and co-occurring attention-deficit/hyperactivity disorder using proton magnetic resonance spectroscopy. Impulsivity is a key feature of BPD and can be related to anterior cingulate cortex function. To investigate whether anterior cingulate cortex metabolism may be altered in BPD and correlates with BPD pathology. Cross-sectional proton magnetic resonance spectroscopy study. Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany. Thirty unmedicated female subjects meeting DSM-IV criteria for BPD and 31 age-matched healthy female control participants. Neurometabolite concentrations in the anterior cingulate cortex and correlation of glutamate levels with self-reported measures of impulsivity and severity of borderline symptoms. Significantly higher levels of glutamate in the anterior cingulate cortex were found in subjects with BPD as compared with healthy controls. A positive correlation between glutamate concentration and the Barratt Impulsiveness Scale total score as well as between glutamate concentration and the subscore for cognitive impulsivity were observed irrespective of diagnosis. We also found a positive correlation between glutamate concentrations and dissociation as well as between glutamate concentration and subscores of the Borderline Symptom List in the patient group. Our results support the hypothesis that higher glutamate concentration in the anterior cingulate cortex is associated with both severity of BPD symptoms and subjective impulsivity ratings, the latter independent of BPD. Further studies should confirm the association between enhanced glutamate concentration in the anterior cingulate cortex and behavioral measures of impulsivity.

Changes in brain metabolism associated with remission in unipolar major depression.

Functional brain correlates of remission in patients with major depressive disorder (MDD) are measured with positron emission tomography (PET) and 18F-fluorodeoxyglucose. Glucose metabolism was measured in patients (n = 41) with moderate to severe MDD during acute depression and in the remitted state defined as a period of asymptomatic condition over 12 weeks. Data analyses used a region-of-interest (ROI) approach and statistical parametric mapping (SPM). There were significant decreases in metabolism upon remission with respect to the baseline scan in left prefrontal, anterior temporal and anterior cingulate cortex and bilateral thalamus (SPM analysis) and bilateral putamen and cerebellum (SPM and ROI analyses). There was a significant asymmetry in prefrontal and anterior cingulate cortex metabolism with lower metabolism in the left hemisphere that persisted despite clinical remission. These findings support the hypothesis that selective monoamine reuptake inhibition leads to an attenuation of a brain circuit that mediates depressive symptomatology.