Metabolite activity in the anterior cingulate cortex during a painful stimulus using functional MRS

Abstract To understand neurochemical brain responses to pain, proton magnetic resonance spectroscopy (1H-MRS) is used in humans in vivo to examine various metabolites. Recent MRS investigations have adopted a functional approach, where acquisitions of MRS are performed over time to track task-related changes. Previous studies suggest glutamate is of primary interest, as it may play a role during cortical processing of noxious stimuli. The objective of this study was to examine the metabolic effect (i.e., glutamate) in the anterior cingulate cortex during noxious stimulation using fMRS. The analysis addressed changes in glutamate and glutamate + glutamine (Glx) associated with the onset of pain, and the degree by which fluctuations in metabolites corresponded with continuous pain outcomes. Results suggest healthy participants undergoing tonic noxious stimulation demonstrated increased concentrations of glutamate and Glx at the onset of pain. Subsequent reports of pain were not accompanied by corresponding changes in glutamate of Glx concentrations. An exploratory analysis on sex revealed large effect size changes in glutamate at pain onset in female participants, compared with medium-sized effects in male participants. We propose a role for glutamate in the ACC related to the detection of a noxious stimulus.

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A review of altered biochemistry in the anterior cingulate cortex of first-episode psychosis

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796016000895 ◽

2017 ◽

Vol 26 (2) ◽

pp. 122-128 ◽

Cited By ~ 3

Author(s):

L. Squarcina ◽

J. A. Stanley ◽

M. Bellani ◽

C. A. Altamura ◽

P. Brambilla

Keyword(s):

Anterior Cingulate Cortex ◽

Psychotic Disorders ◽

Cingulate Cortex ◽

First Episode Psychosis ◽

Anterior Cingulate ◽

First Episode ◽

Resonance Spectroscopy ◽

Chronic Patients ◽

Episode Psychosis

Relevant biochemicals of the brain can be quantified in vivo, non-invasively, using proton Magnetic Resonance Spectroscopy (¹H MRS). This includes metabolites associated with neural general functioning, energetics, membrane phospholipid metabolism and neurotransmission. Moreover, there is substantial evidence of implication of the frontal and prefrontal areas in the pathogenesis of psychotic disorders such as schizophrenia. In particular, the anterior cingulate cortex (ACC) plays an important role in cognitive control of emotional and non-emotional processes. Thus the study of its extent of biochemistry dysfunction in the early stages of psychosis is of particular interest in gaining a greater understanding of its aetiology. In this review, we selected ¹H MRS studies focused on the ACC of first-episode psychosis (FEP). Four studies reported increased glutamatergic levels in FEP, while other four showed preserved concentrations. Moreover, findings on FEP do not fully mirror those in chronic patients. Due to conflicting findings, larger longitudinal ¹H MRS studies are expected to further explore glutamatergic neurotransmission in ACC of FEP in order to have a better understanding of the glutamatergic mechanisms underlying psychosis, possibly using ultra high field MR scanners.

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Role for NMDA receptors in visceral nociceptive transmission in the anterior cingulate cortex of viscerally hypersensitive rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00452.2007 ◽

2008 ◽

Vol 294 (4) ◽

pp. G918-G927 ◽

Cited By ~ 25

Author(s):

Xiaoyin Wu ◽

Jun Gao ◽

Jin Yan ◽

Jing Fan ◽

Chung Owyang ◽

...

Keyword(s):

Nmda Receptors ◽

Receptor Antagonist ◽

Anterior Cingulate Cortex ◽

Cingulate Cortex ◽

Neuronal Firing ◽

Anterior Cingulate ◽

High Dose ◽

Glutamatergic Transmission ◽

Reverse Microdialysis

We have identified colorectal distension (CRD)-responsive neurons in the anterior cingulate cortex (ACC) and demonstrated that persistence of a heightened visceral afferent nociceptive input to the ACC induces ACC sensitization. In the present study, we confirmed that rostral ACC neurons of sensitized rats [induced by chicken egg albumin (EA)] exhibit enhanced spike responses to CRD. Simultaneous in vivo recording and reverse microdialysis of single ACC neurons showed that a low dose of glutamate (50 μM) did not change basal ACC neuronal firing in normal rats but increased ACC neuronal firing in EA rats from 18 ± 2 to 32 ± 3.8 impulses/10 s. A high dose of glutamate (500 μM) produced 1.95-fold and a 4.27-fold increases of ACC neuronal firing in sham-treated rats and in EA rats, respectively, suggesting enhanced glutamatergic transmission in the ACC neurons of EA rats. Reverse microdialysis of the 3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainite receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 μM) reduced basal and abolished CRD-induced ACC neuronal firing in normal rats. In contrast, microdialysis of N-methyl-d-aspartate (NMDA) receptor antagonist AP5 had no effect on ACC neuronal firing in normal rats. However, AP5 produced 86% inhibition of ACC neuronal firing evoked by 50 mmHg CRD in the EA rats. In conclusion, ACC nociceptive transmissions are mediated by glutamate AMPA receptors in the control rats. ACC responses to CRD are enhanced in viscerally hypersensitive rats. The enhancement of excitatory glutamatergic transmission in the ACC appears to mediate this response. Furthermore, NMDA receptors mediate ACC synaptic responses after the induction of visceral hypersensitivity.

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In vivo evidence for early neurodevelopmental anomaly of the anterior cingulate cortex in bipolar disorder

Acta Psychiatrica Scandinavica ◽

10.1111/j.1600-0447.2007.01069.x ◽

2007 ◽

Vol 116 (6) ◽

pp. 467-472 ◽

Cited By ~ 28

Author(s):

A. Fornito ◽

G. S. Malhi ◽

J. Lagopoulos ◽

B. Ivanovski ◽

S. J. Wood ◽

...

Keyword(s):

Bipolar Disorder ◽

Anterior Cingulate Cortex ◽

Cingulate Cortex ◽

Anterior Cingulate

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Increased myoinositol in the anterior cingulate cortex of veterans with a history of traumatic brain injury: a proton magnetic resonance spectroscopy study

Journal of Neurophysiology ◽

10.1152/jn.00765.2019 ◽

2020 ◽

Vol 123 (5) ◽

pp. 1619-1629

Author(s):

Chandni Sheth ◽

Andrew P. Prescot ◽

Margaret Legarreta ◽

Perry F. Renshaw ◽

Erin McGlade ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Anterior Cingulate Cortex ◽

State Of The Art ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Resonance Spectroscopy ◽

Spectroscopy Study ◽

Magnetic Resonance Spectroscopy Study ◽

History Of

In this study of veterans, we used a state-of-the-art neuroimaging tool to probe the neurometabolic profile of the anterior cingulate cortex in veterans with traumatic brain injury (TBI). We report significantly elevated myoinositol levels in veterans with TBI compared with those without TBI.

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7T Proton Magnetic Resonance Spectroscopy of the Anterior Cingulate Cortex in First-Episode Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sbx190 ◽

2018 ◽

Vol 45 (1) ◽

pp. 180-189 ◽

Cited By ~ 31

Author(s):

Meredith A Reid ◽

Nouha Salibi ◽

David M White ◽

Timothy J Gawne ◽

Thomas S Denney ◽

...

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Anterior Cingulate Cortex ◽

Proton Magnetic Resonance ◽

Proton Magnetic Resonance Spectroscopy ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

First Episode ◽

Resonance Spectroscopy ◽

First Episode Schizophrenia

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Brain Responses during the Anticipation of Dyspnea

Neural Plasticity ◽

10.1155/2016/6434987 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 15

Author(s):

M. Cornelia Stoeckel ◽

Roland W. Esser ◽

Matthias Gamer ◽

Christian Büchel ◽

Andreas von Leupoldt

Keyword(s):

Health Behaviors ◽

Anterior Cingulate Cortex ◽

Sedentary Lifestyle ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Resistive Load ◽

Functional Magnetic Resonance ◽

Activity Avoidance ◽

Brain Responses ◽

Anticipatory Activation

Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea.

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A Proton Magnetic Resonance Spectroscopic Study in Autism Spectrum Disorder Using a 3-Tesla Clinical Magnetic Resonance Imaging (MRI) System: The Anterior Cingulate Cortex and the Left Cerebellum

Journal of Child Neurology ◽

10.1177/0883073817702981 ◽

2017 ◽

Vol 32 (8) ◽

pp. 731-739 ◽

Cited By ~ 9

Author(s):

Hiromichi Ito ◽

Kenji Mori ◽

Masafumi Harada ◽

Sonoka Hisaoka ◽

Yoshihiro Toda ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Magnetic Resonance ◽

Anterior Cingulate Cortex ◽

Proton Magnetic Resonance ◽

Cingulate Cortex ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Anterior Cingulate ◽

Control Group ◽

Resonance Spectroscopy

The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We used proton magnetic resonance spectroscopy to investigate metabolite concentration ratios in the anterior cingulate cortex and left cerebellum in ASD. In the ACC and left cerebellum studies, the ASD group and intelligence quotient- and age-matched control group consisted of 112 and 114 subjects and 65 and 45 subjects, respectively. In the ASD group, γ-aminobutyric acid (GABA)+/ creatine/phosphocreatine (Cr) was significantly decreased in the anterior cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr was significantly decreased in the left cerebellum compared to those in the control group. In addition, both groups showed negative correlations between Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have hypoGABAergic alterations in the anterior cingulate cortex and hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.

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