scholarly journals Increase in ACC GABA+ levels correlate with decrease in migraine frequency, intensity and disability over time

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aimie L. Peek ◽  
Andrew M. Leaver ◽  
Sheryl Foster ◽  
Nicolaas A. Puts ◽  
Georg Oeltzschner ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Clinical Characteristics ◽  
Mean Difference ◽  
Anterior Cingulate ◽  
Protective Mechanism ◽  
Resonance Spectroscopy ◽  
Gamma Aminobutyric Acid ◽  
Migraine Frequency ◽  
Over Time ◽  
Frequency Intensity

Abstract Background An imbalance between inhibitory and excitatory neurometabolites has been implicated in chronic pain. Prior work identified elevated levels of Gamma-aminobutyric acid + macromolecules (“GABA+”) using magnetic resonance spectroscopy (MRS) in people with migraine. What is not understood is whether this increase in GABA+ is a cause, or consequence of living with, chronic migraine. Therefore, to further elucidate the nature of the elevated GABA+ levels reported in migraine, this study aimed to observe how GABA+ levels change in response to changes in the clinical characteristics of migraine over time. Methods We observed people with chronic migraine (ICHD-3) over 3-months as their treatment was escalated in line with the Australian Pharmaceutical Benefits Scheme (PBS). Participants underwent an MRS scan and completed questionnaires regarding migraine frequency, intensity (HIT-6) and disability (WHODAS) at baseline and following the routine 3 months treatment escalation to provide the potential for some participants to recover. We were therefore able to monitor changes in brain neurochemistry as clinical characteristics potentially changed over time. Results The results, from 18 participants who completed both baseline and follow-up measures, demonstrated that improvements in migraine frequency, intensity and disability were associated with an increase in GABA+ levels in the anterior cingulate cortex (ACC); migraine frequency (r = − 0.51, p = 0.03), intensity (r = − 0.51, p = 0.03) and disability (r = − 0.53, p = 0.02). However, this was not seen in the posterior cingulate gyrus (PCG). An incidental observation found those who happened to have their treatment escalated with CGRP-monoclonal antibodies (CGRP-mAbs) (n = 10) had a greater increase in ACC GABA+ levels (mean difference 0.54 IU IQR [0.02 to 1.05], p = 0.05) and reduction in migraine frequency (mean difference 10.3 IQR [2.52 to 18.07], p = 0.01) compared to those who did not (n = 8). Conclusion The correlation between an increase in ACC GABA+ levels with improvement in clinical characteristics of migraine, suggest previously reported elevated GABA+ levels may not be a cause of migraine, but a protective mechanism attempting to suppress further migraine attacks.

scholarly journals Neurophysiological Effects of Whole Coffee Cherry Extract in Older Adults with Subjective Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Pilot Study

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 144
Author(s):  
Jennifer L. Robinson ◽  
Julio A. Yanes ◽  
Meredith A. Reid ◽  
Jerry E. Murphy ◽  
Jessica N. Busler ◽  
...  
Keyword(s):  
Decision Making ◽  
Reaction Time ◽  
Magnetic Resonance ◽  
Primary Objective ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Phytochemical Analysis ◽  
Acute Administration ◽  
Gamma Aminobutyric Acid ◽  
Double Blind

Bioactive plant-based compounds have shown promise as protective agents across multiple domains including improvements in neurological and psychological measures. Methodological challenges have limited our understanding of the neurophysiological changes associated with polyphenol-rich supplements such as whole coffee cherry extract (WCCE). In the current study, we (1) compared 100 mg of WCCE to a placebo using an acute, randomized, double-blind, within-subject, cross-over design, and we (2) conducted a phytochemical analysis of WCCE. The primary objective of the study was to determine the neurophysiological and behavioral changes that resulted from the acute administration of WCCE. We hypothesized that WCCE would increase brain-derived neurotrophic factor (BDNF) and glutamate levels while also increasing neurofunctional measures in cognitive brain regions. Furthermore, we expected there to be increased behavioral performance associated with WCCE, as measured by reaction time and accuracy. Participants underwent four neuroimaging scans (pre- and post-WCCE and placebo) to assess neurofunctional/metabolic outcomes using functional magnetic resonance imaging and magnetic resonance spectroscopy. The results suggest that polyphenol-rich WCCE is associated with decreased reaction time and may protect against cognitive errors on tasks of working memory and response inhibition. Behavioral findings were concomitant with neurofunctional changes in structures involved in decision-making and attention. Specifically, we found increased functional connectivity between the anterior cingulate and regions involved in sensory and decision-making networks. Additionally, we observed increased BDNF and an increased glutamate/gamma-aminobutyric acid (GABA) ratio following WCCE administration. These results suggest that WCCE is associated with acute neurophysiological changes supportive of faster reaction times and increased, sustained attention.

scholarly journals In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Do-Wan Lee ◽  
Jae-Im Kwon ◽  
Chul-Woong Woo ◽  
Hwon Heo ◽  
Kyung Won Kim ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Rat Model ◽  
Resonance Spectroscopy ◽  
Chow Diet ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
In Vivo Measurement ◽  
Hippocampal Lesions ◽  
Total Creatine

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.

scholarly journals Sensory over-responsivity is related to GABAergic inhibition in thalamocortical circuits

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emily T. Wood ◽  
Kaitlin K. Cummings ◽  
Jiwon Jung ◽  
Genevieve Patterson ◽  
Nana Okada ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Sensory Information ◽  
Network Connectivity ◽  
Sensory Stimulation ◽  
Autism Spectrum ◽  
Future Research ◽  
Resonance Spectroscopy ◽  
Gamma Aminobutyric Acid ◽  
Sensory Stimuli ◽  
Brain Responses

AbstractSensory over-responsivity (SOR), extreme sensitivity to or avoidance of sensory stimuli (e.g., scratchy fabrics, loud sounds), is a highly prevalent and impairing feature of neurodevelopmental disorders such as autism spectrum disorders (ASD), anxiety, and ADHD. Previous studies have found overactive brain responses and reduced modulation of thalamocortical connectivity in response to mildly aversive sensory stimulation in ASD. These findings suggest altered thalamic sensory gating which could be associated with an excitatory/inhibitory neurochemical imbalance, but such thalamic neurochemistry has never been examined in relation to SOR. Here we utilized magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to examine the relationship between thalamic and somatosensory cortex inhibitory (gamma-aminobutyric acid, GABA) and excitatory (glutamate) neurochemicals with the intrinsic functional connectivity of those regions in 35 ASD and 35 typically developing pediatric subjects. Although there were no diagnostic group differences in neurochemical concentrations in either region, within the ASD group, SOR severity correlated negatively with thalamic GABA (r = −0.48, p < 0.05) and positively with somatosensory glutamate (r = 0.68, p < 0.01). Further, in the ASD group, thalamic GABA concentration predicted altered connectivity with regions previously implicated in SOR. These variations in GABA and associated network connectivity in the ASD group highlight the potential role of GABA as a mechanism underlying individual differences in SOR, a major source of phenotypic heterogeneity in ASD. In ASD, abnormalities of the thalamic neurochemical balance could interfere with the thalamic role in integrating, relaying, and inhibiting attention to sensory information. These results have implications for future research and GABA-modulating pharmacologic interventions.

scholarly journals Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis

2019 ◽  
Vol 50 (13) ◽  
pp. 2182-2193 ◽  
Author(s):  
Kirsten B. Bojesen ◽  
Bjørn H. Ebdrup ◽  
Kasper Jessen ◽  
Anne Sigvard ◽  
Karen Tangmose ◽  
...  
Keyword(s):  
Psychotic Disorders ◽  
Poor Response ◽  
First Episode Psychosis ◽  
Anterior Cingulate ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Resonance Spectroscopy ◽  
Reference Levels ◽  
Clinical Prognosis ◽  
Episode Psychosis

AbstractBackgroundPoor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).MethodsThirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.ResultsBefore treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.ConclusionGlutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.

scholarly journals M146. NEUROCHEMICAL MODULATION OF AUDITORY CORTEX FUNCTIONAL CONNECTIVITY IN PATIENTS WITH AUDITORY VERBAL HALLUCINATIONS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S191-S191
Author(s):  
Sarah Weber ◽  
Helene Hjelmervik ◽  
Alexander R Craven ◽  
Erik Johnsen ◽  
Rune Kroken ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Temporal Lobe ◽  
Superior Temporal Gyrus ◽  
Underlying Mechanism ◽  
Auditory Hallucinations ◽  
Anterior Cingulate ◽  
Gamma Aminobutyric Acid ◽  
Auditory Verbal Hallucinations ◽  
Left And Right ◽  
Neurochemical Correlates

Abstract Background Auditory hallucinations have been linked to aberrant functioning of the left superior temporal gyrus (STG) and are associated with impaired cognitive control regulated by areas in the prefrontal cortex. However, the mechanisms behind these dysfunctions are still unclear. Methods The current study combined resting state connectivity fMRI with MR spectroscopy (MRS) in a sample of 81 psychosis patients to explore how neurochemical correlates of auditory hallucinations modulate left STG functioning. The analyses were focused on glutamate (Glu) and gamma-aminobutyric acid (GABA), two neurotransmitters with excitatory and inhibitory functions, respectively, since these have previously been implicated in psychosis. Results Glu and GABA showed differential relationships with left STG connectivity in patients with and without hallucinations. Specifically, Glu concentration in the anterior cingulate cortex (ACC) was positively related to functional connectivity between the left and right temporal lobe in hallucinating patients only. In contrast, GABA concentration in the ACC was negatively related to connectivity between the left and right temporal lobe in non-hallucinating patients only. Discussion These findings support a recently proposed model of interhemispheric temporal lobe miscommunication in auditory hallucinations and indicate prefrontal neurochemical modulation as a potential underlying mechanism. The results can further be integrated with previously suggested excitatory/inhibitory imbalances as neurochemical modulators in AVH.

scholarly journals Rapid Spread of the SARS-CoV-2 Variant of Concern 202012/01 in Southern Italy (December 2020–March 2021)

2021 ◽  
Vol 18 (9) ◽  
pp. 4766
Author(s):  
Daniela Loconsole ◽  
Francesca Centrone ◽  
Caterina Morcavallo ◽  
Silvia Campanella ◽  
Anna Sallustio ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Large Scale ◽  
Southern Italy ◽  
Whole Genome ◽  
Third Wave ◽  
Gene Target ◽  
The Third ◽  
Rapid Spread ◽  
Pharmaceutical Interventions ◽  
Over Time

Epidemiological and virological studies have revealed that SARS-CoV-2 variants of concern (VOCs) are emerging globally, including in Europe. The aim of this study was to evaluate the spread of B.1.1.7-lineage SARS-CoV-2 in southern Italy from December 2020–March 2021 through the detection of the S gene target failure (SGTF), which could be considered a robust proxy of VOC B.1.1.7. SGTF was assessed on 3075 samples from week 52/2020 to week 10/2021. A subset of positive samples identified in the Apulia region during the study period was subjected to whole-genome sequencing (WGS). A descriptive and statistical analysis of the demographic and clinical characteristics of cases according to SGTF status was performed. Overall, 20.2% of samples showed SGTF; 155 strains were confirmed as VOC 202012/01 by WGS. The proportion of SGTF-positive samples rapidly increased over time, reaching 69.2% in week 10/2021. SGTF-positive cases were more likely to be symptomatic and to result in hospitalization (p < 0.0001). Despite the implementation of large-scale non-pharmaceutical interventions (NPIs), such as the closure of schools and local lockdowns, a rapid spread of VOC 202012/01 was observed in southern Italy. Strengthened NPIs and rapid vaccine deployment, first among priority groups and then among the general population, are crucial both to contain the spread of VOC 202012/01 and to flatten the curve of the third wave.

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