In Vivo Dentate Nucleus Gamma-aminobutyric Acid Concentration in Essential Tremor vs. Controls

Louis, Elan D.; Hernández, Nora; Dyke, Jonathan P.; Ruoyun, E.; Dydak, Ulrike

doi:10.1007/s12311-017-0891-4

Cited by 28 publications

(21 citation statements)

References 44 publications

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“…The GABA A receptor α1 subunit knockout mice have a 15–19 Hz tremor, 66 which is at a significantly higher frequency than that in ET patients. 11 Third, a recent neuroimaging finding showed that ET patients do not have obvious GABA deficiency in the dentate nucleus, 67 which questions the relevance of this mouse model to ET in humans. Another possibility is that GABA deficiency in ET patients occurs outside the dentate nucleus, such as in the thalamic nucleus 68 or IO neurons, 24 which might cause oscillatory neuronal activities and tremor.…”

Section: Resultsmentioning

confidence: 99%

Animal Models of Tremor: Relevance to Human Tremor Disorders

Pan

et al. 2018

Tremor and Other Hyperkinetic Movements

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Section: Resultsmentioning

confidence: 99%

Animal Models of Tremor: Relevance to Human Tremor Disorders

Pan

et al. 2018

Tremor and Other Hyperkinetic Movements

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“…Louis et al investigated the GABA concentrations in large voxels including the dentate nucleus by the use of MRS. Interestingly they found that the right dentate nucleus GABA concentration was significantly higher than the GABA concentration obtained from the left side, only observed for the ET patients [23].…”

Section: Introductionmentioning

confidence: 85%

“…First, the unpaired non-parametric Mann-Whitney test was used to compare the computed concentrations and ratios obtained from the ET patient group to the resulting concentrations obtained from the healthy controls. Second, due to a previous reported cerebellar GABA+ asymmetry [23], the Mann-Whitney test was also used to investigate a potential thalamic or cerebellar asymmetry of GABA+ in the ET patient group. Third, correlation analyses were performed, correlating the GABA+ and Glx concentrations, and the GABA+/Glx ratio to the computed ETRS score defined previously.…”

Section: Statistical Analysesmentioning

confidence: 99%

A pilot study of essential tremor: cerebellar GABA+/Glx ratio is correlated with tremor severity

et al. 2020

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Objective: Essential tremor is a common movement disorder with an unclear origin. Emerging evidence suggests the role of the cerebellum and the thalamus in tremor pathophysiology. We examined the two main neurotransmitters acting inhibitory (GABA+) and excitatory (Glx) respectively, in the thalamus and cerebellum, in patients diagnosed with severe essential tremor. Furthermore, we also investigated the relationship between determined neurotransmitter concentrations and tremor severity in the essential tremor patients. Methods: Ten essential tremor patients (prior to deep brain stimulation surgery) and six healthy controls, were scanned using a 3 T MR system. GABA+ and Glx concentrations were measured using magnetic resonance spectroscopy (MRS) performed using single voxel MEGA-PRESS. For the purpose of assessing the tremor severity, the essential tremor rating scale (ETRS) was used in accordance with Fahn, Tolosa, and Marin. Results: We demonstrated that the cerebellar GABA+/Glx ratio was positively correlated to the ETRS (r = 0.70, p = 0.03) in essential tremor. Cerebellar and thalamic GABA+ and Glx concentrations did not show any significant difference when comparing essential tremor patients with healthy controls, at the group level. Conclusion: We demonstrated a positive correlation between increasing tremor disability and the ratio of GABA+/ Glx in the cerebellum of essential tremor patients. This highlights the impact of an altered balance of the excitatory and inhibitory neurotransmitters in tremor severity. Rather than a change in GABA+, which was constant, we attribute this finding to an overall decrease of Glx.

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“…Furthermore, during the time of examination, none of the patients were treated with medications known to induce tremor or affect GABA pathways (e.g. Primidone, clonazepam, gabapentin or phenobarbital) [78]. Finally, six right-handed matched healthy controls (62.2 ± 11.4 years, five males) without any medical history of neurological illness were recruited by local advertising.…”

Section: Et Patients and Healthy Controlsmentioning

confidence: 99%

“…Furthermore, the GABA+, Glx and GABA+/Glx ratio was investigated between the ET patient group and the healthy controls by computing unpaired non-parametric Mann-Whitney tests. In addition, due to previous reported cerebellar GABA+ asymmetry in ET [78], the Mann-Whitney test was also used to investigate potential GABA+ asymmetry in the ET patient group. Furthermore, analyses were also performed to correlate the GABA+ and Glx concentrations, and the GABA+/Glx ratio, to the ETRS score.…”

Section: Et Patients Compared With Healthy Controlsmentioning

confidence: 99%

Neurotransmitter Imaging of the Human Brain : Detecting γ-Aminobutyric Acid (GABA) Using Magnetic Resonance Spectroscopy

Tapper

2019

Linköping University Medical Dissertations

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Introduction: In this thesis, MEGA-edited Magnetic Resonance Spectroscopy (MRS) has been used for the purpose of non-invasive detection of !aminobutyric acid (GABA) within the brain. GABA is the main inhibitory neurotransmitter in the human central nervous system, and glutamate is the corresponding main excitatory neurotransmitter. A balance between GABA and glutamate is crucial for healthy neurotransmission within the brain, and regional altered concentrations have been linked to certain neurological disorders. However, it is challenging to measure GABA, and special editing approaches are needed in order to allow reliable quantification. In addition, the GABA measurement is further complicated due to disturbances such as movements during the acquisition that may lead to artifacts in the resulting spectrum. This thesis can be divided into two sections, where the first section focuses on three clinical applications (narcolepsy, irritable bowel syndrome (IBS), and essential tremor (ET)), which were all investigated using MEGA-edited singlevoxel spectroscopy (SVS). The second section focuses on method development, where two statistical retrospective approaches were investigated for the purpose of improving MEGA-edited data. In addition, a new MRS imaging (MRSI) pulse sequence with the purpose of GABA detection using a high spatial resolution, short acquisition time, and full brain coverage was also investigated. Materials and Methods: In total, 164 participants were included and 272 MRS measurements were performed with the voxel placed in the medial prefrontal cortex (mPFC, 136), thalamus (32), and cerebellum (104) using two different but "identical" MR systems. Nineteen narcolepsy patients and 21 matched healthy controls performed an fMRI working memory task using a simultaneous EEG followed by an mPFC GABA-edited MRS measurement. Sixty-four IBS patients and 32 matched healthy controls underwent an mPFC GABA-edited MRS measurement followed by resting state fMRI. In addition, psychological symptoms were assessed using questionnaires. Ten ET patients and six matched healthy controls underwent four GABA-edited MRS measurements with the voxels placed in the thalamus and cerebellum. In this study, the symptom severity was investigated using the essential tremor rating scale (ETRS). All clinical MRS datasets were analyzed using conventional methods for post-processing and quantification. Furthermore, 12 volunteers were recruited for the purpose of investigating statistical retrospective approaches for artifact detection and elimination of MRS data. Each participant underwent three reference measurements and three measurements with induced head Neurotransmitter Imaging of the Human Brain ii movements conducted according to a movement paradigm. Order statistic filtering (OSF) and jackknife correlation (JKC) were investigated as regards to the elimination of artifact-influenced spectra and reliability of the resulting concentrations. Finally, phantom measurements were performed for the purpose of investigating MEGA-edited M...

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In Vivo Dentate Nucleus Gamma-aminobutyric Acid Concentration in Essential Tremor vs. Controls

Cited by 28 publications

References 44 publications

Animal Models of Tremor: Relevance to Human Tremor Disorders

Animal Models of Tremor: Relevance to Human Tremor Disorders

A pilot study of essential tremor: cerebellar GABA+/Glx ratio is correlated with tremor severity

Neurotransmitter Imaging of the Human Brain : Detecting γ-Aminobutyric Acid (GABA) Using Magnetic Resonance Spectroscopy

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