Neurometabolic alterations in children and adolescents with functional neurological disorder

IF 3.4 2区医学 Q2 NEUROIMAGING Neuroimage-Clinical Pub Date : 2024-01-01 DOI:10.1016/j.nicl.2023.103557

Molly Charney , Sheryl Foster , Vishwa Shukla , Wufan Zhao , Sam H. Jiang , Kasia Kozlowska , Alexander Lin

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Abstract

Objectives

In vivo magnetic resonance spectroscopy (MRS) was used to investigate neurometabolic homeostasis in children with functional neurological disorder (FND) in three regions of interest: supplementary motor area (SMA), anterior default mode network (aDMN), and posterior default mode network (dDMN). Metabolites assessed included N-acetyl aspartate (NAA), a marker of neuron function; myo-inositol (mI), a glial-cell marker; choline (Cho), a membrane marker; glutamate plus glutamine (Glx), a marker of excitatory neurotransmission; γ-aminobutyric acid (GABA), a marker of inhibitor neurotransmission; and creatine (Cr), an energy marker. The relationship between excitatory (glutamate and glutamine) and inhibitory (GABA) neurotransmitter (E/I) balance was also examined.

Methods

MRS data were acquired for 32 children with mixed FND (25 girls, 7 boys, aged 10.00 to 16.08 years) and 41 healthy controls of similar age using both short echo point-resolved spectroscopy (PRESS) and Mescher-Garwood point-resolved spectroscopy (MEGAPRESS) sequences in the three regions of interest.

Results

In the SMA, children with FND had lower NAA/Cr, mI/Cr (trend level), and GABA/Cr ratios. In the aDMN, no group differences in metabolite ratios were found. In the pDMN, children with FND had lower NAA/Cr and mI/Cr (trend level) ratios. While no group differences in E/I balance were found (FND vs. controls), E/I balance in the aDMN was lower in children with functional seizures—a subgroup within the FND group. Pearson correlations found that increased arousal (indexed by higher heart rate) was associated with lower mI/Cr in the SMA and pDMN.

Conclusions

Our findings of multiple differences in neurometabolites in children with FND suggest dysfunction on multiple levels of the biological system: the neuron (lower NAA), the glial cell (lower mI), and inhibitory neurotransmission (lower GABA), as well as dysfunction in energy regulation in the subgroup with functional seizures.

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功能性神经紊乱儿童和青少年的神经代谢变化

目的采用体内磁共振波谱（MRS）研究功能性神经紊乱（FND）患儿在三个相关区域的神经代谢平衡：辅助运动区（SMA）、前缺省模式网络（aDMN）和后缺省模式网络（dDMN）。评估的代谢物包括神经元功能标志物 N-乙酰天冬氨酸（NAA）、胶质细胞标志物肌醇（mI）、膜标志物胆碱（Cho）、兴奋性神经传递标志物谷氨酸加谷氨酰胺（Glx）、抑制性神经传递标志物γ-氨基丁酸（GABA）和能量标志物肌酸（Cr）。此外，还研究了兴奋性（谷氨酸和谷氨酰胺）和抑制性（GABA）神经递质（E/I）平衡之间的关系。方法获得了 32 名混合型 FND 儿童（25 名女孩，7 名男孩，年龄为 10.00 至 16.08 岁）和 41 名健康对照组的 MRS 数据。结果在 SMA 中，FND 儿童的 NAA/Cr、mI/Cr（趋势水平）和 GABA/Cr 比率较低。在 aDMN 中，未发现代谢物比率的组间差异。在pDMN中，FND患儿的NAA/Cr和mI/Cr（趋势水平）比率较低。虽然在 E/I 平衡方面没有发现组间差异（FND 与对照组），但在 aDMN 中，功能性癫痫发作患儿（FND 组中的一个亚组）的 E/I 平衡较低。结论我们在 FND 儿童神经代谢物中发现的多种差异表明，生物系统的多个层面存在功能障碍：神经元（NAA 较低）、神经胶质细胞（mI 较低）和抑制性神经传递（GABA 较低），以及功能性癫痫发作亚组的能量调节功能障碍。

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来源期刊

Neuroimage-Clinical NEUROIMAGING-

CiteScore

7.50

自引率

4.80%

发文量

368

审稿时长

52 days

期刊介绍： NeuroImage: Clinical, a journal of diseases, disorders and syndromes involving the Nervous System, provides a vehicle for communicating important advances in the study of abnormal structure-function relationships of the human nervous system based on imaging. The focus of NeuroImage: Clinical is on defining changes to the brain associated with primary neurologic and psychiatric diseases and disorders of the nervous system as well as behavioral syndromes and developmental conditions. The main criterion for judging papers is the extent of scientific advancement in the understanding of the pathophysiologic mechanisms of diseases and disorders, in identification of functional models that link clinical signs and symptoms with brain function and in the creation of image based tools applicable to a broad range of clinical needs including diagnosis, monitoring and tracking of illness, predicting therapeutic response and development of new treatments. Papers dealing with structure and function in animal models will also be considered if they reveal mechanisms that can be readily translated to human conditions.