Imaging signatures of altered brain responses in small-fiber neuropathy: reduced functional connectivity of the limbic system after peripheral nerve degeneration.
Small-fiber neuropathy (SFN) is hallmarked by degeneration of small unmyelinated peripheral nerve fibers in the skin. Traditionally, it has been considered as a pure disorder of the peripheral nervous system. Nevertheless, previous work found that dysfunction of skin nerves led to abnormal recruitment of pain-related regions, suggesting that the brain may be affected in SFN. This report combined structural and functional magnetic resonance imaging to identify structural and functional changes in the brain of 19 patients with SFN compared with 17 healthy controls. We applied tensor-based morphometry to detect brain structural alterations in SFN. Greater volume reduction in pain-processing regions, particularly the bilateral anterior cingulate cortices (ACCs), was associated with greater depletion of intraepidermal nerve fibers, a pathological biomarker of skin nerve degeneration. Based on the hypothesis that structural alterations in the pain-processing regions might impair their functional connectivity, we further applied psychophysiological interaction analysis to assess functional connectivity of the ACCs during noxious heat stimulation. There was significant reduction in functional connectivity from the ACCs to the limbic areas (the parahippocampal gyrus and the posterior cingulate cortex), pain-processing area (the insula), and visuospatial areas (the cuneus). Moreover, the degree of reduction in functional connectivity for the ACC to the amygdala and the precuneus was linearly correlated with the severity of intraepidermal nerve fiber depletion. Our findings suggest that SFN is not a pure peripheral nervous system disorder. The pain-related brain networks tend to break into functionally independent components, with severity linked to the degree of skin nerve degeneration.
Department of Medicine, National Taiwan University, Taipei, Taiwan Department of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan Departments of Neurology and Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
Paul-Chen
PC
Hsieh
Ming-Tsung
MT
Tseng
Chi-Chao
CC
Chao
Yea-Huey
YH
Lin
Wen-Yih I
WI
Tseng
Kuan-Hong
KH
Liu
Ming-Chang
MC
Chiang
Sung-Tsang
ST
Hsieh
D000328:Adult; D000368:Aged; D003952:Diagnostic Imaging; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008032:Limbic System / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D009412:Nerve Fibers / Q000473:pathology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology*; D010146:Pain / Q000473:pathology* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000473:pathology / Q000503:physiopathology*; D012867:Skin / Q000294:innervation