Functional magnetic resonance imaging reveals differences in brain activation in response to thermal stimuli in diabetic patients with and without diabetic peripheral neuropathy

PLoS One. 2018 Jan 5;13(1):e0190699. doi: 10.1371/journal.pone.0190699. eCollection 2018.

Abstract

Introduction: Diabetes affects both the peripheral and central nervous systems. The aim of this study was to explore the changes in brain activity in response to thermal stimuli in diabetic patients with and without diabetic peripheral neuropathy (DPN) using functional magnetic resonance imaging (fMRI).

Methods: A total of 36 right-handed volunteers were enrolled: eight patients with Type-2 diabetes mellitus and DPN, 13 patients with Type-2 diabetes mellitus lacking DPN (NDPN patients), and 15 healthy volunteers (HV). Blood oxygenation level-dependent baseline scans were performed, first without any stimuli, and then with four sessions of thermal stimuli (0, 10, 34, and 44°C, in a random order) applied to the lateral side of the right lower extremity. There was a 240-s rest interval between each thermal stimulation. Each stimulation session consisted of three cycles of 30 s of stimulation followed by 30 s of rest. After each stimuli session, the participant rated pain and itch perception on a visual analog scale. The fMRI data series were analyzed by using Statistical Parametric Mapping 8 and Data Processing Assistant for Resting-State fMRI.

Results: In response to temperature stimuli, DPN patients showed stronger activation than HV and NDPN patients, not only in brain areas that participate in somatosensory pathways (right insula, left caudate nucleus, frontal gyrus, and cingulate cortex), but also in the cognition-related cerebral areas (right temporal lobe, left hippocampus, and left fusiform gyrus). Activation of vermis 1-3 was greater in NDPN patients than in HV in response to 0°C stimulation.

Conclusions: fMRI may be useful for the early detection of central nervous system impairment caused by DPN. Our results indicate that central nervous system impairment related to diabetic neuropathy may not be limited to motion- and sensation-related cortical regions. Cognition-associated cerebral regions such as the hippocampus and fusiform gyrus are also affected by functional changes caused by DPN. This suggests that fMRI can detect the early stages of cognitive impairment in DPN patients before the symptoms become clinically significant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain / diagnostic imaging
  • Brain / physiology*
  • Brain / physiopathology*
  • Brain Mapping
  • Cold Temperature
  • Diabetic Neuropathies / diagnostic imaging*
  • Diabetic Neuropathies / physiopathology*
  • Early Diagnosis
  • Female
  • Hot Temperature
  • Humans
  • Lower Extremity / physiology
  • Lower Extremity / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Oxygen / blood
  • Pain / physiopathology
  • Perception / physiology*
  • Physical Stimulation
  • Pruritus / physiopathology
  • Rest
  • Thermosensing / physiology*

Substances

  • Oxygen

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant number: 81271239 and 91632113, CM), IBMS/CAMS Dean’s Fund (2011RC01, CM), the PUMC Youth Foundation (3332015023, JL), CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-1-004, CM, XW), and Shanghai Brain-Intelligence Project from STCSM (16JC1420502, CM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.