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

Abstract

IntroductionDiabetes 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).MethodsA 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.ResultsIn 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.ConclusionsfMRI 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.

Sensorimotor and pain‐related alterations of the gray matter and white matter in Type 2 diabetic patients with peripheral neuropathy

“…We also observed altered WM in the corticospinal tract, internal capsule, spinothalamic tract, and thalamocortical projecting fibers. Physiologically, the somatosensory cortex, together with the thalamus, spinothalamic tract, and thalamocortical projecting fibers, make up an important component of the somatosensory pathway that governs the central integration and modulation of various peripheral sensations (Li et al, ). The precentral gyrus, paracentral lobule, caudate/putamen (known as the neostriatum), medial pallidum, thalamus, and corticospinal tract/internal capsule constitute a neural pathway that functions in coordinating voluntary movement.…”

“…Similarly, using magnetic resonance spectroscopy, Selvarajah et al () observed a significantly lower N ‐acetyl aspartate to creatine ratio in the thalamus of patients with DPN, suggesting thalamic neuronal dysfunction. One task‐based fMRI study (Li et al ) found that after several sessions applying thermal stimuli to the lower extremities, patients with DPN showed stronger brain activation in somatosensory pathways (e.g., in the right insula and left caudate nucleus) than healthy volunteers or diabetic patients without DPN. A multimodal study combining blood oxygenation level‐dependent and arterial spin labeling data (Segerdahl, Themistocleous, Fido, Bennett, & Tracey, ) reported altered ventrolateral periaqueductal gray (PAG) functional connectivity in patients suffering from painful DPN, and suggested this could be an index of brain‐based pain facilitation for painful DPN.…”

Thermal Perception Abnormalities Can Predict Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients

“…In the past decades, emerging evidence has indicated central nervous system involvement in DPN, and the association between cognitive impairment and DPN in diabetes had been reported [40][41][42]. It is suggested that dysregulation of glycemic control may lead to microvascular dysfunction in the blood-brain barrier, autoimmune damage to neurologic diseases, and changes in the synthesis, availability, or reuptake of neurotransmitters.…”

Central Nervous System Correlates of “Objective” Neuropathy in Alcohol Use Disorder

“…With respect to frontal regions, hereditary neuropathy has been associated with white matter disturbances in frontal regions (Wang et al, 2015); both chemotherapy-induced (Boland et al, 2014, Nudelman et al, 2016) and diabetic (Li et al, 2018, Manor et al, 2012) neuropathies show altered frontal activity. Furthermore, frontoparietal regions are relevant to encoding vibrotactile stimuli (Woolgar and Zopf, 2017) (see also, Godde et al, 2010, Wu et al, 2018, Fassihi et al, 2017, Ku et al, 2007, Soros et al., 2007).…”