Immediate effects of noxious and innocuous thermal stimulation on brain activation in patients with stroke

Sharon Chia-Ju Chen, Miao-Ju Hsu, Yu-Ting Kuo, Ruey-Tay Lin, Sing-Kai Lo, Jau-Hong Lin, Sharon Chia-Ju Chen, Miao-Ju Hsu, Yu-Ting Kuo, Ruey-Tay Lin, Sing-Kai Lo, Jau-Hong Lin

Abstract

Case-control studies have shown that noxious thermal stimulation (TS) can improve arm function in patients with stroke. However, the neural mechanisms underlying this improvement are largely unknown. We explored functional neural activation due to noxious and innocuous TS intervention applied to the paretic arm of patients with stroke. Sixteen participants with unilateral cortical infarctions were allocated to one of two groups: noxious TS (8 patients; temperature combination: hot pain 46°C to 47°C, cold pain 7°C-8°C) or innocuous TS (n = 8; temperature combination: hot 40°C-41°C, cold 20°C-21°C). All subjects underwent fMRI scanning before and after 30 min TS intervention and performed a finger tapping task with the affected hand. Immediate brain activation effects were assessed according to thermal type (noxious vs. innocuous TS) and time (pre-TS vs post-TS). Regions activated by noxious TS relative to innocuous TS (P < .05, adjusted for multiple comparisons) were related to motor performance and sensory function in the bilateral primary somatosensory cortices, anterior cingulate cortex, insula, thalamus, hippocampus and unilateral primary motor cortex, secondary somatosensory cortex at the contralateral side of lesion, and unilateral supplementary motor area at the ipsilateral side of lesion. Greater activation responses were observed in the side contralateral to the lesion, suggesting a significant intervention effect. Our preliminary findings suggest that noxious TS may induce neuroplastic changes unconstrained to the local area.Trial registration: NCT01418404.

Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of study protocol. This protocol includes four parts: (1) clinical assessment of motor performance and function using UE-Br, MAS, and BI; (2) fMRI scan before TS intervention for the finger tapping task; (3) TS intervention for the thermal application at the given temperature combination; and (4) fMRI scan after TS intervention for the finger tapping task. A, finger tapping; R, rest; H, hot; C, cold. BI = Barthel index, MAS = modified Ashworth scale, UE-Br = upper extremity Brunnstrom recovery stage.
Figure 2
Figure 2
Activation map after two-way ANOVA. Variance analysis consisted of two factors (TS_event and TS_type) and a controlled covariate (time since stroke onset). (A) The main effect of TS_event was determined by contrasting pre- and post-TS between the 2 TS groups. (B) The main effect of TS_type was tested by contrasting nTS and inTS over two sessions. (C) The interaction effect of TS_event and TS_type was examined to determine whether TS interventions were effective due to the thermal combination. Clusters were selected according to a P value = .05 and the extra constraint of cluster size (P < .05). inTS = innocuous TS, nTS = noxious TS.
Figure 3
Figure 3
Scatterplot and histogram over the three effects of two-way ANOVA. (A)–(C) Scatterplots of post-TS vs pre-TS as the function of signal change compared to the basement for the main effect of TS_event, main effect of TS_type, and their interactive effect. ×, inTS; ○, nTS. (D)–(F) Histograms of 2 temperature combinations of TS for the 3 effects. The dashed line shows the location measure. inTS = innocuous TS, nTS = noxious TS.

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