Theoretical predication of temperature effects at 20 ℃-42 ℃ on adaptive processes in simulated amyotrophic lateral sclerosis

Abstract

Strength-duration time constants, rheobase currents, and recovery cycles allow the nerve adaptive processes to single or pairs of depolarizing stimuli to be assessed. This study investigates the temperature dependence of these excitability indices of human motor nerve fibers with one of three increasingly-severe type of amyotrophic lateral sclerosis pathology, referred to as ALS1, ALS2, and ALS3. The temperature dependence of the excitability indices was investigated during hypothermia (≤25 ℃), hyperthermia (≥40 ℃), and in the physiological temperature range (30-37 ℃). Numerical solutions were computed using a temperature-dependent multi-layered model. Results showed the following trends: (i) while the strength-duration time constants gradually decreased with a temperature increase from 20 ℃ to 42 ℃, they were longer in the three ALS cases than those of the normal case; (ii) the reciprocally dependent strength-duration time constants and rheobase currents were more sensitive to hyperthermia, especially at 42oC, than at temperatures across the physiological range of 30-37 ℃; (iii) the shape of temperature-dependent recovery cycles was similar for both the normal and ALS1 cases; (iv) in the ALS2 case, each test stimulus applied at the end of 100 ms recovery cycle failed to initiate a second action potential during hypothermia at 20 ℃; and (v) in the ALS3 case during hypothermia, hyperthermia and across the physiological temperature range, each test stimulus applied beyond a given conditioning-test interval was blocked. This blockage was a result of the spontaneous action potential generation caused by the conditioning (first) stimulus. The changes obtained for the temperature-dependent strength-duration time constants, rheobase currents, and recovery cycles reflect nodal and internodal ion channel dysfunctions in the three amyotrophic lateral sclerosis cases. It is proposed that these excitability indices can be applied clinically as specific indicators for amyotrophic lateral sclerosis motor neuron disease.

Keywords

• |temperature|myelinated axons|als|strength-duration time constant|rheobase current|recovery cycle|computational neuroscience