Invited review article
The unique neuromodulation using water immersion
2021 年 21 巻 1 号 p. 2-11
詳細
2021 年 21 巻 1 号 p. 2-11
The acquisition and consolidation of motor skills are essential in our lives. Neural plasticity of the primary motor cortex (M1) is strongly involved in the consolidation of motor skills. Recent studies have shown that the M1 plasticity can be altered by prior neural activity, termed ‘Metaplasticity’. Consequently, if we can demonstrate effective interventions that enhance M1 plasticity, we might propose new methodologies to promote the consolidation of motor skills. Although a variety of interventions have been reported, our research group has focused on a unique intervention: water immersion (WI). Our research has shown several possibilities that WI can be a neuromodulation of increasing M1 plasticity by altering the activity of sensory-motor-related areas. Herein, we briefly summarised previous research on the consolidation of motor skills through motor learning and M1 plasticity and introduced unique neuromodulation using WI, which temporarily increased M1 plasticity, including previous and present studies in our research group.
New motor skills can be acquired through repeated motor learning. However, not everyone achieves the desired effect in the same manner. Alternatively, there is vast individual variability in motor skill acquisition through motor learning. This individual variability is an important concern in the field of physical education and rehabilitation, where ‘learners who want to acquire motor skills’ and ‘instructors who want to help learners acquire motor skills’ face each other.
Motor learning proceeds through fast learning, slow learning, and retention [1]. It is well known that a wide range of brain regions, such as the prefrontal cortex, medial temporal lobe, sensorimotor cortex, cerebellum, and striatum, are involved in this process depending on the stage of learning. In the early stages of learning, the prefrontal cortex and medial temporal lobe are prominent and are involved in primary working memory, control of attentional resources, and monitoring of behaviour. As learning progresses, the sensorimotor cortex, parietal cortex, cerebellum, and striatum become more active and are responsible for consolidation and long-term memory.
In particular, the primary motor cortex plays an important role in the consolidation of motor skills. When the excitability of the primary motor cortex is reduced by repetitive transcranial magnetic stimulation (rTMS) after motor learning, the learning effect disappears [2]. Additionally, a study that examined the relationship between changes in the excitability of the primary motor cortex before and after motor learning and the consolidation of motor skills reported that the greater the increase in M1 excitability by motor learning, the higher the consolidation [3]. These results suggest that M1 plasticity is involved in the consolidation of motor skills through motor learning.
In this review, we briefly summarised previous research on the consolidation of motor skills through motor learning and M1 plasticity and introduced unique neuromodulation using water immersion (WI), which temporarily increased M1 plasticity, including previous and present studies in our research group.
It is known that the time elapsed after motor learning is important for the consolidation of motor skills. Brashers-Krug, et al. [4] showed that consolidation of motor skills was disrupted when a motor task was learned immediately after the first motor learning. Conversely, there was no disruption if 4 h elapsed between learning the two motor skills. In a previous review, Ungerleider, et al. [5] pointed out that the consolidation of motor skills requires more than 6 h, and also described that this is involved in the slow and dynamic plastic changes in M1 through motor learning. The involvement of plastic changes in M1 in the consolidation of motor skills has been investigated in studies using non-invasive brain stimulation (NIBS). For example, it has been reported that the consolidation of motor skills is inhibited by rTMS, which reduces M1 excitability [6]. Furthermore, Richardson, et al. [7] showed that suppression of M1 excitability after learning reduced motor skills and motor learning performance the following day. These studies indicate that plastic changes in M1 play an important role in the consolidation of motor skills through motor learning.
Interestingly, M1 plasticity is known to be modulated not only by various intercellular signalling molecules directly but also by neural activity at one point in time. The latter is neural activity at one point in time that can change neural plasticity, termed ‘metaplasticity’ [8]. This shows that the threshold of activity-dependent synaptic plasticity is not always constant, but varies dynamically depending on the prior activity of the postsynaptic neuron. If the prior postsynaptic neuron activity is high or low, the threshold of synaptic plasticity (θm) is reduced or increased when the activity of the presynaptic neuron is high or low. It has been reported that this priming effect occurs not only regardless of whether the prior neural activity itself induces plastic changes [9], but also by prior stimulation of other areas with strong neural contacts to M1 [10,11]. To date, we have proposed several neuromodulations that enhance M1 plasticity by prior neural activity. We introduced unique neuromodulation using WI.
Before discussing the specificity of WI as neuromodulation, we describe the characteristics of WI for physiological and neurophysiological aspects in humans. Numerous previous studies have reported that WI induces several physiological changes, including decreased heart rate and increased cardiac output [12], unloaded anti-gravity muscle activity during upright standing [13], decreased noradrenaline and adrenaline concentrations [14] and increased parasympathetic nervous activity [14,15]. However, the neurophysiological effect of WI remains unclear.
Humans receive several somatosensory stimuli from water through sensory receptors in the WI environment, such as tactile, pressure, thermal, and proprioceptive inputs. The first study that examined WI-induced neural activity was focused on the somatosensory and motor-related cortex during WI as there is no evidence of whether WI activates neural activity in the cerebral cortex. In this study, functional near-infrared spectroscopy (fNIRS) was used to measure the haemoglobin concentration by measuring the absorbance of near-infrared light of different wavelengths emitted from the scalp. Based on the principle of neurovascular coupling, fNIRS can indirectly evaluate neural activity by changing the oxygenated haemoglobin (oxyHb) concentration. OxyHb levels were dramatically increased in the somatosensory and motor-related areas of the cerebral cortex (Figure 1) [16,17]. However, we had to evaluate somatosensory neural activity during WI directly as these results might be attributed to increased cardiac output and cerebral blood flow [18]. To resolve this problem, electroencephalography was used to evaluate somatosensory cortical activity during WI. We examined the effect of WI on short-latency somatosensory evoked potentials (SEPs) elicited by median nerve stimuli, which can evaluate excitability in S1 (Figure 2) [19]. In line with our hypothesis, SEPs significantly decreased during WI compared to those on land, and WI could induce neural activity in S1. Additionally, we examined whether WI affects neural activity not only in S1 but also in M1 as S1 has strong neural connectivity with M1. To test the M1 excitability during WI, single- and paired-pulse TMS methods were used. These methodologies can evaluate corticospinal excitability and intracortical inhibition and facilitation, respectively (see review for detailed methodology and mechanism [20]). We found that WI significantly decreased the activation of inhibitory circuits in the sensorimotor integration process (Figure 3) [21]. Since this inhibitory circuit is reported to be modulated by cholinergic and GABAergic neural activity (see review for Ziemann, et al. [22]), decreased inhibitory activation during WI could be explained by decreased cholinergic neural activity and/or GABAergic activity. In summary, WI can induce neural activity in the somatosensory and motor cortex due to several somatosensory inputs from water.
Since prior neural activity modulates neural plasticity [8], we examined whether WI would alter M1 plasticity using the NIBS protocol. A variety of NIBS protocols can be used to explore the neurophysiological mechanisms underlying synaptic plasticity in the human cortex. Paired associative stimulation (PAS) [23] involves applying an electrical stimulus to the median nerve at the wrist followed by TMS over the M1 25 ms later (PAS25). Repeated pairings at this interval increase corticospinal excitability for 30–60 min, as measured by motor evoked potentials. Previous studies have reported that PAS25-induced plasticity modulates the history of prior neural activity, such as NIBS [24,25] and motor learning [26]. As described above, WI is a simple way to modulate cortical activity in the sensorimotor system [19,21]. Our previous study showed that WI decreased inhibitory neural activity that arises from cholinergic and GABAergic modulation [21] and a follow-up study revealed that this inhibitory circuit temporarily increased after WI (Figure 4) [27]. We then tested the hypothesis that the sequential neural activities induced by WI would alter M1 plasticity. Consequently, prior WI significantly enhanced PAS25-induced plasticity without high inter-individual variability (Figure 5) [27]. We speculated that a homeostatic response of the cholinergic inhibitory circuit between the sensory and motor areas occurs after WI, which would facilitate the PAS25 response. Cholinergic activity is not only a modulator of arousal level but also a powerful regulator of synaptic plasticity. In animal studies, cholinergic blockade reduced neural plasticity in the hippocampus, piriform cortex, and neocortex [28,29,30], and in humans, use-dependent plasticity in the motor cortex is facilitated by an acetylcholinesterase inhibitor and blocked by a cholinergic antagonist [31,32]. Additionally, Kuo, et al. [33] reported that acetylcholine enhanced the synapse-specific cortical excitability increase induced by PAS25 and consolidated the PAS10-induced reduction in motor cortical excitability. They described that cholinergic nervous activity improved the efficacy of PAS by (1) enhancing the signal-to-noise ratio; thereby, facilitating the processing of meaningful (associative) inputs and (2) suppressing non-meaningful/irrelevant asynchronous inputs. Therefore, the enhanced plasticity following WI may be related to increased cholinergic activity associated with WI-induced homeostatic aftereffects.
Although prior WI has been shown to enhance M1 plasticity, WI is accompanied by tedious activities such as changing clothes and drying bodies. To incorporate this into rehabilitation, it must be simplified to perform. Recently, we found that partial WI (only forearm) with ‘water flow (WF) stimulation’ significantly altered the inhibitory circuit that was modulated by GABAergic neurons in M1 (Figure 6) [34]. WF stimulation is a unique peripheral stimulation in which 40 L of water per minute is presented to the hand using a custom-made device. This stimulation induced skin and muscle vibrations ranging from 15 Hz to 150 Hz on the target muscle. The partial WI of the forearm alone does not change the neural activity of M1 because there is not enough sensory input; however, adding WF stimulation can increase the excitability of M1. Moreover, WF stimulation increased M1 excitability due to neural disinhibition not only at rest but also during movement (Figure 7). Considering that neural disinhibition is a precursor for plastic alteration, WF stimulation will be an available methodology for the enhancement of M1 plasticity.
In this review, we summarised the somatosensory and motor cortical activity associated with WI and its applicability for enhancing M1 plasticity. To date, whether WI promotes behavioural adaptation through learning processes such as motor learning and other adaptations has been unclear, although WI seems to enhance M1 plasticity due to alteration of the inhibitory circuit induced by WI. Additionally, since previous studies reported that water temperature and depth influenced cerebral blood flow during WI, further studies examining optimal conditions of WI for neural and behavioural plastic alteration are needed.
This work was supported by a Grant-in-Aid for Young Scientists (B) 23700687, Challenging Exploratory Research 15K12712, Challenging Research (Exploratory) 19K21793, Scientific Research (B) 18H03134 from the Japan Society for the Promotion of Science.
