Myoclonic Twitching and Sleep-Dependent Plasticity in the Developing Sensorimotor System

Abstract

As bodies grow and change throughout early development and across the lifespan, animals must develop, refine, and maintain accurate sensorimotor maps. Here we review evidence that myoclonic twitches—brief and discrete contractions of the muscles, occurring exclusively during REM (or active) sleep, that result in jerks of the limbs—help animals map their ever-changing bodies by activating skeletal muscles to produce corresponding sensory feedback, or reafference. First, we highlight the spatiotemporal characteristics of twitches. Second, we review findings in infant rats regarding the multitude of brain areas that are activated by twitches during sleep. Third, we discuss evidence demonstrating that the sensorimotor processing of twitches is different from that of wake movements; this state-related difference in sensorimotor processing provides perhaps the strongest evidence yet that twitches are uniquely suited to drive certain aspects of sensorimotor development. Finally, we suggest that twitching may help inform our understanding of neurodevelopmental disorders, perhaps even providing opportunities for their early detection and treatment.

It’s not you, it’s me: Corollary discharge in precerebellar nuclei of sleeping infant rats

“…8 Second, the remaining LRN units (12/27 units, 44%) exhibited broader twitch-related 9 activity profiles consisting of a peak in activity around twitch onset (+10 ms) and/or a peak 10 with a latency of >10 ms ( Figure 3G, right). The latter peak is what is expected from a 11 short-latency reafferent responses (Tiriac and Blumberg, 2016;Tiriac et al, 2014). Indeed, 12 6 of these 12 units also responded to exafferent stimulation of either the forelimb or 13 hindlimb with an average latency of 40 ms ( Figure 3H Zeeuw et al, 1998;Saint-Cyr and Courville, 1981;Lakke, 1997;Onodera and Hicks, 2009;19 Zuk et al, 1983) and are therefore directly involved in the generation of movements 20 (Fukushima, 1991;Morris et al, 2015;Onodera and Hicks, 1996;Williams et al, 2014).…”

“…19 With respect to (b), although the IO can receive short-latency reafferent signals 20 (Gellman et al, 1983;Sedgwick and Williams, 1967), it is unlikely that reafference can 21 account for the short-latency peaks observed here. Consider that for the structures in 22 which we have seen clear evidence of twitch-related reafference (e.g., ECN), we have also 23 seen clear evidence of exafferent responses (Tiriac et al, 2014;Tiriac and Blumberg, 1 2016). In contrast, of the IO units that exhibited sharp peaks with a latency of +10 ms, 2 none responded to exafferent stimulation.…”

“…6 It has been suggested that the infant brain does not distinguish between these two sources 7 of input and that twitch-related reafference serves merely as a "proxy" for exafferent 8 stimulation (Akhmetshina et al, 2016;McVea et al, 2016). This suggestion rests in part 9 on the observation that both forms of stimulation, despite their very different origins, trigger 10 similar patterns of cortical activity (Akhmetshina et al, 2016;Tiriac et al, 2012;Yang et 11 al., 2013). Thus, with our finding that CD accompanies the production of twitches, it is now 12 clear that there exists a mechanism with which the infant brain can distinguish self-13 generated from other-generated movements; the ability to make this distinction is thought 14 to rely in part on the cerebellum (Blakemore et al, 2000;Wolpert et al, 1998).…”

Theta Oscillations during Active Sleep Synchronize the Developing Rubro-Hippocampal Sensorimotor Network

“…Bursts of oscillatory activity can contribute to a variety of developmental processes, including synapse formation, cell differentiation and migration [27], and map formation and refinement [25]. Importantly, the close temporal association between twitching and brief bursts of cortical [7,31] and hippocampal [30] activity inspired the hypothesis that twitch-related reafference contributes to the development of these forebrain networks [6,7,9]. The present findings extend these ideas to brainstem structures like the RN [10].…”

“…Of the two primary sub-states of sleep, active sleep (AS, or REM sleep) occurs at its highest rates in the perinatal period and has long been considered a critical contributor to early brain development [4,5]. In addition, myoclonic twitching is a prominent phasic component of AS that triggers patterned neural activity throughout the neuraxis and, by doing so, can contribute to the experience-dependent development of sensorimotor networks [6–9]. …”