Dynamics of Motor System Excitability during Auditory Anticipation

The ability to anticipate complex sounds, like words in speech or the beat in music, is an important aspect of human perception. However, the changes of excitability in the motor system during auditory anticipation have not been characterized. Here, we applied singlepulse Transcranial Magnetic Stimulation (TMS) to the primary motor cortex to elicit motor evoked potentials (MEPs) from the first dorsal interosseous muscle, the amplitude of which indexes motor system excitability. Healthy right-handed participants (N = 20) underwent TMS stimulation during listening to regular (periodic) tone sequences at three rates (200ms, 550ms, and 900ms) and irregular tone sequences. We assessed MEP amplitudes over time, to test fluctuations in excitability during auditory anticipation (listening to regular sequences), and in the absence of auditory anticipation (listening to irregular sequences). We hypothesize that motor system excitability fluctuates at the rate of auditory stimulation, and peaks in anticipation of regular sounds. Results do not show evidence that motor system excitability fluctuates at the rate of regular or irregular auditory tones. Also, the results do not show evidence of an increase in excitability in anticipation of regular or irregular sounds. These results do not suggest synchronization of motor system excitability to regular sounds, informing our understanding of auditorymotor integration. FLUCTUATIONS OF MOTOR EXCITABILITY 3 Fluctuations of Motor Excitability by Isochronous Tone Sequences Listening to music is an activity most people partake in on a daily basis. There are also many situations where we are required to integrate auditory information into a motor response such as in dance or when playing a musical instrument. Auditory-motor integration is also involved in conversation, where music is thought to share some underlying mechanisms with language such as perception of temporal patterns (Fedorenko, Patel, Casasanto, Winawer, & Gibson, 2009). Some of the more evident mechanisms involved with auditory-motor integration are the perception of temporal patterns, and then the anticipation of future tones to coordinate synchronized movement. Perception of temporal patterns and anticipation are fundamental to normal hearing, speech, motor control, and music. This study aims to learn more about the underlying neural correlates behind the auditory-motor integration processes of perception and anticipation. Auditory-Motor Interactions We often see interactions between the auditory system and the motor system, such as when we listen to music, and are then able to tap along to it. There is a noticeable difference between tapping to an irregular beat, and tapping along to a beat with regular intervals (isochronous). Tapping to an irregular beat is often reactive, meaning that the movement is initiated after the stimulus. With isochronous tones, tones allow for anticipatory movements to tap at the same time as the stimulus. Brain areas found to be involved in movement initiation such as the basal ganglia and supplementary motor areas (SMAs) are also involved in motor prediction (Rao et al., 1997). Previous studies have looked at motor system activation with movement to tempos (length of temporal interval), such as the study by Keiichiro et al. (2002), which found greater motor activation for faster movements and tempos. As tempos increased FLUCTUATIONS OF MOTOR EXCITABILITY 4 from slow to fast, the relationship between movement and tone switched from synchronized to syncopated. This shows that anticipation effects are more likely in faster tempos, than very slow tempos. Imaging studies have shown that the motor system is activated while listening to rhythms, even when there is no action being performed, in particular the supplementary motor area (SMA), basal ganglia, cerebellum, and the premotor cortex (Grahn & Brett, 2007). The fMRI study by Grahn and Brett (2007) used rhythms to investigate which specific motor regions respond to the beat (regular, underlying pulse) in music. They demonstrated that motor areas are not only active in the production of music by movement, but also in the perception of music. These activations were found to be different in response to different stimuli, such as stronger activation for rhythms with strong regular accents. The strong regular accents can be compared to isochronous tones in their property of a constant interval between stimuli. Other imaging studies have looked at neural representations of temporal patterns in performing movement. A study by Fujioka et al. (2012) found that activity in auditory cortices and motor-related areas increases in anticipation to isochronous tones, and synchronizes to tone rates. Using human magnetoencephalography (MEG) in a task of listening to tones with no movement, the study found modulation of beta amplitude in synchronization with the tempo of sound stimulation in brain areas such as the sensorimotor cortex, inferior-frontal gyrus, SMAs, and cerebellum. These changes in beta amplitude represent periodic waves where the periods match the tempo; as the temporal intervals increased from 390ms, 585ms, to 780ms, a pattern is seen. There is a decrease in the excitability wave directly after a stimulus, and a subsequent rebound where excitability increases until the next stimulus in anticipation. The rebound slope in excitability depended on stimulus rate, suggesting anticipatory effects from an internalized FLUCTUATIONS OF MOTOR EXCITABILITY 5 temporal interval. The beta waves are made up of beta bands which are waves of electrical activity constant in the brain at a frequency of 25-30 Hz. Normally they are desynchronized, but it was found that they synchronize to auditory rhythms and create the characteristic beta waves. Beta waves were found to play a role in functional auditory-motor communication. The patterns of brain activity shown in the study by Fujioka et al. (2012) show synchronization of neuronal activity primarily in auditory systems. Due to auditory-motor interactions, there is strong evidence for a possibility for patterns of synchronization in motor systems, which may provide more insight into the mechanism for being able to synchronize movements with auditory stimuli. Transcranial Magnetic Stimulation Transcranial Magnetic Stimulation (TMS) is a method for inferring causal relationships between brain structures and their functions. TMS consists of non-invasive stimulation of the brain using a transient magnetic field generated by triggering an electrical current through the coil. When the TMS coil is placed over the primary motor cortex, it can produce motor evoked potentials (MEPs), which when large enough, can be seen as a muscle twitch. MEPs are measured used an electromyogram (EMG) machine. A methodological basis for using TMSelicited MEPs as a measure of motor excitability to auditory stimuli is the study by Watkins and Paus (2004). This study measured the increase in the excitability of the orofacial motor system during speech perception. They combined positron emission tomography (PET) with TMS to investigate motor areas activated during speech perception. They found increased excitability in the motor areas underlying speech production in response to speech perception with no speech output required. This proposed that there are motor areas which prime the motor system to respond to auditory stimuli. The study also showed a larger MEP to M1 stimulation of the face area which correlated with cerebral blood flow in the language area. This provides support for FLUCTUATIONS OF MOTOR EXCITABILITY 6 TMS not only being able to infer causal relationships between brain areas and their function, but also measuring changes in excitability as a function of differences in MEP amplitude, where the amplitude of MEPS is able to index real-time excitability in the motor system. Studies have shown that several motor areas respond to the presence of a regular beat. Since the premotor cortex and the SMA feed into the primary motor cortex (M1), we expect subthreshold excitability changes in M1. The changes in amplitude of an MEP can be used as a measure of changes in motor cortex excitability. Greater excitability of M1, due to greater activation in premotor cortex and SMA, results in larger MEPs. A study by Cameron, Stewart, Pearce, and Grube (2012) used metrically strong music, metrically weak music, or tone sequences. While listening to these sounds, TMS pulses were timed to fire either on the beat or before the beat. MEPs were measured in two leg muscles, the lateral gastrocnemius (LG) and the tibialis anterior (TA). They found that the amplitudes of the MEPs elicited by TMS stimulation depended on the metrically of the auditory stimuli and the position of the stimulus sequence at which the TMS was fired. Motor excitability showed temporal specificity, with a larger MEP on the beat and a smaller MEP off the beat in metrically strong tone sequences. The study also found larger MEPS for metrically strong than metrically weak music when TMS was fired on the beat. It is expected that there will be larger MEPS elicited on and before the beat or tone stimulus, compared to MEPs in positions further from the beat. There is evidence that TMS can been used to look at motor excitability in an on/off fashion, where there is a larger amplitude MEP on the beat than off the beat. There has been no past research in the time course of these changes in MEP amplitudes, or how motor excitability is changing over time. As mentioned earlier in the paper by Fujioka et al. (2012), activity over FLUCTUATIONS OF MOTOR EXCITABILITY 7 time was measured using fMRI, where there is evident synchronization to isochronous tones in the auditory system. Like the Fujioka paper, we will also be using isochronous tones as the auditory stimuli. The piece of information which is missing, is whether the motor system is also synchronizing in a similar way as the audito