Beta oscillations, timing, and stuttering

It has been proposed that one of the causes of stuttering is a deficit in brain timing networks (Alm, 2004; Ludlow and Loucks, 2004; Etchell et al., 2014). In stuttering, there appear to be structural and functional abnormalities in brain areas (such as the basal ganglia and supplementary motor area) that provide the substrate for internal timing (the ability to time movements without an external cue; Alm, 2010; Etchell et al., 2014). There are also structural and functional abnormalities in areas (such the cerebellum and premotor cortex) linked to external timing (the ability to time movements with an external cue), which are thought to represent compensatory plastic changes in stuttering (De Nil et al., 2008; Watkins et al., 2008; Lu et al., 2012). Currently, it remains unknown whether such deficits in internal timing mechanisms in stuttering may be manifest in any measurable neural marker. One possible candidate is oscillatory activity in the beta frequency band. The beta band and internal timing Neural oscillations in the beta frequency band (15–30 Hz) are classically related to motor activity (see Kilavik et al., 2013 for review): decreasing in power prior to movement and then rebounding once the movement has finished (Pfurtscheller, 1981). Recently there has been considerable interest in the role beta oscillations might play in the brain's ability to represent temporal information because the observed associations between beta band power modulations and the timing of auditory beats (Arnal, 2012; Arnal et al., 2014). These investigations are only in their infancy but have already produced some intriguing observations. For example, Fujioka et al. (2012) used magnetoencephalography (MEG) to measure beta oscillations while subjects passively listened to sounds at regular (390, 585, and 780 ms) and irregular intervals (varying between 390 and 780 ms). Whereas the slope of the decrease in beta power after the onset of sounds was identical across conditions, the rising slope of beta power was maximal prior to the onset of the next expected sound for the regular but not the irregular conditions. The authors concluded that modulations in beta oscillatory activity represented an internalization of predictable intervals between sounds. More recently, Cirelli et al. (2014) replicated these results in an electroencephalography (EEG) study showing a similar pattern of anticipatory beta activity across multiple temporal intervals. Arnal (2012) contends that the beta modulation observed in the Fujioka et al. (2012) study may reflect the motor system generating efference copy signals at the tempo of stimulation. Empirical support for this prediction comes from recent work by Arnal et al. (2014) who showed that correctly judging whether or not a target tone had been delayed in time was associated with greater cortical beta power before the target tone. There is good evidence to suggest that beta oscillations in the cortex reflect oscillatory activity originating in subcortical structures. Much of our knowledge of beta oscillatory activity in subcortical regions comes from studies in animals or humans with deep brain implants to treat Parkinson's disease (e.g., Levy et al., 2000) because it is not routinely possible to make such invasive recordings in healthy adults. Nevertheless, the pattern of beta desynchronization and resynchronization observed in the cortex during and subsequent to movement can also be observed in the basal ganglia of humans (Brittain and Brown, 2014) and macaques (Courtemanche et al., 2003). MEG experiments indicate the basal ganglia and cortical regions are connected via functional loops (see Jenkinson and Brown, 2011) further suggesting there is a relationship between beta oscillations at different levels of the brain. Consistent with this line of reasoning, Klostermann et al. (2007) reported that in humans, beta band power recorded from the basal ganglia (using depth electrodes) and the scalp (using EEG) during a cued choice reaction time task was correlated in phase and amplitude (measured by magnitude-squared coherence). Likewise, it has been demonstrated experimentally that the cortex and the subthalamic nucleus exhibit beta band amplitude and phase coherence, and it is hypothesized that such an interaction relies on the striatum (Hirschmann et al., 2011). The relationship between cortical and subcortical beta oscillations, together with the fact that beta oscillations in the motor and auditory cortices are related to internal timing (Fujioka et al., 2012), suggests that beta oscillations in the striatum might also be related to internal timing. Accordingly, Bartolo et al. (2014) examined the role of beta oscillations in timing by recording local field potentials from microelectrodes implanted in the putamen of healthy macaques during a synchronization and continuation task. This task requires that the macaques tap in time with a beat (the synchronization phase) and that they continue to tap once the beat has been removed (the continuation phase). Whereas the synchronization phase is an index of external timing (due to the presence of an external stimulus), the continuation phase is an index of internal timing (due to the absence of an external stimulus; Teki, 2014). The main finding from the Bartolo et al. (2014) study was that beta activity was strongly biased to the continuation phase as opposed to the synchronization phase of the task indicating that putamenal beta oscillations are tuned to internal rather than external timing of movement. There is evidence that beta oscillations can be recorded from the striatum during self-paced movements in humans. Intracranial recordings from the putamen of an epileptic patient showed that beta power peaks near the onset of self-paced bimanual finger extensions (Sochurkova and Rektor, 2003). While not focusing directly on beta oscillations, there is evidence from functional neuroimaging to implicate the striatum in internal timing in healthy adults. For example, Grahn and Rowe (2013) demonstrated that the putamen responds to the detection of regularity rather than the detection of beats, suggesting that it is involved in internally paced movement rather than simply the detection of the presence or absence of a beat. The basal ganglia are also more active during subjective judgments of temporal intervals relative to judgments of externally timed intervals (Coull et al., 2013) and the putamen shows greater activity during continuation tapping but not synchronization tapping as compared to rest (Rao et al., 1997). Interestingly, individuals with bilateral lesions to the basal ganglia perform poorly on the continuation but not the synchronization phase of a rhythmic tapping task (Coslett et al., 2010). Such evidence suggests that the putamen is essential for internal timing.