Paul F. Sowman

Multimodal functional imaging of motor imagery using a novel paradigm

Neuroimaging studies have shown that the neural mechanisms of motor imagery (MI) overlap substantially with the mechanisms of motor execution (ME). Surprisingly, however, the role of several regions of the motor circuitry in MI remains controversial, a variability that may be due to differences in neuroimaging techniques, MI training, instruction types, or tasks used to evoke MI. The objectives of this study were twofold: (i) to design a novel task that reliably invokes MI, provides a reliable behavioral measure of MI performance, and is transferable across imaging modalities; and (ii) to measure the common and differential activations for MI and ME with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). We present a task in which it is difficult to give accurate responses without the use of either motor execution or motor imagery. The behavioral results demonstrate that participants performed similarly on the task when they imagined vs. executed movements and this performance did not change over time. The fMRI results show a spatial overlap of MI and ME in a number of motor and premotor areas, sensory cortices, cerebellum, inferior frontal gyrus, and ventrolateral thalamus. MI uniquely engaged bilateral occipital areas, left parahippocampus, and other temporal and frontal areas, whereas ME yielded unique activity in motor and sensory areas, cerebellum, precuneus, and putamen. The MEG results show a robust event-related beta band desynchronization in the proximity of primary motor and premotor cortices during both ME and MI. Together, these results further elucidate the neural circuitry of MI and show that our task robustly and reliably invokes motor imagery, and thus may prove useful for interrogating the functional status of the motor circuitry in patients with motor disorders.

Behavioral and multimodal neuroimaging evidence for a deficit in brain timing networks in stuttering: a hypothesis and theory

The fluent production of speech requires accurately timed movements. In this article, we propose that a deficit in brain timing networks is one of the core neurophysiological deficits in stuttering. We first discuss the experimental evidence supporting the involvement of the basal ganglia and supplementary motor area (SMA) in stuttering and the involvement of the cerebellum as a possible mechanism for compensating for the neural deficits that underlie stuttering. Next, we outline the involvement of the right inferior frontal gyrus (IFG) as another putative compensatory locus in stuttering and suggest a role for this structure in an expanded core timing-network. Subsequently, we review behavioral studies of timing in people who stutter and examine their behavioral performance as compared to people who do not stutter. Finally, we highlight challenges to existing research and provide avenues for future research with specific hypotheses.

Self-initiation and temporal cueing of monaural tones reduce the auditory N1 and P2

Event-related potentials (ERPs) to tones that are self-initiated are reduced in their magnitude in comparison with ERPs to tones that are externally generated. This phenomenon has been taken as evidence for an efference copy of the motor command acting to suppress the sensory response. However, self-initiation provides a strong temporal cue for the stimulus which might also contribute to the ERP suppression for self-initiated tones. The current experiment sought to investigate the suppression of monaural tones by temporal cueing and also whether the addition of self-initiation enhanced this suppression. Lastly, the experiment sought to investigate the lateralisation of the ERP suppression via presenting these monaural tones to each ear respectively. We examined source waveforms extracted from the lateralised auditory cortices and measured the modulation of the N1 and P2 components by cueing and self-initiation. Self-initiation significantly reduced the amplitude of the N1 component. Temporal cueing without self-initiation significantly reduced the P2 component. There were no significant differences in the amplitude of either the N1 or the P2 between self-initiation and temporal cuing. There was a significant lateralisation effect on the N1—it being significantly larger contralateral to the ear of stimulation. There was no interaction between lateralisation and side of the temporal cue or side of self-initiation suggesting that the effects of self-initiation and temporal cuing are equal bilaterally. We conclude that a significant proportion of ERP suppression by self-initiation is a result of inherent temporal cueing.

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 brains 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 Parkinsons 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.

Abnormal time course of low beta modulation in non-fluent preschool children: A magnetoencephalographic study of rhythm tracking.

Stuttering is a disorder of speech affecting millions of people around the world. Whilst the exact aetiology of stuttering remains unknown, it has been hypothesised that it is a disorder of the neural mechanisms that support speech timing. In this article, we used magnetoencephalography (MEG) to examine activity from auditory regions of the brain in stuttering and non-stuttering children aged 3-9years. For typically developing children, we found that MEG oscillations in the beta band responded to rhythmic sounds with a peak near the time of stimulus onset. In contrast, stuttering children showed an opposite phase of beta band envelope, with a trough of activity at stimulus onset. These results suggest that stuttering may result from abnormalities in predictive brain responses which are reflected in abnormal entrainment of the beta band envelope to rhythmic sounds.

Lateralization of Brain Activation in Fluent and Non-Fluent Preschool Children: A Magnetoencephalographic Study of Picture-Naming

The neural causes of stuttering remain unknown. One explanation comes from neuroimaging studies that have reported abnormal lateralization of activation in the brains of people who stutter. However, these findings are generally based on data from adults with a long history of stuttering, raising the possibility that the observed lateralization anomalies are compensatory rather than causal. The current study investigated lateralization of brain activity in language-related regions of interest in young children soon after the onset of stuttering. We tested 24 preschool-aged children, half of whom had a positive diagnosis of stuttering. All children participated in a picture-naming experiment whilst their brain activity was recorded by magnetoencephalography. Source analysis performed during an epoch prior to speech onset was used to assess lateralized activation in three regions of interest. Activation was significantly lateralized to the left hemisphere in both groups and not different between groups. This study shows for the first time that significant speech preparatory brain activation can be identified in young children during picture-naming and supports the contention that, in stutterers, aberrant lateralization of brain function may be the result of neuroplastic adaptation that occurs as the condition becomes chronic.

Diffuse noxious inhibitory control evoked by tonic craniofacial pain in humans

Tonic pain in one body segment can inhibit the perception of pain in another body segment. This phenomenon is mediated by diffuse noxious inhibitory controls (DNIC), and its efficacy in craniofacial regions is investigated in this study. A compressive device that evoked a tonic, moderate/severe, headache‐like, conditioning pain (∼8/10 on a visual analogue scale) was applied for 15 min. Eleven males participated in the study. Pressure pain threshold (PPT) and pressure pain tolerance (PPTol) at multiple heterosegmental body sites (right masseter, splenius capitis, second intermediate phalange, brachioradialis and tibialis anterior) were measured before, during and at multiple time points (5, 20 and 35 min) after the termination of the conditioning pain. PPTs and PPTols were compared within participants across two experimental sessions; one that included painful conditioning stimulation, and a separate control session on a different day. Painful conditioning increased PPT significantly during pain over the masseter (p <0.05) and over the tibialis anterior (p <0.01). PPTol was unchanged. In the period after the painful conditioning stimulation PPT was depressed compared to control. This study shows that pain evoked from the craniofacial region evokes DNIC‐like mechanisms on segmental as well as heterosegmental sites.Tonic pain in one body segment can inhibit the perception of pain in another body segment. This phenomenon is mediated by diffuse noxious inhibitory controls (DNIC), and its efficacy in craniofacial regions is investigated in this study. A compressive device that evoked a tonic, moderate/severe, headache-like, conditioning pain (∼8/10 on a visual analogue scale) was applied for 15min. Eleven males participated in the study. Pressure pain threshold (PPT) and pressure pain tolerance (PPTol) at multiple heterosegmental body sites (right masseter, splenius capitis, second intermediate phalange, brachioradialis and tibialis anterior) were measured before, during and at multiple time points (5, 20 and 35min) after the termination of the conditioning pain. PPTs and PPTols were compared within participants across two experimental sessions; one that included painful conditioning stimulation, and a separate control session on a different day. Painful conditioning increased PPT significantly during pain over the masseter (p<0.05) and over the tibialis anterior (p<0.01). PPTol was unchanged. In the period after the painful conditioning stimulation PPT was depressed compared to control. This study shows that pain evoked from the craniofacial region evokes DNIC-like mechanisms on segmental as well as heterosegmental sites.

Transcranial magnetic stimulation reduces masseter motoneuron pool excitability throughout the cortical silent period

OBJECTIVE To evaluate the time-course of changes in masseter motoneuron pool excitability following transcranial magnetic stimulation of motor cortex, and relate this to the duration of the masseter cortical silent period (CSP). METHODS Surface EMG was recorded bilaterally from masseter and digastric muscles in 13 subjects. Focal TMS was applied at 1.3x active motor threshold (AMT) to motor cortex of one hemisphere to elicit a muscle evoked potential (MEP) and silent period bilaterally in masseter as subjects maintained an isometric bite at approximately 10% maximum. With jaw muscles relaxed, a servo-controlled stretcher evoked a stretch reflex in masseter which was conditioned by TMS (1.3x AMT) at 14 different conditioning-testing intervals. There were 20 trials at each interval, in random order. TMS evoked no MEP in resting masseter, but often produced a small MEP in digastric. RESULTS Mean (+/-SE) masseter CSP was 67+/-3ms. The masseter stretch reflex was facilitated when stretch preceded TMS by 8 and 10ms, which we attribute to spatial summation of corticobulbar and Ia-afferent excitatory inputs to masseter. Masseter stretch reflex amplitude was reduced when TMS was given up to 75ms before stretch, and for up to 2ms afterwards. CONCLUSIONS We conclude that descending corticobulbar activity evoked by TMS acts bilaterally on brainstem interneurons that either inhibit masseter motoneurons or increase pre-synaptic inhibition of Ia-afferent terminals for up to 75ms after TMS. The reduction of masseter motoneuron pool excitability following TMS has a similar time-course to the CSP. SIGNIFICANCE In contrast to the situation for spinal and facial (CN VII) muscles, the masseter CSP appears to have no component that can be attributed exclusively to cortical mechanisms. Abnormalities in the masseter cortical silent period observed in neurological conditions may be due to pathophysiological changes at cortical and/or sub-cortical levels.

Augmenting melodic intonation therapy with non-invasive brain stimulation to treat impaired left-hemisphere function: two case studies

The purpose of this study was to investigate whether or not the right hemisphere can be engaged using Melodic Intonation Therapy (MIT) and excitatory repetitive transcranial magnetic stimulation (rTMS) to improve language function in people with aphasia. The two participants in this study (GOE and AMC) have chronic non-fluent aphasia. A functional Magnetic Resonance Imaging (fMRI) task was used to localize the right Brocas homolog area in the inferior frontal gyrus for rTMS coil placement. The treatment protocol included an rTMS phase, which consisted of 3 treatment sessions that used an excitatory stimulation method known as intermittent theta burst stimulation, and a sham-rTMS phase, which consisted of 3 treatment sessions that used a sham coil. Each treatment session was followed by 40 min of MIT. A linguistic battery was administered after each session. Our findings show that one participant, GOE, improved in verbal fluency and the repetition of phrases when treated with MIT in combination with TMS. However, AMC showed no evidence of behavioral benefit from this brief treatment trial. Post-treatment neural activity changes were observed for both participants in the left Brocas area and right Brocas homolog. These case studies indicate that a combination of MIT and rTMS applied to the right Brocas homolog has the potential to improve speech and language outcomes for at least some people with post-stroke aphasia.

Neuromagnetic brain activity associated with anticipatory postural adjustments for bimanual load lifting

During bimanual load lifting, the brain must anticipate the effects of unloading upon the load-bearing arm. Little is currently known about the neural networks that coordinate these anticipatory postural adjustments. We measured neuromagnetic brain activity with whole-head magnetoencephalography while participants performed a bimanual load-lifting task. Anticipatory adjustments were associated with reduction in biceps brachii muscle activity of the load-bearing arm and pre-movement desynchronization of the cortical beta rhythm. Beamforming analyses localized anticipatory brain activity to the precentral gyrus, basal ganglia, supplementary motor area, and thalamus, contralateral to the load-bearing arm. To our knowledge this is the first human neuroimaging study to directly investigate anticipatory postural adjustments and to explicitly partition the anticipatory and volitional aspects of brain activity in bimanual load lifting. These data contribute to our understanding of the neural systems supporting anticipatory postural adjustments in healthy adults.