Reduced Auditory Perception and Brain Response with Quiet TMS Coil.

BACKGROUND: Electromagnetic forces in transcranial magnetic stimulation (TMS) coils generate a loud clicking sound that produces confounding auditory activation and is potentially hazardous to hearing. To reduce this noise while maintaining stimulation efficiency similar to conventional TMS coils, we previously developed a quiet TMS double containment coil (qTMS-DCC). OBJECTIVE: To compare the stimulation strength, perceived loudness, and EEG response between qTMS-DCC and a commercial TMS coil. METHODS: Nine healthy volunteers participated in a within-subject study design. The resting motor thresholds (RMTs) for qTMS-DCC and MagVenture Cool-B65 were measured. Psychoacoustic titration matched the Cool-B65 loudness to qTMS-DCC pulsed at 80, 100, and 120% RMT. Event-related potentials (ERPs) were recorded for both coils. The psychoacoustic titration and ERPs were acquired with the coils both on and 6 cm off the scalp, the latter isolating the effects of airborne auditory stimulation from body sound and electromagnetic stimulation. The ERP comparisons focused on a centro-frontal region that encompassed peak responses in the global signal. RESULTS: RMT did not differ significantly between the coils, with or without the EEG cap on the head. qTMS-DCC was perceived to be substantially quieter than Cool-B65. For example, qTMS-DCC at 100% coil-specific RMT sounded like Cool-B65 at 34% RMT. The general ERP waveform and topography were similar between the two coils, as were early-latency components, indicating comparable electromagnetic brain stimulation in the on-scalp condition. qTMS-DCC had a significantly smaller P180 component in both on-scalp and off-scalp conditions, supporting reduced auditory activation. CONCLUSIONS: The stimulation efficiency of qTMS-DCC matched Cool-B65, while having substantially lower perceived loudness and auditory-evoked potentials. Highlights: qTMS coil is subjectively and objectively quieter than conventional Cool-B65 coilqTMS coil at 100% motor threshold was as loud as Cool-B65 at 34% motor thresholdAttenuated coil noise reduced auditory N100 and P180 evoked response componentsqTMS coil enables reduction of auditory activation without masking.

Transcranial magnetic stimulation input-output curve slope differences suggest variation in recruitment across muscle representations in primary motor cortex.

Measurement of the input-output (IO) curves of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) can be used to assess corticospinal excitability and motor recruitment. While IO curves have been used to study disease and pharmacology, few studies have compared the IO curves across the body. This study sought to characterize IO curve parameters across the dominant and non-dominant sides of upper and lower limbs in healthy participants. Laterality preferences were assessed in eight healthy participants and IO curves were measured bilaterally for the first dorsal interosseous (FDI), biceps brachii (BB), and tibialis anterior (TA) muscles. Results show that FDI has lower motor threshold than BB which is, in turn, lower than TA. In addition, both BB and TA have markedly shallower logarithmic IO curve slopes from small to large MEP responses than FDI. After normalizing these slopes by their midpoints to account for differences in motor thresholds, which could result from geometric factors such as the target depth, large differences in logarithmic slopes remain present between all three muscles. The differences in slopes between the muscles could not be explained by differences in normalized IO curve spreads, which relate to the extent of the cortical representation and were comparable across the muscles. The IO curve differences therefore suggest muscle-dependent variations in TMS-evoked recruitment across the primary motor cortex, which should be considered when utilizing TMS-evoked MEPs to study disease states and treatment effects.

Parametric information about eye movements is sent to the ears.

Eye movements alter the relationship between the visual and auditory spatial scenes. Signals related to eye movements affect neural pathways from the ear through auditory cortex and beyond, but how these signals contribute to computing the locations of sounds with respect to the visual scene is poorly understood. Here, we evaluated the information contained in eye movement-related eardrum oscillations (EMREOs), pressure changes recorded in the ear canal that occur in conjunction with simultaneous eye movements. We show that EMREOs contain parametric information about horizontal and vertical eye displacement as well as initial/final eye position with respect to the head. The parametric information in the horizontal and vertical directions can be modeled as combining linearly, allowing accurate prediction of the EMREOs associated with oblique (diagonal) eye movements. Target location can also be inferred from the EMREO signals recorded during eye movements to those targets. We hypothesize that the (currently unknown) mechanism underlying EMREOs could impose a two-dimensional eye-movement-related transfer function on any incoming sound, permitting subsequent processing stages to compute the positions of sounds in relation to the visual scene.

Conserved features of eye movement related eardrum oscillations (EMREOs) across humans and monkeys.

Auditory and visual information involve different coordinate systems, with auditory spatial cues anchored to the head and visual spatial cues anchored to the eyes. Information about eye movements is therefore critical for reconciling visual and auditory spatial signals. The recent discovery of eye movement-related eardrum oscillations (EMREOs) suggests that this process could begin as early as the auditory periphery. How this reconciliation might happen remains poorly understood. Because humans and monkeys both have mobile eyes and therefore both must perform this shift of reference frames, comparison of the EMREO across species can provide insights to shared and therefore important parameters of the signal. Here we show that rhesus monkeys, like humans, have a consistent, significant EMREO signal that carries parametric information about eye displacement as well as onset times of eye movements. The dependence of the EMREO on the horizontal displacement of the eye is its most consistent feature, and is shared across behavioural tasks, subjects and species. Differences chiefly involve the waveform frequency (higher in monkeys than in humans) and patterns of individual variation (more prominent in monkeys than in humans), and the waveform of the EMREO when factors due to horizontal and vertical eye displacements were controlled for. This article is part of the theme issue 'Decision and control processes in multisensory perception'.

Individual similarities and differences in eye-movement-related eardrum oscillations (EMREOs).

We recently discovered a unique type of low-frequency otoacoustic emission (OAE) time-locked to the onset (and offset) of saccadic eye movements and occurring in the absence of external sound (Gruters et al., 2018). How and why these eye-movement-related eardrum oscillations (EMREOs) are generated is unknown, with a role in visual-auditory integration being the likeliest candidate. Clues to both the drivers of EMREOs and their purpose can be gleaned by examining responses in normal hearing human subjects. Do EMREOs occur in all individuals with normal hearing? If so, what components of the response occur most consistently? Understanding which attributes of EMREOs are similar across participants and which show more variability will provide the groundwork for future comparisons with individuals with hearing abnormalities affecting the ear's various motor components. Here we report that in subjects with normal hearing thresholds and normal middle ear function, all ears show (a) measurable EMREOs (mean: 58.7 dB SPL; range 45-67 dB SPL for large contralateral saccades), (b) a phase reversal for contra- versus ipsilaterally-directed saccades, (c) a large peak in the signal occurring soon after saccade onset, (d) an additional large peak time-locked to saccade offset and (e) evidence that saccade duration is encoded in the signal. We interpret the attributes of EMREOs that are most consistent across subjects as the ones that are most likely to play an essential role in their function. The individual differences likely reflect normal variation in individuals' auditory system anatomy and physiology, much like traditional measures of auditory function such as auditory-evoked OAEs, tympanometry and auditory-evoked potentials. Future work will compare subjects with different types of auditory dysfunction to population data from normal hearing subjects. Overall, these findings provide important context for the widespread observations of visual- and eye-movement related signals found in cortical and subcortical auditory areas of the brain.

Conserved features of eye movement related eardrum oscillations (EMREOs) across humans and monkeys.

Auditory and visual information involve different coordinate systems, with auditory spatial cues anchored to the head and visual spatial cues anchored to the eyes. Information about eye movements is therefore critical for reconciling visual and auditory spatial signals. The recent discovery of eye movement-related eardrum oscillations (EMREOs) suggests that this process could begin as early as the auditory periphery. How this reconciliation might happen remains poorly understood. Because humans and monkeys both have mobile eyes and therefore both must perform this shift of reference frames, comparison of the EMREO across species can provide insights to shared and therefore important parameters of the signal. Here we show that rhesus monkeys, like humans, have a consistent, significant EMREO signal that carries parametric information about eye displacement as well as onset times of eye movements. The dependence of the EMREO on the horizontal displacement of the eye is its most consistent feature, and is shared across behavioral tasks, subjects, and species. Differences chiefly involve the waveform frequency (higher in monkeys than in humans) and patterns of individual variation (more prominent in monkeys than humans), and the waveform of the EMREO when factors due to horizontal and vertical eye displacements were controlled for.

Accuracy of robotic coil positioning during transcranial magnetic stimulation.

OBJECTIVE: Robotic positioning systems for transcranial magnetic stimulation (TMS) promise improved accuracy and stability of coil placement, but there is limited data on their performance. Investigate the usability, accuracy, and limitations of robotic coil placement with a commercial system, ANT Neuro, in a TMS study. APPROACH: 21 subjects underwent a total of 79 TMS sessions corresponding to 160 hours under robotic coil control. Coil position and orientation were monitored concurrently through an additional neuronavigation system. MAIN RESULTS: Robot setup took on average 14.5 min. The robot achieved low position and orientation error with median 3.54 mm (overall, 1.34 mm without coil-head spacing) and 3.48°. The error increased over time at a rate of 0.4%/minute for both position and orientation. SIGNIFICANCE: Robotic TMS systems can provide accurate and stable coil position and orientation in long TMS sessions. Lack of pressure feedback and of manual adjustment of all coil degrees of freedom were limitations of this robotic system.

Excitatory TMS modulates memory representations.

Brain stimulation technologies have seen increasing application in basic science investigations, specifically toward the goal of improving memory function. However, proposals concerning the neural mechanisms underlying cognitive enhancement often rely on simplified notions of excitation. As a result, most applications examining the effects of transcranial magnetic stimulation (TMS) on functional neuroimaging measures have been limited to univariate analyses of brain activity. We present here analyses using representational similarity analysis (RSA) and encoding-retrieval similarity (ERS) analysis to quantify the effect of TMS on memory representations. To test whether an increase in local excitability in PFC can have measurable influences on upstream representations in earlier temporal memory regions, we compared 1 and 5Hz stimulation to the left dorsolateral PFC (DLPFC). We found that 5Hz rTMS, relative to 1Hz, had multiple effects on neural representations: 1) greater representational similarity during both encoding and retrieval in ventral stream regions, 2) greater ERS in the hippocampus, and, critically, 3) increasing ERS in MTL was correlated with increasing univariate activity in DLPFC, and greater functional connectivity for hits than misses between these regions. These results provide the first evidence of rTMS modulating semantic representations and strengthen the idea that rTMS may affect the reinstatement of previously experienced events in upstream regions.

The eardrums move when the eyes move: A multisensory effect on the mechanics of hearing.

Interactions between sensory pathways such as the visual and auditory systems are known to occur in the brain, but where they first occur is uncertain. Here, we show a multimodal interaction evident at the eardrum. Ear canal microphone measurements in humans (n = 19 ears in 16 subjects) and monkeys (n = 5 ears in three subjects) performing a saccadic eye movement task to visual targets indicated that the eardrum moves in conjunction with the eye movement. The eardrum motion was oscillatory and began as early as 10 ms before saccade onset in humans or with saccade onset in monkeys. These eardrum movements, which we dub eye movement-related eardrum oscillations (EMREOs), occurred in the absence of a sound stimulus. The amplitude and phase of the EMREOs depended on the direction and horizontal amplitude of the saccade. They lasted throughout the saccade and well into subsequent periods of steady fixation. We discuss the possibility that the mechanisms underlying EMREOs create eye movement-related binaural cues that may aid the brain in evaluating the relationship between visual and auditory stimulus locations as the eyes move.

Frequency-specific neuromodulation of local and distant connectivity in aging and episodic memory function.

A growing literature has focused on the brain's ability to augment processing in local regions by recruiting distant communities of neurons in response to neural decline or insult. In particular, both younger and older adult populations recruit bilateral prefrontal cortex (PFC) as a means of compensating for increasing neural effort to maintain successful cognitive function. However, it remains unclear how local changes in neural activity affect the recruitment of this adaptive mechanism. To address this problem, we combined graph theoretical measures from functional MRI with diffusion weighted imaging and repetitive transcranial magnetic stimulation (rTMS) to resolve a central hypothesis: how do aged brains flexibly adapt to local changes in cortical activity? Specifically, we applied neuromodulation to increase or decrease local activity in a cortical region supporting successful memory encoding (left dorsolateral PFC or DLPFC) using 5 or 1 Hz rTMS, respectively. We then assessed a region's local within-module degree, or the distributed between-module degree (BMD) between distant cortical communities. We predicted that (1) local stimulation-related deficits may be counteracted by boosting BMD between bilateral PFC, and that this effect should be (2) positively correlated with structural connectivity. Both predictions were confirmed; 5 Hz rTMS increased local success-related activity and local increases in PFC connectivity, while 1 Hz rTMS decreases local activity and triggered a more distributed pattern of bilateral PFC connectivity to compensate for this local inhibitory effect. These results provide an integrated, causal explanation for the network interactions associated with successful memory encoding in older adults. Hum Brain Mapp 38:5987-6004, 2017. © 2017 Wiley Periodicals, Inc.

Skilled Bimanual Training Drives Motor Cortex Plasticity in Children With Unilateral Cerebral Palsy.

Background Intensive bimanual therapy can improve hand function in children with unilateral spastic cerebral palsy (USCP). We compared the effects of structured bimanual skill training versus unstructured bimanual practice on motor outcomes and motor map plasticity in children with USCP. Objective We hypothesized that structured skill training would produce greater motor map plasticity than unstructured practice. Methods Twenty children with USCP (average age 9.5; 12 males) received therapy in a day camp setting, 6 h/day, 5 days/week, for 3 weeks. In structured skill training (n = 10), children performed progressively more difficult movements and practiced functional goals. In unstructured practice (n = 10), children engaged in bimanual activities but did not practice skillful movements or functional goals. We used the Assisting Hand Assessment (AHA), Jebsen-Taylor Test of Hand Function (JTTHF), and Canadian Occupational Performance Measure (COPM) to measure hand function. We used single-pulse transcranial magnetic stimulation to map the representation of first dorsal interosseous and flexor carpi radialis muscles bilaterally. Results Both groups showed significant improvements in bimanual hand use (AHA; P < .05) and hand dexterity (JTTHF; P < .001). However, only the structured skill group showed increases in the size of the affected hand motor map and amplitudes of motor evoked potentials (P < .01). Most children who showed the most functional improvements (COPM) had the largest changes in map size. Conclusions These findings uncover a dichotomy of plasticity: the unstructured practice group improved hand function but did not show changes in motor maps. Skill training is important for driving motor cortex plasticity in children with USCP.

Enhancement of Neuromodulation with Novel Pulse Shapes Generated by Controllable Pulse Parameter Transcranial Magnetic Stimulation.

BACKGROUND: Standard repetitive transcranial magnetic stimulation (rTMS) devices generate bidirectional biphasic sinusoidal pulses that are energy efficient, but may be less effective than monophasic pulses that induce a more unidirectional electric field. To enable pulse shape optimization, we developed a controllable pulse parameter TMS (cTMS) device. OBJECTIVE: We quantified changes in cortical excitability produced by conventional sinusoidal bidirectional pulses and by three rectangular-shaped cTMS pulses, one bidirectional and two unidirectional (in opposite directions), and compared their efficacy in modulating motor evoked potentials (MEPs) produced by stimulation of motor cortex. METHODS: Thirteen healthy subjects completed four sessions of 1 Hz rTMS of the left motor cortex. In each session, the rTMS electric field pulse had one of the four shapes. Excitability changes due to rTMS were measured by applying probe TMS pulses before and after rTMS, and comparing resultant MEP amplitudes. Separately, we measured the latency of the MEPs evoked by each of the four pulses. RESULTS: While the three cTMS pulses generated significant mean inhibitory effects in the subject group, the conventional biphasic cosine pulses did not. The strongest inhibition resulted from a rectangular unidirectional pulse with dominant induced current in the posterior-anterior direction. The MEP latency depended significantly on the pulse shape. CONCLUSIONS: The pulse shape is an important factor in rTMS-induced neuromodulation. The standard cosine biphasic pulse showed the smallest effect on cortical excitability, while the greatest inhibition was observed for an asymmetric, unidirectional, rectangular pulse. Differences in MEP latency across the various rTMS pulse shapes suggest activation of distinct subsets of cortical microcircuitry.

Quiet transcranial magnetic stimulation: Status and future directions.

A significant limitation of transcranial magnetic stimulation (TMS) is that the magnetic pulse delivery is associated with a loud clicking sound as high as 140 dB resulting from electromagnetic forces. The loud noise significantly impedes both basic research and clinical applications of TMS. It effectively makes TMS less focal since every click activates auditory cortex, brainstem, and other connected regions, synchronously with the magnetic pulse. The repetitive clicking sound can induce neuromodulation that can interfere with and confound the intended effects at the TMS target. As well, there are known concerns regarding blinding of TMS studies, hearing loss, induction of tinnitus, as well as tolerability. Addressing this need, we are developing a quiet TMS (qTMS) device that incorporates two key concepts: First, the dominant frequency components of the TMS pulse sound (typically 2-5 kHz) are shifted to higher frequencies that are above the human hearing upper threshold of about 20 kHz. Second, the TMS coil is designed electrically and mechanically to generate suprathreshold electric field pulses while minimizing the sound emitted at audible frequencies (<; 20 kHz). The enhanced acoustic properties of the coil are accomplished with a novel, layered coil design. We summarize a proof-of-concept qTMS prototype demonstrating noise loudness reduction by 19 dB(A) with ultrabrief pulses at conventional amplitudes. Further, we outline next steps to accomplish further sound reduction and suprathreshold pulse amplitudes.