TMS of the left primary motor cortex improves tremor intensity and postural control in primary orthostatic tremor.

A ponto-cerebello-thalamo-cortical network is the pathophysiological correlate of primary orthostatic tremor. Affected patients often do not respond satisfactorily to pharmacological treatment. Consequently, the objective of the current study was to examine the effects of a non-invasive neuromodulation by theta burst repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) and dorsal medial frontal cortex (dMFC) on tremor frequency, intensity, sway path and subjective postural stability in primary orthostatic tremor. In a cross-over design, eight patients (mean age 70.2 ± 5.4 years, 4 female) with a primary orthostatic tremor received either rTMS of the left M1 leg area or the dMFC at the first study session, followed by the other condition (dMFC or M1 respectively) at the second study session 30 days later. Tremor frequency and intensity were quantified by surface electromyography of lower leg muscles and total sway path by posturography (foam rubber with eyes open) before and after each rTMS session. Patients subjectively rated postural stability on the posturography platform following each rTMS treatment. We found that tremor frequency did not change significantly with M1- or dMFC-stimulation. However, tremor intensity was lower after M1- but not dMFC-stimulation (p = 0.033/ p = 0.339). The sway path decreased markedly after M1-stimulation (p = 0.0005) and dMFC-stimulation (p = 0.023) compared to baseline. Accordingly, patients indicated a better subjective feeling of postural stability both with M1-rTMS (p = 0.007) and dMFC-rTMS (p = 0.01). In conclusion, non-invasive neuromodulation particularly of the M1 area can improve postural control and tremor intensity in primary orthostatic tremor by interference with the tremor network.

Targeted rhythmic visual stimulation at individual participants' intrinsic alpha frequency causes selective increase of occipitoparietal BOLD-fMRI and EEG functional connectivity.

Neural oscillations in distinct frequency bands are ubiquitous in the brain and play a role in many cognitive processes. The "communication by coherence" hypothesis, poses that the synchronization through phase coupling of frequency-specific neural oscillations regulate information flow across distribute brain regions. Specifically, the posterior alpha frequency band (7-12 Hz) is thought to gate bottom-up visual information flow by inhibition during visual processing. Evidence shows that increased alpha phase coherency positively correlates with functional connectivity in resting state connectivity networks, supporting alpha mediates neural communication through coherency. However, these findings have mainly been derived from spontaneous changes in the ongoing alpha rhythm. In this study, we experimentally modulate the alpha rhythm by targeting individuals' intrinsic alpha frequency with sustained rhythmic light to investigate alpha-mediated synchronous cortical activity in both EEG and fMRI. We hypothesize increased alpha coherency and fMRI connectivity should arise from modulation of the intrinsic alpha frequency (IAF) as opposed to control frequencies in the alpha range. Sustained rhythmic and arrhythmic stimulation at the IAF and at neighboring frequencies within the alpha band range (7-12 Hz) was implemented and assessed in a separate EEG and fMRI study. We observed increased cortical alpha phase coherency in the visual cortex during rhythmic stimulation at the IAF as in comparison to rhythmic stimulation of control frequencies. In the fMRI, we found increased functional connectivity for stimulation at the IAF in visual and parietal areas as compared to other rhythmic control frequencies by correlating time courses from a set of regions of interest for the different stimulation conditions and applying network-based statistics. This suggests that rhythmic stimulation at the IAF frequency induces a higher degree of synchronicity of neural activity across the occipital and parietal cortex, which supports the role of the alpha oscillation in gating information flow during visual processing.

Self-initiation Inhibits the Postural and Electrophysiological Responses to Optic Flow and Button Pressing.

As we move through our environment, our visual system is presented with optic flow, a potentially important cue for perception, navigation and postural control. How does the brain anticipate the optic flow that arises as a consequence of our own movement? Converging evidence suggests that stimuli are processed differently by the brain if occurring as a consequence of self-initiated actions, compared to when externally generated. However, this has mainly been demonstrated with auditory stimuli. It is not clear how this occurs with optic flow. We measured behavioural, neurophysiological and head motion responses of 29 healthy participants to radially expanding, vection-inducing optic flow stimuli, simulating forward transitional motion, which were either initiated by the participant's own button-press ("self-initiated flow") or by the computer ("passive flow"). Self-initiation led to a prominent and left-lateralized inhibition of the flow-evoked posterior event-related alpha desynchronization (ERD), and a stabilisation of postural responses. Neither effect was present in control button-press-only trials, without optic flow. Additionally, self-initiation also produced a large event-related potential (ERP) negativity between 130-170 ms after optic flow onset. Furthermore, participants' visual induced motion sickness (VIMS) and vection intensity ratings correlated positively across the group - although many participants felt vection in the absence of any VIMS, none reported the opposite combination. Finally, we found that the simple act of making a button press leads to a detectable head movement even when using a chin rest. Taken together, our results indicate that the visual system is capable of predicting optic flow when self-initiated, to affect behaviour.

Different EEG brain activity in right and left handers during visually induced self-motion perception.

Visually induced self-motion perception (vection) relies on visual-vestibular interaction. Imaging studies using vestibular stimulation have revealed a vestibular thalamo-cortical dominance in the right hemisphere in right handers and the left hemisphere in left handers. We investigated if the behavioural characteristics and neural correlates of vection differ between healthy left and right-handed individuals. 64-channel EEG was recorded while 25 right handers and 25 left handers were exposed to vection-compatible roll motion (coherent motion) and a matched, control condition (incoherent motion). Behavioural characteristics, i.e. vection presence, onset latency, duration and subjective strength, were also recorded. The behavioural characteristics of vection did not differ between left and right handers (all p > 0.05). Fast Fourier Transform (FFT) analysis revealed significant decreases in alpha power during vection-compatible roll motion (p < 0.05). The topography of this decrease was handedness-dependent, with left handers showing a left lateralized centro-parietal decrease and right handers showing a bilateral midline centro-parietal decrease. Further time-frequency analysis, time locked to vection onset, revealed a comparable decrease in alpha power around vection onset and a relative increase in alpha power during ongoing vection, for left and right handers. No effects were observed in theta and beta bands. Left and right-handed individuals show vection-related alpha power decreases at different topographical regions, possibly related to the influence of handedness-dependent vestibular dominance in the visual-vestibular interaction that facilitates visual self-motion perception. Despite this difference in where vection-related activity is observed, left and right handers demonstrate comparable perception and underlying alpha band changes during vection.

Shift in lateralization during illusory self-motion: EEG responses to visual flicker at 10 Hz and frequency-specific modulation by tACS.

Self-motion perception is a key aspect of higher vestibular processing, suggested to rely upon hemispheric lateralization and alpha-band oscillations. The first aim of this study was to test for any lateralization in the EEG alpha band during the illusory sense of self-movement (vection) induced by large optic flow stimuli. Visual stimuli flickered at alpha frequency (approx. 10 Hz) in order to produce steady state visually evoked potentials (SSVEPs), a robust EEG measure which allows probing the frequency-specific response of the cortex. The first main result was that differential lateralization of the alpha SSVEP response was found during vection compared with a matched random motion control condition, supporting the idea of lateralization of visual-vestibular function. Additionally, this effect was frequency-specific, not evident with lower frequency SSVEPs. The second aim of this study was to test for a causal role of the right hemisphere in producing this lateralization effect and to explore the possibility of selectively modulating the SSVEP response. Transcranial alternating current stimulation (tACS) was applied over the right hemisphere simultaneously with SSVEP recording, using a novel artefact removal strategy for combined tACS-EEG. The second main result was that tACS enhanced SSVEP amplitudes, and the effect of tACS was not confined to the right hemisphere. Subsequent control experiments showed the effect of tACS requires the flicker frequency and tACS frequency to be closely matched and tACS to be of sufficient intensity. Combined tACS-SSVEPs are a promising method for future investigation into the role of neural oscillations and for optimizing tACS.

Mobile steady-state evoked potential recording: Dissociable neural effects of real-world navigation and visual stimulation.

BACKGROUND: The ability to record brain activity in humans during movement, and in real world environments, is an important step towards understanding cognition. Electroencephalography (EEG) is well suited to mobile applications but suffers from the problem of artefacts introduced into the signal during movement. Steady state visually evoked potentials (SSVEPs) give an excellent signal-to-noise ratio and averaging a sufficient number of trials will eventually remove any noise not phase locked to the visual flicker. NEW METHOD: Here we present a method for producing SSVEPs of real world environments using modified LCD shutter glasses, which are commonly used for 3D TV, by adapting the glass to flicker at neurophysiologically relevant frequencies (alpha band). Participants viewed a room whilst standing and walking. Either the left or right side of the room was illuminated, to test if it is possible to recover the resulting SSVEPs when walking, as well as to probe the effect of walking on neural activity. Additionally, by using a signal generator to produce "simulated SSVEPs" on the scalp we can demonstrate that this method is able to accurately recover evoked neural responses during walking. RESULTS: The amplitude of SSVEPs over right parietal cortex was reduced by walking. Furthermore, the waveform and phase of the SSVEPs is highly preserved between walking and standing, but was sensitive to whether the left or right side of the room was illuminated. CONCLUSIONS: This method allows probing neural responses during natural movements within real environments, potentially at a wide range of frequencies.

Right frontal eye field has perceptual and oculomotor functions during optokinetic stimulation and nystagmus.

The right frontal eye field (rFEF) is associated with visual perception and eye movements. rFEF is activated during optokinetic nystagmus (OKN), a reflex that moves the eye in response to visual motion (optokinetic stimulation, OKS). It remains unclear whether rFEF plays causal perceptual and/or oculomotor roles during OKS and OKN. To test this, participants viewed a leftward-moving visual scene of vertical bars and judged whether a flashed dot was moving. Single pulses of transcranial magnetic stimulation (TMS) were applied to rFEF on half of trials. In half of blocks, to explore oculomotor control, participants performed an OKN in response to the OKS. rFEF TMS, during OKN, made participants more accurate on trials when the dot was still, and it slowed eye movements. In separate blocks, participants fixated during OKS. This not only controlled for eye movements but also allowed the use of EEG to explore the FEF's role in visual motion discrimination. In these blocks, by contrast, leftward dot motion discrimination was impaired, associated with a disruption of the frontal-posterior balance in alpha-band oscillations. None of these effects occurred in a control site (M1) experiment. These results demonstrate multiple related yet dissociable causal roles of the right FEF during optokinetic stimulation.NEW & NOTEWORTHY This study demonstrates causal roles of the right frontal eye field (FEF) in motion discrimination and eye movement control during visual scene motion: previous work had only examined other stimuli and eye movements such as saccades. Using combined transcranial magnetic stimulation and EEG and a novel optokinetic stimulation motion-discrimination task, we find evidence for multiple related yet dissociable causal roles within the FEF: perceptual processing during optokinetic stimulation, generation of the optokinetic nystagmus, and the maintenance of alpha oscillations.

Egocentric processing in the roll plane and dorsal parietal cortex: A TMS-ERP study of the subjective visual vertical.

The intraparietal sulcus within the dorsal right posterior parietal cortex is associated with spatial orientation and attention in relation to egocentric reference frames, such as left or right hemifield. It remains unclear whether it plays a causal role in the human in the roll plane (i.e. when visual stimuli are tilted clockwise or anticlockwise) which this is an important aspect of egocentric visual processing with clinical relevance in vestibular disorders. The subjective visual vertical (SVV) task measures the deviation between an individual's subjective vertical perception and the veridical vertical, involves the integration of visual, and vestibular information, and relies on a distributed network of multisensory regions that shows right lateralization and inter-areal inhibition. This study used combined TMS-EEG to investigate the role of the human dorsal parietal cortex in verticality perception using the SVV task in darkness. Participants were sorted according to their baseline bias at this task i.e. those with either a slight counterclockwise versus clockwise bias when judging a line to be truly vertical. Right parietal TMS facilitated verticality perception, reducing the difference between groups. ERPs suggested that the behavioral TMS effect occurred through normalizing individual SVV biases, evident frontally and late in the trial, and which was abolished after right parietal TMS. Effects were site and task specific, shown with a homologous left hemisphere control, and a landmark task performed on the same stimuli. These results support a right lateralization of visual-vestibular cognition and a distinct representation of the roll plane for egocentric processing in dorsal parietal cortex.

Cognition and higher vestibular disorders: developing tools for assessing vection.

Visually induced vection is the illusory sensation of self-motion caused by visual stimuli (such as a dot cloud) that emulate what is seen when an agent moves through space. The sufficient stimulus parameters to generate vection are unknown, but elucidating this is of interest in the study of higher (cognitive) neurological disorders where the relationship between visual and vestibular processing is disturbed. Here, we selectively eliminate that radial motion angle from vection displays and show that vection is still present, although weaker than during normal optic flow, and that vection strength was strikingly variable across individuals.

Sustained Aftereffect of α-tACS Lasts Up to 70 min after Stimulation.

Transcranial alternating current stimulation (tACS) has been repeatedly demonstrated to increase power of endogenous brain oscillations in the range of the stimulated frequency after stimulation. In the alpha band this aftereffect has been shown to persist for at least 30 min. However, in most experiments the aftereffect exceeded the duration of the measurement. Thus, it remains unclear how the effect develops beyond these 30 min and when it decays. The current study aimed to extend existing findings by monitoring the physiological aftereffect of tACS in the alpha range for an extended period of 90 min post-stimulation. To this end participants received either 20 min of tACS or sham stimulation with intensities below their individual sensation threshold at the individual alpha frequency (IAF). Electroencephalogram (EEG) was acquired during 3 min before and 90 min after stimulation. Subjects performed a visual vigilance task during the whole measurement. While the enhanced power in the individual alpha band did not return back to pre-stimulation baseline in the stimulation group, the difference between stimulation and sham diminishes after 70 min due to a natural alpha increase of the sham group.

Transcranial Alternating Current Stimulation with Sawtooth Waves: Simultaneous Stimulation and EEG Recording.

Transcranial alternating current stimulation (tACS) has until now mostly been administered as an alternating sinusoidal wave. Despite modern tACS stimulators being able to deliver alternating current with any arbitrary shape there has been no systematic exploration into the relative benefits of different waveforms. As tACS is a relatively new technique there is a huge parameter space of unexplored possibilities which may prove superior or complimentary to the traditional sinusoidal waveform. Here, we begin to address this with an investigation into the effects of sawtooth wave tACS on individual alpha power. Evidence from animal models suggests that the gradient and direction of an electric current should be important factors for the subsequent neural firing rate; we compared positive and negative ramp sawtooth waves to test this. An additional advantage of sawtooth waves is that the resulting artifact in the electroencephalogram (EEG) recording is significantly simpler to remove than a sine wave; accordingly we were able to observe alpha oscillations both during and after stimulation. We found that positive ramp sawtooth, but not negative ramp sawtooth, significantly enhanced alpha power during stimulation relative to sham (p < 0.01). In addition we tested for an after-effect of both sawtooth and sinusoidal stimulation on alpha power but in this case did not find any significant effect. This preliminary study paves the way for further investigations into the effect of the gradient and direction of the current in tACS which could significantly improve the usefulness of this technique.

Functional interaction between right parietal and bilateral frontal cortices during visual search tasks revealed using functional magnetic imaging and transcranial direct current stimulation.

The existence of a network of brain regions which are activated when one undertakes a difficult visual search task is well established. Two primary nodes on this network are right posterior parietal cortex (rPPC) and right frontal eye fields. Both have been shown to be involved in the orientation of attention, but the contingency that the activity of one of these areas has on the other is less clear. We sought to investigate this question by using transcranial direct current stimulation (tDCS) to selectively decrease activity in rPPC and then asking participants to perform a visual search task whilst undergoing functional magnetic resonance imaging. Comparison with a condition in which sham tDCS was applied revealed that cathodal tDCS over rPPC causes a selective bilateral decrease in frontal activity when performing a visual search task. This result demonstrates for the first time that premotor regions within the frontal lobe and rPPC are not only necessary to carry out a visual search task, but that they work together to bring about normal function.