Effect of Stimulation Current in Transcutaneous Vagus Nerve Stimulation (tVNS): A Study Using Concurrent Magnetoencephalography (MEG).

Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive method of brain stimulation that has been investigated for its use in the clinical treatment of a number of different conditions. There has been little investigation into the stimulation current that is delivered and the effect on individual variability in response to tVNS.Seventeen participants underwent tVNS, and stimulation current was determined based on individual pain threshold. To investigate individual variability, brain dynamics were measured concurrently using magnetoencephalography (MEG) in response to two different stimulation protocols of tVNS. The first protocol consisted of a sequence of equally spaced short (1ms) stimulation pulses applied 24 times per second (24 Hz), and the second consisted of a sequence of 24 pulses per second spaced according to a 6 Hz pulse frequency modulation (PFM). Both stimulation sequences were delivered to the cymba concha in the left ear.The difference in brain responses to the two sequences was initially calculated using a one-sample t-test at the group level, based on z-scoring of the data at the individual level, and no statistically significant differences were observed. Further investigation of individual variability suggested that participants fell into two groups; one that responded more strongly to 24 Hz and one that responded more strongly to the irregular spacing of pulses in the PFM protocol.We tested whether the stimulation current that the participant received could predict how they would respond to the stimulation, but we did not observe any correlation. This supports the literature that suggests that selecting stimulation current based on individual pain threshold is a suitable procedure for tVNS, and higher stimulation intensities does not correspond to stronger brain response. Further investigation into individual variability in response to different frequencies and pulse spacing of tVNS should also be investigated further and may lead to the development of personalised stimulation protocols.Clinical relevance- The stimulation current at which tVNS is delivered does not appear to influence brain response to stimulation, and the value of stimulation current should be selected based on individual participant comfort.

Functional Connectivity Analysis of Transcutaneous Vagus Nerve Stimulation (tVNS) Using Magnetoencephalography (MEG).

Altered brain functional connectivity has been observed in conditions such as schizophrenia, dementia and depression and may represent a target for treatment. Transcutaneous vagus nerve stimulation (tVNS) is a form of non-invasive brain stimulation that is increasingly used in the treatment of a variety of health conditions. We previously combined tVNS with magnetoencephalography (MEG) and observed that various stimulation frequencies affected different brain areas in healthy individuals. We further investigated whether tVNS had an effect on functional connectivity with a focus on brain regions associated with mood. We compared functional connectivity (whole-head and region of interest) in response to four stimulation frequencies of tVNS using data collected from concurrent MEG and tVNS in 17 healthy participants using Weighted Phase Lag Index (WPLI) to calculate correlation between brain areas. Different frequencies of stimulation lead to changes in functional connectivity across multiple regions, notably areas linked to the default mode network (DMN), salience network (SN) and the central executive network (CEN). It was observed that tVNS delivered at a frequency of 24 Hz was the most effective in increasing functional connectivity between these areas and sub-networks in healthy participants. Our results indicate that tVNS can alter functional connectivity in regions that have been associated with mood and memory disorders. Varying the stimulation frequency led to alterations in different brain areas, which may suggest that personalized stimulation protocols can be developed for the targeted treatment of different medical conditions using tVNS.

Measuring brain response to transcutaneous vagus nerve stimulation (tVNS) using simultaneous magnetoencephalography (MEG).

Objective.Transcutaneous vagus nerve stimulation (tVNS) is a form of non-invasive brain stimulation that delivers a sequence of electrical pulses to the auricular branch of the vagus nerve and is used increasingly in the treatment of a number of health conditions such as epilepsy and depression. Recent research has focused on the efficacy of tVNS to treat different medical conditions, but there is little conclusive evidence concerning the optimal stimulation parameters. There are relatively few studies that have combined tVNS with a neuroimaging modality, and none that have attempted simultaneous magnetoencephalography (MEG) and tVNS due to the presence of large stimulation artifacts produced by the electrical stimulation which are many orders of magnitude larger than underlying brain activity.Approach.The aim of this study is to investigate the utility of MEG to gain insight into the regions of the brain most strongly influenced by tVNS and how variation of the stimulation parameters can affect this response in healthy participants.Main results.We have successfully demonstrated that MEG can be used to measure brain response to tVNS. We have also shown that varying the stimulation frequency can lead to a difference in brain response, with the brain also responding in different anatomical regions depending on the frequency.Significance.The main contribution of this paper is to demonstrate the feasibility of simultaneous pulsed tVNS and MEG recording, allowing direct investigation of the changes in brain activity that result from different stimulation parameters. This may lead to the development of customised therapeutic approaches for the targeted treatment of different conditions.

A randomized controlled trial investigating the neurocognitive effects of Lacprodan® PL-20, a phospholipid-rich milk protein concentrate, in elderly participants with age-associated memory impairment: the Phospholipid Intervention for Cognitive Ageing Reversal (PLICAR): study protocol for a randomized controlled trial.

BACKGROUND: Age-related cognitive decline (ARCD) is of major societal concern in an ageing population, with the development of dietary supplements providing a promising avenue for amelioration of associated deficits. Despite initial interest in the use of phospholipids (PLs) for ARCD, in recent years there has been a hiatus in such research. Because of safety concerns regarding PLs derived from bovine cortex, and the equivocal efficacy of soybean-derived PLs, there is an important need for the development of new PL alternatives. Phospholipids derived from milk proteins represent one potential candidate treatment. METHODS: In order to reduce the effects of age-associated memory impairment (AAMI) the Phospholipid Intervention for Cognitive Ageing Reversal (PLICAR) was developed to test the efficacy of a milk protein concentrate rich in natural, non-synthetic milk phospholipids (Lacprodan® PL-20). PLICAR is a randomized, double-blind, placebo-controlled parallel-groups study where 150 (N = 50/group) AAMI participants aged > 55 years will be randomized to receive a daily supplement of Lacprodan® PL-20 or one of two placebos (phospholipid-free milk protein concentrate or inert rice starch) over a 6-month (180-day) period. Participants will undergo testing at baseline, 90 days and 180 days. The primary outcome is a composite memory score from the Rey Auditory Verbal Learning Test. Secondary outcomes include cognitive (verbal learning, working memory, prospective and retrospective memory, processing speed and attention), mood (depression, anxiety, stress and visual analogue scales), cardiovascular (blood pressure, blood velocity and pulse wave pressure), gastrointestinal microbiota and biochemical measures (oxidative stress, inflammation, B vitamins and Homocysteine, glucoregulation and serum choline). Allelic differences in the Apolipoprotein E and (APOE) and Methylenetetrahydrofolate reductase (MTHFR) gene will be included for subgroup analysis. A subset (N = 60; 20/group)) will undergo neuroimaging using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in order to further explore in vivo central mechanisms of action of Lacprodan® PL-20. This study will enable evaluation of the efficacy of milk-derived phospholipids for AAMI, and their mechanisms of action. TRIAL REGISTRATION: The trial is jointly funded by Arla Foods and Swinburne University of Technology, currently recruiting and is registered on the Australian New Zealand Clinical Trials Registry as ACTRN12613000347763.

Involvement of right STS in audio-visual integration for affective speech demonstrated using MEG.

Speech and emotion perception are dynamic processes in which it may be optimal to integrate synchronous signals emitted from different sources. Studies of audio-visual (AV) perception of neutrally expressed speech demonstrate supra-additive (i.e., where AV>[unimodal auditory+unimodal visual]) responses in left STS to crossmodal speech stimuli. However, emotions are often conveyed simultaneously with speech; through the voice in the form of speech prosody and through the face in the form of facial expression. Previous studies of AV nonverbal emotion integration showed a role for right (rather than left) STS. The current study therefore examined whether the integration of facial and prosodic signals of emotional speech is associated with supra-additive responses in left (cf. results for speech integration) or right (due to emotional content) STS. As emotional displays are sometimes difficult to interpret, we also examined whether supra-additive responses were affected by emotional incongruence (i.e., ambiguity). Using magnetoencephalography, we continuously recorded eighteen participants as they viewed and heard AV congruent emotional and AV incongruent emotional speech stimuli. Significant supra-additive responses were observed in right STS within the first 250 ms for emotionally incongruent and emotionally congruent AV speech stimuli, which further underscores the role of right STS in processing crossmodal emotive signals.

Spatiotemporal reconstruction of the auditory steady-state response to frequency modulation using magnetoencephalography.

The aim of this study was to investigate the mechanisms involved in the perception of perceptually salient frequency modulation (FM) using auditory steady-state responses (ASSRs) measured with magnetoencephalography (MEG). Previous MEG studies using frequency-modulated amplitude modulation as stimuli (Luo et al., 2006, 2007) suggested that a phase modulation encoding mechanism exists for low (<5 Hz) FM modulation frequencies but additional amplitude modulation encoding is required for faster FM modulation frequencies. In this study single-cycle sinusoidal FM stimuli were used to generate the ASSR. The stimulus was either an unmodulated 1-kHz sinusoid or a 1-kHz sinusoid that was frequency-modulated with a repetition rate of 4, 8, or 12 Hz. The fast Fourier transform (FFT) of each MEG channel was calculated to obtain the phase and magnitude of the ASSR in sensor-space and multivariate Hotelling's T(2) statistics were used to determine the statistical significance of ASSRs. MEG beamformer analyses were used to localise the ASSR sources. Virtual electrode analyses were used to reconstruct the time series at each source. FFTs of the virtual electrode time series were calculated to obtain the amplitude and phase characteristics of each source identified in the beamforming analyses. Multivariate Hotelling's T(2) statistics were used to determine the statistical significance of these reconstructed ASSRs. The results suggest that the ability of auditory cortex to phase-lock to FM is dependent on the FM pulse rate and that the ASSR to FM is lateralised to the right hemisphere.