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.

Critical Review of Transcutaneous Vagus Nerve Stimulation: Challenges for Translation to Clinical Practice.

Several studies have illustrated that transcutaneous vagus nerve stimulation (tVNS) can elicit therapeutic effects that are similar to those produced by its invasive counterpart, vagus nerve stimulation (VNS). VNS is an FDA-approved therapy for the treatment of both depression and epilepsy, but it is limited to the management of more severe, intervention-resistant cases as a second or third-line treatment option due to perioperative risks involved with device implantation. In contrast, tVNS is a non-invasive technique that involves the application of electrical currents through surface electrodes at select locations, most commonly targeting the auricular branch of the vagus nerve (ABVN) and the cervical branch of the vagus nerve in the neck. Although it has been shown that tVNS elicits hypo- and hyperactivation in various regions of the brain associated with anxiety and mood regulation, the mechanism of action and influence of stimulation parameters on clinical outcomes remains predominantly hypothetical. Suppositions are largely based on correlations between the neurobiology of the vagus nerve and its effects on neural activity. However, tVNS has also been investigated for several other disorders, including tinnitus, migraine and pain, by targeting the vagus nerve at sites in both the ear and the neck. As most of the described methods differ in the parameters and protocols applied, there is currently no firm evidence on the optimal location for tVNS or the stimulation parameters that provide the greatest therapeutic effects for a specific condition. This review presents the current status of tVNS with a focus on stimulation parameters, stimulation sites, and available devices. For tVNS to reach its full potential as a non-invasive and clinically relevant therapy, it is imperative that systematic studies be undertaken to reveal the mechanism of action and optimal stimulation modalities.

The influence of COMT rs4680 on functional connectivity in healthy adults: A systematic review.

The aim of this systematic review was to qualitatively synthesise the available research that investigated the influence of COMT genotype at SNP rs4680 on both task-based and resting-state connectivity in healthy adults. Thirty-five studies were identified that met inclusion criteria. Of the included studies, 20 studies reported resting-state findings and 16 studies reported task-based findings (emotion-processing, memory, working memory, reward-based learning and executive function). Studies were highly heterogeneous but an overall trend towards an association of the Val allele with greater resting-state connectivity and the Met allele with greater task-based connectivity is reported. A possible interpretation of current findings is discussed, whereby the Val allele is associated with improved cognitive flexibility allowing integration of novel relevant stimuli, and the Met allele allows improved sustained attention and targeted neural processing, particularly between limbic regions and prefrontal cortex. The most promising brain regions implicated in a COMT genotype influence on functional connectivity include prefrontal regions, amygdala and hippocampus.

Source-level Cortical Power Changes for Xenon and Nitrous Oxide-induced Reductions in Consciousness in Healthy Male Volunteers.

BACKGROUND: Investigations of the electrophysiology of gaseous anesthetics xenon and nitrous oxide are limited revealing inconsistent frequency-dependent alterations in spectral power and functional connectivity. Here, the authors describe the effects of sedative, equivalent, stepwise levels of xenon and nitrous oxide administration on oscillatory source power using a crossover design to investigate shared and disparate mechanisms of gaseous xenon and nitrous oxide anesthesia. METHODS: Twenty-one healthy males underwent simultaneous magnetoencephalography and electroencephalography recordings. In separate sessions, sedative, equivalent subanesthetic doses of gaseous anesthetic agents nitrous oxide and xenon (0.25, 0.50, and 0.75 equivalent minimum alveolar concentration-awake [MACawake]) and 1.30 MACawake xenon (for loss of responsiveness) were administered. Source power in various frequency bands were computed and statistically assessed relative to a conscious/pre-gas baseline. RESULTS: Observed changes in spectral-band power (P < 0.005) were found to depend not only on the gas delivered, but also on the recording modality. While xenon was found to increase low-frequency band power only at loss of responsiveness in both source-reconstructed magnetoencephalographic (delta, 208.3%, 95% CI [135.7, 281.0%]; theta, 107.4%, 95% CI [63.5, 151.4%]) and electroencephalographic recordings (delta, 260.3%, 95% CI [225.7, 294.9%]; theta, 116.3%, 95% CI [72.6, 160.0%]), nitrous oxide only produced significant magnetoencephalographic high-frequency band increases (low gamma, 46.3%, 95% CI [34.6, 57.9%]; high gamma, 45.7%, 95% CI [34.5, 56.8%]). Nitrous oxide-not xenon-produced consistent topologic (frontal) magnetoencephalographic reductions in alpha power at 0.75 MACawake doses (44.4%; 95% CI [-50.1, -38.6%]), whereas electroencephalographically nitrous oxide produced maximal reductions in alpha power at submaximal levels (0.50 MACawake, -44.0%; 95% CI [-48.1,-40.0%]). CONCLUSIONS: Electromagnetic source-level imaging revealed widespread power changes in xenon and nitrous oxide anesthesia, but failed to reveal clear universal features of action for these two gaseous anesthetics. Magnetoencephalographic and electroencephalographic power changes showed notable differences which will need to be taken into account to ensure the accurate monitoring of brain state during anaesthesia.

Cortical excitation-inhibition ratio mediates the effect of pre-attentive auditory processing deficits on interpersonal difficulties.

Several lines of evidence identify aberrant excitatory-inhibitory neural processes across autism and schizophrenia spectrum disorders, particularly within the psychosocial domain. Such neural processes include increased excitatory glutamate and reduced inhibitory GABA concentrations, which may affect auditory pre-attentive processing as indexed by the mismatch negativity (MMN); thus, an excitation-inhibition imbalance might lead to aberrant MMN, which might in turn drive the relationship between the MMN and psychosocial difficulties. This research has the potential to enhance the neurochemical understanding of the relationship between electrophysiology (MMN) and behavioural/clinical measures (psychosocial difficulties). Thirty-eight adults (18 male, 18-40 years) completed the Schizotypal Personality Questionnaire (SPQ) and Autism-Spectrum Quotient (AQ). Glutamate and GABA concentrations in bilateral superior temporal cortex (STC) were quantified using proton magnetic resonance spectroscopy (1H-MRS) while auditory MMN to a duration deviant was measured with magnetoencephalography. Spearman correlations probed the relationships between STC glutamate/GABA ratios, MMN amplitude and latency, and AQ and SPQ dimensions. Mediation effects of glutamate/GABA ratios on the relationship between MMN and AQ-SPQ dimensions were probed using causal mediation analysis. Only SPQ-interpersonal and AQ-communication were significantly correlated with right hemisphere glutamate/GABA ratios and MMN latency (ps < 0.05), which were themselves correlated (p = .035). Two mediation models were investigated, with right MMN latency as predictor and SPQ-interpersonal and AQ-communication as outcome variables. Right STC glutamate/GABA ratios significantly mediated the relationship between MMN latency and SPQ-interpersonal scores, but only partially mediated the relationship between MMN latency and AQ-communication scores. These findings support the growing body of literature pointing toward an excitation-inhibition imbalance that is central to psychosocial functioning across multi-dimensional spectrum disorders, such as autism and schizophrenia, and provides neurochemical indicators of the processes that underlie psychosocial dysfunction.

Prediction-error signals to violated expectations about person identity and head orientation are doubly-dissociated across dorsal and ventral visual stream regions.

Predictive coding theories of perception highlight the importance of constantly updated internal models of the world to predict future sensory inputs. Importantly, such theories suggest that prediction-error signalling should be specific to the violation of predictions concerning distinct attributes of the same stimulus. To interrogate this as yet untested prediction, we focused on two different aspects of face perception (identity and orientation) and investigated whether cortical regions which process particular stimulus attributes also signal prediction violations with respect to those same stimulus attributes. We employed a paradigm using sequential trajectories of images to create perceptual expectations about face orientation and identity, and then parametrically violated each attribute. Using MEG data, we identified double dissociations of expectancy violations in the dorsal and ventral visual streams, such that the right fusiform gyrus showed greater prediction-error signals to identity violations than to orientation violations, whereas the left angular gyrus showed the converse pattern of results. Our results suggest that perceptual prediction-error signalling is directly linked to regions associated with the processing of different stimulus properties.

Recording Brain Electromagnetic Activity During the Administration of the Gaseous Anesthetic Agents Xenon and Nitrous Oxide in Healthy Volunteers.

Anesthesia arguably provides one of the only systematic ways to study the neural correlates of global consciousness/unconsciousness. However to date most neuroimaging or neurophysiological investigations in humans have been confined to the study of γ-Amino-Butyric-Acid-(GABA)-receptor-agonist-based anesthetics, while the effects of dissociative N-Methyl-D-Aspartate-(NMDA)-receptor-antagonist-based anesthetics ketamine, nitrous oxide (N2O) and xenon (Xe) are largely unknown. This paper describes the methods underlying the simultaneous recording of magnetoencephalography (MEG) and electroencephalography (EEG) from healthy males during inhalation of the gaseous anesthetic agents N2O and Xe. Combining MEG and EEG data enables the assessment of electromagnetic brain activity during anesthesia at high temporal, and moderate spatial, resolution. Here we describe a detailed protocol, refined over multiple recording sessions, that includes subject recruitment, anesthesia equipment setup in the MEG scanner room, data collection and basic data analysis. In this protocol each participant is exposed to varying levels of Xe and N2O in a repeated measures cross-over design. Following relevant baseline recordings participants are exposed to step-wise increasing inspired concentrations of Xe and N2O of 8, 16, 24 and 42%, and 16, 32 and 47% respectively, during which their level of responsiveness is tracked with an auditory continuous performance task (aCPT). Results are presented for a number of recordings to highlight the sensor-level properties of the raw data, the spectral topography, the minimization of head movements, and the unequivocal level dependent effects on the auditory evoked responses. This paradigm describes a general approach to the recording of electromagnetic signals associated with the action of different kinds of gaseous anesthetics, which can be readily adapted to be used with volatile and intravenous anesthetic agents. It is expected that the method outlined can contribute to the understanding of the macro-scale mechanisms of anesthesia by enabling methodological extensions involving source space imaging and functional network analysis.

Magnetoencephalography reveals an increased non-target P3a, but not target P3b, that is associated with high non-clinical psychosocial deficits.

Auditory processing deficits are frequently identified in autism and schizophrenia, and the two disorders have been shown to share psychosocial difficulties. This study used magnetoencephalography to investigate auditory processing differences for those with a high degree of a non-clinical autistic and schizotypal trait phenotype, Social Disorganisation (SD). Participants were 18 low (9 female) and 19 high (9 female) SD scorers (18-40 years) who completed a three-stimulus auditory oddball paradigm of speech sounds (standard: 100ms 'o', deviant: 150ms 'o', novel: 150ms 'e'). Spatio-temporal cluster analysis revealed increased amplitude for the high SD group in a left (p = 0.006) and a right (p = 0.020) hemisphere cluster in response to the novel non-target. No cluster differences were found in response to the target deviant. These findings suggest that those with a high degree of the SD phenotype recruit more cortical resources when processing unattended, novel speech stimuli, which may lead to psychosocial deficits.

Spatio-temporal source cluster analysis reveals fronto-temporal auditory change processing differences within a shared autistic and schizotypal trait phenotype.

Social Disorganisation (SD) is a shared autistic and schizotypal phenotype that is present in the subclinical population. Auditory processing deficits, particularly in mismatch negativity/field (MMN/F) have been reported across both spectrum disorders. This study investigates differences in MMN/F cortical spatio-temporal source activity between higher and lower quintiles of the SD spectrum. Sixteen low (9 female) and 19 high (9 female) SD subclinical adults (18-40years) underwent magnetoencephalography (MEG) during an MMF paradigm where standard tones (50ms) were interrupted by infrequent duration deviants (100ms). Spatio-temporal source cluster analysis with permutation testing revealed no difference between the groups in source activation to the standard tone. To the deviant tone however, there was significantly reduced right hemisphere fronto-temporal and insular cortex activation for the high SD group (p= 0.038). The MMF, as a product of the cortical response to the deviant minus that to the standard, did not differ significantly between the high and low Social Disorganisation groups. These data demonstrate a deficit in right fronto-temporal processing of an auditory change for those with more of the shared SD phenotype, indicating that right fronto-temporal auditory processing may be associated with psychosocial functioning.

Mismatch field latency, but not power, may mark a shared autistic and schizotypal trait phenotype.

The auditory mismatch negativity (MMN), a preattentive processing potential, and its magnetic counterpart (MMF) are consistently reported as reduced in schizophrenia and autism spectrum disorders. This study investigates whether MMF characteristics differ between subclinically high and low scorers on the recently discovered shared autism and schizophrenia phenotype, Social Disorganisation. A total of 18 low (10 females) and 19 high (9 females) Social Disorganisation scorers underwent magnetoencephalography (MEG) during a MMF paradigm of 50ms standard (1000Hz, 85%) and 100ms duration deviant tones. MMF was measured from the strongest active magnetometer over the right and left hemispheres (consistent across groups) after 100ms. No differences in MMF power were found, however there was a significant delay in the MMF peak (p=0.007). The P3am (following the MMF) was significantly reduced across both hemispheres for the high Social Disorganisation group (p=0.025), there were no specific hemispheric differences in P3am power or latency. Right MMF peak latency increased with higher scores on the schizotypal subscales Odd Speech, Odd Behaviour and Constricted Affect. Findings suggest that MMF peak latency delay marks a convergence of the autism and schizophrenia spectra at a subclinical. These findings have significant implications for future research methodology, as well as clinical practice.

Interactions between visual and semantic processing during object recognition revealed by modulatory effects of age of acquisition.

The age of acquisition (AoA) of objects and their names is a powerful determinant of processing speed in adulthood, with early-acquired objects being recognized and named faster than late-acquired objects. Previous research using fMRI (Ellis et al., 2006. Traces of vocabulary acquisition in the brain: evidence from covert object naming. NeuroImage 33, 958-968) found that AoA modulated the strength of BOLD responses in both occipital and left anterior temporal cortex during object naming. We used magnetoencephalography (MEG) to explore in more detail the nature of the influence of AoA on activity in those two regions. Covert object naming recruited a network within the left hemisphere that is familiar from previous research, including visual, left occipito-temporal, anterior temporal and inferior frontal regions. Region of interest (ROI) analyses found that occipital cortex generated a rapid evoked response (~75-200 ms at 0-40 Hz) that peaked at 95 ms but was not modulated by AoA. That response was followed by a complex of later occipital responses that extended from ~300 to 850 ms and were stronger to early- than late-acquired items from ~325 to 675 ms at 10-20 Hz in the induced rather than the evoked component. Left anterior temporal cortex showed an evoked response that occurred significantly later than the first occipital response (~100-400 ms at 0-10 Hz with a peak at 191 ms) and was stronger to early- than late-acquired items from ~100 to 300 ms at 2-12 Hz. A later anterior temporal response from ~550 to 1050 ms at 5-20 Hz was not modulated by AoA. The results indicate that the initial analysis of object forms in visual cortex is not influenced by AoA. A fastforward sweep of activation from occipital and left anterior temporal cortex then results in stronger activation of semantic representations for early- than late-acquired objects. Top-down re-activation of occipital cortex by semantic representations is then greater for early than late acquired objects resulting in delayed modulation of the visual response.

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.

The neural basis of the right visual field advantage in reading: an MEG analysis using virtual electrodes.

Right-handed participants respond more quickly and more accurately to written words presented in the right visual field (RVF) than in the left visual field (LVF). Previous attempts to identify the neural basis of the RVF advantage have had limited success. Experiment 1 was a behavioral study of lateralized word naming which established that the words later used in Experiment 2 showed a reliable RVF advantage which persisted over multiple repetitions. In Experiment 2, the same words were interleaved with scrambled words and presented in the LVF and RVF to right-handed participants seated in an MEG scanner. Participants read the real words silently and responded "pattern" covertly to the scrambled words. A beamformer analysis created statistical maps of changes in oscillatory power within the brain. Those whole-brain maps revealed activation of the reading network by both LVF and RVF words. Virtual electrode analyses used the same beamforming method to reconstruct the responses to real and scrambled words in three regions of interest in both hemispheres. The middle occipital gyri showed faster and stronger responses to contralateral than to ipsilateral stimuli, with evidence of asymmetric channeling of information into the left hemisphere. The left mid fusiform gyrus at the site of the 'visual word form area' responded more strongly to RVF than to LVF words. Activity in speech-motor cortex was lateralized to the left hemisphere, and stronger to RVF than LVF words, which is interpreted as representing the proximal cause of the RVF advantage for naming written words.

Functional asymmetries in the representation of noise-vocoded speech.

It is generally accepted that, while speech is processed bilaterally in auditory cortical areas, complementary analyses of the speech signal are carried out across the hemispheres. However, the Asymmetric Sampling in Time (AST) model (Poeppel, 2003) suggests that there is functional asymmetry due to different time scales of temporal integration in each hemisphere. The right hemisphere preferentially processes slow modulations commensurate with the theta frequency band (~4-8 Hz), whereas the left hemisphere is more sensitive to fast temporal modulations in the gamma frequency range (~25-50 Hz). Here we examined the perception of noise-vocoded, i.e. spectrally-degraded, words. Magnetoencephalography (MEG) beamformer analyses were used to determine where and how noise-vocoded speech is represented in terms of changes in power resulting from neuronal activity. The outputs of beamformer spatial filters were used to delineate the temporal dynamics of these changes in power. Beamformer analyses localised low-frequency "delta" (1-4 Hz) and "theta" (3-6 Hz) changes in total power to the left hemisphere and high-frequency "gamma" (60-80 Hz, 80-100 Hz) changes in total power to the right hemisphere. Time-frequency analyses confirmed the frequency content and timing of changes in power in the left and right hemispheres. Together the beamformer and time-frequency analyses demonstrate a functional asymmetry in the representation of noise-vocoded words that is inconsistent with the AST model, at least in brain areas outside of primary auditory cortex.

Non-parametric statistical thresholding of baseline free MEG beamformer images.

Magnetoencephalography (MEG) provides excellent temporal resolution when examining cortical activity in humans. Inverse methods such as beamforming (a spatial filtering approach) provide the means by which activity at cortical locations can be estimated. To date, the majority of work in this field has been based upon power changes between active and baseline conditions. Recent work, however, has focused upon other properties of the time series data reconstructed by these methods. One such metric, the Source Stability Index (SSI), relates to the consistency of the time series calculated only over an active period without the use of a baseline condition. In this paper we apply non-parametric statistics to SSI volumetric maps of simulation, auditory and somatosensory data in order to provide a robust and principled method of statistical inference in the absence of a baseline condition.

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.

Neural responses to rigidly moving faces displaying shifts in social attention investigated with fMRI and MEG.

A widely adopted neural model of face perception (Haxby, Hoffman, & Gobbini, 2000) proposes that the posterior superior temporal sulcus (STS) represents the changeable features of a face, while the face-responsive fusiform gyrus (FFA) encodes invariant aspects of facial structure. 'Changeable features' of a face can include rigid and non-rigid movements. The current study investigated neural responses to rigid, moving faces displaying shifts in social attention. Both functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) were used to investigate neural responses elicited when participants viewed video clips in which actors made a rigid shift of attention, signalled congruently from both the eyes and head. These responses were compared to those elicited by viewing static faces displaying stationary social attention information or a scrambled video displaying directional motion. Both the fMRI and MEG analyses demonstrated heightened responses along the STS to turning heads compared to static faces or scrambled movement conditions. The FFA responded to both turning heads and static faces, showing only a slight increase in response to the dynamic stimuli. These results establish the applicability of the Haxby model to the perception of rigid face motions expressing changes in social attention direction. Furthermore, the MEG beamforming analyses found an STS response in an upper frequency band (30-80 Hz) which peaked in the right anterior region. These findings, derived from two complementary neuroimaging techniques, clarify the contribution of the STS during the encoding of rigid facial action patterns of social attention, emphasising the role of anterior sulcal regions alongside previously observed posterior areas.