It has been suggested that the brain pre-empts changes in the visual environment through generating predictions, although real-time eletrophysiological evidence of prediction violations remains elusive. In a series of experiments we showed participants sequences of images that followed a predictable implied sequence or whose final image violated the implied sequence. Through careful design we were able to use the same final image transitions across predictable and unpredictable conditions, ensuring that any differences in neural responses were due only to preceding context and not to the images themselves. EEG and MEG recordings showed that early/mid-latency visual evoked potentials were robustly modulated by images that violated the implied sequence across a range of types of image change (expression deformations, rigid-rotations and visual field location). This modulation occurred irrespective of stimulus object category. Although the stimuli were static images, MEG source reconstruction of the early latency signal (N/M170) localised expectancy violation signals to brain areas associated with motion perception. Our findings suggest that the N/M170 can index mismatches between predicted and actual visual inputs in a system that predicts trajectories based on ongoing context. This has important implications for understanding the N/M170 and investigating how the brain represents context to generate perceptual predictions.

An unresolved goal in face perception is to identify brain areas involved in face processing and simultaneously understand the timing of their involvement. Currently, high spatial resolution imaging techniques identify the fusiform gyrus as subserving processing of invariant face features relating to identity. High temporal resolution imaging techniques localize an early latency evoked component—the N/M170—as having a major generator in the fusiform region; however, this evoked component is not believed to be associated with the processing of identity. To resolve this, we used novel magnetoencephalographic beamformer analyses to localize cortical regions in humans spatially with trial-by-trial activity that differentiated faces and objects and to interrogate their functional sensitivity by analyzing the effects of stimulus repetition. This demonstrated a temporal sequence of processing that provides category-level and then item-level invariance. The right fusiform gyrus showed adaptation to faces (not objects) at ∼150 ms after stimulus onset regardless of face identity; however, at the later latency of ∼200–300 ms, this area showed greater adaptation to repeated identity faces than to novel identities. This is consistent with an involvement of the fusiform region in both early and midlatency face-processing operations, with only the latter showing sensitivity to invariant face features relating to identity.SIGNIFICANCE STATEMENTNeuroimaging techniques with high spatial-resolution have identified brain structures that are reliably activated when viewing faces and techniques with high temporal resolution have identified the time-varying temporal signature of the brain's response to faces. However, until now, colocalizing face-specific mechanisms in both time and space has proven notoriously difficult. Here, we used novel magnetoencephalographic analysis techniques to spatially localize cortical regions with trial-by-trial temporal activity that differentiates between faces and objects and to interrogate their functional sensitivity by analyzing effects of stimulus repetition on the time-locked signal. These analyses confirm a role for the right fusiform region in early to midlatency responses consistent with face identity processing and convincingly deliver upon magnetoencephalography's promise to resolve brain signals in time and space simultaneously.

Objectives Neuroimaging in chronic breathlessness is challenging. The study objective was to test the feasibility of magnetoencephalography (MEG) for functional neuroimaging of people with chronic breathlessness. Design Feasibility pilot study. Setting Respiratory clinic out-patients. Participants 8 patients (mean age=62; (range 47–83); 4 men) with chronic non-malignant lung disease; modified MRC breathlessness score ≥3 (median mMRC=4), intensity of exercise-induced breathlessness >3/10; no contraindication to MRI scanning. Methods and measures 4 MEG scans were conducted for each participant: (1) at rest (5 mins), (2) postseated leg exercise-induced breathlessness during recovery (10 mins). Recovery scans (2) were conducted with/without facial airflow in random order; both scans were repeated 1 h later. Participants rated breathlessness intensity (0–10 Numerical Rating Scale (NRS)) at baseline, maximal exertion and every minute during recovery, and rated acceptability of study procedures at the end of the study (0–10 NRS). A structural MRI scan was conducted for MEG coregistration and source-space analyses. Rest data were compared with data from healthy volunteers (N=6; 5 men; mean age=30.7 years±3.9 years). Results Exercises and MEG scanning were acceptable to all participants; 7/8 completed the MRI scans. Maximum breathlessness intensity was induced by 5 min’ exercise. The same level was induced for repeat scans (median=8; IQR=7–8). All recovered to baseline by 10 min. Time-frequency profiles of data from the first and last 3 min were analysed in MEG source space based on breathlessness location estimates. Source localisation was performed, but anatomical source inference was limited to the level of the lobe. Differences in areas of activity were seen: during recovery scans; with and without airflow; and between participants/normal volunteers at rest. Conclusions MEG is a feasible method to investigate exercise-induced breathlessness in people breathless with chronic lung disease, and able to identify neural activity related to changes in breathlessness.

Prior evidence for early activity in Broca's area during reading may reflect fast access to articulatory codes in left inferior frontal gyrus pars opercularis (LIFGpo). We put this hypothesis to test using a benchmark for articulatory involvement in reading known as the masked onset priming effect (MOPE). In masked onset priming, briefly presented pronounceable strings of letters that share an initial phoneme with subsequently presented target words (e.g., gilp-GAME) facilitate word naming responses compared with unrelated primes (dilp-GAME). Crucially, these priming effects only occur when the task requires articulation (naming), and not when it requires lexical decisions. A standard explanation of masked onset priming is that it reflects fast computation of articulatory output codes from letter representations. We therefore predicted 1) that activity in left IFG pars opercularis would be modulated by masked onset priming, 2) that priming-related modulation in LIFGpo would immediately follow activity in occipital cortex, and 3) that this modulation would be greater for naming than for lexical decision. These predictions were confirmed in a magnetoencephalography (MEG) priming study. MOPEs emerged in left IFG at ∼100 ms posttarget onset, and the priming effects were more sustained when the task involved articulation.

Background: Neuroimaging in chronic dyspnoea is challenging.Aim: Feasibility of MEG in chronic dyspnoeaMethods: An exploratory cohort had chronic respiratory disease (mMRC dyspnoea 3,4). Patients performed seated leg exercise. Baseline data: cause/duration/intensity of dyspnoea. Four MEG scans were conducted: 1) at rest (5 mins), 2) post exercise dyspnoea recovery (10 mins); 1+2 repeated after an hour. Recovery scans were conducted +/- facial airflow in random order. Patients rated dyspnoea intensity (0-10 NRS) at baseline, maximal exertion and every minute during recovery. A structural MRI scan was conducted. Data was compared with banked data from normal volunteers.Results: 7/8 patients(mean age=62;[47-83]; 4 males; median mMRC=4) completed all scans except one MRI.Maximum dyspnoea intensity was induced by 5 minutes, and induced to the same level for repeat scans (median=8; IQR=7-8). All recovered to baseline by 10 minutes.Virtual Electrodes (VEs)(time-series estimates at specified points)were generated from the first and last 3 minutes of post-exercise data and the time/frequency profile plotted. VEs were based on dyspnoea pathway location estimates: prefrontal cortex; amygdala; anterior cingulate cortex; anterior insula; post and precentral gyrus. Predominant activity frequencies were in the beta (13-30 Hz) and gamma (30-80 Hz) bands. Preliminary beamformer-source localisation in individuals shows differences in areas of activity: post-exercise/on recovery; with/without airflow; between patients/normal volunteers at rest.Conclusions: MEG is a feasible, potentially useful method to investigate chronic dyspnoea, able to identify neural activity related to changes in dyspnoea.

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.

In this study we investigate whether stimulus variability affects the auditory steady-state response (ASSR). We present cosinusoidal AM pulses as stimuli where we are able to manipulate waveform shape independently of the fixed repetition rate of 4 Hz. We either present sounds in which the waveform shape, the pulse-width, is fixed throughout the presentation or where it varies pseudo-randomly. Importantly, the average spectra of all the fixed-width AM stimuli are equal to the spectra of the mixed-width AM. Our null hypothesis is that the average ASSR to the fixed-width AM will not be significantly different from the ASSR to the mixed-width AM. In a region of interest beamformer analysis of MEG data, we compare the 4 Hz component of the ASSR to the mixed-width AM with the 4 Hz component of the ASSR to the pooled fixed-width AM. We find that at the group level, there is a significantly greater response to the variable mixed-width AM at the medial boundary of the Middle and Superior Temporal Gyri. Hence, we find that adding variability into AM stimuli increases the amplitude of the ASSR. This observation is important, as it provides evidence that analysis of the modulation waveform shape is an integral part of AM processing. Therefore, standard steady-state studies in audition, using sinusoidal AM, may not be sensitive to a key feature of acoustic processing.

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.

Speech contains complex amplitude modulations that have envelopes with multiple temporal cues. The processing of these complex envelopes is not well explained by the classical models of amplitude modulation processing. This may be because the evidence for the models typically comes from the use of simple sinusoidal amplitude modulations. In this study we used magnetoencephalography (MEG) to generate source space current estimates of the steady-state responses to simple one-component amplitude modulations and to a two-component amplitude modulation. A two-component modulation introduces the simplest form of modulation complexity into the waveform; the summation of the two-modulation rates introduces a beat-like modulation at the difference frequency between the two modulation rates. We compared the cortical representations of responses to the one-component and two-component modulations. In particular, we show that the temporal complexity in the two-component amplitude modulation stimuli was preserved at the cortical level. The method of stimulus normalization that we used also allows us to interpret these results as evidence that the important feature in sound modulations is the relative depth of one modulation rate with respect to another, rather than the absolute carrier-to-sideband modulation depth. More generally, this may be interpreted as evidence that modulation detection accurately preserves a representation of the modulation envelope. This is an important observation with respect to models of modulation processing, as it suggests that models may need a dynamic processing step to effectively model non-stationary stimuli. We suggest that the classic modulation filterbank model needs to be modified to take these findings into account.

This paper introduces a lead field formulation for use in beamformer analysis of MEG data. This 'dual source beamformer' is a technique to image two temporally correlated sources using beamformer methodology. We show that while the standard, single source beamformer suppresses the reconstructed power of two spatially separate but temporally correlated sources, the dual source beamformer allows for their accurate reconstruction. The technique is proven to be accurate using simulations. We also show that it can be used to image accurately the auditory steady state response, which is correlated between the left and right auditory cortices. We suggest that this technique represents a useful way of locating correlated sources, particularly if a seed location can be defined a priori for one of the two sources. Such a priori information could be based on previous studies using similar paradigms, or from other functional neuroimaging techniques.

MEG beamformer algorithms work by making the assumption that correlated and spatially distinct local field potentials do not develop in the human brain. Despite this assumption, images produced by such algorithms concur with those from other non-invasive and invasive estimates of brain function. In this paper we set out to develop a method that could be applied to raw MEG data to explicitly test his assumption. We show that a promax rotation of MEG channel data can be used as an approximate estimator of the number of spatially distinct correlated sources in any frequency band.