Krish D. Singh

YNIMG Journal 2021 Journal Article

A comparison of GABA-ergic (propofol) and non-GABA-ergic (dexmedetomidine) sedation on visual and motor cortical oscillations, using magnetoencephalography

• Neeraj Saxena
• Suresh D. Muthukumaraswamy
• Lewys Richmond
• Adele Babic
• Krish D. Singh
• Judith E. Hall
• Richard G. Wise
• Alexander D. Shaw

Studying changes in cortical oscillations can help elucidate the mechanistic link between receptor physiology and the clinical effects of anaesthetic drugs. Propofol, a GABA-ergic drug produces divergent effects on visual cortical activity: increasing induced gamma-band responses (GBR) while decreasing evoked responses. Dexmedetomidine, an α2- adrenergic agonist, differs from GABA-ergic sedatives both mechanistically and clinically as it allows easy arousability from deep sedation with less cognitive side-effects. Here we use magnetoencephalography (MEG) to characterize and compare the effects of GABA-ergic (propofol) and non-GABA-ergic (dexmedetomidine) sedation, on visual and motor cortical oscillations. Sixteen male participants received target-controlled infusions of propofol and dexmedetomidine, producing mild-sedation, in a placebo-controlled, cross-over study. MEG data was collected during a combined visuomotor task. The key findings were that propofol significantly enhanced visual stimulus induced GBR (44% increase in amplitude) while dexmedetomidine decreased it (40%). Propofol also decreased the amplitudes of the Mv100 (visual M100) (27%) and Mv150 (52%) visual evoked fields (VEF), whilst dexmedetomidine had no effect on these. During the motor task, neither drug had any significant effect on movement related gamma synchrony (MRGS), movement related beta de-synchronisation (MRBD) or Mm100 (movement-related M100) movement-related evoked fields (MEF), although dexmedetomidine slowed the Mm300. Dexmedetomidine increased (92%) post-movement beta synchronisation/rebound (PMBR) power while propofol reduced it (70%, statistically non- significant). Overall, dexmedetomidine and propofol, at equi-sedative doses, produce contrasting effects on visual induced GBR, VEF, PMBR and MEF. These findings provide a mechanistic link between the known receptor physiology of these sedative drugs with their known clinical effects and may be used to explore mechanisms of other anaesthetic drugs on human consciousness.

YNIMG Journal 2021 Journal Article

Measuring robust functional connectivity from resting-state MEG using amplitude and entropy correlation across frequency bands and temporal scales

• Megan Godfrey
• Krish D. Singh

Recent studies have shown how MEG can reveal spatial patterns of functional connectivity using frequency-specific oscillatory coupling measures and that these may be modified in disease. However, there is a need to understand both how repeatable these patterns are across participants and how these measures relate to the moment-to-moment variability (or ‘irregularity) of neural activity seen in healthy brain function. In this study, we used Multi-scale Rank-Vector Entropy (MRVE) to calculate the dynamic timecourses of signal variability over a range of temporal scales. The correlation of MRVE timecourses was then used to detect functional connections in resting state MEG recordings that were robust over 183 participants and varied with temporal scale. We compared these MRVE connectivity patterns to those derived using the more conventional method of oscillatory amplitude envelope correlation (AEC) using methods designed to quantify the consistency of these patterns across participants. Using AEC, the most consistent connectivity patterns, across the cohort, were seen in the alpha and beta frequency bands. At fine temporal scales (corresponding to ‘scale frequencies, f S = 30-150Hz), MRVE correlation detected mostly occipital and parietal connections. These showed high similarity with the networks identified by AEC in the alpha and beta frequency bands. The most consistent connectivity profiles between participants were given by MRVE correlation at f S = 75Hz and AEC in the beta band. The physiological relevance of MRVE was also investigated by examining the relationship between connectivity strength and local variability. It was found that local activity at frequencies f S ≳ 10Hz becomes more regular when a region exhibits high levels of resting state connectivity, as measured by fine scale MRVE correlation ( f S ∼ 30-150Hz) and by alpha and beta band AEC. Analysis of the EOG recordings also revealed that eye movement affected both connectivity measures. Higher levels of eye movement were associated with stronger frontal connectivity, as measured by MRVE correlation. More eye movement was also associated with reduced occipital and parietal connectivity strength for both connectivity measures, although this was not significant after correction for multiple comparisons.

YNICL Journal 2021 Journal Article

Motor-related oscillatory activity in schizophrenia according to phase of illness and clinical symptom severity

• Lauren E. Gascoyne
• Matthew J. Brookes
• Mohanbabu Rathnaiah
• Mohammad Zia Ul Haq Katshu
• Loes Koelewijn
• Gemma Williams
• Jyothika Kumar
• James T.R. Walters

Magnetoencephalography (MEG) measures magnetic fields generated by synchronised neural current flow and provides direct inference on brain electrophysiology and connectivity, with high spatial and temporal resolution. The movement-related beta decrease (MRBD) and the post-movement beta rebound (PMBR) are well-characterised effects in magnetoencephalography (MEG), with the latter having been shown to relate to long-range network integrity. Our previous work has shown that the PMBR is diminished (relative to controls) in a group of schizophrenia patients. However, little is known about how this effect might differ in patients at different stages of illness and degrees of clinical severity. Here, we extend our previous findings showing that the MEG derived PMBR abnormality in schizophrenia exists in 29 recent-onset and 35 established cases (i.e., chronic patients), compared to 42 control cases. In established cases, PMBR is negatively correlated with severity of disorganization symptoms. Further, using a hidden Markov model analysis, we show that transient pan-spectral oscillatory "bursts", which underlie the PMBR, differ between healthy controls and patients. Results corroborate that PMBR is associated with disorganization of mental activity in schizophrenia.

YNICL Journal 2020 Journal Article

Patient, interrupted: MEG oscillation dynamics reveal temporal dysconnectivity in schizophrenia

• Golnoush Alamian
• Annalisa Pascarella
• Tarek Lajnef
• Laura Knight
• James Walters
• Krish D. Singh
• Karim Jerbi

Current theories of schizophrenia emphasize the role of altered information integration as the core dysfunction of this illness. While ample neuroimaging evidence for such accounts comes from investigations of spatial connectivity, understanding temporal disruptions is important to fully capture the essence of dysconnectivity in schizophrenia. Recent electrophysiology studies suggest that long-range temporal correlation (LRTC) in the amplitude dynamics of neural oscillations captures the integrity of transferred information in the healthy brain. Thus, in this study, 25 schizophrenia patients and 25 controls (8 females/group) were recorded during two five-minutes of resting-state magnetoencephalography (once with eyes-open and once with eyes-closed). We used source-level analyses to investigate temporal dysconnectivity in patients by characterizing LRTCs across cortical and sub-cortical brain regions. In addition to standard statistical assessments, we applied a machine learning framework using support vector machine to evaluate the discriminative power of LRTCs in identifying patients from healthy controls. We found that neural oscillations in schizophrenia patients were characterized by reduced signal memory and higher variability across time, as evidenced by cortical and subcortical attenuations of LRTCs in the alpha and beta frequency bands. Support vector machine significantly classified participants using LRTCs in key limbic and paralimbic brain areas, with decoding accuracy reaching 82%. Importantly, these brain regions belong to networks that are highly relevant to the symptomology of schizophrenia. These findings thus posit temporal dysconnectivity as a hallmark of altered information processing in schizophrenia, and help advance our understanding of this pathology.

YNIMG Journal 2018 Journal Article

Spatial attention modulates visual gamma oscillations across the human ventral stream

• Lorenzo Magazzini
• Krish D. Singh

Oscillatory synchronization in the gamma frequency range has been proposed as a neuronal mechanism to prioritize processing of relevant stimuli over competing ones. Recent studies in animals found that selective spatial attention enhanced gamma-band synchronization in high-order visual areas (V4) and increased the gamma peak frequency in V1. The existence of such mechanisms in the human visual system is yet to be fully demonstrated. In this study, we used MEG, in combination with an optimised stimulus design, to record visual gamma oscillations from human early visual cortex, while participants performed a visuospatial attention cueing task. First, we reconstructed virtual sensors in V1/V2, where gamma oscillations were strongly induced by visual stimulation alone. Second, following the results of a statistical comparison between conditions of attention, we reconstructed cortical activity also in inferior occipital-temporal regions (V4). The results indicated that gamma amplitude was modulated by spatial attention across the cortical hierarchy, both in the early visual cortex and in higher-order regions of the ventral visual pathway. In contrast, we found no evidence for an increase in the gamma peak frequency in V1/V2 with attention. The gamma response tended to peak earlier in V1/V2 than in V4 by approximately 70 ms, consistent with a feed-forward role of gamma-band activity in propagating sensory representations across the visual cortical hierarchy. Together, these findings suggest that differences in experimental design or methodology can account for the inconsistencies in previous animal and human studies. Furthermore, our results are in line with the hypothesis of enhanced gamma-band synchronization as an attentional mechanism in the human visual cortex.

YNIMG Journal 2018 Journal Article

Spatial frequency supports the emergence of categorical representations in visual cortex during natural scene perception

• Diana C. Dima
• Gavin Perry
• Krish D. Singh

In navigating our environment, we rapidly process and extract meaning from visual cues. However, the relationship between visual features and categorical representations in natural scene perception is still not well understood. Here, we used natural scene stimuli from different categories and filtered at different spatial frequencies to address this question in a passive viewing paradigm. Using representational similarity analysis (RSA) and cross-decoding of magnetoencephalography (MEG) data, we show that categorical representations emerge in human visual cortex at ∼180 ms and are linked to spatial frequency processing. Furthermore, dorsal and ventral stream areas reveal temporally and spatially overlapping representations of low and high-level layer activations extracted from a feedforward neural network. Our results suggest that neural patterns from extrastriate visual cortex switch from low-level to categorical representations within 200 ms, highlighting the rapid cascade of processing stages essential in human visual perception.

YNIMG Journal 2017 Journal Article

Assessment and elimination of the effects of head movement on MEG resting-state measures of oscillatory brain activity

• Eirini Messaritaki
• Loes Koelewijn
• Diana C. Dima
• Gemma M. Williams
• Gavin Perry
• Krish D. Singh

Magnetoencephalography (MEG) is increasingly being used to study brain function because of its excellent temporal resolution and its direct association with brain activity at the neuronal level. One possible cause of error in the analysis of MEG data comes from the fact that participants, even MEG-experienced ones, move their head in the MEG system. Head movement can cause source localization errors during the analysis of MEG data, which can result in the appearance of source variability that does not reflect brain activity. The MEG community places great importance in eliminating this source of possible errors as is evident, for example, by recent efforts to develop head casts that limit head movement in the MEG system. In this work we use software tools to identify, assess and eliminate from the analysis of MEG data any possible correlations between head movement in the MEG system and widely-used measures of brain activity derived from MEG resting-state recordings. The measures of brain activity we study are a) the Hilbert-transform derived amplitude envelope of the beamformer time series and b) functional networks; both measures derived by MEG resting-state recordings. Ten-minute MEG resting-state recordings were performed on healthy participants, with head position continuously recorded. The sources of the measured magnetic signals were localized via beamformer spatial filtering. Temporal independent component analysis was subsequently used to derive resting-state networks. Significant correlations were observed between the beamformer envelope time series and head movement. The correlations were substantially reduced, and in some cases eliminated, after a participant-specific temporal high-pass filter was applied to those time series. Regressing the head movement metrics out of the beamformer envelope time series had an even stronger effect in reducing these correlations. Correlation trends were also observed between head movement and the activation time series of the default-mode and frontal networks. Regressing the head movement metrics out of the beamformer envelope time series completely eliminated these correlations. Additionally, applying the head movement correction resulted in changes in the network spatial maps for the visual and sensorimotor networks. Our results a) show that the results of MEG resting-state studies that use the above-mentioned analysis methods are confounded by head movement effects, b) suggest that regressing the head movement metrics out of the beamformer envelope time series is a necessary step to be added to these analyses, in order to eliminate the effect that head movement has on the amplitude envelope of beamformer time series and the network time series and c) highlight changes in the connectivity spatial maps when head movement correction is applied.

YNIMG Journal 2016 Journal Article

Transcranial modulation of brain oscillatory responses: A concurrent tDCS–MEG investigation

• Claire J. Hanley
• Krish D. Singh
• David J. McGonigle

Despite the increasing use of transcranial direct current stimulation (tDCS), the physiological mechanisms underlying its effects are still largely unknown. One approach to directly investigate the effects of the neuromodulation technique on the brain is to integrate tDCS with non-invasive neuroimaging in humans. To provide new insight into the neurobiology of the method, DC stimulation (1mA, 600s) was applied concurrently with Magnetoencephalography (MEG), while participants engaged in a visuomotor task before, during and after a period of tDCS. Responses in the motor beta band (15–30Hz) and visual gamma band (30–80Hz) were localised using Synthetic Aperture Magnetometry (SAM). The resulting induced and evoked oscillatory responses were subsequently analysed. A statistically significant reduction of average power in the visual gamma band was observed for anodal compared to sham stimulation. The magnitude of motor evoked responses was also found to be significantly modulated by anodal stimulation. These results demonstrate that MEG can be used to derive inferences on the cortical mechanisms of tDCS.

YNIMG Journal 2015 Journal Article

Corrigendum to “The contribution of pre-s timulus neural oscillatory activity to spontaneous response time variability” [Neuroimage 107 (2015) 34–45]

• Aline Bompas
• Petroc Sumner
• Suresh D. Muthukumaraswamy
• Krish D. Singh
• Iain D. Gilchrist

YNIMG Journal 2015 Journal Article

The contribution of pre-stimulus neural oscillatory activity to spontaneous response time variability

• Aline Bompas
• Petroc Sumner
• Suresh D. Muthumumaraswamy
• Krish D. Singh
• Iain D. Gilchrist

Large variability between individual response times, even in identical conditions, is a ubiquitous property of animal behavior. However, the origins of this stochasticity and its relation to action decisions remain unclear. Here we focus on the state of the perception–action network in the pre-stimulus period and its influence on subsequent saccadic response time and choice in humans. We employ magnetoencephalography (MEG) and a correlational source reconstruction approach to identify the brain areas where pre-stimulus oscillatory activity predicted saccadic response time to visual targets. We find a relationship between future response time and pre-stimulus power, but not phase, in occipital (including V1), parietal, posterior cingulate and superior frontal cortices, consistently across alpha, beta and low gamma frequencies, each accounting for between 1 and 4% of the RT variance. Importantly, these correlations were not explained by deterministic sources of variance, such as experimental factors and trial history. Our results further suggest that occipital areas mainly reflect short-term (trial to trial) stochastic fluctuations, while the frontal contribution largely reflects longer-term effects such as fatigue or practice. Parietal areas reflect fluctuations at both time scales. We found no evidence of lateralization: these effects were indistinguishable in both hemispheres and for both saccade directions, and non-predictive of choice — a finding with fundamental consequences for models of action decision, where independent, not coupled, noise is normally assumed.

YNIMG Journal 2014 Journal Article

Almost winning: Induced MEG theta power in insula and orbitofrontal cortex increases during gambling near-misses and is associated with BOLD signal and gambling severity

• Simon Dymond
• Natalia S. Lawrence
• Benjamin T. Dunkley
• Kenneth S.L. Yuen
• Elanor C. Hinton
• Mark R. Dixon
• W. Miles Cox
• Alice E. Hoon

In slot machine gambling, the “near-miss effect” (when a losing display physically resembles an actual win display) has been implicated in pathological gambling (PG). Functional magnetic resonance imaging (fMRI) with PG and non-PG participants shows that near-misses recruit reward-related circuitry, but little is known about the temporal dynamics and oscillatory changes underlying near-misses. The present multi-modal imaging study investigated the near-miss effect by combining the spatial resolution of blood oxygen-level dependent (BOLD)-fMRI with the spatial and temporal resolution of magnetoencephalography (MEG) during a slot machine task in PG and non-PG groups. Given previous findings on outcome (win and near-miss) processing, functional overlap was hypothesized between induced changes in temporal oscillations and BOLD response to wins and near-misses in PG. We first validated our task in a sample of varying gambling severity using BOLD-fMRI and then compared PG and non-PG participants using MEG to investigate changes in induced oscillatory power associated with win and near-miss, relative to loss, outcomes. Across both modalities, near-misses recruited similar brain regions to wins, including right inferior frontal gyrus and insula. Using MEG, increased theta-band (4–7Hz) oscillations to near-misses were observed in the insula and right orbitofrontal cortex (OFC). Furthermore, this theta-band activity was positively associated with gambling severity. These findings demonstrate that the near-miss effect in insula and OFC is associated with induced theta oscillations. The significance of these findings for theories of PG and the development of potential biomarkers and therapeutic targets is discussed.

YNIMG Journal 2013 Journal Article

Spatial attention increases high-frequency gamma synchronisation in human medial visual cortex

• Loes Koelewijn
• Anina N. Rich
• Suresh D. Muthukumaraswamy
• Krish D. Singh

Visual information processing involves the integration of stimulus and goal-driven information, requiring neuronal communication. Gamma synchronisation is linked to neuronal communication, and is known to be modulated in visual cortex both by stimulus properties and voluntarily-directed attention. Stimulus-driven modulations of gamma activity are particularly associated with early visual areas such as V1, whereas attentional effects are generally localised to higher visual areas such as V4. The absence of a gamma increase in early visual cortex is at odds with robust attentional enhancements found with other measures of neuronal activity in this area. Here we used magnetoencephalography (MEG) to explore the effect of spatial attention on gamma activity in human early visual cortex using a highly effective gamma-inducing stimulus and strong attentional manipulation. In separate blocks, subjects tracked either a parafoveal grating patch that induced gamma activity in contralateral medial visual cortex, or a small line at fixation, effectively attending away from the gamma-inducing grating. Both items were always present, but rotated unpredictably and independently of each other. The rotating grating induced gamma synchronisation in medial visual cortex at 30–70Hz, and in lateral visual cortex at 60–90Hz, regardless of whether it was attended. Directing spatial attention to the grating increased gamma synchronisation in medial visual cortex, but only at 60–90Hz. These results suggest that the generally found increase in gamma activity by spatial attention can be localised to early visual cortex in humans, and that stimulus and goal-driven modulations may be mediated at different frequencies within the gamma range.

YNIMG Journal 2013 Journal Article

The properties of induced gamma oscillations in human visual cortex show individual variability in their dependence on stimulus size

• Gavin Perry
• Khalid Hamandi
• Lisa M. Brindley
• Suresh D. Muthukumaraswamy
• Krish D. Singh

The role of gamma-band (typically 30–100Hz) oscillations in visual processing is a topic of increasing interest. One hypothesis is that gamma oscillations reflect the action of GABAergic inhibitory processes in the visual cortex responsible for surround-suppression. Evidence from primate neurophysiology [Gieselmann & Thiele, A. , 2008. European Journal of Neuroscience 28, 447–459. ] suggests that the amplitude of the gamma-band response increases as a visual grating stimulus expands outside of the classical receptive field into the inhibitory surround; with the amplitude of the response increasing, and the frequency of the response decreasing, monotonically with stimulus size. In this study, we tested the relationship between the gamma-band response and the size of visual grating stimuli in humans using MEG. In two initial experiments we found that, while the absolute magnitude of the gamma-band response varied considerably across participants, in all cases the amplitude of the response had a monotonically increasing relationship with size. In contrast, we did not find any relationship between the frequency of the response and the size of the stimulus. Previously, the frequency of the visual gamma-band response has been found to correlate across individuals with the surface area of cortical area V1 [Schwarzkopf et al. , 2012. Journal of Neuroscience 32, 1507–12. ] We, however, were unable to find any correlation between the frequency or the magnitude of the gamma-band response and the dimensions of V1 cortical gray matter as measured from participants' MR images. Consistent with a saturation of the gamma-band response found for some individuals in the first two experiments, in a third experiment we found that the magnitude of the response to our largest stimulus (8°) was less than that predicted from the response to the stimulus' parts.

YNIMG Journal 2012 Journal Article

Which “neural activity” do you mean? fMRI, MEG, oscillations and neurotransmitters

• Krish D. Singh

Over the last 20years, BOLD-FMRI has proved itself to be a powerful and versatile tool for the study of the neural substrate underpinning many of our cognitive and perceptual functions. However, exactly how it is coupled to the underlying neurophysiology, and how this coupling varies across the brain, across tasks and across individuals is still unclear. The story is further complicated by the fact that within the same cortical region, multiple evoked and induced oscillatory effects may be modulated during task execution, supporting different cognitive roles, and any or all of these may have metabolic demands that then drive the BOLD response. In this paper I shall concentrate on one experimental approach to shedding light on this problem i. e. the execution of the same experimental tasks using MEG and fMRI in order to reveal which electrophysiological responses best match the BOLD response spatially, temporally and functionally. The results demonstrate a rich and complex story that does not fit with a simplistic view of BOLD reflecting “neural activity” and suggests that we could consider the coupling between BOLD and the various parameters of neural function as an ill-posed inverse problem. Finally, I describe recent work linking individual variability in both cortical oscillations and the BOLD-fMRI response to variability in endogenous GABA concentration.

YNIMG Journal 2011 Journal Article

Induced and evoked neural correlates of orientation selectivity in human visual cortex

• Loes Koelewijn
• Julie R. Dumont
• Suresh D. Muthukumaraswamy
• Anina N. Rich
• Krish D. Singh

Orientation discrimination is much better for patterns oriented along the horizontal or vertical (cardinal) axes than for patterns oriented obliquely, but the neural basis for this is not known. Previous animal neurophysiology and human neuroimaging studies have demonstrated only a moderate bias for cardinal versus oblique orientations, with fMRI showing a larger response to cardinals in primary visual cortex (V1) and EEG demonstrating both increased magnitudes and reduced latencies of transient evoked responses. Here, using MEG, we localised and characterised induced gamma and transient evoked responses to stationary circular grating patches of three orientations (0, 45, and 90° from vertical). Surprisingly, we found that the sustained gamma response was larger for oblique, compared to cardinal, stimuli. This “inverse oblique effect” was also observed in the earliest (80ms) evoked response, whereas later responses (120ms) showed a trend towards the reverse, “classic”, oblique response. Source localisation demonstrated that the sustained gamma and early evoked responses were localised to medial visual cortex, whilst the later evoked responses came from both this early visual area and a source in a more inferolateral extrastriate region. These results suggest that (1) the early evoked and sustained gamma responses manifest the initial tuning of V1 neurons, with the stronger response to oblique stimuli possibly reflecting increased tuning widths for these orientations, and (2) the classic behavioural oblique effect is mediated by an extrastriate cortical area and may also implicate feedback from extrastriate to primary visual cortex.

YNIMG Journal 2010 Journal Article

Visual gamma oscillations and evoked responses: Variability, repeatability and structural MRI correlates

• Suresh D. Muthukumaraswamy
• Krish D. Singh
• Jennifer B. Swettenham
• Derek K. Jones

There is increasing interest in the role gamma oscillations (∼40 Hz) play in visual information processing. Despite this interest, and in contrast to the classically studied visual evoked potential, surprisingly little is known about the intra-individual repeatability of induced gamma oscillations. Similarly, little is known about inter-individual variability in terms of gamma oscillation frequency, bandwidth and amplitude with no extant normative data for these parameters. The purpose of the current study was therefore to examine the repeatability of visual gamma oscillations and to provide the first normative data on them. Our results demonstrate that evoked responses were highly repeatable across recording sessions whereas for induced visual gamma oscillations a large amount of inter-individual variability existed in terms of frequency, bandwidth and amplitude. However, these parameters and the general morphology of the gamma band response were stable within the same individuals for at least 4 weeks. The high degree of individual variability in gamma oscillations for gamma amplitude, bandwidth and frequency suggests that between-group studies on gamma oscillations will be difficult, requiring relatively large amounts of data to detect differences. However, the high degree of individual repeatability for gamma oscillation frequency, bandwidth and amplitude suggests that these dependent variables will be well suited for repeated-measure designs such as pharmacological studies. A number of individuals are described which show clear evoked responses yet a near absence of gamma oscillations and vice versa suggesting dissociations between the generative mechanisms of these responses. Our results also demonstrate that gamma frequency tends to decline with age and is positively correlated with the thickness of the pericalcarine cortex.

YNIMG Journal 2008 Journal Article

Spatiotemporal frequency tuning of BOLD and gamma band MEG responses compared in primary visual cortex

• Suresh D. Muthukumaraswamy
• Krish D. Singh

In this study, the spatial and temporal frequency tuning characteristics of the MEG gamma (40–60 Hz) rhythm and the BOLD response in primary visual cortex were measured and compared. In an identical MEG/fMRI paradigm, 10 participants viewed reversing square wave gratings at 2 spatial frequencies [0. 5 and 3 cycles per degree (cpd)] reversing at 5 temporal frequencies (0, 1 6, 10, 15 Hz). Three-dimensional images of MEG source power were generated with synthetic aperture magnetometry (SAM) and showed a high degree of spatial correspondence with BOLD responses in primary visual cortex with a mean spatial separation of 6. 5 mm, but the two modalities showed different tuning characteristics. The gamma rhythm showed a clear increase in induced power for the high spatial frequency stimulus while BOLD showed no difference in activity for the two spatial frequencies used. Both imaging modalities showed a general increase of activity with temporal frequency, however, BOLD plateaued around 6–10 Hz while the MEG generally increased with a dip exhibited at 6 Hz. These results demonstrate that the two modalities may show activation in similar spatial locations but that the functional pattern of these activations may differ in a complex manner, suggesting that they may be tuned to different aspects of neuronal activity.

YNIMG Journal 2007 Journal Article

The spatial distribution and temporal dynamics of brain regions activated during the perception of object and non-object patterns

• Frances A. Maratos
• Stephen J. Anderson
• Arjan Hillebrand
• Krish D. Singh
• Gareth R. Barnes

Both animal and human studies suggest that the efficiency with which we are able to grasp objects is attributable to a repertoire of motor signals derived directly from vision. This is in general agreement with the long-held belief that the automatic generation of motor signals by the perception of objects is based on the actions they afford. In this study, we used magnetoencephalography (MEG) to determine the spatial distribution and temporal dynamics of brain regions activated during passive viewing of object and non-object targets that varied in the extent to which they afforded a grasping action. Synthetic Aperture Magnetometry (SAM) was used to localize task-related oscillatory power changes within specific frequency bands, and the time course of activity within given regions-of-interest was determined by calculating time–frequency plots using a Morlet wavelet transform. Both single subject and group-averaged data on the spatial distribution of brain activity are presented. We show that: (i) significant reductions in 10–25 Hz activity within extrastriate cortex, occipito-temporal cortex, sensori-motor cortex and cerebellum were evident with passive viewing of both objects and non-objects; and (ii) reductions in oscillatory activity within the posterior part of the superior parietal cortex (area Ba7) were only evident with the perception of objects. Assuming that focal reductions in low-frequency oscillations (<30 Hz) reflect areas of heightened neural activity, we conclude that: (i) activity within a network of brain areas, including the sensori-motor cortex, is not critically dependent on stimulus type and may reflect general changes in visual attention; and (ii) the posterior part of the superior parietal cortex, area Ba7, is activated preferentially by objects and may play a role in computations related to grasping.

YNIMG Journal 2006 Journal Article

A verifiable solution to the MEG inverse problem

• Gareth R. Barnes
• Paul L. Furlong
• Krish D. Singh
• Arjan Hillebrand

Magnetoencephalography (MEG) is a non-invasive brain imaging technique with the potential for very high temporal and spatial resolution of neuronal activity. The main stumbling block for the technique has been that the estimation of a neuronal current distribution, based on sensor data outside the head, is an inverse problem with an infinity of possible solutions. Many inversion techniques exist, all using different a-priori assumptions in order to reduce the number of possible solutions. Although all techniques can be thoroughly tested in simulation, implicit in the simulations are the experimenter's own assumptions about realistic brain function. To date, the only way to test the validity of inversions based on real MEG data has been through direct surgical validation, or through comparison with invasive primate data. In this work, we constructed a null hypothesis that the reconstruction of neuronal activity contains no information on the distribution of the cortical grey matter. To test this, we repeatedly compared rotated sections of grey matter with a beamformer estimate of neuronal activity to generate a distribution of mutual information values. The significance of the comparison between the un-rotated anatomical information and the electrical estimate was subsequently assessed against this distribution. We found that there was significant (P < 0. 05) anatomical information contained in the beamformer images across a number of frequency bands. Based on the limited data presented here, we can say that the assumptions behind the beamformer algorithm are not unreasonable for the visual-motor task investigated.

YNIMG Journal 2005 Journal Article

GLM-beamformer method demonstrates stationary field, alpha ERD and gamma ERS co-localisation with fMRI BOLD response in visual cortex

• Matthew J. Brookes
• Andrew M. Gibson
• Stephen D. Hall
• Paul L. Furlong
• Gareth R. Barnes
• Arjan Hillebrand
• Krish D. Singh
• Ian E. Holliday

Recently, we introduced a new ‘GLM-beamformer’ technique for MEG analysis that enables accurate localisation of both phase-locked and non-phase-locked neuromagnetic effects, and their representation as statistical parametric maps (SPMs). This provides a useful framework for comparison of the full range of MEG responses with fMRI BOLD results. This paper reports a ‘proof of principle’ study using a simple visual paradigm (static checkerboard). The five subjects each underwent both MEG and fMRI paradigms. We demonstrate, for the first time, the presence of a sustained (DC) field in the visual cortex, and its co-localisation with the visual BOLD response. The GLM-beamformer analysis method is also used to investigate the main non-phase-locked oscillatory effects: an event-related desynchronisation (ERD) in the alpha band (8–13 Hz) and an event-related synchronisation (ERS) in the gamma band (55–70 Hz). We show, using SPMs and virtual electrode traces, the spatio-temporal covariance of these effects with the visual BOLD response. Comparisons between MEG and fMRI data sets generally focus on the relationship between the BOLD response and the transient evoked response. Here, we show that the stationary field and changes in oscillatory power are also important contributors to the BOLD response, and should be included in future studies on the relationship between neuronal activation and the haemodynamic response.

YNIMG Journal 2005 Journal Article

The missing link: analogous human and primate cortical gamma oscillations

• Stephen D. Hall
• Ian E. Holliday
• Arjan Hillebrand
• Krish D. Singh
• Paul L. Furlong
• Avgis Hadjipapas
• Gareth R. Barnes

Recent animal studies highlighting the relationship between functional imaging signals and the underlying neuronal activity have revealed the potential capabilities of non-invasive methods. However, the valuable exchange of information between animal and human studies remains restricted by the limited evidence of direct physiological links between species. In this study we used magnetoencephalography (MEG) to investigate the occurrence of 30–70 Hz (gamma) oscillations in human visual cortex, induced by the presentation of visual stimuli of varying contrast. These oscillations, well described in the animal literature, were observed in retinotopically concordant locations of visual cortex and show striking similarity to those found in primate visual cortex using surgically implanted electrodes. The amplitude of the gamma oscillations increases linearly with stimulus contrast in strong correlation with the gamma oscillations found in the local field potential (LFP) of the macaque. We demonstrate that non-invasive magnetic field measurements of gamma oscillations in human visual cortex concur with invasive measures of activation in primate visual cortex, suggesting both a direct representation of underlying neuronal activity and a concurrence between human and primate cortical activity.

YNIMG Journal 2004 Journal Article

A general linear model for MEG beamformer imaging

• Matthew J. Brookes
• Andrew M. Gibson
• Stephen D. Hall
• Paul L. Furlong
• Gareth R. Barnes
• Arjan Hillebrand
• Krish D. Singh
• Ian E. Holliday

A new general linear model (GLM) beamformer method is described for processing magnetoencephalography (MEG) data. A standard nonlinear beamformer is used to determine the time course of neuronal activation for each point in a predefined source space. A Hilbert transform gives the envelope of oscillatory activity at each location in any chosen frequency band (not necessary in the case of sustained (DC) fields), enabling the general linear model to be applied and a volumetric T statistic image to be determined. The new method is illustrated by a two-source simulation (sustained field and 20 Hz) and is shown to provide accurate localization. The method is also shown to locate accurately the increasing and decreasing gamma activities to the temporal and frontal lobes, respectively, in the case of a scintillating scotoma. The new method brings the advantages of the general linear model to the analysis of MEG data and should prove useful for the localization of changing patterns of activity across all frequency ranges including DC (sustained fields).

YNIMG Journal 2003 Journal Article

Group imaging of task-related changes in cortical synchronisation using nonparametric permutation testing

• Krish D. Singh
• Gareth R. Barnes
• Arjan Hillebrand

Synthetic aperture magnetometry (SAM) is a nonlinear beamformer technique for producing 3D images of cortical activity from magnetoencephalography data. We have previously shown how SAM images can be spatially normalised and averaged to form a group image. In this paper we show how nonparametric permutation methods can be used to make robust statistical inference about group SAM data. Data from a biological motion direction discrimination experiment were analysed using both a nonparametric analysis toolbox (SnPM) and a conventional parametric approach utilising Gaussian field theory. In data from a group of six subjects, we were able to show robust group activation at the P < 0. 05 (corrected) level using the nonparametric methods, while no significant clusters were found using the conventional parametric approach. Activation was found using SnPM in several regions of right occipital–temporal cortex, including the superior temporal sulcus, V5/MT, the fusiform gyrus, and the lateral occipital complex.

YNIMG Journal 2002 Journal Article

fMRI of Thermal Pain: Effects of Stimulus Laterality and Attention

• Jonathan C.W. Brooks
• Turo J. Nurmikko
• William E. Bimson
• Krish D. Singh
• Neil Roberts

Brain activity was studied by fMRI in 18 healthy subjects during stimulation of the thenar eminence of the hand with either warm (nonpainful, 40°C) or hot (painful, 46–49°C) stimuli using a contact thermode. Experiments were performed on the right and left hand independently and with two attentional contexts: subjects either attended to pain or attended to a visual global motion discrimination task (to distract them from pain). Group analysis demonstrated that attended warm stimulation of the right hand did not produce any significantly activated clusters. Painful thermal stimulation of either hand elicited significant activity over a large network of brain regions, including insula, inferior frontal gyrus, cingulate gyrus, secondary somatosensory cortex, cerebellum, and medial frontal gyrus (corrected P < 0. 05). Insula activity was distributed along its anterior–posterior axis and depended on the hand stimulated and attentional context. In particular, activity within the posterior insula was contralateral to the site of stimulation, tested using regions of interest (ROI) analysis: significant side × site interaction (P = 0. 001). With attention diverted from the painful stimulus bilateral anterior insula activity moved posteriorly to midinsula and decreased in extent (ROI analysis: significant main effect of attention (P = 0. 03)). The role of the insula in thermosensation and attention is discussed.

YNIMG Journal 2002 Journal Article

Task-Related Changes in Cortical Synchronization Are Spatially Coincident with the Hemodynamic Response

• Krish D. Singh
• Gareth R. Barnes
• Arjan Hillebrand
• Emer M.E. Forde
• Adrian L. Williams

Using group functional Magnetic Resonance Imaging (fMRI) and group Magnetoencephalography (MEG) we studied two cognitive paradigms: A language task involving covert letter fluency and a visual task involving biological motion direction discrimination. The MEG data were analyzed using an adaptive beam-former technique known as Synthetic Aperture Magnetometry (SAM), which provides continuous 3-D images of cortical power changes. These images were spatially normalized and averaged across subjects to provide a group SAM image in the same template space as the group fMRI data. The results show that frequency-specific, task-related changes in cortical synchronization, detected using MEG, match those areas of the brain showing an evoked cortical hemodynamic response with fMRI. The majority of these changes were event-related desynchronizations (ERDs) in the 5–10 Hz and 15–25 Hz frequency ranges. Our study demonstrates how SAM, spatial normalization, and intersubject averaging enable group MEG studies to be performed. SAM analysis also allows the MEG experiment to have exactly the same task design as the corresponding fMRI experiment. This new analysis framework represents an important advance in the use of MEG as a cognitive neuroimaging technique and also allows mutual cross-validation with fMRI.

YNIMG Journal 1997 Journal Article

Magnetoencephalographic Investigation of Human Cortical Area V1 Using Color Stimuli

• Fiona Fylan
• Ian E. Holliday
• Krish D. Singh
• Stephen J. Anderson
• Graham F.A. Harding

The aim of this study was to determine the response properties of the human visual cortex to chromatic stimuli using magnetoencephalography (MEG). Evoked responses were recorded to isoluminant red/green sinusoidal gratings for a wide range of spatial and temporal frequencies. For each condition the response was dominated by a single major component which was well modeled by an equivalent current dipole. Coregistration of MEG and MRI data provided evidence that the principal evoked cortical activity originated from visual area V1. To investigate the chromatic response properties of this area, the maximum global field power of the evoked response was plotted as a function of stimulus spatial and temporal frequency. The spatial-frequency tuning was lowpass and the temporal-frequency tuning was multimodal, with peaks at 0 and 4 Hz. The results demonstrate the use of MEG as a technique for investigating activity from discrete regions of cortex.