ORCID Profile
0000-0001-7042-3920
Current Organisation
The University of Auckland
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Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.NEUROIMAGE.2013.04.108
Abstract: 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 30-70 Hz, and in lateral visual cortex at 60-90 Hz, regardless of whether it was attended. Directing spatial attention to the grating increased gamma synchronisation in medial visual cortex, but only at 60-90 Hz. 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.
Publisher: Elsevier BV
Date: 07-2003
DOI: 10.1016/S0278-2626(03)00077-0
Abstract: To compare mental rotation and mental size transformation, 128-channel EEG was recorded while subjects performed both tasks using random two-dimensional shapes as stimuli. Behavioural results showed significant linear effects of both size transformation and mental rotation on reaction times. Rotation ERPs showed experimental effects at two latencies: a bilateral component distributed over posterior parietal electrodes at a latency of approximately 232-300ms and a second component at approximately 424-492ms distributed over right anterior parietal electrodes. The latency and spatial distribution of this second effect is consistent with previous research indicating a functional connection between this component and mental rotation. ERPs for the size-transformation task showed an effect at 180-228ms distributed bilaterally over occipital-temporal electrodes. These results are consistent with previous hemodynamic imaging studies that show involvement of parietal cortex in mental rotation and also the involvement of BA 19 in size-transformation tasks. However, the superior temporal resolution of the present data indicates that BA 19 activation may occur at a latency that is more likely related to apparent motion than to the size-transformation operation per se.
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.BRAINRES.2005.11.053
Abstract: In this experiment, the oscillatory responses of the MEG were characterized during the observation of four viewing conditions: (a) observation of mouth movements, (b) observation of a non-biological motion stimulus (a mechanical aperture opening and shutting), (c) observation of object-directed mouth movements and (d) observation of speech-like mouth movements. Data were analyzed using synthetic aperture magnetometry (SAM) in three frequency bands, beta (15-35 Hz), gamma (35-70 Hz) and alpha/mu (8-15 Hz). Results showed that observations of biological motion resulted in beta desynchronization over lateral sensorimotor areas, while observations of non-biological motion resulted in a more medial desynchronization, an effect that may be related to the processing of a structured event sequence. Observation of linguistic movements resulted in less alpha/beta desynchronization in posterior brain regions in comparison to biological motion stimuli, suggesting that linguistically-relevant stimuli are processed with different neuronal systems than those recruited by normal action observation. We suggest that non-linguistic actions recruit dorsal systems while linguistic actions engage ventral processing systems. Object-directed movements showed the largest sensorimotor activations, suggesting that, as is the case for observations of hand movements, motoric processing is particularly sensitive to the viewing of goal-directed actions. Taken together, the results indicate that the brain utilizes multiple action encoding strategies, tailored to the function of the observed movement.
Publisher: Informa UK Limited
Date: 02-2007
Publisher: Elsevier BV
Date: 08-2004
Publisher: Springer Science and Business Media LLC
Date: 19-11-2019
DOI: 10.1038/S41598-019-51974-4
Abstract: Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal ersity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal ersity. Time-referenced and neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal ersity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.
Publisher: Elsevier BV
Date: 04-2004
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2020
DOI: 10.1097/ALN.0000000000003169
Abstract: 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. 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 re-gas baseline. 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%]). 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.
Publisher: Cold Spring Harbor Laboratory
Date: 04-05-2022
DOI: 10.1101/2022.05.03.490402
Abstract: Neural mechanisms are complex and difficult to image. This paper presents a new space-time resolved whole-brain imaging framework, called Neurophysiological Mechanism Imaging (NMI), that identifies neurophysiological mechanisms within cerebral cortex at the macroscopic scale. By fitting neural mass models to electromagnetic source imaging data using a novel nonlinear inference method, population averaged membrane potentials and synaptic connection strengths are efficiently and accurately imaged across the whole brain at a resolution afforded by source imaging. The efficiency of the framework enables return of the augmented source imaging results overnight using high performance computing. This suggests it can be used as a practical and novel imaging tool. To demonstrate the framework, it has been applied to resting-state magnetoencephalographic source estimates. The results suggest that endogenous inputs to cingulate, occipital, and inferior frontal cortex are essential modulators of resting-state alpha power. Moreover, endogenous input and inhibitory and excitatory neural populations play varied roles in mediating alpha power in different resting-state sub-networks. The framework can be applied to arbitrary neural mass models and has broad applicability to image neural mechanisms in different brain states. The whole-brain imaging framework can disclose the neurophysiological substrates of complicated brain functions in a spatiotemporal manner. Developed a semi-analytical Kalman filter to estimate neurophysiological variables in the nonlinear neural mass model efficiently and accurately from large-scale electromagnetic time-series. The semi-analytical Kalman filter is 7.5 times faster and 5% more accurate in estimating model parameters than the unscented Kalman filter. Provided several group-level statistical observations based on neurophysiological variables and visualised them in a whole-brain manner to show different perspectives of neurophysiological mechanisms. Applied the framework to study resting-state alpha oscillation and found novel relationships between local neurophysiological variables in specific brain regions and alpha power.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.NEUROIMAGE.2010.11.045
Abstract: 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 (80 ms) evoked response, whereas later responses (120 ms) 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.
Publisher: Springer Science and Business Media LLC
Date: 21-04-2014
DOI: 10.1038/ONC.2014.106
Abstract: A feature of many gliomas is the lification of the epidermal growth factor receptor (EGFR), resulting in its overexpression. Missense mutations or deletions within the extracellular domain are associated with this lification and can lead to constitutive activation of the receptor, with the Domain I/II deletion, EGFRvIII, being the most common. These changes have also been associated with increased sensitivity to EGFR inhibition using small molecule inhibitors. We have expressed, in human glioma cells, EGFR containing four glioma-specific EGFR missense mutations within Domain IV (C620Y, C624F, C628Y and C636Y) to analyze their biological properties and sensitivity to EGFR inhibition. One of these mutants, C620Y, exhibited an enhanced basal phosphorylation, which was partially dependent on an EGFR-ligand autocrine loop. All Domain IV mutants responded equally as well as wildtype EGFR (wtEGFR) to ligand stimulation. Biochemical analysis revealed that a pre-formed, disulfide-bonded dimer associated with these mutations was underglycosylated, inactive and cytoplasmically retained. Ligand stimulation resulted in the formation of a tyrosine-phosphorylated, disulfide-bonded dimer for all Domain IV mutants but not for wtEGFR. Following treatment with the next-generation, irreversible pan-ErbB inhibitor dacomitinib, the C620Y, C624F and EGFRvIII mutants were inactivated, covalently dimerized and were retained in the cytoplasm, resulting in cell-surface receptor loss and, for C620Y and C624F, decreased binding of EGF. Dacomitinib treatment significantly reduced the in vivo growth of human glioma xenografts bearing C620Y, but not wtEGFR. Collectively, these data indicate that the unique biochemical traits of Domain IV EGFR cysteine mutants can be exploited for enhanced sensitivity to EGFR small molecule inhibitors, with potential clinical applications.
Publisher: Springer Science and Business Media LLC
Date: 29-07-2020
Publisher: Wiley
Date: 07-11-2003
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.BPSC.2019.07.002
Abstract: The rapid-acting clinical effects of ketamine as a novel treatment for depression along with its complex pharmacology have made it a growing research area. One of the key mechanistic hypotheses for how ketamine works to alleviate depression is by enhancing long-term potentiation (LTP)-mediated neural plasticity. The objective of this study was to investigate the plasticity hypothesis in 30 patients with depression noninvasively using visual LTP as an index of neural plasticity. In a double-blind, active placebo-controlled crossover trial, electroencephalography-based LTP was recorded approximately 3 to 4 hours following a single 0.44-mg/kg intravenous dose of ketamine or active placebo (1.7 ng/mL remifentanil) in 30 patients. Montgomery-Åsberg Depression Rating Scale scores were used to measure clinical symptoms. Visual LTP was measured as a change in the visually evoked potential following high-frequency visual stimulation. Dynamic causal modeling investigated the underlying neural architecture of visual LTP and the contribution of ketamine. Montgomery-Åsberg Depression Rating Scale scores revealed that 70% of participants experienced 50% or greater reduction in their depression symptoms within 1 day of receiving ketamine. LTP was demonstrated in the N1 (p = .00002) and P2 (p = 2.31 × 10 This study provides evidence that LTP-based neural plasticity increases within the time frame of the antidepressant effects of ketamine in humans and supports the hypothesis that changes to neural plasticity may be key to the antidepressant properties of ketamine.
Publisher: Elsevier BV
Date: 06-2007
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.PNPBP.2019.109838
Abstract: A single subanaesthetic dose of ketamine rapidly alleviates the symptoms of major depressive disorder (MDD). However, few studies have investigated the acute effects of ketamine on the BOLD pharmacological magnetic resonance imaging (phMRI) response and EEG spectra. In a randomised, double-blind, active placebo-controlled crossover trial, resting-state simultaneous EEG/fMRI was collected during infusion of ketamine or active placebo (remifentanil) in 30 participants with MDD. Montgomery-Asberg depression rating scale scores showed a significant antidepressant effect of ketamine compared to placebo (69% response rate). phMRI analyses showed BOLD signal increases in the anterior cingulate and medial prefrontal cortices and sensitivity of the decrease in subgenual anterior cingulate cortex (sgACC) BOLD signal to noise correction. EEG spectral analysis showed increased theta, high beta, low and high gamma power, and decreased delta, alpha, and low beta power with differing time-courses. Low beta and high gamma power time courses explained significant variance in the BOLD signal. Interestingly, the variance explained by high gamma power was significantly associated with non-response to ketamine, but significant associations were not found for other neurophysiological markers when noise correction was implemented. The results suggest that the decrease in sgACC BOLD signal is potentially noise and unrelated to ketamine's antidepressant effect, highlighting the importance of noise correction and multiple temporal regressors for phMRI analyses. The lack of effects significantly associated with antidepressant response suggests the phMRI methodology employed was unable to detect such effects, the effect sizes are relatively small, or that other processes, e.g. neural plasticity, underlie ketamine's antidepressant effect.
Publisher: American Institute of Mathematical Sciences (AIMS)
Date: 2014
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Suresh Muthukumaraswamy.