Thomas P. White

Aberrant salience network (bilateral insula and anterior cingulate cortex) connectivity during information processing in schizophrenia

A salience network, comprising bilateral insula and anterior cingulate cortex (ACC), is thought to play a role in recruiting relevant brain regions for the processing of sensory information. Here, we present a functional network connectivity (FNC) analysis of spatial networks identified during somatosensation, performed to test the hypothesis that salience network connectivity is disturbed during information processing in schizophrenia. 19 medicated individuals with schizophrenia and 19 matched healthy controls participated in a functional magnetic resonance imaging study. 100 Hz vibrotactile stimuli were presented to the right index fingertip while whole-head blood oxygenation level-dependent contrast gradient-echo echo-planar images were acquired. Six spatial components of interest were identified using group independent component analysis: (1) bilateral insula, superior temporal and precentral gyrus (INS); (2) dorsal ACC; (3) left dorsolateral frontal and parietal cortex (left central executive network (LCEN)); (4) right dorsolateral frontal and parietal cortex (RCEN); (5) ventromedial frontal cortex (FDMN); and (6) precuneus, posterior cingulate and angular gyrus (PDMN). Maximal-lagged correlation was examined between all pairwise combinations of components. Significantly reduced FNC was observed in schizophrenia compared to controls between: INS and ACC; INS and FDMN; and LCEN and PDMN. There was no evidence of increased FNC in schizophrenia. Reduced salience network connectivity during information processing in schizophrenia suggests disturbance to the system which effects changes between contextually-relevant functional brain states. This aberrance may provide a mechanistic explanation of several clinical features of the disorder.

Changes in brain network activity during working memory tasks: A magnetoencephalography study

In this study, we elucidate the changes in neural oscillatory processes that are induced by simple working memory tasks. A group of eight subjects took part in modified versions of the N-back and Sternberg working memory paradigms. Magnetoencephalography (MEG) data were recorded, and subsequently processed using beamformer based source imaging methodology. Our study shows statistically significant increases in θ oscillations during both N-back and Sternberg tasks. These oscillations were shown to originate in the medial frontal cortex, and further to scale with memory load. We have also shown that increases in θ oscillations are accompanied by decreases in β and γ band oscillations at the same spatial coordinate. These decreases were most prominent in the 20-40 Hz frequency range, although spectral analysis showed that γ band power decrease extends up to at least 80 Hz. β/γ Power decrease also scales with memory load. Whilst θ increases were predominately observed in the medial frontal cortex, β/γ decreases were associated with other brain areas, including nodes of the default mode network (for the N-back task) and areas associated with language processing (for the Sternberg task). These observations are in agreement with intracranial EEG and fMRI studies. Finally, we have shown an intimate relationship between changes in β/γ band oscillatory power at spatially separate network nodes, implying that activity in these nodes is not reflective of uni-modal task driven changes in spatially separate brain regions, but rather represents correlated network activity. The utility of MEG as a non-invasive means to measure neural oscillatory modulation has been demonstrated and future studies employing this technology have the potential to gain a better understanding of neural oscillatory processes, their relationship to functional and effective connectivity, and their correspondence to BOLD fMRI.

fMRI analysis of active, passive and electrically stimulated ankle dorsiflexion

Ankle dorsiflexion (ADF) is an integral component in gait. The objective of this study was to define, using functional magnetic resonance imaging (fMRI) in healthy volunteers (n=12), the brain regions that are activated during Electrical Stimulation (ES)-induced ADF movements, and compare this to the pattern of activation occurring during active and passive ADF. Concurrent electromyography (EMG) was used to monitor the tibialis anterior muscle activity so as to allow EMG-guided fMRI analysis to be performed. Patterns of cortical and sub-cortical activation in response to active, passive and ES-induced ADF movement were identified. EMG-guided fMRI analysis was shown to improve detection and reduce inter-session variance for active and ES tasks. A significantly greater number of voxels were activated during active and ES-induced ADF compared to passive ADF in contralateral primary motor (M1), primary sensory (SI), and secondary somatosensory (SII) areas, as well as in supplementary motor area (SMA) and cingulate motor areas (CMA); bilateral dorsal and ventral premotor areas and cerebellum VI. The contrast of active greater than ES-induced ADF showed increased activation in SMA, contralateral PMdr; bilateral PMvr, dorsolateral prefrontal cortex and CMA; and ipsilateral cerebellum IV. Active ADF generated greater activation in brain areas responsible for motor planning, execution and visuomotor co-ordination. ES-induced activation was greater in bilateral SII and insula than for active ADF, hypothesised to result from increased sensory integration, but also possibly due to a nociceptive component to ES.

Folding of the Prefrontal Cortex in Schizophrenia: Regional Differences in Gyrification

BACKGROUNDnAnatomy of prefrontal cortex in schizophrenia has been studied previously by quantifying the degree of gyrification. Conflicting results exist, with some studies showing hypergyria and others showing hypogyria. It is likely that regional variations in cortical folding exist within the prefrontal cortex that could be explored by studying the anatomical subdivisions formed by the sulci and gyri. With surface reconstructions from magnetic resonance imaging, we studied the gyrification within anatomically meaningful subdivisions of prefrontal cortex in schizophrenia.nnnMETHODSnPrefrontal cortex was studied with an automated method to obtain Local Gyrification Index, reflecting the degree of cortical folding in 57 patients with schizophrenia and 42 control subjects. Regional differences within prefrontal cortex were compared between the two groups with a sulcogyral atlas. Effects of hemisphere and age were subsequently assessed.nnnRESULTSnPatients with schizophrenia had significant hypogyria in most prefrontal regions except the frontomarginal region, which showed hypergyria. The normal left > right pattern of prefrontal gyrification was reversed in schizophrenia. Patients with schizophrenia also showed significant age-related reduction in gyrification at the hypogyric regions.nnnCONCLUSIONSnThe differences between reported findings regarding prefrontal gyrification might reflect regional variation in the nature of the abnormal process of gyrification in schizophrenia. Prefrontal gyrification is significantly influenced by age in schizophrenia, in addition to the influence of neurodevelopmental factors.

Reality distortion is related to the structure of the salience network in schizophrenia

BACKGROUNDnAn intrinsic cerebral network comprising the anterior cingulate and anterior insula (the salience network) is considered to play an important role in salience detection in healthy volunteers. Aberrant salience has been proposed as an important mechanism in the production of psychotic symptoms such as delusions and hallucinations (reality distortion). We investigated whether structural deficits in the salience network are associated with the reality distortion seen in schizophrenia.nnnMETHODnA sample of 57 patients in a clinically stable state of schizophrenia and 41 controls were studied with high-resolution magnetic resonance imaging.nnnRESULTSnBilateral volume reduction was seen in the anterior cingulate and anterior insula in patients with schizophrenia. Reduced volume in the two left-sided regions of the salience network was significantly correlated with the severity of reality distortion.nnnCONCLUSIONSnThese findings suggest that a deficit of grey matter in the salience network leads to an impaired attribution of salience to stimuli that is associated with delusions and hallucinations in schizophrenia.

Regional contraction of brain surface area involves three large-scale networks in schizophrenia

In schizophrenia, morphological changes in the cerebral cortex have been primarily investigated using volumetric or cortical thickness measurements. In healthy subjects, as the brain size increases, the surface area expands disproportionately when compared to the scaling of cortical thickness. In this structural MRI study, we investigated the changes in brain surface area in schizophrenia by constructing relative areal contraction/expansion maps showing group differences in surface area using Freesurfer software in 57 patients and 41 controls. We observed relative areal contraction affecting Default Mode Network, Central Executive Network and Salience Network, in addition to other regions in schizophrenia. We confirmed the surface area reduction across these three large-scale brain networks by undertaking further region-of-interest analysis of surface area. We also observed a significant hemispheric asymmetry in the surface area changes, with the left hemisphere showing a greater reduction in the areal contraction maps. Our findings suggest that a fundamental disturbance in cortical expansion is likely in individuals who develop schizophrenia.

Motion-related artefacts in EEG predict neuronally plausible patterns of activation in fMRI data

The simultaneous acquisition and subsequent analysis of EEG and fMRI data is challenging owing to increased noise levels in the EEG data. A common method to integrate data from these two modalities is to use aspects of the EEG data, such as the amplitudes of event-related potentials (ERP) or oscillatory EEG activity, to predict fluctuations in the fMRI data. However, this relies on the acquisition of high quality datasets to ensure that only the correlates of neuronal activity are being studied. In this study, we investigate the effects of head-motion-related artefacts in the EEG signal on the predicted T2*-weighted signal variation. We apply our analyses to two independent datasets: 1) four participants were asked to move their feet in the scanner to generate small head movements, and 2) four participants performed an episodic memory task. We created T2*-weighted signal predictors from indicators of abrupt head motion using derivatives of the realignment parameters, from visually detected artefacts in the EEG as well as from three EEG frequency bands (theta, alpha and beta). In both datasets, we found little correlation between the T2*-weighted signal and EEG predictors that were not convolved with the canonical haemodynamic response function (cHRF). However, all convolved EEG predictors strongly correlated with the T2*-weighted signal variation in various regions including the bilateral superior temporal cortex, supplementary motor area, medial parietal cortex and cerebellum. The finding that movement onset spikes in the EEG predict T2*-weighted signal intensity only when the time course of movements is convolved with the cHRF, suggests that the correlated signal might reflect a BOLD response to neural activity associated with head movement. Furthermore, the observation that broad-spectral EEG spikes tend to occur at the same time as abrupt head movements, together with the finding that abrupt movements and EEG spikes show similar correlations with the T2*-weighted signal, indicates that the EEG spikes are produced by abrupt movement and that continuous regressors of EEG oscillations contain motion-related noise even after stringent correction of the EEG data. If not properly removed, these artefacts complicate the use of EEG data as a predictor of T2*-weighted signal variation.

Reduced event‐related low frequency EEG activity in schizophrenia during an auditory oddball task

This study examines EEG low frequency characteristics which have been linked to specific cognitive functions such as stimulus encoding and attention during an auditory oddball task in schizophrenia patients and healthy controls. EEG data was recorded from 17 young schizophrenia patients in a stable phase of their illness and 17 healthy controls performing an auditory oddball task. Evoked and induced delta and theta activity, N100, P300 amplitude were computed. Between 200-500 ms after a stimulus was presented, patients displayed significantly reduced P300, less evoked and induced delta and theta activity than controls. We conclude that the well known finding of P300 reduction in schizophrenia can be linked to reductions in delta and theta activity, which are a manifestation of impaired stimulus evaluation, memory retrieval, and a lack of sustained attention.

Alpha-gamma interactions are disturbed in schizophrenia: a fusion of electroencephalography and functional magnetic resonance imaging.

OBJECTIVEnTo delineate regional brain activity associated with the alpha oscillations related to perception of sensory stimuli, and test the hypothesis that the synchronisation of alpha oscillations with stimulus onset is impaired in schizophrenia.nnnMETHODSnJoint independent component analysis was applied to electroencephalographic and functional magnetic resonance imaging data recorded in 19 individuals with schizophrenia and 19 healthy individuals during a vibrotactile somatosensory task.nnnRESULTSnIn healthy individuals the strongest component was dominated by alpha oscillations, and was associated not only with activity in somatosensory regions but also in the insula and anterior cingulate cortex (the salience network). In schizophrenia, the strongest component had low alpha power and activity was limited mainly to somatosensory regions. Furthermore, in the healthy group, but not the patients, significant correlation was observed between the strongest component and evoked gamma power.nnnCONCLUSIONnThe correlation between the alpha-dominated component and evoked gamma power is consistent with the hypothesis that gamma localised to sensory cortex elicits stimulus-locking of spatially distinct, large-scale ongoing alpha oscillations. Furthermore, this hypothesised mechanism appears to be disrupted in schizophrenia.nnnSIGNIFICANCEnThese findings suggest that a weakened alpha-gamma interaction underlies impaired recruitment of the brain during sensory information processing in schizophrenia.

fMRI and MEG analysis of visceral pain in healthy volunteers.

Backgroundu2002 Although many studies of painful rectal stimulation have found activation in the insula, cingulate, somatosensory, prefrontal cortices and thalamus, there is considerable variability when comparing functional magnetic resonance imaging (fMRI) results. Multiple factors may be responsible, including the model used in fMRI data analysis. Here, we assess the temporal response of activity to rectal barostat distension using novel fMRI and magnetoencephalography (MEG) analysis.