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Biomedical subjects

Peter G Morris

Publications and source records attributed to Peter G Morris.

7 recordsLinked to original sources

Beamformer reconstruction of correlated sources using a modified source model.

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.

Auditory Cortex↗

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

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.

Adult↗

Behavioural and pharmacological magnetic resonance imaging assessment of the effects of methylphenidate in a potential new rat model of attention deficit hyperactivity disorder.

RATIONALE: The psychomotor stimulant methylphenidate is used in the treatment of attention deficit hyperactivity disorder (ADHD). Whereas the mechanism is not fully understood it is suggested to involve restoration of impaired dopamine function found in ADHD. OBJECTIVES: The aim of this study was to determine the effects of methylphenidate on brain region activation in vivo using pharmacological magnetic resonance imaging (phMRI) in a potential rat model of ADHD. METHODS: Rats were treated bi-daily [from postnatal day (PND) 24] for 4 days with the dopamine re-uptake inhibitor GBR 12909 (30 mg/kg i.p) or vehicle (control). On PND 57 rats were administered methylphenidate (4 mg/kg i.p) and locomotor activity measured. In a separate group of animals, blood oxygen level dependent (BOLD) response was measured using phMRI to determine changes in brain region activation produced by methylphenidate (4 mg/kg i.p.) in GBR 12909-pretreated or control rats. RESULTS: Methylphenidate produced a greater locomotor-stimulant response in controls compared with GBR 12909 rats. Pretreatment with GBR 12909 reduced the BOLD response produced by methylphenidate compared with that in control animals. The main effects of methylphenidate on the BOLD response were seen in the caudate, frontal cortex, hippocampus and hypothalamus. CONCLUSIONS: Short-term treatment with GBR 12909 in young rats causes long-term changes in dopaminergic systems, altering the methylphenidate-induced behavioural response and brain region activation compared with that in vehicle-pretreated rats. The results further support the view that altered dopaminergic function may be an important factor in ADHD and the value of animal models with this functional neurochemical deficit.

Analysis of Variance↗

The neuroprotective effect of progesterone after traumatic brain injury in male mice is independent of both the inflammatory response and growth factor expression.

Previous studies suggest that progesterone may possess neuroprotective properties after traumatic insult but, with the exception of reduced formation of cerebral oedema, limited experimental evidence has been presented to support this claim. In the present study we focused on the effect of progesterone treatment on structural and functional deficits in an experimental model of traumatic brain injury. Female mice exhibited significantly (P = 0.0445) reduced lesion volumes compared with males after aseptic cryogenic cerebral injury (ACI), suggesting that female sex steroids provide protection against this injury. In male mice, progesterone treatment after injury (three intraperitoneal doses of 8 mg/kg) reduced lesion volume (P = 0.0429) and improved performance in a spatial cognitive task (Morris water maze; P = 0.0014). However, progesterone had no demonstrable effect on the formation of oedema as measured using T2-weighted magnetic resonance imaging, nor did it affect brain water content. The pro-inflammatory cytokines TNF-alpha and IL-1beta, and growth factors BDNF and G-CSF, were all strongly transcriptionally activated after ACI. However, progesterone administration did not affect expression of these genes. This study provides strong evidence that progesterone possesses neuroprotective properties in a mouse model of traumatic brain injury, but suggests that the steroid achieves this effect through mechanism(s) independent of the inflammatory response or growth factor up-regulation.

Animals↗

Antagonism of the interleukin-1 receptor following traumatic brain injury in the mouse reduces the number of nitric oxide synthase-2-positive cells and improves anatomical and functional outcomes.

Interleukin (IL)-1beta plays an important role in the inflammatory response that results from traumatic brain injury and antagonism of the actions of this cytokine can affect outcome. We subjected male mice to aseptic cryogenic injury and assessed recovery through anatomical, histological and functional measures following treatment with recombinant mouse IL-1 receptor antagonist (IL-1ra). A single dose (1 microg, i.c.v.) at the time of injury reduced lesion volume 3 days later, as assessed by Nissl staining, and also the number (30%) of FluoroJade-positive degenerating neurones. Mice treated with IL-1ra performed better on the beam balance and in the grid test as compared with vehicle-treated animals. Furthermore, IL-1ra-treated animals showed fewer (40%) nitric oxide synthase-2-positive cells in and around the lesion. These data suggest that activation of the IL-1 receptor following trauma contributes to the pathology and that antagonism can reduce both anatomical and functional consequences of neuroinflammation.

Animals↗

A general linear model for MEG beamformer imaging.

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).

Algorithms↗

A method for the direct electrical stimulation of the auditory system in deaf subjects: a functional magnetic resonance imaging study.

PURPOSE: To develop a safe functional magnetic resonance imaging (fMRI) procedure for auditory assessment of deaf subjects. MATERIALS AND METHODS: A gold-plated tungsten electrode has been developed which has zero magnetic susceptibility. Used with carbon leads and a carbon reference pad, it enables safe, distortion-free fMRI studies of deaf subjects following direct electrical stimulation of the acoustic nerve. Minor pickup of the radio frequency (RF) pulses by the electrode assembly is difficult to eliminate, and a SPARSE acquisition sequence is used to avoid any effects of unintentional auditory nerve stimulation. RESULTS: The procedure is demonstrated in a deaf volunteer. Activation is observed in the contralateral but not the ipsilateral primary auditory cortex. This is in sharp contrast to studies of auditory processing in hearing subjects, but consistent with the small number of previous positron emission tomography (PET) and MR studies on adult deaf subjects. CONCLUSION: The fMRI procedure is able to demonstrate whether the auditory pathway is fully intact, and may provide a useful method for preoperative assessment of candidates for cochlear implantation.

Adult↗