Bradley J Macintosh

University of Oxford, Oxford, ENG, United Kingdom

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Publications (22)114.34 Total impact

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    Article: Physical Activity in the Prevention of Ischemic Stroke and Improvement of Outcomes: A Narrative Review.
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    ABSTRACT: Physical activity is an integral component of stroke prevention. Although approximately 80% of strokes are due to cerebral ischemia, the mechanisms linking physical activity to the incidence of and recovery from ischemic stroke are not completely understood. This review summarizes evidence from human and animal studies regarding physical activity in the prevention of overt and covert ischemic stroke and associated injury. In cohort studies, people who are physically active have reduced rates of overt ischemic stroke and ischemic stroke mortality. However, few human studies have examined physical activity and the incidence of covert stroke. Evidence from animal models of ischemic stroke indicates that physical activity reduces injury after ischemic stroke by reducing infarct size and apoptotic cell death. Accordingly, physical activity may reduce the magnitude of injury from ischemic stroke so that there are fewer or less severe symptoms. Future research should investigate physical activity and incidence of covert stroke prospectively, ascertain the optimal dose and type of exercise to prevent ischemic injury, and identify the underlying neuroprotective mechanisms.
    Neuroscience & Biobehavioral Reviews 11/2012; · 8.65 Impact Factor
  • Article: Evaluating quantitative approaches to dynamic susceptibility contrast MRI among carotid endarterectomy patients.
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    ABSTRACT: PURPOSE: To evaluate two dynamic susceptibility contrast (DSC) quantification methods in symptomatic carotid artery disease patients undergoing carotid endarterectomy (CEA) surgery by comparing methods directly and assessing the reliability of each method in the hemisphere contralateral to surgery. MATERIALS AND METHODS: Absolute cerebral blood flow (CBF) and volume (CBV) was calculated in putamen and sensorimotor gray matter of 17 patients using two methods: 1) The Bookend method that scales relative DSC images to CBV values calculated from the ratio of pre- and postcontrast T1-weighted images, and 2) the Tail-scaling method that uses the ratio of area under the tails of the venous and arterial concentration time-courses to scale the DSC images. RESULTS: There was a positive correlation between the methods with significant correlation post-CEA (P < 0.035). Intersession correlation was greater when using the Tail-scaling method contralateral to surgery (P < 0.004). CONCLUSION: We have demonstrated correlation between methods that is significant after surgery and have found that the Tail-scaling method produces better test-retest reliability than our implementation of the Bookend method. Results from this study suggest that DSC has the potential to measure hemodynamic changes after endarterectomy and future work is required to establish clinical value. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 10/2012; · 2.70 Impact Factor
  • Article: A control point interpolation method for the non-parametric quantification of cerebral haemodynamics from dynamic susceptibility contrast MRI.
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    ABSTRACT: DSC-MRI analysis is based on tracer kinetic theory and typically involves the deconvolution of the MRI signal in tissue with an arterial input function (AIF), which is an ill-posed inverse problem. The current standard singular value decomposition (SVD) method typically underestimates perfusion and introduces non-physiological oscillations in the resulting residue function. An alternative vascular model (VM) based approach permits only a restricted family of shapes for the residue function, which might not be appropriate in pathologies like stroke. In this work a novel deconvolution algorithm is presented that can estimate both perfusion and residue function shape accurately without requiring the latter to belong to a specific class of functional shapes. A control point interpolation (CPI) method is proposed that represents the residue function by a number of control points (CPs), each having two degrees of freedom (in amplitude and time). A complete residue function shape is then generated from the CPs using a cubic spline interpolation. The CPI method is shown in simulation to be able to estimate cerebral blood flow (CBF) with greater accuracy giving a regression coefficient between true and estimated CBF of 0.96 compared to 0.83 for VM and 0.71 for the circular SVD (oSVD) method. The CPI method was able to accurately estimate the residue function over a wide range of simulated conditions. The CPI method has also been demonstrated on clinical data where a marked difference was observed between the residue function of normally appearing brain parenchyma and infarcted tissue. The CPI method could serve as a viable means to examine the residue function shape under pathological variations.
    NeuroImage 09/2012; 64C:560-570. · 5.89 Impact Factor
  • Article: Visualization of altered neurovascular coupling in chronic stroke patients using multimodal functional MRI.
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    ABSTRACT: Evaluation of cortical reorganization in chronic stroke patients requires methods to accurately localize regions of neuronal activity. Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is frequently employed; however, BOLD contrast depends on specific coupling relationships between the cerebral metabolic rate of oxygen (CMRO(2)), cerebral blood flow (CBF), and volume (CBV), which may not exist following stroke. The aim of this study was to understand whether CBF-weighted (CBFw) and CBV-weighted (CBVw) fMRI could be used in sequence with BOLD to characterize neurovascular coupling mechanisms poststroke. Chronic stroke patients (n=11) with motor impairment and age-matched controls (n=11) performed four sets of unilateral motor tasks (60 seconds/30 seconds off/on) during CBFw, CBVw, and BOLD fMRI acquisition. While control participants elicited mean BOLD, CBFw, and CBVw responses in motor cortex (P<0.01), patients showed only mean changes in CBF (P<0.01) and CBV (P<0.01), but absent mean BOLD responses (P=0.20). BOLD intersubject variability was consistent with differing coupling indices between CBF, CBV, and CMRO(2). Thus, CBFw and/or CBVw fMRI may provide crucial information not apparent from BOLD in these patients. A table is provided outlining distinct vascular and metabolic uncoupling possibilities that elicit different BOLD responses, and the strengths and limitations of the multimodal protocol are summarized.Journal of Cerebral Blood Flow & Metabolism advance online publication, 25 July 2012; doi:10.1038/jcbfm.2012.105.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 07/2012; · 5.46 Impact Factor
  • Article: Modeling dispersion in arterial spin labeling: Validation using dynamic angiographic measurements.
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    ABSTRACT: A major assumption in arterial spin labeling (ASL) MRI perfusion quantification is the time course of the signal on arrival in the capillary network. The normally assumed square label profile is not preserved during transit of the label through the vasculature. This change in profile can be attributed to a number of effects collectively denoted as dispersion. A number of models for this effect have been proposed, but they have been difficult to validate. In this study ASL data acquired whilst the label was still within larger arteries was used to compare models of label dispersion. Models were fit using a probabilistic algorithm and evaluated according to their ability to fit the data. Data from an elderly population were considered including both healthy controls and patients with a variety of vascular disease. The authors conclude that modeling ASL dispersion using a convolution of the ideal ASL label profile with a dispersion kernel is most appropriate, where the kernel itself takes the form of a gamma distribution. This model provided a best fit to the data considered, was consistent with the measured flow profile in arteries and was sufficiently mathematically simple to make it practical for ASL tissue perfusion quantification. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 04/2012; · 2.96 Impact Factor
  • Article: Plaque features associated with increased cerebral infarction after minor stroke and TIA: a prospective, case-control, 3-T carotid artery MR imaging study.
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    ABSTRACT: The goal of this study was to determine whether a 3-T magnetic resonance imaging (MRI) protocol combining carotid atherosclerotic plaque and brain imaging can identify features of high-risk acutely symptomatic plaque that correlate with brain injury. It has previously been demonstrated that, in asymptomatic patients, MRI can identify features of carotid plaque that are associated with stroke, such as the presence of a large lipid core. We hypothesized that the early phase (<7 days) after a cerebrovascular event, when risk of recurrence is highest, may be associated with particular plaque characteristics that associate with cerebral injury. Eighty-one patients (41 presenting acutely with transient ischemic attack [TIA] or minor stroke and 40 asymptomatic controls) underwent multicontrast carotid artery MRI on 2 separate occasions, each accompanied by diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) imaging of the brain. Complex (American Heart Association [AHA] type VI) plaques were seen in 22 of 41 patients (54%) in the symptomatic group versus 8 of 40 (20%) in the asymptomatic group (p < 0.05). They were caused by intraplaque hemorrhage (34% vs. 18%; p = 0.08), surface rupture (24% vs. 5%; p = 0.03), or luminal thrombus (7% vs. 0%; p = 0.24). Noticeably, 17 of 30 (57%) cases of AHA type VI plaque were in vessels with <70% stenosis. At follow-up scanning (>6 weeks later), only 2 cases of symptomatic AHA type VI plaque showed evidence of full healing. The presence of fibrous cap rupture was associated with higher DWI brain injury at presentation and higher total cerebral FLAIR signal at follow-up (p < 0.05). Early carotid wall MRI in patients experiencing minor stroke or TIA showed a higher proportion of "complex" plaques compared with asymptomatic controls; a majority were in arteries of <70% stenosis. Fibrous cap rupture was associated with increases in DWI and FLAIR lesions in the brain. Combined carotid plaque and brain MRI may aid risk stratification and treatment selection in acute stroke and TIA.
    JACC. Cardiovascular imaging 04/2012; 5(4):388-96. · 14.29 Impact Factor
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    Chapter: Use of Optoelectronics to Measure Biosignals Concurrently During Functional Magnetic Resonance Imaging of the Brain
    Bradley J MacIntosh, Fred Tam, Simon J Graham
    10/2011; , ISBN: 978-953-307-576-1
  • Article: Intracranial hemodynamics is altered by carotid artery disease and after endarterectomy: a dynamic magnetic resonance angiography study.
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    ABSTRACT: Carotid endarterectomy (CEA) has become a routine procedure to treat symptomatic carotid artery disease and reduce the risk of recurrent cerebral ischemic events. The purpose of this study was to use an arterial spin labeling dynamic magnetic resonance angiography technique to characterize intracranial hemodynamics before and after CEA. Thirty-seven carotid artery disease patients participated in this study, of whom 24 underwent magnetic resonance imaging before and after CEA. Seventeen control subjects spanning 5 decades underwent magnetic resonance imaging to assess age-related changes. Hemodynamic metrics (that is, relative time to peak and amplitude) were calculated with a γ-variate model. Linear regression was used to relate carotid artery disease burden to downstream hemodynamics in the circle of Willis. Relative time to peak increased with age in controls (P<0.020). For patients, relative time to peak was positively correlated with percent stenosis (P<0.050), independent of age. At 1 day after CEA, the middle cerebral artery ipsilateral to the CEA showed significant dynamic magnetic resonance angiography changes: relative time to peak decreased (P<0.017) and the flow amplitude increased (P<0.009). No pre- versus post-CEA changes were significant in the contralateral middle cerebral artery or posterior segments. This noninvasive, arterial spin labeling-based method produced time-resolved images that were used to characterize intracranial arterial flow associated with aging, extracranial carotid artery disease, and CEA. Results demonstrate that the technique has the sensitivity to detect hemodynamic changes after CEA.
    Stroke 02/2011; 42(4):979-84. · 5.73 Impact Factor
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    Article: Coupling of simultaneously acquired electrophysiological and haemodynamic responses during visual stimulation.
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    ABSTRACT: We investigate the relationship between the temporal variation in the magnitude of occipital visual evoked potentials (VEPs) and of haemodynamic measures of brain activity obtained using both blood oxygenation level dependent (BOLD) and perfusion sensitive (ASL) functional magnetic resonance imaging (fMRI). Volunteers underwent a continuous BOLD fMRI scan and/or a continuous perfusion-sensitive (gradient and spin echo readout) ASL scan, during which 30 second blocks of contrast reversing visual stimuli (at 4 Hz) were interleaved with 30 second blocks of rest (visual fixation). Electroencephalography (EEG) and fMRI were simultaneously recorded and following EEG artefact cleaning, VEPs were averaged across the whole stimulation block (120 reversals, VEP(120)) and at a finer timescale (15 reversals, VEP(15)). Both BOLD and ASL time-series were linearly modelled to establish: (1) the mean response to visual stimulation, (2) transient responses at the start and end of each stimulation block, (3) the linear decrease between blocks, (4) the nonlinear between-block variation (covariation with VEP(120)), (5) the linear decrease within block and (6) the nonlinear variation within block (covariation with VEP(15)). VEPs demonstrated a significant linear time-dependent reduction in amplitude, both within and between blocks of stimulation. Consistent with the VEPs finding, both BOLD and perfusion measures showed significant linear time-dependent reductions in response amplitude between blocks. In addition, there were significant linear time-dependent within-block reductions in BOLD response as well as between-block variations positively correlating with VEP(120) (medial occipital and frontal) and within-block variations positively correlating with VEP(15) (occipital and thalamus). Both electrophysiological and haemodynamic (BOLD and ASL) measures of visual activity showed steady habituation through the experiment. Beyond this, the VEP measures were predictive of shorter timescale (3-30 second) localised variations in BOLD response engaging both occipital cortex and other regions such as anterior cingulate and parietal regions, implicating attentional processes in the modulation of the VEP signal.
    Magnetic Resonance Imaging 10/2010; 28(8):1066-77. · 1.99 Impact Factor
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    Article: Separation of macrovascular signal in multi-inversion time arterial spin labelling MRI.
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    ABSTRACT: Arterial spin labeling (ASL) provides a noninvasive method to measure brain perfusion and is becoming an increasingly viable alternative to more invasive MR methods due to improvements in acquisition, such as the use of a three-dimensional GRASE readout. A potential source of error in ASL measurements is signal arising from intravascular blood that is destined for more distal tissue. This is typically suppressed using diffusion gradients in many ASL sequences. However, several problems exist with this approach, such as the choice of cutoff velocity and gradient direction and incompatibility with certain readout modules. An alternative approach is to explicitly model the intravascular signal. This study exploits this approach by using multi-inversion time ASL data with a recently developed model-fitting method. The method employed permits the intravascular contribution to be discarded in voxels where there is no support in the data for its inclusion, thereby addressing the issue of overfitting. It is shown by comparing data with and without flow suppression, and by comparing the intravascular contribution in GRASE ASL data to MR angiographic images, that the model-fitting approach can provide a viable alternative to flow suppression in ASL where suppression is either not feasible or not desirable.
    Magnetic Resonance in Medicine 05/2010; 63(5):1357-65. · 2.96 Impact Factor
  • Article: Absolute arterial cerebral blood volume quantification using inflow vascular-space-occupancy with dynamic subtraction magnetic resonance imaging.
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    ABSTRACT: In patients with steno-occlusive disease of the internal carotid artery (ICA), cerebral blood flow may be maintained by autoregulatory increases in arterial cerebral blood volume (aCBV). Therefore, characterizing aCBV may be useful for understanding hemodynamic compensation strategies. A new 'inflow vascular-space-occupancy with dynamic subtraction (iVASO-DS)' MRI approach is presented where aCBV (mL blood/100 mL parenchyma) is quantified without contrast agents using the difference between images with and without inflowing blood water signal. The iVASO-DS contrast mechanism is investigated (3.0 T, spatial resolution=2.4 x 2.4 x 5 mm(3)) in healthy volunteers (n=8; age=29+/-5 years), and patients with mild (n=7; age=72+/-8 years) and severe (n=10; age=73+/-8 years) ICA stenoses. aCBV was quantified in right and left hemispheres in controls, and, alongside industry standard dynamic susceptibility contrast (DSC), contralateral (cont), and ipsilateral (ips) to maximum stenosis in patients. iVASO contrast significantly correlated (R=0.67, P<0.01) with DSC-CBV after accounting for transit time discrepancies. Gray matter aCBV (mL/100 mL) was 1.60+/-0.10 (right) versus 1.61+/-0.20 (left) in controls, 1.59+/-0.38 (cont) and 1.65+/-0.37 (ips) in mild stenosis patients, and 1.72+/-0.18 (cont) and 1.58+/-0.20 (ips) in severe stenosis patients. aCBV was asymmetric (P<0.01) in 41% of patients whereas no asymmetry was found in any control. The potential of iVASO-DS for autoregulation studies is discussed in the context of existing hemodynamic literature.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 02/2010; 30(7):1329-42. · 5.46 Impact Factor
  • Article: Assessment of arterial arrival times derived from multiple inversion time pulsed arterial spin labeling MRI.
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    ABSTRACT: The purpose of this study was to establish a normal range for the arterial arrival time (AAT) in whole-brain pulsed arterial spin labeling (PASL) cerebral perfusion MRI. Healthy volunteers (N = 36, range: 20 to 35 years) provided informed consent to participate in this study. AAT was assessed in multiple brain regions, using three-dimensional gradient and spin echo (GRASE) pulsed arterial spin labeling at 3.0 T, and found to be 641 +/- 95, 804 +/- 91, 802 +/- 126, and 935 +/- 108 ms in the temporal, parietal, frontal, and occipital lobes, respectively. Mean gray matter AAT was found to be 694 +/- 89 ms for females (N = 15), which was significantly shorter than for men, 814 +/- 192 ms (N = 21; P < 0.0003), and significant after correcting for brain volume (P < 0.001). Significant AAT sex differences were also found using voxelwise permutation testing. An atlas of AAT values across the healthy brain is presented here and may be useful for future experiments that aim to quantify cerebral blood flow from ASL data, as well as for clinical comparisons where disease pathology may lead to altered AAT. Pulsed arterial spin labeling signals were simulated using an identical sampling scheme as the empiric study and revealed AAT can be estimated robustly when simulated arrival times are well beyond the normal range.
    Magnetic Resonance in Medicine 02/2010; 63(3):641-7. · 2.96 Impact Factor
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    Article: fMRI-Compatible Registration of Jaw Movements Using a Fiber-Optic Bend Sensor.
    Peter Sörös, Bradley J Macintosh, Fred Tam, Simon J Graham
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    ABSTRACT: A functional magnetic resonance imaging (fMRI)-compatible fiber-optic bend sensor was investigated to assess whether the device could be used effectively to monitor opening and closing of the jaw during an fMRI experiment at 3 T. In contrast to surface electromyography, a bend sensor fixed to the chin of the participant is fast and easy to use and is not affected by strong electromagnetic fields. Bend sensor recordings are characterized by high validity (compared with concurrent video recordings of mouth opening) and high reliability (comparing two independent measurements). The results of this study indicate that a bend sensor is able to record the opening and closing of the jaw associated with different overt speech conditions (producing the utterances /a/, /pa/, /pataka/) and the opening of the mouth without speech production. Data post-processing such as filtering was not necessary. There are several potential applications for bend sensor recordings of speech-related jaw movements. First, bend sensor recordings are a valuable tool to assess behavioral performance, such as response latencies, accuracies, and completion times, which is particularly important in children, seniors, or patients with various neurological or psychiatric conditions. Second, the timing information provided by bend sensor data may improve the predicted hemodynamic response that is used for fMRI analysis based on the general linear model (GLM). Third, bend sensor recordings may be included in GLM analyses not for statistical contrast purposes, but as a covariate of no interest, accounting for part of the data variance to model fMRI artifacts due to motion outside the field of view.
    Frontiers in Human Neuroscience 01/2010; 4:24. · 2.34 Impact Factor
  • Article: Cerebral blood flow, blood volume, and oxygen metabolism dynamics in human visual and motor cortex as measured by whole-brain multi-modal magnetic resonance imaging.
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    ABSTRACT: The development of neuroimaging methods to characterize flow-metabolism coupling is crucial for understanding mechanisms that subserve oxygen delivery. Functional magnetic resonance imaging (fMRI) using blood-oxygenation-level-dependent (BOLD) contrast reflects composite changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and the cerebral metabolic rate of oxygen consumption (CMRO(2)). However, it is difficult to separate these parameters from the composite BOLD signal, thereby hampering MR-based flow-metabolism coupling studies. Here, a novel, noninvasive CBV-weighted MRI approach (VASO-FLAIR with 3D GRASE (GRadient-And-Spin-Echo)) is used in conjunction with CBF-weighted and BOLD fMRI in healthy volunteers (n=7) performing simultaneous visual (8 Hz flashing-checkerboard) and motor (1 Hz unilateral joystick) tasks. This approach allows for CBV, CBF, and CMRO(2) to be estimated, yielding (mean+/-s.d.): DeltaCBF=63%+/-12%, DeltaCBV=17%+/-7%, and DeltaCMRO(2)=13%+/-11% in the visual cortex, and DeltaCBF=46%+/-11%, DeltaCBV=8%+/-3%, and DeltaCMRO(2)=12%+/-13% in the motor cortex. Following the visual and motor tasks, the BOLD signal became more negative (P=0.003) and persisted longer (P=0.006) in the visual cortex compared with the motor cortex, whereas CBV and CBF returned to baseline earlier and equivalently. The proposed whole-brain technique should be useful for assessing regional discrepancies in hemodynamic reactivity without the use of intravascular contrast agents.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 08/2009; 29(11):1856-66. · 5.46 Impact Factor
  • Article: Opioids depress cortical centers responsible for the volitional control of respiration.
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    ABSTRACT: Respiratory depression limits provision of safe opioid analgesia and is the main cause of death in drug addicts. Although opioids are known to inhibit brainstem respiratory activity, their effects on cortical areas that mediate respiration are less well understood. Here, functional magnetic resonance imaging was used to examine how brainstem and cortical activity related to a short breath hold is modulated by the opioid remifentanil. We hypothesized that remifentanil would differentially depress brain areas that mediate sensory-affective components of respiration over those that mediate volitional motor control. Quantitative measures of cerebral blood flow were used to control for hypercapnia-induced changes in blood oxygen level-dependent (BOLD) signal. Awareness of respiration, reflected by an urge-to-breathe score, was profoundly reduced with remifentanil. Urge to breathe was associated with activity in the bilateral insula, frontal operculum, and secondary somatosensory cortex. Localized remifentanil-induced decreases in breath hold-related activity were observed in the left anterior insula and operculum. We also observed remifentanil-induced decreases in the BOLD response to breath holding in the left dorsolateral prefrontal cortex, anterior cingulate, the cerebellum, and periaqueductal gray, brain areas that mediate task performance. Activity in areas mediating motor control (putamen, motor cortex) and sensory-motor integration (supramarginal gyrus) were unaffected by remifentanil. Breath hold-related activity was observed in the medulla. These findings highlight the importance of higher cortical centers in providing contextual awareness of respiration that leads to appropriate modulation of respiratory control. Opioids have profound effects on the cortical centers that control breathing, which potentiates their actions in the brainstem.
    Journal of Neuroscience 07/2009; 29(25):8177-86. · 7.11 Impact Factor
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    Article: Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele.
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    ABSTRACT: The APOE epsilon4 allele is a risk factor for late-life pathological changes that is also associated with anatomical and functional brain changes in middle-aged and elderly healthy subjects. We investigated structural and functional effects of the APOE polymorphism in 18 young healthy APOE epsilon4-carriers and 18 matched noncarriers (age range: 20-35 years). Brain activity was studied both at rest and during an encoding memory paradigm using blood oxygen level-dependent fMRI. Resting fMRI revealed increased "default mode network" (involving retrosplenial, medial temporal, and medial-prefrontal cortical areas) coactivation in epsilon4-carriers relative to noncarriers. The encoding task produced greater hippocampal activation in epsilon4-carriers relative to noncarriers. Neither result could be explained by differences in memory performance, brain morphology, or resting cerebral blood flow. The APOE epsilon4 allele modulates brain function decades before any clinical or neurophysiological expression of neurodegenerative processes.
    Proceedings of the National Academy of Sciences 05/2009; 106(17):7209-14. · 9.68 Impact Factor
  • Article: Electrodermal recording and fMRI to inform sensorimotor recovery in stroke patients.
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    ABSTRACT: Functional magnetic resonance imaging (fMRI) appears to be useful for investigating motor recovery after stroke. Some of the potential confounders of brain activation studies, however, could be mitigated through complementary physiological monitoring. To investigate a sensorimotor fMRI battery that included simultaneous measurement of electrodermal activity in subjects with hemiparetic stroke to provide a measure related to the sense of effort during motor performance. Bilateral hand and ankle tasks were performed by 6 patients with stroke (2 subacute, 4 chronic) during imaging with blood oxygen level-dependent (BOLD) fMRI using an event-related design. BOLD percent changes, peak activation, and laterality index values were calculated in the sensorimotor cortex. Electrodermal recordings were made concurrently and used as a regressor. Sensorimotor BOLD time series and percent change values provided evidence of an intact motor network in each of these well-recovered patients. During tasks involving the hemiparetic limb, electrodermal activity changes were variable in amplitude, and electrodermal activity time-series data showed significant correlations with fMRI in 3 of 6 patients. No such correlations were observed for control tasks involving the unaffected lower limb. Electrodermal activity activation maps implicated the contralesional over the ipsilesional hemisphere, supporting the notion that stroke patients may require higher order motor processing to perform simple tasks. Electrodermal activity recordings may be useful as a physiological marker of differences in effort required during movements of a subject's hemiparetic compared with the unaffected limb during fMRI studies.
    Neurorehabilitation and neural repair 10/2008; 22(6):728-36. · 4.49 Impact Factor
  • Article: Measuring the effects of remifentanil on cerebral blood flow and arterial arrival time using 3D GRASE MRI with pulsed arterial spin labelling.
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    ABSTRACT: Arterial spin labelling (ASL) has proved to be a promising magnetic resonance imaging (MRI) technique to measure brain perfusion. In this study, volumetric three-dimensional (3D) gradient and spin echo (GRASE) ASL was used to produce cerebral blood flow (CBF) and arterial arrival time (AAT) maps during rest and during an infusion of remifentanil. Gradient and spin echo ASL perfusion-weighted images were collected at multiple inflow times (500 to 2,500 ms in increments of 250 ms) to accurately fit an ASL perfusion model. Fit estimates were assessed using z-statistics, allowing voxels with a poor fit to be excluded from subsequent analyses. Nonparametric permutation testing showed voxels with a significant difference in CBF and AAT between conditions across a group of healthy participants (N=10). Administration of remifentanil produced an increase in end-tidal CO(2), an increase in CBF from 57+/-12.0 to 77+/-18.4 mL/100 g tissue per min and a reduction in AAT from 0.73+/-0.073 to 0.64+/-0.076 sec. Within grey matter, remifentanil produced a cerebrovascular response of 5.7+/-1.60 %CBF per mm Hg. Significant differences between physiologic conditions were observed in both CBF and AAT maps, indicating that 3D GRASE-ASL has the sensitivity to study changes in physiology at a voxel level.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 05/2008; 28(8):1514-22. · 5.46 Impact Factor
  • Article: Remifentanil-induced cerebral blood flow effects in normal humans: dose and ApoE genotype.
    Anesthesia and analgesia 02/2008; 106(1):347; author reply 347-8. · 3.08 Impact Factor
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    Article: Brain activity during a motor learning task: an fMRI and skin conductance study.
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    ABSTRACT: Measuring electrodermal activity (EDA) during fMRI is an effective means of studying the influence of task-related arousal, inferred from autonomic nervous system activity, on brain activation patterns. The goals of this study were: (1) to measure reliable EDA from healthy individuals during fMRI involving an effortful unilateral motor task, (2) to explore how EDA recordings can be used to augment fMRI data analysis. In addition to conventional hemodynamic modeling, skin conductance time series data were used as model waveforms to generate activation images from fMRI data. Activations from the EDA model produced significantly different brain regions from those obtained with a standard hemodynamic model, primarily in the insula and cingulate cortices. Onsets of the EDA changes were synchronous with the hemodynamic model, but EDA data showed additional transient features, such as a decrease in amplitude with time, and helped to provide behavioral evidence suggesting task difficulty decreased with movement repetition. Univariate statistics also confirmed that several brain regions showed early versus late session effects. Partial least squares (PLS) multivariate analysis of EDA and fMRI data provided complimentary, additional insight on how the motor network varied over the course of a single fMRI session. Brain regions identified in this manner included the insula, cingulate gyrus, pre- and postcentral gyri, putamen and parietal cortices. These results suggest that recording EDA during motor fMRI experiments provides complementary information that can be used to improve the fMRI analysis, particularly when behavioral or task effects are difficult to model a priori.
    Human Brain Mapping 01/2008; 28(12):1359-67. · 5.88 Impact Factor

Institutions

  • 2008–2012
    • University of Oxford
      • Nuffield Department of Clinical Neurosciences
      Oxford, ENG, United Kingdom
  • 2004–2012
    • University of Toronto
      • Sunnybrook Health Sciences Centre
      Toronto, Ontario, Canada
  • 2007–2010
    • Sunnybrook Health Sciences Centre
      Toronto, Ontario, Canada
  • 2009
    • John Radcliffe Hospital
      • Department of Clinical Neurology
      Oxford, ENG, United Kingdom