Maher Quraan - Academia.edu (original) (raw)

Papers by Maher Quraan

Research paper thumbnail of Blood-brain barrier leakage in systemic lupus erythematosus is associated with gray matter loss and cognitive impairment

Blood-brain barrier leakage in systemic lupus erythematosus is associated with gray matter loss and cognitive impairment

Annals of the Rheumatic Diseases

ObjectivesTo examine the association between blood-brain barrier (BBB) integrity, brain volume an... more ObjectivesTo examine the association between blood-brain barrier (BBB) integrity, brain volume and cognitive dysfunction in adult patients with systemic lupus erythematosus (SLE).MethodsA total of 65 ambulatory patients with SLE and 9 healthy controls underwent dynamic contrast-enhanced MRI scanning, for quantitative assessment of BBB permeability. Volumetric data were extracted using the VolBrain pipeline. Global cognitive function was evaluated using a screening battery consisting of tasks falling into five broad cognitive domains, and was compared between patients with normal versus extensive BBB leakage.ResultsPatients with SLE had significantly higher levels of BBB leakage compared with controls (p=0.04). Extensive BBB leakage (affecting over >9% of brain volume) was identified only in patients with SLE (16/65; 24.6%), who also had smaller right and left cerebral grey matter volumes compared with controls (p=0.04). Extensive BBB leakage was associated with lower global cogni...

Research paper thumbnail of Altered Resting State Brain Dynamics in Temporal Lobe Epilepsy Can Be Observed in Spectral Power, Functional Connectivity and Graph Theory Metrics

PLoS ONE, 2013

Despite a wealth of EEG epilepsy data that accumulated for over half a century, our ability to un... more Despite a wealth of EEG epilepsy data that accumulated for over half a century, our ability to understand brain dynamics associated with epilepsy remains limited. Using EEG data from 15 controls and 9 left temporal lobe epilepsy (LTLE) patients, in this study we characterize how the dynamics of the healthy brain differ from the ''dynamically balanced'' state of the brain of epilepsy patients treated with anti-epileptic drugs in the context of resting state. We show that such differences can be observed in band power, synchronization and network measures, as well as deviations from the small world network (SWN) architecture of the healthy brain. The h (4-7 Hz) and high a (10-13 Hz) bands showed the biggest deviations from healthy controls across various measures. In particular, patients demonstrated significantly higher power and synchronization than controls in the h band, but lower synchronization and power in the high a band. Furthermore, differences between controls and patients in graph theory metrics revealed deviations from a SWN architecture. In the h band epilepsy patients showed deviations toward an orderly network, while in the high a band they deviated toward a random network. These findings show that, despite the focal nature of LTLE, the epileptic brain differs in its global network characteristics from the healthy brain. To our knowledge, this is the only study to encompass power, connectivity and graph theory metrics to investigate the reorganization of resting state functional networks in LTLE patients.

Research paper thumbnail of Evaluation of multiple-sphere head models for MEG source localization

Physics in Medicine and Biology, 2011

Magnetoencephalography (MEG) source analysis has largely relied on spherical conductor models of ... more Magnetoencephalography (MEG) source analysis has largely relied on spherical conductor models of the head to simplify forward calculations of the brain's magnetic field. Multiple-(or overlapping, local) sphere models, where an optimal sphere is selected for each sensor, are considered an improvement over single-sphere models and are computationally simpler than realistic models. However, there is limited information available regarding the different methods used to generate these models and their relative accuracy. We describe a variety of single-and multiple-sphere fitting approaches, including a novel method that attempts to minimize the field error. An accurate boundary element method simulation was used to evaluate the relative field measurement error (12% on average) and dipole fit localization bias (3.5 mm) of each model over the entire brain. All spherical models can contribute in the order of 1 cm to the localization bias in regions of the head that depart significantly from a sphere (inferior frontal and temporal). These spherical approximation errors can give rise to larger localization differences when all modeling effects are taken into account and with more complex source configurations or other inverse techniques, as shown with a beamformer example. Results differed noticeably depending on the source location, making it difficult to recommend a fitting method that performs best in general. Given these limitations, it may be advisable to expand the use of realistic head models. 5621

Research paper thumbnail of Final state interactions in 2H(γ,ppπ-) near the Δ(1232) resonance

Final state interactions in 2H(γ,ppπ-) near the Δ(1232) resonance

Physical Review C, 1998

ABSTRACT The 2H(γ,ppπ-) reaction cross section has been measured in the energy range 220 MeV&... more ABSTRACT The 2H(γ,ppπ-) reaction cross section has been measured in the energy range 220 MeV<=Eγ<=280 MeV at the Saskatchewan Accelerator Laboratory using the Saskatchewan-Alberta Large Acceptance Detector. This is the first reported measurement of the γ2H-->ppπ- cross section covering a wide range of phase space in an attempt to study final state interactions. The cross section for this reaction is compared to the calculation of Blomqvist and Laget with various contributions from final state interactions. Blomqvist and Laget's theory is successful in describing the shapes of the distributions, as well as the overall magnitude of the cross section. The different final state interactions have an overall effect of 10%-15% on the single differential cross section, with the calculation that includes the Δ-N interaction having the best agreement with the data.

Research paper thumbnail of Reaction mechanisms in C12(γ, pp) near 200 MeV

Reaction mechanisms in C12(γ, pp) near 200 MeV

Physical Review C, 1996

ABSTRACT Inclusive 12C(gamma,pp) cross sections have been measured with tagged photons in the ran... more ABSTRACT Inclusive 12C(gamma,pp) cross sections have been measured with tagged photons in the range Egamma=187-227 MeV using the Saskatchewan-Alberta Large Acceptance Detector (SALAD). The large angular acceptance allowed the measurement of noncoplanar pp emission. The cross sections were compared to a Monte Carlo intranuclear cascade calculation. Agreement was reasonable for the shapes of the cross sections but the calculated total cross section was 3.9 times larger than the data.

Research paper thumbnail of TWIST- The TRIUMF weak interaction symmetry test the Michel parameters from μ+ decay

Nuclear Physics B - Proceedings Supplements, 2001

Research paper thumbnail of Drift chambers for a precision measurement of the Michel parameters in muon decay

Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2001

Planar drift chambers will be used in a solenoidal magnetic field to measure the Michel parameter... more Planar drift chambers will be used in a solenoidal magnetic field to measure the Michel parameters in muon decay. The chamber manufacture procedure uses flat glass tables and precise ceramic glass spacers to provide precise anodecathode spacing. Results of bench and beam tests of the prototype chambers are discussed. #

Research paper thumbnail of EEG Power Asymmetry and Functional Connectivity as a Marker of Treatment Effectiveness in DBS Surgery for Depression

Neuropsychopharmacology, 2014

Recently, deep brain stimulation (DBS) has been evaluated as an experimental therapy for treatmen... more Recently, deep brain stimulation (DBS) has been evaluated as an experimental therapy for treatment-resistant depression. Although there have been encouraging results in open-label trials, about half of the patients fail to achieve meaningful benefit. Although progress has been made in understanding the neurobiology of MDD, the ability to characterize differences in brain dynamics between those who do and do not benefit from DBS is lacking. In this study, we investigated EEG resting-state data recorded from 12 patients that have undergone DBS surgery. Of those, six patients were classified as responders to DBS, defined as an improvement of 50% or more on the 17-item Hamilton Rating Scale for Depression (HAMD-17). We compared hemispheric frontal theta and parietal alpha power asymmetry and synchronization asymmetry between responders and non-responders. Hemispheric power asymmetry showed statistically significant differences between responders and non-responders with healthy controls showing an asymmetry similar to responders but opposite to non-responders. This asymmetry was characterized by an increase in frontal theta in the right hemisphere relative to the left combined with an increase in parietal alpha in the left hemisphere relative to the right in non-responders compared with responders. Hemispheric mean synchronization asymmetry showed a statistically significant difference between responders and non-responders in the theta band, with healthy controls showing an asymmetry similar to responders but opposite to non-responders. This asymmetry resulted from an increase in frontal synchronization in the right hemisphere relative to the left combined with an increase in parietal synchronization in the left hemisphere relative to the right in non-responders compared with responders. Connectivity diagrams revealed long-range differences in frontal/central-parietal connectivity between the two groups in the theta band. This pattern was observed irrespective of whether EEG data were collected with active DBS or with the DBS stimulation turned off, suggesting stable functional and possibly structural modifications that may be attributed to plasticity.

Research paper thumbnail of Auditory evoked fields to vocalization during passive listening and active generation in adults who stutter

NeuroImage, 2010

We used magnetoencephalography to investigate auditory evoked responses to speech vocalizations a... more We used magnetoencephalography to investigate auditory evoked responses to speech vocalizations and non-speech tones in adults who do and do not stutter. Neuromagnetic field patterns were recorded as participants listened to a 1 kHz tone, playback of their own productions of the vowel /i/ and vowel-initial words, and actively generated the vowel /i/ and vowel-initial words. Activation of the auditory cortex at approximately 50 and 100 ms was observed during all tasks. A reduction in the peak amplitudes of the M50 and M100 components was observed during the active generation versus passive listening tasks dependent on the stimuli. Adults who stutter did not differ in the amount of speech-induced auditory suppression relative to fluent speakers. Adults who stutter had shorter M100 latencies for the actively generated speaking tasks in the right hemisphere relative to the left hemisphere but the fluent speakers showed similar latencies across hemispheres. During passive listening tasks, adults who stutter had longer M50 and M100 latencies than fluent speakers. The results suggest that there are timing, rather than amplitude, differences in auditory processing during speech in adults who stutter and are discussed in relation to hypotheses of auditory-motor integration breakdown in stuttering.

Research paper thumbnail of ICA-based artifact correction improves spatial localization of adaptive spatial filters in MEG

ICA-based artifact correction improves spatial localization of adaptive spatial filters in MEG

NeuroImage, 2013

Beamformers are one of the most common inverse models currently used in the estimation of source ... more Beamformers are one of the most common inverse models currently used in the estimation of source activity from magnetoencephelography (MEG) data. They rely on a minimization of total power while constraining the gain in the voxel of interest, resulting in the suppression of background noise. Nonetheless, in cases where background noise is strong compared to the source of interest, or when many sources are present, the ability of the beamformer to detect and accurately localize weak sources is reduced. In visual paradigms, two main background sources can substantially impact an accurate estimation of weaker sources. Ocular artifacts are orders of magnitude higher than neural sources making it difficult for the beamformer to effectively suppress them. Primary visual activations also result in strong signals that can impede localization of weak sources. In this paper, we systematically evaluated how neural (visual) and non-neural (eye, heart) sources affect the localization accuracy of frontal and medial temporal sources in visual tasks. These sources are of tremendous interest in learning and memory studies as well as in clinical settings (Alzheimer's/epilepsy) and are typically difficult to localize robustly in MEG. Empirical data from two tasks - active learning and control - were used to evaluate our analysis techniques. Global field power calculations showed multiple time periods where active learning was significantly different from response selection with dominant sources converging to the eyes. Extensive leakage of eye activity into frontal and visual that evoked responses into parietal cortices was also observed. Contributions from ocular activity to the reconstructed time series were indiscernible from task-based recruitment of frontal sources in the original data. Removing artifacts (eye movements, cardiac, and muscular) by means of independent component analysis (ICA) led to a significant improvement in detection and localization of frontal and medial temporal sources. We verified our results by using simulations of sources placed in frontal and medial temporal regions with various types of background noise (eye, heart, and visual). We report that the detection and localization accuracy of frontal and medial temporal sources with beamformer techniques is highly dependent on the magnitude and location of background sources and that removing artifacts can substantially improve the beamformer's performance.

Research paper thumbnail of Speech-induced suppression of evoked auditory fields in children who stutter

NeuroImage, 2011

Auditory responses to speech sounds that are self-initiated are suppressed compared to responses ... more Auditory responses to speech sounds that are self-initiated are suppressed compared to responses to the same speech sounds during passive listening. This phenomenon is referred to as speech-induced suppression, a potentially important feedback-mediated speech-motor control process. In an earlier study, we found that both adults who do and do not stutter demonstrated a reduced amplitude of the auditory M50 and M100 responses to speech during active production relative to passive listening. It is unknown if auditory responses to self-initiated speech-motor acts are suppressed in children or if the phenomenon differs between children who do and do not stutter. As stuttering is a developmental speech disorder, examining speech-induced suppression in children may identify possible neural differences underlying stuttering close to its time of onset. We used magnetoencephalography to determine the presence of speech-induced suppression in children and to characterize the properties of speech-induced suppression in children who stutter. We examined the auditory M50 as this was the earliest robust response reproducible across our child participants and the most likely to reflect a motor-to-auditory relation. Both children who do and do not stutter demonstrated speech-induced suppression of the auditory M50. However, children who stutter had a delayed auditory M50 peak latency to vowel sounds compared to children who do not stutter indicating a possible deficiency in their ability to efficiently integrate auditory speech information for the purpose of establishing neural representations of speech sounds.

Research paper thumbnail of Hippocampal Lateralization and Memory in Children and Adults

Journal of the International Neuropsychological Society, 2013

The neural organization of cognitive processes, particularly hemispheric lateralization, changes ... more The neural organization of cognitive processes, particularly hemispheric lateralization, changes throughout childhood and adolescence. Differences in the neural basis of relational memory between children and adults are not well characterized. In this study we used magnetoencephalography to observe the lateralization differences of hippocampal activation in children and adults during performance of a relational memory task, transverse patterning (TP). The TP task was paired with an elemental control task, which does not depend upon the hippocampus. We contrasted two hypotheses; the compensation hypothesis would suggest that more bilateral activation in children would lead to better TP performance, whereas the maturation hypothesis would predict that a more adult-like right-lateralized pattern of hippocampal activation would lead to better performance. Mean-centered partial least squares analysis was used to determine unique patterns of brain activation specific to each task per group, while diminishing activation that is consistent across tasks. Our findings support the maturation hypothesis that a more adult-like pattern of increased right hippocampal lateralization in children leads to superior performance on the TP task. We also found dynamic changes of lateralization throughout the time course for all three groups, suggesting that caution is needed when interpreting conclusions about brain lateralization. (JINS, 2013, 19, 1-11)

Research paper thumbnail of Continuous head localization and data correction in MEG

International Congress Series, 2007

We describe a system that monitors head movement continuously and corrects the data to remove the... more We describe a system that monitors head movement continuously and corrects the data to remove the effects of motion. Head position is monitored by real-time analysis of signals of three small coils mounted on the subject's head. Data correction is done off-line. Tests of the system with both dipole fitting and SAM beamformer analysis show that it allows correction of errors in source locations due to head movement to ∼ 1 mm.

Research paper thumbnail of Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy

Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy

Epilepsia, 2013

The clinical relevance of resting state functional connectivity in neurologic disorders, includin... more The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change. Functional magnetic resonance imaging (fMRI) resting state scans and neuropsychological memory assessments (Warrington Recognition Tests for Words and Faces) were performed on 19 healthy controls, 20 patients with right mTLE, and 18 patients with left mTLE. In addition, postsurgical fMRI resting state and memory change (postsurgical memory performance-presurgical memory performance) data were available for half of these patients. Patients with mTLE showed reduced connectivity from the posterior cingulate cortex (PCC) to the epileptogenic HC and increased PCC connectivity to the contralateral HC. Stronger PCC connectivity to the epileptogenic HC was associated with better presurgical memory and with greater postsurgical memory decline. Stronger PCC connectivity to the contralateral HC was associated with less postsurgical memory decline. Following surgery, PCC connectivity to the remaining HC increased from presurgical values and showed enhanced correlation with postsurgical memory function. It is notable that this index was superior to others (hippocampal volume, preoperative memory scores) in explaining variance in memory change following surgery. Our results demonstrate the striking clinical significance of the brain's intrinsic connectivity in evaluating cognitive capacity and indicating the potential of postsurgical cognitive morbidity in patients with mTLE.

Research paper thumbnail of Techniques for Detection and Localization of Weak Hippocampal and Medial Frontal Sources Using Beamformers in MEG

Techniques for Detection and Localization of Weak Hippocampal and Medial Frontal Sources Using Beamformers in MEG

Brain Topography, 2012

Magnetoencephalography provides precise information about the temporal dynamics of brain activati... more Magnetoencephalography provides precise information about the temporal dynamics of brain activation and is an ideal tool for investigating rapid cognitive processing. However, in many cognitive paradigms visual stimuli are used, which evoke strong brain responses (typically 40-100 nAm in V1) that may impede the detection of weaker activations of interest. This is particularly a concern when beamformer algorithms are used for source analysis, due to artefacts such as "leakage" of activation from the primary visual sources into other regions. We have previously shown (Quraan et al. 2011) that we can effectively reduce leakage patterns and detect weak hippocampal sources by subtracting the functional images derived from the experimental task and a control task with similar stimulus parameters. In this study we assess the performance of three different subtraction techniques. In the first technique we follow the same post-localization subtraction procedures as in our previous work. In the second and third techniques, we subtract the sensor data obtained from the experimental and control paradigms prior to source localization. Using simulated signals embedded in real data, we show that when beamformers are used, subtraction prior to source localization allows for the detection of weaker sources and higher localization accuracy. The improvement in localization accuracy exceeded 10 mm at low signal-to-noise ratios, and sources down to below 5 nAm were detected. We applied our techniques to empirical data acquired with two different paradigms designed to evoke hippocampal and frontal activations, and demonstrated our ability to detect robust activations in both regions with substantial improvements over image subtraction. We conclude that removal of the common-mode dominant sources through data subtraction prior to localization further improves the beamformer's ability to project the n-channel sensor-space data to reveal weak sources of interest and allows more accurate localization.

Research paper thumbnail of Detection and localization of hippocampal activity using beamformers with MEG: A detailed investigation using simulations and empirical data

Human Brain Mapping, 2011

The ability to detect neuronal activity emanating from deep brain structures such as the hippocam... more The ability to detect neuronal activity emanating from deep brain structures such as the hippocampus using magnetoencephalography has been debated in the literature. While a significant number of recent publications reported activations from deep brain structures, others reported their inability to detect such activity even when other detection modalities confirmed its presence. In this article, we relied on realistic simulations to show that both sides of this debate are correct and that these findings are reconcilable. We show that the ability to detect such activations in evoked responses depends on the signal strength, the amount of brain noise background, the experimental design parameters, and the methodology used to detect them. Furthermore, we show that small signal strengths require contrasts with control conditions to be detected, particularly in the presence of strong brain noise backgrounds. We focus on one localization technique, the adaptive spatial filter (beamformer), and examine its strengths and weaknesses in reconstructing hippocampal activations, in the presence of other strong brain sources such as visual activations, and compare the performance of the vector and scalar beamformers under such conditions. We show that although a weight-normalized beamformer combined with a multisphere head model is not biased in the presence of uncorrelated random noise, it can be significantly biased in the presence of correlated brain noise. Furthermore, we show that the vector beamformer performs significantly better than the scalar under such conditions. We corroborate our findings empirically using real data and demonstrate our ability to detect and localize such sources. Hum Brain Mapp 00:000-000,

Research paper thumbnail of Blood-brain barrier leakage in systemic lupus erythematosus is associated with gray matter loss and cognitive impairment

Blood-brain barrier leakage in systemic lupus erythematosus is associated with gray matter loss and cognitive impairment

Annals of the Rheumatic Diseases

ObjectivesTo examine the association between blood-brain barrier (BBB) integrity, brain volume an... more ObjectivesTo examine the association between blood-brain barrier (BBB) integrity, brain volume and cognitive dysfunction in adult patients with systemic lupus erythematosus (SLE).MethodsA total of 65 ambulatory patients with SLE and 9 healthy controls underwent dynamic contrast-enhanced MRI scanning, for quantitative assessment of BBB permeability. Volumetric data were extracted using the VolBrain pipeline. Global cognitive function was evaluated using a screening battery consisting of tasks falling into five broad cognitive domains, and was compared between patients with normal versus extensive BBB leakage.ResultsPatients with SLE had significantly higher levels of BBB leakage compared with controls (p=0.04). Extensive BBB leakage (affecting over >9% of brain volume) was identified only in patients with SLE (16/65; 24.6%), who also had smaller right and left cerebral grey matter volumes compared with controls (p=0.04). Extensive BBB leakage was associated with lower global cogni...

Research paper thumbnail of Altered Resting State Brain Dynamics in Temporal Lobe Epilepsy Can Be Observed in Spectral Power, Functional Connectivity and Graph Theory Metrics

PLoS ONE, 2013

Despite a wealth of EEG epilepsy data that accumulated for over half a century, our ability to un... more Despite a wealth of EEG epilepsy data that accumulated for over half a century, our ability to understand brain dynamics associated with epilepsy remains limited. Using EEG data from 15 controls and 9 left temporal lobe epilepsy (LTLE) patients, in this study we characterize how the dynamics of the healthy brain differ from the ''dynamically balanced'' state of the brain of epilepsy patients treated with anti-epileptic drugs in the context of resting state. We show that such differences can be observed in band power, synchronization and network measures, as well as deviations from the small world network (SWN) architecture of the healthy brain. The h (4-7 Hz) and high a (10-13 Hz) bands showed the biggest deviations from healthy controls across various measures. In particular, patients demonstrated significantly higher power and synchronization than controls in the h band, but lower synchronization and power in the high a band. Furthermore, differences between controls and patients in graph theory metrics revealed deviations from a SWN architecture. In the h band epilepsy patients showed deviations toward an orderly network, while in the high a band they deviated toward a random network. These findings show that, despite the focal nature of LTLE, the epileptic brain differs in its global network characteristics from the healthy brain. To our knowledge, this is the only study to encompass power, connectivity and graph theory metrics to investigate the reorganization of resting state functional networks in LTLE patients.

Research paper thumbnail of Evaluation of multiple-sphere head models for MEG source localization

Physics in Medicine and Biology, 2011

Magnetoencephalography (MEG) source analysis has largely relied on spherical conductor models of ... more Magnetoencephalography (MEG) source analysis has largely relied on spherical conductor models of the head to simplify forward calculations of the brain's magnetic field. Multiple-(or overlapping, local) sphere models, where an optimal sphere is selected for each sensor, are considered an improvement over single-sphere models and are computationally simpler than realistic models. However, there is limited information available regarding the different methods used to generate these models and their relative accuracy. We describe a variety of single-and multiple-sphere fitting approaches, including a novel method that attempts to minimize the field error. An accurate boundary element method simulation was used to evaluate the relative field measurement error (12% on average) and dipole fit localization bias (3.5 mm) of each model over the entire brain. All spherical models can contribute in the order of 1 cm to the localization bias in regions of the head that depart significantly from a sphere (inferior frontal and temporal). These spherical approximation errors can give rise to larger localization differences when all modeling effects are taken into account and with more complex source configurations or other inverse techniques, as shown with a beamformer example. Results differed noticeably depending on the source location, making it difficult to recommend a fitting method that performs best in general. Given these limitations, it may be advisable to expand the use of realistic head models. 5621

Research paper thumbnail of Final state interactions in 2H(γ,ppπ-) near the Δ(1232) resonance

Final state interactions in 2H(γ,ppπ-) near the Δ(1232) resonance

Physical Review C, 1998

ABSTRACT The 2H(γ,ppπ-) reaction cross section has been measured in the energy range 220 MeV&... more ABSTRACT The 2H(γ,ppπ-) reaction cross section has been measured in the energy range 220 MeV<=Eγ<=280 MeV at the Saskatchewan Accelerator Laboratory using the Saskatchewan-Alberta Large Acceptance Detector. This is the first reported measurement of the γ2H-->ppπ- cross section covering a wide range of phase space in an attempt to study final state interactions. The cross section for this reaction is compared to the calculation of Blomqvist and Laget with various contributions from final state interactions. Blomqvist and Laget's theory is successful in describing the shapes of the distributions, as well as the overall magnitude of the cross section. The different final state interactions have an overall effect of 10%-15% on the single differential cross section, with the calculation that includes the Δ-N interaction having the best agreement with the data.

Research paper thumbnail of Reaction mechanisms in C12(γ, pp) near 200 MeV

Reaction mechanisms in C12(γ, pp) near 200 MeV

Physical Review C, 1996

ABSTRACT Inclusive 12C(gamma,pp) cross sections have been measured with tagged photons in the ran... more ABSTRACT Inclusive 12C(gamma,pp) cross sections have been measured with tagged photons in the range Egamma=187-227 MeV using the Saskatchewan-Alberta Large Acceptance Detector (SALAD). The large angular acceptance allowed the measurement of noncoplanar pp emission. The cross sections were compared to a Monte Carlo intranuclear cascade calculation. Agreement was reasonable for the shapes of the cross sections but the calculated total cross section was 3.9 times larger than the data.

Research paper thumbnail of TWIST- The TRIUMF weak interaction symmetry test the Michel parameters from μ+ decay

Nuclear Physics B - Proceedings Supplements, 2001

Research paper thumbnail of Drift chambers for a precision measurement of the Michel parameters in muon decay

Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2001

Planar drift chambers will be used in a solenoidal magnetic field to measure the Michel parameter... more Planar drift chambers will be used in a solenoidal magnetic field to measure the Michel parameters in muon decay. The chamber manufacture procedure uses flat glass tables and precise ceramic glass spacers to provide precise anodecathode spacing. Results of bench and beam tests of the prototype chambers are discussed. #

Research paper thumbnail of EEG Power Asymmetry and Functional Connectivity as a Marker of Treatment Effectiveness in DBS Surgery for Depression

Neuropsychopharmacology, 2014

Recently, deep brain stimulation (DBS) has been evaluated as an experimental therapy for treatmen... more Recently, deep brain stimulation (DBS) has been evaluated as an experimental therapy for treatment-resistant depression. Although there have been encouraging results in open-label trials, about half of the patients fail to achieve meaningful benefit. Although progress has been made in understanding the neurobiology of MDD, the ability to characterize differences in brain dynamics between those who do and do not benefit from DBS is lacking. In this study, we investigated EEG resting-state data recorded from 12 patients that have undergone DBS surgery. Of those, six patients were classified as responders to DBS, defined as an improvement of 50% or more on the 17-item Hamilton Rating Scale for Depression (HAMD-17). We compared hemispheric frontal theta and parietal alpha power asymmetry and synchronization asymmetry between responders and non-responders. Hemispheric power asymmetry showed statistically significant differences between responders and non-responders with healthy controls showing an asymmetry similar to responders but opposite to non-responders. This asymmetry was characterized by an increase in frontal theta in the right hemisphere relative to the left combined with an increase in parietal alpha in the left hemisphere relative to the right in non-responders compared with responders. Hemispheric mean synchronization asymmetry showed a statistically significant difference between responders and non-responders in the theta band, with healthy controls showing an asymmetry similar to responders but opposite to non-responders. This asymmetry resulted from an increase in frontal synchronization in the right hemisphere relative to the left combined with an increase in parietal synchronization in the left hemisphere relative to the right in non-responders compared with responders. Connectivity diagrams revealed long-range differences in frontal/central-parietal connectivity between the two groups in the theta band. This pattern was observed irrespective of whether EEG data were collected with active DBS or with the DBS stimulation turned off, suggesting stable functional and possibly structural modifications that may be attributed to plasticity.

Research paper thumbnail of Auditory evoked fields to vocalization during passive listening and active generation in adults who stutter

NeuroImage, 2010

We used magnetoencephalography to investigate auditory evoked responses to speech vocalizations a... more We used magnetoencephalography to investigate auditory evoked responses to speech vocalizations and non-speech tones in adults who do and do not stutter. Neuromagnetic field patterns were recorded as participants listened to a 1 kHz tone, playback of their own productions of the vowel /i/ and vowel-initial words, and actively generated the vowel /i/ and vowel-initial words. Activation of the auditory cortex at approximately 50 and 100 ms was observed during all tasks. A reduction in the peak amplitudes of the M50 and M100 components was observed during the active generation versus passive listening tasks dependent on the stimuli. Adults who stutter did not differ in the amount of speech-induced auditory suppression relative to fluent speakers. Adults who stutter had shorter M100 latencies for the actively generated speaking tasks in the right hemisphere relative to the left hemisphere but the fluent speakers showed similar latencies across hemispheres. During passive listening tasks, adults who stutter had longer M50 and M100 latencies than fluent speakers. The results suggest that there are timing, rather than amplitude, differences in auditory processing during speech in adults who stutter and are discussed in relation to hypotheses of auditory-motor integration breakdown in stuttering.

Research paper thumbnail of ICA-based artifact correction improves spatial localization of adaptive spatial filters in MEG

ICA-based artifact correction improves spatial localization of adaptive spatial filters in MEG

NeuroImage, 2013

Beamformers are one of the most common inverse models currently used in the estimation of source ... more Beamformers are one of the most common inverse models currently used in the estimation of source activity from magnetoencephelography (MEG) data. They rely on a minimization of total power while constraining the gain in the voxel of interest, resulting in the suppression of background noise. Nonetheless, in cases where background noise is strong compared to the source of interest, or when many sources are present, the ability of the beamformer to detect and accurately localize weak sources is reduced. In visual paradigms, two main background sources can substantially impact an accurate estimation of weaker sources. Ocular artifacts are orders of magnitude higher than neural sources making it difficult for the beamformer to effectively suppress them. Primary visual activations also result in strong signals that can impede localization of weak sources. In this paper, we systematically evaluated how neural (visual) and non-neural (eye, heart) sources affect the localization accuracy of frontal and medial temporal sources in visual tasks. These sources are of tremendous interest in learning and memory studies as well as in clinical settings (Alzheimer's/epilepsy) and are typically difficult to localize robustly in MEG. Empirical data from two tasks - active learning and control - were used to evaluate our analysis techniques. Global field power calculations showed multiple time periods where active learning was significantly different from response selection with dominant sources converging to the eyes. Extensive leakage of eye activity into frontal and visual that evoked responses into parietal cortices was also observed. Contributions from ocular activity to the reconstructed time series were indiscernible from task-based recruitment of frontal sources in the original data. Removing artifacts (eye movements, cardiac, and muscular) by means of independent component analysis (ICA) led to a significant improvement in detection and localization of frontal and medial temporal sources. We verified our results by using simulations of sources placed in frontal and medial temporal regions with various types of background noise (eye, heart, and visual). We report that the detection and localization accuracy of frontal and medial temporal sources with beamformer techniques is highly dependent on the magnitude and location of background sources and that removing artifacts can substantially improve the beamformer's performance.

Research paper thumbnail of Speech-induced suppression of evoked auditory fields in children who stutter

NeuroImage, 2011

Auditory responses to speech sounds that are self-initiated are suppressed compared to responses ... more Auditory responses to speech sounds that are self-initiated are suppressed compared to responses to the same speech sounds during passive listening. This phenomenon is referred to as speech-induced suppression, a potentially important feedback-mediated speech-motor control process. In an earlier study, we found that both adults who do and do not stutter demonstrated a reduced amplitude of the auditory M50 and M100 responses to speech during active production relative to passive listening. It is unknown if auditory responses to self-initiated speech-motor acts are suppressed in children or if the phenomenon differs between children who do and do not stutter. As stuttering is a developmental speech disorder, examining speech-induced suppression in children may identify possible neural differences underlying stuttering close to its time of onset. We used magnetoencephalography to determine the presence of speech-induced suppression in children and to characterize the properties of speech-induced suppression in children who stutter. We examined the auditory M50 as this was the earliest robust response reproducible across our child participants and the most likely to reflect a motor-to-auditory relation. Both children who do and do not stutter demonstrated speech-induced suppression of the auditory M50. However, children who stutter had a delayed auditory M50 peak latency to vowel sounds compared to children who do not stutter indicating a possible deficiency in their ability to efficiently integrate auditory speech information for the purpose of establishing neural representations of speech sounds.

Research paper thumbnail of Hippocampal Lateralization and Memory in Children and Adults

Journal of the International Neuropsychological Society, 2013

The neural organization of cognitive processes, particularly hemispheric lateralization, changes ... more The neural organization of cognitive processes, particularly hemispheric lateralization, changes throughout childhood and adolescence. Differences in the neural basis of relational memory between children and adults are not well characterized. In this study we used magnetoencephalography to observe the lateralization differences of hippocampal activation in children and adults during performance of a relational memory task, transverse patterning (TP). The TP task was paired with an elemental control task, which does not depend upon the hippocampus. We contrasted two hypotheses; the compensation hypothesis would suggest that more bilateral activation in children would lead to better TP performance, whereas the maturation hypothesis would predict that a more adult-like right-lateralized pattern of hippocampal activation would lead to better performance. Mean-centered partial least squares analysis was used to determine unique patterns of brain activation specific to each task per group, while diminishing activation that is consistent across tasks. Our findings support the maturation hypothesis that a more adult-like pattern of increased right hippocampal lateralization in children leads to superior performance on the TP task. We also found dynamic changes of lateralization throughout the time course for all three groups, suggesting that caution is needed when interpreting conclusions about brain lateralization. (JINS, 2013, 19, 1-11)

Research paper thumbnail of Continuous head localization and data correction in MEG

International Congress Series, 2007

We describe a system that monitors head movement continuously and corrects the data to remove the... more We describe a system that monitors head movement continuously and corrects the data to remove the effects of motion. Head position is monitored by real-time analysis of signals of three small coils mounted on the subject's head. Data correction is done off-line. Tests of the system with both dipole fitting and SAM beamformer analysis show that it allows correction of errors in source locations due to head movement to ∼ 1 mm.

Research paper thumbnail of Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy

Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy

Epilepsia, 2013

The clinical relevance of resting state functional connectivity in neurologic disorders, includin... more The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change. Functional magnetic resonance imaging (fMRI) resting state scans and neuropsychological memory assessments (Warrington Recognition Tests for Words and Faces) were performed on 19 healthy controls, 20 patients with right mTLE, and 18 patients with left mTLE. In addition, postsurgical fMRI resting state and memory change (postsurgical memory performance-presurgical memory performance) data were available for half of these patients. Patients with mTLE showed reduced connectivity from the posterior cingulate cortex (PCC) to the epileptogenic HC and increased PCC connectivity to the contralateral HC. Stronger PCC connectivity to the epileptogenic HC was associated with better presurgical memory and with greater postsurgical memory decline. Stronger PCC connectivity to the contralateral HC was associated with less postsurgical memory decline. Following surgery, PCC connectivity to the remaining HC increased from presurgical values and showed enhanced correlation with postsurgical memory function. It is notable that this index was superior to others (hippocampal volume, preoperative memory scores) in explaining variance in memory change following surgery. Our results demonstrate the striking clinical significance of the brain's intrinsic connectivity in evaluating cognitive capacity and indicating the potential of postsurgical cognitive morbidity in patients with mTLE.

Research paper thumbnail of Techniques for Detection and Localization of Weak Hippocampal and Medial Frontal Sources Using Beamformers in MEG

Techniques for Detection and Localization of Weak Hippocampal and Medial Frontal Sources Using Beamformers in MEG

Brain Topography, 2012

Magnetoencephalography provides precise information about the temporal dynamics of brain activati... more Magnetoencephalography provides precise information about the temporal dynamics of brain activation and is an ideal tool for investigating rapid cognitive processing. However, in many cognitive paradigms visual stimuli are used, which evoke strong brain responses (typically 40-100 nAm in V1) that may impede the detection of weaker activations of interest. This is particularly a concern when beamformer algorithms are used for source analysis, due to artefacts such as "leakage" of activation from the primary visual sources into other regions. We have previously shown (Quraan et al. 2011) that we can effectively reduce leakage patterns and detect weak hippocampal sources by subtracting the functional images derived from the experimental task and a control task with similar stimulus parameters. In this study we assess the performance of three different subtraction techniques. In the first technique we follow the same post-localization subtraction procedures as in our previous work. In the second and third techniques, we subtract the sensor data obtained from the experimental and control paradigms prior to source localization. Using simulated signals embedded in real data, we show that when beamformers are used, subtraction prior to source localization allows for the detection of weaker sources and higher localization accuracy. The improvement in localization accuracy exceeded 10 mm at low signal-to-noise ratios, and sources down to below 5 nAm were detected. We applied our techniques to empirical data acquired with two different paradigms designed to evoke hippocampal and frontal activations, and demonstrated our ability to detect robust activations in both regions with substantial improvements over image subtraction. We conclude that removal of the common-mode dominant sources through data subtraction prior to localization further improves the beamformer's ability to project the n-channel sensor-space data to reveal weak sources of interest and allows more accurate localization.

Research paper thumbnail of Detection and localization of hippocampal activity using beamformers with MEG: A detailed investigation using simulations and empirical data

Human Brain Mapping, 2011

The ability to detect neuronal activity emanating from deep brain structures such as the hippocam... more The ability to detect neuronal activity emanating from deep brain structures such as the hippocampus using magnetoencephalography has been debated in the literature. While a significant number of recent publications reported activations from deep brain structures, others reported their inability to detect such activity even when other detection modalities confirmed its presence. In this article, we relied on realistic simulations to show that both sides of this debate are correct and that these findings are reconcilable. We show that the ability to detect such activations in evoked responses depends on the signal strength, the amount of brain noise background, the experimental design parameters, and the methodology used to detect them. Furthermore, we show that small signal strengths require contrasts with control conditions to be detected, particularly in the presence of strong brain noise backgrounds. We focus on one localization technique, the adaptive spatial filter (beamformer), and examine its strengths and weaknesses in reconstructing hippocampal activations, in the presence of other strong brain sources such as visual activations, and compare the performance of the vector and scalar beamformers under such conditions. We show that although a weight-normalized beamformer combined with a multisphere head model is not biased in the presence of uncorrelated random noise, it can be significantly biased in the presence of correlated brain noise. Furthermore, we show that the vector beamformer performs significantly better than the scalar under such conditions. We corroborate our findings empirically using real data and demonstrate our ability to detect and localize such sources. Hum Brain Mapp 00:000-000,