Background: Migraine affects roughly 10% of youth aged 5-15 years, however the underlying mechani... more Background: Migraine affects roughly 10% of youth aged 5-15 years, however the underlying mechanisms of migraine in youth are poorly understood. Multiple structural and functional alterations have been shown in the brains of adult migraine sufferers. This study aims to investigate the effects of migraine on resting-state functional connectivity during the period of transition from childhood to adolescence, a critical period of brain development and the time when rates of pediatric chronic pain spikes. Methods: Using independent component analysis, we compared resting state network spatial maps and power spectra between youth with migraine aged 7-15 and age-matched controls. Statistical comparisons were conducted using a MANCOVA analysis. Results: We show (1) group by age interaction effects on connectivity in the visual and salience networks, group by sex interaction effects on connectivity in the default mode network and group by pubertal status interaction effects on connectivity in visual and frontal parietal networks, and (2) relationships between connectivity in the visual networks and the migraine cycle, and age by cycle interaction effects on connectivity in the visual, default mode and sensorimotor networks. Conclusions: We demonstrate that brain alterations begin early in youth with migraine and are modulated by development. This highlights the need for further study into the neural mechanisms of migraine in youth specifically, to aid in the development of more effective treatments.
Introduction Tourette's syndrome (TS) affects approximately 1% of children. This study will deter... more Introduction Tourette's syndrome (TS) affects approximately 1% of children. This study will determine the efficacy and safety of paired comprehensive behavioural intervention for tics (CBIT) plus repetitive transcranial magnetic stimulation (rTMS) treatment in children with Tourette's syndrome. We hypothesise that CBIT and active rTMS to the supplementary motor area (SMA) will (1) decrease tic severity, and (2) be associated with changes indicative of enhanced neuroplasticity (eg, changes in in vivo metabolite concentrations and TMS neurophysiology measures). Methods and analysis This study will recruit 50 youth with TS, aged 6-18 for a phase II, double-blind, block randomised, sham-controlled trial comparing active rTMS plus CBIT to sham rTMS plus CBIT in a 1:1 ratio. The CBIT protocol is eight sessions over 10 weeks, once a week for 6 weeks and then biweekly. The rTMS protocol is 20 sessions of functional MRIguided, low-frequency (1 Hz) rTMS targeted to the bilateral SMA over 5 weeks (weeks 2-6). MRI, clinical and motor assessments and neurophysiological evaluations including motor mapping will be performed 1 week before CBIT start, 1 week after rTMS treatment and 1 week after CBIT completion. The primary outcome measure is Tourette's symptom change from baseline to post-CBIT treatment, as measured by the Yale Global Tic Severity Scale. Secondary outcomes include changes in imaging, neurophysiological and behavioural markers. Ethics and dissemination Ethical approval by the Conjoint Health Research Ethics Board (REB18-0220). The results of this study will be published in peer-reviewed scientific journals, on ClinicalTrials. gov and shared with the Tourette and OCD Alberta Network. The results will also be disseminated through the Alberta Addictions and Mental Health Research Hub. Trial registration NCT03844919.
Objective:Compared to typically developing (TD) peers, children with attention deficit hyperactiv... more Objective:Compared to typically developing (TD) peers, children with attention deficit hyperactivity disorder (ADHD) manifest reduced short interval cortical inhibition (SICI) in the dominant motor cortex measured with transcranial magnetic stimulation (TMS). This multimodal study investigates the inhibitory neurophysiology and neurochemistry by evaluating the relationship between SICI and γ-amino butyric acid (GABA+) levels, measured with magnetic resonance spectroscopy (MRS).Methods:Across two sites, 37 children with ADHD and 45 TD children, ages 8-12 years, participated. Single and paired pulse TMS to left motor cortex quantified SICI during REST and at times of action selection (GO) and inhibition (STOP) during a modified Slater-Hammel stop signal reaction task. MRS quantified GABA+ levels in the left sensorimotor cortex.Relationships between SICI and GABA+, as well as stopping efficiency and clinical symptoms, were analyzed with correlation and repeated-measure, mixed-models.Results:In both groups, higher GABA+ levels correlated with less SICI. In TD children only, higher GABA+ levels correlated with larger TMS motor evoked potentials (MEPs) at REST. In GO and STOP trials, higher GABA+ was associated with smaller MEP amplitudes, for both groups. Overall, GABA+ levels did not differ between groups or correlate with ADHD clinical symptoms.Conclusions:In children with higher motor cortex GABA+, motor cortex is less responsive to inhibitory TMS (SICI). Comparing the relationships between MRS-GABA+ levels and responses to TMS at REST vs. GO/STOP trials suggests differences in inhibitory neurophysiology and neurotransmitters in children with ADHD. These differences are more prominent at rest than during response inhibition task engagement.Significance:Evaluating relationships between GABA+ and SICI may provide a biomarker useful for understanding behavioral diagnoses.
Background: Magnetic resonance spectroscopy (MRS) has been used to identify gamma-aminobutyric ac... more Background: Magnetic resonance spectroscopy (MRS) has been used to identify gamma-aminobutyric acid (GABA) alterations in mood disorders, particularly in the medial prefrontal cortex (mPFC) where decreased concentrations have been associated with anhedonia. In major depressive disorder (MDD), prior work suggests that repetitive transcranial magnetic stimulation (rTMS) increases mPFC GABA concentrations proportional to antidepressant response. To our knowledge, this has not been examined in acute bipolar depression. Methods: As part of a multicentre 4-week randomized, double-blind, sham-controlled trial using intermittent theta-burst stimulation (iTBS) of the left dorsolateral prefrontal cortex (DLPFC) in individuals with acute bipolar depression, we quantified mPFC GABA and Glx (glutamate+glutamine) concentrations using a 3T MRS scan at baseline and after the intervention. Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale-17 (HRDS-17), and anhedonia was measured using the Snaith-Hamilton Pleasure Scale (SHAPS). Results: The trial was terminated for futility and magnetic resonance spectroscopy data was acquired for 18 participants. At baseline, there were no associations between GABA or Glx concentrations and anhedonia, however GABA was negative correlated with depressive symptom severity on the HRDS-17. Compared to the sham-iTBS group, participants receiving active-iTBS had a significant increase in mPFC GABA concentrations. This was unrelated to antidepressant outcomes or improvements in anhedonia. Diederichs et al. mPFC GABA Concentration After iTBS Conclusion: Our data suggests that iTBS targeting the DLPFC is associated with physiological changes in the mPFC. In acute bipolar depression, our preliminary data suggests that mPFC GABA is dissociated from antidepressant iTBS treatment outcomes and anhedonia.
Transcranial magnetic stimulation (TMS) is a widely used tool for noninvasive modulation of brain... more Transcranial magnetic stimulation (TMS) is a widely used tool for noninvasive modulation of brain activity, that is thought to interact primarily with excitatory and inhibitory neurotransmitter systems. Neurotransmitters such as glutamate and GABA can be measured by magnetic resonance spectoscopy (MRS). An important prerequisite for studying the relationship between MRS neurotransmitter levels and responses to TMS is that both modalities should examine the same regions of brain tissue. However, co-registration of TMS and MRS has been little studied to date. This study reports on a procedure for the co-registration and co-visualization of MRS and TMS, successfully localizing the hand motor cortex, as subsequently determined by its functional identification using TMS. Sixteen healthy subjects took part in the study; in 14 of 16 subjects, the TMS determined location of motor activity intersected the (2.5 cm) 3 voxel selected for MRS, centered on the so called 'hand knob' of the precentral gyrus. It is concluded that MRS voxels
Committee. RAEE receives salary support from NIH grants R01 EB016089, R01 EB023693 and P41 EB0159... more Committee. RAEE receives salary support from NIH grants R01 EB016089, R01 EB023693 and P41 EB015909. CONFLICTS OF INTEREST: GJB receives Honoraria for teaching from General Electric Healthcare, and acts as a consultant for IXICO. RML is an employee of General Electric Healthcare.
ImportanceThe antidepressant effects of transcranial magnetic stimulation protocols for major dep... more ImportanceThe antidepressant effects of transcranial magnetic stimulation protocols for major depressive disorder (MDD) are thought to depend on synaptic plasticity. The theta-burst stimulation (TBS) protocol synaptic plasticity is known to be N-methyl-D-aspartate (NMDA)–receptor dependent, yet it is unknown whether enhancing NMDA-receptor signaling improves treatment outcomes in MDD.ObjectiveTo test whether low doses of the NMDA-receptor partial-agonist, D-cycloserine, would enhance intermittent TBS (iTBS) treatment outcomes in MDD.Design, Setting, and ParticipantsThis was a single-site 4-week, double-blind, placebo-controlled, randomized clinical trial conducted from November 6, 2019, to December 24, 2020, including 50 participants with MDD. Participants were recruited via advertisements and referral. Inclusion criteria were as follows: age 18 to 65 years with a primary diagnosis of MDD, a major depressive episode with score of 18 or more on the 17-item Hamilton Depression Rating ...
BackgroundTactile processing plays a pivotal role in the early stages of human development; howev... more BackgroundTactile processing plays a pivotal role in the early stages of human development; however, little is known about tactile function in young children. An understanding of how tactile processing changes with age from early childhood to adulthood is fundamental in understanding altered tactile experiences in neurodevelopmental disorders, such as autism spectrum disorder.MethodsIn this cross‐sectional study, 142 children and adults aged 3–23 years completed a vibrotactile testing battery consisting of 5 tasks, which rely on different cortical and cognitive mechanisms. The battery was designed to be suitable for testing in young children to investigate how tactile processing changes from early childhood to adulthood.ResultsOur results suggest a pattern of rapid, age‐related changes in tactile processing toward lower discrimination thresholds (lower discrimination thresholds = greater sensitivity) across early childhood, though we acknowledge limitations with cross‐sectional data...
In vivo quantification of glutamate (Glu) and γ‐aminobutyric acid (GABA) using MRS is often achie... more In vivo quantification of glutamate (Glu) and γ‐aminobutyric acid (GABA) using MRS is often achieved using two separate sequences: a short‐echo point resolved spectroscopy (PRESS) acquisition for Glu and a Mescher‐Garwood PRESS (MEGA‐PRESS) acquisition for GABA. The purpose of this study was to examine the agreement of Glu and Glx (the combined signal of glutamate + glutamine) quantified from two different GABA‐edited MEGA‐PRESS acquisitions (GABA plus macromolecules, GABA+, TE = 68 ms, and macromolecule suppressed, MMSup, TE = 80 ms) with Glu and Glx quantified from a short‐echo PRESS (PRESS‐35, TE = 35 ms) acquisition. Fifteen healthy male volunteers underwent a single scan session, in which data were acquired using the three acquisitions (GABA+, MMSup and PRESS‐35) in both the sensorimotor and anterior cingulate cortices using a voxel size of 3 × 3 × 3 cm3. Glx and Glu were quantified from the MEGA‐PRESS data using both the OFF sub‐spectra and the difference (DIFF) spectra. Agree...
Several recent studies have reported an inter-individual correlation between regional GABA concen... more Several recent studies have reported an inter-individual correlation between regional GABA concentration, as measured by MRS, and the amplitude of the functional blood oxygenation level dependent (BOLD) response in the same region. In this study, we set out to investigate whether this coupling generalizes across cortex. In 18 healthy participants, we performed edited MRS measurements of GABA and BOLD-fMRI experiments using regionally related activation paradigms. Regions and tasks were the: occipital cortex with a visual grating stimulus; auditory cortex with a white noise stimulus; sensorimotor cortex with a finger-tapping task; frontal eye field with a saccade task; and dorsolateral prefrontal cortex with a working memory task. In contrast to the prior literature, no correlation between GABA concentration and BOLD activation was detected in any region. The origin of this discrepancy is not clear. Subtle differences in study design or insufficient power may cause differing results;...
Change in signal intensity due to acute ischemic stroke can be detected on diffusion-weighted (DW... more Change in signal intensity due to acute ischemic stroke can be detected on diffusion-weighted (DW) images soon after symptom onset. Fluid-attenuated inversion recovery (FLAIR) DW imaging suppresses signal intensity from water and has been suggested to be better than conventional DW imaging as a diagnostic imaging technique in acute stroke. We compared the signal intensity-to-noise ratio (SNR) and contrast-to-noise-ratio (CNR) between ischemic and normal tissues by using these two sequences. Twenty stroke patients underwent imaging less than 6 hours after stroke onset by using both acquisition methods. The SNR of six regions of interest in normal brain and one region in ischemic brain were compared on both DW imaging and FLAIR DW imaging. We also compared CNR in normal and ischemic tissues. The calculated apparent diffusion coefficient (ADC) maps from each acquisition technique were similarly assessed. The SNR was significantly lower for FLAIR DW imaging than for DW imaging (P < ....
Purpose: To assess the feasibility of measuring pulmonary artery (PA) pulse wave velocity (PWV) i... more Purpose: To assess the feasibility of measuring pulmonary artery (PA) pulse wave velocity (PWV) in children breathing ambient air and 12% oxygen. Methods: Velocity-encoded phase-contrast MR images of the PA were acquired in 15 children, aged 9-12 years, without evidence of cardiac or pulmonary diseases. PWV was derived as the ratio of flow to area changes during early systole. Each child was scanned twice, in air and after at least 20 minutes into inspiratory hypoxic challenge. Intra-observer and inter-observer variability and repeatability were also compared. Results: PA PWV, which was successfully measured in all subjects, increased from 1.31 ± 0.32 m/s in air to 1.61 ± 0.58 m/s under hypoxic challenge (p = 0.03). Intra-and inter-observer coefficients of variations were 9.0% and 15.6% respectively. Good correlation within and between observers of r = 0.92 and r = 0.72 respectively was noted for PA PWV measurements. Mean (95% limit of agreement) intra-and inter-observer agreement on Bland-Altman analysis were − 0.02 m/s (− 0.41-0.38 m/s) and -0.28 m/s (−1.06-0.49 m/s). Conclusion: PA PWV measurement in children using velocity-encoded MRI is feasible, reproducible and sufficiently sensitive to detect differences in PA compliance between normoxia and hypoxia. This technique can be used to detect early changes of PA compliance and monitor PAH in children.
Purpose: The conventional spectral-editing experiment used to measure GABA in the human brain als... more Purpose: The conventional spectral-editing experiment used to measure GABA in the human brain also contains a contribution from macromolecules (MM), and the combined GABA plus MM signal is often referred to as "GABAþ". More recently, methods have been developed to estimate GABA free from MM contamination. In this study, the relationship between GABA acquired with MM suppression and conventional GABAþ measurements was examined. Methods: GABA-edited MEGA-PRESS experiments with and without MM suppression were performed in the sensorimotor and occipital cortex of 12 healthy subjects at 3 Tesla. The correlation between GABAþ and MM-suppressed GABA measures was then determined. Results: Across all data, a significant correlation between GABAþ and MM-suppressed GABA was found (r ¼ 0.48; P ¼ 0.02). Regionally, the sensorimotor voxel showed a trend toward a correlation of r ¼ 0.53, P ¼ 0.07 and the occipital voxel did not show a correlation, r ¼ 0.058, P ¼ 0.9. Conclusion: GABAþ and MM-suppressed GABA are moderately correlated, but statistical power to reveal this relationship may vary regionally. The MM signal, while often assumed to be functionally irrelevant, appears to show inter-individual and inter-regional variance that impacts the correlation of GABAþ and MM-suppressed GABA. Magn Reson Med 000:000-000, 2014. V C 2014 Wiley Periodicals, Inc.
Background: Migraine affects roughly 10% of youth aged 5-15 years, however the underlying mechani... more Background: Migraine affects roughly 10% of youth aged 5-15 years, however the underlying mechanisms of migraine in youth are poorly understood. Multiple structural and functional alterations have been shown in the brains of adult migraine sufferers. This study aims to investigate the effects of migraine on resting-state functional connectivity during the period of transition from childhood to adolescence, a critical period of brain development and the time when rates of pediatric chronic pain spikes. Methods: Using independent component analysis, we compared resting state network spatial maps and power spectra between youth with migraine aged 7-15 and age-matched controls. Statistical comparisons were conducted using a MANCOVA analysis. Results: We show (1) group by age interaction effects on connectivity in the visual and salience networks, group by sex interaction effects on connectivity in the default mode network and group by pubertal status interaction effects on connectivity in visual and frontal parietal networks, and (2) relationships between connectivity in the visual networks and the migraine cycle, and age by cycle interaction effects on connectivity in the visual, default mode and sensorimotor networks. Conclusions: We demonstrate that brain alterations begin early in youth with migraine and are modulated by development. This highlights the need for further study into the neural mechanisms of migraine in youth specifically, to aid in the development of more effective treatments.
Introduction Tourette's syndrome (TS) affects approximately 1% of children. This study will deter... more Introduction Tourette's syndrome (TS) affects approximately 1% of children. This study will determine the efficacy and safety of paired comprehensive behavioural intervention for tics (CBIT) plus repetitive transcranial magnetic stimulation (rTMS) treatment in children with Tourette's syndrome. We hypothesise that CBIT and active rTMS to the supplementary motor area (SMA) will (1) decrease tic severity, and (2) be associated with changes indicative of enhanced neuroplasticity (eg, changes in in vivo metabolite concentrations and TMS neurophysiology measures). Methods and analysis This study will recruit 50 youth with TS, aged 6-18 for a phase II, double-blind, block randomised, sham-controlled trial comparing active rTMS plus CBIT to sham rTMS plus CBIT in a 1:1 ratio. The CBIT protocol is eight sessions over 10 weeks, once a week for 6 weeks and then biweekly. The rTMS protocol is 20 sessions of functional MRIguided, low-frequency (1 Hz) rTMS targeted to the bilateral SMA over 5 weeks (weeks 2-6). MRI, clinical and motor assessments and neurophysiological evaluations including motor mapping will be performed 1 week before CBIT start, 1 week after rTMS treatment and 1 week after CBIT completion. The primary outcome measure is Tourette's symptom change from baseline to post-CBIT treatment, as measured by the Yale Global Tic Severity Scale. Secondary outcomes include changes in imaging, neurophysiological and behavioural markers. Ethics and dissemination Ethical approval by the Conjoint Health Research Ethics Board (REB18-0220). The results of this study will be published in peer-reviewed scientific journals, on ClinicalTrials. gov and shared with the Tourette and OCD Alberta Network. The results will also be disseminated through the Alberta Addictions and Mental Health Research Hub. Trial registration NCT03844919.
Objective:Compared to typically developing (TD) peers, children with attention deficit hyperactiv... more Objective:Compared to typically developing (TD) peers, children with attention deficit hyperactivity disorder (ADHD) manifest reduced short interval cortical inhibition (SICI) in the dominant motor cortex measured with transcranial magnetic stimulation (TMS). This multimodal study investigates the inhibitory neurophysiology and neurochemistry by evaluating the relationship between SICI and γ-amino butyric acid (GABA+) levels, measured with magnetic resonance spectroscopy (MRS).Methods:Across two sites, 37 children with ADHD and 45 TD children, ages 8-12 years, participated. Single and paired pulse TMS to left motor cortex quantified SICI during REST and at times of action selection (GO) and inhibition (STOP) during a modified Slater-Hammel stop signal reaction task. MRS quantified GABA+ levels in the left sensorimotor cortex.Relationships between SICI and GABA+, as well as stopping efficiency and clinical symptoms, were analyzed with correlation and repeated-measure, mixed-models.Results:In both groups, higher GABA+ levels correlated with less SICI. In TD children only, higher GABA+ levels correlated with larger TMS motor evoked potentials (MEPs) at REST. In GO and STOP trials, higher GABA+ was associated with smaller MEP amplitudes, for both groups. Overall, GABA+ levels did not differ between groups or correlate with ADHD clinical symptoms.Conclusions:In children with higher motor cortex GABA+, motor cortex is less responsive to inhibitory TMS (SICI). Comparing the relationships between MRS-GABA+ levels and responses to TMS at REST vs. GO/STOP trials suggests differences in inhibitory neurophysiology and neurotransmitters in children with ADHD. These differences are more prominent at rest than during response inhibition task engagement.Significance:Evaluating relationships between GABA+ and SICI may provide a biomarker useful for understanding behavioral diagnoses.
Background: Magnetic resonance spectroscopy (MRS) has been used to identify gamma-aminobutyric ac... more Background: Magnetic resonance spectroscopy (MRS) has been used to identify gamma-aminobutyric acid (GABA) alterations in mood disorders, particularly in the medial prefrontal cortex (mPFC) where decreased concentrations have been associated with anhedonia. In major depressive disorder (MDD), prior work suggests that repetitive transcranial magnetic stimulation (rTMS) increases mPFC GABA concentrations proportional to antidepressant response. To our knowledge, this has not been examined in acute bipolar depression. Methods: As part of a multicentre 4-week randomized, double-blind, sham-controlled trial using intermittent theta-burst stimulation (iTBS) of the left dorsolateral prefrontal cortex (DLPFC) in individuals with acute bipolar depression, we quantified mPFC GABA and Glx (glutamate+glutamine) concentrations using a 3T MRS scan at baseline and after the intervention. Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale-17 (HRDS-17), and anhedonia was measured using the Snaith-Hamilton Pleasure Scale (SHAPS). Results: The trial was terminated for futility and magnetic resonance spectroscopy data was acquired for 18 participants. At baseline, there were no associations between GABA or Glx concentrations and anhedonia, however GABA was negative correlated with depressive symptom severity on the HRDS-17. Compared to the sham-iTBS group, participants receiving active-iTBS had a significant increase in mPFC GABA concentrations. This was unrelated to antidepressant outcomes or improvements in anhedonia. Diederichs et al. mPFC GABA Concentration After iTBS Conclusion: Our data suggests that iTBS targeting the DLPFC is associated with physiological changes in the mPFC. In acute bipolar depression, our preliminary data suggests that mPFC GABA is dissociated from antidepressant iTBS treatment outcomes and anhedonia.
Transcranial magnetic stimulation (TMS) is a widely used tool for noninvasive modulation of brain... more Transcranial magnetic stimulation (TMS) is a widely used tool for noninvasive modulation of brain activity, that is thought to interact primarily with excitatory and inhibitory neurotransmitter systems. Neurotransmitters such as glutamate and GABA can be measured by magnetic resonance spectoscopy (MRS). An important prerequisite for studying the relationship between MRS neurotransmitter levels and responses to TMS is that both modalities should examine the same regions of brain tissue. However, co-registration of TMS and MRS has been little studied to date. This study reports on a procedure for the co-registration and co-visualization of MRS and TMS, successfully localizing the hand motor cortex, as subsequently determined by its functional identification using TMS. Sixteen healthy subjects took part in the study; in 14 of 16 subjects, the TMS determined location of motor activity intersected the (2.5 cm) 3 voxel selected for MRS, centered on the so called 'hand knob' of the precentral gyrus. It is concluded that MRS voxels
Committee. RAEE receives salary support from NIH grants R01 EB016089, R01 EB023693 and P41 EB0159... more Committee. RAEE receives salary support from NIH grants R01 EB016089, R01 EB023693 and P41 EB015909. CONFLICTS OF INTEREST: GJB receives Honoraria for teaching from General Electric Healthcare, and acts as a consultant for IXICO. RML is an employee of General Electric Healthcare.
ImportanceThe antidepressant effects of transcranial magnetic stimulation protocols for major dep... more ImportanceThe antidepressant effects of transcranial magnetic stimulation protocols for major depressive disorder (MDD) are thought to depend on synaptic plasticity. The theta-burst stimulation (TBS) protocol synaptic plasticity is known to be N-methyl-D-aspartate (NMDA)–receptor dependent, yet it is unknown whether enhancing NMDA-receptor signaling improves treatment outcomes in MDD.ObjectiveTo test whether low doses of the NMDA-receptor partial-agonist, D-cycloserine, would enhance intermittent TBS (iTBS) treatment outcomes in MDD.Design, Setting, and ParticipantsThis was a single-site 4-week, double-blind, placebo-controlled, randomized clinical trial conducted from November 6, 2019, to December 24, 2020, including 50 participants with MDD. Participants were recruited via advertisements and referral. Inclusion criteria were as follows: age 18 to 65 years with a primary diagnosis of MDD, a major depressive episode with score of 18 or more on the 17-item Hamilton Depression Rating ...
BackgroundTactile processing plays a pivotal role in the early stages of human development; howev... more BackgroundTactile processing plays a pivotal role in the early stages of human development; however, little is known about tactile function in young children. An understanding of how tactile processing changes with age from early childhood to adulthood is fundamental in understanding altered tactile experiences in neurodevelopmental disorders, such as autism spectrum disorder.MethodsIn this cross‐sectional study, 142 children and adults aged 3–23 years completed a vibrotactile testing battery consisting of 5 tasks, which rely on different cortical and cognitive mechanisms. The battery was designed to be suitable for testing in young children to investigate how tactile processing changes from early childhood to adulthood.ResultsOur results suggest a pattern of rapid, age‐related changes in tactile processing toward lower discrimination thresholds (lower discrimination thresholds = greater sensitivity) across early childhood, though we acknowledge limitations with cross‐sectional data...
In vivo quantification of glutamate (Glu) and γ‐aminobutyric acid (GABA) using MRS is often achie... more In vivo quantification of glutamate (Glu) and γ‐aminobutyric acid (GABA) using MRS is often achieved using two separate sequences: a short‐echo point resolved spectroscopy (PRESS) acquisition for Glu and a Mescher‐Garwood PRESS (MEGA‐PRESS) acquisition for GABA. The purpose of this study was to examine the agreement of Glu and Glx (the combined signal of glutamate + glutamine) quantified from two different GABA‐edited MEGA‐PRESS acquisitions (GABA plus macromolecules, GABA+, TE = 68 ms, and macromolecule suppressed, MMSup, TE = 80 ms) with Glu and Glx quantified from a short‐echo PRESS (PRESS‐35, TE = 35 ms) acquisition. Fifteen healthy male volunteers underwent a single scan session, in which data were acquired using the three acquisitions (GABA+, MMSup and PRESS‐35) in both the sensorimotor and anterior cingulate cortices using a voxel size of 3 × 3 × 3 cm3. Glx and Glu were quantified from the MEGA‐PRESS data using both the OFF sub‐spectra and the difference (DIFF) spectra. Agree...
Several recent studies have reported an inter-individual correlation between regional GABA concen... more Several recent studies have reported an inter-individual correlation between regional GABA concentration, as measured by MRS, and the amplitude of the functional blood oxygenation level dependent (BOLD) response in the same region. In this study, we set out to investigate whether this coupling generalizes across cortex. In 18 healthy participants, we performed edited MRS measurements of GABA and BOLD-fMRI experiments using regionally related activation paradigms. Regions and tasks were the: occipital cortex with a visual grating stimulus; auditory cortex with a white noise stimulus; sensorimotor cortex with a finger-tapping task; frontal eye field with a saccade task; and dorsolateral prefrontal cortex with a working memory task. In contrast to the prior literature, no correlation between GABA concentration and BOLD activation was detected in any region. The origin of this discrepancy is not clear. Subtle differences in study design or insufficient power may cause differing results;...
Change in signal intensity due to acute ischemic stroke can be detected on diffusion-weighted (DW... more Change in signal intensity due to acute ischemic stroke can be detected on diffusion-weighted (DW) images soon after symptom onset. Fluid-attenuated inversion recovery (FLAIR) DW imaging suppresses signal intensity from water and has been suggested to be better than conventional DW imaging as a diagnostic imaging technique in acute stroke. We compared the signal intensity-to-noise ratio (SNR) and contrast-to-noise-ratio (CNR) between ischemic and normal tissues by using these two sequences. Twenty stroke patients underwent imaging less than 6 hours after stroke onset by using both acquisition methods. The SNR of six regions of interest in normal brain and one region in ischemic brain were compared on both DW imaging and FLAIR DW imaging. We also compared CNR in normal and ischemic tissues. The calculated apparent diffusion coefficient (ADC) maps from each acquisition technique were similarly assessed. The SNR was significantly lower for FLAIR DW imaging than for DW imaging (P < ....
Purpose: To assess the feasibility of measuring pulmonary artery (PA) pulse wave velocity (PWV) i... more Purpose: To assess the feasibility of measuring pulmonary artery (PA) pulse wave velocity (PWV) in children breathing ambient air and 12% oxygen. Methods: Velocity-encoded phase-contrast MR images of the PA were acquired in 15 children, aged 9-12 years, without evidence of cardiac or pulmonary diseases. PWV was derived as the ratio of flow to area changes during early systole. Each child was scanned twice, in air and after at least 20 minutes into inspiratory hypoxic challenge. Intra-observer and inter-observer variability and repeatability were also compared. Results: PA PWV, which was successfully measured in all subjects, increased from 1.31 ± 0.32 m/s in air to 1.61 ± 0.58 m/s under hypoxic challenge (p = 0.03). Intra-and inter-observer coefficients of variations were 9.0% and 15.6% respectively. Good correlation within and between observers of r = 0.92 and r = 0.72 respectively was noted for PA PWV measurements. Mean (95% limit of agreement) intra-and inter-observer agreement on Bland-Altman analysis were − 0.02 m/s (− 0.41-0.38 m/s) and -0.28 m/s (−1.06-0.49 m/s). Conclusion: PA PWV measurement in children using velocity-encoded MRI is feasible, reproducible and sufficiently sensitive to detect differences in PA compliance between normoxia and hypoxia. This technique can be used to detect early changes of PA compliance and monitor PAH in children.
Purpose: The conventional spectral-editing experiment used to measure GABA in the human brain als... more Purpose: The conventional spectral-editing experiment used to measure GABA in the human brain also contains a contribution from macromolecules (MM), and the combined GABA plus MM signal is often referred to as "GABAþ". More recently, methods have been developed to estimate GABA free from MM contamination. In this study, the relationship between GABA acquired with MM suppression and conventional GABAþ measurements was examined. Methods: GABA-edited MEGA-PRESS experiments with and without MM suppression were performed in the sensorimotor and occipital cortex of 12 healthy subjects at 3 Tesla. The correlation between GABAþ and MM-suppressed GABA measures was then determined. Results: Across all data, a significant correlation between GABAþ and MM-suppressed GABA was found (r ¼ 0.48; P ¼ 0.02). Regionally, the sensorimotor voxel showed a trend toward a correlation of r ¼ 0.53, P ¼ 0.07 and the occipital voxel did not show a correlation, r ¼ 0.058, P ¼ 0.9. Conclusion: GABAþ and MM-suppressed GABA are moderately correlated, but statistical power to reveal this relationship may vary regionally. The MM signal, while often assumed to be functionally irrelevant, appears to show inter-individual and inter-regional variance that impacts the correlation of GABAþ and MM-suppressed GABA. Magn Reson Med 000:000-000, 2014. V C 2014 Wiley Periodicals, Inc.
Uploads
Papers by Ashley Harris