Bruce Pike

Event-Related fMRI of the Auditory Cortex

An event-related protocol was designed to permit auditory fMRI studies minimally affected by the echo-planar noise artifact; a long time interval (TR = 10 s) between each cerebral volume acquisition was combined with stroboscopic data acquisition, and event-related curves were reconstructed with a 1-s resolution. The cerebral hemodynamic-response time course to a target auditory stimulus was measured in five individual subjects using this method. Clear bell-shaped event-related responses were observed bilaterally in all individuals in primary auditory cortex (A1) as well as in laterally extending secondary cortical fields. Group-average event-related curves attained their maxima (0.5-0.7%) 3 s after stimulus onset in A1 (4 s for more anterior and lateral regions of auditory cortex), and signal had returned to near-baseline level 6 s after stimulus onset. The stroboscopic event-related method appeared effective in minimizing effects of the interaction between scanning noise and experimental auditory stimulation; it adds useful temporal information to the spatial resolution afforded by fMRI in studies of human auditory function, while allowing presentation of auditory stimuli on a silent background.

The BOLD response to interictal epileptiform discharges.

We studied single-event and average BOLD responses to EEG interictal epileptic discharges (IEDs) in four patients with focal epilepsy, using continuous EEG-fMRI during 80-min sessions. The detection of activated areas was performed by comparing the BOLD signal at each voxel to a model of the expected signal. Since little is known about the BOLD response to IEDs, we modeled it with the response to brief auditory events (G. H., NeuroImage 9, 416-429). For each activated area, we then obtained the time course of the BOLD signal for the complete session and computed the actual average hemodynamic response function (HRF) to IEDs. In two of four patients, we observed clear BOLD responses to single IEDs. The average response was composed of a positive lobe peaking between 6 and 7 s in all patients and a negative undershoot in three patients. There were important variations in amplitude and shape between average HRFs across patients. The average HRF presented a wider positive lobe than the Glover model in three patients and a longer undershoot in two. There was a remarkable similarity in the shape of the HRF across areas for patients presenting multiple activation sites. There was no clear correlation between the amplitude of individual BOLD responses and the amplitude of the corresponding EEG spike. The possibility of a longer HRF could be used to improve statistical detection of activation in simultaneous EEG-fMRI. The variability in average HRFs across patients could reflect in part different pathophysiological mechanisms.

fMRI Activation in Continuous and Spike-triggered EEG-fMRI Studies of Epileptic Spikes

Summary:  Purpose: To evaluate functional magnetic resonance imaging (fMRI) with simultaneous EEG for finding metabolic sources of epileptic spikes. To find the localizing value of activated regions and factors influencing fMRI responses.

Brain Size and Folding of the Human Cerebral Cortex

During evolution, the mammalian cerebral cortex has expanded disproportionately to brain volume. As a consequence, most mammals with large brains have profusely convoluted cortices. The human cortex is a good example of this trend, however, given the large variability in human brain size, it is not clear how cortical folding varies from the smallest to the largest brains. We analyzed cortical folding in a large cohort of human subjects exhibiting a 1.7-fold variation in brain volume. We show that the same disproportionate increase of cortical surface relative to brain volume observed across species can be also observed across human brains: the largest brains can have up to 20% more surface than a scaled-up small brain. We introduce next a novel local measure of cortical folding, and we show that the correlation between cortical folding and size varies along a rostro-caudal gradient, being especially significant in the prefrontal cortex. The expansion of the cerebral cortex, and in particular that of its prefrontal region, is a major evolutionary landmark in the emergence of human cognition. Our results suggest that this may be, at least in part, a natural outcome of increasing brain size.

Imaging speech production using fMRI

Human speech is a well-learned, sensorimotor, and ecological behavior ideal for the study of neural processes and brain-behavior relations. With the advent of modern neuroimaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), the potential for investigating neural mechanisms of speech motor control, speech motor disorders, and speech motor development has increased. However, a practical issue has limited the application of fMRI to issues in spoken language production and other related behaviors (singing, swallowing). Producing these behaviors during volume acquisition introduces motion-induced signal changes that confound the activation signals of interest. A number of approaches, ranging from signal processing to using silent or covert speech, have attempted to remove or prevent the effects of motion-induced artefact. However, these approaches are flawed for a variety of reasons. An alternative approach, that has only recently been applied to study single-word production, uses pauses in volume acquisition during the production of natural speech motion. Here we present some representative data illustrating the problems associated with motion artefacts and some qualitative results acquired from subjects producing short sentences and orofacial nonspeech movements in the scanner. Using pauses or silent intervals in volume acquisition and block designs, results from individual subjects result in robust activation without motion-induced signal artefact. This approach is an efficient method for studying the neural basis of spoken language production and the effects of speech and language disorders using fMRI.

Hippocampal volume is as variable in young as in older adults: implications for the notion of hippocampal atrophy in humans.

Previous studies in humans have shown the presence of an age-related reduction of hippocampal (HC) volume, as well as the presence of reduced HC volume in psychiatric populations suffering from schizophrenia, depression or post-traumatic stress disorder. Altogether, these data suggested that aging or psychiatric disease can have neurotoxic effects on the hippocampus, and lead to HC atrophy. However, these two sets of findings imply that HC volume in young healthy adults should present less variability than HC volume in older adults and psychiatric populations. In the present study, we assessed HC volume in 177 healthy men and women aged from 18 to 85 years of age. We show that the dispersion around the mean of HC volume is not different in young and older adults, so that 25% of young healthy adults present HC volume as small as the average participants aged 60 to 75 years. This shows that HC volume is as variable in young as in older adults and suggests that smaller HC volume attributed to the aging process in previous studies could in fact represent HC volume determined early in life. We also report that within similar age groups, the percentage of difference in HC volume between the individuals with the smallest HC volume (smallest quartile) and the group average is greater than the percentage of difference reported to exist between psychiatric populations and normal control in recent meta-analyses. Taken together, these results confront the notion of hippocampal atrophy in humans and raise the possibility that pre-determined inter-individual differences in HC volume in humans may determine the vulnerability for age-related cognitive impairments or psychopathology throughout the lifetime.

Genes, maternal smoking, and the offspring brain and body during adolescence: Design of the Saguenay Youth Study

The search for genes of complex traits is aided by the availability of multiple quantitative phenotypes collected in geographically isolated populations. Here we provide rationale for a large‐scale study of gene‐environment interactions influencing brain and behavior and cardiovascular and metabolic health in adolescence, namely the Saguenay Youth Study (SYS). The SYS is a retrospective study of long‐term consequences of prenatal exposure to maternal cigarette smoking (PEMCS) in which multiple quantitative phenotypes are acquired over five sessions (telephone interview, home, hospital, laboratory, and school). To facilitate the search for genes that modify an individuals response to an in utero environment (i.e. PEMCS), the study is family‐based (adolescent sibships) and is carried out in a relatively geographically isolated population of the Saguenay Lac‐Saint‐Jean (SLSJ) region in Quebec, Canada. DNA is acquired in both biological parents and in adolescent siblings. A genome‐wide scan will be carried out with sib‐pair linkage analyses, and fine mapping of identified loci will be done with family‐based association analyses. Adolescent sibships (12–18 years of age; two or more siblings per family) are recruited in high schools throughout the SLSJ region; only children of French‐Canadian origin are included. Based on a telephone interview, potential participants are classified as exposed or nonexposed prenatally to maternal cigarette smoking; the two groups are matched for the level of maternal education and the attended school. A total of 500 adolescent participants in each group will be recruited and phenotyped. The following types of datasets are collected in all adolescent participants: (1) magnetic resonance images of brain, abdominal fat, and kidneys, (2) standardized and computer‐based neuropsychological tests, (3) hospital‐based cardiovascular, body‐composition and metabolic assessments, and (4) questionnaire‐derived measures (e.g. life habits such as eating and physical activity; drug, alcohol use and delinquency; psychiatric symptoms; personality; home and school environment; academic and vocational attitudes). Parents complete a medical questionnaire, home‐environment questionnaire, a handedness questionnaire, and a questionnaire about their current alcohol and drug use, depression, anxiety, and current and past antisocial behavior. To date, we have fully phenotyped a total of 408 adolescent participants. Here we provide the description of the SYS and, using the initial sample, we present information on ascertainment, demographics of the exposed and nonexposed adolescents and their parents, and the initial MRI‐based assessment of familiality in the brain size and the volumes of grey and white matter. Hum Brain Mapp 2007.

T2 relaxometry can lateralize mesial temporal lobe epilepsy in patients with normal MRI.

In unselected patients with intractable temporal lobe epilepsy (TLE), approximately 15% do not have detectable hippocampal atrophy on MRI. The purpose of this study was to evaluate whether T2 relaxometry can identify hippocampal pathology and lateralize the epileptic focus in patients with intractable TLE, who do not demonstrate hippocampal atrophy on volumetric MRI (MRIV). We selected 14 patients with unilateral TLE who had unilateral atrophy and 11 patients with unilateral TLE who had no evidence of atrophy on MRIV. Images were acquired on a 1.5 T MR scan using a dual echo sequence with 23 contiguous oblique coronal slices in all patients and in 14 healthy subjects. Fitting a single exponential decay equation to the imaging data generated T2 maps. Averages of six slices containing the head, body, and tail of the hippocampus were used to calculate hippocampal T2 relaxation times (HT2). The epileptic focus was defined by history, video-EEG, and surgical response. All TLE patients with hippocampal atrophy and 9/11 (82%) patients with normal MRI had abnormally high HT2 ipsilateral to the epileptic focus. Bilateral abnormal HT2 were found in 6/14 (43%) of patients with unilateral hippocampal atrophy and 2/11 (18%) of patients with normal MRI. However, this increase was always greater ipsilateral to the epileptic focus. Qualitative hippocampal pathology showed gliosis and neuronal loss in 10/14 operated patients with hippocampal atrophy on MRIV and in 5/7 operated patients with normal MRI. In conclusion, hippocampal T2 mapping provides evidence of hippocampal damage in the majority of patients with intractable TLE who have no evidence of atrophy on MRI and can correctly lateralize the epileptic focus in most patients.

Informed consent for MRI and fMRI research: analysis of a sample of Canadian consent documents.

BackgroundResearch ethics and the measures deployed to ensure ethical oversight of research (e.g., informed consent forms, ethics review) are vested with extremely important ethical and practical goals. Accordingly, these measures need to function effectively in real-world research and to follow high level standards.MethodsWe examined approved consent forms for Magnetic Resonance Imaging (MRI) and functional Magnetic Resonance Imaging (fMRI) studies approved by Canadian research ethics boards (REBs).ResultsWe found evidence of variability in consent forms in matters of physical and psychological risk reporting. Approaches used to tackle the emerging issue of incidental findings exposed extensive variability between and within research sites.ConclusionThe causes of variability in approved consent forms and studies need to be better understood. However, mounting evidence of administrative and practical hurdles within current ethics governance systems combined with potential sub-optimal provision of information to and protection of research subjects support other calls for more scrutiny of research ethics practices and applicable revisions.

Handedness, motor skills and maturation of the corticospinal tract in the adolescent brain

With anatomical magnetic resonance imaging, the signal intensity of the corticospinal tract (CST) at the level of the internal capsule is often paradoxically similar to that of grey matter. As shown previously in histological studies, this is likely due to the presence of very large axons. We measured the apparent grey‐matter density (aGMd) of the putative CST (pCST) in a large cohort of adolescents (n = 409, aged 12–18 years). We tested the following hypotheses: (1) The aGMd in the pCST shows a hemispheric asymmetry that is, in turn, related to hand preference; (2) the maturation of the CST during adolescence differs between both sexes, due to the influence of testosterone; (3) variations in aGMd in the pCST reflect inter‐individual differences in manual skills. We confirmed the first two predictions. Thus, we found a strong left > right hemispheric asymmetry in aGMd that was, on average, less marked in the 40 left‐handed subjects. Apparent GMd in the pCST increased with age in adolescent males but not females, and this was particularly related to rising plasma levels of testosterone in male adolescents. This finding is compatible with the idea that testosterone influences axonal calibre rather than myelination. The third prediction, namely that of a relationship between age‐related changes in manual skills and maturation of the pCST, was not confirmed. We conclude that the leftward asymmetry of the pCST may reflect an early established asymmetry in the number of large corticomotoneuronal fibres in the pCST. Hum Brain Mapp, 2009.