David Gasston

Mapping Infant Brain Myelination with Magnetic Resonance Imaging

Myelination, the elaboration of myelin surrounding neuronal axons, is essential for normal brain function. The development of the myelin sheath enables rapid synchronized communication across the neural systems responsible for higher order cognitive functioning. Despite this critical role, quantitative visualization of myelination in vivo is not possible with current neuroimaging techniques including diffusion tensor and structural magnetic resonance imaging (MRI). Although these techniques offer insight into structural maturation, they reflect several different facets of development, e.g., changes in axonal size, density, coherence, and membrane structure; lipid, protein, and macromolecule content; and water compartmentalization. Consequently, observed signal changes are ambiguous, hindering meaningful inferences between imaging findings and metrics of learning, behavior or cognition. Here we present the first quantitative study of myelination in healthy human infants, from 3 to 11 months of age. Using a new myelin-specific MRI technique, we report a spatiotemporal pattern beginning in the cerebellum, pons, and internal capsule; proceeding caudocranially from the splenium of the corpus callosum and optic radiations (at 3–4 months); to the occipital and parietal lobes (at 4–6 months); and then to the genu of the corpus callosum and frontal and temporal lobes (at 6–8 months). Our results also offer preliminary evidence of hemispheric myelination rate differences. This work represents a significant step forward in our ability to appreciate the fundamental process of myelination, and provides the first ever in vivo visualization of myelin maturation in healthy human infancy.

Isotropic resolution diffusion tensor imaging with whole brain acquisition in a clinically acceptable time

Our objective was to develop a diffusion tensor MR imaging pulse sequence that allows whole brain coverage with isotropic resolution within a clinically acceptable time. A single‐shot, cardiac‐gated MR pulse sequence, optimized for measuring the diffusion tensor in human brain, was developed to provide whole‐brain coverage with isotropic (2.5 × 2.5 × 2.5 mm) spatial resolution, within a total imaging time of approximately 15 min. The diffusion tensor was computed for each voxel in the whole volume and the data processed for visualization in three orthogonal planes. Anisotropy data were further visualized using a maximum‐intensity projection algorithm. Finally, reconstruction of fiber‐tract trajectories i.e., ‘tractography’ was performed. Images obtained with this pulse sequence provide clear delineation of individual white matter tracts, from the most superior cortical regions down to the cerebellum and brain stem. Because the data are acquired with isotropic resolution, they can be reformatted in any plane and the sequence can therefore be used, in general, for macroscopic neurological or psychiatric neuroimaging investigations. The 3D visualization afforded by maximum intensity projection imaging and tractography provided easy visualization of individual white matter fasciculi, which may be important sites of neuropathological degeneration or abnormal brain development. This study has shown that it is possible to obtain robust, high quality diffusion tensor MR data at 1.5 Tesla with isotropic resolution (2.5 × 2.5 × 2.5 mm) from the whole brain within a sufficiently short imaging time that it may be incorporated into clinical imaging protocols. Hum. Brain Mapping 15:216–230, 2002.

Allocentric Spatial Memory Activation of the Hippocampal Formation Measured With fMRI

Hippocampal activation was investigated, comparing allocentric and egocentric spatial memory. Healthy participants were immersed in a virtual reality circular arena, with pattern-rendered walls. In a viewpoint-independent task, they moved toward a pole, which was then removed. They were relocated to another position and had to move to the prior location of the pole. For viewpoint-dependent memory, the participants were not moved to a new starting point, but the patterns were rotated to prevent them from indicating the final position. Hippocampal and parahippocampal activation were found in the viewpoint-independent memory encoding phase. Viewpoint-dependent memory did not result in such activation. These results suggest differential activation of the hippocampal formation during allocentric encoding, in partial support of the spatial mapping hypothesis as applied to humans.

Limbic and prefrontal responses to facial emotion expressions in depersonalization

Depersonalization disorder, characterized by emotional detachment, has been associated with increased prefrontal cortical and decreased autonomic activity to emotional stimuli. Event-related fMRI with simultaneous measurements of skin conductance levels occurred in nine depersonalization disorder patients and 12 normal controls to neutral, mild and intense happy and sad facial expressions. Patients, but not controls, showed decreases in subcortical limbic activity to increasingly intense happy and sad facial expressions, respectively. For both happy and sad expressions, negative correlations between skin conductance measures in bilateral dorsal prefrontal cortices occurred only in depersonalization disorder patients. Abnormal decreases in limbic activity to increasingly intense emotional expressions, and increases in dorsal prefrontal cortical activity to emotionally arousing stimuli may underlie the emotional detachment of depersonalization disorder.

Cerebral and autonomic responses to emotional facial expressions in depersonalisation disorder

BACKGROUND Depersonalisation disorder is characterised by emotion suppression, but the cerebral mechanisms of this symptom are not yet fully understood. AIMS To compare brain activation and autonomic responses of individuals with the disorder and healthy controls. METHOD Happy and sad emotion expressions in increasing intensities (neutral to intense) were presented in an implicit event-related functional magnetic resonance imaging (fMRI) design with simultaneous measurement of autonomic responses. RESULTS Participants with depersonalisation disorder showed fMRI signal decreases, whereas the control group showed signal increases in response to emotion intensity increases in both happy and sad expressions. The analysis of evoked haemodynamic responses from regions exhibiting functional connectivity between central and autonomic nervous systems indicated that in depersonalisation disorder initial modulations of haemodynamic response occurred significantly earlier (2 s post-stimulus) than in the control group (4-6 s post-stimulus). CONCLUSIONS The results suggest that fMRI signal decreases are possible correlates of emotion suppression in depersonalisation disorder.

Implementation and evaluation of simultaneous video-electroencephalography and functional magnetic resonance imaging.

The objective of this study was to demonstrate that the addition of simultaneous and synchronised video to electroencephalography (EEG)-correlated functional magnetic resonance imaging (fMRI) could increase recorded information without data quality reduction. We investigated the effect of placing EEG, video equipment and their required power supplies inside the scanner room, on EEG, video and MRI data quality, and evaluated video-EEG-fMRI by modelling a hand motor task. Gradient-echo, echo-planner images (EPI) were acquired on a 3-T MRI scanner at variable camera positions in a test object [with and without radiofrequency (RF) excitation], and human subjects. EEG was recorded using a commercial MR-compatible 64-channel cap and amplifiers. Video recording was performed using a two-camera custom-made system with EEG synchronization. An in-house script was used to calculate signal to fluctuation noise ratio (SFNR) from EPI in test object with variable camera positions and in human subjects with and without concurrent video recording. Five subjects were investigated with video-EEG-fMRI while performing hand motor task. The fMRI time series data was analysed using statistical parametric mapping, by building block design general linear models which were paradigm prescribed and video based. Introduction of the cameras did not alter the SFNR significantly, nor did it show any signs of spike noise during RF off conditions. Video and EEG quality also did not show any significant artefact. The Statistical Parametric Mapping{T} maps from video based design revealed additional blood oxygen level-dependent responses in the expected locations for non-compliant subjects compared to the paradigm prescribed design. We conclude that video-EEG-fMRI set up can be implemented without affecting the data quality significantly and may provide valuable information on behaviour to enhance the analysis of fMRI data.

Complex motor task associated with non-linear BOLD responses in cerebro-cortical areas and cerebellum

Previous studies have used fMRI to address the relationship between grip force (GF) applied to an object and BOLD response. However, whilst the majority of these studies showed a linear relationship between GF and neural activity in the contralateral M1 and ipsilateral cerebellum, animal studies have suggested the presence of non-linear components in the GF–neural activity relationship. Here, we present a methodology for assessing non-linearities in the BOLD response to different GF levels, within primary motor as well as sensory and cognitive areas and the cerebellum. To be sensitive to complex forms, we designed a feasible grip task with five GF targets using an event-related visually guided paradigm and studied a cohort of 13 healthy volunteers. Polynomial functions of increasing order were fitted to the data. Major findings: (1) activated motor areas irrespective of GF; (2) positive higher-order responses in and outside M1, involving premotor, sensory and visual areas and cerebellum; (3) negative correlations with GF, predominantly involving the visual domain. Overall, our results suggest that there are physiologically consistent behaviour patterns in cerebral and cerebellar cortices; for example, we observed the presence of a second-order effect in sensorimotor areas, consistent with an optimum metabolic response at intermediate GF levels, while higher-order behaviour was found in associative and cognitive areas. At higher GF levels, sensory-related cortical areas showed reduced activation, interpretable as a redistribution of the neural activity for more demanding tasks. These results have the potential of opening new avenues for investigating pathological mechanisms of neurological diseases.

Cognitive load and autonomic response patterns under negative priming demand in depersonalization‐derealization disorder

Previous studies have yielded evidence for cognitive processing abnormalities and alterations of autonomic functioning in depersonalization‐derealization disorder (DPRD). However, multimodal neuroimaging and psychophysiology studies have not yet been conducted to test for functional and effective connectivity under cognitive stress in patients with DPRD. DPRD and non‐referred control subjects underwent a combined Stroop/negative priming task, and the neural correlates of Stroop interference effect, negative priming effect, error rates, cognitive load span and average amplitude of skin conductance responses were ascertained for both groups. Evoked haemodynamic responses for basic Stroop/negative priming activations were compared. For basic Stroop to neutral contrast, patients with DPRD differed in the location (inferior vs. superior lobule) of the parietal region involved, but showed similar activations in the left frontal region. In addition, patients with DPRD also co‐activated the dorsomedial prefrontal cortex (BA9) and posterior cingulate cortex (BA31), which were also found to be the main between‐group difference regions. These regions furthermore showed connectivity with frequency of depersonalization states. Evoked haemodynamic responses drawn from regions of interest indicated significant between‐group differences in 30–40% of time points. Brain‐behaviour correlations differed mainly in laterality, yet only slightly in regions. A reversal of autonomic patterning became evident in patients with DPRD for cognitive load spans, indicating less effective arousal suppression under cognitive stress – patients with DPRD showed positive associations of cognitive load with autonomic responses, whereas controls exhibit respective inverse association. Overall, the results of the present study show only minor executive cognitive peculiarities, but further support the notion of abnormalities in autonomic functioning in patients with DPRD.

S34-04 - Genetic and non-genetic influences on brain function in schizophrenia: an fMRI study in twins

Introduction Altered neurocognitive function in schizophrenia could reflect both genetic and illness-specific effects. Objectives To use functional magnetic resonance imaging to discriminate between the influences of the genetic risk for schizophrenia and environmental factors on the neural substrate of verbal fluency, a candidate schizophrenia endophenotype using a case control twin design. Methods We studied 23 monozygotic twin pairs: 13 pairs discordant for schizophrenia and 10 pairs of healthy volunteer twins. Groups were matched for age, gender, handedness, level of education, parental socio-economic status, and ethnicity. Behavioural performance and regional brain activation during a phonological verbal fluency task were assessed. Results Relative to healthy control twins, both patients and their non-psychotic co-twins produced fewer correct responses and showed less activation in the medial temporal region and inferior frontal gyrus. Twins with schizophrenia showed greater activation than both their non-psychotic co-twins and controls in right lateral temporal cortex, reflecting reduced deactivation during word generation while their non-psychotic co-twins showed greater activation in the left temporal cortex. Conclusions Both genetic vulnerability to schizophrenia and schizophrenia were associated with impaired verbal fluency performance, reduced engagement of the medial temporal region and dorsal inferior frontal gyrus. Schizophrenia was specifically associated with an additional reduction in deactivation in the right temporal cortex.

An investigation of spatial memory using virtual reality and fMRI

Introduction. According the to the cognitive mapping theory of O’Keefe and Nadel(1978), the hippocampus provides the neural substrates for a spatial map, orientating the animal in relation to distal cues, irrespective of their current direction. In humans, O’Keefe and Nadel (1978)suggested that the hippocampus subserves r&centric (viewer-independent) spatial processing. A small number of studies have found hippo/parahippocampal activation during navigation tasks using imaging techniques (e.g. Maguire et al, 1998 IPET], Aguirre et al, 1996 [fMRI’j). A paradigm was developed designed specifically to contrast neural activation during allocentric and egocentric (viewer-dependant) spatial processing. It was hypothesised that allocentric spatial processing would show activation in the hippo/parahippocampai area and that egocentric processing would be found in extrahippocampal areas. Further, in accordance with previous imaging studies, if hippo/parahippocampal activation was found in the allocentric experiment it was hypothesised that this would be right-sided.