Joe Gati

Repetition priming and the time course of object recognition: an fMRI study.

We investigated the effects of repetition priming on the time course of recognition in several visual areas of the brain using fMRI. We slowed down recognition by gradually revealing the stimuli, in order to prolong the pre-recognition phase. Activation was lower for primed than for non-primed objects overall in both the occipitotemporal region (OTR) and the intraparietal region (IPR). A difference was found between primed and non-primed objects in the rate of increase of OTR activation. We concluded that the IPR, in addition to the OTR, was affected by repetition priming, and that this effect was different from that seen in the OTR.

Brain reorganization in patients with spinal cord compression evaluated using fMRI

Objective: This prospective study characterizes the reorganization that occurs within the primary sensorimotor cortices following decompression of cervical spinal stenosis. Methods: Twelve right-handed patients with cervical myelopathy underwent blood oxygenation level dependent functional MRI (fMRI) prior to decompression and 6 months following surgery. Ten right-handed controls also underwent fMRI. All subjects performed a finger-tapping paradigm with the right hand. Volume time course data were corrected for temporal serial correlation and % normalized before inclusion in the general linear model. Activation maps were created for each group using a threshold of p < 0.005 with Bonferroni correction. Between-group differences in left hemisphere volume of activation (VOA) were measured along the precentral gyrus (PrCG) and postcentral gyrus (PoCG). Each subject also completed clinical questionnaires. Results: Prior to surgery, patients demonstrated a larger VOA (1.23 cm3, tmax = 11.8) in comparison to controls within the PrCG. This difference increased following surgery (2.99 cm3, tmax = 13.6). Within the PoCG, controls demonstrated a larger VOA (0.53 cm3, tmax = 8.28) than preoperative patients. This difference decreased by 0.12 cm3 (tmax = 7.05) following surgery. Preoperatively, patients had a 21.7 cm3 VOA (tmax = 29.4) within the sensorimotor cortex with the center of gravity located within Brodmann area (BA) 3. Following surgery, the VOA increased to 23.1 cm3 (tmax = 26.1) within BA 3. There were significant improvements in clinical outcomes following surgery. Conclusions: Spinal cord compression resulted in an increase in volume of activation (VOA) within the precentral gyrus (PrCG) and a loss of VOA within the postcentral gyrus (PoCG) in comparison to controls. Surgical decompression results in cortical reorganization with enlarging VOA within both the PrCG and PoCG.

In vivo normative atlas of the hippocampal subfields using multi-echo susceptibility imaging at 7 Tesla

Objectives: To generate a high‐resolution atlas of the hippocampal subfields using images acquired from 7 T, multi‐echo, gradient‐echo MRI for the evaluation of epilepsy and neurodegenerative disorders as well as investigating R2* (apparent transverse relaxation rate) and quantitative volume magnetic susceptibility (QS) of the subfields. Experimental Design: Healthy control subjects (nu2009=u200917) were scanned at 7 T using a multi‐echo gradient‐echo sequence and susceptibility‐weighted magnitude images, R2* and QS maps were reconstructed. We defined a hippocampal subfield labeling protocol for the magnitude image produced from the average of all echoes and assessed reproducibility through volume and shape metrics. A group‐wise diffeomorphic registration procedure was used to generate an average atlas of the subfields for the whole subject cohort. The quantitative MRI maps and subfield labels were then warped to the average atlas space and used to measure mean values of R2* and QS characterizing each subfield. Principal Observations: We were able to reliably label hippocampal subfields on the multi‐echo susceptibility images. The group‐averaged atlas accurately aligns these structures to produce a high‐resolution depiction of the subfields, allowing assessment of both quantitative susceptibility and R2* across subjects. Our analysis of variance demonstrates that there are more apparent differences between the subfields on these quantitative maps than the normalized magnitude images. Conclusion: We constructed a high‐resolution atlas of the hippocampal subfields for use in voxel‐based studies and demonstrated in vivo quantification of susceptibility and R2* in the subfields. This work is the first in vivo quantification of susceptibility values within the hippocampal subfields at 7 T. Hum Brain Mapp 35:3588–3601, 2014.

Origins of R2* orientation dependence in gray and white matter.

Significance Differences in the apparent transverse relaxation rate () between tissues are exploited in numerous magnetic resonance imaging (MRI) techniques from functional MRI to susceptibility weighted imaging. Recent results show a surprising dependence of tissue on orientation. This study demonstrates that the orientation dependence of in both white and cortical gray matter has a sinusoidal dependence on tissue orientation and a linear dependence on the perturber volume fraction (measured by quantitative histology). A biophysical model is used to relate the observed orientation dependence to the local Larmor frequency shift and volume magnetic susceptibility of the tissue. Estimates of the apparent transverse relaxation rate () can be used to quantify important properties of biological tissue. Surprisingly, the mechanism of dependence on tissue orientation is not well understood. The primary goal of this paper was to characterize orientation dependence of in gray and white matter and relate it to independent measurements of two other susceptibility based parameters: the local Larmor frequency shift (fL) and quantitative volume magnetic susceptibility (Δχ). Through this comparative analysis we calculated scaling relations quantifying (reversible contribution to the transverse relaxation rate from local field inhomogeneities) in a voxel given measurements of the local Larmor frequency shift. is a measure of both perturber geometry and density and is related to tissue microstructure. Additionally, two methods (the Generalized Lorentzian model and iterative dipole inversion) for calculating Δχ were compared in gray and white matter. The value of Δχ derived from fitting the Generalized Lorentzian model was then connected to the observed orientation dependence using image-registered optical density measurements from histochemical staining. Our results demonstrate that the and fL of white and cortical gray matter are well described by a sinusoidal dependence on the orientation of the tissue and a linear dependence on the volume fraction of myelin in the tissue. In deep brain gray matter structures, where there is no obvious symmetry axis, and fL have no orientation dependence but retain a linear dependence on tissue iron concentration and hence Δχ.In many neurological diseases such as multiple sclerosis, Alzheimer’s, and Parkinson, and in conditions following traumatic brain injury, microstructural changes occur in gray and white matter (1–4). One method for quantifying these microstructural changes is the mapping of the effective transverse relaxation rate (). Along with the longitudinal relaxation rate (R1) and transverse relaxation rate (R2), has been viewed as a fundamental MRI tissue parameter, affected by several factors including myelin content (5, 6), endogenous ferritin-based (Fe3+) iron (7, 8), tissue microstructure (6), and paramagnetic, blood deoxyhemoglobin (9). However, a number of recent studies have reported a somewhat surprising dependence of on tissue orientation, at least in white matter (10–12). The purpose of this paper was to investigate the mechanisms that could contribute to this orientation dependence of in both gray and white matter. Because is influenced by magnetic field perturbations, we examined the role of local Larmor frequency shift (fL) and quantitative magnetic susceptibility (Δχ), parameters that relate field and frequency. Through this analysis we identified unique scaling relations that relate to the local Larmor frequency shift calculated after removal of macroscopic field inhomogeneities. Additionally, we compared two methods for computing Δχ in gray and white matter: (i) fitting the Generalized Lorentzian (GL) model of field perturbers (13) to fL measured at multiple brain orientations and (ii) magnitude-regularized dipole inversion (14). The difference between these two estimates represents the local frequency shift due to a cylindrical, axon geometry and is a marker of axonal integrity. n nHaving modeled the orientation dependence, we next examined the effect of myelin and iron on both and Δχ. We demonstrated a linear correlation between these quantities and optical density (OD) derived from diaminobenzidine (DAB)-enhanced Perls stain (sensitive to ferritin-based iron) for cortical gray matter. Similarly, using OD derived from solochrome cyanine-R (ScR)–stained slides in rat brain major white matter fiber regions, we showed strong positive correlations between the transverse relaxation constants, R2 and , and myelin density. Taken together, our results demonstrate that observed values in ex vivo brains can be explained by a sinusoidal dependence on tissue microstructure orientation in conjunction with a linear dependence on the myelin concentration in cortical gray and white matter. In deeper gray matter structures with no preferred symmetry axis, does not have an orientation dependence but retains a linear dependence on iron concentration.

Comparison of Multiecho Postprocessing Schemes for SWI with Use of Linear and Nonlinear Mask Functions

BACKGROUND AND PURPOSE: SWI is an MR technique conventionally implemented with single-echo gradient-echo data. The purpose of this study was to compare single-echo SWI processing and 2 multiecho SWI processing schemes: postaverage, where an SWI image is created for each echo and then averaged to create a single volume; and frequency-based, where a SWI image is generated from an average frequency image. Linear and nonlinear mask functions were investigated for all 3 processing schemes. MATERIALS AND METHODS: Comprehensive optimizations were performed. Single and multigradient-echo data were acquired at 3T in 10 volunteers. Contrast-to-noise ratio was measured in various structures. Visibilities of the same structures were ranked in different SWI images by trained raters. RESULTS: When image evaluation was based on measurements of contrast-to-noise ratio, the nonlinear mask and frequency-based scheme were superior. However, when image evaluation was based on ranks of qualitative visibility, the linear mask and postaverage scheme were superior. Although the nonlinear mask and frequency-based scheme allow increased contrast of paramagnetic perturbers such as the globus pallidus, periventricular veins, red nucleus, and subthalamic nucleus, they do not necessarily increase the information content of the image; rather, they result in a harsh contrast that is visually unpleasing to radiologists and wherein more subtle structure is relatively less apparent. CONCLUSIONS: Linearly masked postaverage SWI is the recommended implementation of multiecho SWI for radiologic use; however, nonlinearly masked frequency-based SWI may have use in computer-based segmentation or registration.

4-T fMRI of the motor and sensory cortices in patients with polymicrogyria and epilepsy.

OBJECTIVEnMalformations of cortical development (MCD) are an increasingly recognized cause of medically intractable epilepsy. We assessed the role of fMRI in evaluating the motor and somatosensory cortices, as well as if there is possible reorganization of these vital areas in patients with polymicrogyria.nnnMETHODSnWe included 2 patients with polymicrogyria and epilepsy. Somatosensory and motor cortices were assessed with a 4T fMRI. These findings were compared with direct cortical stimulation.nnnRESULTSnLocalization of the sensorimotor cortices was adequately identified by fMRI. These vital areas did not reorganize outside the malformation of cortical development.nnnCONCLUSIONnfMRI is a tool that can allow identification of these vital areas of the brain in a non-invasive manner.nnnPRACTICE IMPLICATIONSnAdequate localization of the sensorimotor cortices is important for optimal patient selection, surgical strategy, and to determine the maximal extent of the resection. The clinical implications for such understanding are not limited to it; these findings should help researchers understand more of the neurobiology of MCDs and even possibly clues to the mechanisms of epileptogenesis associated with such malformations.

T165. ULTRA-HIGH FIELD MORPHOMETRY IN DRUG-NAïVE FIRST EPISODE PSYCHOSIS

Abstract Background Structural neuroimaging studies report distributed grey matter volume (GMV) deficits in drug-naïve first episode psychosis (FEP), though their relevance to symptom burden and cognitive deficits is currently unclear. When compared to studies in medicated patients and/or patients with established later-stage of psychosis, the GMV deficits reported have been limited in both spatial distribution and effect size, indicating the possibility of stage-specific progression during the clinical course of psychosis. TOPSY (Tracking Outcomes of Psychosis) is one of the first studies intending to track the neurobiological trajectory using ultra-high field (7T) imaging starting from a drug-naïve first episode state. Here, we report the initial findings from the voxel-based morphometry (VBM) of GMV. To our knowledge, this is the first VBM report from drug-naïve FEP subjects obtained using a 7T MRI acquisition. Methods We used ultra-high field (7 Tesla) MRI in 28 patients with FEP (satisfying criterion A of DSM-5 schizophrenia) and 18 controls, to evaluate differences in the grey matter. Volume in a voxelwise manner. FEP and controls were matched for age, sex and parental socioeconomic status. Patients were recruited at an early intervention unit (PEPP, London Ontario) and had active psychotic symptoms at the time of scanning. We also obtained abbreviated PANSS (8 items) scores to index the severity of psychosis. Analysis was done using SPM12, after DARTEL based registration and segmentation but without spatial smoothing. 2-tailed voxelwise T-test with FDR correction (p=0.05, 5% rate for false positives) was used. We used multiple regression analysis to predict the scores from processing speed measure (modified Symbol Substitution Test) and the severity of Delusions and Unusual Thought Content (P1 and G9), the 2 symptoms for which most subjects sought treatment in the first place. Results Patients had a significant reduction in GMV in left fusiform gyrus (Hedge’s g = 1.98, T= 6.7), and increased GMV in the right precuneus (Hedge’s g = 1.63, T= 5.5) and lingual cortex (Hedge’s g = 1.19, T= 4.0). We did not find any other areas of significant GMV change. Of these 3 circumscribed GMV changes, reduced fusiform GMV was found among FEP patients with lower processing speed (ß=0.45, p=0.04), higher severity of delusions (ß=-0.43, p=0.049) and unusual thought content (ß=-0.59, p=0.01). Increased precuneus GMV was found among FEP patients with higher severity of delusions (ß=0.62, p=0.008) and unusual thought content (ß=0.50, p=0.03). Right lingual changes were not related to the severity of delusions or processing speed scores. Discussion Our findings suggest that (1) GMV deficits are minimal in drug-naïve FEP subjects, with large effect-size changes concentrated around face processing (fusiform) region (2) GMV increases co-occur with GMV reduction especially in those with most severe delusions and cognitive deficits indicating a role for compensatory plasticity. Subtle early brain structural changes appear to predict symptom burden and cognitive deficits at the time of first clinical presentation with psychosis. Focusing on treatments that manipulate the structure of fusiform cortex could potentially reduce the severity of some of the early symptoms in FEP.

T164. STRUCTURAL COVARIANCE IN DRUG-NAïVE FIRST EPISODE PSYCHOSIS: AN ULTRA-HIGH FIELD MRI STUDY

Abstract Background Structural neuroimaging studies report disrupted morphological relationship in the grey matter volume (structural covariance) in patients with schizophrenia, indicating an impairment in functional and/or developmental plasticity. To our knowledge, no studies have examined the alterations in structural covariance across the entire brain in drug-naïve first episode psychosis. TOPSY (Tracking Outcomes of Psychosis) is one of the first studies intending to track the neurobiological trajectory using ultra-high field (7T) imaging starting from a drug-naïve first episode state. Here, we report the initial findings from the structural covariance of grey matter volume. To our knowledge, this is the first structural covariance analysis being reported using a 7T anatomical MRI acquisition. Methods We used ultra-high field (7 Tesla) MRI in 28 patients with FEP (satisfying criterion A of DSM-5 schizophrenia) and 18 controls, to estimate grey matter volume in a voxelwise manner. FEP and controls were matched for age, sex and parental socioeconomic status. Patients were recruited at an early intervention unit (PEPP, London Ontario) and had active psychotic symptoms at the time of scanning. Morphometric analysis was done using SPM12, after DARTEL based registration and segmentation but without spatial smoothing on 160 brain regions (6mm spheres) obtained using Dosenbach’s atlas. Correlation matrix for each group was constructed from 160*160 pearson correlation coefficients, followed by estimation of a bias matrix for each subject using jack-knife bias estimation. Bias values for each pair of nodes in an individual subject quantified the contribution of that subject to the overall within-group covariance. Higher positive values meant greater covariance between the two given nodes in that subject, relative to the rest of the group. These bias matrices can be considered equivalent to demeaned and normalised matrices of structural covariance. Structural covariance across all possible regional pairwise connections was tested using 2-tailed voxelwise T-test with FDR correction (p=0.05, 5% rate for false positives). Results Patients had a significant reduction in structural covariance affecting between right posterior insula and right precentral gyrus (within sensorimotor network, t=3.86, Hedge’s g = 1.15); between right posterior insula and left ventral prefrontal cortex (between sensorimotor and salience network, t=3.71, Hedge’s g = 1.10); and between right anterior cingulate cortex and right dorsal prefrontal cortex (between sensorimotor and default-mode network, t=3.10, Hedge’s g = 0.92). There were no pairwise connections with increased structural covariance among FEP subjects compared to healthy controls. Discussion Our findings suggest that (1) structural covariance is disrupted even by the time of first-episode of psychosis; thus, the disruptions in morphological relationships reported in schizophrenia are not explicable by antipsychotic usage or illness duration (2) sensorimotor network regions show a predominant disruption in structural covariance, affecting morphological relationships with both salience and default mode regions. The functional and developmental plasticity of sensorimotor networks may be crucial for the early trajectory of psychosis.

Swallowing Preparation and Execution: Insights from a Delayed-Response Functional Magnetic Resonance Imaging (fMRI) Study

The present study sought to elucidate the functional contributions of sub-regions of the swallowing neural network in swallowing preparation and swallowing motor execution. Seven healthy volunteers participated in a delayed-response, go, no-go functional magnetic resonance imaging study involving four semi-randomly ordered activation tasks: (i) “prepare to swallow,” (ii) “voluntary saliva swallow,” (iii) “do not prepare to swallow,” and (iv) “do not swallow.” Results indicated that brain activation was significantly greater during swallowing preparation, than during swallowing execution, within the rostral and intermediate anterior cingulate cortex bilaterally, premotor cortex (leftxa0>xa0right hemisphere), pericentral cortex (leftxa0>xa0right hemisphere), and within several subcortical nuclei including the bilateral thalamus, caudate, and putamen. In contrast, activation within the bilateral insula and the left dorsolateral pericentral cortex was significantly greater in relation to swallowing execution, compared with swallowing preparation. Still other regions, including a more inferior ventrolateral pericentral area, and adjoining Brodmann area 43 bilaterally, and the supplementary motor area, were activated in relation to both swallowing preparation and execution. These findings support the view that the preparation, and subsequent execution, of swallowing are mediated by a cascading pattern of activity within the sub-regions of the bilateral swallowing neural network.