Biomedical subjects

Gary F Egan

Publications and source records attributed to Gary F Egan.

At least 19 recordsLinked to original sources

PubMed2007

Observer-independent analysis of high-resolution MR images of the human cerebral cortex: in vivo delineation of cortical areas.

Using high-resolution MRI, it is now possible to examine the living human cortex down to a resolution of less than 300 mum. Thus, in vivo imaging is now approaching the resolution that has been successfully used in histological analysis of the cerebral cortex for many years, e.g., low-magnification light microscopy. This allows unprecedented views of cortical microstructure that reflect defined histological features, specifically, individual cortical layers. As in histological brain mapping, it is possible to use the changes in the cortical lamination patterns to define individual cortical areas. This allows in vivo neuroanatomical maps to be generated for individual subjects and precise correlation of the results from functional imaging studies in these subjects with their own microanatomical information. To this end, we adapted the well-established observer-independent cytoarchitectonic mapping techniques for defining cortical borders based on changes in cortical lamination for in vivo parcellation of high-resolution structural MR images.

Brain Mapping↗

PubMed2006

Perinatal risk factors altering regional brain structure in the preterm infant.

Neuroanatomical structure appears to be altered in preterm infants, but there has been little insight into the major perinatal risk factors associated with regional cerebral structural alterations. MR images were taken to quantitatively compare regional brain tissue volumes between term and preterm infants and to investigate associations between perinatal risk factors and regional neuroanatomical alterations in a large cohort of preterm infants. In a large prospective longitudinal cohort study of 202 preterm and 36 term infants, MR scans at term equivalent were undertaken for volumetric estimates of cortical and deep nuclear grey matter, unmyelinated and myelinated white matter (WM) and CSF within 8 parcellated regions for each hemisphere of the brain. Perinatal correlates analysed in relation to regional brain structure included gender, gestational age, intrauterine growth restriction, bronchopulmonary dysplasia, white matter injury (WMI) and intraventricular haemorrhage. Results revealed region-specific reductions in brain volumes in preterm infants compared with term controls in the parieto-occipital (preterm mean difference: -8.1%; 95% CI = -13.8--2.3%), sensorimotor (-11.6%; -18.2--5.0%), orbitofrontal (-30.6%; -49.8--11.3%) and premotor (-7.6%; -14.2--0.9%) regions. Within the sensorimotor and orbitofrontal regions cortical grey matter and unmyelinated WM were most clearly reduced in preterm infants, whereas deep nuclear grey matter was reduced mainly within the parieto-occipital and subgenual regions. CSF (ventricular and extracerebral) was doubled in volume within the superior regions in preterm infants compared with term controls. Cerebral WMI and intrauterine growth restriction were both associated with a more posterior reduction in brain volumes, whereas bronchopulmonary dysplasia was associated with a more global reduction across all regions. In contrast degree of immaturity was not related to regional brain structure among preterm infants. In summary, preterm birth is associated with regional cerebral tissue reductions, with the adverse pattern varying between risk factors. These findings add to our understanding of the potential pathways leading to altered brain structure and outcome in the preterm infant.

Brain↗

PubMed2006

Pain sensitivity and fMRI pain-related brain activity in Alzheimer's disease.

People with Alzheimer's disease are administered fewer analgesics and report less clinical pain than cognitively intact peers with similar painful diseases or injuries, prompting speculation about the likely impact of neurodegeneration on central pain processing. The present study measured pain ratings and functional MRI (fMRI) brain responses following mechanical pressure simulation in 14 patients with Alzheimer's disease and 15 age-matched controls. Contrary to the prevailing hypothesis that this disease is likely to differentially reduce emotional responses to pain, we show that activity in both medial and lateral pain pathways is preserved. Moderate pain was evoked with similar stimuli in both groups, and was associated with a common network of pain-related activity incorporating cingulate, insula and somatosensory cortices. Between-group analyses showed no evidence of diminished pain-related activity in Alzheimer's disease patients compared with controls. In fact, compared with controls, patients showed greater amplitude and duration of pain-related activity in sensory, affective and cognitive processing regions consistent with sustained attention to the noxious stimulus. The results of this study show that pain perception and processing are not diminished in Alzheimer's disease, thereby raising concerns about the current inadequate treatment of pain in this highly dependent and vulnerable patient group.

Aged↗

PubMed2006

Unique, common, and interacting cortical correlates of thirst and pain.

This study used positron-emission tomography to establish the patterns of brain activity involved in the isolated and concurrent experiences of thirst and pain. Ten subjects were scanned while experiencing pain evoked with noxious pressure, while experiencing thirst after the infusion of hypertonic saline, and while experiencing pain when thirsty. After the onset of thirst, noxious pressure evoked more intense sensations of pain. Noxious pressure did not change subjective ratings of thirst. Thirst caused activation in the anterior cingulate (Brodmann area 32) and the insula. Enhanced pain responses were associated with increased activity in cortical regions that are known to correlate with pain intensity, and also with unique activity in the pregenual anterior cingulate and ventral orbitofrontal cortex. These findings suggest a role for limbic and prefrontal cortices in the modulation of pain during the experience of thirst.

Adult↗

PubMed2006

Human medullary responses to cooling and rewarming the skin: a functional MRI study.

A fall in skin temperature precipitates a repertoire of thermoregulatory responses that reduce the likelihood of a decrease in core temperature. Studies in animals suggest that medullary raphé neurons are essential for cold-defense, mediating both the cutaneous vasoconstrictor and thermogenic responses to ambient cooling; however, the involvement of raphé neurons in human thermoregulation has not been investigated. This study used functional MRI with an anatomically guided region of interest (ROI) approach to characterize changes in the blood oxygen level-dependent (BOLD) signal within the human medulla of nine normal subjects during non-noxious cooling and rewarming of the skin by a water-perfused body suit. An ROI covering 4.9 +/- 0.3 mm(2) in the ventral midline of the medulla immediately caudal to the pons (the rostral medullary raphé) showed an increase in BOLD signal of 3.9% (P < 0.01) during periods of skin cooling, compared with other times. Overall, that signal showed a strong inverse correlation (R = 0.48, P < 0.001) with skin temperature. A larger ROI covering the internal medullary cross section at the same level (area, 126 +/- 15 mm(2)) showed no significant change in mean BOLD signal with cooling (+0.2%, P > 0.05). These findings demonstrate that human rostral medullary raphé neurons are selectively activated in response to a thermoregulatory challenge and point to the location of thermoregulatory neurons homologous to those of the raphé pallidus nucleus in rodents.

Adult↗

PubMed2006

Motivation and synthesis of the FIAC experiment: Reproducibility of fMRI results across expert analyses.

The Functional Imaging Analysis Contest (FIAC) culminated in the FIAC Workshop held at the 11th Annual Meeting of the Organization for Human Brain Mapping in Toronto in 2005. This special issue summarizes various analyses used by contestants with a single functional magnetic resonance imaging (fMRI) study, a cortical-language study using sentence repetition. The results from the cognitive neuroscientists who developed the test-base language study, and report their data analysis, are complemented by expert analyses of the same test-base data by most of the major groups actively developing fMRI software packages. Analyses include many variants of the general linear model (GLM), cutting-edge spatial- and temporal-wavelets, permutation-based, and ICA approaches. A number of authors also include surface-based approaches. Several articles describe the important emerging areas of diagnostics for GLM analysis, multivariate predictive modeling, and functional connectivity analysis. While the FIAC did not achieve all of its goals, it helped identify new activation regions in the test-base data, and more important, through this special issue it illustrates the significant methods-driven variability that potentially exists in the literature. Variable results from different methods reported here should provide a cautionary note and motivate the Human Brain Mapping community to explore more thoroughly the methodologies they use for analyzing fMRI data.

Brain Mapping↗

PubMed2006

Evolution of brain activation with good and poor motor recovery after stroke.

OBJECTIVE: To characterize the evolution of brain activation in stroke patients with variable motor recovery and quantify changes relative to healthy controls. METHODS: Serial PET activation studies, using a simple finger-tapping task, and quantitative measures of motor performance were obtained in 9 patients (2-7 weeks poststroke and 6 months later) and compared with serial healthy volunteer data. RESULTS: Patients with moderate impairment and good recovery (n = 5) activated the primary sensorimotor cortex (SM1) contralateral to the paretic hand moved, bilateral supplementary motor area (SMA), contralateral cingulate gyrus, and ipsilateral lateral premotor cortex. Activation in the bilateral SMA was greater at the initial study but reduced over time compared to healthy controls and poor recoverers. Patients with severe impairment and poor recovery (n =4) showed limited activation of contralateral SM1 and SMA at both studies and no significant change over time. A posterior shift in SM1 activation was evident in good and poor recoverers. CONCLUSIONS: Activation of typical motor regions and recruitment of additional sites occur subacutely poststroke, with evolution to normal patterns in moderately impaired patients who recover well. In comparison, severely impaired, poor-recovery patients show persistent, reduced activation. Dynamic changes in SMA, differentially observed in good recoverers over 6 months, highlight its importance in recovery.

Aged↗

PubMed2005

Abnormal frontal and parietal activity during working memory updating in post-traumatic stress disorder.

This study used event-related potentials (ERPs) to investigate the timing and scalp topography of working memory in post-traumatic stress disorder (PTSD). This study was designed to investigate ERPs associated with a specific working memory updating process. ERPs were recorded from 10 patients and 10 controls during two visual tasks where (a) targets were a specific word or (b) targets were consecutive matching words. In the first task, nontarget words are not retained in working memory. In the second task, as in delay-match-to-sample tasks, a non-target word defines a new target identity, so these words are retained in working memory. This working memory updating process was related to large positive ERPs over frontal and parietal areas at 400-800 ms, which were smaller in PTSD. Estimation of cortical source activity indicated abnormal patterns of frontal and parietal activity in PTSD, which were also observed in regional cerebral blood flow [Clark, C.R., McFarlane, A.C., Morris, P., Weber, D.L., Sonkkilla, C., Shaw, M., Marcina, J., Tochon-Danguy, H., Egan, G., 2003. Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Biological Psychiatry 53, 474-481]. Frontal and parietal cortex are known to be involved in distributed networks for working memory processes, interacting with medial temporal areas during episodic memory processes. Abnormal function in these brain networks helps to explain everyday concentration and memory difficulties in PTSD.

Brain Mapping↗

PubMed2005

Mathematically gifted male adolescents activate a unique brain network during mental rotation.

Mental rotation involves the creation and manipulation of internal images, with the later being particularly useful cognitive capacities when applied to high-level mathematical thinking and reasoning. Many neuroimaging studies have demonstrated mental rotation to be mediated primarily by the parietal lobes, particularly on the right side. Here, we use fMRI to show for the first time that when performing 3-dimensional mental rotations, mathematically gifted male adolescents engage a qualitatively different brain network than those of average math ability, one that involves bilateral activation of the parietal lobes and frontal cortex, along with heightened activation of the anterior cingulate. Reliance on the processing characteristics of this uniquely bilateral system and the interplay of these anterior/posterior regions may be contributors to their mathematical precocity.

Adolescent↗

PubMed2005

Cortical, thalamic, and hypothalamic responses to cooling and warming the skin in awake humans: a positron-emission tomography study.

Thermoregulatory mechanisms are remarkably efficient, ensuring minimal temperature variation within the core of the human body under physiological conditions. Diverse afferent and efferent neural pathways contribute to the monitoring of core and skin temperature, generation of heat, and control of thermal exchange with the external environment. We have investigated the cortical, thalamic, and hypothalamic responses to cooling and warming by using positron-emission tomography activation imaging of subjects clad in a water-perfused suit, which enabled rapid change of their skin-surface temperature. Human brain regions that respond to changes in skin temperature have been identified in the somatosensory cortex, insula, anterior cingulate, thalamus, and hypothalamus, with evidence that the hypothalamic response codes for the direction of temperature change. We conclude that signals from thermosensors in the skin providing crucial afferent information to the brain are integrated with signals from central thermosensors, resulting in thermoregulatory responses that maintain core temperature within a remarkably narrow range.

Adult↗

PubMed2005

Motor impairment and recovery in the upper limb after stroke: behavioral and neuroanatomical correlates.

BACKGROUND AND PURPOSE: Motor recovery after stroke is associated with cerebral reorganization. However, few studies have investigated the relationship directly, and findings are equivocal. We therefore aimed to characterize the relationship between motor impairment, motor recovery, and task-related changes in regional cerebral blood flow (DeltarCBF) longitudinally. METHODS: We obtained a profile of motor impairment and recovery in the upper limb and conducted positron emission tomography motor activation studies using a simple finger-tapping task in 9 stroke patients 2 to 7 weeks after stroke and 6 months later. For correlation analysis, mean images of task-related DeltarCBF for each individual were linearly regressed with motor impairment scores. Motor recovery was correlated with longitudinal DeltarCBF images. RESULTS: Patients (7 males; 72.0+/-9.8 years) demonstrated a wide range of impairment severity and variable recovery. Upper-limb motor function was linearly correlated with task-related DeltarCBF. Importantly, sites of correlated DeltarCBF differed over time. Subacutely correlated DeltarCBF was observed in supplementary motor area (SMA), bilateral cingulate, and contralesional insula with a small area in ipsilesional primary sensorimotor cortex (SM1). Conversely, at the 6-month study, correlated DeltarCBF was primarily in ipsilesional SM1, extending to the cingulate gyrus. Better motor recovery was correlated with reduction in contralesional activity and increase in ipsilesional SM1. CONCLUSIONS: Upper-limb motor function and recovery are correlated with DeltarCBF in SMA, cingulate, insula, and SM1, highlighting the role of these areas in the recovery process. The dynamic nature of the relationship suggests ongoing adaptation within motor networks.

Aged↗

PubMed2005

Functional connectivity during Stroop task performance.

Using covariance-based multivariate analysis, we examined patterns of functional connectivity in rCBF on a practice-extended version of the Stroop color-word paradigm. Color-word congruent and incongruent conditions were presented in six AB trials to healthy subjects during 12 H2(15)O PET scans. Analyses identified two reproducible canonical eigenimages (CE) from the PET data, which were converted to a standard Z score scale after cross-validation resampling and correction for random subject effects. The first CE corresponded to practice-dependent changes in covarying rCBF that occurred over early task repetitions and correlated with improved behavioral performance. This included many regions previously implicated by PET and fMRI studies of this task, which we suggest may represent two "parallel" networks: (i) a cingulo-frontal system that was initially engaged in selecting and mapping a task-relevant response (color naming) when the attentional demands of the task were greatest; and (ii) a ventral visual processing stream whose concurrent decrease in activity represented the task-irrelevant inhibition of word reading. The second CE corresponded to a consistent paradigmatic effect of Stroop interference on covarying rCBF. Coactivations were located in dorsal and ventral prefrontal regions as well as frontopolar cortex. This pattern supports existing evidence that prefrontal regions are involved in maintaining attentional control over conflicting response systems. Taken together, these findings may be more in line with theoretical models that emphasize a role for practice in the emergence of Stroop phenomena. These findings may also provide some additional insight into the nature of anterior cingulate- and prefrontal cortical contributions to implementing cognitive control in the brain.

Arousal↗

PubMed2005

High-resolution MRI reflects myeloarchitecture and cytoarchitecture of human cerebral cortex.

Maps of cytoarchitectonically defined cortical areas have proven to be a valuable tool for anatomic localization of activated brain regions revealed by functional imaging studies. However, architectonic data require observations in a sample of postmortem brains. They can only be used reliably for comparison with functional data as probabilistic maps after spatial normalization to a common reference space. The complete architectonic analysis of an individual living brain has not been achievable to date, because the relationship remains unclear between laminar gray value changes of cerebral cortex in magnetic resonance (MR) images and those of cyto- and myeloarchitectonic histologic sections. We examined intensity profiles through the cortex in five imaging modalities: in vivo T1 and postmortem T2 MRI, one cell body stain, and two myelin stains. After visualizing the dissimilarities in the shapes of these profiles using a canonical analysis, differences between the profiles from the different image modalities were compared quantitatively. Subsequently, the profiles extracted from the in vivo T1-weighted images were estimated from profiles extracted from cyto- and myeloarchitectonic sections using linear combinations. We could verify statistically the mixed nature of the cortical T1 signal obtained in vivo: The MR intensity profiles were significantly more similar to myeloarchitectonic than to cytoarchitectonic profiles, but a weighted sum of both fitted the T1 profiles best.

Brain Mapping↗

PubMed2005

Brain activity associated with painfully hot stimuli applied to the upper limb: a meta-analysis.

The capacity of pain to alert against potential injury or focus attention on damaged tissue is enhanced by the intrinsically aversive nature of the experience. Finding methods to relieve pain will ultimately be facilitated by deeper understanding of the processes that contribute to the experience, and functional brain imaging has contributed substantially toward that end. An impressive body of literature has identified a distributed network of pain-related activity in the brain that is subject to considerable modulation by different stimulus parameters, contextual factors, and clinical conditions. The fundamental substrates of the pain network are yet to be distilled from the highly variable results of studies published thus far. Qualitative reviews of the pain-imaging literature have been contributory, but lack the greater surety of quantitative methods. We employ the activation likelihood estimation (ALE) meta-analytic technique to establish the most consistent activations among studies reporting brain responses subsequent to the application of noxious heat. A network of pain-related activity was replicated for stimuli to either upper limb that included two discernible regions of the mid-anterior cingulate cortex, bilateral thalami, insula, and opercula cortices, posterior parietal cortex, premotor cortex, supplementary motor area, and cerebellum. The findings of the meta-analysis resonate with other streams of information that continue to enhance our understanding of pain in the brain. The results also point toward new areas of research that may be fruitful for the exploration of central pain processing.

Brain↗

PubMed2005

Real and imaginary rotary motion processing: functional parcellation of the human parietal lobe revealed by fMRI.

Functional magnetic resonance imaging was performed in 16 healthy subjects while they undertook orientation discrimination tasks of real rotating and mentally rotating alphanumeric characters. Perception of rotating and stationary abstract characters was also performed. Mental rotation and the perception of alphanumeric characters undergoing real rotation activated equivalent cortical areas, in keeping with the analogue hypothesis of mental rotation. In addition, areas along the dorsal stream, including the V5/middle temporal complex and the intraparietal sulcus (IPS), were activated during both the real and imaginary rotary conditions. Within the parietal lobe there were areas of convergence (i.e., recruited by all three motion conditions) and areas of divergence (i.e., selectively activated by a particular condition). Tasks requiring canonical-mirror orientation discrimination revealed involvement of neural substrates localized to the ventrolateral bank of the IPS. Tasks in which this judgment was not performed and during which the subject viewed rotary motion of abstract stimuli recruited activity in the medial bank of the IPS. These results indicate subspecialization of the human posterior parietal lobe according to function.

Adult↗

PubMed2004

Changes in effective connectivity models in the presence of task-correlated motion: an fMRI study.

We investigated the effects of motion-correction strategy and time course selection method when structural equation modeling is applied to fMRI data in the presence of task-correlated motion. Three motion-correction methods were employed for a group of 12 subjects performing an orthographic lexical retrieval task: (1) a rigid body realignment as implemented in SPM99, (2) a rigid body realignment combined with the inclusion of motion parameters in the statistical model, and (3) the FLIRT motion correction followed by an ICA analysis aiming to identify and remove the motion-related components and the ghosting artifacts. For each motion correction, the time courses of the activated regions were selected in three ways: (1) using the voxels with the highest Z scores, (2) using the average across all the statistically significant voxels in the region of interest, and (3) using a within-region, across-subjects, singular value decomposition. The resulting models of effective connectivity were markedly different, although the activation pattern was not substantially altered by the motion-correction method. Higher values for the path coefficients were obtained for the models fitted to the covariance matrices based on the average time courses than for the covariance matrices based on a single voxel time course. Our results suggest caution with the interpretation of task-induced changes in effective connectivity since, for higher-order cognitive brain functions, multiple models can be fitted to a given data set and these models cannot be rejected on an anatomical or cognitive basis. Hum. Brain Mapping 21:49-63, 2004.

Brain Mapping↗

PubMed2003

Cortical activation associated with the experience of auditory hallucinations and perception of human speech in schizophrenia: a PET correlation study.

A [H(2)(15)O] PET correlation analysis technique was employed to correlate brain activations associated with self-reports of auditory hallucinations in hallucinating patients (n=8) and perception of transient, random human speech in non-hallucinating (n=7) patients and normal control subjects (n=8). Perception of externally generated human speech amongst the non-hallucinating and normal control participants was associated with a consistent pattern of extensive bilateral auditory cortex activation (Brodmann areas 40/41/42/22). Hallucinating participants demonstrated a network of cortical activations including bilateral auditory cortex, left limbic regions, right medial frontal and right prefrontal regions. The observed pattern of activation is consistent with models of auditory hallucinations as mis-remembered episodic memories of speech.

Adult↗

PubMed2003

Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study.

BACKGROUND: This study examined cerebral function in posttraumatic stress disorder (PTSD) during the updating of working memory to trauma-neutral, verbal information. METHODS: Ten PTSD and matched control subjects completed a visuoverbal target detection task involving continuous updating (Variable target condition) or no updating (Fixed target condition) of target identity, with updating activity estimated by condition comparison. RESULTS: Normal updating activity using this paradigm involved bilateral activation of the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobe. The PTSD group lacked this activation in the left hemisphere and was significantly different from control subjects in this regard, but showed additional activation in the superior parietal lobe, bilaterally. CONCLUSIONS: The pattern of parietal activation suggests a dependence on visuospatial coding for working memory representation of trauma-neutral, verbal information. Group differences in the relative involvement of the DLPFC indicate less dependence in PTSD on the executive role normally attributed to the left DLPFC for monitoring and manipulation of working memory content in posterior regions of the brain.

Female↗