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K Worsley

Publications and source records attributed to K Worsley.

11 recordsLinked to original sources

Functional abnormalities in symptomatic concussed athletes: an fMRI study.

Our aim was to quantify with functional magnetic resonance imaging (fMRI) changes in brain activity in concussed athletes and compare the results with those of normal control subjects. Regional brain activations associated with a working memory task were obtained from a group of concussed athletes (15 symptomatic, 1 asymptomatic) and eight matched control subjects, using blood oxygen level dependent (BOLD) fMRI. The average percent signal change from baseline to working memory condition in each region of interest was computed. Symptomatic concussed athletes demonstrated task-related activations in some but not all the regions of interest, even when they performed as well as the control subjects. Furthermore, several concussed athletes had additional increases in activity outside the regions of interest, not seen in the control group. Quantitative analysis of BOLD signals within regions of interest revealed that, in general, concussed athletes had different BOLD responses compared to the control subjects. The task-related activation pattern of the one symptom-free athlete was comparable to that of the control group. We also repeated the study in one athlete whose symptoms had resolved. On the first study, when he was still symptomatic, less task-related activations were observed. On follow-up, once his symptoms had disappeared, the task-related activations became comparable to those of the control group. These results demonstrate the potential of fMRI, in conjunction with the working memory task, to identify an underlying pathology in symptomatic concussed individuals with normal structural imaging results.

Adult↗

Random field-union intersection tests for EEG/MEG imaging.

Electrophysiological (EEG/MEG) imaging challenges statistics by providing two views of the same spatiotemporal data: topographic and tomographic. Until now, statistical tests for these two situations have developed separately. This work introduces statistical tests for assessing simultaneously the significance of spatiotemporal event-related potential/event-related field (ERP/ERF) components and that of their sources. The test for detecting a component at a given time instant is provided by a Hotelling's T(2) statistic. This statistic is constructed in such a manner to be invariant to any choice of reference and is based upon a generalized version of the average reference transform of the data. As a consequence, the proposed test is a generalization of the well-known Global Field Power statistic. Consideration of tests at all time instants leads to a multiple comparison problem addressed by the use of Random Field Theory (RFT). The Union-Intersection (UI) principle is the basis for testing hypotheses about the topographic and tomographic distributions of such ERP/ERF components. The performance of the method is illustrated with actual EEG recordings obtained from a visual experiment of pattern reversal stimuli.

Algorithms↗

Unmyelinated tactile afferents signal touch and project to insular cortex.

There is dual tactile innervation of the human hairy skin: in addition to fast-conducting myelinated afferent fibers, there is a system of slow-conducting unmyelinated (C) afferents that respond to light touch. In a unique patient lacking large myelinated afferents, we found that activation of C tactile (CT) afferents produced a faint sensation of pleasant touch. Functional magnetic resonance imaging (fMRI) analysis during CT stimulation showed activation of the insular region, but not of somatosensory areas S1 and S2. These findings identify CT as a system for limbic touch that may underlie emotional, hormonal and affiliative responses to caress-like, skin-to-skin contact between individuals.

Adult↗

Wisconsin Card Sorting revisited: distinct neural circuits participating in different stages of the task identified by event-related functional magnetic resonance imaging.

The Wisconsin Card Sorting Task (WCST) has been used to assess dysfunction of the prefrontal cortex and basal ganglia. Previous brain imaging studies have focused on identifying activity related to the set-shifting requirement of the WCST. The present study used event-related functional magnetic resonance imaging (fMRI) to study the pattern of activation during four distinct stages in the performance of this task. Eleven subjects were scanned while performing the WCST and a control task involving matching two identical cards. The results demonstrated specific involvement of different prefrontal areas during different stages of task performance. The mid-dorsolateral prefrontal cortex (area 9/46) increased activity while subjects received either positive or negative feedback, that is at the point when the current information must be related to earlier events stored in working memory. This is consistent with the proposed role of the mid-dorsolateral prefrontal cortex in the monitoring of events in working memory. By contrast, a cortical basal ganglia loop involving the mid-ventrolateral prefrontal cortex (area 47/12), caudate nucleus, and mediodorsal thalamus increased activity specifically during the reception of negative feedback, which signals the need for a mental shift to a new response set. The posterior prefrontal cortex response was less specific; increases in activity occurred during both the reception of feedback and the response period, indicating a role in the association of specific actions to stimuli. The putamen exhibited increased activity while matching after negative feedback but not while matching after positive feedback, implying greater involvement during novel than routine actions.

Adolescent↗

Structural maturation of neural pathways in children and adolescents: in vivo study.

Structural maturation of fiber tracts in the human brain, including an increase in the diameter and myelination of axons, may play a role in cognitive development during childhood and adolescence. A computational analysis of structural magnetic resonance images obtained in 111 children and adolescents revealed age-related increases in white matter density in fiber tracts constituting putative corticospinal and frontotemporal pathways. The maturation of the corticospinal tract was bilateral, whereas that of the frontotemporal pathway was found predominantly in the left (speech-dominant) hemisphere. These findings provide evidence for a gradual maturation, during late childhood and adolescence, of fiber pathways presumably supporting motor and speech functions.

Adolescent↗

Imaging motor-to-sensory discharges in the human brain: an experimental tool for the assessment of functional connectivity.

We present a new approach to studying functional connectivity in the human brain. This approach is based on the observation that when we engage in motor activity, a discharge corollary to the motor command is sent from motor to sensory structures. Thus, as long as movement-related sensory input is either prevented or masked, modulation of neuronal activity in sensory structures would indicate the presence of functional connectivity between the motor and the sensory regions. Using positron emission tomography, such a central interaction between motor and sensory regions can be assessed by measuring regional changes in cerebral blood flow (CBF) in sensory regions. In this paper, we describe the experimental design and the results of two studies of corollary discharges, namely those generated during eye movements and speech. In these studies, a graded approach was used to establish the relationship between the number of eye movements or utterances and CBF in visual or auditory regions, respectively. Significant covariations between the number of movements and CBF in sensory regions were found, thus indicating the presence of functional connectivity between motor and sensory regions. In addition, interregional CBF covariations were computed and the effect of removing the intersubject variance on these covariations was evaluated. The corollary-discharge-based approach to studying functional connectivity is discussed in the context of more traditional computational approaches to network analysis in functional brain imaging.

Brain↗

Determination of the lumped constant for the alpha-methyltryptophan method of estimating the rate of serotonin synthesis.

The lumped constant (LC) for the alpha-methyl-L-tryptophan method to convert the brain's uptake of labeled alpha-methyl-L-tryptophan into the regional rate of serotonin synthesis was estimated. The method involved independently estimating the unidirectional uptake constant of the tracer (alpha-[14C]methyl-L-tryptophan) to the tissue and the tracee (tryptophan) (with the addition of a radioactive compound) and calculating their ratio. The LC was estimated from logarithmically transformed data. Similar experiments were performed using rats treated with the drug probenecid, which blocks the efflux of 5-hydroxyindoleacetic acid (a metabolite of serotonin) from the brain. The experiments using probenecid, corrected for the difference in the levels of plasma free tryptophan (increased in probenecid-treated rats) relative to control experiments, gave an average LC for the rat brain of 0.46 +/- 0.14 (mean +/- SD). This value was not significantly different from the one obtained in controls (0.43 +/- 0.13). In addition, the LC was also calculated using unidirectional uptake constants in the probenecid-treated rats for alpha-methyl-L-tryptophan and L-tryptophan. This LC value was 0.39 +/- 0.10. There was no significant difference between these three LC values. Thus, an average +/- SD LC of 0.42 +/- 0.07 for 28 brain structures investigated in this study was obtained. Statistically the LC obtained in different structures had a variability that could be accounted for by errors in measurements alone. In other words, dispersion in the LC values could be fully accounted for by chance alone. Data confirmed that the LC value did not change when the rate of serotonin synthesis was increased by probenecid treatment. We also showed that the rate of 5-hydroxyindoleacetic acid accumulation in probenecid-treated rats was 58 pmol g-1 min-1 (rat brain), which is about twice as much as reported by others for a normal rat. This difference could also be accounted for by the increase in the plasma level of free tryptophan in probenecid-treated rats.

Animals↗

Anatomical mapping of functional activation in stereotactic coordinate space.

Numerous applications have been reported for the stereotactic mapping of focal changes in cerebral blood flow during sensory and cognitive activation as measured with positron emission tomography (PET) subtraction images. Since these images lack significant anatomical information, analysis of these kinds of data has been restricted to an automated search for peaks in the PET subtraction dataset and localization of the peak coordinates within a standardized stereotactic atlas. This method is designed to identify isolated foci with dimensions smaller than the image resolution. Details of activation patterns that may extend over finite distances, following the underlying anatomical structures, will not be apparent. We describe the combined mapping into stereotactic coordinate space of magnetic resonance imaging (MRI) and PET information from each of a set of subjects such that the major features of the activation pattern, particularly extended tracts of increased blood flow, can be immediately assessed within their true anatomical context as opposed to that presumed using a standard atlas alone. Near areas of high anatomical variability, e.g., central sulcus, or of sharp curvature, e.g., frontal and temporal poles, this information can be essential to the localization of a focus to the correct gyrus or for the rejection of extracerebral peaks. It also allows for the removal from further analysis of data from cognitively-normal subjects with abnormal anatomy such as enlarged ventricles. In patients with neuropathology, e.g., Alzheimer's disease, arteriovenous malformation, stroke, or neoplasm, the use of correlated MRI is mandatory for correct localization of functional activation.

Adult↗

The effect of nimodipine on the evolution of human cerebral infarction studied by PET.

Fourteen patients were studied by positron emission tomography (PET) within 48 h of onset of a hemispheric ischemic stroke and again 7 days later. After the first set of PET scans, the patients were randomized to receive either nimodipine (n = 7) or a carrier solution (n = 7) by intravenous infusion. The infusions were maintained until the end of the second PET studies. CBF, cerebral blood volume (CBV), oxygen extraction ratio (OER), CMRO2, and CMRglc were measured each time. These metabolic and perfusion measurements were performed by standard methods. A surface map of each metabolic and perfusion measurement in the cortical mantle was generated by interpolating between the available slices. The various surface maps representing the physiological characteristics determined in the same or subsequent studies were aligned so that all data sets could be analyzed identically using an array of square regions of interest (ROIs). The functional status of each ROI was recorded at the two intervals following the cerebrovascular accident to characterize the evolution of the infarct, penumbra, and normal brain regions. We presumed the ischemic penumbra to be cortical regions in the proximity of the infarct and perfused at CBF values between 12 and 18 ml/100 g/min on the first PET scan, while densely ischemic regions had CBF of less than 12 nl/100 g/min and normally perfused brain greater than 18 ml/100 g/min. In the densely ischemic zone, CBF increased more in the nimodipine-treated group than in the carrier group. As well, in this region nimodipine reversed the decline in CMRO2 noted in the carrier group, the difference in the changes being significant. In the penumbra zone, comparable trends were noted in OER and CMRO2 but the difference in the changes between the two groups did not reach statistical significance. Changes in CMRglc and CBV were comparable between the two groups in both cortical regions.

Adult↗

Effect of generalized spike-and-wave discharge on glucose metabolism measured by positron emission tomography.

Positron emission tomography was used to study the cerebral metabolic rate for glucose (CMRGlc) in 7 adult patients with generalized spike-and-wave activity in the electroencephalogram. No consistent changes were seen in the CMRGlc. There was a slight trend toward an increased CMRGlc in 2 patients with primary generalized epilepsy, while in the 5 other patients with minor deviations from this condition or with secondary generalized epilepsy, the CMRGlc was unaffected by spike-and-wave activity or was below the normal range. Neither the amount of spike-and-wave activity in the EEG nor the presence of clinically evident absence seizures appeared to influence the CMRGlc. Therefore, we conclude that neuronal activity underlying spike-and-wave discharge does not seem to require increased glucose utilization.

Adolescent↗