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Biomedical subjects

Chris Rorden

Publications and source records attributed to Chris Rorden.

At least 19 recordsLinked to original sources

Structural white matter abnormalities in patients with idiopathic dystonia.

We investigated whether structural white matter abnormalities, in the form of disruption of axonal coherence and integrity as measured with diffusion tensor imaging (DTI), constitute an underlying pathological mechanism of idiopathic dystonia (ID), independent of genotype status. We studied seven subjects with ID: all had cervical dystonia as their main symptom (one patient also had spasmodic dysphonia and two patients had concurrent generalized dystonia, both DYT1-negative). We compared DTI MR images of patients with 10 controls, evaluating differences in mean diffusivity (MD) and fractional anisotropy (FA). ID was associated with increased FA values in the thalamus and adjacent white matter, and in the white matter underlying the middle frontal gyrus. ID was also associated with increase in MD in adjacent white matter to the pallidum and putamen bilaterally, left caudate, and in subcortical hemispheric regions, including the postcentral gyrus. Abnormal FA and MD in patients with ID indicate that abnormal axonal coherence and integrity contribute to the pathophysiology of dystonia. These findings suggest that ID is not only a functional disorder, but also associated with structural brain changes. Impaired connectivity and disrupted flow of information may contribute to the impairment of motor planning and regulation in dystonia.

Adult↗

Microstructural white matter abnormalities in nodular heterotopia with overlying polymicrogyria.

Nodular heterotopia (NH) with overlying polymicrogyria can result in medically uncontrolled seizures. Most patients also exhibit deficits of function related to the location of the abnormal cortex. However, functional imaging studies show that the abnormal cortex can retain some function, making surgical planning difficult. It is not known if the connectivity of the abnormal cortex is normal. In this article, we performed an evaluation of molecular diffusion within the white matter in a patient with refractory epilepsy due to NH with overlying polymicrogyria. We observed that the white matter underlying the polymicrogyric area shows signs of microstructural abnormalities. This result suggests that the deficit of function from polymicrogyria result from both the structurally abnormal cortex and from its impaired connectivity.

Adult↗

Gray matter atrophy associated with duration of temporal lobe epilepsy.

Hippocampal sclerosis is the most common abnormality associated with medial temporal lobe epilepsy (MTLE). Converging evidence supports that hippocampal sclerosis progresses with time. However, it is unclear whether extrahippocampal atrophy in patients with MTLE, similarly to hippocampal sclerosis, is an unremitting progressive process. In this article, we investigate the relationship between duration of epilepsy and gray matter concentration reduction in patients with MTLE within and outside the hippocampus. We employed a voxel-based morphometry study of MRI of the entire brain of 36 patients with drug refractory MTLE and 49 neurologically healthy age-matched controls. We performed a voxel-based parametric and nonparametric investigation of the association between gray matter concentration, age and duration of epilepsy. We complemented the investigation by extracting the gray matter concentration of regions of interest (ROIs) within the limbic system, and we investigated the association between the gray matter concentration on the ROIs and duration of epilepsy. Patients with MTLE exhibited gray matter concentration reduction that is negatively correlated with the duration of epilepsy within the ipsilateral hippocampus, temporal lobes as well as extratemporal limbic structures that are closely connected with the hippocampus. In conclusion, longer duration of refractory epilepsy was associated with a more intense hippocampal and extrahippocampal atrophy in patients with MTLE. The mechanism of progressive neuronal damage in MTLE may be related to active seizure activity within a limbic network, and early seizure control may prevent further brain atrophy in patients with refractory MTLE.

Adolescent↗

Speech apraxia without oral apraxia: can normal brain function explain the physiopathology?

Apraxia of speech, usually associated with stroke, refers to the inability to perform speech motor movements typically with an intact ability to execute non-speech oral movements. It is uncertain whether apraxia of speech results from damage affecting the insula or the inferior frontal gyrus. The controversy started because of conflicting results from studies investigating patients with disrupted brain structure, when dysfunction of both sites can coexist. We conducted a functional magnetic resonance imaging study of individuals without neurological disorders comparing speech and non-speech movements. Speech movements did not recruit the insula, but activated the left inferior frontal gyrus, suggesting that Broca's area, but not the insula, is critical for speech articulation.

Adolescent↗

Disturbed line bisection is associated with posterior brain lesions.

Neglect patients classically fail to orient and respond to stimuli appearing on their contralesional side. Traditionally, the neglect syndrome has been associated with damage to the right inferior parietal lobule (IPL) and the right temporo-parietal junction (TPJ). Neglect is popularly assessed by two different tasks: line bisection and cancellation. In a previous study (S. Ferber, H.-O. Karnath, How to assess spatial neglect-line bisection or cancellation tasks. J. Clin. Exp. Neuropsychol. 23 (2001) 599-607), we observed that performance on the cancellation task correlates well with the characteristic behavioral disorders used to clinically diagnose spatial neglect, while line bisection was a poor predictor. This might indicate that the disability to correctly bisect lines is a distinct disorder separable from spatial neglect. Here, we assess the anatomy of the patients investigated in that study, and reveal that damage to the temporo-occipital junction correlates with poor performance in the line bisection task. This work extends previous work by Binder et al. (J. Binder, R. Marshall, R. Lazar, J. Benjamin, J.P. Mohr, Distinct syndromes of hemineglect. Arch. Neurol. 49 (1992) 1187-1194) suggesting that line bisection and cancellation identify distinct syndromes. The data suggest that these two tasks dissociate both in terms of behavior and anatomy. This anatomical distinction may help reconcile our recent finding that spatial neglect is associated with damage to the superior temporal cortex and insula, while others have identified the IPL and TPJ. Specifically, we note that our previous anatomical studies did not use the line bisection task to select neglect patients, while many others used this task. We suggest that anatomical studies that combine patients from both of these two distinct groups may result in misleading findings.

Adult↗

Memory and language impairments and their relationships to hippocampal and perirhinal cortex damage in patients with medial temporal lobe epilepsy.

Chronic medial temporal lobe epilepsy (MTLE) is associated with memory loss due to damage in the hippocampal system. To investigate the relationship between volume of medial temporal lobe structures and performance on neuropsychological tests, we studied 39 consecutive patients with MTLE and unilateral hippocampal atrophy (HA) determined by volumetric magnetic resonance imaging (MRI). Structures of interest comprised hippocampus, amygdala, and entorhinal, perirhinal, parahippocampal, and temporopolar cortices. The findings indicated that (1) performance was significantly worse in the group with left HA as compared with the group with right HA on general memory, verbal memory, delayed recall, and verbal fluency tests and the Boston Naming Test (BNT), and (2) the volume of the left hippocampus and also the degree of asymmetry of perirhinal cortex volume were significant and independent predictors of performance on general memory, verbal memory, and verbal fluency tests and the BNT in patients with MTLE.

Adolescent↗

Measuring the hemodynamic response in chronic hypoperfusion.

Although structural brain scans help assess brain injury in stroke, they cannot identify regions that are functionally disabled due to disrupted perfusion. Perfusion and functional MRI have the potential for determining the functional consequences of stroke. Here we examine the effectiveness of functional MRI to measure brain function in a single patient (LB) with chronic hypoperfusion. When LB made sustained hand movements we observed a sustained decrease in the fMRI signal, while normal individuals exhibit a sustained increase in signal while conducting this task. This work has clear implications for understanding stroke using functional MRI.

Brain Injuries↗

Voxel-based morphometry reveals excess gray matter concentration in patients with focal cortical dysplasia.

PURPOSE: Many patients with focal cortical dysplasia (FCD) continue to have seizures after surgical treatment. The usual explanation for the poor surgical outcome is the presence of residual dysplastic tissue missed by the preoperative neuroimaging investigation and therefore not resected during surgery. We apply a voxel-based morphometry (VBM) analysis to the magnetic resonance imaging (MRI) scans from patients with epilepsy and visually detected FCD to investigate whether (a) VBM is able to detect gray-matter concentration (GMC) abnormalities in patients with FCD, and (b) whether the extent of GMC abnormalities in the brain of these patients differs from the regions observed by using visual inspection. METHODS: We studied 11 patients with visually detected FCD (eight of them with histologic confirmation of FCD). The GMC from each one of these patients was compared with the mean GMC from a control group of 96 normal healthy subjects by using an optimized VBM protocol. RESULTS: Ten of 11 patients showed statistically significant GMC excess, and among patients with GMC excess, only one showed GMC excess that was not exactly correspondent to the visually detected FCD. Seven patients exhibited excess in GMC extending beyond the area of visually detected FCD. CONCLUSIONS: This preliminary neuroimaging study suggests that (a) VBM can detect GMC excess in patients with FCD, and (b) GMC excess in these patients can extend to brain areas not visually defined as abnormal. Abnormal areas detected by VBM can possibly correspond to mild malformations of cortical development, supporting the notion that the surgical refractoriness observed in patients with FCD can be due to the incomplete resection of the dysplastic tissue.

Adolescent↗

Statistical voxel-wise analysis of ictal SPECT reveals pattern of abnormal perfusion in patients with temporal lobe epilepsy.

OBJECTIVE: To investigate the pattern of perfusion abnormalities in ictal and interictal brain perfusion SPECT images (BSI) from patients with temporal lobe epilepsy (TLE). METHOD: It was acquired interictal and ictal BSI from 24 patients with refractory TLE. BSIs were analyzed by visual inspection and statistical parametric mapping (SPM2). Statistical analysis compared the patients group to a control group of 50 volunteers. The images from patients with left-TLE were left-right flipped. RESULTS: It was not observed significant perfusional differences in interictal scans with SPM. Ictal BSI in SPM analysis revealed hyperperfusion within ipsilateral temporal lobe (epileptogenic focus) and also contralateral parieto-occipital region, ipsilateral posterior cingulate gyrus, occipital lobes and ipsilateral basal ganglia. Ictal BSI also showed areas of hypoperfusion. CONCLUSION: In a group analysis of ictal BSI of patients with TLE, voxel-wise analysis detects a network of distant regions of perfusional alteration which may play active role in seizure genesis and propagation.

Adolescent↗

Voxel-based morphometry of the thalamus in patients with refractory medial temporal lobe epilepsy.

Previous research has suggested that patients with refractory medial temporal lobe epilepsy (MTLE) show gray matter atrophy both within the temporal lobes as well as in the thalamus. However, these studies have not distinguished between different nuclei within the thalamus. We examined whether thalamic atrophy correlates with the nuclei's connections to other regions in the limbic system. T1-weighted MRI scans were obtained from 49 neurologically healthy control subjects and 43 patients diagnosed with chronic refractory MTLE that was unilateral in origin (as measured by ictal EEG and hippocampal atrophy observed on MRI). Measurements of gray matter concentration (GMC) were made using automated segmentation algorithms. GMC was analyzed both voxel-by-voxel (preserving spatial precision) as well as using predefined regions of interest. Voxel-based morphometry revealed intense GMC reduction in the anterior portion relative to posterior thalami. Furthermore, thalamic atrophy was greater ipsilateral to the MTLE origin than on the contralateral side. Here we demonstrate that the thalamic atrophy is most intense in the thalamic nuclei that have strong connections with the limbic hippocampus. This finding suggests that thalamic atrophy reflects this region's anatomical and functional association with the limbic system rather than a general vulnerability to damage.

Adolescent↗

Attentional functions of parietal and frontal cortex.

A model of normal attentional function, based on the concept of competitive parallel processing, is used to compare attentional deficits following parietal and frontal lobe lesions. Measurements are obtained for visual processing speed, capacity of visual short-term memory (VSTM), spatial bias (bias to left or right hemifield) and top-down control (selective attention based on task relevance). The results show important differences, but also surprising similarities, in parietal and frontal lobe patients. For processing speed and VSTM, deficits are selectively associated with parietal lesions, in particular lesions of the temporoparietal junction. We discuss explanations based on either grey matter or white matter lesions. In striking contrast, measures of attentional weighting (spatial bias and top-down control) are predicted by simple lesion volume. We suggest that attentional weights reflect competition between broadly distributed object representations. Parietal and frontal mechanisms work together, both in weighting by location and weighting by task context.

Acoustic Stimulation↗

Transcranial magnetic stimulation of the left human frontal eye fields eliminates the cost of invalid endogenous cues.

Humans are able to selectively attend to specific regions of space without moving their eyes. However, there is mounting evidence that these covert shifts of attention may employ many of the same brain regions involved when executing the eye movements. For example, functional magnetic resonance imaging (fMRI) studies show that the oculomotor region known as the frontal eye fields (FEF) are activated by the covert shifts of attention. However, it remains possible that the activations seen in these studies result from actively inhibiting eye movements rather than as a direct result of modulating perceptual processing. Here we provide direct evidence for the role of this region in endogenously driven spatial attention. We show that briefly disrupting the left FEFs with transcranial magnetic stimulation (TMS) eliminated the slow response times associated with the invalid strategic cues when the target appeared in the right visual field. At first glance, our findings appear incompatible with the results reported by Grosbras and Paus (Grosbras, M. -H., & Paus, T. (2002). Transcranial magnetic stimulation of the human frontal eye field: effects on visual perception and attention. Journal of Cognitive Neuroscience, 14(7), 1109--1120) and we suggest this is likely due to the design differences. Specifically, we disrupted the FEF at the time of cue onset, rather than target onset. Taken together with the findings of Grosbras and Paus, our findings suggest that the FEF plays an early role in the inhibition of perceptual information. Furthermore, our findings complement work by Ro et al. (Ro, T., Farne, F., & Chang, E. (2003). Inhibition of return and the frontal eye fields. Experimental Brain Research, 150, 290--296) who report that stimulation of the frontal eye fields disrupts the inhibitory consequences of reflexive attention shifts.

Adult↗

Brain damage and cortical compensation in foreign accent syndrome.

Foreign Accent Syndrome (FAS) is a well-known neurological deficit whose underlying cause has remained obscure despite almost a century of study. Combining structural and functional imaging, our studies suggest that FAS represents a compensatory response to impaired motor regulation of speech. We describe a patient who acquired FAS as a result of an ischemic stroke in the left basal ganglia. In addition to this case being exceptionally clean, we were able to confirm a specific lesion location as well as provide strong evidence that impaired motor speech regulation resulted in compensation by other areas of the cortical motor speech network.

Brain Injuries↗

The anatomy of spatial neglect based on voxelwise statistical analysis: a study of 140 patients.

A major challenge for any anatomical study of spatial neglect in neurological patients is that human lesions vary tremendously in extent and location between individuals. Approaches to this problem used in previous studies were to focus on subgroups of patients that are more homogeneous either with respect to the branch territory affected by the stroke or with respect to existing additional neurological symptoms (e.g. additional visual field defects). It could be argued that such strategies might bias the conclusions on the critical substrate associated with spatial neglect. The present study thus addressed the high variability inherent in naturally occurring lesions by using an unselected, but very large sample size and by comparing a neglect group with a non-neglect group using voxelwise statistical testing. We investigated an unselected 7 year sample of 140 consecutively admitted patients with right hemisphere strokes. Seventy-eight had spatial neglect, 62 did not show the disorder. The incidence of visual field defects was comparable in both groups. For assessing lesion location, in a first step, we used conventional lesion density plots together with subtraction analysis. Moreover, due to the large size of the sample voxelwise statistical testing was possible to objectively estimate which brain regions are more frequently compromised in neglect patients relative to patients without neglect. The results demonstrate that the right superior temporal cortex, the insula and subcortically putamen and caudate nucleus are the neural structures damaged significantly more often in patients with spatial neglect.

Adult↗

Exogenous orienting of attention depends upon the ability to execute eye movements.

Shifts of attention can be made overtly by moving the eyes or covertly with attention being allocated to a region of space that does not correspond to the current direction of gaze. However, the precise relationship between eye movements and the covert orienting of attention remains controversial. The influential premotor theory proposes that the covert orienting of attention is produced by the programming of (unexecuted) eye movements and thus predicts a strong relationship between the ability to execute eye movements and the operation of spatial attention. Here, we demonstrate for the first time that impaired spatial attention is observed in an individual (AI) who is neurologically healthy but who cannot execute eye movements as a result of a congenital impairment in the elasticity of her eye muscles. This finding provides direct support for the role of the eye-movement system in the covert orienting of attention and suggests that whereas intact cortical structures may be necessary for normal attentional reflexes, they are not sufficient. The ability to move our eyes is essential for the development of normal patterns of spatial attention.

Adult↗

Voxel-based morphometry reveals gray matter network atrophy in refractory medial temporal lobe epilepsy.

BACKGROUND: Conventional volumetric studies have shown that brain structures functionally and anatomically related to the hippocampus are smaller in patients with drug-refractory medial temporal lobe epilepsy (MTLE). OBJECTIVES: To determine the extent of gray matter atrophy in the brains of patients with MTLE and to examine the pattern of atrophy. DESIGN: We performed a voxel-based morphometric study of 43 consecutive patients with unilateral drug-refractory MTLE (21 patients with right-sided MTLE and 22 patients with left-sided MTLE) whose magnetic resonance images showed signs of unilateral hippocampal atrophy. The data from the patients with MTLE were compared with the data from 49 healthy control subjects to identify differences between groups in gray matter concentration (GMC). SETTING: Academic hospital's epilepsy clinic. RESULTS: We observed that patients with left- and right-sided MTLE exhibited GMC reduction in the hippocampus ipsilateral to the seizure origin. In addition, we found GMC reduction in the ipsilateral parahippocampal and isocortical temporal regions. Patients with MTLE also showed GMC reduction in subcortical nuclei such as the thalamus and caudate, in the cerebellum, in the midbrain, and in parieto-occipital regions. CONCLUSIONS: Patients with MTLE exhibit a reduction in GMC in regions outside the temporal lobe, specifically in areas that are connected to the hippocampus and parahippocampal region, suggesting an anatomical route for atrophy.

Adult↗

The effect of ipsilesional cues on line-bisection errors: the importance of predictive value.

Patients with unilateral neglect were tested on a line-bisection task in which vertical lines were added to the ipsilesional or contralesional end. During some blocks, these vertical lines accurately predicted the horizontal length of the line, while on other blocks the vertical lines had little predictive value. We found that much of the improvement for ipsilesional vertical bars can be explained by their ability to predict the extent of the horizontal line. These results suggest that the predictive value of a ipsilesional cue is responsible for the reduction in line-bisection errors noted by Halligan and Marshall [Neuropsychologia 32 (1994) 13]. This effect of the predictive ipsilesional cue may work in combination with the expanded attentional effects posited by the ipsilesional contraction model that they proposed.

Aged↗