Chris Rorden

Stereotaxic display of brain lesions

Traditionally lesion location has been reported using standard templates, text based descriptions or representative raw slices from the patients CT or MRI scan. Each of these methods has drawbacks for the display of neuroanatomical data. One solution is to display MRI scans in the same stereotaxic space popular with researchers working in functional neuroimaging. Presenting brains in this format is useful as the slices correspond to the standard anatomical atlases used by neuroimagers. In addition, lesion position and volume are directly comparable across patients. This article describes freely available software for presenting stereotaxically aligned patient scans. This article focuses on MRI scans, but many of these tools are also applicable to other modalities (e.g. CT, PET and SPECT). We suggest that this technique of presenting lesions in terms of images normalized to standard stereotaxic space should become the standard for neuropsychological studies.

Spatial normalization of brain images with focal lesions using cost function masking.

In studies of patients with focal brain lesions, it is often useful to coregister an image of the patients brain to that of another subject or a standard template. We refer to this process as spatial normalization. Spatial normalization can improve the presentation and analysis of lesion location in neuropsychological studies; it can also allow other data, for example from functional imaging, to be compared to data from other patients or normal controls. In functional imaging, the standard procedure for spatial normalization is to use an automated algorithm, which minimizes a measure of difference between image and template, based on image intensity values. These algorithms usually optimize both linear (translations, rotations, zooms, and shears) and nonlinear transforms. In the presence of a focal lesion, automated algorithms attempt to reduce image mismatch between template and image at the site of the lesion. This can lead to significant inappropriate image distortion, especially when nonlinear transforms are used. One solution is to use cost-function masking-masking the areas used in the calculation of image difference-to exclude the area of the lesion, so that the lesion does not bias the transformations. We introduce and evaluate this technique using normalizations of a selection of brains with focal lesions and normal brains with simulated lesions. Our results suggest that cost-function masking is superior to the standard approach to this problem, which is affine-only normalization; we propose that cost-function masking should be used routinely for normalizations of brains with focal lesions.

Using human brain lesions to infer function: a relic from a past era in the fMRI age?

Recent technological advances, such as functional imaging techniques, allow neuroscientists to measure and localize brain activity in healthy individuals. These techniques avoid many of the limitations of the traditional method for inferring brain function, which relies on examining patients with brain lesions. This has fueled the zeitgeist that the classical lesion method is an inferior and perhaps obsolescent technique. However, although the lesion method has important weaknesses, we argue that it complements the newer activation methods (and their weaknesses). Furthermore, recent developments can address many of the criticisms of the lesion method. Patients with brain lesions provide a unique window into brain function, and this approach will fill an important niche in future research.

Non-spatially lateralized mechanisms in hemispatial neglect

Hemispatial neglect is a common, disabling disorder that results from brain damage, most frequently stroke. Research on patients with neglect has provided important insights into normal brain mechanisms involved in directing attention, representing space and controlling movement. Although much work has focused on the lateralized components of neglect, recent investigations have also revealed deficits that are not spatially lateralized, consistent with new findings from functional imaging, human neuropsychological and monkey electrophysiological studies. Here we propose that understanding the interactions between spatially lateralized and non-lateralized mechanisms provides important insights into the neglect syndrome and the normal functions of brain structures that are commonly damaged in neglect patients, and will contribute to the development of treatments for the condition.

Motor role of human inferior parietal lobe revealed in unilateral neglect patients

The exact role of the parietal lobe in spatial cognition is controversial. One influential hypothesis proposes that it subserves spatial perception, whereas other accounts suggest that its primary role is to direct spatial movement,. For humans, it has been suggested that these functions may be divided between inferior and superior parietal lobes, respectively,. In apparent support of a purely perceptual function for the inferior parietal lobe (IPL), patients with lesions to this structure, particularly in the right hemisphere, exhibit unilateral spatial neglect (deficient awareness for the side of space opposite to that of their lesion). Here we show that patients with right IPL lesions also have a specific difficulty in initiating leftward movements towards visual targets on the left side of space. This motor impairment was not found in neglect patients with frontal lesions, contrary to previous proposals that motor aspects of neglect are particularly associated with anterior damage. Our results suggest that the human IPL operates as a sensorimotor interface, rather than subserving only perceptual functions.

Enhancing the Sensitivity of a Sustained Attention Task to Frontal Damage: Convergent Clinical and Functional Imaging Evidence

Despite frequent reports of poor concentration following traumatic brain injury, studies have generally failed to find disproportionate time-on-task decrements using vigilance measures in this patient group. Using a rather different definition, neuropsychological and functional imaging research has however linked sustained attention performance to right prefrontal function – a region likely to be compromised by such injuries. These studies have emphasized more transitory lapses of attention during dull and ostensibly unchallenging activities. Here, an existing attention measure was modified to reduce its apparent difficulty or ‘challenge’. Compared with the standard task, its capacity to discriminate traumatically head-injured participants from a control group was significantly enhanced. Unlike existing functional imaging studies, that have compared a sustained attention task with a no-task control, in study 2 we used positron emission tomography to contrast the two levels of the same task. Significantly increased blood flow in the dorsolateral region of the right prefrontal cortex was associated with the low challenge condition. While the results are discussed in terms of a frontal system involved in the voluntary maintenance of performance under conditions of low stimulation, alternative accounts in terms of strategy application are considered.

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 nucleis 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 regions anatomical and functional association with the limbic system rather than a general vulnerability to damage.

Medial temporal lobe atrophy in patients with refractory temporal lobe epilepsy

Objective: The objective of this study was to assess the volumes of medial temporal lobe structures using high resolution magnetic resonance images from patients with chronic refractory medial temporal lobe epilepsy (MTLE). Methods: We studied 30 healthy subjects, and 25 patients with drug refractory MTLE and unilateral hippocampal atrophy (HA). We used T1 magnetic resonance images with 1 mm isotropic voxels, and applied a field non-homogeneity correction and a linear stereotaxic transformation into a standard space. The structures of interest are the entorhinal cortex, perirhinal cortex, parahippocampal cortex, temporopolar cortex, hippocampus, and amygdala. Structures were identified by visual examination of the coronal, sagittal, and axial planes. The threshold of statistical significance was set to p<0.05. Results: Patients with right and left MTLE showed a reduction in volume of the entorhinal (p<0.001) and perirhinal (p<0.01) cortices ipsilateral to the HA, compared with normal controls. Patients with right MTLE exhibited a significant asymmetry of all studied structures; the right hemisphere structures had smaller volume than their left side counterparts. We did not observe linear correlations between the volumes of different structures of the medial temporal lobe in patients with MTLE. Conclusion: Patients with refractory MTLE have damage in the temporal lobe that extends beyond the hippocampus, and affects the regions with close anatomical and functional connections to the hippocampus.

ATTENTIONAL FUNCTIONS IN DORSAL AND VENTRAL SIMULTANAGNOSIA

Whole report of brief letter arrays is used to analyse basic attentional deficits in dorsal and ventral variants of simultanagnosia. Using Bundesens Theory of Visual Attention (TVA), a number of previous theoretical suggestions are formalised and tested, including primary deficit in processing more than one display element, attentional stickiness, foveal bias, and global weakness of the visual representation. Interestingly, data from two cases, one dorsal and one ventral, show little true deficit in simultaneous perception, or selective deficit in those TVA parameters (short‐term memory capacity, attentional weighting) specifically associated with multi‐element displays. Instead there is a general reduction in speed of visual processing (processing rate in TVA), effective even for a single display element but compounded when two or more elements compete.

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.