Normalized perfusion MRI to identify common areas of dysfunction: patients with basal ganglia neglect

doi:10.1093/brain/awh629 Brain (2005), 128, 2462–2469 Normalized perfusion MRI to identify common areas of dysfunction: patients with basal ganglia neglect Hans-Otto Karnath,1 Regine Zopf,1 Leif Johannsen,1 Monika Fruhmann Berger,1 Thomas Nägele2 and Uwe Klose3 1 Section Neuropsychology, Department of Cognitive Neurology, Hertie-Institute for Clinical Brain Research, 2Department of Neuroradiology and 3Section Experimental MR of the CNS, Department of Neuroradiology, University of Tübingen, Tübingen, Germany Correspondence to: Prof. Hans-Otto Karnath, MD, PhD, Center of Neurology, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076 Tübingen, Germany E-mail: Perfusion-weighted imaging (PWI) is used to identify brain regions that are receiving enough blood supply to remain structurally intact, but not enough to function normally. Previous observations suggest that spatial neglect due to subcortical stroke can be explained by dysfunction of cortical areas rather than through the neuronal loss in the subcortical structures itself. The present study aimed to identify the dysfunctional cortical regions induced by basal ganglia stroke in patients with spatial neglect. In a patient group with stroke lesions centring on the basal ganglia, we examined the common area(s) of structurally intact but dysfunctional cortical tissue by using spatial normalization of PWI maps as well as symmetric voxel-wise inter-hemispheric comparisons. These new techniques allow comparison of the structurally intact but abnormally perfused areas of different individuals in the same stereotaxic space, and at the same time avoid problems due to regional perfusion differences and to possible observer-dependent biases. We found that strokes centring on the right basal ganglia which provoke spatial neglect induce abnormal perfusion in a circumscribed area of intact cortex that typically involves those three regions that have previously been described to provoke spatial neglect when damaged directly by cortical infarction: the superior temporal gyrus, the inferior parietal lobule and the inferior frontal gyrus. The data suggest that spatial neglect following a right basal ganglia lesion typically is caused by the dysfunction of (part of) these specific cortical areas. Keywords: spatial neglect; basal ganglia; attention; visual search; exploration; perfusion-weighted imaging; human Abbreviations: PWI = perfusion-weighted imaging; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion-recovery Received April 2, 2005. Revised July 12, 2005. Accepted August 8, 2005. Advance Access publication September 8, 2005 Introduction To explain behavioural defects after stroke, MRI and CT are used to determine brain areas of irreversible damaged neural tissue. The idea that the left hemisphere is dominant for language processing while the right is specialized for spatial orientation is linked to the observation that lesions of cortical structures straddling the sylvian fissure in the left hemisphere typically induce aphasia, while right-sided damage of these structures typically causes spatial neglect. Beyond cortical structures, lesions restricted to the basal ganglia or thalamus have been reported to induce the same behavioural disorders (see recent overviews in Karnath et al., 2002; Radanovic and Scaff, 2003). However, for a precise understanding of the representation of brain functions, it might be helpful to analyse not only the irreversible damage but also the pattern of (structurally intact but) dysfunctional tissue in stroke patients. Advanced magnetic resonance imaging techniques now provide new, noninvasive methods to address this issue. Diffusion-weighted imaging (DWI) is sensitive to shifts of water between extracellular and intracellular spaces and, thus, can detect brain # The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: Structurally intact but dysfunctional cortical tissue in basal ganglia neglect regions undergoing irreversible cell death (the ‘ischaemic core region’) very early after stroke onset and shows high accuracy in predicting final infarct size (Ricci et al., 1999; Schaefer et al., 2002). For acute/subacute cerebral infarcts T2-weighted fluidattenuated inversion-recovery (FLAIR) images provide high sensitivity in detecting such regions (Brant-Zawadzki et al., 1996; Noguchi et al., 1997). On the other hand, perfusionweighted imaging (PWI) measures the amount and latency of blood flow reaching different regions of the brain. It allows identification of structurally intact but abnormally perfused brain tissue. In the acute stage of a stroke, regions with normal diffusion but abnormal perfusion, i.e. regions showing a PWI/DWI mismatch, often surround the irreversibly damaged ischaemic core region and are thought to represent the ‘ischaemic penumbra’ (Schlaug et al., 1999). Such regions not only are observed with ischaemic strokes but also can occur with intracerebral haemorrhage (Sills et al., 1996; Kidwell et al., 2001). Neurons in these ‘mismatch areas’ are undergoing potentially reversible cellular changes due to reduced availability of essential nutrition and oxygen. They represent zones that are receiving enough blood supply to remain structurally intact, but not enough to function normally. For example, local EEG signals disappear if blood flow is reduced from an average of 50 to 15–20 ml/100g/min (Hossmann, 1994). Moreover, the size of the tissue with perfusion abnormalities has been found to correlate with the general behavioural dysfunction measured by stroke scales (Barber et al., 1998; Tong et al., 1998; Beaulieu et al., 1999; NeumannHaefelin et al., 1999; Baird et al., 2000). It has also been shown that perfusion deficits in Wernicke’s area following subcortical stroke predict language dysfunction (Hillis et al., 2001). In order to explain behavioural defects after stroke, PWI thus seems to complement the information about irreversible damaged tissue deriving from MRI and CT. The present article focuses on the phenomenon of spatial neglect due to stroke centring on the right basal ganglia. Spatial neglect is a lateralized disorder of space-related behaviour in stroke patients that describes a characteristic failure to explore the side of space contralateral to the lesion, and to react or respond to stimuli or subjects located on this side (Karnath and Zihl, 2003). The patients typically show spontaneous deviation of the head and the eyes towards the ipsilesional side and orient towards that side when addressed from the front or the left (Fruhmann-Berger and Karnath, 2005). Within the basal ganglia, the right putamen and caudate nucleus were identified to be the crucial structures associated with spatial neglect (Karnath et al., 2002). First, metabolic, single photon emission computed tomography (SPECT) studies of patients with such infarcts revealed a decrease (...truncated)