Hans-Otto Karnath

Improving Lesion-Symptom Mapping

Measures of brain activation (e.g., changes in scalp electrical potentials) have become the most popular method for inferring brain function. However, examining brain disruption (e.g., examining behavior after brain injury) can complement activation studies. Activation techniques identify regions involved with a task, whereas disruption techniques are able to discover which regions are crucial for a task. Voxel-based lesion mapping can be used to determine relationships between behavioral measures and the location of brain injury, revealing the function of brain regions. Lesion mapping can also correlate the effectiveness of neurosurgery with the location of brain resection, identifying optimal surgical targets. Traditionally, voxel-based lesion mapping has employed the chi-square test when the clinical measure is binomial and the Students t test when measures are continuous. Here we suggest that the Liebermeister approach for binomial data is more sensitive than the chi-square test. We also suggest that a test described by Brunner and Munzel is more appropriate than the t test for nonbinomial data because clinical and neuropsychological data often violate the assumptions of the t test. We test our hypotheses comparing statistical tests using both simulated data and data obtained from a sample of stroke patients with disturbed spatial perception. We also developed software to implement these tests (MRIcron), made freely available to the scientific community.

Spatial awareness is a function of the temporal not the posterior parietal lobe

Our current understanding of spatial behaviour and parietal lobe function is largely based on the belief that spatial neglect in humans (a lack of awareness of space on the side of the body contralateral to a brain injury) is typically associated with lesions of the posterior parietal lobe. However, in monkeys, this disorder is observed after lesions of the superior temporal cortex, a puzzling discrepancy between the species. Here we show that, contrary to the widely accepted view, the superior temporal cortex is the neural substrate of spatial neglect in humans, as it is in monkeys. Unlike the monkey brain, spatial awareness in humans is a function largely confined to the right superior temporal cortex, a location topographically reminiscent of that for language on the left. Hence, the decisive phylogenetic transition from monkey to human brain seems to be a restriction of a formerly bilateral function to the right side, rather than a shift from the temporal to the parietal lobe. One may speculate that this lateralization of spatial awareness parallels the emergence of an elaborate representation for language on the left side.

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.

Parietal lobe contributions to orientation in 3D space

An overview of current thinking in parietal lobe functions. The text is divided into five sections dealing with the areas of functional anatomy and specific contributions of the parietal lobes to eye movements; reaching and grasping; attention and perception; and the representation of space. It includes recent findings that emphasize their general implications for an understanding of the role of parietal lobe processing. The book aims to unite neurophysiological and neuropsychological approaches. It reviews work based on monkeys and on the study of patients with parietal lobe lesions. The interrelationship of the two is discussed.

Awareness of the Functioning of One's Own Limbs Mediated by the Insular Cortex?

Normally, we are aware of the current functions of our arms and legs. However, this self-evident status may change dramatically after brain damage. Some patients with “anosognosia” typically are convinced that their limbs function normally, although they have obvious motor defects after stroke. Such patients may experience their own paretic limbs as strange or as not belonging to them and may even attribute ownership to another person and try to push their paralyzed limb out of bed. These odd beliefs have been attributed to disturbances somewhere in the right hemisphere. Here, we use lesion mapping in 27 stroke patients to show that the right posterior insula is commonly damaged in patients with anosognosia for hemiplegia/hemiparesis but is significantly less involved in hemiplegic/hemiparetic patients without anosognosia. The function of the posterior insular cortex has been controversially discussed. Recent neuroimaging results in healthy subjects revealed specific involvement of this area in the subjects feeling of being versus not being involved in a movement. Our finding corresponds with this observation and suggests that the insular cortex is integral to self-awareness and to ones beliefs about the functioning of body parts.

New insights into the functions of the superior temporal cortex

One of the mysteries of the brain is the role of superior temporal cortex. Recent data have shed new light on the function of this area, supporting the idea that the rostral part of the superior temporal cortex acts as an interface between the dorsal and ventral streams of visual input processing to allow the exploration of both object-related and space-related information. The superior temporal cortex is also involved in processing species-specific vocalizations. It seems that, during evolution, the formerly bilateral functions of the superior temporal cortex have been segregated in the human brain between the left hemisphere, which subserves language, and the right hemisphere, which mediates spatial awareness and exploration.

How to Assess Spatial Neglect - Line Bisection or Cancellation Tasks?

Spatial neglect is usually assessed using cancellation tests or line bisection. A recent comparison of these tests has revealed a double dissociation, in which one neglect patient was impaired in line bisection but not in star cancellation whereas another showed the reverse deficit. This dissociation has prompted the question whether neglect is still a meaningful theoretical entity. We compared line bisection and cancellation tasks regarding their accuracy in detecting spatial neglect. We tested 35 patients with well-defined spatial neglect using a line bisection task and four different cancellation tasks. The line bisection test missed 40% of our neglect patients. Far superior were the letter cancellation and bells tests, each of which missed only 6% of the cases. A deviation in line bisection is not fundamentally related to spatial neglect, but may also arise from other causes (e.g., hemianopia, or which hand is used), and therefore, should be treated with caution in clinical diagnosis. Cancellation tests, such as the bells test and letter cancellation, are more helpful tools to detect spatial neglect.

Age-specific CT and MRI templates for spatial normalization

Spatial normalization reshapes an individuals brain to match the shape and size of a template image. This is a crucial step required for group-level statistical analyses. The most popular standard templates are derived from MRI scans of young adults. We introduce specialized templates that allow normalization algorithms to be applied to stroke-aged populations. First, we developed a CT template: while this is the dominant modality for many clinical situations, there are no modern CT templates and popular algorithms fail to successfully normalize CT scans. Importantly, our template was based on healthy individuals with ages similar to what is commonly seen in stroke (mean 65 years old). This template allows studies where only CT scans are available. Second, we derived a MRI template that approximately matches the shape of our CT template as well as processing steps that aid the normalization of scans from older individuals (including lesion masking and the ability to generate high quality cortical renderings despite brain injury). The benefit of this strategy is that the resulting templates can be used in studies where mixed modalities are present. We have integrated these templates and processing algorithms into a simple SPM toolbox (http://www.mricro.com/clinical-toolbox/spm8-scripts).

The origin of contraversive pushing: Evidence for a second graviceptive system in humans

Background: Stroke patients may exhibit the peculiar behavior of actively pushing away from the nonhemiparetic side, leading to lateral postural imbalance and a tendency to fall toward the paralyzed side. This phenomenon has been called the “pusher syndrome.” Objective: The current study analyzes the mechanism leading to contraversive pushing. Methods: The subjective postural vertical (SPV) and subjective visual vertical (SVV) were determined in five consecutively admitted patients with severe contraversive pushing and in controls. Whereas adjustment of the SPV reflects the perceived upright orientation of the body, the SVV provides a sensitive and direction-specific measurement of peripheral and central vestibular dysfunction. Results: The deficit leading to contraversive pushing is an altered perception of the body’s orientation in relation to gravity. Pusher patients experience their body as oriented “upright” when it is tilted 18° to the nonhemiparetic, ipsilesional side. In contrast, perception of the SVV was undisturbed. Conclusions: A separate pathway seems to be present in humans for sensing the orientation of gravity apart from the one for orientation perception of the visual world. This second graviceptive system decisively contributes to humans’ control of upright body posture. Contraversive pushing occurring after stroke lesions may represent the behavioral correlate of a disturbed neural representation of this system.

Neck muscle vibration induces lasting recovery in spatial neglect

Objectives: To evaluate whether neck muscle vibration is an effective technique for neglect rehabilitation, with lasting beneficial effects. Methods: The effects of differential treatment of visual exploration training alone or in combination with neck muscle vibration were evaluated in a crossover study of two matched groups of 10 patients suffering from left sided neglect. Each group received a sequence of 15 consecutive sessions of exploration training and combined treatment. The effects of treatment were assessed with respect to different aspects of the neglect disorder such as impaired perception of the egocentric midline, exploration deficits in visual and tactile modes, and visual size distortion. The transfer of treatment effects to activities of daily living was examined by a reading test and a questionnaire of neglect related everyday problems. All variables were measured six times: three baseline measurements, two post-treatment measurements, and one follow up after two months. Results: The results showed superior effects of combination treatment. A specific and lasting reduction in the symptoms of neglect was achieved in the visual mode, which transferred to the tactile mode with a concomitant improvement in activities of daily living. The improvement was evident two months after the completion of treatment. In contrast, isolated exploration training resulted in only minor therapeutic benefits in visual exploration without any significant transfer effects to other tasks. Conclusions: Neck muscle vibration is a decisive factor in the rehabilitation of spatial neglect and induces lasting recovery when given as a supplement to conventional exploration training.