Neglect is a possible consequence of right-hemisphere brain damage and is characterised by a dramatic failure to orient toward, explore and respond to stimuli presented on the contralesional side, even when these items appear in isolation or for sustained periods of time. For example, neglect patients often only talk to people on their right and fail to eat food from the left side of their plate. Interestingly, while neglect patients fail to respond to certain regions of space, primary sensory loss is not the main cause of neglect. In other words, neglect represents a failure to perceive despite intact sensory processing. In this lab we study the causal mechanisms and neural basis of this neuropsychological syndrome using functional MRI, TMS and behavioural studies in both neurological healthy subjects and neurological patients.
 

Extinction patients can detect a single stimulus at any spatial location. However, when two stimuli are presented simultaneously, subjects are impaired at perceiving the contralesional item. In other words, the contralesional stimulus is extinguished when an ipsilesional stimulus is present. Extinction has most commonly been associated with damage to the temporoparietal junction of the right hemisphere. Extinction is often considered to be the result of biased competitive interactions between the ipsilesional and contralesional stimuli and is most commonly seen as an exaggeration of the difficulty that normal subjects have while trying to attend to multiple targets simultaneously. In this lab we study both neurologically healthy subjects and neurological patients with the aid of methods like TMS, fMRI, lesion mapping and behavioural studies to resolve questions concerning the anatomy and the underlying mechanisms of extinction.

Our rich behavioural repertoire is based on the integration of spatial and temporal information about the environment and internal states of movement effectors. It enables us to react to environmental demands and challenges, actively explore and investigate our surroundings, and manipulate objects and tools for a specific purpose. Investigating neurological patients suffering from movement coordination disorders, like apraxia or optic ataxia, our work focuses on the system level of action control. We strive for functional neuroanatomical models and hypotheses that agree with the patients' behaviour thereby explaining the pathomechanism of the specific disorder on the one hand and verifying respective models of action control on the other hand. Acute and chronic neurological patients after stroke are examined with state-of-the-art kinematic tracking devices for eye, head, and hand movements. These investigations are complemented by behavioural experiments in healthy humans and functional neuroimaging.

-Himmelbach M, Karnath H-O (2005). Dorsal and ventral stream interaction: Contributions from optic ataxia. J Cogn Neurosci 17: 632-640.
-Goldenberg G, Hermsdörfer J, Glindemann R, Rorden C, Karnath H-O (2007). Pantomime of tool use depends on integrity of left inferior  frontal cortex. Cerebral Cortex 17: 2769-2776.

Despite the movements of eyes, head, and body, a healthy person perceives its environment as a constant visual and acoustical unit. Humans also show a remarkable ability to attend to and localise sounds. By means of functional MRI, we search for the neural correlates underlying these mechanisms. Likewise, in a soundproof room behavioral studies are carried out to clarify the mechanisms of auditory localisation in multisound environments. Our studies are carried out with healthy subjects as well as stroke patients.


-Zimmer U, Lewald J, Karnath H-O (2003). Disturbed sound lateralization in patients with spatial neglect. J Cog Neurosci 15: 683-693.
-Zimmer U, Lewald J, Erb M, Karnath H-O (2006). Processing of auditory spatial cues in human cortex: an fMRI study. Neuropsychologia  44: 454-461.  

Stroke patients may exhibit the peculiar behavior of actively pushing away from the non-hemiparetic side leading to lateral postural imbalance and a tendency to fall towards the paralyzed side. This phenomenon has been called the "Pusher Syndrome". We investigate the cognitive, visual, and vestibular contributions to understand the mechanism leading to contraversive pushing.


                        Schematic drawing of pusher patients' perceived postural vertical (SPV) with occluded eyes
                        (A) and while viewing their surroundings (B). The patient's SPV shows a marked ipsiversive
                        deviation from the earth-vertical with occluded eyes.

-Karnath H-O (2007). Pusher syndrome - a frequent but little-known disturbance of body orientation perception. J Neurol 254: 415-24.

Our ability to recognize objects from many viewpoints is remarkable. To identify objects regardless of position, scale or viewpoint, we must match them with mental representations of previously seen objects. Patients with brain damage may have normal object recognition skills but an impaired sense of object orientation. This has been taken as evidence that object recognition is processed independetly of our knowledge of object orientation. Studies in patients with brain damage and in normal subjects using functional MRI aim at clarifying these processes.

Human object-perception has been a major focus of perceptual investigation over the last decade. Besides psychophysical methods, electrophysiological methods and functional neuroimaging have provided a detailed map of areas located in the occipito-temporal cortex that are involved in object recognition. However, the perception of our environment not only requires the perception of individual objects, but also the integration of multiple objects to a global gestalt (e.g. the integration of individual trees giving rise to the coherent perception of a forest). Patients with brain-damage of the temporo-occipital cortex may show a deficit in global gestalt perception involving complex visual arrays that consist of multiple objects. This deficit has been termed simultanagnosia. The mechanisms underlying disturbed global gestalt perception remain largely unknown. We investigate such patients to reveal the parameters that play a critical role in object integration and further improve our understanding of the underlying mechanisms. In addition, functional neuroimaging might allow for the identification of the contributing cortical and subcortical structures.

-Clavagnier S, Fruhmann Berger M, Klockgether T, Moskau S, Karnath H-O (2006). Restricted ocular exploration does not seem to explain  simultanagnosia. Neuropsychologia 44: 2330-2336.
-Huberle E, Rupek P, Lappe M, Karnath H-O (2009). Perception of global gestalt by temporal integration in simultanagnosia. European  Journal of Neuroscience 29: 197-204.

Patients with anosognosia for hemiparesis typically are convinced that their limbs function normally although they have obvious motor defects after stroke. They may experience the paretic limbs as strange or as not belonging to them, or even may attribute ownership to another person. We evaluate such phenomena in stroke patients to elucidate the mechanisms leading to anosognosia, the brain structures typically involved when patients exhibit this behaviour, as well as its relation to unilateral spatial neglect.

-Karnath H-O, Baier B, Naegele T (2005). Awareness of the functioning of one’s own limbs mediated by the insular cortex?  Journal of  Neuroscience 25: 7134-7138.
-Baier B, Karnath H-O (2008). Tight link between our sense of limb ownership and self-awareness of actions. Stroke 39: 486-488.

The cerebellum is usually associated with motor control and learning. However, accumulating evidence suggests that it may also be involved in cognitive functions and affect. This assumption is supported both by patient and functional imaging studies. We investigate probable cognitive functions of the cerebellum with the help of language, visuo-spatial and executive tasks. Localisation of functions in the cerebellum is studied with the help of lesion mapping procedures. We use 3D-MR images to precisely localize the cerebellar lesion and associate its localisation and extent with probable cognitive deficits.


                       Individual lesions in patients with posterior inferior cerebellar (PICA) infarction (A), and superior
                       cerebellar (SCA) infarction (B) superimposed on horizontal MR sections of a healthy adult brain.


-Richter S, Schoch B, Kaiser O, Groetschel H, Hein-Kropp C, Maschke M, Dimitrova A, Gizewski E, Ziegler W, Karnath H-O, Timmann D  (2005). Children and adolescents with chronic cerebellar lesions show no clinically relevant signs of aphasia or neglect. Journal of  Neurophysiology 94: 4108-4120.
-Frank B, Schoch B, Richter S, Frings M, Karnath H-O, Timmann D (2007). Cerebellar lesion studies of cognitive function in children and  adolescents – limitations and negative findings. Cerebellum 6: 242-253.

Patients with pure alexia suffer from severe reading problems while other language-related skills such as speaking, listening comprehension, or writing are typically intact. One of the most characteristic clinical features of this acquired reading disorder is laborious letter-by-letter reading, which results in a disproportionate prolongation of reading times when the number of letters per word is increased. We investigate this disorder with a series of tasks that include systematic word-form manipulations and use eye movement recordings to analyse the reading behaviour of patients and healthy subjects.

Using diffusion-weighted (DWI), fluid-attenuated inversion-recovery (FLAIR) magnetic resonance imaging (MRI) as well as spiral computerized tomography (Spiral-CT) scans we identify the lesion location(s) typically associated with specific cognitive disorders. Statistical voxelwise lesion-behaviour mapping (VLBM) is used to determine relationships between behavioral measures/disorders and the location of brain injury, revealing the function of brain regions. Together with Prof. Chris Rorden, University of South Carolina, we improve and develop new VLBM approaches. Prof. Rorden also developed software to implement these procedures (MRIcron), made freely available to the scientific community. Statistical lesion mapping can also correlate the effectiveness of neurosurgery with the location of brain resection, identifying optimal surgical targets. Moreover, brain regions identified via VLBM might serve as starting points for research with healthy subjects using fMRT and/or TMS.


-Rorden C, Karnath H-O (2004). Using human brain lesions to infer function: a relic from a past era in the fMRI age? Nature Reviews  Neuroscience 5: 813-819.
-Rorden C, Karnath H-O, Bonilha L (2007). Improving lesion-symptom mapping. Journal of Cognitive Neuroscience 19: 1081-1088.

In patients with stroke lesions, we use PWI to identify the abnormally perfused brain area(s) that receive enough blood supply to remain structurally intact, but not enough to function normally. In order to recognize these common areas in groups of patients, we analyse the increase of time-to-peak (or TTP) lesion-inducted delays 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.


-Karnath H-O, Zopf R, Johannsen L, Fruhmann Berger M, Nagele T, Klose U (2005). Normalized perfusion MRI to identify common areas of  dysfunction: patients with basal ganglia neglect. Brain 128: 2462-9.

In healthy subjects a temporary brain lesion can be induced by transcranial magnetic stimulation (TMS). A magnetic field induces electrical activity in the cortex and disorganizes neural activity and thus the normal neural processes for a very short time. We use this so-called „virtual lesion approach" to establish a more detailed view of neuronal anatomy and the anatomical functions of cortical regions identified in previous fMRI and/or lesion mapping studies. The ability of TMS to elicit a very focal and transient disruption of ongoing neural activation allows us the causal investigation of brain function at a high spatial and temporal resolution.

We compare the functional neuroanatomy of attentional orienting between human and non-human primates. We aim to bridge the gap between the vast amount of neurophysiological data in monkeys on the one and the exponentially growing functional imaging data in humans on the other side. The long-range goal is to understand the neural mechanisms of selective visual attention at the level of the individual neuron and the cortical circuit and to relate these to perception and conscious awareness. We seek to understand this selection process using a combination of fMRI and neurophysiology.

We use sensors in a pulsed magnetic field to monitor movements of head, body and limbs. Multiple sensors can be tracked in 3D with a temporal resolution of 10ms. The sensors are connected to a multi-purpose measurement plattform. This allows us to integrate the measurement of spatial position with eye movements and other real-time data. A video tracking system based on reflective markers is used to study limb movements. By attaching small adhesive reflectors to points of interest, we can measure movements in space, uninihibited by cables.

We use video- and coil based tracking systems that allow us to monitor eye movements in subjects with good temporal and spatial resolution. Analyzing the direction of gaze is used to infer attentional processes and patterns, both common and pathological. Further, eye and head tracking is used as a means of documenting fixation.

Based on neuropsychological findings and hypotheses we use BOLD fMRI to localise neuroanatomical modules and networks contributing to intact cognitive and sensorimotor functions. Our research projects are conducted using 3 Tesla and 1.5 Tesla Siemens scanners located at the university hospital Tuebingen. The close vicinity to the Center of Neurology permits the safe inclusion of neurological patients in neuroimaging experiments. The equipment comprises diverse setups for stimulus presentation and response collection including a state-of-the-art eye SMI eye tracker system and custom build MR-compatible video cameras for motion tracking. Data analysis is primarily conducted with the SPM package developed and distributed by the Wellcome Trust Centre for Neuroimaging and BrainVoyager.