Thalamocortical disconnection involved in pusher syndrome.

The presence of both isolated thalamic and isolated cortical lesions have been reported in the context of pusher syndrome-a disorder characterized by a disturbed perception of one's own upright body posture, following unilateral left- or right-sided stroke. In recent times, indirect quantification of functional and structural disconnection increases the knowledge derived from focal brain lesions by inferring subsequent brain network damage from the respective lesion. We applied both measures to a sample of 124 stroke patients to investigate brain disconnection in pusher syndrome. Our results suggest a hub-like function of the posterior and lateral portions of the thalamus in the perception of one's own postural upright. Lesion network symptom mapping investigating functional disconnection indicated cortical diaschisis in cerebellar, frontal, parietal and temporal areas in patients with thalamic lesions suffering from pusher syndrome, but there was no evidence for functional diaschisis in pusher patients with cortical stroke and no evidence for the convergence of thalamic and cortical lesions onto a common functional network. Structural disconnection mapping identified posterior thalamic disconnection to temporal, pre-, post- and paracentral regions. Fibre tracking between the thalamic and cortical pusher lesion hotspots indicated that in cortical lesions of patients with pusher syndrome, it is disconnectivity to the posterior thalamus caused by accompanying white matter damage, rather than the direct cortical lesions themselves, that lead to the emergence of pusher syndrome. Our analyses thus offer the first evidence for a direct thalamo-cortical (or cortico-thalamic) interconnection and, more importantly, shed light on the location of the respective thalamo-cortical disconnections. Pusher syndrome seems to be a consequence of direct damage or of disconnection of the posterior thalamus.

The effect of brain lesions on sound localization in complex acoustic environments.

Localizing sound sources of interest in cluttered acoustic environments--as in the 'cocktail-party' situation--is one of the most demanding challenges to the human auditory system in everyday life. In this study, stroke patients' ability to localize acoustic targets in a single-source and in a multi-source setup in the free sound field were directly compared. Subsequent voxel-based lesion-behaviour mapping analyses were computed to uncover the brain areas associated with a deficit in localization in the presence of multiple distracter sound sources rather than localization of individually presented sound sources. Analyses revealed a fundamental role of the right planum temporale in this task. The results from the left hemisphere were less straightforward, but suggested an involvement of inferior frontal and pre- and postcentral areas. These areas appear to be particularly involved in the spectrotemporal analyses crucial for effective segregation of multiple sound streams from various locations, beyond the currently known network for localization of isolated sound sources in otherwise silent surroundings.

Perfusion imaging in Pusher syndrome to investigate the neural substrates involved in controlling upright body position.

Brain damage may induce a dysfunction of upright body position termed "pusher syndrome". Patients with such disorder suffer from an alteration of their sense of body verticality. They experience their body as oriented upright when actually tilted nearly 20 degrees to the ipsilesional side. Pusher syndrome typically is associated with posterior thalamic stroke; less frequently with extra-thalamic lesions. This argued for a fundamental role of these structures in our control of upright body posture. Here we investigated whether such patients may show additional functional or metabolic abnormalities outside the areas of brain lesion. We investigated 19 stroke patients with thalamic or with extra-thalamic lesions showing versus not showing misperception of body orientation. We measured fluid-attenuated inversion-recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), and perfusion-weighted imaging (PWI). This allowed us to determine the structural damage as well as to identify the malperfused but structural intact tissue. Pusher patients with thalamic lesions did not show dysfunctional brain areas in addition to the ones found to be structurally damaged. In the pusher patients with extra-thalamic lesions, the thalamus was neither structurally damaged nor malperfused. Rather, these patients showed small regions of abnormal perfusion in the structurally intact inferior frontal gyrus, middle temporal gyrus, inferior parietal lobule, and parietal white matter. The results indicate that these extra-thalamic brain areas contribute to the network controlling upright body posture. The data also suggest that damage of the neural tissue in the posterior thalamus itself rather than additional malperfusion in distant cortical areas is associated with pusher syndrome. Hence, it seems as if the normal functioning of both extra-thalamic as well as posterior thalamic structures is integral to perceiving gravity and controlling upright body orientation in humans.

"Pusher syndrome" following cortical lesions that spare the thalamus.

Stroke patients with "pusher syndrome" show severe misperception of their own upright body orientation although visual-vestibular processing is almost intact. This dissociation argues for a second graviceptive system in humans for the perception of body orientation. Recent studies revealed that the posterior thalamus is an important part of this system. The present investigation aimed to study the cortical representation of this system beyond the thalamus. We evaluated 45 acute patients with and without contraversive pushing following left-or right-sided cortical lesions sparing the thalamus. In both hemispheres, the simple lesion overlap associated with contraversive pushing typically centered on the insular cortex and parts of the postcentral gyrus. The comparison between pusher patients and controls who were matched with respect to age, lesion size, and the frequency of spatial neglect, aphasia and visual field defects revealed only very small regions that were specific for the pusher patients with cortical damage sparing the thalamus. Obviously, the cortical structures representing our control of upright body orientation are in close anatomical proximity to those areas that induce aphasia in the left hemisphere and spatial neglect in the right hemisphere when lesioned. We conclude that in addition to the subcortical area previously identified in the posterior thalamus, parts of the insula and postcentral gyrus appear to contribute at cortical level to the processing of the afferent signals mediating the graviceptive information about upright body orientation.

Processing of auditory spatial cues in human cortex: an fMRI study.

The issue of where in the human cortex coding of sound location is represented still is a matter of debate. It is unclear whether there are cortical areas that are specifically activated depending on the location of sound. Are identical or distinct cortical areas in one hemisphere involved in processing of sounds from the left and right? Also, the possibility has not been investigated so far that distinct areas have a preference for processing of central and eccentric sound locations. The present study focussed on these issues by using functional magnetic resonance imaging (fMRI). Activations evoked by left, right and central sounds were analysed separately, and contrasts were computed between these conditions. We did not find areas, which were involved in the processing of exclusively left, right or central sound positions. Large overlapping areas rather were observed for the three sound stimuli, located in the temporal, parietal and frontal cortices of both hemispheres. This result argues for the idea of a widely distributed bilateral network accessing an internal representation of the body to encode stimulus position in relation to the body median plane. However, two areas (right BA 40 and left BA 37) also were found to have preferences for sound position. In particular, BA 40 turned out to be significantly more activated by processing central positions, compared to eccentric stimuli. In line with previous findings on visual perception, the latter observation supports the assumption that the right inferior parietal cortex may be preferentially involved in the perception of central stimulus positions in relation to the body.

Is there a role of visual cortex in spatial hearing?

The integration of auditory and visual spatial information is an important prerequisite for accurate orientation in the environment. However, while visual spatial information is based on retinal coordinates, the auditory system receives information on sound location in relation to the head. Thus, any deviation of the eyes from a central position results in a divergence between the retinal visual and the head-centred auditory coordinates. It has been suggested that this divergence is compensated for by a neural coordinate transformation, using a signal of eye-in-head position. Using functional magnetic resonance imaging, we investigated which cortical areas of the human brain participate in such auditory-visual coordinate transformations. Sounds were produced with different interaural level differences, leading to left, right or central intracranial percepts, while subjects directed their gaze to visual targets presented to the left, to the right or straight ahead. When gaze was to the left or right, we found the primary visual cortex (V1/V2) activated in both hemispheres. The occipital activation did not occur with sound lateralization per se, but was found exclusively in combination with eccentric eye positions. This result suggests a relation of neural processing in the visual cortex and the transformation of auditory spatial coordinates responsible for maintaining the perceptual alignment of audition and vision with changes in gaze direction.

Impaired perception of temporal order in auditory extinction.

It has been proposed that patients with extinction show a chronic bias of spatial attention towards the ipsilesional side. In this case, the law of 'prior entry' predicts that ipsilesional events should be perceived earlier than physically synchronous contralesional stimuli. In line with this prediction, previous studies have revealed substantial delays of awareness for contralesional visual and tactile events in patients with visual and with tactile extinction. The present study provides evidence that a 'prior entry' bias also occurs in the auditory modality. Patients with auditory extinction perceived two acoustic events (one presented to the left ear, the other to the right ear) as being 'simultaneous' when the contralesional sound was leading by 270 ms. The magnitude of this asynchrony was quite similar to that measured previously in the visual modality. Thus, the pathological delay of awareness for contralesional events may be independent of the sensory modality of the stimuli.