The prognosis of allocentric and egocentric neglect : evidence from clinical scans

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome

The relation of object naming and other visual speech production tasks: A large scale voxel-based morphometric study.

We report a lesion–symptom mapping analysis of visual speech production deficits in a large group (280) of stroke patients at the sub-acute stage (<120 days post-stroke). Performance on object naming was evaluated alongside three other tests of visual speech production, namely sentence production to a picture, sentence reading and nonword reading. A principal component analysis was performed on all these tests' scores and revealed a ‘shared’ component that loaded across all the visual speech production tasks and a ‘unique’ component that isolated object naming from the other three tasks. Regions for the shared component were observed in the left fronto-temporal cortices, fusiform gyrus and bilateral visual cortices. Lesions in these regions linked to both poor object naming and impairment in general visual–speech production. On the other hand, the unique naming component was potentially associated with the bilateral anterior temporal poles, hippocampus and cerebellar areas. This is in line with the models proposing that object naming relies on a left-lateralised language dominant system that interacts with a bilateral anterior temporal network. Neuropsychological deficits in object naming can reflect both the increased demands specific to the task and the more general difficulties in language processing

Neural Correlates of Spatial Attention and Target Detection in a Multi-Target Environment

Our ability to attend and respond in a multi-target environment is an essential and distinct human skill, as is dramatically demonstrated in stroke patients suffering from extinction. We performed an fMRI study to determine the neural anatomy associated with attending and responding to simultaneously presented targets. In healthy subjects, we tested the hypothesis that the right intraparietal sulcus (IPS) is associated both with the top-down direction of attention to multiple target locations and the bottom-up detection of multiple targets, whereas the temporo-parietal junction (TPJ) is predominantly associated with the bottom-up detection of multiple targets. We used a cued target detection task with a high proportion of catch trials to separately estimate top-down cue-related and bottom-up target-related neural activity. Both cues and targets could be presented unilaterally or bilaterally. We found no evidence of target-related neural activation specific to bilateral situations in the TPJ, but observed both cue-related and target-related neural activation specific to bilateral situations in the right IPS and target-related neural activity specific to bilateral situations in the right inferior frontal gyrus (IFG). We conclude that the IPS and the IFG of the right hemisphere underlie our ability to attend and respond in a multi-target environment.This work was supported by the fortüne-Programm of the Medical Faculty of the University of Tübingen (2003-0-0) and the Deutsche Forschungsgemeinschaft (KA 1258/10-1 and HA 5839/3-1)

Anatomical correlates for visual extinction - a fMRI study

Hintergrund: Gesunde Erwachsene können nur eine begrenzte Menge an Informationen verarbeiten. Bei Patienten mit visueller Extinktion, einer Erkrankung die nach rechtshemisphärischen Schlaganfällen auftreten kann, ist diese natürliche Limitierung gesteigert und resultiert darin, dass Patienten bei Präsentation beidseitiger Stimuli den kontraläsionellen Reiz auslöschen. Ziel dieser Studie war es, Bereiche des Gehirns zu identifizieren, die für die Verarbeitung multipler visueller Reize verantwortlich sind. Unter Berücksichtigung der “top-down-” und bottom-up”-Aufmerksamkeitsmodelle und der Ergebnisse von TMS- (transcranielle Magnetstimulation) und fMRT- (funktionelle Kernspintomographie) Studien, wurde die Hypothese gestellt, dass dem rechtshemisphärischen intraparietalen Sulcus (IPS) eine wichtige Rolle bei der Aufmerksamkeitslenkung auf bilaterale Reize und der temporoparietale junction (TPJ) eine wichtige Rolle bei der Erkennung dieser bilateralen Reize zukommt. Methoden: 24 Probanden nahmen an einem fMRT-Experiment teil welches in fünf Einheiten mit je 400 Versuchsdurchgängen gegliedert war. Ein Versuchsdurchgang bestand aus einem neutralen oder informativen Hinweisreiz (HR) welcher in Richtung eines rechtsseitigen, linksseitigen oder beidseitigen Zielkastens wies. Nach einem variablen Zeitintervall erschienen im jeweils angekündigtem Zielkasten ein Zielreiz (ZR) oder ein Ablenkreiz (AR). Augenbewegungen und Reaktionszeiten wurden aufgezeichnet. Statistische Auswertung der Bildgebungsdaten und die Erstellung der nachfolgend genannten Kontraste erfolgte mittels SPM8 (Statistical parametric mapping). Kontrastmodelle waren: a) unilateraler HR links vs. bilateraler HR, b) unilateraler HR rechts vs. bilateraler HR, c) unilateraler ZR links vs. bilateraler ZR, d) unilateraler HR rechts vs. bilateraler HR. Durch Überlappung der einzelnen Kontraste (sog. Konjunktionsbilder) wurden diejenigen Voxel sichtbar, welche stärker auf Präsentation bilateraler HRs und ZRs reagiert haben als auf die jeweiligen unilateralen Reize. Ergebnisse: In 97,6 ± 2,5% der Versuchszeit fixierten die Probanden einen zentralen Fixationspunkt. Reaktionszeiten (RTs) für ZR die einem informativen HR folgten, waren signifikant schneller. Die Detektion bilateraler ZR resultierte in längeren RTs als die Detektion einzelner ZR. Das Konjunktionsbild der HR-Bedingung zeigte eine Überlappung im rechtshemisphärischem inferiorem frontalen Gyrus (IFG) und das der ZR-Bedingung im rechtshemisphärischem IPS und Gyrus cinguli (CG)/ superiorem frontalen Gyrus (SFG). Diskussion: Die schnelleren RTs für erwartete ZR deuten darauf hin, dass die Probanden aufmerksam waren und die HR als Informationsquelle nutzten. Die langsameren RTs bei der Detektion bilateraler ZR könnten durch eine größere kognitive Herausforderung bedingt sein. Die Bildgebungsdaten für die Bedingungen HR und ZR zeigten Aktivierungen in den okzipitalen Regionen korrespondierend zu den bekannten Arealen der Sehbahn nach rechts- und linksseitiger Stimulation und resultierend aus einer durch den HR modulierten Aktivierung in den entsprechenden visuellen Cortices. Die fMRT Ergebnisse der Konjunktionsbilder [bilateral vs unilateraler HR links + bilateraler vs unilateraler HR rechts] und [bilateraler vs ZR links + bilateraler vs ZR rechts] zeigten insgesamt mehr Aktivierungen in der rechten Gehirnhemisphäre. Diese Ergebnisse stimmen mit bekannten Läsionsstudien überein und unterstützen die Annahme einer rechtshemisphärischen Dominanz für räumliche Aufmerksamkeit. Bilaterale HRs erzeugten Aktivierungen im rechtshemisphärischen IFG. Als Teil des ventroparietalen Netzwerkes ist war diese Aktivierung unerwartet, jedoch in Studien mit ähnlichem Versuchsaufbau bereits vorbeschrieben. Anders als erwartet kam es im Bereich des IPS nur in der ZR-Bedingung zu Aktivierungen und nicht in der HR-Bedingung. Diese Studie ist die erste Bildgebungsstudie welche IPS-Aktivierungen während dem Erkennen beidseitiger ZR zeigt. Diese Ergebnisse stehen im Einklang mit Ergebnissen von früheren TMS-Studien. Die Rolle des CG/SFG beim Erkennen beidseitiger ZR ist bis dato unklar und bedarf weiteren Untersuchungen. Bislang waren diese Hirnareale v.a. mit psychiatrischen Funktionsstörungen aber auch mit zielorientiertem Verhalten assoziiert. Schlussfolgerung Aktivierungen im IPS in der HR-Bedingung und TPJ-Aktivierung in der ZR-Bedingung konnten nicht nachgewiesen werden. Stattdessen konnten Aktivierungen im IPS in der ZR-Bedingung demonstriert werden, sodass dennoch von einer wichtigen Rolle des IPS beim Erkennen multipler Reize auszugehen ist. Unsere Ergebnisse weisen daraufhin, dass der rechtshemisphärische IFG eine wichtige Aufgabe bei der Lenkung von Aufmerksamkeit auf beidseitige und erwartete ZR übernimmt. Die fehlende TPJ-Aktivierung ist möglicherweise durch den Versuchsaufbau erklärt

Unravelling the high-dimensional structure of spatial neglect and visuospatial attention: A multivariate approach to lesion-behaviour mapping

One of the most studied and elaborated neurological disorders after stroke is probably spatial neglect, a disorder of spatial exploration, attention and awareness occurring in about two third of all right hemispheric stroke patients. A characteristic symptom these patients show is a failure to orient or respond to information on the contralesional side of space including a general orientation to the ipsilesional side. It is still not possible to come to a common consensus regarding this syndrome on theoretical, anatomical and behavioural aspects. The investigation of the anatomical substrates of spatial neglect, however, offers chances to shed light on crucial pathophysiological processes and inform theoretical models. Therefore, a complete research field dedicated several decades of research to the question where in the brain the syndrome of spatial neglect might have its´ pathogenesis and how this information can help us to understand cognitive processes of normal spatial exploration and attentional processing. A method which largely contributed to this field is called lesion-behaviour mapping by drawing statistical inference about the functional brain architecture from focal brain damage. Following the development within the last five to ten years, a new era of computerised lesion-behaviour mapping techniques became widely available, allowing to reiterate and challenge previous findings and to account for the high-dimensional information present in brain lesions. In my thesis I employed these new techniques to unravel the anatomical substrates of the syndrome of spatial neglect and related spatial attentional deficits. I want to show that these methods can be deployed to make valuable contributions to the understanding of the pathophysiology of the syndrome. In my first empirical work, the presence of a large right-hemispheric network related to the behavioural severity of spatial neglect can be confirmed, closing longstanding controversies. It shows that multivariate machine-learning based lesion-behaviour mapping techniques are particularly suited to detect critical brain areas and to evaluate the predictive performance of underlying statistical models. In the second and third empirical work, I complemented these primary findings by applying the same statistical methodology to parameters of remote disconnection and to different diagnostic tools in the assessment of spatial neglect. These works show crucial areas and anatomical hubs severely disconnected to other areas of the brain and contributing to the development of lateralised deficits in spatial neglect patients. Finally, with the last empirical work, contributions to controversial views concerning the anatomical substrates of the extinction phenomenon, a further spatial attentional deficit, were made. By evaluating lesion-behaviour relationships in spatial neglect, as it was done in the present thesis, it will become possible to inform clinical staff how to direct patients to more effective management and treatment schedules, essential for rehabilitation, while spatial neglect generally is considered as a negative prognosis factor for stroke recovery

The role of temporo-parietal cortex in subcortical visual extinction

Visual extinction is an intriguing defect of awareness in stroke patients, referring to the unsuccessful perception of contralesional events under conditions of competition. Previous studies have investigated the cortical and subcortical brain structures that, when damaged or inactivated, provoke visual extinction. The present experiment asked how lesions of subcortical structures may contribute to the appearance of visual extinction. We investigated whether lesions centering on right basal ganglia may induce dysfunction in distant, structurally intact cortical structures. Normalized perfusion-weighted MRI was used to identify structurally intact but abnormally perfused brain tissue, that is, zones that are receiving enough blood supply to remain structurally intact but not enough to function normally. We compared patients with right basal ganglia lesions showing versus not showing visual extinction. In the extinction patients, the contrast revealed cortical malperfusion that clustered around the right TPJ. It seems as if malfunction of this area is a critical aspect in visual extinction not only after cortical lesion but also in the case of subcortical basal ganglia damage. Our results support the idea that a normally functioning TPJ area plays a decisive role for the attentional network involved in detecting of visual stimuli under conditions of competition

The neural basis of object perception: dissociating action and semantic processing

This thesis has evaluated the roles of dorsal and ventral processing streams in recognition and use of objects. Four main empirical studies are presented. First, to investigate how the cortical brain processes semantic and action knowledge in different object-related tasks, I examined structural data from stroke patients (Chapter 2) and functional data from healthy individuals (Chapter 3) using a voxel-wise statistical analysis method. Using data of different modalities (structural CT, fMRI) from different sources (patients’ lesions; healthy subjects’ functional activity) handled with a systematic analysis approach, I attempted to find convergent evidence to support the dissociation of semantic and action processing. Second, I also looked into the potential differentiation within the mechanisms underlying object-related action (Chapter 4) and object naming (Chapter 5) separately. Overall, comparable findings were provided from the voxel-based morphometric analysis of patients’ lesion data and the fMRI study with healthy participants: an association was observed between ventral brain structures and the retrieval of semantic knowledge/object recognition while a dorsal fronto-parietal-occipital network was found to support the processing of action knowledge/object-oriented action. Specific dissociations were also observed within the representations for object-oriented actions as well as the mechanisms underlying naming of objects