Theta Burst Stimulation Over the Right Broca's Homologue Induces Improvement of Naming in Aphasic Patients

Improvements of language production in aphasic patients have been reported following repeated 1-Hz transcranial magnetic stimulation over the nondamaged right hemisphere. Most studies examined aphasic patients in the chronic phase. The effect of transcranial magnetic stimulation application in acute or subacute patients has not been systematically studied. We aimed to evaluate whether continuous theta burst stimulation, an inhibitory protocol with a shorter application time than the common 1-Hz protocol, is able to improve naming performance in aphasic patients in different poststroke phases.

Theta burst stimulation reduces disability during the activities of daily living in spatial neglect

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour.

Tumor architecture exerts no bias on nuclear grading in breast cancer diagnosis

We recently reported that nuclear grading in prostate cancer is subject to a strong confirmation bias induced by the tumor architecture. We now wondered whether a similar bias governs nuclear grading in breast carcinoma. An unannounced test was performed at a pathology conference. Pathologists were asked to grade nuclei in a PowerPoint presentation. Circular high power fields of 27 invasive ductal carcinomas were shown, superimposed over low power background images of either tubule-rich or tubule-poor carcinomas. We found (a) that diagnostic reproducibility of nuclear grades was poor to moderate (weighed kappa values between 0.07 and 0.54, 27 cases, 44 graders), but (b) that nuclear grades were not affected by the tumor architecture. We speculate that the categorized grading in breast cancer, separating tubule formation, nuclear pleomorphism, and mitotic figure counts in a combined three tier score, prevents the bias that architecture exerts on nuclear grades in less well-controlled situations.

What was I thinking? Eye-tracking experiments underscore the bias that architecture exerts on nuclear grading in prostate cancer

We previously reported that nuclear grade assignment of prostate carcinomas is subject to a cognitive bias induced by the tumor architecture. Here, we asked whether this bias is mediated by the non-conscious selection of nuclei that "match the expectation" induced by the inadvertent glance at the tumor architecture. 20 pathologists were asked to grade nuclei in high power fields of 20 prostate carcinomas displayed on a computer screen. Unknown to the pathologists, each carcinoma was shown twice, once before a background of a low grade, tubule-rich carcinoma and once before the background of a high grade, solid carcinoma. Eye tracking allowed to identify which nuclei the pathologists fixated during the 8 second projection period. For all 20 pathologists, nuclear grade assignment was significantly biased by tumor architecture. Pathologists tended to fixate on bigger, darker, and more irregular nuclei when those were projected before kigh grade, solid carcinomas than before low grade, tubule-rich carcinomas (and vice versa). However, the morphometric differences of the selected nuclei accounted for only 11% of the architecture-induced bias, suggesting that it can only to a small part be explained by the unconscious fixation on nuclei that "match the expectation". In conclusion, selection of « matching nuclei » represents an unconscious effort to vindicate the gravitation of nuclear grades towards the tumor architecture.

Unmasking the contribution of low-level features to the guidance of attention

The role of low-level stimulus-driven control in the guidance of overt visual attention has been difficult to establish because low- and high-level visual content are spatially correlated within natural visual stimuli. Here we show that impairment of parietal cortical areas, either permanently by a lesion or reversibly by repetitive transcranial magnetic stimulation (rTMS), leads to fixation of locations with higher values of low-level features as compared to control subjects or in a no-rTMS condition. Moreover, this unmasking of stimulus-driven control crucially depends on the intrahemispheric balance between top-down and bottom-up cortical areas. This result suggests that although in normal behavior high-level features might exert a strong influence, low-level features do contribute to guide visual selection during the exploration of complex natural stimuli.

Interhemispheric balance of overt attention: a theta burst stimulation study

Interhemispheric imbalance is discussed as a pathophysiological mechanism in visuospatial neglect. It is suggested that after a lesion of the right hemisphere the mutual transcallosal inhibition is impaired, resulting in an increased activity of the left hemisphere. We investigated the interhemispheric balance of attention in healthy subjects by using a free visual exploration task and by interfering with the neural activity of the posterior parietal cortex (PPC) of either hemisphere using an inhibitory transcranial magnetic stimulation routine with theta burst stimulation (TBS). Subjects explored colour photographs of real-life scenes presented on a computer screen under four conditions: (i) without TBS; (ii) after TBS over the right PPC; (iii) after TBS over the left PPC; and (iv) after TBS over the right PPC and, after the first half of the task, over the left PPC. Eye movements were measured, and distribution of mean cumulative fixation duration over screen halves was analyzed. TBS over the right PPC resulted in a significant rightward shift of mean cumulative fixation duration of approximately 30 min. The shift could be reversed when a subsequent train of TBS was applied over the left PPC. However, left PPC stimulation alone had no significant effect on visual exploration behaviour. The present study shows that the effect of TBS on the PPC depends on which hemisphere is stimulated and on the state of the contralateral homologue area. These findings are in accordance with the predictions of the interhemispheric rivalry model in neglect.

Linking physiology with behaviour: Functional specialisation of the visual field is reflected in gaze patterns during visual search

Based on neurophysiological findings and a grid to score binocular visual field function, two hypotheses concerning the spatial distribution of fixations during visual search were tested and confirmed in healthy participants and patients with homonymous visual field defects. Both groups showed significant biases of fixations and viewing time towards the centre of the screen and the upper screen half. Patients displayed a third bias towards the side of their field defect, which represents oculomotor compensation. Moreover, significant correlations between the extent of these three biases and search performance were found. Our findings suggest a new, more dynamic view of how functional specialisation of the visual field influences behaviour.

Neglect-like visual exploration behaviour after theta burst transcranial magnetic stimulation of the right posterior parietal cortex

The right posterior parietal cortex (PPC) is critically involved in visual exploration behaviour, and damage to this area may lead to neglect of the left hemispace. We investigated whether neglect-like visual exploration behaviour could be induced in healthy subjects using theta burst repetitive transcranial magnetic stimulation (rTMS). To this end, one continuous train of theta burst rTMS was applied over the right PPC in 12 healthy subjects prior to a visual exploration task where colour photographs of real-life scenes were presented on a computer screen. In a control experiment, stimulation was also applied over the vertex. Eye movements were measured, and the distribution of visual fixations in the left and right halves of the screen was analysed. In comparison to the performance of 28 control subjects without stimulation, theta burst rTMS over the right PPC, but not the vertex, significantly decreased cumulative fixation duration in the left screen-half and significantly increased cumulative fixation duration in the right screen-half for a time period of 30 min. These results suggest that theta burst rTMS is a reliable method of inducing transient neglect-like visual exploration behaviour.

One session of repeated parietal theta burst stimulation trains induces long-lasting improvement of visual neglect

BACKGROUND AND PURPOSE: Visual neglect is a frequent disability in stroke and adversely affects mobility, discharge destination, and length of hospital stay. It is assumed that its severity is enhanced by a released interhemispheric inhibition from the unaffected toward the affected hemisphere. Continuous theta burst transcranial magnetic stimulation (TBS) is a new inhibitory brain stimulation protocol which has the potential to induce behavioral effects outlasting stimulation. We aimed to test whether parietal TBS over the unaffected hemisphere can induce a long-lasting improvement of visual neglect by reducing the interhemispheric inhibition. METHODS: Eleven patients with left-sided visual neglect attributable to right hemispheric stroke were tested in a visual perception task. To evaluate the specificity of the TBS effect, 3 conditions were tested: 2 TBS trains over the left contralesional posterior parietal cortex, 2 trains of sham stimulation over the contralesional posterior parietal cortex, and a control condition without any intervention. To evaluate the lifetime of repeated trains of TBS in 1 session, 4 trains were applied over the contralesional posterior parietal cortex. RESULTS: Two TBS trains significantly increased the number of perceived left visual targets for up to 8 hours as compared to baseline. No significant improvement was found with sham stimulation or in the control condition without any intervention. The application of 4 TBS trains significantly increased the number of perceived left targets up to 32 hours. CONCLUSIONS: The new approach of repeating TBS at the same day may be promising for therapy of neglect.