Transcorneal Electrical Stimulation for the Treatment of Retinitis Pigmentosa: A Multicenter Safety Study of the OkuStim® System (TESOLA-Study).

BACKGROUND: Transcorneal electrical stimulation (TES) has been suggested as a possible treatment for retinitis pigmentosa (RP). OBJECTIVE: To expand the safety assessment of repeated applications of an electrical current from a DTL-like electrode in patients with RP. METHODS: This single-arm open label interventional safety trial included a total of 105 RP patients from 11 European centers, who received weekly TES for 6 months on 1 eye followed by observation for another 6 months without stimulation. The primary outcome measure was safety, indicated by the frequency and severity of adverse events. Secondary measures included intraocular pressure and central retinal thickness. Visual field and visual acuity were examined using the methods available at each site. RESULTS: Dry eye sensation was the most common adverse event recorded (37.5%). Serious adverse events secondary to TES were not observed. Most adverse events were mild and all resolved without sequelae. The secondary outcome measures revealed no significant or clinically relevant changes. CONCLUSION: The present results confirm the excellent safety profile of TES. Transient dry eye symptoms were the most common adverse event.

Testing the dual-pathway model for auditory processing in human cortex.

Analogous to the visual system, auditory information has been proposed to be processed in two largely segregated streams: an anteroventral ("what") pathway mainly subserving sound identification and a posterodorsal ("where") stream mainly subserving sound localization. Despite the popularity of this assumption, the degree of separation of spatial and non-spatial auditory information processing in cortex is still under discussion. In the present study, a statistical approach was implemented to investigate potential behavioral dissociations for spatial and non-spatial auditory processing in stroke patients, and voxel-wise lesion analyses were used to uncover their neural correlates. The results generally provided support for anatomically and functionally segregated auditory networks. However, some degree of anatomo-functional overlap between "what" and "where" aspects of processing was found in the superior pars opercularis of right inferior frontal gyrus (Brodmann area 44), suggesting the potential existence of a shared target area of both auditory streams in this region. Moreover, beyond the typically defined posterodorsal stream (i.e., posterior superior temporal gyrus, inferior parietal lobule, and superior frontal sulcus), occipital lesions were found to be associated with sound localization deficits. These results, indicating anatomically and functionally complex cortical networks for spatial and non-spatial auditory processing, are roughly consistent with the dual-pathway model of auditory processing in its original form, but argue for the need to refine and extend this widely accepted hypothesis.

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.

Neural correlates of sound localization in complex acoustic environments.

Listening to and understanding people in a "cocktail-party situation" is a remarkable feature of the human auditory system. Here we investigated the neural correlates of the ability to localize a particular sound among others in an acoustically cluttered environment with healthy subjects. In a sound localization task, five different natural sounds were presented from five virtual spatial locations during functional magnetic resonance imaging (fMRI). Activity related to auditory stream segregation was revealed in posterior superior temporal gyrus bilaterally, anterior insula, supplementary motor area, and frontoparietal network. Moreover, the results indicated critical roles of left planum temporale in extracting the sound of interest among acoustical distracters and the precuneus in orienting spatial attention to the target sound. We hypothesized that the left-sided lateralization of the planum temporale activation is related to the higher specialization of the left hemisphere for analysis of spectrotemporal sound features. Furthermore, the precuneus - a brain area known to be involved in the computation of spatial coordinates across diverse frames of reference for reaching to objects - seems to be also a crucial area for accurately determining locations of auditory targets in an acoustically complex scene of multiple sound sources. The precuneus thus may not only be involved in visuo-motor processes, but may also subserve related functions in the auditory modality.

Male advantage in sound localization at cocktail parties.

Sex differences exist in the structural organization of the human brain and are related to cognitive abilities. Females usually outperform men in verbal fluency, verbal memory, perceptual speed, numerical calculation, and fine motor skills, whereas males are superior in visuospatial abilities, throwing accuracy, and mathematical reasoning. Here we demonstrated a male advantage in spatial abilities for the auditory modality. We employed a sound localization task based on the so-called "cocktail party situation", requiring extraction of auditory information of a specific sound source when multiple competing sound sources were present. The results indicated better performance of males than females for localizing target sounds in a multi-source sound environment. This finding suggests a sex difference in the attentional mechanisms extracting spatial information of one acoustic event of interest from an auditory scene composed of multiple sound sources. It seems that the known male superiority in spatial abilities may be supramodal, rather than a specificity of the visual modality.

Brain activation during immediate and delayed reaching in optic ataxia.

Patients with optic ataxia after lesions of the occipito-parietal cortex demonstrate gross deviations of movements to visual targets in their peripheral visual field. When the same patients point to remembered target locations their accuracy improves considerably. Taking into account opposite findings in a single patient suffering from visual form agnosia due to bilateral occipito-temporal lesions (D.F.), this paradoxical improvement was attributed to brain structures outside the dorsal stream, and supposed to be specifically associated with delayed movement execution. This conclusion was based on the still unverified assumption that the dorsal system is almost completely lacking any localization function in patients with optic ataxia who demonstrate the paradoxical delay effect. We thus investigated brain activity associated with immediately executed and delayed movements in a patient with optic ataxia due to extensive bilateral lesions (I.G.) and in 16 healthy subjects using functional magnetic resonance imaging. Our analysis revealed robust and indistinguishable activation of intact dorsal occipital and parietal areas adjacent to the patient's lesions for both types of movements. In healthy subjects, we found the same visuomotor network activated during immediate and delayed movements as well as additionally higher signal increases for movements to visible targets than for delayed movements in bilateral occipito-parietal and occipito-temporal areas. Our results suggest that in healthy subjects as well as in the optic ataxia patient I.G. dorsal areas are not only involved in immediate but also in delayed reaching. This observation questions the hypothesis that residual visuospatial abilities in patients with optic ataxia could only be mediated by a system outside of the dorsal stream.