Krunoslav Stingl

Artificial vision with wirelessly powered subretinal electronic implant alpha-IMS

This study aims at substituting the essential functions of photoreceptors in patients who are blind owing to untreatable forms of hereditary retinal degenerations. A microelectronic neuroprosthetic device, powered via transdermal inductive transmission, carrying 1500 independent microphotodiode-amplifier-electrode elements on a 9 mm2 chip, was subretinally implanted in nine blind patients. Light perception (8/9), light localization (7/9), motion detection (5/9, angular speed up to 35 deg s−1), grating acuity measurement (6/9, up to 3.3 cycles per degree) and visual acuity measurement with Landolt C-rings (2/9) up to Snellen visual acuity of 20/546 (corresponding to decimal 0.037 or corresponding to 1.43 logMAR (minimum angle of resolution)) were restored via the subretinal implant. Additionally, the identification, localization and discrimination of objects improved significantly (n = 8; p < 0.05 for each subtest) in repeated tests over a nine-month period. Three subjects were able to read letters spontaneously and one subject was able to read letters after training in an alternative-force choice test. Five subjects reported implant-mediated visual perceptions in daily life within a field of 15° of visual angle. Control tests were performed each time with the implants power source switched off. These data show that subretinal implants can restore visual functions that are useful for daily life.

The Insulin-Mediated Modulation of Visually Evoked Magnetic Fields Is Reduced in Obese Subjects

Background Insulin is an anorexigenic hormone that contributes to the termination of food intake in the postprandial state. An alteration in insulin action in the brain, named “cerebral insulin resistance”, is responsible for overeating and the development of obesity. Methodology/Principal Findings To analyze the direct effect of insulin on food-related neuronal activity we tested 10 lean and 10 obese subjects. We conducted a magnetencephalography study during a visual working memory task in both the basal state and after applying insulin or placebo spray intranasally to bypass the blood brain barrier. Food and non-food pictures were presented and subjects had to determine whether or not two consecutive pictures belonged to the same category. Intranasal insulin displayed no effect on blood glucose, insulin or C-peptide concentrations in the periphery; however, it led to an increase in the components of evoked fields related to identification and categorization of pictures (at around 170 ms post stimuli in the visual ventral stream) in lean subjects when food pictures were presented. In contrast, insulin did not modulate food-related brain activity in obese subjects. Conclusions/Significance We demonstrated that intranasal insulin increases the cerebral processing of food pictures in lean whereas this was absent in obese subjects. This study further substantiates the presence of a “cerebral insulin resistance” in obese subjects and might be relevant in the pathogenesis of obesity.

Neuronal correlates of reduced memory performance in overweight subjects.

There is growing evidence that excessive body weight correlates with impaired cognitive performance like executive function, attention and memory. In our study, we applied a visual working memory task to quantify associations between body weight and executive function. In total, 34 lean (BMI 22±2.1 kg/m(2)) and 34 obese (BMI 30.4±3.2 kg/m(2)) subjects were included. Magnetic brain activity and behavioral responses were recorded during a one-back visual memory task with food and non-food pictures, which were matched for color, size and complexity. Behavioral responses (reaction time and accuracy) were reduced in obese subjects independent of the stimulus category. Neuronal activity at the source level showed a positive correlation between the right dorsolateral prefrontal cortex (DLPFC) activity and BMI only for the food category. In addition, a negative correlation between BMI and neuronal activity was observed in the occipital area for both categories. Therefore we conclude that increased body weight is associated with reduced task performance and specific neuronal changes. This altered activity is probably related to executive function as well as encoding and retrieval of information.

Insulin modulation of magnetoencephalographic resting state dynamics in lean and obese subjects.

Lean and obese subjects can exhibit differences in neuronal activity during resting state and tasks. Changes in hormonal status and their action related to increased body weight may be the determining factor for these differences. One prime candidate is insulin, which until recently was mainly related to its metabolic function for the transport and regulation of glucose in the periphery. However insulin also acts as an anorexic signal in the central nervous system contributing to the termination of food intake in the postprandial state. In our study, we examined with whole-head magnetoencephalography the effect of intranasal insulin on the dynamics of the resting state network in a placebo controlled study. Weighted clustering coefficient C, which describes local interconnectedness, and weighted path length L, a measure of global interconnectedness, were computed. These parameters showed high intraindividual reliability. However, no difference for the network dynamics was found between lean and obese subjects in the basal state. The application of insulin led to subject specific changes and we found a statistically significant positive correlation between the insulin induced change in path length in the theta band (4–8 Hz) and body mass index. The change in pathway length after insulin administration indicates a strong insulin modulation on global communication efficiency, which is probably related to the signaling between different regions involved in satiation and homeostatic control.

The temporal sequence of magnetic brain activity for food categorization and memorization — an exploratory study

The importance of food stimuli for all living organisms is defined by their relevance for survival. Therefore, visual processing of food stimuli is influenced by many factors, such as cultural and societal background. In this magnetoencephalography (MEG) study, we examined the categorization and memorization of visual food and non-food stimuli in lean subjects, using a one-back working memory task. We found an increase in neural activity in several different regions of the brain elicited by food stimuli in comparison to non-food stimuli. The first observed significant difference was found in low-level visual areas as early as 120 ms after stimulus onset. The stimulus category of the previous picture did not influence this effect. However, preceding stimuli modulated behavioral measures (reaction time and accuracy of responses) and later components of the evoked responses around 350 ms. The evoked magnetic field of this late component showed a significant increase inactivity in the temporal cortex for food versus non-food objects. This late component exhibited a significant correlation with the reaction time. The difference of category-specific effects in the early components and the behavioral modulation of late components could be useful for further investigations of the cortical activity in response to food stimuli, e.g. in subjects with eating disorders or obesity.

Polymorphism rs3123554 in CNR2 reveals gender-specific effects on body weight and affects loss of body weight and cerebral insulin action

The cannabinoid‐receptor system is involved in the regulation of food intake. Here, we test whether single nucleotide polymorphisms (SNPs) in CNR2, encoding the cannabinoid‐receptor 2, are associated with weight in a cross‐sectional cohort. Furthermore, we wanted to investigate if the identified hits influence weight loss during lifestyle intervention; and study a potential involvement of cerebral insulin action.

Working memory‐related brain activity is associated with outcome of lifestyle intervention

Lifestyle interventions including reduction of caloric intake are still the most pursued option to treat obesity. However, their outcome in terms of weight loss strongly differs between participants. In our study, we hypothesized that initial differences in brain activation in a food specific memory task are associated with weight change during a lifestyle intervention.

[What can blind patients see in daily life with the subretinal Alpha IMS implant? Current overview from the clinical trial in Tübingen].

ZusammenfassungEin subretinales visuelles Implantat ist ein Forschungsansatz, bei erblichen Netzhautdegenerationen im Endstadium die Photorezeptoren durch mikroelektronische Chips zu ersetzen. In einer klinischen Studie in Tübingen werden diese Implantate an blinden Freiwilligen geprüft. Durch Benutzen des Implantates in alltäglichen Situationen konnten bislang wertvolle visuelle Erfahrungen berichtet werden. Der subretinale Mikrochip vermittelt subjektiv nützliche Informationen sowohl im Nahbereich als auch in der Fernsicht.AbstractThe subretinal visual implant is a scientific research approach to restore partial vision in end-stage hereditary retinal diseases by replacing the function of the degenerated photoreceptors by microelectronic chips. In a clinical trial in Tübingen these implants were tested on voluntary blind patients. By using the implants in daily living the patients reported valuable visual information. The subretinal microchip mediates subjectively useful visual information in near as well as in distant vision.The subretinal visual implant is a scientific research approach to restore partial vision in end-stage hereditary retinal diseases by replacing the function of the degenerated photoreceptors by microelectronic chips. In a clinical trial in Tübingen these implants were tested on voluntary blind patients. By using the implants in daily living the patients reported valuable visual information. The subretinal microchip mediates subjectively useful visual information in near as well as in distant vision.

Was können blinde Patienten mit dem subretinalen Alpha-IMS-Implantat im Alltag sehen?

ZusammenfassungEin subretinales visuelles Implantat ist ein Forschungsansatz, bei erblichen Netzhautdegenerationen im Endstadium die Photorezeptoren durch mikroelektronische Chips zu ersetzen. In einer klinischen Studie in Tübingen werden diese Implantate an blinden Freiwilligen geprüft. Durch Benutzen des Implantates in alltäglichen Situationen konnten bislang wertvolle visuelle Erfahrungen berichtet werden. Der subretinale Mikrochip vermittelt subjektiv nützliche Informationen sowohl im Nahbereich als auch in der Fernsicht.AbstractThe subretinal visual implant is a scientific research approach to restore partial vision in end-stage hereditary retinal diseases by replacing the function of the degenerated photoreceptors by microelectronic chips. In a clinical trial in Tübingen these implants were tested on voluntary blind patients. By using the implants in daily living the patients reported valuable visual information. The subretinal microchip mediates subjectively useful visual information in near as well as in distant vision.The subretinal visual implant is a scientific research approach to restore partial vision in end-stage hereditary retinal diseases by replacing the function of the degenerated photoreceptors by microelectronic chips. In a clinical trial in Tübingen these implants were tested on voluntary blind patients. By using the implants in daily living the patients reported valuable visual information. The subretinal microchip mediates subjectively useful visual information in near as well as in distant vision.

Weighted Phase Lag Index and Graph Analysis: Preliminary Investigation of Functional Connectivity during Resting State in Children

Resting state functional connectivity of MEG data was studied in 29 children (9-10 years old). The weighted phase lag index (WPLI) was employed for estimating connectivity and compared to coherence. To further evaluate the network structure, a graph analysis based on WPLI was used to determine clustering coefficient (C) and betweenness centrality (BC) as local coefficients as well as the characteristic path length (L) as a parameter for global interconnectedness. The networks modular structure was also calculated to estimate functional segregation. A seed region was identified in the central occipital area based on the power distribution at the sensor level in the alpha band. WPLI reveals a specific connectivity map different from power and coherence. BC and modularity show a strong level of connectedness in the occipital area between lateral and central sensors. C shows different isolated areas of occipital sensors. Globally, a network with the shortest L is detected in the alpha band, consistently with the local results. Our results are in agreement with findings in adults, indicating a similar functional network in children at this age in the alpha band. The integrated use of WPLI and graph analysis can help to gain a better description of resting state networks.