Design and Evaluation of a Fiber-Optic Grip Force Sensor with Compliant 3D-Printable Structure for (f)MRI Applications

Grip force sensors compatible with magnetic resonance imaging (MRI) are used in human motor control and decision-making research, providing objective and sensitive behavioral outcome measures. Commercial sensors are expensive, cover limited force ranges, rely on pneumatic force transmission that cannot detect fast force changes, or are electrically active, which increases the risk of electromagnetic interference. We present the design and evaluation of a low-cost, 3D-printed, inherently MRI-compatible grip force sensor based on a commercial intensity-based fiber-optic sensor. A compliant monobloc structure with flexible hinges transduces grip force to a linear displacement captured by the fiber-optic sensor. The structure can easily be adapted for different force ranges by changing the hinge thickness. A prototype designed for forces up to 800 N was manufactured and showed a highly linear behavior (nonlinearity of 2.37%) and an accuracy of 1.57% in a range between zero and 500 N. It can be printed and assembled within one day and for less than $300. Accurate performance was confirmed, both inside and outside a 3 T MRI scanner within a pilot study. Given its simple design allowing for customization of sensing properties and ergonomics for different applications and requirements, the proposed grip force handle offers researchers a valuable scientific tool

Lensfree Fluorescent On-Chip Imaging of Transgenic Caenorhabditis elegans Over an Ultra-Wide Field-of-View

We demonstrate lensfree on-chip fluorescent imaging of transgenic Caenorhabditis elegans (C. elegans) over an ultra-wide field-of-view (FOV) of e.g., >2–8 cm2 with a spatial resolution of ∼10µm. This is the first time that a lensfree on-chip platform has successfully imaged fluorescent C. elegans samples. In our wide-field lensfree imaging platform, the transgenic samples are excited using a prism interface from the side, where the pump light is rejected through total internal reflection occurring at the bottom facet of the substrate. The emitted fluorescent signal from C. elegans samples is then recorded on a large area opto-electronic sensor-array over an FOV of e.g., >2–8 cm2, without the use of any lenses, thin-film interference filters or mechanical scanners. Because fluorescent emission rapidly diverges, such lensfree fluorescent images recorded on a chip look blurred due to broad point-spread-function of our platform. To combat this resolution challenge, we use a compressive sampling algorithm to uniquely decode the recorded lensfree fluorescent patterns into higher resolution images, demonstrating ∼10 µm resolution. We tested the efficacy of this compressive decoding approach with different types of opto-electronic sensors to achieve a similar resolution level, independent of the imaging chip. We further demonstrate that this wide FOV lensfree fluorescent imaging platform can also perform sequential bright-field imaging of the same samples using partially-coherent lensfree digital in-line holography that is coupled from the top facet of the same prism used in fluorescent excitation. This unique combination permits ultra-wide field dual-mode imaging of C. elegans on a chip which could especially provide a useful tool for high-throughput screening applications in biomedical research

How rewards and reward-related cues influence human behaviour

Investigation of the influence of reward and reward-related cues on behaviour has a longstanding tradition in animal research and dates back to typical Pavlovian and operant conditioning experiments from famous behaviourists such as Thorndike, Skinner and Pavlov. However, recent developments in neuroimaging (i.e. new imaging and analysis techniques) and new concepts from neuroeconomics and decision making have led to the field’s rise in popularity in human neuroscience. This thesis investigated how reward and reward-predicting cues influence: 1) human motor behaviour / control and 2) goal-directed / motivated behaviour. Understanding the influence of reward on these behavioural domains will help develop our understanding of psychiatric diseases characterised by impaired reward and / or learning processes (i.e. autistic spectrum disorder, addictive behaviour), and improve motor performance in sports or rehabilitation. The first study investigated how reward can be used to modulate a phenomenon called motor slowing (i.e. decrease / slowing in maximal finger tapping speed over time). Behavioural data were combined with neuroimaging data (electroencephalography (EEG), functional magnetic resonance imaging (fMRI)) to establish the neurophysiological correlates / markers of this phenomenon. We show that reward decreases motor slowing significantly by increasing neural activity within the motor network. These findings stress the strong link between the reward and motor system, putatively via a dopaminergic pathway. The second study investigated the influence of reward-predicting cues on goal-directed behaviour by using an experimental paradigm called Pavlovian-to-instrumental transfer (PIT). Multiple types of reward, such as money, food, or social approval, are capable of driving human behaviour. However, most previous investigations have only focused on one of these reward classes in isolation, and even fewer have equated the value of different reward classes. Therefore it is not clear whether different reward classes have a unique influence on behaviour or whether the subjective value of the reward, rather than reward type per se, is most important for driving behaviour. Our findings suggest that individually matched monetary, food and social rewards are equally effective as appetitive reinforcers. These findings strengthen the hypotheses that subjective value is crucial for determining how much reward-related stimuli influence behaviour. In a third study we apply a similar experimental paradigm (i.e. PIT) to a clinical population, and additionally measure the participant’s eye movements. Obese individuals have been shown to exhibit abnormal sensitivity to rewards and reward-predicting cues, such as food-associated cues frequently used in advertisements. It has also been shown that food-associated cues can increase goal-directed behaviour but it is unknown whether this effect differs between normal-weight, overweight, and obese individuals. Our results suggest that overweight individuals are more susceptible to food-related cues than normal-weight controls and obese individuals. These findings might also have clinical implications, for example, in targeting overweight individuals with a behavioural therapy (e.g. extinction training, attentional control training, response training). Finally, we discuss the practical relevance of our results and suggest future directions for the two lines of research. To conclude, rewards and reward-predicting cues strongly influence human motor behaviour / control and goal-directed / motivated behaviour, which makes it relevant for practical applications and further basic / translational research.Forschung zum Einfluss von Belohnungen und Hinweisen, die mit Belohnungen assoziiert werden, haben eine lange Tradition. Diese reicht bis zu den klassischen Lernexperimenten (d.h. Pavlovsche und instrumentelle Konditionierung) von den berühmten Verhaltensforschern Thorndike, Skinner und Pavlov. Neuste Errungenschaften im Bereich der neurowissenschaftlichen Methoden und Analysetechniken sowie Konzepte aus der Neuroökonomie haben dieses Forschungsfeld auch am Menschen sehr populär gemacht. Diese Doktorarbeit untersucht wie Belohnungen und mit Belohnung assoziierte Hinweise das menschliche, motorische und zielgerichtete Verhalten beeinflussen. Dies ist möglicherweise relevant um psychische Krankheiten, die durch gestörte Belohnungs- oder Lernprozesse charakterisiert sind (z.B. Autismus, Suchterkrankungen) besser zu verstehen. Zudem können durch die Forschungsergebnisse die Bewegungsleistungen im Sport oder in der Rehabilitation positiv beeinflusst werden. In einer ersten Studie untersuchten wir einerseits, wie Belohnung eingesetzt werden kann um die sogenannte motorische Verlangsamung (d.h. mit der Zeit langsameres maximales Fingertippen) zu verringern. Andererseits suchten wir anhand funktioneller Magnetresonanztomografie (fMRT) und Elektroenzephalografie (EEG) die dazugehörigen neurologischen Korrelate / Erkennungszeichen. Wir zeigen, dass Belohnung die motorische Verlangsamung signifikant reduziert indem die neuronale Aktivität im motorischen System erhöht wird. Diese Resultate heben den Zusammenhang zwischen dem Belohnungs- und Bewegungssystem vermutlich durch dopaminerge Leitungsbahnen hervor. In einer zweiten Studie untersuchten wir den Einfluss von belohnungsassoziierten Hinweisen auf das zielgerichtete Verhalten anhand eines experimentellen Paradigmas, genannt Pavlovscher-instrumenteller Transfer (PIT). Verschiedene Belohnungstypen wie Geld, Nahrung oder soziale Bestätigung sind imstande, das menschliche Verhalten zu beeinflussen. Frühere Studien haben sich dennoch nur auf einen Belohnungstyp fokussiert oder die Belohnungstypen nicht ausgeglichen. Deshalb ist immer noch unklar, ob verschiedene Belohnungstypen einen speziellen Einfluss auf das Verhalten haben oder ob eher der subjektive Wert der Belohnung wichtig ist, um das Verhalten zu beeinflussen. Unsere Ergebnisse zeigen, dass alle individuell angepassten Belohnungstypen (d.h. Geld, Nahrung, soziale Bestätigung) gleich effektive positive Verstärker sind. Sie festigen die Hypothese, dass der subjektive Belohnungswert sehr wichtig dafür ist, wie stark belohnungsassoziierte Hinweise das Verhalten beeinflussen. In einer dritten Studie wandten wir ein gleiches experimentelles Paradigma (d.h. PIT) wie in der zweiten Studie an, dieses Mal jedoch auf eine klinische Population. Zusätzlich massen wir die Augenbewegungen der Studienteilnehmenden. Es wurde früher gezeigt, dass adipöse Personen eine abnormale Sensitivität gegenüber Belohnungen und belohnungsassoziierten Hinweisen haben (wie z.B. Werbung). Es wurde auch nachgewiesen, dass solche nahrungsassoziierten Hinweise zielgerichtetes Verhalten beeinflussen können. Es ist jedoch unklar, ob sich dieser Effekt zwischen normalgewichtigen, übergewichtigen und adipösen Personen unterscheidet. Unsere Ergebnisse zeigen, dass übergewichtige Personen empfindlicher auf nahrungsassoziierte Hinweise reagieren als normalgewichtige und adipöse Personen. Diese Resultate haben auch eine klinische Relevanz, wobei besonders übergewichtige Personen als Zielgruppe für Verhaltenstherapie interessant sein könnten (z.B. Auslöschungstraining, Aufmerksamkeitskontrolltraining, Reaktionstraining). Abschliessend diskutieren wir die praktische Relevanz unserer Resultate und schlagen eine zukünftige Ausrichtung der beiden Forschungsfelder vor. Belohnungen und belohnungsassoziierte Hinweise beeinflussen das motorische und zielgerichtete Verhalten des Menschen sehr stark, was es für praktische Anwendungen aber auch für weitere Grundlagen- und translatorische Forschung relevant macht

Observing back pain provoking lifting actions modulates corticomotor excitability of the observer's primary motor cortex

ISSN:1873-3514ISSN:0028-393

Food-predicting stimuli differentially influence eye movements and goal-directed behavior in normal-weight, overweight, and obese Individuals

Obese individuals have been shown to exhibit abnormal sensitivity to rewards and reward-predicting cues as for example food-associated cues frequently used in advertisements. It has also been shown that food-associated cues can increase goal-directed behavior but it is currently unknown, whether this effect differs between normal-weight, overweight, and obese individuals. Here, we investigate this question by using a Pavlovian-to-instrumental transfer (PIT) task in normal-weight (N = 20), overweight (N = 17), and obese (N = 17) individuals. Furthermore, we applied eye tracking during Pavlovian conditioning to measure the participants’ conditioned response as a proxy of the incentive salience of the predicted reward. Our results show that the goal-directed behavior of overweight individuals was more strongly influenced by food-predicting cues (i.e., stronger PIT effect) than that of normal-weight and obese individuals (p 0.646). Our findings are largely consistent with the incentive sensitization theory predicting that overweight individuals are more susceptible to food-related cues than normal-weight controls. However, this hypersensitivity might be reduced in obese individuals, possibly due to habitual/compulsive overeating or differences in reward valuation

Human motor fatigability as evoked by repetitive movements results from a gradual breakdown of surround inhibition

Motor fatigability emerges when demanding tasks are executed over an extended period of time. Here, we used repetitive low-force movements that cause a gradual reduction in movement speed (or ‘motor slowing’) to study the central component of fatigability in healthy adults. We show that motor slowing is associated with a gradual increase of net excitability in the motor network and, specifically, in primary motor cortex (M1), which results from overall disinhibition. Importantly, we link performance decrements to a breakdown of surround inhibition in M1, which is associated with high coactivation of antagonistic muscle groups. This is consistent with the model that a loss of inhibitory control might broaden the tuning of population vectors such that movement patterns become more variable, ill-timed and effortful. We propose that the release of inhibition in M1 is an important mechanism underpinning motor fatigability and, potentially, also pathological fatigue as frequently observed in patients with brain disorders.ISSN:2050-084

Monetary, food, and social rewards induce similar pavlovian-to-instrumental transfer effects

Multiple types of reward, such as money, food or social approval, are capable of driving behavior. However, most previous investigations have only focused on one of these reward classes in isolation, as such it is not clear whether different reward classes have a unique influence on instrumental responding or whether the subjective value of the reward, rather than the reward type per se, is most important in driving behavior. Here, we investigate behavior using a well-established reward paradigm, Pavlovian-to-instrumental transfer (PIT), and three different reward types: monetary, food and social rewards. The subjective value of each reward type was matched using a modified Becker-DeGroot-Marschak (BDM) auction where subjective reward value was expressed through physical effort using a bimanual grip force task. We measured the influence of reward-associated stimuli on how participants distributed forces between hands when reaching a target effort range on the screen bimanually and on how much time participants spent in this target range. Participants spent significantly more time in the target range (15% ± 2% maximal voluntary contraction) when a stimulus was presented that was associated with a reward used during instrumental conditioning or Pavlovian conditioning compared to a stimulus associated with a neutral outcome (i.e., general PIT). The strength of the PIT effect was modulated by subjective value (i.e., individuals who showed a stronger PIT effect rated the value of rewards more highly), but not by reward type, demonstrating that stimuli of all reward types were able to act as appetitive reinforcers and influenced instrumental responding, when matched to the same subjective reward value. This is the first demonstration that individually matched monetary, food and social rewards are equally effective as appetitive reinforcers in PIT. These findings strengthen the hypotheses that the subjective value is crucial for how much reward-associated stimuli influence behavior.ISSN:1662-515

Food-Predicting Stimuli Differentially Influence Eye Movements and Goal-Directed Behavior in Normal-Weight, Overweight, and Obese Individuals

Obese individuals have been shown to exhibit abnormal sensitivity to rewards and reward-predicting cues as for example food-associated cues frequently used in advertisements. It has also been shown that food-associated cues can increase goal-directed behavior but it is currently unknown, whether this effect differs between normal-weight, overweight, and obese individuals. Here, we investigate this question by using a Pavlovian-to-instrumental transfer (PIT) task in normal-weight (N = 20), overweight (N = 17), and obese (N = 17) individuals. Furthermore, we applied eye tracking during Pavlovian conditioning to measure the participants’ conditioned response as a proxy of the incentive salience of the predicted reward. Our results show that the goal-directed behavior of overweight individuals was more strongly influenced by food-predicting cues (i.e., stronger PIT effect) than that of normal-weight and obese individuals (p 0.646). Our findings are largely consistent with the incentive sensitization theory predicting that overweight individuals are more susceptible to food-related cues than normal-weight controls. However, this hypersensitivity might be reduced in obese individuals, possibly due to habitual/compulsive overeating or differences in reward valuation.ISSN:1664-064

Disrupted prediction errors index social deficits in autism spectrum disorder

In healthy individuals the anterior cingulate gyrus signals social prediction errors: discrepancies between an actual outcome and the perceived expectations of another person. Balsters et al. demonstrate that this crucial social signal is altered in individuals with autism, and that variability in social prediction error signalling indexes social symptom severity

Disrupted prediction errors index social deficits in autism spectrum disorder

Social deficits are a core symptom of autism spectrum disorder; however, the perturbed neural mechanisms underpinning these deficits remain unclear. It has been suggested that social prediction errors—coding discrepancies between the predicted and actual outcome of another’s decisions—might play a crucial role in processing social information. While the gyral surface of the anterior cingulate cortex signalled social prediction errors in typically developing individuals, this crucial social signal was altered in individuals with autism spectrum disorder. Importantly, the degree to which social prediction error signalling was aberrant correlated with diagnostic measures of social deficits. Effective connectivity analyses further revealed that, in typically developing individuals but not in autism spectrum disorder, the magnitude of social prediction errors was driven by input from the ventromedial prefrontal cortex. These data provide a novel insight into the neural substrates underlying autism spectrum disorder social symptom severity, and further research into the gyral surface of the anterior cingulate cortex and ventromedial prefrontal cortex could provide more targeted therapies to help ameliorate social deficits in autism spectrum disorder