Direct activation of zebrafish neurons by ultrasonic stimulation revealed by whole CNS calcium imaging.

OBJECTIVE: Ultrasounds (US) use in neural engineering is so far mainly limited to ablation through high intensity focused ultrasound, but interesting preliminary results show that low intensity low frequency ultrasound could be used instead to modulate neural activity. However, the extent of this modulatory ability of US is still unclear, as in in vivo studies it is hard to disentangle the contribution to neural responses of direct activation of the neuron by US stimulation and indirect activation due either to sensory response to mechanical stimulation associated to US, or to propagation of activity from neighboring areas. Here, we aim to show how to separate the three effects and assess the presence of direct response to US stimulation in zebrafish. APPROACH: We observed in zebrafish larvae brain-wide US-induced activity patterns through calcium imaging microscopy. Sensory response to mechanical stimulation was assessed with a US shield. Activity propagation was assessed with inter-area latency evaluation. MAIN RESULTS: We prove that in selected brain regions the zebrafish's neural response is mainly due to direct activation, later spreading to the other regions. Shielding the neurons from direct US stimulation resulted in a significantly attenuated response, showing that sensory stimulation does not play a prominent role. SIGNIFICANCE: US non-invasive neuromodulatory approach might lead to novel ways to test and control neural activity, and hence to novel neuromodulatory therapies. Future studies will focus on the biophysical structure of directly responsive neurons to capture the mechanisms of US induced activity.

Subthalamic Neural Activity Patterns Anticipate Economic Risk Decisions in Gambling.

Economic decision-making is disrupted in individuals with gambling disorder, an addictive behavior observed in Parkinson's disease (PD) patients receiving dopaminergic therapy. The subthalamic nucleus (STN) is involved in the inhibition of impulsive behaviors; however, its role in impulse control disorders and addiction is still unclear. Here, we recorded STN local field potentials (LFPs) in PD patients with and without gambling disorder during an economic decision-making task. Reaction times analysis showed that for all patients, the decision whether to risk preceded task onset. We compared then for both groups the STN LFP preceding high- and low-risk economic decisions. We found that risk avoidance in gamblers correlated with larger STN LFP low-frequency (<12-Hz) fluctuations preceding task onset. In particular, the amplitude of low-frequency LFP fluctuations carried significant information about future decisions. Decisions of patients not affected by gambling disorder were instead not correlated with pretask STN LFP. Our results suggest that STN activity preceding task onset affects risk decisions by preemptively inhibiting attraction to high but unlikely rewards in favor of a long-term payoff.

Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation.

OBJECTIVE: The vestibular system provides essential information about balance and spatial orientation via the brain to other sensory and motor systems. Bilateral vestibular loss significantly reduces quality of life, but vestibular implants (VIs) have demonstrated potential to restore lost function. However, optimal electrical stimulation strategies have not yet been identified in patients. In this study, we compared the two most common strategies, pulse amplitude modulation (PAM) and pulse rate modulation (PRM), in patients. APPROACH: Four subjects with a modified cochlear implant including electrodes targeting the peripheral vestibular nerve branches were tested. Charge-equivalent PAM and PRM were applied after adaptation to baseline stimulation. Vestibulo-ocular reflex eye movement responses were recorded to evaluate stimulation efficacy during acute clinical testing sessions. MAIN RESULTS: PAM evoked larger amplitude eye movement responses than PRM. Eye movement response axes for lateral canal stimulation were marginally better aligned with PRM than with PAM. A neural network model was developed for the tested stimulation strategies to provide insights on possible neural mechanisms. This model suggested that PAM would consistently cause a larger ensemble firing rate of neurons and thus larger responses than PRM. SIGNIFICANCE: Due to the larger magnitude of eye movement responses, our findings strongly suggest PAM as the preferred strategy for initial VI modulation.

Decoding bipedal locomotion from the rat sensorimotor cortex.

OBJECTIVE: Decoding forelimb movements from the firing activity of cortical neurons has been interfaced with robotic and prosthetic systems to replace lost upper limb functions in humans. Despite the potential of this approach to improve locomotion and facilitate gait rehabilitation, decoding lower limb movement from the motor cortex has received comparatively little attention. Here, we performed experiments to identify the type and amount of information that can be decoded from neuronal ensemble activity in the hindlimb area of the rat motor cortex during bipedal locomotor tasks. APPROACH: Rats were trained to stand, step on a treadmill, walk overground and climb staircases in a bipedal posture. To impose this gait, the rats were secured in a robotic interface that provided support against the direction of gravity and in the mediolateral direction, but behaved transparently in the forward direction. After completion of training, rats were chronically implanted with a micro-wire array spanning the left hindlimb motor cortex to record single and multi-unit activity, and bipolar electrodes into 10 muscles of the right hindlimb to monitor electromyographic signals. Whole-body kinematics, muscle activity, and neural signals were simultaneously recorded during execution of the trained tasks over multiple days of testing. Hindlimb kinematics, muscle activity, gait phases, and locomotor tasks were decoded using offline classification algorithms. MAIN RESULTS: We found that the stance and swing phases of gait and the locomotor tasks were detected with accuracies as robust as 90% in all rats. Decoded hindlimb kinematics and muscle activity exhibited a larger variability across rats and tasks. SIGNIFICANCE: Our study shows that the rodent motor cortex contains useful information for lower limb neuroprosthetic development. However, brain-machine interfaces estimating gait phases or locomotor behaviors, instead of continuous variables such as limb joint positions or speeds, are likely to provide more robust control strategies for the design of such neuroprostheses.

Decoding the activity of grasping neurons recorded from the ventral premotor area F5 of the macaque monkey.

Many neurons in the monkey ventral premotor area F5 discharge selectively when the monkey grasps an object with a specific grip. Of these, the motor neurons are active only during grasping execution, whereas the visuomotor neurons also respond to object presentation. Here we assessed whether the activity of 90 task-related F5 neurons recorded from two macaque monkeys during the performance of a visually-guided grasping task can be used as input to pattern recognition algorithms aiming to decode different grips. The features exploited for the decoding were the mean firing rate and the mean interspike interval calculated over different time spans of the movement period (all neurons) or of the object presentation period (visuomotor neurons). A support vector machine (SVM) algorithm was applied to the neural activity recorded while the monkey grasped two sets of objects. The original set contained three objects that were grasped with different hand shapes, plus three others that were grasped with the same grip, whereas the six objects of the special set were grasped with six distinctive hand configurations. The algorithm predicted with accuracy greater than 95% all the distinct grips used to grasp the objects. The classification rate obtained using the first 25% of the movement period was 90%, whereas it was nearly perfect using the entire period. At least 16 neurons were needed for accurate performance, with a progressive increase in accuracy as more neurons were included. Classification errors revealed by confusion matrices were found to reflect similarities of hand grips used to grasp the objects. The use of visuomotor neurons' responses to object presentation yielded grip classification accuracy similar to that obtained from actual grasping execution. We suggest that F5 grasping-related activity might be used by neural prostheses to tailor hand shape to the specific object to be grasped even before movement onset.

Activities on PNS neural interfaces for the control of hand prostheses.

The development of interfaces linking the human nervous system with artificial devices is an important area of research. Several groups are working on the development of devices able to restore sensory-motor function in subjects affected by neurological disorders, injuries or amputations. Neural electrodes implanted in peripheral nervous system, and in particular intrafascicular electrodes, seem to be a promising approach for the control of hand prosthesis thanks to the possibility to selectively access motor and sensory fibers for decoding motor commands and delivering sensory feedback. In this paper, activities on the use of PNS interfaces for the control of hand prosthesis are presented. In particular, the design and feasibility study of a self-opening neural interface is presented together with the decoding of ENG signals in one amputee to control a dexterous hand prosthesis.

Intrafascicular thin-film multichannel electrodes for sensory feedback: Evidences on a human amputee.

The performance of motor neuroprostheses or robotic arm prostheses can be significantly improved by delivering sensory feed-back related to the ongoing motor task (e.g. the slippage of an object during grasping). Microfabricated neural electrodes implantable in peripheral nervous system seem a promising approach to this aim. New generation of thin-film intrafascicular electrodes longitudinally implantable in peripheral nerves (tf-LIFE4) has been developed and tested for afferent stimulation in human amputee case study.

On the control of a robot hand by extracting neural signals from the PNS: preliminary results from a human implantation.

The development of hybrid neuroprosthetic systems (HBSs) linking the human nervous system with artificial devices is an important area of research that is currently addressed by several groups to restore sensorimotor function in people affected by different disabilities. It is particularly important to establish a fast, intuitive, bidirectional flow of information between the nervous system of the user and the smart robotic device. Among the possible solutions to achieve this goal, interfaces with the peripheral nervous system and in particular intraneural electrodes can represent an interesting choice. In the present study, thin-film longitudinal intra-fascicular electrodes were implanted in the median and ulnar nerves of an amputee. The possibility of restoring the bidirectional link between the subject and the external world was investigated during a 4 week trial. The result showed that both the extraction of motor information and the restoration of sensory function are possible.

Classification of upper arm EMG signals during object-specific grasp.

Electromyographic (EMG) signals can represent an interesting solution to control artificial hands because they are easy to record and can allow the user to control different robotic systems. However, after limb amputation the 'homologous' muscles are no more available to control the prosthetic device and for this reason complex pattern recognition approaches have to be developed to extract the voluntary commands by the user. This makes the control strategy less natural and acceptable and asks for alternative approaches. At the same time, it has been recently shown that (in monkeys) it is possible to discriminate grasping tasks just analyzing the activation onset/offset of upper limb muscles during the reaching phase. This kind of information can be very interesting because it can allow the development of a natural EMG-based control strategy based on the natural muscular activities selected by the central nervous system. In this paper, preliminary experiments have been carried out in order to verify whether these results can be confirmed also in human beings. In particular, a support vector machine (SVM) based pattern recognition algorithm has been developed and used for the prediction of grip types from the EMG recorded from proximal and distal muscles during reach to grasp movements of three able bodied subjects.

Experiments on the development and use of a new generation of intra-neural electrodes to control robotic devices.

The development of interfaces linking the human nervous system with artificial devices is an important area of research and several groups are now addressing it. Interfaces represent the key enabling technology for the development of devices usable for the restoration of motor and sensory function in subjects affected by neurological disorders, injuries or amputations. For example, current hand prostheses use electromyographic (EMG) signals to extract volitional commands but this limits the possibility of controlling several degrees of freedom and of delivering sensory feedback. To achieve these goals, implantable neural interfaces are required. Among the candidate interfaces with the peripheral nervous system intra-neural electrodes seem to be an interesting solution due to their bandwidth and ability to access volition and deliver sensory feedback. However, several drawbacks have to be addressed in order to increase their usability. In this paper, experiments to address many of these issues are presented as part of the development of a new generation of intra-neural electrodes. The results showed seem to confirm that these new interfaces seem to have interesting properties and that they can represent a significant improvement of the state of the art. Extensive experiments will be carried out in the future to validate these results.

A simple highly efficient non invasive EMG-based HMI.

Muscle activity recorded non-invasively is sufficient to control a mobile robot if it is used in combination with an algorithm for its asynchronous analysis. In this paper, we show that several subjects successfully can control the movements of a robot in a structured environment made up of six rooms by contracting two different muscles using a simple algorithm. After a small training period, subjects were able to control the robot with performances comparable to those achieved manually controlling the robot.

Characterization of upper arm synergies during reaching tasks in able-bodied and hemiparetic subjects.

BACKGROUND: In the past, several studies showed the existence of a synergistic behavior between elbow and shoulder joints during reaching movements in able-bodied subjects. The aim of this paper was to characterize the modifications of upper arm synergies during reaching induced by stroke. METHODS: Ten able-bodied right-handed subjects, eight right-handed subjects with hemiparesis affecting the right (dominant) upper limb participated in the experiments. The kinematics of shoulder and elbow joints have been recorded in all the participants during selected reaching movements. From the eight-like plots characterizing the relationship between shoulder and elbow angular velocities, a topological parameter (named as C approximately ) representing the linear approximation of the synergy between the two angular velocities has been extracted. FINDINGS: The results of these experiments showed that C approximately could be used as a figure of merit for the comparison of performance in able-bodied and hemiparetic persons. The hemiparetic subjects showed a significantly higher spreading of the values of C approximately for the different reaching movements when compared with the performance of able-bodied subjects. INTERPRETATION: This work showed that hemiparesis modified upper arm synergies and could provide a protocol for the assessment of upper limb function. Moreover, important applications of this method could be found in the development of biomimetic algorithms for the control of upper extremities during reaching in humanoid robots, and in the design of customized "games" in neurorehabilitation procedures implemented by using robotic and mechatronic platforms.

A protocol for the assessment of 3D movements of the head in persons with cervical dystonia.

OBJECTIVE: To design and test a protocol for the assessment of neck movements in patients affected by cervical dystonia by using an electromagnetic system. This approach could overcome the limits of the current assessment scales in this specific field. BACKGROUND: Initial assessment and function recovery during treatments are diagnosed by the clinician using outcome scales which present many drawbacks in terms of easiness of use, sensitivity, and reliability. DESIGN: A three-dimensional motion analysis system was used to record six different head movements. METHODS: Six able-bodied subjects and 10 subjects affected by cervical dystonia participated in this study. For the different head movements three kinematic parameters (a symmetry index and two indexes related to the reduction of the range of motion) have been extracted in order to compare the performance of able-bodied and disabled persons. RESULTS: The features selected allowed highlighting of the differences between able-bodied and disabled subjects for the degrees of freedom of the neck. CONCLUSIONS: Using a motion analysis system, three kinematic features were extracted from head movements. They seem to allow a more objective assessment of the disability and a more appropriated strategy for the management of patients affected by cervical dystonia.

Does hypnotizability affect human upright stance?

Subjects highly (Highs) and low susceptible to hypnosis (Lows) show different imagery and attentional capabilities and also peculiar somatomotor, vegetative and electroencephalographic differences in basal and task conditions. Since attention is one of the main component of hypnotic susceptibility and also a relevant factor for postural control, the aim of the experiment was to study actual differences between Highs and Lows at the eyes closure during upright stance. Visual and motor imagery as well as attentional/disattentional capabilities were evaluated through psychological tests. Posture was monitored though Elite systems during upright stance with open and closed eyes. At the eyes closure, Highs and Lows exhibited a different body sway modulation. Possible different compensation mechanisms are suggested for the two groups and interactions between attentional/arousal systems responsible of hypnotic phenomenology and postural control are underlined.