Mario Tombini

Double nerve intraneural interface implant on a human amputee for robotic hand control

OBJECTIVES The principle underlying this project is that, despite nervous reorganization following upper limb amputation, original pathways and CNS relays partially maintain their function and can be exploited for interfacing prostheses. Aim of this study is to evaluate a novel peripheral intraneural multielectrode for multi-movement prosthesis control and for sensory feed-back, while assessing cortical reorganization following the re-acquired stream of data. METHODS Four intrafascicular longitudinal flexible multielectrodes (tf-LIFE4) were implanted in the median and ulnar nerves of an amputee; they reliably recorded output signals for 4 weeks. Artificial intelligence classifiers were used off-line to analyse LIFE signals recorded during three distinct hand movements under voluntary order. RESULTS Real-time control of motor output was achieved for the three actions. When applied off-line artificial intelligence reached >85% real-time correct classification of trials. Moreover, different types of current stimulation were determined to allow reproducible and localized hand/fingers sensations. Cortical organization was observed via TMS in parallel with partial resolution of symptoms due to the phantom-limb syndrome (PLS). CONCLUSIONS tf-LIFE4s recorded output signals in human nerves for 4 weeks, though the efficacy of sensory stimulation decayed after 10 days. Recording from a number of fibres permitted a high percentage of distinct actions to be classified correctly. Reversal of plastic changes and alleviation of PLS represent corollary findings of potential therapeutic benefit. SIGNIFICANCE This study represents a breakthrough in robotic hand use in amputees.

CONVERSION FROM MILD COGNITIVE IMPAIRMENT TO ALZHEIMER'S DISEASE IS PREDICTED BY SOURCES AND COHERENCE OF BRAIN ELECTROENCEPHALOGRAPHY RHYTHMS

Objective. Can quantitative electroencephalography (EEG) predict the conversion from mild cognitive impairment (MCI) to Alzheimers disease (AD)? Methods. Sixty-nine subjects fulfilling criteria for MCI were enrolled; cortical connectivity (spectral coherence) and (low resolution brain electromagnetic tomography) sources of EEG rhythms (delta=2-4 Hz; theta=4-8 Hz; alpha 1=8-10.5 Hz; alpha 2=10.5-13 Hz: beta 1=13-20 Hz; beta 2=20-30 Hz; and gamma=30-40) were evaluated at baseline (time of MCI diagnosis) and follow up (about 14 months later). At follow-up, 45 subjects were still MCI (MCI Stable) and 24 subjects were converted to AD (MCI Converted). Results. At baseline, fronto-parietal midline coherence as well as delta (temporal), theta (parietal, occipital and temporal), and alpha 1 (central, parietal, occipital, temporal, limbic) sources were stronger in MCI Converted than stable subjects (P<0.05). Cox regression modeling showed low midline coherence and weak temporal source associated with 10% annual rate AD conversion, while this rate increased up to 40% and 60% when strong temporal delta source and high midline gamma coherence were observed respectively. Interpretation. Low-cost and diffuse computerized EEG techniques are able to statistically predict MCI to AD conversion.

Modulation of brain plasticity in stroke: a novel model for neurorehabilitation

Noninvasive brain stimulation (NIBS) techniques can be used to monitor and modulate the excitability of intracortical neuronal circuits. Long periods of cortical stimulation can produce lasting effects on brain function, paving the way for therapeutic applications of NIBS in chronic neurological disease. The potential of NIBS in stroke rehabilitation has been of particular interest, because stroke is the main cause of permanent disability in industrial nations, and treatment outcomes often fail to meet the expectations of patients. Despite promising reports from many clinical trials on NIBS for stroke recovery, the number of studies reporting a null effect remains a concern. One possible explanation is that the interhemispheric competition model—which posits that suppressing the excitability of the hemisphere not affected by stroke will enhance recovery by reducing interhemispheric inhibition of the stroke hemisphere, and forms the rationale for many studies—is oversimplified or even incorrect. Here, we critically review the proposed mechanisms of synaptic and functional reorganization after stroke, and suggest a bimodal balance–recovery model that links interhemispheric balancing and functional recovery to the structural reserve spared by the lesion. The proposed model could enable NIBS to be tailored to the needs of individual patients.

Slow Repetitive TMS for Drug-resistant Epilepsy: Clinical and EEG Findings of a Placebo-controlled Trial

Summary:  Purpose: To assess the effectiveness of slow repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for drug‐resistant epilepsy.

Anodal Transcranial Direct Current Stimulation Enhances Procedural Consolidation

The primary motor cortex (M1) area recruitment enlarges while learning a finger tapping sequence. Also M1 excitability increases during procedural consolidation. Our aim was to investigate whether increasing M1 excitability by anodal transcranial DC stimulation (AtDCS) when procedural consolidation occurs was able to induce an early consolidation improvement. Forty-seven right-handed healthy participants were trained in a nine-element serial finger tapping task (SFTT) executed with the left hand. Random series blocks were interspersed with training series blocks. Anodal or sham tDCS was administered over the right M1 after the end of the training session. After stimulation, the motor skills of both trained and a new untrained sequential series blocks were tested again. For each block, performance was estimated as the median execution time of correct series. Early consolidation of the trained series, assessed by the performance difference between the first block after and the last block before stimulation normalized by the random, was enhanced by anodal and not by sham tDCS. Stimulation did not affect random series execution. No stimulation effect was found on the on-line learning of the trained and new untrained series. Our results suggest that AtDCS applied on M1 soon after training improves early consolidation of procedural learning. Our data highlight the importance of neuromodulation procedures for understanding learning processes and support their use in the motor rehabilitation setting, focusing on the timing of the application.

Resting EEG sources correlate with attentional span in mild cognitive impairment and Alzheimer's disease

Previous evidence has shown that resting delta and alpha electroencephalographic (EEG) rhythms are abnormal in patients with Alzheimers disease (AD) and its potential preclinical stage (mild cognitive impairment, MCI). Here, we tested the hypothesis that these EEG rhythms are correlated with memory and attention in the continuum across MCI and AD. Resting eyes‐closed EEG data were recorded in 34 MCI and 53 AD subjects. EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). EEG cortical sources were estimated by low‐resolution brain electromagnetic tomography (LORETA). These sources were correlated with neuropsychological measures such as Rey list immediate recall (word short‐term memory), Rey list delayed recall (word medium‐term memory), Digit span forward (immediate memory for digits probing focused attention), and Corsi span forward (visuo‐spatial immediate memory probing focused attention). A statistically significant negative correlation (Bonferroni corrected, P < 0.05) was observed between Corsi span forward score and amplitude of occipital or temporal delta sources across MCI and AD subjects. Furthermore, a positive correlation was shown between Digit span forward score and occipital alpha 1 sources (Bonferroni corrected, P < 0.05). These results suggest that cortical sources of resting delta and alpha rhythms correlate with neuropsychological measures of immediate memory based on focused attention in the continuum of MCI and AD subjects.

Baroreflex Buffering of Sympathetic Activation During Sleep. Evidence From Autonomic Assessment of Sleep Macroarchitecture and Microarchitecture

Abstract—We examined the effects of sleep microstructure, ie, the cyclic alternating pattern (CAP), on heart rate (HR)- and blood pressure (BP)-regulating mechanisms and on baroreflex control of HR in healthy humans and tested the hypothesis that sympathetic activation occurring in CAP epochs during non-rapid eye movement (non-REM) sleep periods is buffered by the arterial baroreflex. Ten healthy males underwent polysomnography and simultaneous recording of BP, ECG, and respiration. Baroreflex sensitivity (BRS) was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate R-R interval (RRI) and BP variabilities. During overall non-REM sleep, BP decreased and RRI increased in comparison to wakefulness, with concomitant decreases in low-frequency RRI and BP oscillations and increases in high-frequency RRI oscillations. These changes were reversed during REM to wakefulness levels, with the exception of RRI. During CAP, BP increased significantly in comparison to non-CAP and did not differ from REM and wakefulness. The low-frequency component of BP variability was significantly higher during CAP than non-CAP. RRI and its low-frequency spectral component did not differ between CAP and non-CAP. BRS significantly increased during CAP in comparison to non-CAP. BRS was not different during CAP and REM and was greater during both in comparison with the awake state. Even during sleep stages, like non-REM sleep, characterized by an overall vagal predominance, phases of sustained sympathetic activation do occur that resemble that occurring during REM. Throughout the overnight sleep period, the arterial baroreflex acts to buffer surges of sympathetic activation by means of rapid changes in cardiac vagal circuits.

Brain activity preceding a 2D manual catching task.

We investigated the event-related desynchronization (ERD) and synchronization (ERS) properties of cortical EEG rhythms in regions of interest (ROI) during the preparation of a 2D task for manual catching of a moving object. EEG signals were recorded through a 32-channel system in eleven healthy subjects during the interception task consisting of 2D catching with the right hand of a handle moving at constant velocity (1.5 m/s) on a predefined straight trajectory. The first session of catching movements (CATCHING_PRE) was compared with a second session after 1 h with identical characteristics (CATCHING_POST) and with other two conditions, where the subjects had to reach and grasp the handle fixed in the medium of platform (REACHING) and they looked at the object moving without catching it (GAZE TRACKING). Changes of cortical rhythms were correlated with dynamic and kinematic indexes of motor performance in both catching sessions. Movements requiring different strategies (predictive versus prospective) are supported by specific changes of cortical EEG rhythms: in the CATCHING condition a more evident power decrease (ERD) in alpha 2 and beta band in the sensorimotor region contralateral to the catching hand was observed, while in the REACHING one a bilateral ERD in beta band was found. Motor learning and movement automatization were characterized by a significant reduction of theta ERS in the anterior cingulate cortex (ACC), a ROI linked to focused attention, and with a shift of neuronal activation in alpha 2 band from the bilateral superior parietal areas to the homologous area of the left hemisphere. Finally, our EEG findings are consistent with the role of supplementary motor (SMA), premotor and prefrontal areas in motor planning and preparation. In particular, theta ERS in left SMA significantly correlated with an improvement of motor performance, as evidenced by its correlation with the training-related reduction of interception time (IT).

Free copper and resting temporal EEG rhythms correlate across healthy, mild cognitive impairment, and Alzheimer's disease subjects.

OBJECTIVE The present study tested the hypothesis that the serum copper abnormalities were correlated with alterations of resting electroencephalographic (EEG) rhythms across the continuum of healthy elderly (Hold), mild cognitive impairment (MCI), and AD subjects. METHODS Resting eyes-closed EEG rhythms delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), beta 2 (20-30Hz), and gamma (30-40Hz), estimated by LORETA, were recorded in 17 Hold, 19 MCI, 27 AD- (MMSE< or =20), and 27 AD+ (MMSE20) individuals and correlated with copper biological variables. RESULTS Across the continuum of Hold, MCI and AD subjects, alpha sources in parietal, occipital, and temporal areas were decreased, while the magnitude of the delta and theta EEG sources in parietal, occipital, and temporal areas was increased. The fraction of serum copper unbound to ceruloplasmin positively correlated with temporal and frontal delta sources, regardless of the effects of age, gender, and education. CONCLUSIONS These results sustain the hypothesis of a toxic component of serum copper that is correlated with functional loss of AD, as revealed by EEG indexes. SIGNIFICANCE The present study represents the first demonstration that the fraction of serum copper unbound to ceruloplasmin is correlated with cortical delta rhythms across Hold, MCI, and AD subjects, thus unveiling possible relationships among the biological parameter, advanced neurodegenerative processes, and synchronization mechanisms regulating the relative amplitude of selective EEG rhythms.

Decoding of grasping information from neural signals recorded using peripheral intrafascicular interfaces

BackgroundThe restoration of complex hand functions by creating a novel bidirectional link between the nervous system and a dexterous hand prosthesis is currently pursued by several research groups. This connection must be fast, intuitive, with a high success rate and quite natural to allow an effective bidirectional flow of information between the users nervous system and the smart artificial device. This goal can be achieved with several approaches and among them, the use of implantable interfaces connected with the peripheral nervous system, namely intrafascicular electrodes, is considered particularly interesting.MethodsThin-film longitudinal intra-fascicular electrodes were implanted in the median and ulnar nerves of an amputees stump during a four-week trial. The possibility of decoding motor commands suitable to control a dexterous hand prosthesis was investigated for the first time in this research field by implementing a spike sorting and classification algorithm.ResultsThe results showed that motor information (e.g., grip types and single finger movements) could be extracted with classification accuracy around 85% (for three classes plus rest) and that the user could improve his ability to govern motor commands over time as shown by the improved discrimination ability of our classification algorithm.ConclusionsThese results open up new and promising possibilities for the development of a neuro-controlled hand prosthesis.