New Perspectives on the Dialogue between Brains and Machines

Brain-machine interfaces (BMIs) are mostly investigated as a means to provide paralyzed people with new communication channels with the external world. However, the communication between brain and artificial devices also offers a unique opportunity to study the dynamical properties of neural systems. This review focuses on bidirectional interfaces, which operate in two ways by translating neural signals into input commands for the device and the output of the device into neural stimuli. We discuss how bidirectional BMIs help investigating neural information processing and how neural dynamics may participate in the control of external devices. In this respect, a bidirectional BMI can be regarded as a fancy combination of neural recording and stimulation apparatus, connected via an artificial body. The artificial body can be designed in virtually infinite ways in order to observe different aspects of neural dynamics and to approximate desired control policies

IRIS study: a phase II study of the steroid sulfatase inhibitor Irosustat when added to an aromatase inhibitor in ER-positive breast cancer patients

Purpose: Irosustat is a first-generation, orally active, irreversible steroid sulfatase inhibitor. We performed a multicentre, open label phase II trial of the addition of Irosustat to a first-line aromatase inhibitor (AI) in patients with advanced BC to evaluate the safety of the combination and to test the hypothesis that the addition of Irosustat to AI may further suppress estradiol levels and result in clinical benefit. Experimental design: Postmenopausal women with ER-positive locally advanced or metastatic breast cancer who had derived clinical benefit from a first-line AI and who subsequently progressed were enrolled. The first-line AI was continued and Irosustat (40 mg orally daily) added. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included safety, tolerability, and pharmacodynamic end points. Results: Twenty-seven women were recruited, four discontinued treatment without response assessment. Based on local reporting, the CBR was 18.5% (95% CI 6.3–38.1%) on an intent to treat basis, increasing to 21.7% (95% CI 7.4–43.7%) by per-protocol analysis. In those patients that achieved clinical benefit (n = 5), the median (interquartile range) duration was 9.4 months (8.1–11.3) months. The median progression-free survival time was 2.7 months (95% CI 2.5–4.6) in both the ITT and per-protocol analyses. The most frequently reported grade 3/4 toxicities were dry skin (28%), nausea (13%), fatigue (13%), diarrhoea (8%), headache (7%), anorexia (7%) and lethargy (7%). Conclusions: The addition of Irosustat to aromatase inhibitor therapy resulted in clinical benefit with an acceptable safety profile. The study met its pre-defined success criterion by both local and central radiological assessments

VIBRISSAL MOTOR CORTEX SHORT-TERM PLASTICITY AFTER HOMOTOPIC CORTEX INACTIVATION IN ADULT RATS

A large number of reports point out to functional and structural changes of motor cortex as the effect of the injury in the corresponding region in the opposite hemisphere (homotopic cortex). Nevertheless in the non-damaged hemisphere, the nature of electrophysiological changes remains unclear. In rats, the organization of the vibrissal motor system is bilateral and the vibrissa motor cortex (VMC) is an area rich in interhemispheric connections. The purpose of the present study was to investigate the short-term reorganization of the VMC after inactivation of the homotopic cortex. To this end, 7 adult rats underwent injections of Lidocaine 3% (15 μL ) (L-group) delivered through a Hamilton syringe at a depth of 1mm from the pial surface into three different sites within the left VMC (Coordinate in mm: Bregma +1, L +1; Bregma +2, L+1,5 and Bregma +3, L1,5). Rats underwent intracortical microstimulation (ICMS) for VMC mapping in both hemispheres after VMC inactivation in one hemisphere. Moreover, VMC mapping was performed in both hemispheres in Control-(n=5) and Sham-group (n=5) of rats. Under ketamine anaesthesia (50mg\Kg i.p.) the ICMS (30 ms trains of 0.2 ms cathodal pulses at 300 Hz, stimulation current ≤60μA) was delivered at a depth of 1.5mm from the pial surface using glass-insulated tungsten microelettrodes (impedance:0.6-1.2MΩ). There was no difference in VMC output in Control vs. Sham-group (p>0.05). In the L-group, in comparison with Control one, a significant shrinkage of the VMC size and a significant decrease of the VMC excitability was observed (mean size L-group: 2.3±0.8mm2 vs. Control: 3.8±0.6mm2, p<0.0007; mean threshold for vibrissa movement in L-group: 29.4±4.1μA vs. Control: 20.7±1.9μA, p<0.0008 ANOVA). These results suggest that the VMC of the two hemispheres continuously interact through excitatory influences for maintaining normal VCM output

Postnatal development of vibrissae motor output following neonatal infraorbital nerve manipulation

Using the model of infraorbital nerve (IoN) injury, we have studied the role IoN signals have on the developing vibrissal motor system. To this end, in ten rats, the IoN was severed on the day of birth: in five rats, the IoN was repaired to promote axon regeneration (Reinnervated group) while axon regeneration was prevented in the remaining five rats (Deafferented group). In another five rats, the isolated IoN was left intact (Sham group) and still another group of five rats was left untouched (Control group). After these rats had reached adulthood, the compound muscle action potential (MAP) was recorded from the vibrissa muscle and intracortical microstimulation (ICMS)-evoked movements were mapped in the frontal cortex contralateral to the operated side. We found: (i) no difference between Control, Sham and Reinnervated groups in the integrated MAPs and in the size and excitability of the M1 vibrissal representation. (ii) the Deafferented group showed a 42.9% decrease in the integrated MAP plus a 47.2% and 36.9% reduction, respectively, in the size and excitability of the M1 vibrissae representation. We conclude that, during perinatal life, IoN signals regulate the development of both the peripheral and central vibrissal motor system and that IoN reinnervation restores sensory signals able to stabilize normal development of the vibrissal motor system

Cerebellar Modulation of Cortically Evoked Complex Movements in Rats.

Intracortical microstimulation (ICMS) delivered to the motor cortex (M1) via long- or short-train duration (long- or short-duration ICMS) can evoke coordinated complex movements or muscle twitches, respectively. The role of subcortical cerebellar input in M1 output, in terms of long- and short-duration ICMS-evoked movement and motor skill performance, was evaluated in rats with bilateral lesion of the deep cerebellar nuclei. After the lesion, distal forelimb movements were seldom observed, and almost 30% of proximal forelimb movements failed to match criteria defining the movement class observed under control conditions. The classifiable movements could be evoked in different cortical regions with respect to control and many kinematic variables were strongly affected. Furthermore, movement endpoints within the rat's workspace shrunk closer to the body, while performance in the reaching/grasping task worsened. Surprisingly, neither the threshold current values for evoking movements nor the overall size of forelimb movement representation changed with respect to controls in either long- or short-duration ICMS. We therefore conclude that cerebellar input via the motor thalamus is crucial for expressing the basic functional features of the motor cortex

Superior electrochemical performance of carbon nanotubes directly grown on sharp microelectrodes

We report for the first time how coatings made by directly growing carbon nanotubes (CNTs) on the tip of neural microelectrodes outperform others made by electrodeposited CNT composites. Not only do they reduce microelectrode impedance but they also are able to inject high currents without degradation and are stable in time. These results suggest that they are excellent candidates for chronic applications especially when both neural recording and stimulation have to be performed by the same microelectrode. \ua9 2011 American Chemical Society

Biologically Compatible Neural Interface To Safely Couple Nanocoated Electrodes to the Surface of the Brain

The ongoing interest in densely packed miniaturized electrode arrays for high-resolution epicortical recordings has induced many researchers to explore the use of nanomaterial coatings to reduce electrode impedance while increasing signal-to-noise ratio and charge injection capability. Although these materials are very effective, their use in clinical practice is strongly inhibited by concerns about the potential risks derived from the use of nanomaterials in direct contact with the human brain. In this work we propose a novel approach to safely couple nanocoated electrodes to the brain surface by encapsulating them with a biocompatible hydrogel. We prove that fibrin hydrogel coating over nanocoated high-density arrays of epicortical microelectrodes is electrically transparent and allows avoiding direct exposure of the brain tissue to the nanocoatings while maintaining all the advantages derived from the nanostructured electrode surface. This method may make available acute and sub-acute neural recordings with nanocoated high-resolution arrays for clinical applications

Shaping the Dynamics of a Bidirectional Neural Interface

Progress in decoding neural signals has enabled the development of interfaces that translate cortical brain activities into commands for operating robotic arms and other devices. The electrical stimulation of sensory areas provides a means to create artificial sensory information about the state of a device. Taken together, neural activity recording and microstimulation techniques allow us to embed a portion of the central nervous system within a closed-loop system, whose behavior emerges from the combined dynamical properties of its neural and artificial components. In this study we asked if it is possible to concurrently regulate this bidirectional brain-machine interaction so as to shape a desired dynamical behavior of the combined system. To this end, we followed a well-known biological pathway. In vertebrates, the communications between brain and limb mechanics are mediated by the spinal cord, which combines brain instructions with sensory information and organizes coordinated patterns of muscle forces driving the limbs along dynamically stable trajectories. We report the creation and testing of the first neural interface that emulates this sensory-motor interaction. The interface organizes a bidirectional communication between sensory and motor areas of the brain of anaesthetized rats and an external dynamical object with programmable properties. The system includes (a) a motor interface decoding signals from a motor cortical area, and (b) a sensory interface encoding the state of the external object into electrical stimuli to a somatosensory area. The interactions between brain activities and the state of the external object generate a family of trajectories converging upon a selected equilibrium point from arbitrary starting locations. Thus, the bidirectional interface establishes the possibility to specify not only a particular movement trajectory but an entire family of motions, which includes the prescribed reactions to unexpected perturbations

Carbon nanotube composite coating of neural microelectrodes preferentially improves the multiunit signal-to-noise ratio

Extracellular metal microelectrodes are widely used to record single neuron activity in vivo. However, their signal-to-noise ratio (SNR) is often far from optimal due to their high impedance value. It has been recently reported that carbon nanotube (CNT) coatings may decrease microelectrode impedance, thus improving their performance. To tease out the different contributions to SNR of CNT-coated microelectrodes we carried out impedance and noise spectroscopy measurements of platinum/tungsten microelectrodes coated with a polypyrrole-CNT composite. Neuronal signals were recorded in vivo from rat cortex by employing tetrodes with two recording sites coated with polypyrrole-CNT and the remaining two left untreated. We found that polypyrrole-CNT coating significantly reduced the microelectrode impedance at all neuronal signal frequencies (from 1 to 10 000 Hz) and induced a significant improvement of the SNR, up to fourfold on average, in the 150-1500 Hz frequency range, largely corresponding to the multiunit frequency band. An equivalent circuit, previously proposed for porous conducting polymer coatings, reproduced the impedance spectra of our coated electrodes but could not explain the frequency dependence of SNR improvement following polypyrrole-CNT coating. This implies that neither the neural signal amplitude, as recorded by a CNT-coated metal microelectrode, nor noise can be fully described by the equivalent circuit model we used here and suggests that a more detailed approach may be needed to better understand the signal propagation at the electrode-solution interface. Finally, the presence of significant noise components that are neither thermal nor electronic makes it difficult to establish a direct relationship between the actual electrode noise and the impedance spectra