Future developments in brain-machine interface research.

Neuroprosthetic devices based on brain-machine interface technology hold promise for the restoration of body mobility in patients suffering from devastating motor deficits caused by brain injury, neurologic diseases and limb loss. During the last decade, considerable progress has been achieved in this multidisciplinary research, mainly in the brain-machine interface that enacts upper-limb functionality. However, a considerable number of problems need to be resolved before fully functional limb neuroprostheses can be built. To move towards developing neuroprosthetic devices for humans, brain-machine interface research has to address a number of issues related to improving the quality of neuronal recordings, achieving stable, long-term performance, and extending the brain-machine interface approach to a broad range of motor and sensory functions. Here, we review the future steps that are part of the strategic plan of the Duke University Center for Neuroengineering, and its partners, the Brazilian National Institute of Brain-Machine Interfaces and the École Polytechnique Fédérale de Lausanne (EPFL) Center for Neuroprosthetics, to bring this new technology to clinical fruition.

Future developments in brain-machine interface research

Neuroprosthetic devices based on brain-machine interface technology hold promise for the restoration of body mobility in patients suffering from devastating motor deficits caused by brain injury, neurologic diseases and limb loss. During the last decade, considerable progress has been achieved in this multidisciplinary research, mainly in the brain-machine interface that enacts upper-limb functionality. However, a considerable number of problems need to be resolved before fully functional limb neuroprostheses can be built. To move towards developing neuroprosthetic devices for humans, brain-machine interface research has to address a number of issues related to improving the quality of neuronal recordings, achieving stable, long-term performance, and extending the brain-machine interface approach to a broad range of motor and sensory functions. Here, we review the future steps that are part of the strategic plan of the Duke University Center for Neuroengineering, and its partners, the Brazilian National Institute of Brain-Machine Interfaces and the École Polytechnique Fédérale de Lausanne (EPFL) Center for Neuroprosthetics, to bring this new technology to clinical fruition.

The differential role of motor cortex in stretch reflex modulation induced by changes in environmental mechanics and verbal instruction.

The motor cortex assumes an increasingly important role in higher mammals relative to that in lower mammals. This is true to such an extent that the human motor cortex is deeply involved in reflex regulation and it is common to speak of "transcortical reflex loops." Such loops appear to add flexibility to the human stretch reflex, once considered to be immutable, allowing it to adapt across a range of functional tasks. However, the purpose of this adaptation remains unclear. A common proposal is that stretch reflexes contribute to the regulation of limb stability; increased reflex sensitivity during tasks performed in unstable environments supports this hypothesis. Alternatively, before movement onset, stretch reflexes can assist an imposed stretch, opposite to what would be expected from a stabilizing response. Here we show that stretch reflex modulation in tasks that require changes in limb stability is mediated by motor cortical pathways, and that these differ from pathways contributing to reflex modulation that depend on how the subject is instructed to react to an imposed perturbation. By timing muscle stretches such that the modulated portion of the reflex occurred within a cortical silent period induced by transcranial magnetic stimulation, we abolished the increase in reflex sensitivity observed when individuals stabilized arm posture within a compliant environment. Conversely, reflex modulation caused by altered task instruction was unaffected by cortical silence. These results demonstrate that task-dependent changes in reflex function can be mediated through multiple neural pathways and that these pathways have task-specific roles.

Effects of glucose and glutamine concentration in the formulation of the artificial cerebrospinal fluid (ACSF).

The composition of the ACSF is fundamental in controlling the extracellular environment of the brain slice preparation. 'Typical' formulations lack amino acids and contain a higher concentration of glucose (10 mM) than in the cerebrospinal fluid (0.47-4.4 mM). We examined the effects of different concentrations of glutamine, the most abundant amino acid in the CSF, and glucose on rat hippocampal slice physiology. Bipolar paired-pulse stimulation was applied to the Schaffer collaterals and population spikes were monitored in the CA1 pyramidal layer for approximately 1 hour. Addition of glutamine (0.5 mM) to slices superfused with 10 mM of glucose did not enhance population spike amplitude. Higher concentration of glutamine (2-5 mM) resulted in spreading-depression. Decreasing glucose concentration from 10 mM to 5 mM, in the absence of glutamine, attenuated population spikes. Decreasing glucose to 2 mM, in the absence of glutamine, suppressed evoked population spikes. Superfusing brain slices with ACSF containing 'physiological' concentrations of both glucose (2 mM) and glutamine (0.5 mM) similarly suppressed population spikes. In separate experiments, during high-K+ induced epileptiform activity, glutamine (0.5 mM) did not affect the burst duration, frequency or waveform. These results suggest that the concentration of glucose in ACSF should conservatively be 10 mM in order to maximize paired-pulse population responses while the presence of physiological concentration of glutamine (0.5 mM) has minimal effects on paired-pulse responses and high-K+ induced epileptiform activity. These results are discussed in the context of fundamental differences between in vitro brain slice superfusion and in vivo brain perfusion.

Spike timing amplifies the effect of electric fields on neurons: implications for endogenous field effects.

Despite compelling phenomenological evidence that small electric fields (<5 mV/mm) can affect brain function, a quantitative and experimentally verified theory is currently lacking. Here we demonstrate a novel mechanism by which the nonlinear properties of single neurons "amplify" the effect of small electric fields: when concurrent to suprathreshold synaptic input, small electric fields can have significant effects on spike timing. For low-frequency fields, our theory predicts a linear dependency of spike timing changes on field strength. For high-frequency fields (relative to the synaptic input), the theory predicts coherent firing, with mean firing phase and coherence each increasing monotonically with field strength. Importantly, in both cases, the effects of fields on spike timing are amplified with decreasing synaptic input slope and increased cell susceptibility (millivolt membrane polarization per field amplitude). We confirmed these predictions experimentally using CA1 hippocampal neurons in vitro exposed to static (direct current) and oscillating (alternating current) uniform electric fields. In addition, we develop a robust method to quantify cell susceptibility using spike timing. Our results provide a precise mechanism for a functional role of endogenous field oscillations (e.g., gamma) in brain function and introduce a framework for considering the effects of environmental fields and design of low-intensity therapeutic neurostimulation technologies.