Intracortical Microstimulation: Regaining the senses of touch and movement

Artificially activating certain neurons in the cortex can make a tetraplegic patient feel naturalistic sensations of skin pressure and arm movement.
  1. Victor de Lafuente  Is a corresponding author
  1. National Autonomous University of Mexico, México

When we reach for a cup of coffee, our muscles and joints send feedback signals that inform our brain about changes in the position of our limbs and the forces acting on them. Then, when we actually grab the cup, our skin helps us make a successful grip by sensing that we have made contact with an object and relaying information about its temperature, weight and so on (Johansson and Flanagan, 2009). Without proprioceptive information – the sensory feedback from our tendons and muscles – and our sense of touch, it would be extremely difficult to perform even trivial tasks.

This is especially relevant to efforts to help people with damaged limbs or spinal cords regain their independence (Nicolelis, 2003). Thanks to recent advances in neuroscience and engineering, such patients can now be equipped with sophisticated robotic prostheses that enable them to walk or reach for objects. But these individuals are still missing the important senses of touch and proprioception that are needed to feel and control either paralyzed or artificial limbs (Bensmaia and Miller, 2014).

Now, in eLife, Richard Andersen of the California Institute of Technology and colleagues – including Michelle Salas and Luke Bashford as joint first authors – report that it is possible, in principle, to restore lost tactile and proprioceptive sensations in humans by directly activating the relevant neurons in the brain (Salas et al., 2018). In an amazing feat of neurosurgery and engineering, a tetraplegic patient was surgically implanted with metal electrodes in the somatosensory cortex, the area of the brain that processes internal and external sensations. Small electric currents were then injected through these electrodes, activating the neurons in the vicinity.

The power of intracortical microstimulation, as this technique is called, was first demonstrated almost 30 years ago when William T. Newsome and colleagues used it to show that perception of visual motion could be manipulated by injecting small currents near motion-sensitive neurons in the cortex of Rhesus monkeys (Salzman et al., 1990). As they wrote in their original report: “… it is remarkable that local microstimulation of directionally selective neurons can cause a substantial change in perception.” More recent work, also in non-human primates, has revealed that artificially activating touch or vision-related neurons elicits behavioral responses that are consistent with the animals having felt a mechanical vibration or a visual stimulus (Romo et al., 1998; Murphey and Maunsell, 2007).

However, microstimulation experiments in non-human animals cannot provide us with information about the subjective quality of the sensations evoked by the artificial activation of neurons. What does having information directly fed to our cortical neurons actually feel like? This question can only be answered by performing experiments on humans. A recent groundbreaking experiment by Robert Gaunt and collaborators, in which they used microstimulation on a tetraplegic patient, revealed that the majority of the tactile sensations evoked by the technique felt possibly natural by the participant (Flesher et al., 2016).

The new study by Salas et al. – who are based at Caltech, the Keck School of Medicine of USC and the Rancho Los Amigos National Rehabilitation Center – goes a step further by being able to generate sensations of proprioception. Salas et al. showed that microstimulation of touch-related neurons within the somatosensory cortex of a tetraplegic patient can evoke natural sensations, similar to those experienced before the injury. In particular, the patient reported feeling sensations that resembled skin pressure, tapping and vibration, and also proprioceptive experiences that are normally associated with movements of the arm and hand. Microstimulation therefore appears to be a promising therapeutic way to restore both touch and proprioception in tetraplegic individuals.

However, for the technique to be an effective therapy, the interface between the electrode array and the cortical neurons needs to remain viable for years, if not decades. For this to be possible, future research should focus on replacing metal electrodes with electrodes made from new materials that are better suited to providing a long-lasting neuronal interface to the brain (Bareket-Keren and Hanein, 2012). In turn, this interface would allow the plastic nature of the brain to learn, better interpret, and ultimately embody the artificial electric signals originating from the neuronal implant. More generally, a successful neural interface would permit a constant and seamless interaction between our brains and future advances in technology. In addition to helping patients recover lost functions, such an interface might also help them gain new abilities like enhanced vision and hearing, or perception of magnetic fields.

References

Article and author information

Author details

  1. Victor de Lafuente

    Victor de Lafuente is in the Institute of Neurobiology, National Autonomous University of Mexico, Querétaro, México

    For correspondence
    lafuente@unam.mx
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1047-1354

Publication history

  1. Version of Record published: April 10, 2018 (version 1)

Copyright

© 2018, de Lafuente

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,027
    Page views
  • 144
    Downloads
  • 3
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Victor de Lafuente
(2018)
Intracortical Microstimulation: Regaining the senses of touch and movement
eLife 7:e36137.
https://doi.org/10.7554/eLife.36137
  1. Further reading

Further reading

    1. Neuroscience
    Lei Yang, Jingtao Zhang ... Chen Zhang
    Tools and Resources Updated

    Synapse is the fundamental structure for neurons to transmit information between cells. The proper synapse formation is crucial for developing neural circuits and cognitive functions of the brain. The aberrant synapse formation has been proved to cause many neurological disorders, including autism spectrum disorders and intellectual disability. Synaptic cell adhesion molecules (CAMs) are thought to play a major role in achieving mechanistic cell-cell recognition and initiating synapse formation via trans-synaptic interactions. Due to the diversity of synapses in different brain areas, circuits and neurons, although many synaptic CAMs, such as Neurexins (NRXNs), Neuroligins (NLGNs), Synaptic cell adhesion molecules (SynCAMs), Leucine-rich-repeat transmembrane neuronal proteins (LRRTMs), and SLIT and NTRK-like protein (SLITRKs) have been identified as synaptogenic molecules, how these molecules determine specific synapse formation and whether other molecules driving synapse formation remain undiscovered are unclear. Here, to provide a tool for synapse labeling and synaptic CAMs screening by artificial synapse formation (ASF) assay, we generated synaptotagmin-1-tdTomato (Syt1-tdTomato) transgenic mice by inserting the tdTomato-fused synaptotagmin-1 coding sequence into the genome of C57BL/6J mice. In the brain of Syt1-tdTomato transgenic mice, the tdTomato-fused synaptotagmin-1 (SYT1-tdTomato) signals were widely observed in different areas and overlapped with synapsin-1, a widely-used synaptic marker. In the olfactory bulb, the SYT1-tdTomato signals are highly enriched in the glomerulus. In the cultured hippocampal neurons, the SYT1-tdTomato signals showed colocalization with several synaptic markers. Compared to the wild-type (WT) mouse neurons, cultured hippocampal neurons from Syt1-tdTomato transgenic mice presented normal synaptic neurotransmission. In ASF assays, neurons from Syt1-tdTomato transgenic mice could form synaptic connections with HEK293T cells expressing NLGN2, LRRTM2, and SLITRK2 without immunostaining. Therefore, our work suggested that the Syt1-tdTomato transgenic mice with the ability to label synapses by tdTomato, and it will be a convenient tool for screening synaptogenic molecules.

    1. Neuroscience
    Daniel R Schonhaut, Aditya M Rao ... Michael J Kahana
    Research Article Updated

    Memory formation depends on neural activity across a network of regions, including the hippocampus and broader medial temporal lobe (MTL). Interactions between these regions have been studied indirectly using functional MRI, but the bases for interregional communication at a cellular level remain poorly understood. Here, we evaluate the hypothesis that oscillatory currents in the hippocampus synchronize the firing of neurons both within and outside the hippocampus. We recorded extracellular spikes from 1854 single- and multi-units simultaneously with hippocampal local field potentials (LFPs) in 28 neurosurgical patients who completed virtual navigation experiments. A majority of hippocampal neurons phase-locked to oscillations in the slow (2–4 Hz) or fast (6–10 Hz) theta bands, with a significant subset exhibiting nested slow theta × beta frequency (13–20 Hz) phase-locking. Outside of the hippocampus, phase-locking to hippocampal oscillations occurred only at theta frequencies and primarily among neurons in the entorhinal cortex and amygdala. Moreover, extrahippocampal neurons phase-locked to hippocampal theta even when theta did not appear locally. These results indicate that spike-time synchronization with hippocampal theta is a defining feature of neuronal activity in the hippocampus and structurally connected MTL regions. Theta phase-locking could mediate flexible communication with the hippocampus to influence the content and quality of memories.