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Miniaturized Technologies for Enhancement of Motor Plasticity.

Moorjani S - Front Bioeng Biotechnol (2016)

Bottom Line: The idea that the damaged brain can functionally reorganize itself - so when one part fails, there lies the possibility for another to substitute - is an exciting discovery of the twentieth century.This is a very significant alteration from our previously static view of the brain and has profound implications for the rescue of function after a motor injury.Presentation of the right cues, applied in relevant spatiotemporal geometries, is required to awaken the dormant plastic forces essential for repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, and the Washington National Primate Research Center, University of Washington , Seattle, WA , USA.

ABSTRACT
The idea that the damaged brain can functionally reorganize itself - so when one part fails, there lies the possibility for another to substitute - is an exciting discovery of the twentieth century. We now know that motor circuits once presumed to be hardwired are not, and motor-skill learning, exercise, and even mental rehearsal of motor tasks can turn genes on or off to shape brain architecture, function, and, consequently, behavior. This is a very significant alteration from our previously static view of the brain and has profound implications for the rescue of function after a motor injury. Presentation of the right cues, applied in relevant spatiotemporal geometries, is required to awaken the dormant plastic forces essential for repair. The focus of this review is to highlight some of the recent progress in neural interfaces designed to harness motor plasticity, and the role of miniaturization in development of strategies that engage diverse elements of the neuronal machinery to synergistically facilitate recovery of function after motor damage.

No MeSH data available.


Related in: MedlinePlus

Restoration of function after brain injury using a closed-loop electronic neural interface. (A) Left panel shows normal connectivity of primary motor cortex (M1), primary somatosensory cortex (S1), and premotor cortex (PM). Both M1 and PM send substantial outputs to the spinal cord. Right panel shows disruptions in connectivity between M1 and other regions (S1, PM, spinal cord) due to a focal M1 injury. The dashed line indicates enhanced functional connectivity between PM and S1, proposed to be mitigated by a brain–machine–brain interface (BMBI), which might contribute to the recovery of forelimb function after injury by restoration of somatosensory–motor communication. (B) Performance of rats after injury to M1. The plot compares success on a skilled reaching task, which is a sensitive measure of forelimb motor function, between groups of rats that received activity-dependent stimulation (ADS), open-loop stimulation (OLS), and no electrical stimulation (Control) after a M1 lesion. ADS involved detection of spikes in PM and subsequent delivery of electrical stimulation to S1 after a 7.5-ms delay. The OLS group received S1 stimulation uncorrelated with spikes in PM, while the control rats had no implanted microdevices. The dashed line indicates pre-lesion pellet-retrieval performance, with the 95% confidence interval shown by the gray box bounding it. Error bars represent 95% confidence intervals. Asterisks indicate P < 0.05 significance between ADS and OLS groups. Rats were included in the analysis even if the microdevice was no longer functional, which is indicated by #. Diamonds, squares, and triangles represent individual animal data points. Image adapted, with permission, from Guggenmos et al. (2013).
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Figure 2: Restoration of function after brain injury using a closed-loop electronic neural interface. (A) Left panel shows normal connectivity of primary motor cortex (M1), primary somatosensory cortex (S1), and premotor cortex (PM). Both M1 and PM send substantial outputs to the spinal cord. Right panel shows disruptions in connectivity between M1 and other regions (S1, PM, spinal cord) due to a focal M1 injury. The dashed line indicates enhanced functional connectivity between PM and S1, proposed to be mitigated by a brain–machine–brain interface (BMBI), which might contribute to the recovery of forelimb function after injury by restoration of somatosensory–motor communication. (B) Performance of rats after injury to M1. The plot compares success on a skilled reaching task, which is a sensitive measure of forelimb motor function, between groups of rats that received activity-dependent stimulation (ADS), open-loop stimulation (OLS), and no electrical stimulation (Control) after a M1 lesion. ADS involved detection of spikes in PM and subsequent delivery of electrical stimulation to S1 after a 7.5-ms delay. The OLS group received S1 stimulation uncorrelated with spikes in PM, while the control rats had no implanted microdevices. The dashed line indicates pre-lesion pellet-retrieval performance, with the 95% confidence interval shown by the gray box bounding it. Error bars represent 95% confidence intervals. Asterisks indicate P < 0.05 significance between ADS and OLS groups. Rats were included in the analysis even if the microdevice was no longer functional, which is indicated by #. Diamonds, squares, and triangles represent individual animal data points. Image adapted, with permission, from Guggenmos et al. (2013).

Mentions: The early 2000s have seen the implantation of electronic chips with advanced functionalities to operate as sophisticated closed-loop systems. An example is the “Neurochip,” which is an autonomous head-fixed recurrent brain–computer interface (rBCI), developed by Fetz and coworkers, that records activity of neurons and processes this activity in real time to deliver electrical stimulation contingent on neural events (Mavoori et al., 2005; Jackson et al., 2006b). This rBCI can operate continuously during days of unrestrained animal behavior, which permits detailed investigations of synaptic plasticity and behavioral adaptation. Jackson et al. employed the Neurochip in the motor cortex of monkeys to create artificial connections between neuronal sites by using action potentials recorded on one microwire electrode to trigger electrical stimuli, which were delivered to a neighboring site. At the end of their conditioning, the motor output elicited from the recording sites (Nrec) shifted toward the output evoked from the stimulation sites (Nstim), while the output from the nearby control sites (Nctrl) remained unchanged (Figure 1). The induced plasticity lasted for up to ten days post conditioning (Jackson et al., 2006a). This conditioning paradigm has also been used to modify corticospinal connections in freely-behaving monkeys through an artificial recurrent connection between single corticomotoneuronal cells and their terminal spinal sites (Nishimura et al., 2013). Such experiments provide important insights into the function and interaction of brain sites during behavior. Corresponding to these fundamental research opportunities are prospects for translating circuit-retraining investigations into clinical therapies. By delivering stimuli synchronized with cell activity, continuous operation of the Neurochip can strengthen weak biological connections. Also, the artificial connections created by such bidirectional interfaces can bridge impaired neural circuitry to replace lost or damaged pathways. Two studies have provided compelling evidence underscoring the clinical applicability of closed-loop electronic neural interfaces. First, Moritz et al. created a direct connection between cortical cells and forearm muscles to restore volitional control of movement to paralyzed limbs in monkeys (Moritz et al., 2008). In a second study, a miniaturized head-mounted wireless neuroprosthesis, similar, in principle, to the Neurochip, was used to bridge communication between motor and somatosensory areas in the cerebral cortex for restoration of reaching and grasping functions in adult rats after a traumatic brain injury (Figure 2; Guggenmos et al., 2013).


Miniaturized Technologies for Enhancement of Motor Plasticity.

Moorjani S - Front Bioeng Biotechnol (2016)

Restoration of function after brain injury using a closed-loop electronic neural interface. (A) Left panel shows normal connectivity of primary motor cortex (M1), primary somatosensory cortex (S1), and premotor cortex (PM). Both M1 and PM send substantial outputs to the spinal cord. Right panel shows disruptions in connectivity between M1 and other regions (S1, PM, spinal cord) due to a focal M1 injury. The dashed line indicates enhanced functional connectivity between PM and S1, proposed to be mitigated by a brain–machine–brain interface (BMBI), which might contribute to the recovery of forelimb function after injury by restoration of somatosensory–motor communication. (B) Performance of rats after injury to M1. The plot compares success on a skilled reaching task, which is a sensitive measure of forelimb motor function, between groups of rats that received activity-dependent stimulation (ADS), open-loop stimulation (OLS), and no electrical stimulation (Control) after a M1 lesion. ADS involved detection of spikes in PM and subsequent delivery of electrical stimulation to S1 after a 7.5-ms delay. The OLS group received S1 stimulation uncorrelated with spikes in PM, while the control rats had no implanted microdevices. The dashed line indicates pre-lesion pellet-retrieval performance, with the 95% confidence interval shown by the gray box bounding it. Error bars represent 95% confidence intervals. Asterisks indicate P < 0.05 significance between ADS and OLS groups. Rats were included in the analysis even if the microdevice was no longer functional, which is indicated by #. Diamonds, squares, and triangles represent individual animal data points. Image adapted, with permission, from Guggenmos et al. (2013).
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Related In: Results  -  Collection

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Figure 2: Restoration of function after brain injury using a closed-loop electronic neural interface. (A) Left panel shows normal connectivity of primary motor cortex (M1), primary somatosensory cortex (S1), and premotor cortex (PM). Both M1 and PM send substantial outputs to the spinal cord. Right panel shows disruptions in connectivity between M1 and other regions (S1, PM, spinal cord) due to a focal M1 injury. The dashed line indicates enhanced functional connectivity between PM and S1, proposed to be mitigated by a brain–machine–brain interface (BMBI), which might contribute to the recovery of forelimb function after injury by restoration of somatosensory–motor communication. (B) Performance of rats after injury to M1. The plot compares success on a skilled reaching task, which is a sensitive measure of forelimb motor function, between groups of rats that received activity-dependent stimulation (ADS), open-loop stimulation (OLS), and no electrical stimulation (Control) after a M1 lesion. ADS involved detection of spikes in PM and subsequent delivery of electrical stimulation to S1 after a 7.5-ms delay. The OLS group received S1 stimulation uncorrelated with spikes in PM, while the control rats had no implanted microdevices. The dashed line indicates pre-lesion pellet-retrieval performance, with the 95% confidence interval shown by the gray box bounding it. Error bars represent 95% confidence intervals. Asterisks indicate P < 0.05 significance between ADS and OLS groups. Rats were included in the analysis even if the microdevice was no longer functional, which is indicated by #. Diamonds, squares, and triangles represent individual animal data points. Image adapted, with permission, from Guggenmos et al. (2013).
Mentions: The early 2000s have seen the implantation of electronic chips with advanced functionalities to operate as sophisticated closed-loop systems. An example is the “Neurochip,” which is an autonomous head-fixed recurrent brain–computer interface (rBCI), developed by Fetz and coworkers, that records activity of neurons and processes this activity in real time to deliver electrical stimulation contingent on neural events (Mavoori et al., 2005; Jackson et al., 2006b). This rBCI can operate continuously during days of unrestrained animal behavior, which permits detailed investigations of synaptic plasticity and behavioral adaptation. Jackson et al. employed the Neurochip in the motor cortex of monkeys to create artificial connections between neuronal sites by using action potentials recorded on one microwire electrode to trigger electrical stimuli, which were delivered to a neighboring site. At the end of their conditioning, the motor output elicited from the recording sites (Nrec) shifted toward the output evoked from the stimulation sites (Nstim), while the output from the nearby control sites (Nctrl) remained unchanged (Figure 1). The induced plasticity lasted for up to ten days post conditioning (Jackson et al., 2006a). This conditioning paradigm has also been used to modify corticospinal connections in freely-behaving monkeys through an artificial recurrent connection between single corticomotoneuronal cells and their terminal spinal sites (Nishimura et al., 2013). Such experiments provide important insights into the function and interaction of brain sites during behavior. Corresponding to these fundamental research opportunities are prospects for translating circuit-retraining investigations into clinical therapies. By delivering stimuli synchronized with cell activity, continuous operation of the Neurochip can strengthen weak biological connections. Also, the artificial connections created by such bidirectional interfaces can bridge impaired neural circuitry to replace lost or damaged pathways. Two studies have provided compelling evidence underscoring the clinical applicability of closed-loop electronic neural interfaces. First, Moritz et al. created a direct connection between cortical cells and forearm muscles to restore volitional control of movement to paralyzed limbs in monkeys (Moritz et al., 2008). In a second study, a miniaturized head-mounted wireless neuroprosthesis, similar, in principle, to the Neurochip, was used to bridge communication between motor and somatosensory areas in the cerebral cortex for restoration of reaching and grasping functions in adult rats after a traumatic brain injury (Figure 2; Guggenmos et al., 2013).

Bottom Line: The idea that the damaged brain can functionally reorganize itself - so when one part fails, there lies the possibility for another to substitute - is an exciting discovery of the twentieth century.This is a very significant alteration from our previously static view of the brain and has profound implications for the rescue of function after a motor injury.Presentation of the right cues, applied in relevant spatiotemporal geometries, is required to awaken the dormant plastic forces essential for repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, and the Washington National Primate Research Center, University of Washington , Seattle, WA , USA.

ABSTRACT
The idea that the damaged brain can functionally reorganize itself - so when one part fails, there lies the possibility for another to substitute - is an exciting discovery of the twentieth century. We now know that motor circuits once presumed to be hardwired are not, and motor-skill learning, exercise, and even mental rehearsal of motor tasks can turn genes on or off to shape brain architecture, function, and, consequently, behavior. This is a very significant alteration from our previously static view of the brain and has profound implications for the rescue of function after a motor injury. Presentation of the right cues, applied in relevant spatiotemporal geometries, is required to awaken the dormant plastic forces essential for repair. The focus of this review is to highlight some of the recent progress in neural interfaces designed to harness motor plasticity, and the role of miniaturization in development of strategies that engage diverse elements of the neuronal machinery to synergistically facilitate recovery of function after motor damage.

No MeSH data available.


Related in: MedlinePlus