Difference between revisions of "Week9"

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*Introduction/Aims
 
*Introduction/Aims
  
Previous work had shown that GABAA receptors from the brain of patients afflicted with mesial temporal lobe epilepsy (MTLE) become less efficient (run-down) when repetitively activated by GABA. Other distinct mechanisms, however, have also been proposed that could also potentially underlie MTLE. To better understand the underlying mechanims of MTLE the authors test whether the antiepileptic drug, levetiracetam (LEV), which is used as an adjunctive treatment for medically intractable MTLE, counteracts the GABAA receptor run-down.
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*Previous work: Current assistive technologies rely on devices for which an extant function provides a signal that substitutes for missing actions. For example, cameras can monitor eye movements that can be used to point a computer cursor. Although these surrogate devices have been available for some time, they are typically limited in utility, cumbersome to maintain, and disruptive of natural actions. For instance, gaze towards objects of interest disrupts eye-based control. By contrast, an NMP is a type of brain–computer interface (BCI) that can guide movement by harnessing the existing neural substrate for that action—that is, neuronal activity patterns in motor areas.
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For this technology to be successful, there are two basic requirements:
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-There must be persistent activity in the relevant brain areas (in this case M1), despite injury to spinal cord.
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-This activity must be under the subject's  voluntary control (this allows the construction of a control signal).
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*Methods
 
*Methods

Revision as of 19:33, 18 March 2010

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MANUSCRIPT ID

  • Neuronal ensemble control of prosthetic devices by a human with tetraplegia
  • Leigh R. Hochberg, Mijail D. Serruya, Gerhard M. Friehs, Jon A. Mukand, Maryam Saleh, Abraham H. Caplan, Almut Branner, David Chen, Richard D. Penn and John P. Donoghue, Nature 442, 164-171 (13 July 2006)
  • PURPOSE: Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.
  • Neuromotor Prostheses • Tetraplegia • Neuronal ensembles • Control Signal • Linear Filter

MANUSCRIPT Details

  • Introduction/Aims
  • Previous work: Current assistive technologies rely on devices for which an extant function provides a signal that substitutes for missing actions. For example, cameras can monitor eye movements that can be used to point a computer cursor. Although these surrogate devices have been available for some time, they are typically limited in utility, cumbersome to maintain, and disruptive of natural actions. For instance, gaze towards objects of interest disrupts eye-based control. By contrast, an NMP is a type of brain–computer interface (BCI) that can guide movement by harnessing the existing neural substrate for that action—that is, neuronal activity patterns in motor areas.

For this technology to be successful, there are two basic requirements:

-There must be persistent activity in the relevant brain areas (in this case M1), despite injury to spinal cord. -This activity must be under the subject's voluntary control (this allows the construction of a control signal).




  • Methods

The others obtained resectioned brain tissue from the temporal lobe of 5 patients diagnosed with MTLE, along with one non-epileptic patient (diagnosed with glioblastoma) and one patient diagnosed with lateral temporal lobe epilepsy (LTLE)

Tissue was used in one of two ways: 1) Tissue was homogenized in order create membrane vesicles. These vesicles were then injected into xenopus oocytes and allowed to incorporate. 2) Neocortical was prepared into slices.

Whole cell patch clamping was used to record currents of oocytes or pyramidal neurons in response to exogenously puffed GABA. This was done in either the presence or absense of LEV.

  • Results

1) In oocytes it was found that, compared to non-epileptic tissue, the GABA current of epileptic tissue showed significant run down. This rundown was prevented by LEV such that there was no difference in response between epileptic and non-epileptic tissue. There was no difference between epipleptic patients who were taking LEV prior to resection and those that were not.

2) A dose response curve for LEV was constructed. At low doses there is decreasing rundown with increasing concentrations of LEV. In fact, at a dose of 1 uM LEV causes a use dependent increase of the GABA response. At all doses tested above 1 uM LEV there is a run down of ~20% which is comparable to that seen in non-epileptic tissue.

3) The initial results were were confirmed using neocortical slices. They found that, like in oocytes, neocortical slices from epileptics showed a rundown of the GABA current. Again, like ocytes, this run down was prevented by the presence of LEV.

4) They used tissue from the subiculum rather than the neocortex. They found that like cortical tissue there was a rundown of the GABA response in epileptic tissue, however unlike cortical tissue this rundown was not effected by LEV.

5) They tested the effect of LEV on recover from rundown. They applied LEV after GABA rundown was elicited and found that LEV enhanced the recovery.

6) They tested the effect of LEV on tissue from patient diagnosed with LTLE (which is not associated with rundown) and found that there was no effect on overall current or desensitization.

7) Last, because BDNF also prevents rundown they tested whether the effect of LEV is exerted through BDNF. They found that the effect of LEV was unaffected by blockade of the BDNF receptor TrkB. Like BDNF, however, the effect of LEV was blocked by inhibiting PKC.

  • Discussion

This paper confirms previous studies which associated MTLE with a rundown of GABAA currents. It adds to this by showing that the antiepileptic drug LEV prevents this rundown and enhances recovery, suggesting that the rundown is at the core of the disease state. The lack of effect in the subiculum also fits with model because in the subiculum GABA can be excitatory. Thus, maintenance of rundown would act to prevent seizures.

Lastly, this paper validates the use of oocytes as model system for studying epilepsy and suggests that it may serve as a useful way of screening antiepileptic drugs.

MANUSCRIPT ID

  • Title

Learning to Control a Brain–Machine Interface for Reaching and Grasping by Primates


  • Reference

Carmena JM, Lebedev Ma, Crist RE, et al. Learning to control a brain-machine interface for reaching and grasping by primates. PLoS biology. 2003;1(2):E42. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14624244.


  • Abstract

Reaching and grasping in primates depend on the coordination of neural activity in large frontoparietal ensembles. Here we demonstrate that primates can learn to reach and grasp virtual objects by controlling a robot arm through a closed-loop brain-machine interface (BMIc) that uses multiple mathematical models to extract several motor parameters (i.e., hand position, velocity, gripping force, and the EMGs of multiple arm muscles) from the electrical activity of frontoparietal neuronal ensembles. As single neurons typically contribute to the encoding of several motor parameters, we observed that high BMIc accuracy required recording from large neuronal ensembles. Continuous BMIc operation by monkeys led to significant improvements in both model predictions and behavioral performance. Using visual feedback, monkeys succeeded in producing robot reach-and-grasp movements even when their arms did not move. Learning to operate the BMIc was paralleled by functional reorganization in multiple cortical areas, suggesting that the dynamic properties of the BMIc were incorporated into motor and sensory cortical representations.


  • Keywords

BMI, Brain-Machine Interface, Closed Loop, Directional Tuning, Primary Motor Cortex, Macaque, Linear Model, Robotics, Artificial Intelligence


  • Input Author

JJM


MANUSCRIPT DETAILS

  • Introduction/Aims


Spinal cord injuries and neurodegeneration lead to thousands of motor deficits every year. Typically, research is aimed at reconstructing connectivity and function of damaged areas. This paper aims to bypass the damaged area entirely by recording from motor control areas and using those signals to control an external robotic prosthesis.


Primary motor cortex and surrounding areas probably control intentional motor movements, but there are many open questions regarding brain-machine interfaces recording from these areas. These questions include:

*What type of brain signal is the best input? Single unit? Multiunit? Local Field Potentials?

*Which cortical brain region(s) should we record from and contain the most information about motor movements?

*What types of motor commands can be extracted from cortical activity?

*How does an artifiicial actuator like a robot arm affect performance?

*How does use of a BMI reorganize cortical functionality?

This paper aims to explore these questions.


  • Methods



The subjects in this study were two adult female macaque monkeys. Each monkey had training in interacting with a computer while in a chair. Recording arrays were implanted in primary motor cortex, dorsal premotor cortex, and supplementary motor cortex. Monkey 1 also had a recording array in primary sensory cortex. Monkey 2 also had a recording array in the medial intraparietal area of posterior parietal cortex.

Example.jpg

The experimental set-up was as follows. The monkeys were seated in a constrained chair facing a computer screen. In some trials the monkeys controlled a cursor on the screen by moving and squeezing a pole with their left arm. In other trials the pole was absent. Multiunit recording data from the abovementioned cortical areas was passed into a data acquisition box. A linear model was trained on the neural recording data to predict the position and squeeze strength of the cursor. In pole-control mode, the monkey directly controlled a robot arm; in brain-control mode, the linear model controlled the robot arm. The cursor's position on the screen was a reflection of the robot arm's position.


In task 1, the monkey simply had to move the cursor to a target on the screen, and was given a juice reward upon successful completion in less than 5 seconds.

In task 2, the monkey had to apply the correct amount of force to expand the cursor to the proper size.

Task 3 was a combination of task 1 and 2. The monkey had to move the cursor to the target and then apply the correct pressure.

The linear model was a simple linear regression model, which finds the matrix of weights A that minimizes the mean squared error of the actual training outputs Y vs. X*A. Y is the output matrix over time, and X is the input matrix over time. A was found by the equation A = inv(X'X)X'Y, where inv(X) represents the inverse operation on a matrix, and X' represents the transpose operation on a matrix. The first 10 minutes of pole control activity was used as training, then the values of A were frozen in place for prediction.


  • Results



  • Summary



  • Discussion



  • References