Modeling Neural Signals for Brain-Machine Interfaces
1. Brain Machine Interfaces: Modeling Strategies for
Neural Signal Processing
Jose C. Principe, Ph.D.
Distinguished Professor ECE, BME
Computational NeuroEngineering Laboratory
Electrical and Computer Engineering Department
University of Florida
www.cnel.ufl.edu
principe@cnel.ufl.edu
2. Brain Machine Interfaces (BMI)
A man made device that either substitutes a
sensory input to the brain, repairs functional
communication between brain regions or
translates intention of movement.
3. Types of BMIs
Sensory (Input BMI): Providing sensory input to form percepts when
natural systems are damaged.
Ex: Visual, Auditory Prosthesis
Motor (Output BMI): Converting motor intent to a command output
(physical device, damaged limbs)
Ex: Prosthetic Arm Control
Cognitive BMI: Interpret internal neuronal state to deliever feedback to
the neural population.
Ex: Epilepsy, DBS Prosthesis
Computational Neuroscience and Technology developments are
playing a larger role in the development of each of these
areas.
4. J.R. Wolpaw et al. 2002
BCI (BMI) bypasses the brain’s normal pathways of peripheral nerves (and muscles)
General Architecture
6. Levels of Abstraction for Neurotechnology
Brain is an extremely
complex system
1012 neurons
1015 synapses
Specific
interconnectivity
7. Tapping into the Nervous System
The choice and availability of brain signals and
recording methods can greatly influence the ultimate
performance of the BMI.
The level of BMI performance may be attributed to
selection of electrode technology, choice of model, and
methods for extracting rate, frequency, or timing codes.
11. Florida Multiscale Signal Acquisition
EEG
ECoG
Microelectrodes
Least
Invasive
Highest
Resolution
NRG IRB
Approval for
Human
Studies
NRG
IACUC
Approval for
Animal
Studies
Develop a experimental paradigm with a nested hierarchy
for studying neural population dynamics.
12. Common BMI-BCI Methods
BMIs --- Invasive, work with intention of movement
• Spike trains, field potentials, ECoG
• Very specific, potentially better performance
BCIs --- Noninvasive, subjects must learn how to control their
brain activity
• EEG
• Very small bandwidth
13. Computational NeuroScience
Integration of probabilistic models of information processing with
the neurophysiological reality of brain anatomy, physiology and
purpose.
Need to abstract the details of the “wetware” and ask what is the
purpose of the function. Then quantify it in mathematical terms.
Difficult but very promising. One issue is that biological evolution is
a legacy system!
BMI research is an example of a computational neuroscience
approach.
14. How to put it together?
NeoCortical Brain Areas Related to Movement
Posterior Parietal (PP) –
Visual to motor
transformation
Premotor (PM) and Dorsal
Premotor (PMD) -
Planning and guidance
(visual inputs)
Primary Motor (M1) –
Initiates muscle contraction
16. Computational Models of Neural Intent
Two different levels of neurophysiology realism
Black Box models – no realism, function relation between
input desired response
Generative Models – minimal realism, state space models
using neuroscience elements
17. Signal Processing Approaches with Black
Box Modeling
Accessing 2 types of signals (cortical activity and behavior) leads us to a
general class of I/O models.
Data for these models are rate codes obtained by binning spikes on 100
msec windows.
Optimal FIR Filter – linear, feedforward
TDNN – nonlinear, feedforward
Multiple FIR filters – mixture of experts
RMLP – nonlinear, dynamic
18. Linear Model (Wiener-Hopf solution)
Consider a set of spike counts from M neurons, and a hand position vector dC (C
is the output dimension, C = 2 or 3). The spike count of each neuron is
embedded by an L-tap discrete time-delay line. Then, the input vector for a
linear model at a given time instance n is composed as x(n) = [x1(n), x1(n-1) …
x1(n-L+1), x2(n) … xM(n-L+1)]T, xLM, where xi(n-j) denotes the spike count of
neuron i at a time instance n-j.
A linear model estimating hand position at time instance n from the embedded spike
counts can be described as
where yc is the c-coordinate of the estimated hand position by the model, wji is a
weight on the connection from xi(n-j) to yc, and bc is a bias for the c-coordinate.
c
L
i
M
j
c
ji
i
c
b
w
j
n
x
y
1
0 1
)
(
19. Linear Model (Wiener-Hopf solution)
In a matrix form, we can rewrite the previous equation as
where y is a C-dimensional output vector, and W is a weight matrix of
dimension (LM+1)C. Each column of W consists of [w10
c, w11
c, w12
c…, w1L-
1
c, w20
c, w21
c…, wM0
c, …, wML-1
c]T.
x
W
y T
x1(n)
xM(n)
z-1
z-1
…
z-1
z-1
…
…
yx(n)
yy(n)
yz(n)
20. Linear Model (Wiener-Hopf solution)
For the MIMO case, the weight matrix in the Wiener filter system is estimated
by
R is the correlation matrix of neural spike inputs with the dimension of
(LM)(LM),
where rij is the LL cross-correlation matrix between neurons i and j (i ≠ j), and
rii is the LL autocorrelation matrix of neuron i.
P is the (LM)C cross-correlation matrix between the neuronal bin count and
hand position, where pic is the cross-correlation vector between neuron i
and the c-coordinate of hand position. The estimated weights WWiener are
optimal based on the assumption that the error is drawn from white
Gaussian distribution and the data are stationary.
P
R
W 1
Wiener
MM
M
M
M
M
r
r
r
r
r
r
r
r
r
R
2
1
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22
21
1
12
11
MC
M
C
C
p
p
p
p
p
p
P
1
2
21
1
11
21. Linear Model (Wiener-Hopf solution)
The predictor WWiener minimizes the mean square error (MSE) cost function,
Each sub-block matrix rij can be further decomposed as
where rij() represents the correlation between neurons i and j with time lag .
Assuming that the random process xi(k) is ergodic for all i, we can utilize the
time average operator to estimate the correlation function. In this case, the
estimate of correlation between two neurons, rij(m-k), can be obtained by
y
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22. Linear Model (Wiener-Hopf solution)
The cross-correlation vector pic can be decomposed and estimated in the same way,
substituting xj by the desired signal cj.
From the equations, it can be seen that rij(m-k) is equal to rji(k-m). Since these two
correlation estimates are positioned at the opposite side of the diagonal entries of R,
the equality leads to a symmetric R.
The symmetric matrix R, then, can be inverted effectively by using the Cholesky
factorization. This factorization reduces the computational complexity for the inverse of
R from O(N3) using Gaussian elimination to O(N2) where N is the number of
parameters.
)
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i
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i
ij
23. Optimal Linear Model
Normalized LMS with weight
decay is a simple starting point.
Four multiplies, one divide and
two adds per weight update
Ten tap embedding with 105
neurons
For 1-D topology contains 1,050
parameters (3,150)
Alternatively, the Wiener solution
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24. Time-Delay Neural Network (TDNN)
The first layer is a bank of linear
filters followed by a nonlinearity.
The number of delays to span I
second
y(n)= Σ wf(Σwx(n))
Trained with backpropagation
Topology contains a ten tap
embedding and five hidden
PEs– 5,255 weights (1-D)
Principe, UF
25. Multiple Switching Local Models
Multiple adaptive filters that compete to win the modeling of a signal
segment.
Structure is trained all together with normalized LMS/weight decay
Needs to be adapted for input-output modeling.
We selected 10 FIR experts of order 10 (105 input channels)
d(n)
26. Recurrent Multilayer Perceptron (RMLP) –
Nonlinear “Black Box”
Spatially recurrent dynamical
systems
Memory is created by feeding
back the states of the hidden PEs.
Feedback allows for continuous
representations on multiple
timescales.
If unfolded into a TDNN it can be
shown to be a universal mapper
in Rn
Trained with backpropagation
through time
)
)
1
(
)
(
(
)
( 1
1
1
1 b
y
W
x
W
y
t
t
f
t f
2
1
2
2 )
(
)
( b
y
W
y
t
t
27. Motor Tasks Performed
-40 -30 -20 -10 0 10 20 30 40
-40
-30
-20
-10
0
10
20
30
40
Task
1
Task
2
Data
• 2 Owl monkeys – Belle,
Carmen
• 2 Rhesus monkeys –
Aurora, Ivy
• 54-192 sorted cells
• Cortices sampled: PP,
M1, PMd, S1, SMA
• Neuronal activity rate
and behavior is time
synchronized and
downsampled to 10Hz
28. Model Building Techniques
Train the adaptive system with neuronal firing rates
(100 msec) as the input and hand position as the
desired signal.
Training - 20,000 samples (~33 minutes of neuronal
firing)
Freeze weights and present novel neuronal data.
Testing - 3,000 samples – (5 minutes of neuronal
firing)
29. Results (Belle)
Signal to error ratio (dB) Correlation Coefficient
(average) (max) (average) (max)
LMS 0.8706 7.5097 0.6373 0.9528
Kalman 0.8987 8.8942 0.6137 0.9442
TDNN 1.1270 3.6090 0.4723 0.8525
Local Linear 1.4489 23.0830 0.7443 0.9748
RNN 1.6101 32.3934 0.6483 0.9852
Based on 5 minutes of test data, computed over 4 sec
windows (training on 30 minutes)
30. Physiologic Interpretation
When the fitting error is above chance, a sensitivity analysis can
be performed by computing the Jacobian of the output vector
with respect to each neuronal input i
This calculation indicates which inputs (neurons) are most
important for modulating the output/trajectory of the model.
31. Computing Sensitivities Through the
Models
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(
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Feedforward RMLP Eqs.
General form of RMLP
Sensitivity
Feedforward Linear Eq.
General form of Linear
Sensitivity
W
x
y
)
(
)
(
t
t
)
(
)
( t
t Wx
y
Identify the neurons that affect the output the most.
32. Data Analysis : The Effect of Sensitive Neurons on Performance
0 20 40 60
-20
0
20
40
60
Hightest Sensitivity Neurons
0 20 40 60
-20
0
20
40
60
Middle Sensitivity Neurons
0 20 40 60
-20
0
20
40
60
Lowest Sensitivity Neurons
0 20 40 60 80
0
0.2
0.4
0.6
0.8
1
Probability
3D Error Radius (mm)
Movements (hits) of Test Trajectory
10 Highest Sensitivity
84 Intermediate Sensitivity
10 Low est Sensitivity
All Neurons
0 20 40 60 80 100 120
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
Sensitivity
Primate 1, Session 1
Neurons
93
19
29
5
4
84
7
26
45
104
Decay trend appears in all
animals and behavioral
paradigms
33. Directional Tuning vs. Sensitivity of
ranked cells
Tuning Sensitivity
Significance: Sensitivity analysis through trained models automatically
delivers deeply tuned cells that span the space.
34. Reaching Movement Segmentation
0 10 20 30 40 50 60 70
-30
-20
-10
0
10
20
30
40
50
60
70
X
Y
Z
Food to Mouth Mouth to Rest
Rest to Food
How does each cortical area contribute to the reconstruction of this movement?
35. Cortical Contributions Belle Day 2
0 20 40
-20
0
20
40
60
Area 1
0 20 40
-20
0
20
40
60
Area 2
0 20 40
-20
0
20
40
60
Area 3
0 20 40
-20
0
20
40
60
Area 4
0 20 40
-20
0
20
40
60
Areas 12
0 20 40
-20
0
20
40
60
Areas 13
0 20 40
-20
0
20
40
60
Areas 14
0 20 40
-20
0
20
40
60
Areas 23
0 20 40
-20
0
20
40
60
Areas 24
0 20 40
-20
0
20
40
60
Areas 34
0 20 40
-20
0
20
40
60
Areas 123
0 20 40
-20
0
20
40
60
Areas 124
0 20 40
-20
0
20
40
60
Areas 134
0 20 40
-20
0
20
40
60
Areas 234
0 20 40
-20
0
20
40
60
Areas 1234
Area 1 PP
Area 2 M1
Area 3 PMd
Area 4 M1 (right)
Train 15 separate RMLPs with every combination of cortical input.
36. Is there enough information in spike
trains for modeling movement?
Analysis is based on the time embedded model
Correlation with desired is based on a linear filter output for
each neuron
Utilize a non-stationary tracking algorithm
Parameters are updated by LMS
Build a spatial filter
Adaptive in real time
Sparse structure based on regularization for enables
selection
37. Adapted by LMS Adapted by on-line LAR
(Kim et. al., MLSP, 2004)
Architecture
x1(n)
z-1
z-1
y1(n)
w11
w1L
//
xM(n)
z-1
z-1
yM(n)
wM1
wML
//
…
y2(n)
…
c1
cM
)
(
ˆ n
d
c2
38. Training Algorithms
Tap weights for every time lag is updated by LMS
Then, the spatial filter coefficients are obtained by on-line version of
least angle regression (LAR) (Efron et. al. 2004)
i=0 r = y-X = y
Find argmaxi |xi
Tr|
xj
j
r = y-X = y-xjj
Adjust j s.t.
k, |xk
Tr|=|xi
Tr|
.
.
.
x1
xk
y
xj
j
r = y-(xjj+ xkk)
Adjust j & k s.t.
q, |xq
Tr|=|xk
Tr|=|xi
Tr|
k
)
(
)
(
2
)
(
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1
( n
x
n
e
n
w
n
w ij
ij
ij
40. Application to BMI Data – Neuronal
Subset Selection
Hand
Trajectory
(z)
Neuronal
Channel
Index
Early
Part
Late
Part
41. Generative Models for BMIs
Use partial information about the physiological system, normally
in the form of states.
They can be either applied to binned data or to spike trains
directly.
Here we will only cover the spike train implementations.
Difficulty of spike train Analysis:
Spike trains are point processes, i.e. all the information is contained
in the timing of events, not in the amplitude fo the signals!
42. Build an adaptive signal processing framework for
BMI decoding in the spike domain.
Features of Spike domain analysis
Binning window size is not a concern
Preserve the randomness of the neuron behavior.
Provide more understanding of neuron physiology (tuning) and
interactions at the cell assembly level
Infer kinematics online
Deal with nonstationary
More computation with millisecond time resolution
Goal
43. Recursive Bayesian Approach
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,
~
(
~
t
t n
X
H
Z t
t
State Time-series
model cont. observ.
Prediction
)
,
(
~
1
1
t
t
t
t v
X
F
X
Updating
t
Z
P(state|observation)
44. Recursive Bayesian approach
State space representation
First equation (system model) defines a first order Markov process.
Second equation (observation model) defines the likelihood of the
observations p(zt|xt) . The problem is completely defined by the
prior distribution p(x0).
Although the posterior distribution p(x0:t|u1:t,z1:t) constitutes the
complete solution, the filtering density p(xt|u1:t, z1:t) is normally
used for on-line problems.
The general solution methodology is to integrate over the unknown
variables (marginalization).
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45. Recursive Bayesian approach
There are two stages to update the filtering density:
Prediction (Chapman Kolmogorov)
System model p(xt|xt-1) propagates into the future the posterior density
Update
Uses Bayes rule to update the filtering density. The following equations
are needed in the solution.
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46. Kalman filter for BMI decoding
Kinematic
State
Neuron tuning
function Firing rate
Continuous
Observation
P(state|observation)
Prediction
Updating
Gaussian
Linea
r
Linea
r
[Wu et al. 2006]
For Gaussian noises and linear prediction and observation models, there
is an analytic solution called the Kalman Filter.
47. Particle Filter for BMI decoding
Kinematic
State
Neuron tuning
function Firing rate
Continuous
Observation
P(state|observation)
Prediction
Updating
nonGaussian
Linea
r
Exponential
[Brockwell et al. 2004]
In general the integrals need to be approximated by sums using
Monte Carlo integration with a set of samples drawn from the
posterior distribution of the model parameters.
48. State estimation framework for BMI decoding in
spike domain
Tuning function
Kinematics
state
Neural Tuning
function
Multi-spike trains
observation
xk k-1
x
k
F k-1
v
= ( )
,
k
x
k
z
k
H
k
n
= )
( ,
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2
x 10
5
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
time
spi
k
e
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2
x 10
5
-1.5
-1
-0.5
0
0.5
1
1.5
time (ms)
velocity
Decoding
Kinematic dynamic model
Key Idea: work with the probability of spike firing which is a
continuous random variable
49. Adaptive algorithm for point processes
Kinematic
State
Neuron tuning
function spike train
Point process
P(state|observation)
Prediction
Updating
Gaussian
Linea
r
nonlinear
[Brown et al. 2001]
Poisson
Model
50. Monte Carlo Sequential estimation for point process
Kinematic
State
Neuron tuning
function spike train
Point process
P(state|observation)
Prediction
Updating
nonGaussian
nonLinear
nonlinear
[Wang et al. 2006]
Sequential Estimate PDF
51. Monte Carlo sequential estimation framework for
BMI decoding in spike domain
STEP 1. Preprocessing
1. Generate spike trains from stored spike times 10ms interval, (99.62%
binary train)
2. Synchronize all the kinetics with the spike trains.
3. Assign the kinematic vector to reconstruct.
X=[position velocity acceleration]’
(more information, instantaneous state avoid error accumulation,
less computation)
x
52. STEP 2- Neural tuning analysis
Encoding
(Tuning)
kinematics Neural spike trains
A example of a tuned neuron
Metric: Tuning depth:
how differently does a neuron fire across
directions?
D=(max-min)/std (firing rate)
0.05
0.1
0.15
0.2
0.25
30
210
60
240
90
270
120
300
150
330
180 0
neuron No. 72 TuningDepth: 1
Neuron 72: Tuning Depth 1
)
arg(
N
i
N
N
e
r
mean
circular
53. Step 2- Information Theoretic Metric of Tuning
1
,
0
2 )
)
(
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|
(
(
log
)
|
(
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)
;
(
spike
angle
spike
p
angle
spike
p
angle
spike
p
angle
p
angle
spike
I
kinematics
direction angle
neural spikes
Information
)
(
)
,
1
(
)
|
1
(
angle
p
angle
spike
p
angle
spike
p
54. Step 2- Information theoretic Tuning depths for 3
kinds of kinematics (log axis)
55. Step 2- Tuning Function Estimation
Neural firing Model
Assumption :
generation of the spikes depends only on the kinematic
vector we choose.
Linear
filter
nonlinear f Poisson
model
velocity spikes
)
( t
t v
k
f
)
( t
t Poisson
spike
56. Step 2- Linear Filter Estimation
Spike Triggered Average (STA)
Geometry interpretation
]
[
)
]
[
( |
1
v
E
I
v
v
E
k spike
v
T
-30 -20 -10 0 10 20 30
-25
-20
-15
-10
-5
0
5
10
15
20
25
1st Principal Component
2nd
Principal
Component
neuron 72: VpS PCA
Vp
VpS
1st Principal component
2
n
d
Principal
component
60. Step 3: Sequential Estimation Algorithm for
Point Process Filtering
Consider the neuron as an inhomogenous Poisson point process
Observing N(t) spikes in an interval T, the posterior of the spike
model is
The probability of observing an event in t is
And the one step prediction density (Chapman-Kolmogorov)
The posterior of the state vector, given an observation N
}
exp{
)
( k
k
k v
k
t
t
t
t
t
t
N
t
t
N
t
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t
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t
))
(
),
(
),
(
|
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61. Step 3: Sequential Estimation Algorithm for
Point Process Filtering
Monte Carlo Methods are used to estimate the integral. Let
represent a random measure on the posterior density, and represent
the proposed density by
The posterior density can then be approximated by
Generating samples from using the principle of Importance
sampling
By MLE we can find the maximum or use direct estimation with kernels
of mean and variance
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62. Posterior density at a time index
-2.5 -2 -1.5 -1 -0.5 0 0.5
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
velocity
probability
pdf at time index 45.092s
posterior density
desired velocity
velocity by seq. estimation (collapse)
velocity by seq. estimation (MLE)
velocity by adaptive filtering
63. Step 3: Causality concerns
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2
x 10
5
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
time
s
p
i
k
e
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2
x 10
5
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time (ms)
v
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spike
p
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spike
p
lag
KX
spike
p
lag
KX
p
lag
I
lag
64. For 185 neurons, average delay is 220.108 ms
0 50 100 150 200 250 300 350 400 450 500
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
2.2
2.4
time delay (ms)
I
(spk,KX)
(TimeDelay)
I(spk,KX) as function of time delay
neuron 80
neuron 72
neuron 99
neruon 108
neruon 77
Figure 3-14 Mutual information as function of time delay for 5 neurons.
Step 3: Information Estimated Delays
65. Step 4:
Monte Carlo sequential kinematics estimation
)
(
i
i
t
t
X
k
f
Kinematic
State
Neural Tuning
function spike trains
Prediction
i
t
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t
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t v
X
F
X 1
1
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67. Table 3-2 Correlation Coefficients between the Desired Kinematics and the
Reconstructions
CC
Position Velocity Acceleration
x y x y x y
Expectation 0.8161 0.8730 0.7856 0.8133 0.5066 0.4851
MLE 0.7750 0.8512 0.7707 0.7901 0.4795 0.4775
Table 3-3 Correlation Coefficient Evaluated by the Sliding Window
CC
Position Velocity Acceleration
x y x y x y
Expectation
0.84010
0.0738
0.8945
0.0477
0.7944
0.0578
0.8142
0.0658
0.5256
0.0658
0.4460
0.1495
MLE
0.7984
0.0963
0.8721
0.0675
0.7805
0.0491
0.7918
0.0710
0.4950
0.0430
0.4471
0.1399
Results comparison
[Sanchez, 2004]
68. Conclusion
Our results and those from other laboratories show it is possible to
extract intent of movement for trajectories from multielectrode array
data.
The current results are very promising, but the setups have limited
difficulty, and the performance seems to have reached a ceiling at an
uncomfortable CC < 0.9
Recently, spike based methods are being developed in the hope of
improving performance. But difficulties in these models are many.
Experimental paradigms to move the field from the present level need
to address issues of:
Training (no desired response in paraplegic)
How to cope with coarse sampling of the neural population
How to include more neurophysiology knowledge in the design