(options)

A particle move involving annihilation. Before the move:. After the move:
. The constraints
are preserved by this move.
Maple Code
- MEspheres.mw
- Maple Worksheet with examples of how to use the code.
- spread.mpl
- This is the actual program that performs the Swarm Particle Optimization.
- ivols.mpl
- Quasi-Monte Carlo computation of the intersecting volumes of 7 spheres.
- Circ5.mpl
- Image of the intersection regions of 5 circles.
Imaging and Model Building from Nanoprobe Data
New algorithms are currently being developed for 1) the visualization of local neuronal activity using swarm particle optimization and Maximum Entropy, and 2) to model the raw data from the nanoprobes as a discrete dynamic bayesian network. We plan to use the newest methods of bayesian analysis for modeling the joint distribution of the data array by as simple as possible a collection of meaningful parameters. These likelihoods will of course depend on the neuronal circuit under study but we expect some common characteristics to underlie all of them. The raw data from the nanoprobes will be used to produce a temporal sequence of 3D maps of local neuronal activity. These maps will be further assembled into movies with a user specified point of view. The raw data will also be used for estimating the structure and the parameters of a dynamic graphical model This probabilistic network will be used for testing hypotheses about brain activity in the neighborhood of the sensors. A description of both computational aspects follows.
Imaging by Swarm Particle Optimization and Maximum Entropy
To simplify the presentation and illustrate the main ideas of our new
algorithms we think of the array of electrodes as located on a regular
unit 3D lattice. To each electrode in this lattice we associate a
``listening’‘ sphere of radius
, so that spheres that
are nearest neighbors (nn) overlap. After collecting readings
from a central electrode and its 6 nn in thelattice, we would like to estimate the distribution of activity within
the central sphere. We assume the readings
to be
integers. These integers are proportional to the number of charges
inside a given listening sphere. Due to the overlapping of nn spheres
the actual total number
of charges observed by a detector and its
nn, is at most
but the minimum value
for
depends on
. Thus, we are uncertain aboutthe exact location and number of charges within the total volume
of the 7 nn spheres. Now suppose the
charges were distributed
uniformly in
. Then, the expected numbers falling within the
different regions created by the intersection of the 7 nn spheres will
be proportional to the volumes of those
regions. However, these
expectations must agree with the observations
and
that is in general not possible unless the distribution of charges
deviates from the uniform
of volume proportions. We therefore, arrive to a classic constrained
maximum entropy problem:

subject to:

where
is the set of indices of the regions that intersect the
-th
sphere and
.
For a given
we can easily obtain
and
by quasi-monte
carlo. The
sequence is piecewise constant
given by
at
values
. For example if
there are only 7 regions (one per detector)
but as soon as
the value for
jumps to 13, staying
there until
when it becomes 25, etc.
The same quasi-monte carlo
algorithm that produced the
sequence above, is used for estimating
the proportions
for any
. We solved the constrained maximum
entropy problem by simulating annealing. We made use of the assumption
of discrete integral values
to implement simple stochastic
particle moves that always preserve the constrains. We start with
charges at the centers. We then move pairs of particlesat random from one region to another adjacent region in such a way
that the total numbers in each of the spheres remain constant. We
also allow creation and annihilation of charges that change the value
for
(see the above Figure).
This solves the reconstruction problem within one listening sphere. To get a complete image it is sufficient to sweep across the lattice but our preliminary experiments suggest other alternatives. More experimentation will be needed to fully optimize the procedure. We emphasize again that the actual geometry of the nanoprobes is not expected to always fit the assumption of regular spacing in all directions. The basic ideas illustrated above for the special case of a regular 3D lattice still hold whenever the distances between the probes are either known apriori or there is the possibility of estimating them from anatomical information or from other available data.
New Geometric Bayesian Model Selection and Parameter Estimation
To be able to test hypotheses about neural mechanisms we will model
the raw data from the nanoprobes as a discrete dynamic bayesian
network (DBN). Thus, an observation consists of a list of non negative
integers
. Each entry in the list has associated a
spacetime location that is useful for adding prior information and for
pruning the search for best models. Huge simplifications are obtained
by assuming that the data consists of (approximately) independent
identically distributed (iid) chunks of binary variables. For finding
these chunks we are planning to use the newly discovered geometric
model selection method. Once the chunks
are identified we plan to further reduce the dimensionality of the
hypothesis space by performing an stochastic search in model space
guided by the available anatomical and physical constraints.
We anticipate the need to evaluate the performance of
variational bayes, expectation propagation
as well as MCMC methods for computing
posterior expectations of relevant functions of the parameters.
Classification of Pathogens and Behaviors
After fitting probabilistic models for the observations, in the form of a bayesian network, we can exploit those models to obtain characteristic brain activity patterns for the different conditions of our experiments. For example, in the study of the inflammatory response circuit (see below) we can perform a standard bayesian classification algorithm (see e.g. to obtain signatures for the different pathogens. These signatures could lead us to discover some relevant easy to observe variables highly correlated with the different pathogens. An obvious immediate application of this procedure could be the rapid identification of a pathogen from for example body temperatures and blood pressure measurements on an infected organism. The availability of such a procedure would be important in the event of a bio-terrorist attack.
Using Hidden Markov Models for Estimating Neural States
The nanoprobes do not measure the firings of individual neurons directly. They only sense the presence of electrical charges that enter their listening sphere. By design, the nanoprobes in an array are of sizes typically smaller than individual neurons so that a sudden increase of charge within the listening sphere of a probe is expected to be produced by the firing of one (or at most a few) nearby neuron. One of our goals is to be able to reconstruct the activity of the unobserved neural net from the data provided by the nanoprobes. This goal can be achieved by adding extra unobserved parent nodes to our original DBN. These extra nodes represent local brain states at different times and are assumed to follow a finite state Markov Chain. Standard neurophysiology will be used to guide our choice for the hidden Markov Chain (i.e., number of states, labels for the states and the Markov transition diagram). Standard DBN techniques (see for example and open software are available for estimating the parameters of these kinds of models.
.
After the move:
. The constraints
are
preserved by this move.
