Statistical Mechanics of Neocortical Interactions (SMNI) Lester Ingber Lester Ingber Research POB 06440 Wacker Dr PO Sears Tower Chicago, IL 60606 [email protected] • [email protected]and DRW Investments LLC Chicago Mercantile Exchange Center 30 S Wacker Dr Ste 1516 Chicago, IL 60606 [email protected]SMNI RATIONALE—“TOP DOWN” SMNI DEVELOPMENT—“BOTTOM UP” MATHEMATICAL AND NUMERICAL ASPECTS SMNI APPLICATIONS—STM SMNI APPLICATIONS—EEG OTHER APPLICATIONS—MNN AND CHAOS SMNI CANONICAL MOMENTA INDICATORS—EEG SMNI GENERIC FEATURES The latest Adaptive Simulated Annealing (ASA) code and related reprints can be retrieved via WWW from http://www.ingber.com/ or via FTP from ftp.ingber.com. $Id: smni_lecture,v 1.84 1998/11/30 13:59:32 ingber Exp ingber $
Transcript
Statistical Mechanics of Neocortical Interactions (SMNI)
The latest Adaptive Simulated Annealing (ASA) code and related reprints can beretrieved via WWW from http://www.ingber.com/ or via FTP from ftp.ingber.com.
SMNI CANONICAL MOMENTA INDICATORS—EEG . . . . . . 73Canonical Momenta Indicators (CMI). . . . . . . . . . . 74SMNI vs SMFM (SM of Financial Markets) . . . . . . . . . 75SMNI CMI of Genetic Predisposition to Alcoholism. . . . . . 76Data vs SMNI CMI for Alcoholic Group — S1 . . . . . . . . 77Data vs SMNI CMI for Control Group — S1 . . . . . . . . 78Data vs SMNI CMI for Alcoholic Group — S2 Match . . . . . 79Data vs SMNI CMI for Control Group — S2 Match . . . . . . 80Data vs SMNI CMI for Alcoholic Group — S2 No Match . . . . 81Data vs SMNI CMI for Control Group — S2 No Match . . . . . 82
While MRI, PET, and SPECT offer better three-dimensional presentations ofbrain activity, EEG and MEG offer superior temporal resolutions on the order ofneuronal relaxation times, i.e., milliseconds.
Recently, it also has been shown that EEG and MEG offer comparable spatialresolutions on the order of several millimeters; a square millimeter is theapproximate resolution of a macrocolumn representing the activity ofapproximately 105 neurons. This is not quite the same as possessing the ability todiscriminate among alternative choices of sets of dipoles giving rise to similarelectric fields.
SMNI Lester Ingber
EEG ElectrodesA typical map of EEG electrode sites is given as below. Many neuroscientists
are becoming aware that higher electrode densities are required for many studies.For example, if each site below represented 5 closely spaced electrodes, anumerical Laplacian can offer relatively reference-free recordings and betterestimates of localized sources of activity.
SMNI Lester Ingber
EEG Power SpectraLimiting cases of linear (macroscopic) theories of intracortical interaction
predict local wav e phenomena and obtain dispersion relations with typical wav enumbersk = 10 to 100 cm−1 and dominant frequencies in the general range ofhuman spontaneous EEG (1-20 Hz).
However, human scalp potentials are spatially filtered by both distance andtissue between cortical current sources and surface electrodes so that scalp EEGpower is attenuated to about 1%.
The ‘‘alpha mode’’ (9.5 Hz) is consistent with standing wav es, whereas the‘‘mu mode’’ (8.0 Hz) is more consistent with posterior to anterior traveling wav es(ky) across the electrode array.
High resolution estimate of spectral density function |Φ(k,ω)|2 for EEG recordedfrom an awake human subject (eyes closed) using 16 scalp recording sites over theright hemisphere. (a) Mu rhythm at 8.0 Hz. (b) Alpha rhythm at 9.5 Hz from thesame 1 minute record.
Figure courtesy of Paul Nunez
SMNI Lester Ingber
Single Electrode Recording of Dipole ActivityMacrocolumns may be considered as “point sources” of dipole-like
interactions, mainly due to coherent current flow of top-layer afferent interactionsto bottom-layer efferent interactions. However, there is a problem of non-uniqueness of the electric potential that arises from such source activity; Laplacianmeasurements can help to address this problem.
Figure courtesy of Paul Nunez
SMNI Lester Ingber
EEG of Mechanical StringThe mechanical string has linear properties and is connected to local nonlinear
oscillators. Local cortical dynamics in dipole layers is here considered analogousto the nonlinear mechanical oscillators which influence global modes.Macroscopic scalp potentials are analogous to the lower modes of stringdisplacement.
For purposes of illustration, a linear string with attached oscillators, e.g.,nonlinear springs may be compared to a one-dimensional strip of neocortex:
SMNI Lester Ingber
String EquationThe following equation describes the string displacementΦ∂2Φ∂t2
− c2 ∂2Φ∂x2
+ [ω20 + f (Φ)]Φ = 0 ,
for a linear array (lengthl ) of sensors (electrodes) of sizes. Thus, wav e-numbersin the approximate range
πl≤ k ≤
πs
can be observed. If the center to center spacing of sensors is alsos, l = Ms, whereM = (number of sensors - 1),k = 2nπ/R for n = {1, 2, 3,. . .} (string forms closedloop), and sensors span half the string (brain),l = R/2, then
1 ≤ n ≤ M
for some maximumM , which is on the order of 3 to 7 in EEG studies using 16 to64 electrodes in two-dimensional arrays on the cortical surface.
For scalp recordings, the wav enumber restriction is more severe. Forexample, a typical circumference of the neocortex following a coordinate in andout of fissures and sulci isR = 100 cm (about 50 cm along the scalp surface). IfEEG power is mostly restricted tok < 0. 5 cm−1, only modesn < 4 are observed,independent of the number of electrodes.
Theory should be able to be similarly “filtered,” e.g., in order to properly fitEEG data.
SMNI Lester Ingber
String ObservablesThe string displacement (potential within the cortex) is given by
Φ(x, t) =∞
n=1Σ Gn(t) sinknx ,
but the observedΦ is given by
Φ†(x, t) =M
n=1Σ Gn(t) sinknx .
In the linear case, wheref (Φ) = 0 (equal linear oscillators to simulate localcircuit effects in cortical columns), then
∂2Φ∂t2
− c2 ∂2Φ∂x2
+ω20Φ = 0 ,
Φ =∞
n=1Σ An cosωnt sinknx ,
ω2n = ω2
0 + c2k2n ,
giving a dispersion relationωn(kn). For the nonlinear case,f (Φ) ≠ 0, the restoringforce of each spring is amplitude-dependent. In fact, local oscillators may undergochaotic motion.
What can be said about
Φ†(x, t) =M
n=1Σ Gn(t) sinknx ,
the macroscopic observable displacement potential on the scalp or cortical surface?
It would seem thatֆ should be described as a linear or quasi-linear variable,but influenced by the local nonlinear behavior which crosses the hierarchical levelfrom mesoscopic (columnar dipoles) to macroscopic.
How can this intuition be mathematically articulated, for the purposes ofconsistent description as well as to lay the foundation for detailed numericalcalculations?
SMNI Lester Ingber
SMNI DEVELOPMENT—“BOTTOM UP”
SMNI Lester Ingber
Scales Illustrated
Illustrated are three biophysical scales of neocortical interactions: (a)-(a* )-(a’)microscopic neurons; (b)-(b’) mesocolumnar domains; (c)-(c’) macroscopicregions. In (a* ) synaptic interneuronal interactions, averaged over bymesocolumns, are phenomenologically described by the mean and variance of adistribution Ψ. Similarly, in (a) intraneuronal transmissions arephenomenologically described by the mean and variance ofΓ. Mesocolumnarav eraged excitatory (E) and inhibitory (I ) neuronal firings are represented in (a’).In (b) the vertical organization of minicolumns is sketched together with theirhorizontal stratification, yielding a physiological entity, the mesocolumn. In (b’)the overlap of interacting mesocolumns is sketched. In (c) macroscopic regions ofneocortex are depicted as arising from many mesocolumnar domains. These arethe regions designated for study here. (c’) sketches how regions may be coupledby long-ranged interactions.
SMNI Lester Ingber
SMNI vs Artificial Neural Networks
Feature SMNI ANN
spatial unit minicolumn neuron
spatial scale 105 − 106 neurons 102 − 103 neurons
large sets of neurons pre-analysis post-analysis
neuronal features statistical constraints neuronal mechanisms
columnar features columnar interactions columnar formation
scalp EEG applications yes probably not
intra-cortical EEG yes yes
spike EEG no yes
While ANN models use simplified algebraic structures to represent realneurons, SMNI models develop the statistics of large numbers of realistic neuronsrepresenting huge numbers of synaptic interactions—there are 104 to 105 synapsesper neuron. Furthermore, unlike most ANN approaches, SMNI accepts constraintson all its macrocolumnar averaged parameters to be taken from experimentallydetermined ranges of synaptic and neuronal interactions; there are no unphysicalparameters. The stochastic and nonlinear nature of SMNI development is directlyderived from experimentally observed synaptic interactions and from themathematical development of observed minicolumns and macrocolumns ofneurons.
SMNI Lester Ingber
Microscopic NeuronsA derivation has been given of the physics of chemical inter-neuronal and
electrical intra-neuronal interactions. This derivation generalized a previoussimilar derivation. The derivation yields a short-time probability distribution of agiven neuron firing due to its just-previous interactions with other neurons. Withinτ j ∼ 5−10 msec, the conditional probability that neuronj fires (σ j = +1) or does notfire (σ j = −1), given its previous interactions withk neurons, is
pσ j≈ Γ Ψ ≈
exp(−σ j F j )
exp(F j ) + exp(−F j ),
F j =Vj −
kΣ a∗jk v jk
((πk′Σ a∗jk ′(v jk ′
2 +φ jk ′2)))1/2 ,
ajk =1
2Ajk(σ k + 1)+ Bjk .
Γ represents the “intra-neuronal” probability distribution, e.g., of acontribution to polarization achieved at an axon given activity at a synapse, takinginto account averaging over different neurons, geometries, etc.Ψ represents the“inter-neuronal” probability distribution, e.g., of thousands of quanta ofneurotransmitters released at one neuron’s postsynaptic site effecting a(hyper-)polarization at another neuron’s presynaptic site, taking into accountinteractions with neuromodulators, etc. This development is true forΓ Poisson,and forΨ Poisson or Gaussian.
Vj is the depolarization threshold in the somatic-axonal region,v jk is theinduced synaptic polarization ofE or I type at the axon, andφ jk is its variance.The efficacy ajk , related to the inverse conductivity across synaptic gaps, iscomposed of a contributionAjk from the connectivity between neurons which isactivated if the impingingk-neuron fires, and a contributionBjk from spontaneousbackground noise.
Even at the microscopic scale of an individual neuron, with soma≈ 10 µm,this conceptual framework assumes a great deal of statistical aggregation ofmolecular scales of interaction, e.g., of the biophysics of membranes, of thickness≈ 5× 10−3 µm, composed of biomolecular leaflets of phospholipid molecules.
SMNI Lester Ingber
Mesoscopic AggregationThis microscopic scale itself represents a high aggregation of sub-microscopic
scales, aggregating effects of tens of thousands of quanta of chemical transmittersas they influence the 5× 10−3 µm This microscopic scale is aggregated up to themesoscopic scale, using
Pq(q) = ∫ dq1dq2Pq1q2(q1, q2)δ [q − (q1 + q2)] .
The first papers using this approach to aggregate neuronal interactionsappeared inJournal of Social and Biological Structuresin 1981, inPhysica Din1982, and inPhysical Review Ain 1983.
The SMNI approach can be developed without recourse to borrowingparadigms or metaphors from other disciplines. Rather, in the course of a logical,nonlinear, stochastic development of aggregating neuronal and synapticinteractions to larger and larger scales, opportunities are taken to use techniques ofmathematical physics to overcome several technical hurdles. After suchdevelopment, advantage can be taken of associated collateral descriptions andintuitions afforded by such mathematical and physics techniques as they hav e beenused in other disciplines, but paradigms and metaphors do not substitute for logicalSMNI development.
SMNI Lester Ingber
Mesoscopic InteractionsMicroscopic Scale
Retain independence of excitatory (E) and inhibitory (I ) interactionsRetain nonlinear development of probability densities
Macroscopic scaleInclude long-ranged interactions, constraints on mesocolumns
For the purposes of mesoscopic and macroscopic investigation, this biologicalpicture can be cast into an equivalent network. However, the above aspects mustnot be simply cast away.
SMNI Lester Ingber
Mathematical DevelopmentA derived mesoscopic LagrangianLM defines the short-time probability
distribution of firings in a minicolumn, composed of∼ 102 neurons, given its justprevious interactions with all other neurons in its macrocolumnar surround.G isused to represent excitatory (E) and inhibitory (I ) contributions. G designatescontributions from bothE and I .
G′ are minicolumnar-averaged inter-neuronal synaptic efficacies,vG
G′ andφGG′ are averaged means and variances of contributions to neuronal electric
polarizations. MG′ and NG′ in FG are afferent macrocolumnar firings, scaled toefferent minicolumnar firings byN/N * ∼ 10−3, where N * is the number ofneurons in a macrocolumn,∼ 105. Similarly, AG′
G and BG′G have been scaled by
N * / N∼ 103 to keepFG invariant.
SMNI Lester Ingber
Inclusion of Macroscopic CircuitryThe most important features of this development are described by the
LagrangianLG in the negative of the argument of the exponential describing theprobability distribution, and the “threshold factor”FG describing an importantsensitivity of the distribution to changes in its variables and parameters.
To more properly include long-ranged fibers, when it is possible tonumerically include interactions among macrocolumns, theJG terms can bedropped, and more realistically replaced by a modified threshold factorFG,
FG =(VG − a|G|
G′ v|G|G′ N
G′ −1
2A|G|
G′ v|G|G′ M
G′ − a‡EE′ v
EE′N
‡E′ −1
2A‡E
E′ vEE′M
‡E′)
((π[(v|G|G′ )
2 + (φ|G|G′ )
2](a|G|G′ N
G′ +1
2A|G|
G′ MG′ + a‡E
E′ N‡E′ +1
2A‡E
E′ M‡E′)))1/2,
a‡EE′ =
1
2A‡E
E′ + B‡EE′ .
Here, afferent contributions fromN‡E long-ranged excitatory fibers, e.g.,cortico-cortical neurons, have been added, whereN‡E might be on the order of10% of N ∗ : Of the approximately 1010 to 1011 neocortical neurons, estimates ofthe number of pyramidal cells range from 1/10 to 2/3. Nearly every pyramidal cellhas an axon branch that makes a cortico-cortical connection; i.e., the number ofcortico-cortical fibers is of the order 1010.
This is further modified for use in MNN.
SMNI Lester Ingber
Equivalent Nearest-Neighbor InteractionsNearest-neighbor (NN) interactions between mesocolumns are illustrated.
Afferent minicolumns of∼ 102 neurons are represented by the inner circles, andefferent macrocolumns of∼ 105 neurons by the outer circles. Illustrated are the NNinteractions between a mesocolumn, represented by the thick circles, and itsnearest neighbors, represented by thin circles. The area outside the outer thickcircle represents the effective number of efferent macrocolumnar nearest-neighborneurons. I.e., this is the number of neurons outside the macrocolumnar area ofinfluence of the central minicolumn.
This approximation, albeit successful in the 1983Physical Review Acalculations, can be replaced by a more sophisticated algorithm, MNN, publishedin Physical Review A Rapid Communicationsin 1992.
SMNI Lester Ingber
Minima Structure of Nonlinear LagrangianExamination of the minima structure of the spatially-averaged and temporally-
av eraged Lagrangian provides some quick intuitive details about most likely statesof the system. This is supported by further analysis detailing the actual spatial-temporal minima structure. Illustrated is the surface of the static (time-independent) mesoscopic neocortical LagrangianL over the excitatory-inhibitoryfiring plane (M E − M I ), for a specific set of synaptic parameters. All points on thesurface higher than 5× 10−3/τ have been deleted to expose this fine structure.
SMNI Lester Ingber
MATHEMATICAL AND NUMERICAL ASPECTS
SMNI Lester Ingber
Induced Riemannian GeometryA Riemannian geometry is derived as a consequence of nonlinear noise,
reflecting that the probability distribution is invariant under general nonlineartransformations of these variables.
This becomes explicit under a transformation to the midpoint discretization, inwhich the standard rules of differential calculus hold for thesamedistribution:
Calculation of InformationInformation is well defined in terms of a path integral:
I = ∫ DM P ln(P/P)
with respect to a reference distribution P. Like the probability distributionPwhich defines it, information also is an invariant under general nonlineartransformations.
Some investigators have tried to directly fit statistical white-noise models ofmutual information under different electrodes. SMNI first fits observables (electricpotentials or current flows) to probability distributions, describing inter-electrodeinteractions via long-ranged fibers and intra-electrode interactions via short-rangedfibers, before calculating the information.
For example, sensory cortex may transmit information to motor cortex,although they hav e somewhat different neuronal structures or neuronal languages.This information flow can be relatively independent of information flows that takeplace at finer resolutions, e.g., across a subset of synaptic gaps or individualneurons.
The mathematics required to process these stochastic nonlinear forms todescribe multivariate, multiplicative noise, Gaussian Markovian systems wasdeveloped in the late 1970’s in the mathematical physics literature. Thisneocortical system was the first physical system to utilize these techniques. Sincethen, they hav e been used for studies in nuclear physics (Physical Review C & D1984-1986), finance (Physical Review A1990), and large-scale DoD simulations(Mathematical and Computer Modelling1991).
SMNI Lester Ingber
Measures of Nonlinear Nonequilibrium
“Momentum”= ΠG =∂L
∂(∂MG/∂t),
“Mass” = gGG′ =∂2L
∂(∂MG/∂t)∂(∂MG′ /∂t),
“Force” =∂L
∂MG,
“F = ma ”: δ L = 0 =∂L
∂MG−∂∂t
∂L
∂(∂MG/∂t),
where MG are the variables andL is the Lagrangian. These physical entitiesprovide another form of intuitive, but quantitatively precise, presentation of theseanalyses.
SMNI Lester Ingber
Representations of Path IntegralThe Langevin Rate-Equationexhibits a stochastic equation, wherein drifts can
be arbitrarily nonlinear functions, and multiplicative noise is added.
M(t + ∆t) − M(t)∼∆ t f [M(t)] ,
M =dM
dt∼ f ,
M = f + gη ,
< η (t) >η= 0 , <η (t)η (t ′) >η= δ (t − t ′) .
The Diffusion Equationis another equivalent representation of Langevinequations. The first moment ‘‘drift’’ is identified asf , and the second moment‘‘diffusion,’’ the variance, is identified as ˆg2.
∂P
∂t=∂(− fP)
∂M+
1
2
∂2(g2P)
∂M2.
The Path-Integral Lagrangianrepresents yet another equivalent representationof Langevin equations. Recently it has been demonstrated that the drift anddiffusion, in addition to possibly being quite general nonlinear functions of theindependent variables and of time explicitly, may also be explicit functions of thedistributionP itself.
This representation is useful for fitting stochastic data to parameters inL.
SMNI Lester Ingber
PATHINT Calculation of Path IntegralGiven a form for L, we use the path-integral to calculate the long-time
distribution of variables. This is impossible in general to calculate in closed form,and we therefore must use numerical methods. PATHINT is a code developed forcalculating highly nonlinear multivariate Lagrangians.
The path-integral calculation of the long-time distribution, in addition to beinga predictor of upcoming information, provides an internal check that the systemcan be well represented as a nonlinear Gaussian-Markovian system. The use of thepath integral to compare different models is akin to comparing short- and long-timecorrelations. Complex boundary conditions can be cleanly incorporated into thisrepresentation, using a variant of ‘‘boundary element’’ techniques.
The histogram procedure recognizes that the distribution can be numericallyapproximated to a high degree of accuracy as sum of rectangles at pointsMi ofheight Pi and width ∆Mi . For convenience, just consider a one-dimensionalsystem. The above path-integral representation can be rewritten, for each of itsintermediate integrals, as
Adaptive Simulated Annealing (ASA)This algorithm fits empirical data to a theoretical cost function over aD-
dimensional parameter space, adapting for varying sensitivities of parametersduring the fit. This algorithm was first published inMathematical and ComputerModelling in 1989, and made publicly available in November 1992†.
Heuristic arguments have been developed to demonstrate that this algorithm isfaster than the fast Cauchy annealing,Ti = T0/k, and much faster than Boltzmannannealing,Ti = T0/ ln k.
For parameters
α ik ∈ [ Ai , Bi ] ,
sampling with the random variablexi ,
xi ∈ [−1, 1] ,
α ik+1 = α i
k + xi (Bi − Ai ) ,
define the generating function
gT (x) =D
i=1Π
1
2 ln(1+ 1/Ti )(|xi |+Ti )≡
D
i=1Π gi
T (xi ) ,
in terms of parameter “temperatures”
Ti = Ti0 exp(−ci k1/D) .
The cost-functionsL under consideration are of the form
h(M ;α ) = exp(−L/T) ,
L = L∆t +1
2ln(2π∆tg2
t ) ,
whereL is a Lagrangian with dynamic variablesM(t), and parameter-coefficientsα to be fit to data. gt is the determinant of the metric, andT is the cost“temperature.”
For sev eral test problems, ASA has been shown to be orders of magnitudemore efficient than other similar techniques, e.g., genetic algorithms. ASA hasbeen applied to several complex systems, including specific problems inneuroscience, finance and combat systems.
† The latest Adaptive Simulated Annealing (ASA) code and related reprints can beretrieved via WWW from http://www.ingber.com/ or via FTP from ftp.ingber.com.
SMNI Lester Ingber
SMNI APPLICATIONS—STM
SMNI Lester Ingber
Derivation of Short-Term Memory (STM)At this mesoscopic scale, properties of STM— its capacity, duration and
stability—have been calculated, and found to be consistent with empiricalobservations. The first publications on this approach to STM appeared inPhysicalReview Ain 1984.
The maximum STM capacity, consistent with the 7± 2 rule, is obtained whena ‘‘centering mechanism’’ is inv oked. This occurs when the threshold factorFG
takes minima in the interior ofMG firing-space (i.e., not the corners of this space),as empirically observed.
In the SMNI papers, the background noiseBGG′ was reasonably adjusted to
centerFG, with JG = 0, but similar results could have been obtained by adjustingthe influence of the long-ranged fibersM‡G.
Within a time scale of several seconds, the human brain can store only about7±2 auditorychunksof information (4±2 visual chunks).
To derive this, choose empirical ranges of synaptic parameters correspondingto a predominately excitatory case (EC), predominately inhibitory case (IC), and abalanced case (BC) in between. For each case, also consider a ‘‘centeringmechanism’’ (EC’, IC’, BC’), whereby some synaptic parameter is internallymanipulated, e.g., some chemical neuromodulation or imposition of patterns offiring, such that there is a maximal efficiency of matching of afferent and efferentfirings:
MG ≈ M ∗ G ≈ 0 .
This sets conditions on other possible minima of thestaticLagrangianL.
SMNI Lester Ingber
Centering MechanismThe centering effect is quite easy for the neocortex to accommodate. For
example, this can be accomplished simply by readjusting the synaptic backgroundnoise fromBG
E to B′GE ,
B′GE =VG − (
1
2AG
I + BGI )vG
I NI −1
2AG
EvGE NE
vGE NG
for bothG = E andG = I .
This is modified straightforwardly when regional influences fromM‡E areincluded, as used in MNN. In general,BG
E and BGI (and possiblyAG
E and AGI due
to actions of neuromodulators, andJG or M‡E constraints from long-ranged fibers)are available to force the constant in the numerator to zero, giving an extradegree(s) of freedom to this mechanism.
In this context, it is experimentally observed that the synaptic sensitivity ofneurons engaged in selective attention is altered, presumably by the influence ofchemical neuromodulators on postsynaptic neurons.
The threshold factors greatly influence when and how smoothly the ‘‘stepfunctions’’ tanhFG
IC in gG(t) changeMG(t) to MG(t +θ ). I.e., assuming the driftsare a major driving force,
M(t + ∆t) ≈ M(t) −∆t
τ((MG(t) + NG tanhFG(t)))
together with∆t ≤ τ can be used toapproximatelydescribe the influence onefferent firings from their afferent inputs. I.e.,
M(t + ∆t)∼ − NG tanhFG(t)
can be used a first approximation.
An important side result is to drive most probable states, i.e., smallL which isdriven largely by smallFG, to regions where
vGE AG
E M E ≈ |vGI |AG
I M I .
Since I−I efficacies typically are relatively quite small, the probability densityunder the centering mechanism is strongly peaked along the line
vEE AE
E M E ≈ |vEI |AE
I M I .
SMNI Lester Ingber
Applying the Centering Mechanism—“Inhibitory” StateA model of dominant inhibition describes how minicolumnar firings are
suppressed by their neighboring minicolumns. For example, the averaged effect isestablished by inhibitory mesocolumns (IC) by settingAI
E = AEI = 2AE
E = 0. 01N* /N. Since there appears to be relatively littleI − Iconnectivity, setAI
I = 0. 0001N* /N. The background synaptic noise is taken to beBE
I = BIE = 2BE
E = 10BII = 0. 002N* /N. As nonvisual minicolumns are observed to
have∼ 110 neurons and as there appear to be a predominance ofE over I neurons,here takeNE = 80 andNI = 30. UseN* /N = 103, JG = 0 (absence of long-rangedinteractions), andVG, vG
G′ , and φGG′ as estimated previously, i.e.,VG = 10 mV,
|vGG′ | = 0. 1 mV,φG
G′ = 0. 1 mV. The ‘‘threshold factors’’FGIC for this IC model are
then
F EIC =
0. 5M I − 0. 25M E + 3. 0
π1/2(0. 1M I + 0. 05M E + 9. 80)1/2,
F IIC =
0. 005M I − 0. 5M E − 45. 8
π1/2(0. 001M I + 0. 1M E + 11. 2)1/2.
F IIC will cause efferent M I (t + ∆t) to fire for most afferent input firings, as it
will be positive for most values ofMG(t) in F IIC, which is already weighted heavily
with a term -45.8. Looking atF EIC, it is seen that the relatively high positive
weights of afferent M I require at least moderate values of positive afferentM E tocause firings of efferentM E, diminishing the influence ofM E.
Using the centering mechanism,B′EE = 1. 38 and B′ II = 15. 3, andFGIC is
transformed toFGIC′ ,
F EIC′ =
0. 5M I − 0. 25M E
π1/2(0. 1M I + 0. 05M E + 10. 4)1/2,
F IIC′ =
0. 005M I − 0. 5M E
π1/2(0. 001M I + 0. 1M E + 20. 4)1/2.
SMNI Lester Ingber
Contours of “Inhibitory” StateContours of the Lagrangian illustrate ‘‘valleys’’ that trap firing-states of
mesocolumns. (τ L can be as large as 103.)
No interior stable states are observed at scales ofτ L ranging from 103 downto 10−2, until the “centering mechanism” is turned on.
SMNI Lester Ingber
Applying the Centering Mechanism—“Excitatory” StateThe other ‘‘extreme’’ of normal neocortical firings is a model of dominant
excitation, effected by establishing excitatory mesocolumns (EC) by using thesame parameters { BG
G′ , vGG′ ,φ
GG′ , AI
I } as in the IC model, but settingAE
E = 2AIE = 2AE
I = 0. 01N* /N. This yields
F EEC =
0. 25M I − 0. 5M E − 24. 5
π1/2(0. 05M I + 0. 10M E + 12. 3)1/2,
F IEC =
0. 005M I − 0. 25M E − 25. 8
π1/2(0. 001M I + 0. 05M E + 7. 24)1/2.
The negative constants in the numerators ofFGEC enhance efferent firings for
both E and I afferent inputs. However, the increased coefficient of M E in F EEC
(e.g., relative to its corresponding value inF EIC), and the fact thatM E can range up
to NE = 80, readily enhance excitatory relative to inhibitory firings throughoutmost of the range ofM E. This is only a first approximation, and the fullLagrangian must be used to determine the actual evolution.
Using the centering mechanism,B′EE = 10. 2 and B′ II = 8. 62, andFGEC is
transformed toFGEC′ ,
F EEC′ =
0. 25M I − 0. 5M E
π1/2(0. 05M I + 0. 10M E + 17. 2)1/2,
F IEC′ =
0. 005M I − 0. 25M E
π1/2(0. 001M I + 0. 05M E + 12. 4)1/2.
SMNI Lester Ingber
Contours of “Excitatory” StateContours of the Lagrangian illustrate ‘‘valleys’’ that trap firing-states of
mesocolumns. (τ L can be as large as 103.)
No interior stable states are observed at scales ofτ L ranging from 103 downto 10−2, until the “centering mechanism” is turned on.
SMNI Lester Ingber
Applying the Centering Mechanism—“Balanced” StateNow it is natural to examine a balanced case intermediate between IC and EC,
labeled BC. This is accomplished by changingAEE = AI
E = AEI = 0. 005N* /N.
This yields
F EBC =
0. 25M I − 0. 25M E − 4. 50
π1/2(0. 050M E + 0. 050M I + 8. 30)1/2,
F IBC =
0. 005M I − 0. 25M E − 25. 8
π1/2(0. 001M I + 0. 050M E + 7. 24)1/2.
Here the constant in the numerator ofF EBC, while still negative to promoteE
efferent firings, is much greater than that inF EEC, thereby decreasing the net
excitatory activity to a more moderate level. A similar argument applies incomparingF I
BC to F IIC, permitting a moderate level of inhibitory firing.
Applying the centering mechanism to BC,B′EE = 0. 438 andB′ II = 8. 62, andFG
BC is transformed toFGBC′ ,
F EBC′ =
0. 25M I − 0. 25M E
π1/2(0. 050M I + 0. 050M E + 7. 40)1/2,
F IBC′ =
0. 005M I − 0. 5M E
π1/2(0. 001M I + 0. 050M E + 12. 4)1/2.
SMNI Lester Ingber
Contours of “Balanced” State
No interior stable states are observed at scales ofτ L ranging from 103 downto 10−2, until the “centering mechanism” is turned on.
(a) Contours for values less than 0.04 are drawn forτ LBC. The M E axisincreases to the right, from−NE = −80 to NE = 80. TheM I axis increases to theright, from−NI = −30 to NI = 30. In each cluster, the smaller values are closer tothe center. (b) Contours for values less than 0.04 are drawn forτ LBC′ .
SMNI Lester Ingber
Modeling Visual Cortex STMWhen N = 220, modeling the number of neurons per minicolumn in visual
neocortex, then only 5-6 minima are found, consistent with visual STM. Theseminima are narrower, consistent with the sharpness required to store visualpatterns.
SMNI Lester Ingber
STM Stability and DurationThe attractors of these models can be identified. Possible hysteresis and/or
jumps between local minima can be explicitly calculated within the limitations ofstudying a specific attractors.
Detailed calculations identify the inner valleys of the parabolic trough withstable short-term-memory states having durations on the order of tenths of asecond.
Stability is investigated by
δ MG≈ − N2L,GG′δMG′ .
Therefore, minima of the static LagrangianL are minima of the dynamic transientsystem defined byL. The time of first passage is calculated as
tvp≈πN−2|L,GG′(<< M >>p)| L,GG′(<< M >>v)
−1/2
×exp{CNτ [L(<< M >>p) − L(<< M >>v)]} .
For τ L∼ 10−2, the only values found for all three cases of firing, the time offirst passagetvp is found to be several tenths of second for jumps among mostminima, up to 9. There is hysteresis for deeper valleys at 10th-11th minima ofLFBC′ at the corners of theMG plane. The hysteresis occurs in about a fewminutes, which is too long to affect the 7± 2 rule. This result isexponentiallysensitive to N in Φ/D, and exponentially sensitive to (N* N)1/2 in FG, the‘‘threshold factor.’’
Use is made in later development of EEG analyses of the discovered nature ofthe line of stable minima lying in a deep parabolic trough, across a wide range ofcases of extreme types of firings.
SMNI Lester Ingber
PATHINT Calculations of STMPATHINT is an important partner to the ASA code. ASA has made it possible
to perform fits of complex nonlinear short-time probability distributions to EEGdata. PATHINT details the evolution of the attractors of these short-timedistributions, e.g., as studied in 1984.
Now, using ASA, the parameters of the fitted SMNI distribution can be usedto determine a distribution of firings in a short initial time epoch of EEG.
Then, PATHINT can be used to predict the evolution of the system, possiblyto predict oncoming states, e.g., epileptic seizures of patients baselined to a fitteddistribution.
Below is the evolution of model BC′ at 0.01 seconds =τ , after 100 foldings ofthe path integral. In agreement with previous studies, models BC′ and BC′_VISsupport multiple stable states in the interior physical firingMG-space for timescales of a few tenths of a second. Models EC′ and IC′ do not possess theseattributes.
PATHINT STM BC’ t=1
’BCP_001’ 0.0382 0.0306 0.0229 0.0153 0.00764
-500
50 -30-20
-100
1020
00.0050.01
0.0150.02
0.0250.03
0.0350.04
0.0450.05
EI
P
SMNI Lester Ingber
PATHINT Calculations of STM BC ′_VIS
The interior ofMG-space of model BC′_VIS is examined at 0.01 seconds =τ .
These high resolution calculations were published in Ingber and NunezPhysical Review(1995).
SMNI Lester Ingber
Primacy Versus Recency RuleSMNI also presents an explanation, or at least an upper statistical constraint,
on the primacy versus recency rule observed in serial processing.
First-learned items are recalled most error-free, and last-learned items are stillmore error-free than those in the middle. I.e., the deepest minima are more likelyfirst accessed, while the more recent memories or newer patterns have synapticparameters most recently tuned or are more actively rehearsed.
Note that for visual cortex, presentation of 7±2 items would have memoriesdistributed among different clusters, and therefore the recency effect should not beobserved. Instead the 4±2 rule should dictate the number of presented items.
SMNI Lester Ingber
40 Hz Models of STMAn alternate theory of STM, based on after-depolarization (ADP) at synaptic
sites, has been proposed.
Feature SMNI ADP
7 ± 2 Rule attractors ofL 40 Hz subcycles
4 ± 2 Rule attractors of visualL ?
Primacy versus Recency statistics of attractors ?
Large-Scale Influences consistent with EEG ?
Duration local interactions neuromodulators
ADP proposes a “refresher” mechanism of 40 Hz to sustain memories for timescales on the order of tenths of seconds within cycles of 5−12 Hz, even under theinfluence of long-ranged regional firings and neuromodulators. SMNI PATHINTcalculations show a rapid deterioration of attractors in the absence of externalinfluences.
ADP and SMNI together forge a stronger theory of STM than eitherseparately.
SMNI Lester Ingber
SMNI APPLICATIONS—EEG
SMNI Lester Ingber
Local and Global EEGThe derived mesoscopic dispersion relations also are consistent with other
global macroscopic dispersion relations, described by long-range fibers interactingacross regions.
This SMNI model yields oscillatory solutions consistent with the alpharhythm, i.e.,ω ≈ 102 sec−1, equivalent toν = ω/(2π) ≈ 16 Hz. This suggests thatthese complementary local and global theories may be confluent, considered as ajoint set of dispersion relations evolving from the most likely trajectories of a jointLagrangian, referred to as the ‘‘equations of motion,’’ but linearly simplified inneighborhoods of minima of the stationary Lagrangian.
These two approaches, i.e., local mesocolumnar versus global macrocolumnar,give rise to important alternative conjectures:
(1) Is the EEG global resonance of primarily long-ranged cortical interactions? Ifso, can relatively short-ranged local firing patterns effectively modulate thisfrequency and its harmonics, to enhance their information processing acrossmacroscopic regions?
(2) Or, does global circuitry imply boundary conditions on collective mesoscopicstates of local firing patterns, and is the EEG a manifestation of thesecollective local firings?
(3) Or, is the truth some combination of (1) and (2) above? For example, thepossibility of generating EEG rhythms from multiple mechanisms at multiplescales of interactions, e.g., as discussed above, may account for weaklydamped oscillatory behavior in a variety of physiological conditions.
This theory has allowed the local and global approaches to complement eachother at a common level of formal analysis, i.e., yielding the same dispersionrelations derived from the ‘‘equations of motion,’’ analogous toΣ(forces)= d(momentum)/dt describing mechanical systems.
SMNI Lester Ingber
EEG Phenomena—Euler-Lagrange ApproximationThe variational principle permits derivation of the Euler-Lagrange equations.
These equations are then linearized about a given local minima to investigateoscillatory behavior. This calculation was first published inPhysical Review Ain1983.
Here, long ranged constraints in the form of Lagrange multipliersJG wereused to efficiently search for minima, corresponding to roots of the Euler-Lagrangeequations. This illustrates how macroscopic constraints can be imposed on themesoscopic and microscopic systems.
This is approximately within the experimentally observed ranges of thealpha andbetafrequencies.
SMNI Lester Ingber
E-L Nearest-Neighbor ContoursA numerical calculation of the coefficients, gG, of nearest-neighbor
interactions, (∇ MG)2, shows that SMNI can support/describe both spreadingactivation of firings as well as local containment of firings.
gG terms are responsible for the spatial dependence of the EEG dispersionrelations.
SMNI Lester Ingber
E-L Propagation of InformationThe propagation velocityv is calculated from
v = dω/dξ ≈1 cm/sec ,ξ ∼ 30ρ ,
which tests the NN interactions, the weakest part of this theory.
Thus, within 10−1 sec, short-ranged interactions over sev eral minicolumns of10−1 cm may simultaneously interact with long-ranged interactions over tens ofcm, since the long-ranged interactions are speeded by myelinated fibers and havevelocities of 600−900 cm/sec. In other words, interaction among differentneocortical modalities, e.g., visual, auditory, etc., may simultaneously interactwithin the same time scales, as observed.
This propagation velocity is consistent with the observed movement ofattention and with the observed movement of hallucinations across the visual fieldwhich moves at∼ 1/2 mm/sec, about 5 times as slow asv. (I.e., the observedmovement is∼ 8 msec/°, and a macrocolumn∼ mm processes 180° of visual field.)
SMNI Lester Ingber
Macroscopic Linearization Aids Probability DevelopmentThe fitting of the full SMNI probability distribution to EEG data was
published inPhysical Review Ain 1991.
Previous STM studies have detailed that the predominant physics of short-term memory and of (short-fiber contribution) to EEG phenomena takes place in anarrow ‘‘parabolic trough’’ inMG-space, roughly along a diagonal line. I.e.,τ LM
can vary by as much as 105 from the highest peak to the lowest valley inMG-space. Therefore, it is reasonable to assume that a single independent firingvariable might offer a crude description of this physics. Furthermore, the scalppotentialΦ can be considered to be a function of this firing variable.
In an abbreviated notation subscripting the time-dependence,
Φt− << Φ >>= Φ(M Et , M I
t ) ≈ a(M Et − << M E >>) + b(M I
t − << M I >>) ,
wherea andb are constants of the same sign, and <<Φ >> and <<MG >> representa minima in the trough.
Laplacian techniques help to better localize sources of activity, and therebypresent data more suitable for modeling. E.g., thenΦ is more directly related tocolumnar firings, instead of representing the electric potential produced by suchactivity.
This determines an SMNI approach to study EEG under conditions ofselective attention.
SMNI Lester Ingber
EEG Macrocolumnar LagrangianAgain, aggregation is performed,
PΦ[Φt+∆t |Φt ] = ∫ d MEt+∆t dMI
t+∆t dMEt dMI
t PM [M Et+∆t , M I
t+∆t |MEt , M I
t ]
δ [Φt+∆t − Φ(M Et+∆t , M I
t+∆t)]δ [Φt − Φ(M Et , M I
t )] .
Under conditions of selective attention, within the parabolic trough along aline in MG space, the parabolic shapes of the multiple minima, ascertained by thestability analysis, justifies a form
PΦ = (2πσ2dt)−1/2 exp[−(dt/2σ 2) ∫ dxLΦ] ,
LΦ =1
2|∂Φ/∂t|2 −
1
2c2|∂Φ/∂x|2 −
1
2ω2
0|Φ|2 − F(Φ) ,
whereF(Φ) contains nonlinearities away from the trough, and whereσ 2 is on theorder ofN, giv en the derivation of LM above.
SMNI Lester Ingber
EEG Variational EquationPrevious calculations of EEG phenomena showed that the (short-fiber
contribution to the) alpha frequency and the movement of attention across thevisual field are consistent with the assumption that the EEG physics is derived froman average over the fluctuationsσ of the system. I.e., this is described by theEuler-Lagrange equations derived from the variational principle possessed byLΦ,more properly by the ‘‘midpoint-discretized’’LΦ, with its Riemannian terms.Hence,
0 =∂∂t
∂LΦ
∂(∂Φ/∂t)+
∂∂x
∂LΦ
∂(∂Φ/∂x)−∂LΦ
∂Φ.
When expressed in the firing state variables, this leads to the same resultspublished inPhysical Review Ain 1983.
The result for theΦ equation is:
∂2Φ∂t2
− c2 ∂2Φ∂x2
+ω20Φ +
∂F
∂Φ= 0 .
If the identification
∂F
∂Φ= Φ f (Φ) ,
is made, then
∂2Φ∂t2
− c2 ∂2Φ∂x2
+ [ω20 + f (Φ)]Φ = 0 ,
is recovered, i.e., the dipole-like string equation.
The previous application of the variational principle was at the scale ofminicolumns and, with the aid of nearest-neighbor interactions, the spatial-temporal Euler-Lagrange equation gav e rise to dispersion relations consistent withSTM experimental observations.
Here, the scale of interactions is at the macrocolumnar level, and spatialinteractions must be developed taking into account specific regional circuitries.
SMNI Lester Ingber
Macroscopic Coarse-GrainingNow the issue posed previously, how to mathematically justify the intuitive
coarse-graining ofΦ to getΦ†, can be approached.
In LΦ above, consider terms of the form
∫ Φ2dx = ∫ dx∞
nΣ∞
mΣGnGm sinknx sinkmx
=nΣ
mΣGnGm ∫ dxsinknx sinkmx
= (2π/R)nΣG2
n .
By similarly considering all terms inLΦ, a short-time probability distribution forthe change in noden is defined,
pn[Gn(t + ∆t)|Gn(t)] .
Note that in general theF(Φ) term in LΦ will require coupling betweenGn andGm, n ≠ m. This defines
PΦ = p1 p2. . . p∞ .
Now a coarse-graining can be defined that satisfies some physical andmathematical rigor:
PΦ† = ∫ dkM+1dkM+2. . .dk∞ p1 p2
. . . pM pM+1 pM+2. . . p∞ .
I.e., since SMNI is developed in terms ofbona fideprobability distributions,variables which are not observed can be integrated out.
The integration over the fine-grained wav e-numbers tends to smooth out theinfluence of thekn’s for n > M , effectively ‘‘renormalizing’’
Gn → G†n ,
Φ → Φ† ,
LΦ → L†Φ .
This development shows how this probability approach to EEG specificallyaddresses experimental issues at the scale of the more phenomenological dipolemodel.
SMNI Lester Ingber
Development of Macrocolumnar EEG DistributionAdvantage can be taken of the prepoint discretization, where the postpoint
MG(t + ∆t) moments are given by
m ≡< Φν −φ >= a < M E > +b < M I >= agE + bgI ,
σ 2 ≡< (Φν −φ)2 > − < Φν −φ >2= a2gEE + b2gII .
Note that the macroscopic drifts and diffusions of theΦ’s are simply linearlyrelated to the mesoscopic drifts and diffusions of theMG’s. For the prepointMG(t) firings, the same linear relationship in terms of{ φ, a, b } is assumed.
The data being fit are consistent with invoking the “centering” mechanism.Therefore, for the prepointM E(t) firings, the nature of the parabolic trough derivedfor the STM Lagrangian is taken advantage of, and
M I (t) = cME(t) ,
where the slopec is determined for each electrode site. This permits a completetransformation fromMG variables toΦ variables.
Similarly, as appearing in the modified threshold factorFG, each regionalinfluence from electrode siteµ acting at electrode siteν , giv en by afferent firingsM‡E, is taken as
M‡Eµ→ν = dν M E
µ (t −Tµ→ν ) ,
wheredν are constants to be fitted at each electrode site, andTµ→ν is the delaytime estimated for inter-electrode signal propagation, typically on the order of oneto several multiples ofτ = 5 msec. In future fits, some experimentation will beperformed, taking theT ’s as parameters.
This defines the conditional probability distribution for the measured scalppotentialΦν ,
Pν [Φν (t + ∆t)|Φν (t)] =1
(2πσ2∆t)1/2exp(−Lν ∆t) ,
Lν =1
2σ 2(Φν − m)2 .
The probability distribution for all electrodes is taken to be the product of all thesedistributions:
P =νΠ Pν ,
L =νΣ Lν .
SMNI Lester Ingber
Development of EEG Dipole Distribution
The model SMNI, derived forP[MG(t + ∆t)|MG(t)], is for a macrocolumnar-av eraged minicolumn; hence it is expected to be a reasonable approximation torepresent a macrocolumn, scaled to its contribution toΦν . HenceL is used torepresent this macroscopic regional Lagrangian, scaled from its mesoscopicmesocolumnar counterpartL.
However, the expression forPν uses the dipole assumption to also use thisexpression to represent several to many macrocolumns present in a region under anelectrode: A macrocolumn has a spatial extent of about a millimeter. Often mostdata represents a resolution more on the order of up to several centimeters, manymacrocolumns.
A scaling is tentatively assumed, to use the expression for the macrocolumnardistribution for the electrode distribution, and see if the fits are consistent with thisscaling. One argument in favor of this procedure is that it is generallyacknowledged that only a small fraction of firings, those that fire coherently, areresponsible for the observed activity being recorded.
The results obtained here seem to confirm that this approximation is in factquite reasonable. For example, for the nonvisual neocortex, taking the extreme ofpermitting only unit changes inMG firings, it seems reasonable to always be ableto map the observed electric potential valuesΦ from a given electrode onto a mesha fraction of 4NE NI ≈ 104.
It is expected that the use of MNN will make this scaling approximationunnecessary.
SMNI Lester Ingber
Key Indicators of EEG Correlates to Brain StatesThe SMNI probability distribution can be used directly to model EEG data,
instead of using just the variational equations. Some important features notpreviously considered in this field that were used in the 1991Physical Review Apaper were:
• Intra-Electrode Coherencyis determined by the standard deviations ofexcitatory and inhibitory firings under a given electrode as calculated usingSMNI. Once the SMNI parameters are fit, then these firings are calculated astransformations on the EEG data, as described in terms of the SMNI derivedprobability distributions. This is primarily a measure of coherent columnaractivity.
• Inter-Electrode Circuitry is determined by the fraction of available long-ranged fibers under one electrode which actively contribute to activity underanother electrode, within the resolution of time given in the data (which istypically greater than or equal to the relative refractory time of most neurons,about 5−10 msec). This is primarily a measure of inter-regionalactivity/circuitry. Realistic delays can be modeled and fit to data.
The electrical potential of each electrode, labeled byG, is represented by itsdipole-like nature,MG(t), which is influenced by its underlying columnar activityas well as its interactions with other electrodes,MG′ , G ≠ G′. This can beexpressed as:
MG = gG + gG
i ηi ,
gG = −τ −1(MG + NG tanhFG) ,
gGi = (NG/τ )1/2sechFG ,
FG =(VG − a|G|
G′ v|G|G′ N
G′ −1
2A|G|
G′ v|G|G′ M
G′ − a‡EE′ v
EE′N
‡E′ −1
2A‡E
E′ vEE′M
‡E′)
((π[(v|G|G′ )
2 + (φ|G|G′ )
2](a|G|G′ N
G′ +1
2A|G|
G′ MG′ + a‡E
E′ N‡E′ +1
2A‡E
E′ M‡E′)))1/2.
The equivalent Lagrangian is used for the actual fits.
SMNI Lester Ingber
Pilot Study—EEG Correlates to Behavioral StatesIn a 1991 paper, sets of EEG data, given to the author by Henri Begleiter,
Neurodynamics Laboratory at the State University of New York Health Center atBrooklyn, were obtained from subjects while they were reacting to pattern-matching “odd-ball”-type tasks requiring varying states of selective attentiontaxing their short-term memory. Based on psychiatric and family-historyevaluations, 49 subjects were classified into two groups, 25 possibly having high-risk and 24 possibly having low-risk genetic propensities to alcoholism.
After each subject’s data set, representing averages over 190 points of EEGdata, was fitted to its probability distribution, the data were again filtered throughthe fitted Lagrangian, and the mean and mean-square values ofMG were recordedas they were calculated fromΦ. Then, the group’s averages and standarddeviations were calculated, the latter simply from{ [< (MG)2 > − < MG >2]n/(n − 1)} 1/2, where n = 49. This procedure gives themeans and standard deviations of the effective firings,MG, aggregated from allsubjects under each electrode, as well as the weightsd of the time-delayed inter-electrode inputsM ∗ E.
Although MG were permitted to roam throughout their physical ranges of±NE = ±80 and±NI = ±30 (in the nonvisual neocortex, true for all these regions),their observed effective regional-averaged firing states were observed to obey thecentering mechanism. I.e., this numerical result is consistent with the assumptionthat the most likely firing states are centered about the regionMG ≈ 0 ≈ M ∗ E inFG.
Fitted parameters were used to calculate equivalent columnar firing states andtime delays between regions. No statistical differences were observed between thetotal group, the high-risk group, and the low-risk group.
SMNI Lester Ingber
Sample Results — Total GroupTABLE I. Means and standard deviations of averages over EEG recordings
from 49 subjects, representing 190 points of data per subject, are consistent withthe centering mechanism during selective attention tasks. Under each electrode themeans and standard deviations ofMG are given. Also given for each electrode arethe means and standard deviations of the individual-subject standard deviations,here labeled asσ , aggregated from each subject. The physical bounds for allM E
under these nonvisual regions are±NE = ±80. Also given are the weightsd of theregional time-delayed contributionsdM∗ E. The physical bounds for allM E andM ∗ E under these nonvisual regions are±NE = ±N ∗ E = ±80; the physical boundsfor all M I are±NI = ±30.
Lessons LearnedFuture studies will use data obtained by Laplacian recording techniques. E.g.,
patches of 5 closely-spaced electrodes are used to determine a reasonableunderlying source of activity.
The previous study used data collected under the assumptions that:• there is a genetic predisposition to alcoholism, and• that this predisposition could be correlated to EEG activity.
These assumptions were negated by the SMNI study: E.g., there were nostatistical differences in intra-electrode coherencies or in inter-electrode circuitry,or in any other parameter, between the two groups. Especially in light of otherstudies, it seems that if such a predisposition exists, it is a multifactorial issue thatrequires a very large subject population to resolve the many parameters, more thanwas available for this EEG study.
SMNI Lester Ingber
Future Sources of DataLaplacian techniques help to better localize sources of activity, and thereby
become more suitable for the MNN modeling. By virtue of Poisson’s equation,
∇ ⋅ σ (r )∇ φ(r , t) = s(r , t) ,
where σ (r ) is the tissue conductivity,s(r , t) is the macrocolumnar-averagedmicrosource typically≈ 0.1−1µA/mm3, andφ(r , t) is the micropotential.
Thus, the Laplacian of the EEG potential, directly related toφ, presents anEEG variable directly related to columnar firings. E.g.,Φ, instead of representingthe EEG electric potential, then is a direct measure of current flows described bytemporal changes in firingsMG.
There is at least one problem associated with the use of Laplacian filtering, asecond-order differentiation process. Differentiation generally tends to emphasizethe noise contributions owing to their typically sharper curvatures. As in similarmodeling projects in combat analyses and finance, this can be alleviated by usingthe path-integral Lagrangian to determine the proper meshes. Then, this resolutionof data must be available for further modeling.
A recent 1996 study used evoked potential (EP) data from a multi-electrodearray under a variety of conditions. The earlier 1991 study used only averaged EPdata. As the SMNI model suggests, EEG “noise” likely possesses non-constantstructure developed from the statistical mechanics of neocortical interactions, andthe model should be fit directly to the single-sweep data to be able to extract themaximum signal.
SMNI Lester Ingber
Precursor Information of Epileptic SeizuresImprove Temporal Prediction of Seizures
If these SMNI techniques can find patterns of such such upcoming activitysome time before the trained eye of the clinician, then the costs of time and pain inpreparation for surgery can be reduced. This project will determine inter-electrodeand intra-electrode activities prior to spike activity to determine likely electrodecircuitries highly correlated to the onset of seizures. This can only do better thansimple averaging or filtering of such activity, as typically used as input todetermine “dipole” locations of activity prior to the onset of seizures.
Improve Spatial Resolution
If a subset of electrode circuitries are determined to be highly correlated to theonset of seizures, then their associated regions of activity can be used as a firstapproximate of underlying “dipole” sources of brain activity affecting seizures.This first approximate may be better than using a spherical head model to deducesuch a first guess. Such first approximates can then be used for more realisticdipole source modeling, including the actual shape of the brain surface todetermine likely localized areas of diseased tissue.
SMNI Lester Ingber
OTHER APPLICATIONS—MNN AND CHAOS
SMNI Lester Ingber
Generic Mesoscopic Neural Networks• SMNI describes reasonable mechanism for information processing in
neocortex at columnar scales.
• Modern stochastic calculus permits development of alternative descriptions ofpath-integral Lagrangians, Fokker-Planck equations, and Langevin rateequations. The induced Riemannian geometry affords invariance ofprobability distribution under general nonlinear transformations.
• ASA presents a powerful global optimization that has been tested in a varietyof problems defined by nonlinear Lagrangians.
• Parallel-processing computations can be applied to ASA as well as to aneural-network architecture.
This MNN algorithm was published inPhysical Review A RapidCommunicationsin 1992.
SMNI Lester Ingber
Further Development of SMNI for MNNWhile the development of nearest-neighbor interactions into a potential term
V ′ was useful to explore local EEG dispersion relations, for present purposes this isnot necessary and, as permitted in the development of SMNI, minicolumnarinteractions with firingsM†G are simply incorporated intoFG:
FG =VG − v|G|
G′ T|G|G′
((π[(v|G|G′ )
2 + (φ|G|G′ )
2]T |G|G′ ))
1/2 ,
T |G|G′ = a|G|
G′ NG′ +
1
2A|G|
G′ MG′
+a†|G|G′ N†G′ +
1
2A†|G|
G′ M†G′
+a‡|G|G′ N‡G′ +
1
2A‡|G|
G′ M‡G′ ,
a†GG′ =
1
2A†G
G′ + B†GG′ ,
A‡IE = A‡E
I = A‡II = B‡I
E = B‡EI = B‡I
I = 0 ,
a‡EE =
1
2A‡E
E + B‡EE .
MG represent firings internal to a given minicolumn.M†G represent firings amongminicolumns within a macrocolumn.M‡E represent firings among minicolumns inmacrocolumns under different electrodes (onlyG = E firings exist).
SMNI Lester Ingber
MNN Minicolumnar InteractionsMinicolumnar interactions are represented across three scales: intra-
macrocolumnar within a given macrocolumn, intra-regional and inter-macrocolumnar within a given region and between macrocolumns, and inter-regional between regions. The large solid circles represent regions, theintermediate long-dashed circles represent macrocolumns, and the small short-dashed circles represent minicolumns.
MNN permits an overlap in scales being investigated by SMNI and ANN.
SMNI Lester Ingber
MNN Learning“Learning” takes place by presenting the MNN with data, and parametrizing
the data in terms of the “firings,” or multivariateMG “spins.” The “weights,” orcoefficients of functions ofMG appearing in the drifts and diffusions, are fit toincoming data, considering the joint “effective” Lagrangian (including thelogarithm of the prefactor in the probability distribution) as a dynamic costfunction.
The cost function is a sum of effective Lagrangians from each node and overeach time epoch of data.
This program of fitting coefficients in Lagrangian uses methods of adaptivesimulated annealing (ASA). This maximum likelihood procedure (statistically)avoids problems of trapping in local minima, as experienced by other types ofgradient and regression techniques.
SMNI Lester Ingber
MNN Prediction“Prediction” takes advantage of a mathematically equivalent representation of
the Lagrangian path-integral algorithm, i.e., a set of coupled Langevin rate-equations. The Itoˆ (prepoint-discretized) Langevin equation is analyzed in terms ofthe Wiener processdWi , which is rewritten in terms of Gaussian noiseη i = dWi /dtin the limit:
MG(t + ∆t) − MG(t) = dMG = gGdt + gGi dWi ,
dMG
dt= M
G = gG + gGi η
i ,
M = { MG; G = 1,. . . ,Λ } , η = { η i ; i = 1,. . . , N } ,
Moments of an arbitrary functionF(η ) over this stochastic space are defined by apath integral overη i . The Lagrangian diffusions are calculated as
gGG′ =N
i=1Σ gG
i gG′i .
The calculation of the evolution of Langevin systems has been implemented inthe above-mentioned systems using ASA. It has been used as an aid to debug theASA fitting codes, by first generating data from coupled Langevin equations,relaxing the coefficients, and then fitting this data with the effective Lagrangiancost-function algorithm to recapture the original coefficients within the diffusionsdefined bygGG′ .
SMNI Lester Ingber
MNN Parallel ProcessingThe use of parallel processors can make this algorithm even more efficient, as
ASA lends itself well to parallelization.
• During “learning,” blocks of random numbers are generated in parallel, andthen sequentially checked to find a generating point satisfying all boundaryconditions.
• Advantage is taken of the low ratio of acceptance to generated points typicalin ASA, to generate blocks of cost functions, and then sequentially checked tofind the next best current minimum.
• Additionally, when fitting dynamic systems, e.g., the three physical systemsexamined to date, parallelization is attained by independently calculating eachtime epoch’s contribution to the cost function.
• Similarly, during “prediction,” blocks of random numbers are generated tosupport the Langevin-equation calculations, and each node is processed inparallel.
SMNI Lester Ingber
Generic MNNThis SMNI MNN can be generalized to model other large-scale nonlinear
stochastic multivariate systems, by considering general drifts and diffusions tomodel such systems, now lettingG represent an arbitrary number of variables.Ideally, these systems inherently will be of the Fokker-Planck type,
∂P
∂t=∂(−gGP)
∂MG+
1
2
∂2(gGG′P)
∂MG∂MG′ .
The topology, geometry, and connectivity of the MNN can of course begeneralized. E.g., there need not be any restriction to nearest-neighborinteractions, although this is simpler to implement especially on parallelprocessors. Also, “hidden layers” can be included to increase the complexity ofthe MNN, although the inclusion of nonlinear structure in the driftsgG anddiffusionsgGG′ may make this unnecessary for many systems.
This addresses some concerns in the neural network community relating to theability of neural networks to be trusted to generalize to new contexts: If the nodescan be described by mechanisms inherently consistent with system, then moreconfidence can be justified for generalization. This is more desirable and likelymore robust, than using additional “hidden layers” to model such nonlinearstructures.
SMNI Lester Ingber
Nonlinear Dynamics — Chaos?What if EEG has chaotic mechanisms that overshadow the above stochastic
considerations? The real issue is whether the scatter in data can be distinguishedbetween being due to noise or chaos.
The SMNI-derived probability distributions can be used to help determine ifchaos is a viable mechanism in EEG. The probability distribution itself is amathematical measure to which tests can be applied to determine the existence ofother nonlinear mechanisms.
The path integral has been used to compare long-time correlations in data topredictions of models, while calculating their sensitivity, e.g., of second moments,to initial conditions. This also helps to compare alternative models, previouslyhaving their short-time probability distributions fit to data, with respect to theirpredictive power over long time scales.
Similar to serious work undertaken in several fields, the impulse to identify‘‘chaos’’ in a complex system often has been premature. It is not supported by thefacts, tentative as they are because of sparse data. Similar caution should beexercised regarding neocortical interactions.
It is of interest to note a series of experimental and theoretical studies ofnonlinear dynamics of the olfactory bulb in small mammals, in which distinctiveEEG patterns on the bulb surface are shown to be associated with specific odors.Many such studies demonstrating chaos are quite model dependent, and as such itis only fair to present the models as possessing chaos, not necessarily the actualphysical system. However, there are reports of model-independent experimentalobservations of distinctive stimulus-dependent parameters having extremesensitivity to initial conditions.
It has been widely noted that the correlation dimension of data is difficult tocalculate; perhaps it is often not even a well-founded concept, e.g., since the EEGof event-related potentials is likely nonstationary and very much context andsubject dependent. Its calculation, e.g., using the popular Grassberger-Procacciaalgorithm, even when supplemented with finer statistical tests and noise reductiontechniques, may prove fruitful, but likely only as a sensitivity index relative toshifting contexts and complementary to other models of EEG data.
SMNI Lester Ingber
Duffing EEG Analog — Chaos in NoiseNunez and Srinivasan (1993) studied chaos in a model of EEG, cast into a
Duffing analog.
x = f (x, t) ,
f = −α x −ω20x + B cost .
This can be recast as
x = y ,
y = f (x, t) ,
f = −α y −ω20x + B cost .
Note that this is equivalent to a 3-dimensional autonomous set of equations, e.g.,replacing cost by cosz, defining z = β , and takingβ to be some constant.
Ingber, Srinivasan and Nunez (1996) studied a model embedding thisdeterministic Duffing system in moderate noise, e.g., as exists in such models asSMNI. Independent Gaussian-Markovian (“white”) noise is added to both ˙x and y,η j
i , where the variables are represented byi = { x, y} and the noise terms arerepresented byj = {1, 2} ,
x = y + g1xη1 ,
y = f (x, t) + g2yη2 ,
< η j (t) >η= 0 ,
< η j (t),η j ′(t ′) >η= δ jj ′δ (t − t ′) .
In this study, we take moderate noise and simply set ˆgji =1. 0δ j
i .
The equivalent short-time conditional probability distributionP, in terms ofits LagrangianL, corresponding to these Langevin rate-equations is
P[x, y; t + ∆t|x, y, t] =1
(2π∆t)( g11g22)2exp(−L∆t) ,
L =( x − y)2
2( g11)2+
(y − f )2
2( g22)2.
SMNI Lester Ingber
Duffing EEG Analog — Preliminary IndicationsNo differences were seen in the stochastic system, comparing regions of
Duffing parameters that give rise to chaotic and non-chaotic solutions. Morecalculations must be performed for longer durations to draw more definitiveconclusions.
Path Integral Evolution of Non-Chaotic Stochastic Duffing Oscillator
’t=15’ 0.00423 0.00339 0.00254 0.00169
0.000847
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Path Integral Evolution of Chaotic Stochastic Duffing Oscillator
’t=15’ 0.00425 0.0034 0.00255 0.0017 0.00085
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SMNI Lester Ingber
SMNI CANONICAL MOMENTA INDICATORS—EEG
SMNI Lester Ingber
Canonical Momenta Indicators (CMI)Some 1996 papers illustrated how canonical momenta derived from fitted
nonlinear stochastic processes, using ASA to fit models to S&P 500 data, can beuseful indicators of nonequilibrium behavior of financial markets.
“Momentum”= ΠG =∂L
∂(∂MG/∂t)
Tr aining Phase
These techniques are quite generic, and can be applied to the SMNI model. Ina 1997Physical Reviewpaper, a giv en SMNI model is fit to EEG data, e.g., asperformed in the 1991Physical Reviewpaper. This develops a zeroth order guessfor SMNI parameters for a given subject’s training data. Next, ASA is usedrecursively to seek parameterized predictor rules, e.g., modeled according toguidelines used by clinicians. The parameterized predictor rules form an outerASA shell, while regularly fine-tuning the SMNI inner-shell parameters within amoving window (one of the outer-shell parameters). The outer-shell cost functionis defined as some measure of successful predictions of upcoming EEG events.
Testing Phase
In the testing phase, the outer-shell parameters fit in the training phase areused in out-of-sample data. Again, the process of regularly fine-tuning the inner-shell of SMNI parameters is used in this phase.
Utility
These momenta indicators should be considered as supplemental to otherclinical indicators. This is how they are being used in financial trading systems. Inthe context of other invariant measures, the CMI transform covariantly underRiemannian transformations, but are more sensitive measures of neocorticalactivity than other invariants such as the energy density, effectively the square ofthe CMI, or the information which also effectively is in terms of the square of theCMI (essentially integrals over quantities proportional to the energy times a factorof an exponential including the energy as an argument). Neither the energy or theinformation give details of the components as do the CMI. EEG is measuring aquite oscillatory system and the relative signs of such activity are quite important.
SMNI Lester Ingber
SMNI vs SMFM (SM of Financial Markets)
Feature SMNI SMFM
Data EEG coupled marketsTraining a given subject historical dataTesting clinical observation trading for profit/lossASA “Inner-Shell” Momenta EEG-fit SMNI market-fit modelsASA “Outer-Shell” Rules clinical rules trading rules
SMNI Lester Ingber
SMNI CMI of Genetic Predisposition to AlcoholismEach set of results is presented with 6 figures, labeled as [{alcoholic|control} ,
{stimulus 1|match|no-match} , subject, {potential|momenta} ], abbreviated to{a|c}_{1|m|n}_subject.{pot|mom} where match or no-match was performed forstimulus 2 after 3.2 sec of a presentation of stimulus 1. Data includes 10 trials of69 epochs each between 150 and 400 msec after presentation. For each subjectsrun, after fitting 28 parameters with ASA, epoch by epoch averages are developedof the raw data and of the multivariate SMNI canonical momenta. There are fitsand CMI calculations using data sets from 10 control and 10 alcoholic subjects foreach of the 3 paradigms. For some subjects there also are out-of-sample CMIcalculations. All stimuli were presented for 300 msec. Note that the subjectnumber also includes the{alcoholic|control} tag, but this tag was added just to aidsorting of files (as there are contribution from co2 and co3 subjects). Each figurecontains graphs superimposed for 6 electrode sites (out of 64 in the data) whichhave been modeled by SMNI using the circuitry:
Site Contributions From Time Delays (3.906 msec)F3F4T7 F3 1T7 T8 1T8 F4 1T8 T7 1P7 T7 1P7 P8 1P7 F3 2P8 T8 1P8 P7 1P8 F4 2
Data was collected by Henri Begleiter and associates at the NeurodynamicsLaboratory at the State University of New York Health Center at Brooklyn.Calculations were performed on a Sun SPARC 20 at the University of Oregon,Eugene, courtesy of the Department of Psychology.
The SMNI CMI give more signal to noise presentation than the raw data,especially for the significant matching tasks between the control and the alcoholicgroups. The CMI can be processed further as is the raw data, and also used tocalculate “energy” and “information/entropy” densities.
SMNI Lester Ingber
Data vs SMNI CMI for Alcoholic Group — S1
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SMNI Lester Ingber
Data vs SMNI CMI for Control Group — S1
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SMNI Lester Ingber
Data vs SMNI CMI for Alcoholic Group — S2 Match
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SMNI Lester Ingber
Data vs SMNI CMI for Control Group — S2 Match
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SMNI Lester Ingber
Data vs SMNI CMI for Alcoholic Group — S2 No Match
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SMNI Lester Ingber
Data vs SMNI CMI for Control Group — S2 No Match
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SMNI Lester Ingber
SMNI GENERIC FEATURES
SMNI Lester Ingber
Scaling ParadigmThese results, in addition to their importance in reasonably modeling EEG
with SMNI, also have a deeper theoretical importance with respect to the scaling ofneocortical mechanisms of interaction across disparate spatial scales andbehavioral phenomena. These features offer guides to overlap models acrossmultiple scales.
• The derivation of the mesoscopic probability distribution, yields similar algebraicstructures of the threshold factors at the neuronal scale,
F j =Vj −
kΣ ajk v jk
((πk′Σ ajk ′(v
2jk ′ + φ
2jk ′)))
12
,
to be compared with the mesoscopic threshold factor,
FG =(VG − a|G|
G′ v|G|G′ N
G′ −1
2A|G|
G′ v|G|G′ M
G′)
((π[(v|G|G′ )
2 + (φ|G|G′ )
2](a|G|G′ N
G′ +1
2A|G|
G′ MG′)))1/2
,
which contribute to the driftsgG and diffusionsgGG,
gG = −τ −1(MG + NG tanhFG) ,
gGG′ = (gGG′)−1 = δG′
G τ −1NGsech2FG ,
illustrating common forms of interactions between their entities, i.e., neurons andcolumns of neurons, respectively.
• The macroscopic regional probability distribution has the same functional form asthe mesoscopic distribution, where the macroscopic drifts and diffusions of thepotentials described by theΦ’s are simply linearly related to the (nonlinear)mesoscopic drifts and diffusions of the columnar firing states given by theMG’s.
m ≡< Φν −φ >= a < M E > +b < M I >= agE + bgI ,
σ 2 ≡< (Φν −φ)2 > − < Φν −φ >2= a2gEE + b2gII .
• It was possible to scale the macrocolumnar distribution to describe electroderecording areas of several cm2, and have the fitted parameters lie within theirexperimentally observed ranges.
SMNI Lester Ingber
Addressing Phenomena at Multiple ScalesAnalyzing, understanding, and attempting to predict neocortical phenomena at
the spatial scales encountered in EEG scalp recordings involves measuring firingsfrom millions of neurons; in intracortical measurements at least tens of thousandsof neurons are involved. SMNI approaches such scales as new systems withemergent phenomena. Just as physics and chemistry could not have progressedthis century if all theoretical and experimental research were inappropriatelyconstrained to be understood at the level of quantum mechanics (or quarks orstrings), so neuroscience must soon accept that all brain phenomena is not bestunderstood or perhaps understood at all at the level of simple neuron-neuroninteractions (or membrane dynamics or macromolecular interactions). Differentscales present new complex systems that must be approached as such and oftenwith different approaches.
SMNI Lester Ingber
Increasing Signal to Noise/Audit Trail to SourcesLogical and Testable Development Across Multiple Scales
SMNI is a logical, nonlinear, stochastic development of aggregating neuronaland synaptic interactions to larger and larger scales. Paradigms and metaphorsfrom other disciplines do not substitute for logical SMNI development.
Validity Across Multiple Scales
The SMNI theoretical model has independent validity in describing EEGdispersion relations, systematics of short-term memory, velocities of propagationof information across neocortical fields, recency versus primacy effects, etc. Fitsof such models to data should do better in extracting signal from noise thanad hocphenomenological models.
Use of ASA and PATHINT on Nonlinear Stochastic Systems
ASA enables the fitting of quite arbitrary nonlinear stochastic models to suchdata as presented by EEG systems. Once fitted, PATHINT can evolve the system,testing long-time correlations between the model(s) and the data, as well as servingto predict events.
Inclusion of Short-Range and Long-Range Interactions
SMNI proposes that models to be fitted to data include models of activityunder each electrode, e.g., due to short-ranged neuronal fibers, as well as models ofactivity across electrodes, e.g., due to long-ranged fibers.
Riemannian Invariants
Yet to explore are the ramifications of using the derived (not hypothesized)Riemannian metric induced by multivariate Fokker-Plank-type systems. Thisseems to form a natural invariant measure of information, that could/should beused to explore flows of information between neocortical regions.
Renormalization of Attenuated Frequencies
The SMNI approach shows how to “renormalize” the spatial activity to get amodel that more closely matches the experimental situation, wherein there isattenuation of ranges of wav e numbers.
MNN Real-Time Processing and Audit Trail to Finer Scales
The MNN parallel algorithm may offer real-time processing of nonlinearmodeling and fitting of EEG data for clinical use. Regional EEG data can beinterpreted as mechanisms occurring at the minicolumnar scales.
Recursive ASA Optimization of Momenta Indicators + Clinical Rules
Similar to codes developed for financial systems, recursive ASA optimizationsof inner-shell SMNI indicators and outer-shell clinical guides should improvepredictions of and decisions on clinical observations.
SMNI Lester Ingber
Generic Applications to Process Aggregated InformationThis statistical mechanics approach represents the mesoscale as a pattern-
processing computer. The underlying mathematical theory, i.e., the path-integralapproach, specifies a parallel-processing algorithm which statistically finds thoseparameter-regions of firing which contribute most to the overall probabilitydistribution: This is a kind of ‘‘intuitive’’ algorithm, globally searching a largemultivariate data base to find parameter-regions deserving more detailed localinformation-processing. The derived probability distribution can be thought of as afilter, or processor, of incoming patterns of information; and this filter can beadapted, or updated, as it interacts with previously stored patterns of information.
These technical methods are quite general, and I have applied them to:
neuroscience— detailing properties of short-term memory derived from neuronalsynaptic interactions, and calculating most likely frequencies observed in EEG dataand velocities of propagation of information across neocortex.
nuclear physics — detailing Riemannian contributions arising from “velocity-dependent” forces to the binding energy of nucleons interacting via exchanges ofmesons.
combat systems— modeling battalion- and brigade-level attrition, permittingcomparison of combat computer models with field exercise data.
financial markets — defining an approach to perform superior fits of economicmodels to interest-rates, and to perform superior calculations of multivariatesecurities such as bonds and options. Bond-pricing, options-pricing, and manyderivative theories present examples of interesting systems which possess multi-variable, nonlinear, multiplicative-noise, Fokker-Planck dynamics. One class oftheories develops interest rates, determined at several temporal scales, as theindependent stochastic variables. Previous models tested against data have beentwo dimensional generalizations, e.g., short-term and long-term interest rates, ofthe well-known Black-Scholes model, but recent fits argue for the necessity ofincluding at least a third variable, intermediate-term interest rates.
SMNI Lester Ingber
Utility, Parsimony, & BeautySMNI presents a computational algorithm faithful to a model of neocortical
interactions that has been baselined to experimental observations across multiplescales. The present neuroscience project is constructing a tool to be used for real-time study and diagnoses of brain function.
Similarly to the neocortex, in many complex systems, as spatial-temporalscales of observation are increased, new phenomena arise by virtue of synergisticinteractions among smaller-scale entities—perhaps more properly labeled‘‘quasientities’’—which serve to explain much observed data in a parsimonious,usually mathematically aesthetic, fashion. Many complex systems are innonequilibrium, being driven by nonlinear and stochastic interactions of manyexternal and internal degrees of freedom. For these systems, classicalthermodynamical approaches typically do not apply. Such systems are best treatedby respecting some intermediate mesoscale as “fundamental” to drive largermacroscopic processes.
The use of ASA and PATHINT permit the processing of quite generalnonlinear, stochastic, and multivariate descriptions of systems, without beinglimited to equilibrium energy-type cost functions.
Phenomena specific to given scales of interaction must be modeled andstudied, as well as the flow of information across these scales. The stochasticnonlinear SMNI paradigm permits this development.
