Simple Cyclic Movementsas a Distinct Autism Feature:

Computational Approach

Krzysztof DoboszDariusz Mikołajewski

Grzegorz M. WójcikWłodzisław Duch

Department of Informatics, Nicolaus Copernicus University, Toruń

Institute of Computer Science, Maria Curie-Skłodowska University, Lublin

The 12th Cracow Grid Workshop, 22-24 October 2012

Simple Cyclic Movements as a Distinct Autism Feature

Autism – Introduction

Leo Kanner: „extreme aloneness fromthe beginning of life and anxiously obsessive

desire for the preservation of sameness”Leo Kanner: „Autistic disturbances of affective contact”,

Nervous Child 1943, 2: 217–250

Incidence of ASD: estimated to 6 per 1,000 Depends on sex: 4 times more boys suffer from

autism than girls Different forms of autism: „typical” autism,

regressive autism, Asperger syndrome, Rett syndrome, Pervasive Developmental Disorder – Not Otherwise Specified (PDD–NOS), etc.

Autism epidemics?

Simple Cyclic Movements as a Distinct Autism Feature

Autism – Symptoms

Simple Cyclic Movements as a Distinct Autism Feature

Autism – Diagnostic FeaturesThere are at least several common diagnostic features typical for ASD:

preference to be alone and difficulty in mixing with other children insistence on sameness, resists changes in routine difficulty in expressing needs, gestures/pointing instead of words, not

responsive to verbal cues (acts as deaf) inappropriate attachment to objects, spins objects, sustained odd play inappropriate laughing and giggling, may not want cuddling or act cuddly noticeable physical overactivity or extreme

underactivity tantrums – extreme distress for no apparent

reason apparent insensitivity to pain little or no eye contact echolalia

Research Problem

genes

proteins

neurons

brain regions

activation

cognitive functions (attention)

behavior

Simple Cyclic Movements as a Distinct Autism Feature

Diverse etiology: genetic mutations, immunologic/metabolic system disorders, etc.

Many different theories: Minicolumnopathy, Mirror Neuron System, Underconnectivity Theory, Function Connectivity Theory, Empathizing-Systemizing Theory, etc.

We are „data rich and theory poor” – lack of complete theory with satisfactory predictive power

Lack of good computational models joining different levels of analysis:

Simple Cyclic Movements as a Distinct Autism Feature

Emergent Simulator developed since 1995 (previous version known as PDP++) open source, modular, object-oriented, based on C++ cross-platform: MS Windows, Mac OS X, Unix/Linux (GPL) some built-in visualization methods (cluster plots, PCA, SVD,

MDS) point neurons based on Hodgkin-Huxley model

3 types of ion channels: K+, Na+, Cl-

accommodation mechanism controlling neural fatigue (K+)

different types of noise: synaptic, membrane, etc.

dedicated LEABRA algorithm (Local, Error-driven and Associative, Biologically Realistic Algorithm) – combining Hebbian learning and error-driven learning

Simple Cyclic Movements as a Distinct Autism Feature

GENESIS / NESSIE Enviroment GENESIS – GEneral NEural SImulation System developed since 1988 at California Institute of Technology

(J. M. Bower) compartmental neurons and Hodgkin-Huxley model

NESSIE – NEuroinformatic System for Science, Industry and Education

developed at Institute of Computer Science, Maria Curie-Skłodowska University, Lublin

provides easy-access to simulations in GENESIS software

Simple Cyclic Movements as a Distinct Autism Feature

Model of Simple Cyclic Movements

Input layer

Hidden layer

Output layer

4 x 8

18 x 6

18 x 6

Input layer – reflecting movement planning processes Output layer – reflecting processes within motor cortex areas: activation of groups

of neurons in this layer depends on patterns presented in the Input layer Decussating of pyramids was built into the model Adjacent patterns in the Output layer are overlapping

left hand right hand

left arm right arm

left leg right leg

left foot right foot

right hand

right arm

right leg

right foot left foot

left hand

left arm

left leg

Simple Cyclic Movements as a Distinct Autism Feature

Input & Output Patterns

Different body parts are represented by partially overlapping areas in the primary motor cortex

Simple Cyclic Movements as a Distinct Autism Feature

Emergent Model Results For each input pattern several sequences of neural activations

occurring cyclically in the Output layer (motor cortex) Similar behavior like repetitive and stereotyped movements (RSM)

typical for patients with ASD (especially young children) Lack of neural noise leads to high repeatability of simulations Appropriate level of noise resulted in changes in neurodynamics of the

motor cortex layer preventing sequences of activation to follow cyclically and activating different areas of the layer

This corresponds to normal brain dynamics

Simple Cyclic Movements as a Distinct Autism Feature

GENESIS Implementation Moving from point neurons to full compartmental Hodgkin-Huxley

cells will let observe the influence of other substantial parameters on the dynamics of the network

Parameters such as the capacitance of soma, its time constant and the value of potentials responsible for the ionic currents must also play an important role in signal transmission

Good simulation of Hodgkin-Huxley neurons requires high computational power – simulation of 1 ms of biological activity of a HH cell using first order Euler’s method with constant time interval of 1 ms requires 1200 floating point operations

Such simulation most effectively can be conducted in cluster-based environment (for large networks grid architecture may be necessary)

Simple Cyclic Movements as a Distinct Autism Feature

Cluster Architecture Consists of eight double-processor Xenon Quad Core machines

Detailed cluster configuration: 4 Intel Xeon Quad-Core E5320 1,86 GHz

processors 12 Intel Xeon Quad-Core E5405 2 GHz

processors each node of the cluster offers 8 GB of

RAM 7 TB of hard disk in total

Simulation of 1 second of biological activity of the system takes several seconds of the production run of the cluster (still far from real-time simulations)

Simple Cyclic Movements as a Distinct Autism Feature

Future Work1. Investigate the influence of different parameters on the model

behavior including cell dimensions, ion channels conductance, neural fatigue mechanism, strength of connections, number of units, etc.

2. More detailed analysis of attractor dynamics using visualization methods such as Recurrence Plots, Fuzzy Symbolic Dynamics, etc.

3. Joining results of computational modeling on functional segregation and integration with genetic data to provide insight into possible genetic basis of autism

4. Moving the model to the parallel GENESIS environment and with the increased number of neurons and connections prepare it to production runs in grid-based structures

Thank you for your attentionContact: kdobosz@mat.umk.pl