The 4 International Academic Conference

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Nov 16, 2013 (3 years and 10 months ago)

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The 4
th

International Academic Conference

on Environmental and Occupational Medicine



Kunming, Yunnan, PR China

Oct. 16
-
19, 2006


Assessing deficits of central nervous system
functions in the detection of eventual
environmental and occupational health hazards


Michael Bornhausen, MD


Institute of Animal Physiology, Faculty of Veterinary
Medicine, University of Munich, Germany



Former affiliation


Institute of Toxicology

German National Research Centre of Environmental


and Health Sciences (GSF
-
FZ)

München
-
Neuherberg, Germany


Research topics:



-

radiobiology



-

spectral analysis of EEG (FFT)



-

single nerve cell activity, spike train analysis



-

operant
-
behavior



-

learning, memory



-

design and evaluation of alternative methods




in toxicology

General aim

Assessment of the dynamics of changes of
CNS functions


Specific aim

Detection of cognitive effects


eventually induced by chronic exposure to
GSM or UMTS electromagnetic fields in
three consecutive generations of rats

Acknowledgement


Part of this work was supported by the German Federal
Office of Radiation Protection (
B
undesamt
f
ür
S
trahlenschutz, BfS) and done in cooperation with:



Dr. H.
Scheingraber
,
M
ax
-
P
lanck
-
Institute of
E
xtra
-
terrestrial Physics (MPE), Garching,




Dipl.
-
Ing. C.
Kögler
, ck
-
3d IT solutions, Emmering,

Germany



Prof. Ping
LIU
, Prof. Xinan
WU
, Department of Public
Health, Kunming Medical College, Kunming, Yunnan,



PR China

Key words


health hazards


e
lectro
m
agnetic
f
ields (EMFs), cell
-
phone


C
entral
N
ervous
S
ystem (CNS)


cognition (learning, memory)


operant
-
behavior


microstructures (
i
nter
-
r
esponse
i
ntervals,
IRIs)


dynamics of serial properties in operant
-
behavior tests


rats

Literature


M. Bornhausen and H. Scheingraber
: Prenatal exposure to 900 MHz, cell
-
phone electromagnetic fields had no effect on operant
-
behavior
performances of adult rats.

Bioelectromagnetics

21:566
-
574, 2000



C.B. Ferster and B.F. Skinner
: Schedules of Reinforcement. Appleton
-
Century
-
Crofts, New York 1957



R.P.Jensh
: Behavioral testing procedures: a review. In: E.M. Johnson, D.M.
Kochhar (eds.): Handbook of experimental pharmacology, vol. 65.
Teratogenesis and reproductive toxicology. Berlin, Heidelberg, New York:
Springer Verlag, 1983



M.H. Repacholi
: Low
-
level exposure to radiofrequency electromagnetic
fields. Health effects and research needs.
Bioelectromagnetics

19:1
-
19,
1998



B. Weiss, J.M. Ziriax, M. Christopher Newland
: Serial properties of
behavior and their chemical modification.
Animal Learning & Behavior

17(1):83
-
93, 1989





China


U.S.A.

Germany


area



9 598 029 km
2


9 629 047 km
2


357 046 km
2


population


1 288 700 000

291 500 000

82 600 000


population/km
2

134


30


231


CO
2
-
emission/subject

2.5 tons


19.8 tons


10.0 tons


energy consumpt./subj.

880 kg
oe


7 960 kg
oe

4 230 kg
oe


smokers


35.6 %


23.6 %


35 %


meat consumpt./subj.

47 kg


122 kg


87 kg


use of paper/subject

33 kg


331 kg


233 kg


no. of persons/room

1.1


0.5


0.5


water consumpt./subj.

1 203.3 l


5 024.7 l


1 586.3 l



/day
(agriculture, industry, households)


TV
-
sets/1000 subj.

292


844


586


cars/1000 subjects

16


774


565


(Courtesy of
National Geographic,

March 2004; sources UN, WHO; oe = oil equivalent)

American life style


"... If everybody on Earth would live like the
US
-
Americans we would need three
planets to keep our living standard."



Peter RAVEN, botanist and environmentalist



(Courtesy of
National Geographic,

March 2004)



P
ersistent
o
rganic
p
ollutants
(POPs)


Long
-
term exposure to even small doses of


dioxines


furanes


p
oly
c
hlorinated
b
iphenyls (PCB)


endosulfanes


p
oly
b
rominated
d
iphenyl
e
thers (PBDE)


DDT


etc.

may have serious CNS consequences in man.










changes of function are precursors of
structural changes


functions of the
C
entral
N
ervous
S
ystem (CNS) are more sensitive than
functions of other organs


CNS functions are most sensitive during
prenatal development

Rationale for experimental studies of
cognition after chronic exposure to
environmental hazards (e.g. GSM
-

or
UMTS
-
e
lectro
m
agnetic
f
ields [EMFs])


No effects after prenatal
exposure


M. Bornhausen and H. Scheingraber
:


Prenatal exposure to 900 MHz, cell
-
phone electromagnetic fields had no
effect on operant
-
behavior
performances of adult rats.



Bioelectromagnetics

21:566
-
574, 2000



Reasons for the choice of automated

operant
-
behavior tests



Negative example:
Appearance of “developmental landmarks”
(various physical signs and neuromuscular reflexes) in rat pups
must be carefully and repeatedly checked by experienced
personnel

postnatal day


0



day of birth


2



surface righting


4



pinna detachment


8



cliff avoidance


9



negative geotaxis

11



forelimb grasp

15



bar holding

16



eye opening, forelimb hanging, air righting

17



development of fur

19



ear unfolding

25
-
30


descent of testis, opening of vagina

Operant
-
behavior


Operant
-
behavior tests are run in a battery of 10
standardized test chambers (“Skinner boxes“).



Subjects are required to press a lever for food
reinforcement (pellets of 45 mg) .



15h
-
nocturnal test sessions (16:00
-
07:00 CET)
are subdivided by alternating 30 min ON
-

and


60 min OFF
-
cycles.



Final tests require the subjects to respect a
blocking interval of 16 sec after a reinforcement
.

Operant
-
behavior test chambers

(“Skinner boxes“)

Operant
-
behavior schedules



D
ifferential
R
einforcement of
Zero

Rate (
DR0
)


D
ifferential
R
einforcement of
H
igh Rate (
DRH
)


D
ifferential
R
einforcement of
L
ow Rate (
DRL
)

Actual sequence of operant
-
behavior tests


DR0 5 min
(ss. are automatically trained to press a
lever for food reinforcement)


DRH 2/1
(ss. are required to press the lever 2 times in
1 sec for a reinforcement)


DRH 4/2
(ss. are required to press 4 times the lever in
2 sec for a reinforcement)


DRL 1/16
(ss. are required to respect a blocking
interval of 16 sec after a reinforcement; a precocious bar
press resets the interval to its start. The interval is
signaled by a green cue light.)

Actual BfS
-
sponsored

research project


Detection of cognitive effects


if any


after


chronic exposure to GSM
-

or UMTS
-

e
lectro
m
agnetic
f
ields (EMFs) in three
consecutive generations (F0, F1, F2) of
rats


Acceptance problem


Cellular phones are welcome; base stations, however, are
being disputed.


Advantages of individual cellular phones in emergencies and
accidents are recognized.


But people living in the vicinity of base stations and having
visual contact to the antenna, very often say NO.


Controversial discussions concerning an alleged health risk of
base stations are often very emotional and can be
characterized by a syndrome well known to psychologists:


ignorance of scientific facts


unsufficient transfer of knowledge


and “ANGST” (fear of something you don’t understand)

Focus of public concern



digital pulses of cell
-
phone signals are thought to be
particularly dangerous


continuous exposure by base stations


high risk of sensitive people


definition of exposure limits relative to thermal effects only


health hazards by non
-
thermal effects


unsufficient scientific data, especially concerning eventual
consequences of long term exposure


(5 % of the general population in Germany, only, believe that
mobile communication does present health risks.)

Microstructures



Microstructures of operant
-
behavior test
sessions are shown by pattern of
i
nter
-
r
esponse
i
ntervals (IRIs, i.e. time between consecutive
lever presses with a resolution of 1 msec).



IRI
-
pattern differentiate between “learners“ and
“non
-
learners“.

Superimposed scatter plots of the

10 ON
-
cycles of a DRL session


Assessing dynamic



vs. static changes


Static results at the end of a


test session
(f.i. the ratio of correct
responses to all responses)


do not
reflect the dynamics of test
requirement acquisition.

Dynamic signal




When looking at the sequence of 10
consecutive ON
-
cycles of a 15h
-
nocturnal test session
-



a signal becomes apparent that is
proportional to the ability of the subject
to acquire the test requirement


(i.e. to "learn").

Susceptibility of the

"learning" process



We are not only interested in the fact
whether a subject has finally acquired the
test requirement (i.e. has "learnt" the task).



We go further and measure the intrinsic
properties of the "learning" process itself.

The phenomenon of learning

-

can be appropriately described by an

S
-
shaped curve



parameters
:


start time


base line


rise time


saturation


turning point







Measuring serial properties of
operant
-
behavior

I
nter
-
r
esponse
i
ntervals (IRIs) between
consecutive lever presses are recorded (
in
multiples of 1 msec
), weighed and normalized
relative to an empirically determined
standard IRI
-
distribution, and expressed
as "points".

The sequence of points, then, is fitted to an
S
-
shaped curve by an appropriate
algorhythm.

Mathematics

of S
-
shaped curve fit


Minimize the sum of squares of a set of
equations.




x=arg min(sum(func(y)
2
))



Description
:


Return the point which minimizes the sum of squares of
M (non
-
linear) equations in N unknowns given a starting
estimate, x0, using a modification of the Levenberg
-
Marquardt algorhythm.

Examples of actual research


The following graphs (scatter plots and
corresponding S
-
curve fits) are examples of our
actual and ongoing research project focusing on
the
question
:


Are there any deficits of cognition (learning
ability, memory) after long
-
term exposure to
cell
-
phone EMFs in rats ?








Changes of CNS functions


Obviously, the ability of an animal subject


to acquire an operant
-
behavior test
requirement (i.e. to "learn") can be
mathematically assessed (
in terms of

points,
rise time, turning point, saturation, start time,
etc
.) and used to quantify subtle deficits of
CNS functions.



Conclusions


Operant
-
behavior

contingencies are useful in the
assessment of potential health risks, in toxicology,
environmental protection, etc.



The analysis of
microstructures

of operant
-
behavior
test performance is a powerful tool to demonstrate
changes of CNS functions.



The
dynamics of test acquisition

(i.e. "learning”) can
be measured by S
-
curve fits and used to enhance
test sensitivity of CNS functions in situations of
potential health hazards.










Thank you for your attention !