Rutgers Science Review Volume 1, Issue 2 Spring 2012
Pregnancy from a Gene’s Point of View
Arc Protein: A potential Agent in learning
Table of Contents Hysterectomy Overload. The Blame? Uterine Leiomyomas. ARC Protein: A Potential Agent in Learning Pregnancy from a Gene’s Point of View Photonic Crystals: A Brief Introduction
pg 6 pg 8 pg 10 pg 13
An Interview with Dr. Mohan Kalelkar
pg 18
Epilepsy in autism spectrum disorders (asds)
pg 22
Photo Article The World’s Fair:
pg 28
Through the Eras 2 | Rutgers Science Review | Spring 2012
Yellowstone Park: Prismatic Spring
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Hysterectomy Overload. The Blame? Uterine Leiomyomas. By Tori Gartmond in
hormones, estrogen and progesterone, play
they begin to age, but the removal of their
predominantly premenopausal women. As
a vital role in uterine fibroid formation.
reproductive organs, a procedure known
shown in the picture below, leiomyomas
Several hypotheses argue that increased
as a hysterectomy, is not. The number
can grow to be approximately the size
levels of these ovarian steroids can result
of hysterectomies has skyrocketed over
of a cantaloupe, causing a great deal of
in an increased mitotic rate that may
the past decade, largely due to uterine
discomfort in the abdominal area.
contribute to myoma development and
Menopause is expected in women as
pose
many
health
complications
The symptoms of leiomyomas are
growth, with progesterone playing the
leiomyomas
similar in all women, but the prevalence
larger role in this process3,5. In a study,
are, who they affect, and how they can
of fibroids varies among different races,
Dr. Mitchell S. Rein of the North Shore
be prevented. Though much information
and studies have shown that black women
Medical Center investigates the formation
has been collected through this research,
are more susceptible to developing them.
of leiomyomas, which involves somatic
there remain many unanswered questions.
In recent years, researchers have
mutations accompanied by interactions
Uterine leiomyomas (also known as
begun performing many clinical trials to
between growth factors and sex hormones5.
fibroids or myomas) are the most common
find explanations for the cause of uterine
According to Rein, further investigation can
reproductive tract tumors in women1.
fibroids. While many risk factors have been
lead to regulation of the hormones involved
Smooth muscle tissue of the myometrium
investigated, hormones and obesity hold
and even to a successful, effective treatment.
escapes from the uterine lining and forms
the biggest promise for identifying the cause
Obesity has also been linked to
fibroids in other areas of the body3, and
of these fibroids. Of these two potentials,
fibroid formation. As a person’s weight
these fibroids have progressively become
hormones seem to have the strongest basis
increases, so does the number of circulating
a problem in women across the United
since they target cells and change cell
androgens that are converted to a hormone
States. The rate of formation of leiomyomas
activity, causing cells to behave abnormally.
called estrone.2
has been climbing at an astonishing rate;
Many studies have shown that two
leiomyomas. Many studies have tried to understand
what
uterine
This overproduction of
estrogen stimulates growth of the escaped
nearly 70-80% of women are
myometrial
expected to have leiomyomas
lesions that are eventually
at some point in their lives,
implanted
although only 25% of women
parts of the pelvic region.
will show severe symptoms
Through trial and error,
(i.e. excessive uterine bleeding,
certain preventive measures
increased pressure and pain
have been shown to result
on
and
in smaller fibroids that are
various problems related to
less symptomatic and even
pregnancy, such as infertility
significantly reduce the risk of
and
These
fibroid formation altogether.
tumors are benign, yet still
A study in Italy showed that
adjacent
organs,
miscarriage)2, 4.
6 | Rutgers Science Review | Spring 2012
tissue,
on
forming
various
Features eating a higher quantity of vegetables
does not appear to be decreasing in the near
References
allows for more frequent bowel movements,
future, and the number of hysterectomies
which rids the body of excess waste on a
conducted due to these fibroids will likely
more regular basis. Vegetarian women
maintain their current level in the upcoming
seemed to excrete more estrogen in their
years. Fibroid removal and hysterectomies
feces than their meat-eating counterparts,
have both been shown to have great success
had lower urinary estrogen excretion, and
as treatment options, and many women
exhibited 15-20% reduced plasma estrogen
have been happy with the results – though
levels2. The high-fiber diets of these women
a simpler way to reduce the number of
disallowed for reabsorption of excess
hysterectomies would be to raise general
(2003). Etiology and pathogenesis
hormones in the digestive tract, thereby
awareness about myomas among women,
of uterine leiomyomas: A review.
decreasing the rate of fibroid formation.
especially those at high risk. Women should
Environmental Health Perspectives,
Eating healthy and maintaining a
regularly see their gynecologist, schedule
111(8), 1037.
healthy weight appear to significantly
regular appointments, and ask questions.
lower the chances of contracting uterine
They should gather as much information
leiomyomas. Because scientists still have
as they can about uterine leiomyomas to
not been able to pinpoint the exact causes
take the necessary precautions and crack
of uterine fibroids, their rate of formation
down on this hysterectomy overload.
[1] Davis, B. J., Haneke, K. E., Miner, K., Kowalik, A., Barrett, J. C., Peddada, S., et al. (2009). The fibroid growth study: Determinants of therapeutic intervention. Journal of Women’s Health (15409996), 18(5), 725-732. [2] Flake, G. P., Andersen, J., & Dixon, D.
[3] Kim, J. J., & Sefton, E. C. The role of progesterone signaling in the pathogenesis of uterine leiomyoma. Molecular and Cellular Endocrinology. [4] Laughlin, S. K., & Stewart, E. A. (2011). Uterine leiomyomas. Obstetrics & Gynecology, 117 (2), 396-403. [5] Rein, Mitchell S. “Advances in Uterine Leiomyoma Research: The Progesterone
Hypothesis.”
Environmental Health Perspectives Supplements 108 (2000): 791-3. Print.
Spring 2012 | Rutgers Science Review | 7
ARC Protein: A Potential Agent in Learning
What causes us to learn neurotransmitters,
and remember? Before we explore that inquiry, let’s first dissociate
that cross this small gap. The membrane of
implicit
the two types of memory: explicit and
the excited neuron is called pre-synaptic,
forms
implicit. Explicit forms of memory include
while the membrane of the neuron receiving
memory
the things that you can recall about your
the input is post-synaptic.
of
Scott Kilianski
life and other past events – they are aspects
This ability of a synapse to get weaker
of your memory that involve conscious
or stronger is referred to as synaptic
downstream product of the immediate-
recollection. For example, you are using
plasticity. An increase in synaptic strength
early gene Arc. Since immediate-early genes
your explicit memory when you recall the
is called long-term potentiation (LTP) and
are almost exclusively activated in response
names of your second grade classmates.
a decrease is called long-term depression
to stimuli, when the stimuli are absent,
Implicit memories, however, consist of
(LTD). What LTP essentially does is increase
expression of these IEGs is extremely
all the information that is unconsciously
the post-synaptic neuron’s probability of
limited (Caputto). There would be limited
retained.
muscle
firing--which might make a memory more
Arc IEG activity if there wasn’t an increase
memory, and patterns of thought--you
likely to be recalled--and it has been shown
in neuronal excitement, since this is the
don’t necessarily have to “think” about it in
to be a critical process in learning and
stimulus that provokes Arc IEG activation.
order to do it.
forming memories. A protein called Arc is
When NMDA receptors--ion channels in
What’s been determined as essential
thought to play a role in LTP by making
the cell membrane--are extremely excited,
for learning and both types of memory
certain morphological changes to the post-
they allow calcium to enter and initiate
is the strengthening and weakening of
synaptic membrane and perhaps even the
the cascade of events that eventually result
synapses after neuronal activity. A synapse
pre-synaptic membrane, which helps to
in Arc upregulation and then LTP. So, if a
is a small gap located at the point where
stabilize the newly strengthened synaptic
neuron has been strongly stimulated, more
the end of a neuron meets another neuron.
connections (Guzowski).
Arc protein is likely to be present--resulting
They
include
skills,
When a neuron receives enough excitatory
Activity-regulated
cytoskeleton-
input, it relays that input to the adjacent
associated (Arc) protein has also been
neuron
implicated in the consolidation of explicit and
with
chemical
signals,
called
8 | Rutgers Science Review | Spring 2012
(Bramham).
The
Arc
protein
is
a
in the morphological changes thought to be involved in LTP. The hippocampus is a structure that
Features has long been implicated with learning
order to retain memory of the context it’s
“Immediate Early Gene Expression
and memory in both rats and humans, as
been placed into (Matus-Amat). In Tim
Within the Visual System: Light and
the patterns of neuronal excitation in the
Otto’s Learning and Memory lab at Rutgers
Circadian Regulation in the Retina
hippocampus and associated areas are
University, we’re specifically observing Arc
and the Suprachiastmatic Nucleus.”
generally accepted to be the underlying
expression following periods of neuronal
Neurochemical Research 25.1 (2000):
cause of memory (McClelland, 1995). Lab
excitation in rat hippocampi. At our lab,
153-62. Print.
rats can function as animal models for
as well as many others, we are specifically
Guzowski, John F., Gregory L. Lyford,
the human brain since their brains are,
attempting to understand how Arc’s role in
Gail D. Stevenson, Frank P. Houston,
for the most part, homologous to ours,
synaptic plasticity within the hippocampus
James L. McGaugh, Paul F. Worley,
and it was through lesion studies that the
affects
of
and Carol A. Barnes. “Inhibition
hippocampus has been determined to be
different types of spatial and contextual
of Activity-Dependent Arc Protein
necessary for functions that involve learning
memory. Together, we hope to eventually
Expression in the Rat Hippocampus
and memory (Morris). Lesion studies
attain a better knowledge of the biological
Impairs the Maintenance of Long-Term
involve studying a specific brain region that
processes that take place on a cellular level
Potentiation and the Consolidation
has been inactivated chemically, removed
during memory formation and recall.
of Long-Term Memory.” Journal of
the
acquisition
and
recall
completely, or disabled with excessive
Neuroscience 20.11 (2000): 3993-4001.
amounts of electric current. In studies
References
Print.
where rats’ hippocampi are lesioned, an
“Brain Anatomy for Genomics, Proteomics
Matus-Amat, P. “The Role of the Dorsal
attenuation of the rats’ performances on
& Bioinformatics.” Biology @ Davidson.
Hippocampus
spatial memory-dependent processes--like
Davidson College, 2001. Web. 04 Mar.
and Retrieval of Context Memory
navigating through a water maze based
2012. <http://www.bio.davidson.edu/
Representations.”
on cues positioned at different spatial
courses/genomics/method/Brainparts.
Neuroscience 24.10 (2004): 2431-439.
locations--has been observed (Morris). It
html>.
Print.
in
the
Acquisition
Journal
of
has also been seen that it is necessary for
Bramham, Clive R., Maria N. Alme,
McClelland, James L., Bruce L. McNaughton,
a rat to have an intact hippocampus in
Margarethe Bittins, Sjoukje D. Kuipers,
and Randall C. O’Reilly. “Why There
Rajeevkumar
R.
Are Complementary Learning Systems
Nair, Balagopal Pai,
in the Hippocampus and Neocortex:
Debabrata
Insights
Manja
Panja,
Synaptic
Fig. 1 These dark lines in the rat hippocampus are stained cells in three distinct subregions, dentate gyrus, CA1, CA3 that we look at in Tim Otto’s Learning and Memory Lab.
Successes
and
Failures of Connectionist Models of
Soule,
Learning and Memory.”Psychological
Adrian Tiron, and
“The
the
Schubert,
Jonathan
Karin
from
Wibrand. Arc
Review 102.3 (1995): 419-57. Morris, R. G. M., P. Garrud, J. N. P. Rawlins,
of
and J. O’Keefe. “Place Navigation
Memory.”
Impaired in Rats with Hippocampal
Experimental
Brain
Lesions.” Nature 297.5868 (1982): 681-
Research
200.2
83. Print.
(2010): 125-40. Print. Caputto,
B.
L.,
and M. E. Guido.
Spring 2012 | Rutgers Science Review | 9
Pregnancy from a Gene’s Point of View by Ritu Nahar
than that the fetus would prefer to obtain from his mother (Haig, 1993). Some of the implications that may be a result of this conflict are examined in this paper.
It is often thought that mother and
Since the fetus’s genome is only 50%
child work cooperatively sharing the
maternal, the other half or the paternal genes
baby’s survival as a mutual goal. However,
are foreign to the mother’s body and thus
recently there is mounting evidence that
cause the mother’s immune system to view
there may be some discrepancy between
the fetus as a parasite. Evolutionary
the fetus and mother’s perception of the
however, if the mother was unable
pregnancy. In 1974, Robert Trivers used
to tolerate this infiltration of
evolutionary genetics to define his concept
foreign genes, she would
of the “parent-offspring conflict” (POC).
never
The fundamental tenet of POC is the
thus she would have
existence of a slight difference in the amount
little fitness as an
of parental investment that is optimal for
individual.
the child verses the amount of parental
contrast,
investment that is optimal for the parent
mother
(Trivers, 1974). David Haig then applied
to allow every
POC to pregnancies and the relationship
fertilized egg
between mother and fetus. Evolutionarily
to
speaking, the individual with greater fitness
and
is defined as the individual who is able
expend
have greater numbers of progeny. Due to
her resources
sexual reproduction, a mother contributes
on
to only fifty percent of her fetus’s genome.
implanted
Therefore, from the mother’s perspective,
egg,
only half of her genes are passed on per
would
child, and so it would be in her best interest
w a s t i n g
to conserve her maternal resources and
tremendous
have many offspring.
amounts of energy
From the fetus’s
reproduce
and
By if
the
were
implant then all
every
she be
perspective, it is to his or her advantage to
on
children
that
exhaust the maternal resources available as
may not even be
they assist in increasing survival rate and
viable. In reality, it
thereby the odds that all his or genes will
has been shown that
be passed on. Thus from the genes’ point
there is only a 30-40% chance
of view, there seems to be a slight conflict
of there being a successful
of interest between mother and fetus: the
implantation that results in
amount of resources the mother wants
a detectable fetus in any given
to expend on her one fetus is slightly less
menstrual
cycle
(Macklon,
2003).
Features
This data provides evidence for the POC
progesterone inhibits menstruation thereby
evolutionary theory which would explain
preserving the implanted embryo (Brown
the mother’s resistance in accepting a
and Bradbury, 1947; Hanson, 1971; Jia,
pregnancies is shown by examination of the
fetus as an evolutionary designed control
1991). Interestingly it has been noted that
placental hormone hPL. Human placental
mechanism which allows her to preserve
a statistically significant number of women
lactogen (hPL) is generated by the fetus
her resources for highly selected fetuses.
who were nauseous during pregnancy also
and released into the mother’s blood where
Further evidence of this hypothesis has
had higher levels of hCG (Masson, 1985).
it disables the mother’s insulin. Insulin
been shown by the abnormal karyotypes
However the significance and accuracy
is a hormone involved in storing sugars
of
fetuses
of this finding is still under investigation
as glycogen for later use. Thus inactive
chromosomal
(ACOG, 2004). The effects of hCG on the
insulin results in increased levels of blood
abnormalities. (Boue, 1975; Eiben, 1987;
fetus are more definite. Intrauterine growth
sugar and less stored sugar for the mother.
Plachot,
for
restriction (IUGR) refers to the condition
Consequently by releasing hPL into the
spontaneous abortions may have evolved
in which the fetus undergoes improper
mother’s blood system, the baby gains
has a means for the mother to verify and
growth while in mother’s womb and in
greater sugar access through the placenta.
ensure quality of the fetus before making
some cases may subsequently lead to
If this were a mutual relationship
her investment in energy and time that
intrauterine death (IUD) which refers to
in which fetus and mother work as one,
she could be using to raise a different
the death of a fetus after 18 weeks in the
the mother would not counter the fetus’s
healthier fetus (Roberts and Lowe, 1975).
mother’s uterus. It has been shown that
efforts to gain access to more of her sugars.
If this theory is true, there must
hCG is one of three markers that when
However, it has been shown that the
be some mechanism through which the
present in abnormal levels in placentas are
mother counters the fetus’s attempts of
mother evaluates the fetus’s fitness level.
correlated with increased risk of adverse
gaining excess sugar by increasing insulin
One potential mechanism is the ability of
pregnancy outcomes such as intrauterine
production, which is evidence for POC
the fetus to secrete the hormone, human
growth restriction and intrauterine death
(Haig, 1993). Gestational diabetes (GD)
chorionic gonadotropin (hCG) through the
(Dayal, 2011). In addition, there were
further indicates the presence of a power
placenta. When released into the mother’s
significantly decreased hCG staining rates
struggle between mother and fetus. During
blood by the implanted fetus, hCG has
in placentas from obtained from IUGR
pregnancy, a mother’s pancreas may
been shown to increase the fetus’s survival.
and IUD cases (Günyeli, 2009). Both these
generate up to three times the regular levels
Human chorionic gonadotropin binds to
studies show a correlation between hCG
of insulin to overcome the effect of the fetal
the mother’s luteinizing hormone receptor
and the ability of the fetus to survive,
placental hormones on blood sugar levels.
and thereby promotes sustained release of
further evidence that hCG production by
GD
progesterone. The continuous release of
the fetus may be a mechanism by which the
associated with pregnant women who are
human chorionic gonadotropin (hCG)
Human placental lactogen (hPL)
spontaneously
which
revealed
1989).
aborted
distinct
The
mechanism
mother assesses the viability of the fetus. Another
is
a
example
relatively
of
POC
common
in
disease
INsulin
Spring 2012 | Rutgers Science Review | 11
Features insulin resistant and therefore lack the proper ability to form insulin (Carr, 1998). Applying Triver’s “parent-offspring
References ACOG (American College of Obstetrics and
ogy,29(6), 521-525. Haig, D. (1993). Genetic conflicts in human
Gynecology): Practice bulletin: nausea and
pregnancy. Quarterly Review of Biology,
conflict” to the mother-fetus relationship
vomiting of pregnancy. Obstet Gynecol
68, 495-532.
as
2004, 103(4):803-814.
done
by
Haig,
offers
reasonable
explanations for much of the scientific data published
regarding
pregnancy-related
Brown, W. E., andJ. T. Bradbury. 1947. A
Hanson, F. W., J. E. Powell, and V. C. Stevens. 1971. Effects of HCG and human pituitary
study of the physiologic action of human
LH on steroid secretion and functional
diseases such as gestational diabetes,
chorionic hormone. The production of
life of the human corpus luteum. J. Clin.
intrauterine
and
pseudopregnancy in women by chorionic
Endocrinol. & Metab., 32:211-215.
intrauterine death. Such complications
hormone. Am. J. Obstet. Gynecol., 53:749-
tend to result when the balance is tipped
757.
growth
restriction,
to favor either mother or fetus, which
Boue,J., A. Boue, and P. Lazar. 1975. Retrospec-
Jia, X.-C., M. Oikawa, M. Bo, T. Tanaka, T. Ny, I. Boime, and A. J. W. Hsueh. 1991. Expression of human luteinizing hormone
gives evidence that the two do not share
tive and prospective epidemiological stud-
(LH) recep- tor: interaction with LH and
all the same goals. The mother is inclined
ies of 1500 karyotyped spontaneous human
chorionic gonad tropin from human but
to reserve resources for later childbirths
abortions. Teratology, 12:11-26.
not equine, rat, and ovine species. Mol.
in order to maximize her fitness. The
Carr D.B., Gabbe S. (1998).Gestational diabetes;
fetus on the other hand would maximize
detection, management, and implications.
its fitness by depleting the mother of all
Clinical Diabetes,16(1):4–11.
Endocrinol., 5:759-768. Macklon N.S., Geraedts, J.P.M., and Fauser, B.C.J.M. 2002. Conception to ongoing preg-
the resources she would otherwise give
Dayal, M., Gupta P.,Varma M., Ghosh U.K., and
nancy: the ‘black box’ of early pregnancy
to other children. Though pronounced
Bhargava A. (2001). Role of Second Trimes-
loss. Human Reproduction Update 2002.
evidence exists favoring the application of
ter Maternal Serum Markers as Predictor
the parent-offspring conflict in pregnancies,
of Preeclampsia. The Journal of Obstetrics
Serum chorionic gonadotrophin (hCG),
there is no definite proof that it is indeed
and Gynecology of India January/Febru-
schwangerschaftsprotein 1 (SP1), proges-
the
ary. 38-41.
terone and oestradiol levels in patients
correct
explanation.
However
if
proven true, there would be immense
Eiben, B., S. Borgmann, I. Schiubbe, and I. Hans-
implications in the future for the use of
mann. 1987. A cytogenetic study directly
evolutionary genetics in medical research.
from chorionic villi of 140 spontaneous
Masson G.M,, Anthony F, Chau E.1985.
with nausea and vomiting in early pregnancy. Br J Obstet Gynaecol, 92:211-215. Plachot, M. 1989. Chromosome analysis of spon-
abortions. Hum. Genet., 77:137-141.
taneous abortions after IVF. A European
Goodwin, T.M., Hershman J.M., Cole L. (1994).
sur- vey. Hum. Reprod. (Oxf.), 4:425-429.
Increased concentration of the free beta-
Roberts, C. J., and C. R. Lowe. 1975. Where have
subunit of human chorionic gonadotropin
all the conceptions gone? Lancet, 1:498-
in hyperemesis gravidarum. Acta Obstet
499.
Gynecol Scand, 73:770-772. Günyeli, İ., Zergeroğlu, S. S., Danisman, N. N., & Mollamahmutoğlu, L. L. (2009). The
Sheehan P. 2007. Hyperemesis gravidarum-assessment and management. Aust Fam Physician, 36:698-701.
diagnostic significance of hCG and hPL via
Trivers, R. L. (1974). Parent-Offspring Conflict.
immunohistochemistry of placental tissues
American Zoologist 14 (1): 249–264.
in pregnancies diagnosed with IUGR and IUD. Journal Of Obstetrics & Gynaecol-
12 | Rutgers Science Review | Spring 2012
Features
Photonic Crystals A Brief Introduction
By Carlos M. Bledt, III
In the last couple of decades, continuing developments in photonics and optoelectronics have led to an exponential thrust in research efforts towards the development of photonic based structures capable of manipulating light in an analogous manner to that in which semiconductors manipulate electrons. The ability to design and engineer such photonic structures would undoubtedly revolutionize a wide variety of high-tech fields ranging from applied physics to electrical engineering and nanotechnology and would mark an essential step in the development of next generation devices such as all optical computing chips, nanoscale biological sensors, and ultra-fast all optical switches, just to name a few. While semiconducting materials have proven invaluable in the development of electronic devices in that they can be exploited to control electron flow, a practical optical equivalent capable of manipulating light in an analogous manner to that in which semiconductors can manipulate the flow of electrons had until just a few decades ago not yet been proposed, let alone implemented. In 1987, Yablonovitch and John were the first to propose such an optical analogue which became to be widely known as a photonic crystal (PhC). Since then, research into the properties, fabrication, and applications of PhCs has seen exponential growth and continues to be a major topic of study throughout the scientific community, particularly in
the development of next generation optical, photonic, and optoelectronic devices. Through the implementation of photonic crystals, a number of previously unthinkable scientific achievements are possible. One such example includes the sub-wavelength spatial confinement of electromagnetic radiation which could allow for the miniaturization of optical chips in next generation ultra-fast optical computing. Analogous to semiconductors, PhCs owe their functionality to periodic differences within their structures yet instead of interacting with electrons behaving as waves, they interact with photons behaving as waves. While semiconductors rely on a periodic electronic potential resulting from the atomic lattice, photonic crystals rely on the optically active inhomogeneous periodicity arising from regularly repeating regions of alternating non-equal dielectric constant. Furthermore, analogous to semiconductors which exhibit electronic band structures, PhCs exhibit photonic band structures. As such, PhCs can in many aspects be considered the optical equivalent of semiconductors. As briefly introduced, the basic requirement for creating a PhC structure is the spatial periodicity of regions of materials having differing dielectric constants. In practice, this can be achieved through the periodic arrangement of regions consisting of two low absorption materials of dissimilar dielectric constant. The specific structure created from these materials defines the dimensionality of the PhC, which depends on the number of orthogonal directions in which dielectric constant inhomogeneity is present. Figure 1 gives a basic representation of this concept. a)
b)
c)
Figure 1 â&#x20AC;&#x201C; Basic a) 1-D, b) 2-D, and c) 3-D PhC structures
The direction(s) of periodic inhomogeneity directly determine the properties of the PhC, particularily as photonic bandgaps (to be discussed) arise only Spring 2012 | Rutgers Science Review | 13
Features along directions of inhomogeneous dielectric constant. Since the direction(s) of periodicity of a PhC can be chosen so as to create a 1-D, 2-D, or 3-D structure, it is easy to design the structure so as to manipulate the flow of light in any of the three orthogonal directions, thus giving considerable freedom in PhC design for a particular application. It should be noted that unlike as semiconductor, which essentially exhibits a 3-D electronic structure due to the irreducible nature of the crystal lattice, lower dimensionalities are achievable in PhCs. The dimensionality of periodicity will determine the complexity of the specific PhC, with specific structures ranging from the simple multilayer dielectric film stack given in Figure 1.a for the 1-D PhC case, to more complex column or hole structures for 2-D PhCs, to quite complex spatial structures for 3-D PhCs. Figure 2 gives a few examples of some PhC structures, although many more are possible for higher dimensionality PhCs.
a)
b)
c)
d)
preferred over 2-D and 3-D structures making use of two different solid dielectric materials. In semiconductors, the periodic electronic potential resulting from the atomic lattice is directly responsible for the electronic band structure and electronic band structure engineering involves changes to periodic potential through techniques such as doping. For the case of PhCs, the photonic band structure depends on the dimensionality of the given PhC structure and constituent dielectric materials and may thus be engineered and designed to give a specific optical response primarily through modification of the dielectric materials used and the dimensionality of the PhC structure. In this particular treatment, focus will be given to the case of a 1-D PhC structure in which light travels at normal incidence (parallel to the axis of inhomogeneous periodicity) due to the inherent simplicity of this 1-D optical system. The case involving off-axis propagation for 1-D PhC structures as well 2-D and 3-D PhC structures follows the same methodology but involves more complex explanation and is beyond the scope of this treatment. In a 1-D PhC structure, such as the multilayer dielectric film stack presented in Figure 1.a, inhomogeneous periodicity occurs along the direction parallel to the surface normal. Figure 3 shows the general structure of a multilayer dielectric film stack along with the main parameters of importance for study of 1-D PhCs.
Figure 2 – a) square and b) triangular lattice 2-D and c) ‘woodpile’ and d) hole-rod layered 3-D PhC structures
The PhC structures presented in Figure 2 have been widely implemented in practice in the study of PhC. The PhC structures presented in Figure 2 are constructed of a low absorbance material at the desired functional wavelengths and make use of free space (air) as the second dielectric material. Such structures making use of free space as one of the two dielectric materials are in practice the easiest to fabricate and are therefore often 14 | Rutgers Science Review | Spring 2012
Figure 3 - Representative diagram of 1-D PhC multilayer dielectric film
Figure 3 shows the main parameters needed for a basic description of a 1-D PC where a is the period, d1 is the thickness of the thin film of dielectric constant ε1 and d2 is the thickness of thin film of
Features dielectric constant ε2. For the representative diagram it must hold that ε1 < ε2 where ε1 and ε2 ≠ 1 and d2 = a – d1, where d1 > d2. Furthermore, for optimization at a certain free space wavelength λ, the thickness of the individual films must meet the condition in Equation 1. √
Given that both of the materials exhibit near negligible absorbance at the target wavelength range, the PhC can be engineered so as to obtain the desired optical response by changing any of the aforementioned parameters. Most importantly, these parameters have a direct effect on the photonic band structure. If the parameters are chosen appropriately, the band structure will exhibit photonic bandgaps which encompass ranges of light frequencies between the air and dielectric bands analogous to electronic bandgaps which encompass ranges of electron wave frequencies between the valence and conduction bands. Just as electrons having energies located within the electronic bandgaps cannot exist in a semiconductor, photons having energies within the photonic bandgaps cannot propagate in a PhC. For a given set of parameters, the band structure of a PhC can be derived through the plane wave expansion (PWE) method. Figure 4 gives part of the photonic band structure of a 1-D PhC designed as a stop-band filter for green light whose parameters are given in Table 1.
Table 1 – Parameters of 1-D PhC stop-band filter for green light (λ = 535 nm) Parameter
1st Material
2nd Material
ε (n2)
1
4
d
134 nm
67 nm
# Layers (N)
10
10
Determination of the transmittance of the PhC structure can be carried out using a number of techniques. For 1-D PhCs the dimensional simplicity of the multilayer film stack makes the transfer matrix method (TMM) a suitable technique for determination of transmittance. Using the parameters for an all-dielectric stop-band filter for green light, the transmittance of such a 1-D PhC as calculated using TMM is given in Figure 5.
Figure 5 – Transmittance spectrum of a 1-D PhC stop-band filter for green light
Of course, what does this all mean in a practical sense then? The practical implementation of such a 1-D PhC stop-band filer is given in Figure 6. λ2 = 439 nm
λ < λ2
λc = 565 nm λ2 ≤ λ ≤ λ1 λ1 = 681 nm
λ > λ1
Figure 6 – 1-D PhC stop-band filter for green light
Figure 4 – Band structure of a 1-D stop-band filter for green light
In essence, through the creation of a 1-D PhC structure consisting of two materials which are each separately highly transparent for green light (high transmittance at λ = 535 nm), a filter capable Spring 2012 | Rutgers Science Review | 15
Features
of virtually no transmission of green light has been created through careful parameter selection. Alteration of the above-mentioned key parameters allows for the engineering and design of the photonic band structure of PhCs to achieve the optical response necessary for a given application. To briefly show the effect that altering such parameters has on the optical response of the PhC, Figure 7 presents the transmittance spectra for a 1D PhC having ε1 = 1.44, ε2 = 2.25, N = 20 for which the dielectric layer thicknesses are changed. a)
b)
d)
Figure 7 – Transmission spectra for a) d1 = 104 nm, d2 = 83 nm , b) d1 = 125 nm, d2 = 100 nm, c) d1 = 146 nm, d2 = 117 nm, d) d1 = 167 nm, d2 = 133 nm
It is evident that the dimensionality of PhC structures can be designed to give a desired optical response and can be successfully used for the confinement of light necessary for a variety number of applications such as optical chips, waveguides, and nanoscale lasers. Furthermore, while beyond the scope of this treatment, deliberate introduction of defects in PhCs has allowed for the fabrication of advanced photonic devices such as 2-D PhC slab waveguides and photonic crystal fibers (PCFs) – Figure 8. a)
c)
b)
c)
Figure 18 – SEM images of a) a 2-D PhC defect slab waveguide (1), b) a hollow core bandgap-guiding PCF (2), and c) a solid core index-guiding PCF (3)
16 | Rutgers Science Review | Spring 2012
Features The development of PhCs has grown exponentially in the last couple of decades and can be expected to continue growing at such a rate, especially as the push for ultra-fast all optical devices continues to grow. As such PhC engineering and design will undoubtedly continue to further develop and revolutionize next generation photonic devices. References [1]
Yablonovitch, “Inhibited Spontaneous Emission in Solid-State Physics and Electronics,” Physical Review Letters, 58 [20], 2059 – 2062 (1987)
[2]
Joannopoulos, J. D., Johnson, S. G., Mead, R. D., and Winn, J. N., Photonic Crystals: Molding the Flow of Light, Second Edition, Princeton University Press, 2008.
[3]
Johnson, S. G., and Joannopoulos, J. D., Photonic Crystals: The Road from Theory to Practice, First Edition, Springer Publishing, 2002.
[4]
Heavens, O. S.; Optical Properties of Thin Film Solids, First Edition, Dover Publications, Inc., 1991.
[5]
Hecht, E., Optics, Third Edition, Addison-Wesley, 1998.
[6]
Johnson, S. G., “Wave propagation in periodic systems. Bloch’s theorem, the electromagnetic eigenvalue problems, band diagrams, the variational theorem, and the origin of the photonic band gap. 1D, 2D, 3D crystal examples,” Lecture #1, Massachusetts Institute of Technology (2004)
[7]
Fowles, G. R., Introduction to Modern Optics, Second Edition, Dover Publications, Inc., 1975.
[8]
Danner, J., “An introduction to the plane wave expansion method for calculating photonic band diagrams,” University of Illinois at Urbana-Champaign (2011)
[9]
Shumpert, J. D., Modeling of Periodic Dielectric Structures (Electromagnetic Crystals), PhD. Dissertation, The University of Michigan (2001)
Submit to the RSR! We’re interested in your article proposals, editorials, research papers, art, and photography. For more information: Email us submissions@thersr.com On the Web thersr.com/submit
Images (1)
Stobbe, S. and Liu, J., “Fabrication of photonic crystal membranes,” DTU Fotonik – Department of Photonics Engineering, Technical University of Denmark, Copenhagen, Denmark (2009)
(2)
Ramsay, R., “Photonic-crystal fiber characteristics benefit numerous applications,” Crystal Fibre A/S, Sensing & Measurement, SPIE Newsroom (2008)
(3)
“Index-Guiding Photonic-Crystal Fiber,” United States Naval Research Laboratory Technology Transfer Office, Washington D.C., United States (2006)
Spring 2012 | Rutgers Science Review | 17
An Interview With:
Dr. Mohan Kalelkar conducted by neil raju Dr. Mohan Kalelkar is a Professor and Undergraduate Program Director of Physics at Rutgers University. His research interests lie in Elementary-Particle Physics. Could start out by telling us a little about yourself and your
rule in your left front pocket. This identified you as a nerd
background?
[laughs].
Well, I got my bachelor’s degree at Harvard in 1968, and I got my PhD at Columbia in 1974. After that, I was a postdoc at
How has physics changed from the time you were a student?
Columbia for a few years. Then, Rutgers offered me a faculty
Physics has changed dramatically because of the advance
job, and I’ve been at Rutgers ever since. It was in 1978 that
in technology. I wrote my entire PhD thesis on IBM punch
Rutgers offered me a job, so I’ve been at Rutgers since ’78.
cards. When writing computer programs, we would have
Students might find it fun to learn that in my undergraduate
key punch machines, whereby every command is written on
days at Harvard, we were required to have a meal plan and
one card and encoded by a pattern of holes. You could also
have all meals at the dining hall. And, we were required to
write plain text across this; it doesn’t have to be computer
wear a coat and tie to every meal . . . including breakfast. And
code. So I wrote my entire PhD thesis on punch cards. Later,
that was enforced by an enforcer at the entrance; if you didn’t
of course, a secretary typed it up properly. The hardest thing
have a coat and tie, you were sent off [laughs].
was strategically leaving spaces where I knew I was going to need to put things in by hand and leaving some lines where I
How has college changed from when you were a student?
was going to have to put in a formula.
Well, technology was far more primitive back then. We did use computers, but they were all big mainframe computers,
How did you get started in the field of Physics?
so there was no such thing as a personal computer. So, of
While I was a sophomore at Harvard, I asked my physics
course, there was no such thing as a word processor. Internet,
professor, who was named Karl Strauch, for a summer job.
email, and World Wide Web were beyond imagination,
Of course, I wanted a summer job so I could work with
nobody could even dream that such a thing was ever going
somebody. And I was very lucky, he was able to give me a
to happen. Even pocket calculators didn’t become widely
job in the field of experimental high-energy physics, which
available until I was nearly finished with my PhD. We had to
involved atom-smashers. And the specific technology we
do a lot of things using slide rules. From my undergraduate
used was the bubble chamber. That was in use then; today,
up to my graduate year, I was basically doing physics
the bubble chamber is close to being obsolete. So I worked
homework problems and exam problems using a slide rule.
with that, and I became a high-energy physicist for the rest
And, on campus, the classic nerd symbol was to have a slide
of my career because Professor Strauch gave me a job that
18 | Rutgers Science Review | Spring 2012
Interview summer. It’s amazing how things happen by chance: if he
our bodies every second.
had been somebody working in astronomy, I’d probably be an astronomer today.
So after the neutrino experiments came to an end, I spent many years studying electron/anti-electron interactions at the
When I entered Harvard, I was not sure what I wanted to do.
Stanford Linear Accelerator Center. This involved electrons
I thought I might even study economics, because the subject
and anti-electrons annihilating each other at high energy.
interested me. But what happened is that my freshman
When this happens, quarks and gluons get produced...
physics professor was very, very good. His name was Ralph
and we study them. By then, technology had gone well
Baierlein, and he was so good that I was hooked on physics.
past taking photographs. By then, all the reconstructions
Then, as I said, sophomore year I asked Professor Strauch for
were electronic. Here is an example of an event in the
the summer job.
electron/positron interaction [Figure 1]. So think of electrons going into the screen, anti-electrons coming from behind,
Can you tell us a little more about your research?
annihilating, and they produce a quark, an antiquark, and a
So I would continue doing bubble chamber physics into my
gluon. These three fragmented into the tracks that you see
PhD research at Columbia, and my thesis research was on
here.
the interactions on the particles known as π-mesons. The title of my thesis was ‘Meson resonance production in 15 GeV/C π+
What’s the Stanford Linear Accelerator Center? Why did the
interactions with liquid hydrogen’. Π-mesons are amongst
research have to take place there?
the elementary particles, ergo they are not truly elementary:
[SLAC] uses a two-mile long linear accelerator to accelerate
they are made up a quark and an anti-quark, as we know
the electrons and anti-electrons, so it’s a very, very expensive
today. We didn’t know that back then. This thesis research
thing; it’s not as though each university can build its own.
allowed me to measure the properties of extremely short-
But the Department of Energy funded the laboratory at
lived particles that exist for as little as 10-23 seconds. They
Stanford, and that’s where I did my experiments for a large
barely grow a nucleus before decaying, but such particles do
number of years. And this, of course, is big science; we had
exist.
many collaborators, we had a couple of hundred people working on these experiments. You’ve heard of this new one
After I came to Rutgers, I started working on a series of
in Switzerland, the Large Hadron Collider: it’s got thousands
experiments studying the interactions of neutrinos with
of people working on it.
matter. This was at Fermi National Accelerator Laboratory in Illinois, where we had a way of producing a neutrino
What potential breakthroughs do you see in Physics?
beam and having it go into the bubble chamber, and
The main, near-term breakthrough that I’m hoping for is the
took photographs of the interactions that took place. We
discovery of the Higgs-Boson at the LHC in Switzerland.
painstakingly scanned the photographs to learn about the
That is the one missing link in our so-called standard model
interactions. You might find it fun to know that the sun also
of physics. And if we don’t find it, then that may well mean
produces neutrinos, although of a different type. Neutrinos
that the standard model is seriously flawed. In the standard
are particles that very, very rarely interact, so we had to
model, the Higgs-Boson is what is responsible for giving
send millions at a time into the bubble chamber, and maybe
mass to the elementary particles. Now, at the same time, we
one would interact. Most of the neutrinos from the sun go
know that the standard model cannot be the last word: it
straight through the earth without interactions. As you and I
contains several internal contradictions and inconsistencies
are speaking, over 1014 neutrinos are going straight through
at a subtle level. What I’m hoping for in the somewhat
Spring 2012 | Rutgers Science Review | 19
Interview distant future is that we do figure out how to resolve the
Do you have any advice for students interested in pursuing
contradictions.
research in physics? I would say get started as early as possible, that it is so
Could you elaborate on these contradictions? How does the
satisfying, really immensely satisfying. In research, you’re
Higgs-Boson give mass to the elementary particles?
doing something different from the usual end-of-chapter
The contradictions in the standard model are that if we get
homework problems and studying for exams. When you do
to high enough energy, the standard model makes certain
research, you really are working in frontier physics. You’re
predictions that are just absurd, that certain quantities would
working on something that is not a canned homework
become infinite when they cannot be infinite.
problem, but you’re working on research where you don’t
As for the Higgs-Boson, there is a very nice analogy to
know for sure what the outcome is going to be. And it’s just
explain how the Higgs-Boson gives mass to particles; the
so great to do the research and see what happens, trying to
analogy was invented by a Professor David Miller at the
draw conclusions. Rutgers has wonderful research programs;
Imperial College in London. He said to imagine a room that is
I would encourage those who are interested in physics or
crowded with men, as if it’s coffee-break during a conference
other sciences to apply for these research programs.
and the guys are all there, talking and drinking coffee. Then, this very beautiful woman enters the room. As she heads towards the coffee stand, the men start gathering around her and trying to talk to her, and in that sense, she was acquired mass, because the men are impeding her progress towards the coffee. The room full of men is the analog of the Higgs field, and the specific men who are around her are the analog of the Higgs-Boson. However, it was Professor Miller’s wife who thought this was sexist, so he changed the analogy to a group of members of Parliament and made it Margaret Thatcher who was entering the room. So this became widely known as the Margaret Thatcher explanation of the HiggsBoson [laughs].
Figure 1 In this picture you see three jets of particles. One came from the disintegration of a quark, the second from an antiquark, and the third from a gluon.
The SLAC
20 | Rutgers Science Review | Spring 2012
Research Papers
EPILEPSY IN AUTISM SPECTRUM DISORDERS (ASDS) By: Jigar Gandhi
By Jigar Handhi
22 | Rutgers Science Review | Spring 2012
Research Papers
Autism Spectrum Disorders (ASDs) and Epilepsy INTRODUCTION: Leo Kanner, an American psychiatrist and physician, first described autism in 1943. Kanner closely examined 11 children with similar problems of communication, social relatedness and repetitive behaviors, and their progression over an extended period of time in search of causal relations between these behaviors and potential underlying medical, family and social factors. He named this range of symptoms ‘autistic disturbances of affective contact’. He noted that six of the 11 children had severe feeding difficulty since the beginning of life. He also noted that five of the 11 children had relatively large heads. While only one child had seizures with an abnormal electroencephalogram (EEG), and the other 10 had normal EEGs.1 The term “Autism” is frequently used to refer to the whole range of Autistic Spectrum Disorders (ASDs). ASD is an umbrella term for neurological disorders associated with developmental abnormalities of the brain. As per the ASD criteria of Diagnostic and Statistical Manual of Mental Disorders Version IV Text Revision (DSM-IV-TR) listed in Table 1, there are five pervasive developmental disorder subtypes. What these disorders have in common, but with variable severity, is impairment in sociability, language, communicative skills, and imagination along with intellectual and behavioral inflexibility. For example, individuals with some autism-like symptoms and relatively preserved Table 1: DSM-IV-TR criteria for Autism Spectrum Disorders5 A total of six (or more) items from each category
cognitive functioning and language skills are described as having Asperger's syndrome. In addition to abnormal social behavior, ASDs are frequently, but not always, associated with reduced IQ and epilepsy.2
A) Qualitative impairment in social interaction (at least 2) Impairment in nonverbal behaviors such as eye contact
Some early studies reported the prevalence rates of 2 to 5 per
Failure to develop peer Lack of seeking to share enjoyment or interests
10,000 for autism while the recent reports suggest the rates of up to 60
Lack of social or emotional reciprocity
per 10,000 3 (approximately 1 in 150 children). The onset of symptoms
B) Qualitative impairment in communication (at least 1)
can be observed as early as prior to 3 years of age, although the
Delay in or lack of spoken language If speech is present, lack of ability to initiate or sustain conversation
syndrome may not be recognized until later. Autism is 3.5 times more
Stereotyped and repetitive/idiosyncratic language
prevalent in males than females, with unknown etiology in 80–90% of
Lack of pretend/social imitative play
the total cases.2 The fact that ASDs frequently occurs concomitantly
C) Restricted interests/repetitive behavior (at least 1) Preoccupation with restricted interest
with epilepsy, there may be an association with a single gene defect
Inflexible adherence to nonfunctional routines or rituals
conditions called fragile X syndrome, neurofibromatosis, and tuberous
Stereotyped and repetitive motor mannerisms (hand flapping)
sclerosis.4 In addition, various epidemiological and genetic studies have
Persistent preoccupation with parts of objects
suggested autism to be a highly heritable disorder putting the sibling of
an autistic child 2-9% at risk of developing autism. (The specificity of this statistic warrants a citation here)
SEIZURES
AND
EEG ABNORMALITIES
IN
AUTISM:
Autism, with regards to seizures, can be broken down into two types. The first type, 1/3 of the cases, involves normal development of the child until 2-3 years of life. The other type involves children with catastrophic conditions early in life such as
Spring 2012 | Rutgers Science Review | 23
Research papers infantile spasms with hypsarrhythmia (an abnormal interictal pattern, consisting of high amplitude and irregular waves and spikes in a background of chaotic and disorganized activity seen on EEG).6 Thus, it is safe to infer that the onset of epilepsy in ASD patients peaks first in early childhood, and then later on in adolescence. There is emerging basic science data beginning to show that the same mechanisms that lead to epilepsy may, in another group of children, lead to autism, and may, in fact, lead to both epilepsy and autism.7 One of the recent population-based studies investigated the risk of developing ASDs after unprovoked seizures with onset in the first year of life. Patients with symptomatic seizures, specifically infantile spasms, have about 8 to 9 fold increased risk of ASDs, regardless of age and gender.16 The occurrence of seizures in early developmental phases of life are associated with impaired motor development and delayed acquisition of gestures that are important for socialization later on in life.6,7 In addition, patients with greater seizure frequency have lower cognitive skills.7 Children with ASDs often suffer from epilepsy and paroxysmal EEG abnormalities. Up to 40% of people with autism also have electrical discharges on EEG recordings, as opposed to just 2% in a normal population. Primitive lab experiments in rodents have supported the hypothesis that increased incidence of interictal discharges is associated with poor learning and memory skills.8 In fact, the specific learning disabilities such as difficulties with reading, writing, and calculation were shown to correlate with a marked increase in epileptiform discharges during sleep.17 A recent study that was done in Japan involved a total of 1014 autistic children being treated and followed-up for more than 3 years for incidence of epileptic seizures and EEG abnormalities. While epileptic discharges occurred in 86% of these patients, only a 37% of the total autistic children were diagnosed with epilepsy. Furthermore, the participants with lower IQ had a higher incidence of epileptic seizures. In the same trial, digital EEG monitoring of patients revealed that about 65 % of the time that these patients had epileptic seizures during sleep, the seizures developed in the frontal lobe.23 Some data suggests that the behavioral improvement seen in ASD patients can be secondary to suppression of discharges and not as a result of seizure control or mood stabilization.
20
Although a few trials have demonstrated that attentional
problems in benign rolandic epilepsy improves after EEG normalization with treatment,18 the practice of looking at abnormal EEG discharges as treatment targets for autism needs more vigorous evaluations to become truly evidence-based.9 TYPES
OF
SEIZURES
Table 2: ASDs Subtypes and Risk of Epilepsy 9, 12 Autistic Disorder (AD) Significant deficits in all behavioral domains of (1) sociability, (2) language and imagination, and (3) cognitive and behavioral flexibility Symptoms are present since birth, with early regression of above behavioral domains Clinical epilepsy develops by adolescence in more than a third of children, and the risk is associated with the severity of the underlying brain dysfunction
Asperger’s Syndrome AD without mental retardation or delayed language development
IN
AUTISM:
Most often, subclinical complex absences may be mistaken for other childhood behaviors such as failing to respond to one’s name or to participate in a group activity, rendering the diagnosis of epilepsy in autism very complex. In addition, the unusual repetitive behaviors can be difficult to distinguish clinically from seizures. Previously reported data shed light on the possibility of developing any seizure type with autism.10 Both the prevalence of epilepsy and the types of seizures seem to vary with the population studied as illustrated in Table 2. In a Swedish study, the most prevalent seizure types were complex partial, atypical absence, myoclonic, and tonic-clonic seizures,
11
whereas, in a large American
cohort, generalized tonic-clonic and atypical absence seizures were the
Likelihood for developing epilepsy is 5–10% in early childhood
Pervasive developmental disorder not otherwise specified Milder autism that does not fit criteria for any other subtype The risk of epilepsy is probably linked to severity of the brain dysfunction
Disintegrative Disorder Severe AD acquired between ages 2 and 10 years Associated with normal early development of language, sociability and cognition Risk of developing epilepsy may be up to 70%
Rett’s Syndrome X-linked genetic mutations of the MeCP2 gene affecting postnatal brain growth Results in severe mental retardation, motor deficits, and other features The risk of epilepsy is more than 90%
most common.10 Despite some limited observations, the relation between infantile spasms and autism is not presently understood.12 Further evaluation of the seizure characteristics in autistic patients revealed
24 | Rutgers Science Review | Spring 2012
Research Papers that the EEG findings are consistent with paroxysmal abnormalities (44% focal, 12% generalized and 42% mixed) as well as focal abnormalities (31% temporal regions, 18% frontal, 13% occipital, and 5% parietal).13 Another larger study conducted in over 1000 patients with ASDs provides the evidence that up to 60% of EEG abnormalities (spikes) occurred in the frontal lobe, regardless of the clinical manifestations.14 A recently conducted clinical study showed that in many of the children with early-onset ASDs, subclinical epileptiform activity is present especially in the perisylvian regions of the brain, an area known to be associated with Landauâ&#x20AC;&#x201C; Kleffner syndrome (LKS).15 MANAGEMENT
OF
EPILEPSY
IN
ASD
PATIENTS:
The seizures as well as the interictal discharges need to be stopped because of their devastating effects on cognition and reactivity. The treatment of epilepsy in autism does not differ from that of other epilepsies.23 Drug therapy improves EEG and clinical symptoms by reducing attacks and interictal discharges.27 In addition, drug therapy should add to the stability within the CNS. Although antiepileptics (AEDs) and benzodiazepines have promising outcomes; however, the long term safety and efficacy of these treatments is yet to be determined. AEDs with mood stabilizing effects may be used to address affective symptoms of ASD. However, the treatment of autistic patients with epileptiform abnormalities without clinical epilepsy is controversial.23 A few case studies have demonstrated specific improvements in ASD symptoms after therapy to suppress discharges with AEDs.26 Treating patients who have only EEG discharges may prevent subsequent development of epilepsy.27 Unfortunately, these case reports lack controls, and reliable outcome measures. One open label study using leviteracitam (an AED that can suppress interictal discharges) demonstrated remission of measurable auditory processing deficits in four of six children with benign epilepsy of childhood with centrotemporal spikes (BECTS).28 A retrospective pilot study determined the efficacy of divalproex sodium in treating core dimensions and associated features of autism in 14 patients with ASD regardless of their epilepsy status. Ten of 14 patients showed improvements in symptoms of affective instability, impulsivity and aggression as assessed via the Clinical Global Impressions-Improvement scale. It is also worthwhile to note that all patients with either an abnormal EEG or epilepsy benefited from the treatment with divalproex sodium mean dose of 768 mg/day (125-2500 mg/day).19 However, the efficacy and safety of divalproex sodium became questionable when another cross over placebo-controlled trial in patients with epileptiform EEGs showed no improvement in any behavioral symptoms and reported some cognitive and behavioral worsening with valproic acid, leading to a cessation of the trial. 25 In a separate placebocontrolled study of lamotrigine in children with well-controlled epilepsy, showed behavioral improvement only in patients who responded to lamotrigine demonstrating a reduction in the frequency or duration of interictal discharges. 20 Yet another trial with lamotrigine in patients, aged 4 to 21 years, with generalized drug-resistant epilepsy responsive to lamotrigine, showed a reduction in the number of epileptiform discharges in 10 out of 12 patients, and behavioral improvements with more alertness, concentration and performance in all patients at doses ranging from 1-8 mg/kg body weight. This study further suggests that the behavioral improvement from lamotrigine was a result of the discharge suppression, not seizure control or mood stabilization. 21 There is enough evidence in literature to support that the early control of seizures in children with tuberous sclerosis complex (a rare genetic disease that leads to development of non-malignant tumors in the brain) significantly improves cognitive and behavioral outcomes. However, a scant amount of studies have been done to evaluate the same hypothesis in ASDs populations. One trial investigated the use of vigabatrin, which is currently approved for the treatment of infantile spasms in babies 1 month to 2 years old and refractory complex partial seizures in adults, for early control of tuberous sclerosis complex associated seizures in ASDs, showing 100% reduction in the incidence of ASDs development in these patients.22
Spring 2012 | Rutgers Science Review | 25
Research papers At present, there are no controlled data supporting Antiepileptic Drugs (AEDs) Profile 30 AEDs
Behavioral & Cognitive Adverse Events
Benzodiazepines
Agitation, paradoxical reactions, hysteria, psychosis, restlessness
Carbamazepine
Agitation, latent psychosis
the efficacy of treating epileptiform EEG discharges in autism. This void creates difficulties for both practitioners and families, and makes controlled investigations of this phenomenon crucial.
Ethosuximide
Aggressiveness, euphoria, irritability, hyperactivity, psychosis
Felbamate
Manic/paranoid reaction, psychological disturbances
Gabapentin
Emotional lability, hostility, thought disorder, problems with concentration, hyperkinesia, ataxia, somnolence
Lamotrigine
Ataxia, irritability, aggressiveness, hypomania
Levetiracetam
Psychosis, hallucinations, aggression, agitation, anger, anxiety, apathy, depression, emotional lability, hostility, hyperkinesia, irritability, nervousness, neurosis, personality disorder
Oxcarbazepine
Difficulty with concentration, psychomotor slowing, speech or language problems, somnolence, coordination abnormalities, ataxia
Phenobarbital
Somnolence, psychiatric disturbance, hallucinations, emotional disturbances and phobias
Phenytoin
Decreased coordination, dizziness, insomnia, mental confusion, anxiety, aggression, depression
Tiagabine
Impaired concentration, speech or language problems, confusion, somnolence, nervousness
Topiramate
Difficulty with concentration/attention/memory, depression, mood problems, paranoia, nervousness
Valproate
Dizziness, somnolence, emotional lability, abnormal thinking
Vigabatrin
Somnolence, memory impairment, aggression, psychotic symptoms
and, most importantly, cognitive and behavioral side effects
Zonisamide
Somnolence, memory impairment, mental slowing, difficulty concentrating, dizziness
must be considered. It is important to note that treating
CONCLUSION: Treatment of children with autism and epilepsy should follow the same principles of treating childhood epilepsy. Antiepileptic drugs (AEDs) can be selected based on seizure type and clinicians strive for maximum seizure control with minimum side effects. The feasibility of certain treatment choices is very important in ASD. For example, factors such as available formulations (liquid vs. tablets vs. capsules), dosing schedules, need for blood monitoring,
epilepsy does not usually have a major impact on the autism symptoms. Some children may show improvements in cognition, communication, or behavior, but the autism diagnosis does not change. Antiepileptic medications may also adversely affect cognition and behavior in children with epilepsy. These adverse effects are of particular concern in young children who are acquiring new skills and may result in long lasting developmental impact.29 Pharmacological management of seizures appears to be a reasonable approach when regression of ASD symptoms with an abnormal EEG is ongoing. However, the current evidence on the treatment of these conditions is very limited, mainly obtained from case reports with short-term trials and often evaluated with inappropriate outcome measures. Also the therapeutic approach is mostly empirical. At present we lack placebo-controlled, double blind, adequately powered studies, which take into consideration all the variables and which would allow for evidence-based treatment recommendations. The hope is that such studies will bring us close to recommending evidence-based treatment for autistic patients with epilepsy. REFERENCES: 1.
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the worldâ&#x20AC;&#x2122;s fair: through the eras RSR photo article
Lynn Ma
28 | Rutgers Science Review | Spring 2012
Philly, 1876: 1,500 horse power steam engine London, 1851: Crystal Palace The First Worldâ&#x20AC;&#x2122;s Fair
Industrialization Era (1851-1938) Where Technological inventions from around the world were brought together Paris, 1889: La Tour Eiffel
Spring 2012 | Rutgers Science Review | 29
Chicago 1893: 1st Ferris Wheel
New York, 1964: Unisphere “Peace Through Understanding”
Era of Cultural Exchange (1939-1987) “Future-oriented, utopian society, humankind” the signififIcance of cultural dialogue
Montreal, 1967: Geodesic Dome “Man and His World” 30 | Rutgers Science Review | Spring 2012
Nation Branding (1988-present) The advertising of a National image Pavilions for commerce, culture, technology Shanghai, 2010: Expo Boulevard (above) Singapore Pavilion (below)
Spring 2012 | Rutgers Science Review | 31
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