Rutgers Science Review - Spring 2012

Arc Protein: A potential

Agent in learning

Rutgers Science Review

Volume 1, Issue 2Spring 2012

Pregnancy from a Gene’s Point of View

2 | Rutgers Science Review | Spring 2012

Table of Contents

Yellowstone Park: Prismatic Spring

Hysterectomy Overload. The Blame? Uterine Leiomyomas.

An Interview withDr. Mohan Kalelkar

ARC Protein: A Potential Agent in Learning


EPILEPSy In AUTISm SPECTRUm dISORdERS (ASdS)

Photonic Crystals: A Brief Introduction

Photo ArticleThe World’s Fair:

Through the Eras

pg 6

pg 8

pg 10

pg 13

pg 18

pg 22

pg 28

Spring 2012 | Rutgers Science Review | 3

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Menopause is expected in women as

they begin to age, but the removal of their

reproductive organs, a procedure known

as a hysterectomy, is not. The number

of hysterectomies has skyrocketed over

the past decade, largely due to uterine

leiomyomas. Many studies have tried to

understand what uterine leiomyomas

are, who they affect, and how they can

be prevented. Though much information

has been collected through this research,

there remain many unanswered questions.

Uterine leiomyomas (also known as

fibroids or myomas) are the most common

reproductive tract tumors in women1.

Smooth muscle tissue of the myometrium

escapes from the uterine lining and forms

fibroids in other areas of the body3, and

these fibroids have progressively become

a problem in women across the United

States. The rate of formation of leiomyomas

has been climbing at an astonishing rate;

nearly 70-80% of women are

expected to have leiomyomas

at some point in their lives,

although only 25% of women

will show severe symptoms

(i.e. excessive uterine bleeding,

increased pressure and pain

on adjacent organs, and

various problems related to

pregnancy, such as infertility

and miscarriage)2, 4. These

tumors are benign, yet still

pose many health complications in

predominantly premenopausal women. As

shown in the picture below, leiomyomas

can grow to be approximately the size

of a cantaloupe, causing a great deal of

discomfort in the abdominal area.

The symptoms of leiomyomas are

similar in all women, but the prevalence

of fibroids varies among different races,

and studies have shown that black women

are more susceptible to developing them.

In recent years, researchers have

begun performing many clinical trials to

find explanations for the cause of uterine

fibroids. While many risk factors have been

investigated, hormones and obesity hold

the biggest promise for identifying the cause

of these fibroids. Of these two potentials,

hormones seem to have the strongest basis

since they target cells and change cell

activity, causing cells to behave abnormally.

Many studies have shown that two

hormones, estrogen and progesterone, play

a vital role in uterine fibroid formation.

Several hypotheses argue that increased

levels of these ovarian steroids can result

in an increased mitotic rate that may

contribute to myoma development and

growth, with progesterone playing the

larger role in this process3,5. In a study,

Dr. Mitchell S. Rein of the North Shore

Medical Center investigates the formation

of leiomyomas, which involves somatic

mutations accompanied by interactions

between growth factors and sex hormones5.

According to Rein, further investigation can

lead to regulation of the hormones involved

and even to a successful, effective treatment.

Obesity has also been linked to

fibroid formation. As a person’s weight

increases, so does the number of circulating

androgens that are converted to a hormone

called estrone.2 This overproduction of

estrogen stimulates growth of the escaped

myometrial tissue, forming

lesions that are eventually

implanted on various

parts of the pelvic region.

Through trial and error,

certain preventive measures

have been shown to result

in smaller fibroids that are

less symptomatic and even

significantly reduce the risk of

fibroid formation altogether.

A study in Italy showed that

Hysterectomy Overload. The Blame? Uterine Leiomyomas.

By Tori Gartmond

Features


eating a higher quantity of vegetables

allows for more frequent bowel movements,

which rids the body of excess waste on a

more regular basis. Vegetarian women

seemed to excrete more estrogen in their

feces than their meat-eating counterparts,

had lower urinary estrogen excretion, and

exhibited 15-20% reduced plasma estrogen

levels2. The high-fiber diets of these women

disallowed for reabsorption of excess

hormones in the digestive tract, thereby

decreasing the rate of fibroid formation.

Eating healthy and maintaining a

healthy weight appear to significantly

lower the chances of contracting uterine

leiomyomas. Because scientists still have

not been able to pinpoint the exact causes

of uterine fibroids, their rate of formation

does not appear to be decreasing in the near

future, and the number of hysterectomies

conducted due to these fibroids will likely

maintain their current level in the upcoming

years. Fibroid removal and hysterectomies

have both been shown to have great success

as treatment options, and many women

have been happy with the results – though

a simpler way to reduce the number of

hysterectomies would be to raise general

awareness about myomas among women,

especially those at high risk. Women should

regularly see their gynecologist, schedule

regular appointments, and ask questions.

They should gather as much information

as they can about uterine leiomyomas to

take the necessary precautions and crack

down on this hysterectomy overload.

References

[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.

(2003). Etiology and pathogenesis

of uterine leiomyomas: A review.

Environmental Health Perspectives,

111(8), 1037.

[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.


W h a t

causes us to learn

and remember? Before we

explore that inquiry, let’s first dissociate

the two types of memory: explicit and

implicit. Explicit forms of memory include

the things that you can recall about your

life and other past events – they are aspects

of your memory that involve conscious

recollection. For example, you are using

your explicit memory when you recall the

names of your second grade classmates.

Implicit memories, however, consist of

all the information that is unconsciously

retained. They include skills, muscle

memory, and patterns of thought--you

don’t necessarily have to “think” about it in

order to do it.

What’s been determined as essential

for learning and both types of memory

is the strengthening and weakening of

synapses after neuronal activity. A synapse

is a small gap located at the point where

the end of a neuron meets another neuron.

When a neuron receives enough excitatory

input, it relays that input to the adjacent

neuron with chemical signals, called

neurotransmitters,

that cross this small gap. The membrane of

the excited neuron is called pre-synaptic,

while the membrane of the neuron receiving

the input is post-synaptic.

This ability of a synapse to get weaker

or stronger is referred to as synaptic

plasticity. An increase in synaptic strength

is called long-term potentiation (LTP) and

a decrease is called long-term depression

(LTD). What LTP essentially does is increase

the post-synaptic neuron’s probability of

firing--which might make a memory more

likely to be recalled--and it has been shown

to be a critical process in learning and

forming memories. A protein called Arc is

thought to play a role in LTP by making

certain morphological changes to the post-

synaptic membrane and perhaps even the

pre-synaptic membrane, which helps to

stabilize the newly strengthened synaptic

connections (Guzowski).

Activity-regulated cytoskeleton-

associated (Arc) protein has also been

implicated in the consolidation of explicit and

implicit

forms of

m e m o r y

(Bramham). The Arc protein is a

downstream product of the immediate-

early gene Arc. Since immediate-early genes

are almost exclusively activated in response

to stimuli, when the stimuli are absent,

expression of these IEGs is extremely

limited (Caputto). There would be limited

Arc IEG activity if there wasn’t an increase

in neuronal excitement, since this is the

stimulus that provokes Arc IEG activation.

When NMDA receptors--ion channels in

the cell membrane--are extremely excited,

they allow calcium to enter and initiate

the cascade of events that eventually result

in Arc upregulation and then LTP. So, if a

neuron has been strongly stimulated, more

Arc protein is likely to be present--resulting

in the morphological changes thought to be

involved in LTP.

The hippocampus is a structure that

ARC Protein: A Potential

Agent in Learning

Scott Kilianski

Features


has long been implicated with learning

and memory in both rats and humans, as

the patterns of neuronal excitation in the

hippocampus and associated areas are

generally accepted to be the underlying

cause of memory (McClelland, 1995). Lab

rats can function as animal models for

the human brain since their brains are,

for the most part, homologous to ours,

and it was through lesion studies that the

hippocampus has been determined to be

necessary for functions that involve learning

and memory (Morris). Lesion studies

involve studying a specific brain region that

has been inactivated chemically, removed

completely, or disabled with excessive

amounts of electric current. In studies

where rats’ hippocampi are lesioned, an

attenuation of the rats’ performances on

spatial memory-dependent processes--like

navigating through a water maze based

on cues positioned at different spatial

locations--has been observed (Morris). It

has also been seen that it is necessary for

a rat to have an intact hippocampus in

order to retain memory of the context it’s

been placed into (Matus-Amat). In Tim

Otto’s Learning and Memory lab at Rutgers

University, we’re specifically observing Arc

expression following periods of neuronal

excitation in rat hippocampi. At our lab,

as well as many others, we are specifically

attempting to understand how Arc’s role in

synaptic plasticity within the hippocampus

affects the acquisition and recall of

different types of spatial and contextual

memory. Together, we hope to eventually

attain a better knowledge of the biological

processes that take place on a cellular level

during memory formation and recall.

References

“Brain Anatomy for Genomics, Proteomics

& Bioinformatics.” Biology @ Davidson.

Davidson College, 2001. Web. 04 Mar.

2012. <http://www.bio.davidson.edu/

courses/genomics/method/Brainparts.

html>.

Bramham, Clive R., Maria N. Alme,

Margarethe Bittins, Sjoukje D. Kuipers,

Rajeevkumar R.

Nair, Balagopal Pai,

Debabrata Panja,

Manja Schubert,

Jonathan Soule,

Adrian Tiron, and

Karin Wibrand.

“The Arc of

Synaptic Memory.”

Experimental Brain

Research 200.2

(2010): 125-40. Print.

Caputto, B. L.,

and M. E. Guido.

“Immediate Early Gene Expression

Within the Visual System: Light and

Circadian Regulation in the Retina

and the Suprachiastmatic Nucleus.”

Neurochemical Research 25.1 (2000):

153-62. Print.

Guzowski, John F., Gregory L. Lyford,

Gail D. Stevenson, Frank P. Houston,

James L. McGaugh, Paul F. Worley,

and Carol A. Barnes. “Inhibition

of Activity-Dependent Arc Protein

Expression in the Rat Hippocampus

Impairs the Maintenance of Long-Term

Potentiation and the Consolidation

of Long-Term Memory.” Journal of

Neuroscience 20.11 (2000): 3993-4001.

Print.

Matus-Amat, P. “The Role of the Dorsal

Hippocampus in the Acquisition

and Retrieval of Context Memory

Representations.” Journal of

Neuroscience 24.10 (2004): 2431-439.

Print.

McClelland, James L., Bruce L. McNaughton,

and Randall C. O’Reilly. “Why There

Are Complementary Learning Systems

in the Hippocampus and Neocortex:

Insights from the Successes and

Failures of Connectionist Models of

Learning and Memory.”Psychological

Review 102.3 (1995): 419-57.

Morris, R. G. M., P. Garrud, J. N. P. Rawlins,

and J. O’Keefe. “Place Navigation

Impaired in Rats with Hippocampal

Lesions.” Nature 297.5868 (1982): 681-

83. Print.

Fig. 1 These dark lines in the rat hippocampus are stained cells inthree distinct subregions, dentate gyrus, CA1, CA3 that we look at in Tim Otto’s Learning and Memory Lab.


by Ritu nahar

It is often thought that mother and

child work cooperatively sharing the

baby’s survival as a mutual goal. However,

recently there is mounting evidence that

there may be some discrepancy between

the fetus and mother’s perception of the

pregnancy. In 1974, Robert Trivers used

evolutionary genetics to define his concept

of the “parent-offspring conflict” (POC).

The fundamental tenet of POC is the

existence of a slight difference in the amount

of parental investment that is optimal for

the child verses the amount of parental

investment that is optimal for the parent

(Trivers, 1974). David Haig then applied

POC to pregnancies and the relationship

between mother and fetus. Evolutionarily

speaking, the individual with greater fitness

is defined as the individual who is able

have greater numbers of progeny. Due to

sexual reproduction, a mother contributes

to only fifty percent of her fetus’s genome.

Therefore, from the mother’s perspective,

only half of her genes are passed on per

child, and so it would be in her best interest

to conserve her maternal resources and

have many offspring. From the fetus’s

perspective, it is to his or her advantage to

exhaust the maternal resources available as

they assist in increasing survival rate and

thereby the odds that all his or genes will

be passed on. Thus from the genes’ point

of view, there seems to be a slight conflict

of interest between mother and fetus: the

amount of resources the mother wants

to expend on her one fetus is slightly less

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.

Since the fetus’s genome is only 50%

maternal, the other half or the paternal genes

are foreign to the mother’s body and thus

cause the mother’s immune system to view

the fetus as a parasite. Evolutionary

however, if the mother was unable

to tolerate this infiltration of

foreign genes, she would

never reproduce and

thus she would have

little fitness as an

individual. By

contrast, if the

mother were

to allow every

fertilized egg

to implant

and then

expend all

her resources

on every

i m p l a n t e d

egg, she

would be

w a s t i n g

t r e m e n d o u s

amounts of energy

on children that

may not even be

viable. In reality, it

has been shown that

there is only a 30-40% chance

of there being a successful

implantation that results in

a detectable fetus in any given

menstrual cycle (Macklon, 2003).


This data provides evidence for the POC

evolutionary theory which would explain

the mother’s resistance in accepting a

fetus as an evolutionary designed control

mechanism which allows her to preserve

her resources for highly selected fetuses.

Further evidence of this hypothesis has

been shown by the abnormal karyotypes

of spontaneously aborted fetuses

which revealed distinct chromosomal

abnormalities. (Boue, 1975; Eiben, 1987;

Plachot, 1989). The mechanism for

spontaneous abortions may have evolved

has a means for the mother to verify and

ensure quality of the fetus before making

her investment in energy and time that

she could be using to raise a different

healthier fetus (Roberts and Lowe, 1975).

If this theory is true, there must

be some mechanism through which the

mother evaluates the fetus’s fitness level.

One potential mechanism is the ability of

the fetus to secrete the hormone, human

chorionic gonadotropin (hCG) through the

placenta. When released into the mother’s

blood by the implanted fetus, hCG has

been shown to increase the fetus’s survival.

Human chorionic gonadotropin binds to

the mother’s luteinizing hormone receptor

and thereby promotes sustained release of

progesterone. The continuous release of

progesterone inhibits menstruation thereby

preserving the implanted embryo (Brown

and Bradbury, 1947; Hanson, 1971; Jia,

1991). Interestingly it has been noted that

a statistically significant number of women

who were nauseous during pregnancy also

had higher levels of hCG (Masson, 1985).

However the significance and accuracy

of this finding is still under investigation

(ACOG, 2004). The effects of hCG on the

fetus are more definite. Intrauterine growth

restriction (IUGR) refers to the condition

in which the fetus undergoes improper

growth while in mother’s womb and in

some cases may subsequently lead to

intrauterine death (IUD) which refers to

the death of a fetus after 18 weeks in the

mother’s uterus. It has been shown that

hCG is one of three markers that when

present in abnormal levels in placentas are

correlated with increased risk of adverse

pregnancy outcomes such as intrauterine

growth restriction and intrauterine death

(Dayal, 2011). In addition, there were

significantly decreased hCG staining rates

in placentas from obtained from IUGR

and IUD cases (Günyeli, 2009). Both these

studies show a correlation between hCG

and the ability of the fetus to survive,

further evidence that hCG production by

the fetus may be a mechanism by which the

mother assesses the viability of the fetus.

Another example of POC in

pregnancies is shown by examination of the

placental hormone hPL. Human placental

lactogen (hPL) is generated by the fetus

and released into the mother’s blood where

it disables the mother’s insulin. Insulin

is a hormone involved in storing sugars

as glycogen for later use. Thus inactive

insulin results in increased levels of blood

sugar and less stored sugar for the mother.

Consequently by releasing hPL into the

mother’s blood system, the baby gains

greater sugar access through the placenta.

If this were a mutual relationship

in which fetus and mother work as one,

the mother would not counter the fetus’s

efforts to gain access to more of her sugars.

However, it has been shown that the

mother counters the fetus’s attempts of

gaining excess sugar by increasing insulin

production, which is evidence for POC

(Haig, 1993). Gestational diabetes (GD)

further indicates the presence of a power

struggle between mother and fetus. During

pregnancy, a mother’s pancreas may

generate up to three times the regular levels

of insulin to overcome the effect of the fetal

placental hormones on blood sugar levels.

GD is a relatively common disease

associated with pregnant women who are

human chorionic gonadotropin (hCG)

Human placental lactogen (hPL) Insulin

Features


insulin resistant and therefore lack the

proper ability to form insulin (Carr, 1998).

Applying Triver’s “parent-offspring

conflict” to the mother-fetus relationship

as done by Haig, offers reasonable

explanations for much of the scientific data

published regarding pregnancy-related

diseases such as gestational diabetes,

intrauterine growth restriction, and

intrauterine death. Such complications

tend to result when the balance is tipped

to favor either mother or fetus, which

gives evidence that the two do not share

all the same goals. The mother is inclined

to reserve resources for later childbirths

in order to maximize her fitness. The

fetus on the other hand would maximize

its fitness by depleting the mother of all

the resources she would otherwise give

to other children. Though pronounced

evidence exists favoring the application of

the parent-offspring conflict in pregnancies,

there is no definite proof that it is indeed

the correct explanation. However if

proven true, there would be immense

implications in the future for the use of

evolutionary genetics in medical research.

References

ACOG (American College of Obstetrics and

Gynecology): Practice bulletin: nausea and

vomiting of pregnancy. Obstet Gynecol

2004, 103(4):803-814.

Brown, W. E., andJ. T. Bradbury. 1947. A

study of the physiologic action of human

chorionic hormone. The production of

pseudopregnancy in women by chorionic

hormone. Am. J. Obstet. Gynecol., 53:749-

757.

Boue,J., A. Boue, and P. Lazar. 1975. Retrospec-

tive and prospective epidemiological stud-

ies of 1500 karyotyped spontaneous human

abortions. Teratology, 12:11-26.

Carr D.B., Gabbe S. (1998).Gestational diabetes;

detection, management, and implications.

Clinical Diabetes,16(1):4–11.

Dayal, M., Gupta P.,Varma M., Ghosh U.K., and

Bhargava A. (2001). Role of Second Trimes-

ter Maternal Serum Markers as Predictor

of Preeclampsia. The Journal of Obstetrics

and Gynecology of India January/Febru-

ary. 38-41.

Eiben, B., S. Borgmann, I. Schiubbe, and I. Hans-

mann. 1987. A cytogenetic study directly

from chorionic villi of 140 spontaneous

abortions. Hum. Genet., 77:137-141.

Goodwin, T.M., Hershman J.M., Cole L. (1994).

Increased concentration of the free beta-

subunit of human chorionic gonadotropin

in hyperemesis gravidarum. Acta Obstet

Gynecol Scand, 73:770-772.

Günyeli, İ., Zergeroğlu, S. S., Danisman, N. N.,

& Mollamahmutoğlu, L. L. (2009). The

diagnostic significance of hCG and hPL via

immunohistochemistry of placental tissues

in pregnancies diagnosed with IUGR and

IUD. Journal Of Obstetrics & Gynaecol-

ogy,29(6), 521-525.

Haig, D. (1993). Genetic conflicts in human

pregnancy. Quarterly Review of Biology,

68, 495-532.

Hanson, F. W., J. E. Powell, and V. C. Stevens.

1971. Effects of HCG and human pituitary

LH on steroid secretion and functional

life of the human corpus luteum. J. Clin.

Endocrinol. & Metab., 32:211-215.

Jia, X.-C., M. Oikawa, M. Bo, T. Tanaka, T.

Ny, I. Boime, and A. J. W. Hsueh. 1991.

Expression of human luteinizing hormone

(LH) receptor: interaction with LH and

chorionic gonad tropin from human but

not equine, rat, and ovine species. Mol.

Endocrinol., 5:759-768.

Macklon N.S., Geraedts, J.P.M., and Fauser,

B.C.J.M. 2002. Conception to ongoing preg-

nancy: the ‘black box’ of early pregnancy

loss. Human Reproduction Update 2002.

Masson G.M,, Anthony F, Chau E.1985.

Serum chorionic gonadotrophin (hCG),

schwangerschaftsprotein 1 (SP1), proges-

terone and oestradiol levels in patients

with nausea and vomiting in early preg-

nancy. Br J Obstet Gynaecol, 92:211-215.

Plachot, M. 1989. Chromosome analysis of spon-

taneous abortions after IVF. A European

sur- vey. Hum. Reprod. (Oxf.), 4:425-429.

Roberts, C. J., and C. R. Lowe. 1975. Where have

all the conceptions gone? Lancet, 1:498-

499.

Sheehan P. 2007. Hyperemesis gravidarum-

-assessment and management. Aust Fam

Physician, 36:698-701.

Trivers, R. L. (1974). Parent-Offspring Conflict.

American Zoologist 14 (1): 249–264.

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.

Figure 1 – 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

a) b) c)

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.

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

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 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

a) b)

c) d)

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.

Figure 4 – Band structure of a 1-D stop-band filter for green light

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.

Figure 6 – 1-D PhC 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

λc = 565 nm

λ1 = 681 nm

λ2 = 439 nm λ < λ2

λ2 ≤ λ ≤ λ1

λ > λ1

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 1-D PhC having ε1 = 1.44, ε2 = 2.25, N = 20 for which the dielectric layer thicknesses are changed.

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.

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)

a)

b)

c)

d)

b) c)

a)

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)

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)

Features

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Could start out by telling us a little about yourself and your

background?

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

Columbia for a few years. Then, Rutgers offered me a faculty

job, and I’ve been at Rutgers ever since. It was in 1978 that

Rutgers offered me a job, so I’ve been at Rutgers since ’78.

Students might find it fun to learn that in my undergraduate

days at Harvard, we were required to have a meal plan and

have all meals at the dining hall. And, we were required to

wear a coat and tie to every meal . . . including breakfast. And

that was enforced by an enforcer at the entrance; if you didn’t

have a coat and tie, you were sent off [laughs].

How has college changed from when you were a student?

Well, technology was far more primitive back then. We did

use computers, but they were all big mainframe computers,

so there was no such thing as a personal computer. So, of

course, there was no such thing as a word processor. Internet,

email, and World Wide Web were beyond imagination,

nobody could even dream that such a thing was ever going

to happen. Even pocket calculators didn’t become widely

available until I was nearly finished with my PhD. We had to

do a lot of things using slide rules. From my undergraduate

up to my graduate year, I was basically doing physics

homework problems and exam problems using a slide rule.

And, on campus, the classic nerd symbol was to have a slide

rule in your left front pocket. This identified you as a nerd

[laughs].

How has physics changed from the time you were a student?

Physics has changed dramatically because of the advance

in technology. I wrote my entire PhD thesis on IBM punch

cards. When writing computer programs, we would have

key punch machines, whereby every command is written on

one card and encoded by a pattern of holes. You could also

write plain text across this; it doesn’t have to be computer

code. So I wrote my entire PhD thesis on punch cards. Later,

of course, a secretary typed it up properly. The hardest thing

was strategically leaving spaces where I knew I was going to

need to put things in by hand and leaving some lines where I

was going to have to put in a formula.

How did you get started in the field of Physics?

While I was a sophomore at Harvard, I asked my physics

professor, who was named Karl Strauch, for a summer job.

Of course, I wanted a summer job so I could work with

somebody. And I was very lucky, he was able to give me a

job in the field of experimental high-energy physics, which

involved atom-smashers. And the specific technology we

used was the bubble chamber. That was in use then; today,

the bubble chamber is close to being obsolete. So I worked

with that, and I became a high-energy physicist for the rest

of my career because Professor Strauch gave me a job that

An Interview With:

dr. mohan Kalelkar

Dr. Mohan Kalelkar is a Professor and Undergraduate Program Director of Physics at Rutgers University. His

research interests lie in Elementary-Particle Physics.

conducted by neil raju


summer. It’s amazing how things happen by chance: if he

had been somebody working in astronomy, I’d probably be

an astronomer today.

When I entered Harvard, I was not sure what I wanted to do.

I thought I might even study economics, because the subject

interested me. But what happened is that my freshman

physics professor was very, very good. His name was Ralph

Baierlein, and he was so good that I was hooked on physics.

Then, as I said, sophomore year I asked Professor Strauch for

the summer job.

Can you tell us a little more about your research?

So I would continue doing bubble chamber physics into my

PhD research at Columbia, and my thesis research was on

the interactions on the particles known as π-mesons. The title

of my thesis was ‘Meson resonance production in 15 GeV/C π+

interactions with liquid hydrogen’. Π-mesons are amongst

the elementary particles, ergo they are not truly elementary:

they are made up a quark and an anti-quark, as we know

today. We didn’t know that back then. This thesis research

allowed me to measure the properties of extremely short-

lived particles that exist for as little as 10-23 seconds. They

barely grow a nucleus before decaying, but such particles do

exist.

After I came to Rutgers, I started working on a series of

experiments studying the interactions of neutrinos with

matter. This was at Fermi National Accelerator Laboratory

in Illinois, where we had a way of producing a neutrino

beam and having it go into the bubble chamber, and

took photographs of the interactions that took place. We

painstakingly scanned the photographs to learn about the

interactions. You might find it fun to know that the sun also

produces neutrinos, although of a different type. Neutrinos

are particles that very, very rarely interact, so we had to

send millions at a time into the bubble chamber, and maybe

one would interact. Most of the neutrinos from the sun go

straight through the earth without interactions. As you and I

are speaking, over 1014 neutrinos are going straight through

our bodies every second.

So after the neutrino experiments came to an end, I spent

many years studying electron/anti-electron interactions at the

Stanford Linear Accelerator Center. This involved electrons

and anti-electrons annihilating each other at high energy.

When this happens, quarks and gluons get produced...

and we study them. By then, technology had gone well

past taking photographs. By then, all the reconstructions

were electronic. Here is an example of an event in the

electron/positron interaction [Figure 1]. So think of electrons

going into the screen, anti-electrons coming from behind,

annihilating, and they produce a quark, an antiquark, and a

gluon. These three fragmented into the tracks that you see

here.

What’s the Stanford Linear Accelerator Center? Why did the

research have to take place there?

[SLAC] uses a two-mile long linear accelerator to accelerate

the electrons and anti-electrons, so it’s a very, very expensive

thing; it’s not as though each university can build its own.

But the Department of Energy funded the laboratory at

Stanford, and that’s where I did my experiments for a large

number of years. And this, of course, is big science; we had

many collaborators, we had a couple of hundred people

working on these experiments. You’ve heard of this new one

in Switzerland, the Large Hadron Collider: it’s got thousands

of people working on it.

What potential breakthroughs do you see in Physics?

The main, near-term breakthrough that I’m hoping for is the

discovery of the Higgs-Boson at the LHC in Switzerland.

That is the one missing link in our so-called standard model

of physics. And if we don’t find it, then that may well mean

that the standard model is seriously flawed. In the standard

model, the Higgs-Boson is what is responsible for giving

mass to the elementary particles. Now, at the same time, we

know that the standard model cannot be the last word: it

contains several internal contradictions and inconsistencies

at a subtle level. What I’m hoping for in the somewhat

Interview


distant future is that we do figure out how to resolve the

contradictions.

Could you elaborate on these contradictions? How does the

Higgs-Boson give mass to the elementary particles?

The contradictions in the standard model are that if we get

to high enough energy, the standard model makes certain

predictions that are just absurd, that certain quantities would

become infinite when they cannot be infinite.

As for the Higgs-Boson, there is a very nice analogy to

explain how the Higgs-Boson gives mass to particles; the

analogy was invented by a Professor David Miller at the

Imperial College in London. He said to imagine a room that is

crowded with men, as if it’s coffee-break during a conference

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 Higgs-

Boson [laughs].

Do you have any advice for students interested in pursuing

research in physics?

I would say get started as early as possible, that it is so

satisfying, really immensely satisfying. In research, you’re

doing something different from the usual end-of-chapter

homework problems and studying for exams. When you do

research, you really are working in frontier physics. You’re

working on something that is not a canned homework

problem, but you’re working on research where you don’t

know for sure what the outcome is going to be. And it’s just

so great to do the research and see what happens, trying to

draw conclusions. Rutgers has wonderful research programs;

I would encourage those who are interested in physics or

other sciences to apply for these research programs.

Figure 1In 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

Interview

Research Papers


E P I L E P S Y I N A U T I S M S P E C T R U M D I S O R D E R S ( A S D S )

B y : J i g a r G a n d h i

B y J i g a r H a n d h i


A u t i s m S p e c t r u m D i s o r d e r s ( A S D s ) a n d E p i l e p s y I N T R O D U C T I O N :

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

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

Some early studies reported the prevalence rates of 2 to 5 per

10,000 for autism while the recent reports suggest the rates of up to 60

per 10,000 3 (approximately 1 in 150 children). The onset of symptoms

can be observed as early as prior to 3 years of age, although the

syndrome may not be recognized until later. Autism is 3.5 times more

prevalent in males than females, with unknown etiology in 80–90% of

the total cases.2 The fact that ASDs frequently occurs concomitantly

with epilepsy, there may be an association with a single gene defect

conditions called fragile X syndrome, neurofibromatosis, and tuberous

sclerosis.4 In addition, various epidemiological and genetic studies have

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)

S E I Z U R E S A N D E E G A B N O R M A L I T I E S I N A U T I S M :

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

Table 1: DSM-IV-TR criteria for Autism Spectrum Disorders5

A total of six (or more) items from each category A) Qualitative impairment in social interaction (at least 2)

Impairment in nonverbal behaviors such as eye contact

Failure to develop peer

Lack of seeking to share enjoyment or interests

Lack of social or emotional reciprocity

B) Qualitative impairment in communication (at least 1) Delay in or lack of spoken language

If speech is present, lack of ability to initiate or sustain conversation

Stereotyped and repetitive/idiosyncratic language

Lack of pretend/social imitative play

C) Restricted interests/repetitive behavior (at least 1) Preoccupation with restricted interest

Inflexible adherence to nonfunctional routines or rituals

Stereotyped and repetitive motor mannerisms (hand flapping)

Persistent preoccupation with parts of objects

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

T Y P E S O F S E I Z U R E S I N A U T I S M :

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

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

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

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%

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 Landau–

Kleffner syndrome (LKS).15

M A N A G E M E N T O F E P I L E P S Y I N A S D P A T I E N T S :

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 placebo-

controlled 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

Research Papers


At present, there are no controlled data supporting

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.

C O N C L U S I O N :

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,

and, most importantly, cognitive and behavioral side effects

must be considered. It is important to note that treating

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.

R E F E R E N C E S :

1. Creak ME. Childhood psychosis. Br J Psychiatry 1963; 109: 84–89.

2. Messing RO, Rubenstein JH, Nestler EJ (2012). Chapter 390. Biology of Psychiatric Disorders. In D.L. Longo, D.L. Kasper, J.L. Jameson, A.S. Fauci, S.L. Hauser (Eds), Harrison's Principles of Internal Medicine, 18e. Retrieved January 24, 2012 from http://www.accesspharmacy.com/content.aspx?aID=9112128.

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Antiepileptic Drugs (AEDs) Profile 30

AEDs Behavioral & Cognitive Adverse Events Benzodiazepines Agitation, paradoxical reactions, hysteria, psychosis, restlessness

Carbamazepine Agitation, latent psychosis

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

Zonisamide Somnolence, memory impairment, mental slowing, difficulty concentrating, dizziness

Research papers


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15. Mun˜ oz-Yunta JA, Ortiz T, Palau-Baduell M, et al. Magnetoencephalographic pattern of epileptiform activity in children with early-onset autism spectrum disorders. Clin Neurophysiol 2008;119:626–634.

16. Same as 6

17. Piccinelli P, Borgatti R, Aldini A, et al. Academic performance in children with rolandic epilepsy. Dev Med Child Neurol. 2008;50:353–356.

18. Kavros PM, Clarke T, Strug LJ, et al. Attention impairment in rolandic epilepsy: systematic review. Epilepsia. 2008;49:1570–1580.

19. Hollander E, Dolgoff-Kaspar R, Cartwright C, et al. An open trial of divalproex sodium in autism spectrum disorders. J Clin Psychiatry. 2001;62:530–534.

20. Pressler RM, Robinson RO, Wilson GA, Binnie CD. Treatment of epileptiform discharges can improve behavior in children with behavioral problems and epilepsy. J Pediatr. 2005;146:112–117.

21. Eriksson AS, Knutsson E, Nergardh A. The effect of lamotrigine on epileptiform discharges in young patients with drug-resistant epilepsy. Epilepsia. 2001;42:230–236.

22. Bombardieri R, Pinci M, Moavero R, et al. Early control of seizures improves long-term outcome in children with tuberous sclerosis complex. Eur J Paediatr Neurol. 2010;14:146–149.

23. Tuchman R. Treatment of seizures disorders and EEG abnormalities in children with autism spectrum disorders. J Autism Dev Disord. 2000;20:485–489.

24. De Martino A, Tuchman R. Antiepilepic drugs: affective use in autism spectrum disorders. Pediatric Neurol. 2001;25:199–207.

25. Ronen GM, Richards JE, Cunningham C, Secord M, Rosenbloom D 2000 Can sodium valproate improve learning in children with epileptiform bursts but without clinical seizures? Dev Med Child Neurol 42:751–755.

26. Plioplys AV 1994 Autism: electroencephalogram abnormalities and clinical improvement with valproic acid. Arch Pediatr Adolesc Med 148:220–222.

27. Chez MG, Chang M, Krasne V, Coughlan C, Kominsky M, Schwartz A 2006. Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996to 2005. Epilepsy Behav 8:267–271.

28. Kossoff EH, Los JG, Boatman DF 2007 A pilot study transitioning children onto levetiracetam monotherapy to improve language dysfunction associated with benign rolandic epilepsy. Epilepsy Behav 11:514–517.

29. Loring DW, Meadoer KJ. 2004. Cognitive side effects of antiepileptic drugs in children. Neurology 62:872–877.

30. Dewi Frances T. Depositario-Cabacar and Tesfaye-Getaneh Zelleke. Treatment of epilepsy in children with developmental disabilities. Developmental Disabilities Research reviews 16: 239 – 247 (2010).

Research Papers


the world’s

fair: through the eras

Lynn ma

RSR photo article


London, 1851: Crystal PalaceThe First World’s Fair

Paris, 1889: La Tour Eiffel

Philly,1876:1,500 horsepowersteam engine

Chicago 1893: 1st Ferris Wheel

Industrialization Era (1851-1938)Where Technological inventions from

around the world were brought together


montreal, 1967: Geodesic dome“man and His World”

new york, 1964: Unisphere“Peace Through Understanding”

Era of Cultural Exchange (1939-1987)“Future-oriented, utopian society, humankind”

the signififIcance of cultural dialogue


Shanghai, 2010: Expo Boulevard (above)Singapore Pavilion (below)

nation Branding (1988-present)The advertising of a national image

Pavilions for commerce, culture, technology

new york, 1964: Unisphere“Peace Through Understanding”

Era of Cultural Exchange (1939-1987)“Future-oriented, utopian society, humankind”

the signififIcance of cultural dialogue

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