Rutgers Science Review - Spring 2012

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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Articles

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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Spring 2012 | Rutgers Science Review | 27

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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