Welcome to Neuropsychology! June 13, 2011. What is Neuropsychology?

Welcome to Neuropsycholog

y!

June 13, 2011

What is Neuropsychology?

Neuropsychology is… Neuroscience +

Psychology “A science

concerned with the integration of psychological observations on behavior and the mind with neurological observations on the brain and nervous system (Merriam-Webster Dictionary)

NeurosciencePsychology

Biomedical Sciences

NeurosciencePsychology

Biomedical Sciences

Neuropsychology

What is the Main Aim of Neuropsychology?

Overall Goal of Neuropsychology

To gain better understanding of the links between neuroscience and behavior, and to improve the care of individuals with neurologically based behavioral disturbances

~Adapted from Arciniegas & Kaufer 2006

What Do Neuropsychologists Study?

Neuropsychologists Study… Alzheimer’s Disease Anxiety Attention Autism Bipolar Disorder Brain Tumors Cerebral Palsy Depression Development Drug Addiction Epilepsy Headaches Huntington’s Disease Imaging

Language & Speech Learning & Memory Mental Retardation Multiple Sclerosis Personality Pain Parkinson’s Disease Post-Traumatic Stress Schizophrenia Sensation/Perception Sleep Stroke Traumatic Brain Injury And More!!

Why Are Neuropsychologists Important?

Psychiatric Disorders Are a Huge Problem in Adults…

http://www.nimh.nih.gov/statistics/1ANYDIS_ADULT.shtml

…And in Children & Adolescents.

http://www.nimh.nih.gov/statistics/1ANYDIS_CHILD.shtml

They Place a Heavy Burden on The Affected Individual…

http://www.nimh.nih.gov/statistics/2LEAD_CAT.shtml

…And on Society.

http://www.nimh.nih.gov/statistics/4TOT_MC9606.shtml

http://www.nimh.nih.gov/statistics/4EXP2003.shtml

How Do Neuropsychologists Address These Problems?

Many Different Ways!

Image Credits: http://www.scientificamerican.com/blog/post.cfm?id=stem-cells-could-offer-new-source-f-2009-11-25, http://www.genome.gov/pressDisplay.cfm?photoID=5006, http://discovermagazine.com/2009/feb/22-very-tough-rat-big-risk-human-health, http://www.abc.net.au/science/articles/2007/11/15/2092703.htm, http://psyphz.psych.wisc.edu/web/research.html, Raznahan, A., D. Greenstein, et al. "Catechol-o-methyl transferase (COMT) val158met polymorphism and adolescent cortical development in childhood-onset schizophrenia patients, their non-psychotic siblings, and healthy children." NeuroImage In Press, Uncorrected Proof.

Famous Contributions of Neuropsychologists

The Asch Conformity Experiments Harry Harlow's Social Isolation The Milgram Obedience Experiment The Stanford Prison Experiment

Levels of Research

Basic Research

“Pure” or “Fundamental” research Research that satisfies our curiosity

without having a direct solution for a given healthcare problem

Helps us know how the brain functions Examples:

− How do nerves carry information to the brain?− Which neurotransmitter receptor types are

located in a given brain region?

Why is Basic Research Important?

"People cannot foresee the future well enough to predict what's going to develop from basic research. If we only did applied research, we would still be making better spears."

Dr. George Snoot

Applied Research

Focused on solving a particular biomedical problem to improve the human condition

Usually involves development of a new drug, technique, or therapy

Sometimes creates a situation in which we know something works, but we can’t explain why or how!

Also called Translational research

Why is Applied Research Important?

Improves the human condition

Examples:− Can drug X be

developed to more effectively treat the depression?

− Can we use stem cells to treat diseases like diabetes, Parkinson’s, etc?

Clinical Research

Translates findings of basic & applied research into treatments and studies in humans

NIH defines 3 categories:− Patient-oriented research− Epidemiological & behavioral studies− Outcomes & health services research

Examples:− Does Drug X work in humans to treat depression?

Is it safe? What are the side effects?

Clinical Trials

Phase 1: Safety, Dosage, & Side Effects Phase 2: Efficacy & Safety Phase 3: Efficacy, Improvement over current

treatments, Phase 4: Continued studies after marketing

to ensure efficacy in various populations, long-term effects

What Tools Do Neuropsychologists Use for

Their Research?

Tools of Neuropsychology

Animal models Neuroimaging Drug Studies Lesion Studies Interviews & Surveys

Animal Models

Capturing certain aspects of a human disease or behavior in an animal for research purposes

Examples:− Knockout mouse− Selectively bred rodents− Nonhuman primate studies− Viral Infection− Drug Injection

Neuroimaging Assesses the structure or function of

the brain for diagnosis or research Examples:

Lewis-Hanna, L. L., M. D. Hunter, et al. "Enhanced cortical effects of auditory stimulation and auditory attention in healthy individuals prone to auditory hallucinations during partial wakefulness." NeuroImage In Press, Corrected Proof.

D'Ambrosio, N., J. K. Lyo, et al. (2010). "Imaging of Metastatic CNS Neuroblastoma." Am. J. Roentgenol. 194(5): 1223-1229.

Seneca, N., S. Finnema, et al. (2011). "Occupancy of dopamine D<sub>2</sub> and D<sub>3</sub> and serotonin 5-HT<sub>1A</sub> receptors by the novel antipsychotic drug candidate, cariprazine (RGH-188), in monkey brain measured using positron emission tomography." Psychopharmacology: 1-9.

fMRI CT PET

Drug Studies

Involves giving a drug to an animal to affect the levels of certain chemicals in the brain

Can be used to induce a certain behavior or as an effort to learn the mechanisms underlying a disease

Example:− If a drug induces epileptic seizures in a rat, then

we can use that drug to create an animal model for studying epilepsy.

− This also tells us that the chemicals affected by that drug are probably involved in epilepsy.

Lesion Studies A study of changes in behavior or

function following damage to a particular brain region

Kim, S. S., K.-H. Chang, et al. (1999). "Focal Lesion in the Splenium of the Corpus Callosum in Epileptic Patients: Antiepileptic Drug Toxicity?" AJNR Am J Neuroradiol 20(1): 125-129.

Bankiewicz, K. S., R. Sanchez-Pernaute, et al. (2001). Preclinical Models of Parkinson's Disease, John Wiley & Sons, Inc.

Interviews & Surveys

http://www.lexapro.com/check_symptoms/take-a-dep-self-

test.aspx

A Closer Look with PET

PET images provided by:Sanjiv S. Gambhir, M.D., Ph.D.

Let’s Play PETUCLA School of Medicine

Crump Institute for Biological ImagingCopyright 1998 Regents of the University of California

http:/ /www.crump.ucla.edu/lpp/clinpetneuro/function.html.Copyright © 2000 by BSCS and Videodiscovery, Inc.

Permission granted for classroom use.

PET images provided by:Sanjiv S. Gambhir, M.D., Ph.D.

Let’s Play PETUCLA School of Medicine

Crump Institute for Biological ImagingCopyright 1998 Regents of the University of California

http:/ /www.crump.ucla.edu/lpp/clinpetneuro/function.html.Copyright © 2000 by BSCS and Videodiscovery, Inc.

Permission granted for classroom use.

PET images provided by:Sanjiv S. Gambhir, M.D., Ph.D.

Let’s Play PETUCLA School of Medicine

Crump Institute for Biological ImagingCopyright 1998 Regents of the University of California

http:/ /www.crump.ucla.edu/lpp/clinpetneuro/function.html.Copyright © 2000 by BSCS and Videodiscovery, Inc.

Permission granted for classroom use.

PET images provided by:Sanjiv S. Gambhir, M.D., Ph.D.

Let’s Play PETUCLA School of Medicine

Crump Institute for Biological ImagingCopyright 1998 Regents of the University of California

http:/ /www.crump.ucla.edu/lpp/clinpetneuro/function.html.Copyright © 2000 by BSCS and Videodiscovery, Inc.

Permission granted for classroom use.

PET images provided by:Sanjiv S. Gambhir, M.D., Ph.D.

Let’s Play PETUCLA School of Medicine

Crump Institute for Biological ImagingCopyright 1998 Regents of the University of California

http:/ /www.crump.ucla.edu/lpp/clinpetneuro/function.html.Copyright © 2000 by BSCS and Videodiscovery, Inc.

Permission granted for classroom use.

PET images provided by:Sanjiv S. Gambhir, M.D., Ph.D.

Let’s Play PETUCLA School of Medicine

Crump Institute for Biological ImagingCopyright 1998 Regents of the University of California

http:/ /www.crump.ucla.edu/lpp/clinpetneuro/function.html.Copyright © 2000 by BSCS and Videodiscovery, Inc.

Permission granted for classroom use.

What Do These Mean? Who’s Doing What?

What Makes a Good Experiment?

Experimental Design

Determine your question: Not too broad, not too narrow, but just right.

Do background research: What is already known? Don’t re-invent the wheel!

Construct a hypothesis, or “educated guess”. Often written in if-then format

http://www.sciencebuddies.org/mentoring/project_scientific_method.shtml

The Hypothesis

A testable idea about what you think will happen…A tentative explanation for your problem of interest− “If Drug X is an effective anticonvulsant,

then patients taking Drug X will have fewer seizures than those not taking Drug X.”

MUST BE SCIENTIFICALLY TESTABLE!− “Why do people drink coffee?” is not

scientifically testable.

Experiment Away!

Groups− Controls: These are

the “normal” conditions that you are comparing against.

− Experimental Groups: The groups used to test your hypothesis.

Control Group: No Treatment Received

Experimental Group:

Treatment Received with

Drug X

The Variables Independent Variable (IV)

− Controlled by the scientist− May include things like drug dose, type of subject used

(Wild-type or knock-out mouse? Patient with AA genotype or aa?)

Dependent Variable (DV)− Measured by the scientist; changes in response to the IV

“People who exercise regularly will report higher levels of happiness.”− IV? Frequency of exercise− DV? Reported level of happiness

Everything else in the experiment should be held constant, insomuch as it is possible!

But wait…

Say that people who exercise regularly DO report feeling happier than those who don’t.− How do we know this happiness is due

to exercise? − What else could it be due to?− How do we know it wasn’t caused by

random chance?

Enter statistical significance!

Likelihood a result happened solely by chance Expressed by p-value (probability of occurring

by chance) − Standard cutoff in science is p<0.05 (the probability

of getting your result by chance alone is less than 5%)

− Smaller p-values mean higher statistical significance Calculated by a variety of tests…

t-tests, ANOVA, etc Graphs often use * to indicate a

significant difference between experimental groups

3-in-1 Experimental

Design

Journal Articles & Case Studies

Case Studies

What is a Case Study?− A detailed analysis of a person or group,

especially as a model of medical, psychiatric, psychological, or social phenomena.

The American Heritage® Stedman's Medical Dictionary

Why are they important?− Allow doctors, researchers, and medical

professionals to study multiple factors affecting a patient

− No two patients are exactly alike, and their differences can be very important!

− Also provide examples for diagnostic and treatment procedures when dealing with an unknown or atypical problem

Anatomy of a Case Study Abstract Presenting complaints History Patient & Case Assessment Course of treatment Assessment of progress Complicating factors Follow-up Recommendations & Treatment implications References

Journal Articles

What is a Journal Article?− An article featuring recent, novel scientific

discoveries published to advance research in the field.

What is it used for?− Present new research findings (i.e., Our research

suggests that Gene X is involved in depression)− Instruct other researchers on how to perform a

technique (i.e., Scientists may read a journal article to learn how to test anxiety levels in rats).

− Present a review of results from multiple other studies (i.e., Review of antidepressant therapies in treating OCD)

Anatomy of a Journal Article Abstract

− A brief summary Background & Introduction

− What do we already know?− Why is this study important?

Methods Results Discussion & Conclusions

− What do the results mean?− Significance & implication?

References

Do ALL Journal Articles Have Hypotheses?

Well….yes, and no. Some research is descriptive rather than

hypothesis-driven.− “This study will identify genes that are involved

in both epilepsy and depression.”− But I can’t predict which genes…if I could, I

wouldn’t be doing the experiment!− A vague hypothesis for this could be written: “If

epilepsy and depression are occurring simultaneously, then various genes can be identified that are involved in both diseases.”

Journal Article or Case Study?

Journal Article or Case Study?

Journal Article or Case Study?

[project on]

Journal Article or Case Study?

Show Me a Journal Article!

What is the main purpose of this article?− Present a new finding?− Instruct in a method?− Review current knowledge?

IntroductionUnderstanding the biological link between epilepsy and depression is desirable for a host of reasons. Depression has a more profound impact on an epileptic patient's quality of life than seizure severity or frequency ([Johnson et al.,

2004] and [Meldolesi et al., 2006]) … Despite a clear epidemiological link between the two diseases, there is little experimental evidence to support a shared pathology, and there are few animal models that might reveal the potential underlying mechanisms, a deficiency much lamented in recent reviews (e.g. Kanner, 2003).

In an attempt to experimentally confirm the striking comorbidity between TLE and depression and to simultaneously create an animal model, we tested whether rats selectively bred for depression-like phenotypes are more susceptible to kainic acid-induced seizures.

What problem do the researchers hope to address?

What is their hypothesis?

MethodsThe rat lines used were: Swim-Lo active (SwLo), with low motor activity in a Porsolt forced swim test (FST); Swim-Hi active (SwHi), with high motor activity in the FST. Male rats were used for all experiments, and each rat was used in a seizure experiment only once.

Kainic acid was administered to rats as previously described ([Ben-Ari et al., 1980] and McKhann et al., 2003]), but with slight modifications. Rats were injected intraperitoneally (ip) with kainic acid (10 mg/kg), then placed in a clear container and observed closely for behavioral seizures. Latency to various seizure behaviors was scored using a modified version of the Racine scale (Racine, 1972). What is the independent variable? What is the dependent variable?

ResultsWithin 30 min of injection, the rats began to stare, followed by increasingly severe seizure behaviors, including wet-dog shakes, forelimb clonus, rearing and falling, and CT seizures… In general, all lines bred for susceptibility to depression-like phenotypes had higher final seizure severity than their depression-resistant counterparts (P < 0.05 for the depression-susceptible SwLo line compared to its depression-resistant SwHi counterpart).

NS SwLo SwHi SUS RES HYPER MON RES0

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NS SwLo SwHi SUS RES HYPER MON RES0

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NS SwLo SwHi SUS RES HYPER MON RES0

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NS SwLo SwHi SUS RES HYPER MON RES0

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What were the results? Were they statistically

significant? What do you think this means?

Does is support the hypothesis?

Discussion & ConclusionsRats bred for depression-relevant behavioral phenotypes were also susceptible to kainic acid-induced seizures, compared to their counterparts that are resistant to these phenotypes. Furthermore, both the depression-like and seizure phenotypes were stable over multiple generations, indicating co-heritability. Second, the incidence of major depression is particularly high in patients with TLE, ranging from similar 20–70% ([Kanner and Balabanov, 2002] and

[Kuhn et al., 2003]). We found that our rat lines differed in response to kainic acid, which is commonly used to model TLE.

The greatest value of any animal model of disease is as a tool for studying the disease mechanism(s); in this case, monoamine dysfunction is an appealing candidate [Jobe et al. (1999)]…Thorough characterization of monoamine and other systems in these rats, as well as their neuronal and synaptic organization, may yield clues about the underlying mechanisms of epilepsy and depression comorbidity, leading eventually to improved therapy for individuals who suffer from both disorders.

What does this study tell us? Why is it important?

Library Information

Session2:15-3:15 pm

Working With Humans

Research Ethics

Think back to the experiments we talked about this morning…− The Milgram Obedience Experiment− The Stanford Prison Experiment

Are these studies ethical? Think about various populations of

subjects…− Children− Prisoners

Is it ethical to conduct research on these groups?

So How Do We Protect Human Research Participants?

Institutional Review Boards (IRBs)− Review all research

projects involving humans before they begin in order to ensure the rights and welfare of participants

What Are the Requirements for IRB Approval?

Respect for Persons− Not a Means to an End

Beneficence− No Harm Done − Minimized Risk

Justice− Are the experiments fair? Are

participants rewarded appropriately, and are burdens reasonable in relation to benefits?

Other Conditions

Subject Selection is Unbiased− Random Sampling

Informed Consent− Is the participant informed about the study

and any risks?− Does the participant comprehend this

information?− Is the participant volunteering

of their own free will? Monitoring to Ensure Safety Confidentiality

What Makes a Good Survey?

Potential Survey Pitfalls

Survey Limitations

Correlation does NOT imply causation! The results of a survey are only as strong

as the questions asked—GIGO (Garbage in, Garbage out).− Keep it simple, brief, and neutral.− Don’t use leading questions or double

negatives.− Be specific.− Avoid open ended questions

People can skew survey results.

Examples

BAD:− Do you feel sad sometimes?− Wouldn’t you like to take a pill to make

you smarter? BETTER:

− How many days per week do you feel sad?

− Do you support the use of cognitive-enhancing drugs? Y/N

Discussion & Journal Writing