Directing Attention in Serious Games

Eye-movement and attention are important parameters that developers of serious games should be considering in their designs.  Below is information relating to a series of papers and articles discussing these concepts.

Dr. Li Zhaoping provides a page with links to a set of articles discussing the V1 Saliency Hypothesis and Related Experiments

Some of her paper titles include:

• Attention capture by eye of origin singletons even without awareness — a hallmark of a bottom-up saliency map in the primary visual cortex
• Popout by unique eye of origin: A fingerprint of the role of primary visual cortex in bottom-up saliency
• Feature-specific interactions in salience from combined feature contrasts: Evidence for a bottom-up saliency map in V1.
• A theory of a saliency map in primary visual cortex (V1) tested by psychophysics of color-orientation interference in texture segmentation.
• Relative contributions of 2D and 3D cues in a texture segmentation task, implications for the roles of striate and extrastriate cortex in attentional selection

Example Request For Proposal (Past EEG Drug Studies): Pfizer Examines EEG Methods For Pharmaceutical Development

An excerpt of the RFP from Pfizer Website is given below in italics illustrating their interest in using EEG methods for improving drug development.(http://www.pfizer.com/b2b/translational_medicine/neurosciences_es.jsp)

Neurosciences — Request for Proposals (RFP) Executive Summary

Problem

EEG BIOMARKERS OF CENTRAL PHARMACODYNAMIC ACTIVITY AND EFFICACY IN ADHD, SCHIZOPHRENIA AND ALZHEIMER’S DISEASE

Problem Statement

To determine whether EEG and evoked potential biomarkers for neurology, psychiatry, pain or urogenital indications can be used in either healthy volunteers and/or patient populations to demonstrate centrally mediated pharmacological activity and to provide evidence of early efficacy.

In order to improve confidence in the activity of exploratory CNS drugs, it is critical to establish centrally mediated pharmacodynamic activity in humans. In the absence of a PET ligand or clearly linked physiological response, the demonstration of central binding and subsequent activity is particularly challenging. Pfizer research has invested substantially in the use of spontaneous EEG, evoked potential and sleep endpoints as a means to assess central pharmacology. However, the ability to translate these endpoints to healthy volunteer or small Phase IIa patient studies remains unclear. In addition, because of the lack of well-developed pharmacology biomarkers suitable for a healthy volunteer population, the learning extracted from Phase 1 studies with respect to PK/PD properties of compounds and mechanisms is usually limited. As a result, drugs progressing through the pipeline enter late stage development with a less-than-optimal pharmacological knowledge. Furthermore, the opportunities to improve upon a backup candidate’s profile based on rapid learning from the clinic is limited.

It has been demonstrated for various central mechanisms (for example opiate receptor agonists, stimulants and GABA receptor modulators) that exposure-EEG response data in healthy volunteers may provide early signposts of potential issues with respect to time course of effect (i.e. required exposure levels for efficacy, onset, offset, toleration, active metabolites), which can subsequently be managed in a more proactive and rapid manner than currently is the case. In addition, various evoked potential paradigms such as miss-matched negativity in schizophrenics, cognitive dysfunction in early Alzheimer’s disease or EEG paradigms of urinary incontinence, may serve as useful tools to assess efficacy in humans where preclinical models are less than optimal.

Registry of publicly and privately supported clinical trials going on in the United States and around the world

ClinicalTrials.gov provides information about a trial’s purpose, who may participate, locations, and phone numbers for more details.

Had They Used Brain Imaging Methods, Application of Dimebon For Alzheimer’s Treatment Might Have Been Discovered years Ago

WebMD Health News: Used for Decades as an Allergy Drug, Dimebon now Shows Promise in Treating Alzheimer’s Patients, Salynn Boyles. An article describing that a drug that has existed for many years used to treat one health issue may be effective as a therapy for CNS diseases.  Could MOST-EEG be used by drug developers to make such discoveries sooner?  An excerpt from their website is given in italics below.

April 17, 2008 — A nearly forgotten allergy drug first used in Russia more than two decades ago is showing promise for the treatment of Alzheimer’s disease.

In a study of the antihistamine Dimebon, Alzheimer’s patients with mild to moderate disease continued to show improvements in memory, thinking, and daily and overall functioning over six months of treatment.

Some patients showed improvements when treated for up to a year.

Results from the Russian study were presented this week at the 60th annual meeting of the American Academy of Neurology (AAN) in Chicago. Study results were also reported last summer at an international conference on Alzheimer’s disease.

Articles and Web Resources Discussing EEG and Pharmaceutical Development

Pharmafocusasia: Accelerating Central Nervous System Trials: Neurophysiological approaches (opens new window).  An article describing how the time required for Central Nervous System Drug Trials can be shortened using EEG methods.  An excerpt from their website is given in italics below.

The reasons are many as to why CNS drugs are more difficult to develop successfully, namely the sheer complexity of the brain; the presence of CNS-mediated side effects such as nausea, dizziness and seizures; the need for agents to pass the blood-brain barrier; and the lack of validated biomarkers. Yet, with the implementation of targeted strategies, it may be possible to identify more quickly and with greater accuracy those therapeutics agents with the most promise, leading to better GO / NO-GO decisions.

This article focuses on selected techniques that can be used early on, following preclinical work, to launch Phase I studies that determine if compounds are entering the brain, and how this action may be impacted by dose ranging. These techniques are the routine Electroencephalogram (EEG), the Quantitative Electroencephalogram (QEEG) and Evoked Potential (EP). They can be used as tools for translating preclinical findings into first-in-human studies. They may also play a role in later phase studies when compounds shift from being studied in healthy volunteers to CNS patients.

Elsevier, Drug Discovery Today: Technologies:  Imaging technologies in drug development: Anxiety and depression, Eugenii A. Rabiner (opens new window). An journal article describing the positive application of  imaging methods in drug development for treating anxiety and depression

Related Organizations

CNS Response: www.cnsresponse.com CNS Response is an organization that uses EEG methods to tailor central nervous system drug therapy programs to individuals. An excerpt from their website is given below in italics.

One in four people will suffer a diagnosable mental illness in a given year. And when that happens, physicians have over 130 psychotropic drugs from which to choose, no objective guidelines such as x-rays or blood tests, and only subjective, patient-reported symptoms upon which to prescribe treatment. Unfortunately, the dominant approach to prescribing in psychiatry is trial and error medicine. It’s no surprise then that treatment failures in disorders like depression range from 40 to 60 percent.

“CNS Response has discovered biomarkers which predict the probable effectiveness of specific drugs based on the unique electrical signature of a patient’s brain. These markers aren’t used to diagnose, but to specifically guide treatment. Some call it personalized medicine.”

We call it Referenced-EEG®, a patented process which has helped thousands of patients. In a series of clinical trials on patients who suffered for years without responding to treatment, physicians guided over 75 percent of them to medications that worked. Often the right medication was a novel combination of two medications. And sometimes, the right answer was no medication at all. rEEG® provides physicians with objective clinical data to guide treatment based on patient physiology. Physicians using rEEG get superior efficacy in less time with fewer medications.