1 Boring Old Man

In my last post, I tried to synopsize the first two of Brain Resource‘s products – brain training and clinician support tools built from web-based instruments. Now its time to move up several notches to their third product[s] which they gather under the heading research solutions. In this instance, we’ll have to move beyond the confines of their Brain Resource web site which only outlines their iSPOT, Pharmaceutical Trials, and Discovery Science product offerings [some of which are works in progress] – moving to journal articles and clinical trials to flesh out the details.

In this case, the research is on the part of Brain Resource themselves. They’ve initiated two large clinical trials  whose aim is to discover biomarkers that will predict treatment response by casting a very wide net – adding  brain imaging,  genetic testing, electrophysiological testing, and some of the more traditional rating scales to their own proprietary brand of assessment. The link to Personalized Medicine is that they hope to predict medication choices by advance screening. I mentioned this enterprise earlier [poking holes…], but I wasn’t really up to speed so I’m going to begin by repeating what I showed earlier from their web site:

International Study to Predict Optimized Treatment Response (iSPOT) – in depression and ADHD iSPOT is the largest current Personalized Medicine research study in mental health with the potential to change the way we treat depression and ADHD. At present there  is no way to objectively select the correct antidepressant medication to be prescribed in the first instance. Using all the methodology in the picture below, in a standardized manner, iSPOT is assessing  which brain and body markers can predict the right medication for the right person at the right time. This will help to personalize treatment in depression and ADHD. Translational – clinicians will have less trial and error and more objectivity in selecting the right treatment.

Currently, there are two Clinical Trials underway for iSPOT:
• iSPOT-A relates to kids with ADHD treated with Ritalin. The Primary Outcome Measure is "to determine whether the genetic-brain-cognition function markers (or combination of markers) ‘normalise’ with acute drug treatment in ADHD [6 weeks]." The Secondary Outcome Measure is "to determine whether markers of acute treatment prediction are also predictive of functional outcome over 6-12 months."
• iSPOT-D is an adult study with three groups with MDD treated with Celexa, Zoloft, or Effexor, and a group of healthy controls. The Primary Outcome Measure is "to determine whether the genetic-brain-cognition function markers (or combination of markers) ‘normalise’ with acute drug treatment in MDD [8 weeks]." The Secondary Outcome Measure is "to determine whether markers of acute treatment prediction are also predictive of functional outcome over 6-12 months." They’ve written-up the iSPOT-D study protocol:
International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: rationale and protocol.
by Williams LM, Rush AJ, Koslow SH, Wisniewski SR, Cooper NJ, Nemeroff CB, Schatzberg AF, Gordon E.
Trials. 2011 Jan 5;12:4.
This article is available in full text on the Internet and worth a look to see the impressive list of things they’re measuring looking for "markers" [including all the Brain Resource proprietary tests].

Brain Resource, besides running its own clinical trials [iSPOT-A and iSPOT-D] has developed some instruments for use in drug trials by others.

• The Matrics Consensus Cognitive Battery is a set if psychometrics developed by the NIMH for measuring cognitive improvement in drug trials in Schizophrenia. Brain Resource has developed an alternative that does not require a trained psychometrist using a touch-sensitive screen they call IntegNeuro for Cognitive Impairment Associated with Schizophrenia [CIAS].

• Risk Assessment for Convulsions: Brain Resources is involved in searching for predictive Biomarkers. In this case, they have three categories:
^{1. "There are 3 measures of EEG activity that have been shown to reflect brain instability and the potential for epileptiform phenomena. The first measure of Brain instability is reflected in quantitative EEG variability from epoch to epoch across a selected recording period. A second measure reflects the ‘peakiness’ of Alpha activity sharpening and the increase in ‘peakiness’ of Theta activity. Alpha sharpening has been shown to predict Grand Mal Epilepsy and Theta sharpening can result in Petit Mal Epilepsy. The third measure concerns overall EEG brain stability."}
^{2. "Brain Resource owns the IP to fit the model parameters to individual subjects. In essence, the model considers the excitatory gain in the cortex (the Ge parameter) in the EEG Biophysical Model, as well asthalamo-cortical excitation (GeSe parameter). An increase in gain excitation in either the cortex or thalamo-cortex can be considered a marker for potential brain instability, tipping toward convulsive phenomena."}
^{3. "Simultaneous Measure of Arousal and EEG: In Brain Resource’s standardized methodology we simultaneously measure EEGs, heart rate and sweat rate. An increase in Arousal reflects an excitatory drift, and the extent of this excitatory gain can act as a global marker for the risk of brain instability."}
Their idea is to use these Biomarkers in drug trials to determine a drug’s risk for brain instability.
^{"The use of the above Biomarkers can be complimented with the use of insights obtained from our database … which is the largest standardized brain database in the world. Using our database, we can determine the variance for each of these Markers particular to each age range in which the compound is being assessed… This frame of reference allows us to determine the extent of change .. that may indicate a threshold for risk for brain instability for your compound."}
• Integrative Platform for New Drug Discovery: This is the big one and explains the reason for their expansive database.

By maintaining "the world’s largest database" of simultaneous measures of brain parameters [genomics, electrical function, blood flow, structure, general cognition, and social cognition] in multiple conditions, they propose to develop Biomarkers associated with these conditions. The idea is to give a new drug and measure all of these parameters, compare it to the database focusing on biomarker profiles of the various conditions, thereby predicting which condition that drug might be used for. In the pdf [slow to load], they describe this process and their various partnerships involved in the process.

And back to Personalized Medicine:

There is another research product they call the Discovery Science option with which the offer their proprietary instruments to non-grant supported and non-profit organizations at "greatly" reduced rates. I’ve digested the information from this option because the pdf’s included in their write-up offer you the best opportunity to look at the various products one at a time – particularly the non-questionnaire options [LabNeuro, MRI-Neuro, and Molecular-Neuro]. Unless I missed something along the way, I think this is the finale – the last of the Brain Resource products.

The Discovery Science offering grants independent researchers special access to the Brain Resource methodology at greatly reduced rates: Researchers performing academic research aimed at scientific publication and Independent, not for profit Researchers. Services include: access to standardized Brain Resource testing software; rapid scoring of data; and delivery of datasets in comma-delimited format at 3 monthly intervals. • Screening Questionnaires [PDF 100kb]:     BRISC: web-based questionnaire assessment of emotional cognition.     WebQ: set of 22 web-based demographics questionnaires. • General and Emotional Cognition [PDF 107kb]:     WebNeuro [PDF 266kb] : web-based assessments of general and emotional cognition.     IntegNeuro [PDF 254kb]: automated touchscreen neuropsychological tests. • Brain-Body Functions [PDF 104kb]:     LabNeuro [PDF 259kb]: lab-based assessment including psychophysiology [EEG, ERPs, autonomic measures and neuropsychological test batteries]. • MRI, fMRI and DTI [PDF 102kb]:     MRI-Neuro: structural and functional MRI • Genetics [PDF 118kb]:     Molecular-Neuro: collection via cheek swab or saliva method [and in some cases bloods] of DNA for extraction of SNPs and other variants of interest. BRAINnet is an independent foundation set up to provide free access to data in the International Database that Brain Resource has permission to share for the purposes of collaborative research. As a member of BRAINnet, an independent researcher may apply for access to normative data. It is comparable data because it has been collected and scored in exactly the same way as your own Discovery project.

Yet another note from the ghost in the machine: It’s me again. In-so-far as I am capable, this summary of Brain Resource is accurate. I told you it was going to pick up steam. I’ve changed some of the graphics to fit your screen [like they do in the movies] and I’ve condensed some of their descriptions. If any meanings got changed in the process, I apologize. That was not my intent. So now I’m going to stop being a ghost and come back as my regular old self…