Collaborations Drug Testing
CM technology is currently being used in multiple studies to evaluate the efficacy of pharmacological interventions in several different neurological disorders. Previous studies have demonstrated sensitivity of the method to drug effects. In one study (Folger et al, 2008), we investigated the effects of a low dosage of dextromethorphan (60 mg of DXM; over-the counter cough syrup), an NMDAR antagonist, to observe if it had an impact on an individual’s performance. The significance of that study was that while the drug had no significant effect on discriminative measures that are predominantly mediated by peripheral factors, the adaptation metrics were significantly impacted. Over a 3 hour time course, the low dose of cough syrup caused the adaptation metrics to deviate from normative values and returned to baseline. Thus, this demonstrated that the adaptation metric is a sensitive reflection of central information processing, and the sensitivity far exceeds any metrics that can be obtained by modern medical imaging techniques.
Comparison of difference limen (DL; with s.e. bars) between the Control and DXM groups for amplitude discrimination with single-site adaptation at times T0, T1, and T2. No adapting stimulus was applied to either stimulus site in Block 1, and no difference was observed between the two groups at any time for Block 1. The test condition in Block 2 was preceded by an adapting stimulus (1 sec in duration) at the site of the test stimulus. Note that at T1, in Block 2, performance between the groups was significantly different (* ANOVA; p < 0.01). At T2, Block 2 performance values for the DXM group return to baseline levels (p = 0.092).
Impact of medications in the elderly: In a pilot study, we collected data from 20 adults, age range 65-78. 12 of those subjects were essentially medication-free and of those 12, 8 had results that were quite comparable to the data obtained for subjects under the age of 65. (One of the 4 subjects whose date was not comparable to controls was later diagnosed with a mild form of dementia, two of the 4 had fibromyalgia, and another had Parkinson’s). However, 6 subjects had been treated for high blood pressure for 3 or more months, and their data was significantly different from that of the control group. Note that in the graph below, a comparison of data obtained from the two populations between metrics is shown for both discrimination capacity and for adaptation. Although the impact on discriminative capacity in the medicated group is relatively insignificant, the impact of medications on the adaptation metric in this group appears quite significant. One goal of ongoing research is to determine the impact that commonly prescribed medications have on cortical information processing.
Comparison of medicated vs. non- medicated elderly subjects: Note that discrimination capacity is moderately, though not signficantly reduced in the medicated population. The adaptation metric for this population, however, is signficantly impacted. Lower discrimination values indicate that subjects are better at discrimination. Higher values for the adaptation task indicate that subjects adapted more - i.e., low values are markers of poor brain health. In general, the critical value is the difference between an individuals adaptation metric and their disrimination metric - the bigger the difference, the better.
Positive impact of medications: In the plot above, two subjects were given a pharmacological treatment (vulvodynia and autism patients were administered a GABA agonist and citalopram, respectively). The patient with alcoholism was tested at initial sobriety and after twelve weeks of sobriety (during which time he was also administered baclofen, a GABAb agonist). The concussed subject data is a comparison of 3 day and 7 day post--concussion (no drugs administered). Thus, observations such as this one – even though it is non-specific (appears to be sensitive to disruptions caused by a wide spectrum of disorders), have the potential for aiding clinicians with assessing treatment efficacy of multiple neurological disorders.