A debilitating and common cognitive symptom in those with Gulf War Illnesses (GWI) is the inability to retrieve words. This deficit affects one's conversations, the ability to fluidly exchange information verbally, and the ability to retrieve information from memory. Our group has studied the ability to retrieve words using functional neuroimaging (e.g., functional magnetic resonance imaging) and electroencephalography (EEG), and we have discovered three brain regions -- the PreSupplementary Motor Area (preSMA), caudate nucleus, and the thalamus -- that are essential for word retrieval. Additionally, we have detected abnormal EEG signals related to these regions in patients with GWI who have problems retrieving words.

We have used our model of verbal retrieval to design a noninvasive, nonpharmacological treatment that uses High Definition transcranial Direct Current Stimulation (HD tDCS) for those with word retrieval impairments. Using HD tDCS, we are able to deliver small amounts of electric current to specific regions of the head to stimulate the brain regions underlying that electrode location. In particular, we have been able to stimulate the preSMA in multiple sclerosis patients with word retrieval deficits. Following 10 days of stimulation, these patients have had significant improvement in their verbal retrieval that has lasted in some individuals as long as 6 months (last time point we have tested to date in our first patient).

The objective of this proposal is to identify patients with GWI who have a verbal retrieval deficit and determine if delivery of HD tDCS over the preSMA will improve performance in verbal retrieval-related tasks. We will recruit 80 Veterans with possible GWI and administer pre-treatment tests of verbal retrieval measures (assessing finding words, naming of objects, memory of the names of items in a list) while we record brain electrical activity. We will then administer 10 sessions of HD tDCS over the preSMA (20 minutes a session) in half the Veterans, and the other half of the Veterans will go through the same procedures, except the current will not be turned on (called the sham condition). As there is nothing a person feels when the current is on, these subjects will not know whether they are receiving the current or not. We will then compare performance between the "active" group receiving the HD tDCS and the sham group by performing the same tests of verbal retrieval that we performed prior to the treatment at 1 week, 3 months, and 6 months after the last treatment session. This will allow for assessing whether the HD tDCS treatment had a significant effect on performing verbal retrieval tasks and determine if there is a change in the ERP markers to account for how this treatment worked. Additionally, if the treatment is found to be effective, it will be offered to members of the sham group at the end of the study.

At the conclusion of this study, the effectiveness of HD tDCS for improving verbal retrieval will be established, and we will determine if this treatment significantly changes not only performance on neuropsychological tests but also has a positive effect on a person's day-to-day functions. We predict that this treatment regimen will improve patients' ability to get their words out in a conversation and remember the words that they want to say, leading to improved skills in both social and work situations. This new treatment for cognitive impairments in GWI has few if any side effects, except for infrequently causing some skin irritation on the scalp at the site of the stimulating electrode. Transcranial DCS systems are relatively low cost and easy to use. By the end of the study, we will have outlined the standard procedures for physicians to easily perform the treatment by creating a manual on how to apply the treatment in a clinical setting. Thus, it will be immediately available to use the treatment in multiple sites if the proposed study demonstrates that it is efficacious. This treatment can be made widely available for Warrior Transition Units, military clinics, and Department of Veterans Affairs medical centers with the purchase of the tDCS equipment, which can be used over and over across patients after cleaning following administration. In addition, if successful, this could potentially lead to development of other targets of stimulation to improve other cognitive deficits in GWI and help alleviate verbal fluency deficits associated with other disorders.