In year one, we focused on development activities to support a ground-based neuroimaging study of depression. This included development and testing of sensitive tasks for brain function assessment, optimizing neuroimaging protocols, and creating integrated stimulus display and data acquisition systems to enable continuous monitoring of complex bimanual inputs from our study participants during task performance. We also integrated with Dr. James Cartriene's clinical trial of his computer based problem solving therapy for depression. These efforts were designed to generate a rich dataset to quantify the performance effects of a stressor (depression) on neural activity and during complex cognitive-motor performance tasks. In year two, we began our neuroimaging data collection, and also focused on NIN technology development. We completed a second generation NIN prototype device and successfully tested it both in the laboratory and during a parabolic flight for sensitivity to brain hemodynamics. In the coming year, we plan to complete the neuroimaging of depressed participants, and will continue to advance the capabilities for NIN in mobile and spaceflight environments.

If successful, these activities are expected to have two primary impacts. First, identification of brain-based biomarkers for depression will move the countermeasure readiness level (CRL) of brain-based evaluation of depression from CRL 2 to CRL 3. Once depression is objectively identified, there are already suitable depression countermeasures available for deployment in flight (including medications and psychological consults), plus Dr. Cartriene's computer-based therapy in development. Identification of brain based biomarkers would be useful not only in spaceflight, but for the millions of individuals suffering from depression on Earth, by providing a more objective and potentially more readily accessible method for evaluating depression. Second, our technology development efforts have already moved the technology readiness level (TRL) of near-infrared neuroimaging to TRL 5 and we are expecting to reach TRL 6 with coming advances and studies. Our use of relatively inexpensive and unobtrusive NIN technology will enable brain imaging and monitoring not only during spaceflight, but also in a variety of Earth-based contexts including in-office neuroimaging, rural areas, and even under-served communities or first-responder contexts.

1. Depression Biomarkers: We seek to identify biomarkers that are suitable for (i) depression diagnosis, and (ii) assessing depression severity. If a reliable NIN-based biomarker is identified, this would provide initial validation of the lower cost NIN-based evaluation of depressed individuals. Such brain-based biomarkers could then be measured in an office setting and at relatively low cost, thereby enabling access to such capabilities in broader regions than currently possible, including rural or underserved communities. 2. Mobile Neuroimaging: Developing appropriate technologies can enable neuroimaging in mobile environments, including spaceflight analogs and spaceflight itself. Such technologies have the potential to impact a wide range of novel brain monitoring applications on Earth as well, ranging from mobile epilepsy monitoring, to monitoring treatment efficacy via brain imaging in a doctor's office, to battlefield or first-responder head trauma evaluations, as well as generally more available, less expensive methods for diagnosing, monitoring, and treating depression or other disorders involving alterations in brain function. NIN is of particular promise as a brain imaging technology as it is sufficiently low-cost, robust and portable to be made readily available in diverse operational environments including urban, rural, and remote settings.

On the computational front, we completed three major subtasks, including (1) developing software for advanced artifact filtering of NIN data (via an NSBRI-funded student project supporting Mr. Neil Parikh), (2) initial development of software for integrated near-infrared neuroimaging data analysis and display (and an associated peer-reviewed publication), and (3) 18,000 hours of computer processing time to generate models of the distribution of photons migrating through the head from each of 3,555 separate injection points (5mm spacing) around the entire scalp. The simulation data provide by far the most detailed maps of brain sensitivity available for NIN measurements. Together, these three accomplishments will enable significantly more accurate and more automated NIN data recording, analysis and display.

On the device development front, we achieved two major milestones regarding lightweight, mobile recording devices. First, on December 23, 2008, we successfully collected data from the brain using our newest portable near-infrared neuroimaging (NIN) instrument, OpticHolter version 2a. This wearable device provides up to four optical and four electrophysiological recording channels (ECG, respiration and two accelerometer channels), all in a package that weighs under 350 grams. Second, on June 21, 2009, we were able to successfully test our OpticHolter 2a device for synchronous recording of NIN-based hemodynamics, ECG, respiration and dual-axis accelerometry during a ZeroG parabolic flight. Clear changes in cardiac activity, respiration and hemodynamic fluctuations measured from the head were recorded, and all of these parameters demonstrated changes associated with the gravitational transitions generated by the aircraft flight pattern. These efforts strongly support the goal of developing technologies suitable for brain imaging in spaceflight.

Aviat Space Environ Med. 2009 Mar;80(3):287. , Mar-2009

Aviat Space Environ Med. 2009 Mar;80(3):287. , Mar-2009

In our first year, we have focused on development activities to support our ground-based neuroimaging in depression study. This has included development and testing of novel tasks for the brain function assessments, novel scanning protocols, and prototype, integrated stimulus display and data acquisition systems to enable continuous monitoring of complex bimanual inputs from our study participants during task performance. Progress has also involved integration with Dr. James Carter's clinical trial of his CB-PST therapy. These efforts will allow us to acquire a rich dataset to quantify the performance effects of a stressor (depression) on neural activity and during complex cognitive-motor performance tasks. In the coming year, we plan to both initiate and complete the neuroimaging of depressed participants, in concert with Dr. James Carter's NSBRI-funded clinical trial of CB-PST therapy.

1. Depression Biomarkers: We hope to identify biomarkers for (i) depression diagnosis, (ii) depression severity, and (iii) response to treatment. If a valid NIN-based biomarker is identified, this would provide initial validation of (lower cost) NIN-based evaluation of depression-related brain alterations.

2. Potential Biomarkers for Treatment-Resistant Phenotypes: We anticipate also identifying biomarkers suited for detecting a treatment-resistant endophenotype. This could be helpful for treatment planning on Earth, as well as helping understand the neural mechanisms underlying depression.

3. Countermeasure Evaluation: As part of this study, we will test the treatment efficacy of CB-PST for minor depression. Given the prevalence of depression, competitively tested therapies could also substantially reduce suffering and financial costs on Earth associated with treatments of depression. 4. Mobile Neuroimaging: Developing appropriate technologies can enable neuroimaging in mobile environments, including spaceflight analogs and spaceflight itself. Such technologies have the potential to impact a wide range of novel brain monitoring applications on Earth as well, ranging from mobile epilepsy monitoring, to monitoring treatment efficacy via brain imaging in a doctor’s office, to battlefield or first-responder head trauma evaluations, as well as generally more available, less expensive methods for diagnosing, monitoring, and treating depression or other disorders involving brain function alterations. NIN is of particular promise as a brain imaging technology as it is sufficiently low-cost, robust and portable to be made readily available in diverse operational environments including urban, rural, and remote settings.

Mission success can be jeopardized by depression either directly from the potentially life-threatening consequences of lapses in performance, or indirectly by adding to the workload and stress of other crewmembers. The likelihood and potentially serious consequences of depression during spaceflight explains why Bioastronautics Roadmap Risk number 25 namely, human performance failure due to mood alterations such as depression, anxiety or other psychiatric and cognitive problems is a top-priority risk for all mission types (International Space Station, Moon, Mars). Countermeasures are already in place via medications and psychological consultations with ground crews. However, current inflight methods to decide whether a countermeasure should be used depend heavily on subjective self-reports.

The biological basis of mood disorders suggests neural biomarkers may provide a more objective method for assessing depression. Therefore, the first aim of this project seeks to identify neural biomarkers sensitive to, and specific for, depression. These measures will be used in evaluating and validating a flight-capable, noninvasive neuroimaging technology (near-infrared spectroscopy and imaging, or NIRS imaging) for its ability to detect biomarkers of depression and its severity.

As an initial step toward developing novel select-out criteria, aim two will then evaluate which neural biomarkers appear most promising in detecting an endophenotype that identifies individuals at heightened risk for treatment resistance. Finally, when depression is objectively identified, an appropriate countermeasure needs to be selected.

Aim three will therefore focus on evaluating countermeasure efficacy via a randomized controlled trial comparing the NSBRI-funded computer-based problem-solving therapy (CB-PST) with pharmacotherapy currently available inflight.