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4 Resting State Functional Connectivity Impairments Implicate CNS Mechanisms Underlying Chronic Pain and Depression in Gulf War Veterans’ Illness
- Gabriell C Champion, Aliyah M Auerbach, Nayana Ambardekar, Thomas Novak, Anna Woodbury, Sheila A Rauch, Keith McGregor, Albert Y Leung, Kaundinya S Gopinath
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 518-519
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Objective:
Around 200,000 veterans (up to 32% of those deployed) of the 1991 Gulf War (GW) suffer from GW veterans’ illness (GWVI). GWVI is a poorly understood chronic medical condition, characterized by symptoms indicative of brain function deficits in multiple domains. Among the symptoms of brain impairment GWVI-related chronic headaches and body muscle and joint pain conditions (GWVI-HAP) are the most debilitating, affecting around 64% of the GWVI veterans. Further, depression carries a very high co-morbid rate (>50%) in patients with chronic pain, including GWVI-HAP. In this preliminary study, we examined the integrity of brain function networks in a group of GWI-HAP veterans, with resting state fMRI (rsfMRI).
Participants and Methods:Data from the first twenty-two GWVI-HAP veterans from two ongoing parallel clinical trials was examined. Of these 14 subjects (GWVI-HAP-DM) had mild depression (Hamilton Rating Scale for Depression (HSRD < 13); and 8 subjects (GWVI-HAP-DS) had moderate to severe depression (HSRD > 14). Written informed consent was obtained from all participants in the protocol approved by the local Institutional Review Board. RsfMRI data was acquired on a Siemens 3T Prisma-Fit MRI scanner using a 10-minute whole-brain high resolution simultaneous multi-slice (SMS) gradient echo echo-planar imaging (EPI) sequence: TR/TE/FA = 2.2 sec/ 27 msec/80°, and analyzed with well-established image processing pipelines. Functional connectivity (FC) to different regions implicated in depression and chronic pain was assessed with seed-based correlation analysis. Between group differences in FC were obtained with 2-sample t-tests.
Results:GWVI-HAP-DS group exhibited significantly (p < 0.05) reduced FC compared to GWVI-HAP-DM between frontal lobe (medial (mPFC), and dorsolateral (dlPFC) prefrontal cortex) and the striatum. This indicates that malfunction of fronto-striatal circuits could be a source of the increased chronic pain and depression seen in veterans with GWVI- HAP-DS. Dysregulation of fronto-striatal networks has been implicated in major depressive disorder as well as many chronic pain conditions. In addition, FC between mPFC, and salience network (SN; anterior insula and dorsal anterior cingulate) and limbic (subgenual and ventral anterior cingulate) regions were also reduced in GWVI-HAP-DS. Similarly, mPFC and SN also exhibited reduced FC to pain processing regions (posterior insula, centromedian thalamus and cerebellum). These FC impairments could reflect greater deficits in regulation of and salience attribution to emotions and nociception in the GWVI-HAP-DS group. Finally, GWVI-HAP-DS also exhibited reduced FC between nodes of the default mode network. DMN impairments also have been observed in many depressive and chronic pain conditions.
Conclusions:The results of this preliminary analysis implicate impairments in cognitive control of emotion and nociception as a mechanism underlying the enhanced chronic pain and depression observed in GWVI-HAP veterans, especially those with moderate to severe depression. A fuller picture of deficits in FC in brain function networks is expected to emerge as more GWI-HAP subjects of both groups along with age matched healthy controls are examined in this ongoing project. Better understanding of impairments in these networks in GWI-HAP will benefit the rehabilitation of veterans with GWI-HAP.
19 Exploring GABA Concentration Changes in Sensorimotor Cortex in Older Adults During Motor & Cognitive Performance
- Gabriell Champion, Lisa C Krishnamurthy, Joe R Nocera, Thomas S Novak, Kevin M Mammino, Keith M McGregor
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 332-333
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Objective:
Aging is associated with changes in cortical excitability which may affect motor learning and cognitive function via selective modulation of gamma aminobutyric acid (GABA). Previous studies using magnetic resonance spectroscopy (MRS) to measure GABA in older adults found that increased baseline GABA levels in the sensorimotor cortex (M1S1) were associated with better motor performance. GABA levels in M1S1 have tended to decrease during the execution of a repeated motor sequence. The dynamic change in GABA density in M1S1 in older adults is currently unknown and represents a critical gap in our understanding of how it could impact motor learning and cognitive performance. As such, the purpose of the current study is to quantify changes in cortical GABA during motor learning in the aging brain and examine those changes in relation to motor and cognitive performance. We hypothesize that older adults with greater dynamic range in M1S1 GABA levels will display more efficient motor learning and increased cognitive scores.
Participants and Methods:We report on a total of 18 healthy older adults aged 64 to 80 years (M = 70.44, SD = 4.99, 12 females). Using MRS at 3T, we measured changes in GABA concentration in M1S1 at rest, during an eight or 12 finger-movement motor entrainment task, and during a recall task. Gannett was used for GABA quantification relative to water. Change in GABA was calculated by subtracting Rest1 GABA from Recall1 GABA. In a separate session, participants completed a battery of cognitive assessments. We computed linear regressions to examine the relationship between dynamic GABA change, recall accuracy of the motor task and cognitive performance.
Results:In relation to motor performance, we found that both greater baseline (Rest1) GABA levels and greater dynamic change in GABA significantly predicted better recall accuracy on the motor task. For cognitive performance, we found that greater dynamic change in GABA significantly predicted better performance on Word Reading in the Stroop Color and Word Test and Delayed Recall in the Hopkins Verbal Learning Test (HVLT). No additional significant relationships were found for the remaining cognitive assessments.
Conclusions:Older adults who were able to accurately perform the task had a greater dynamic change in GABA and increased baseline GABA levels. These adults with greater dynamic change also had better cognitive performance on HVLT Delay and Stroop Word Reading. This modulation of GABA associated with better performance could be related to changes in neuroplasticity. Although these results are in the preliminary stages, they point to a greater understanding of aging related changes in motor and cognitive performance. We’ll continue to explore the relationship between sensory motor performance and changes in GABA concentration as a potential predictor for cognitive performance and future rehabilitation.
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