Neurovascular Coupling Response to Cognitive Challenges in Gulf War Veterans

Gulf War Illness (GWI) is a multi-symptom disease in Gulf War Veterans associated with cognitive complaints, fatigue, and muscular pain. Neurovascular coupling (NVC) reflects the increase in blood flow in response to elevations in neural activity, and NVC is often diminished in individuals with cognitive impairment. Yet, it remains unclear whether Veterans with GWI have impaired NVC compared to deployment-matched Veterans without GWI. The purpose of this study is to determine whether NVC during acute cognitive challenges is altered in Veterans with GWI. We hypothesized that individuals with GWI would have lower NVC in response to cognitive challenges. This study included30 individuals who served in the Gulf War(60 ± 4 years; 25 males, 5 females). Based on results from the Kansas Case Definition questionnaire, participants were classified as negative for GWI research diagnosis (GWI-; n = 12) or positive for GWI research diagnosis (GWI+; n = 18). After instrumentation, participants underwent baseline recordings, followed by two cognitive challenges (Stroop Color Test and N-back Memory Test). Testing order was randomized, and tests were separated by a washout period. NVC was assessed via mean middle cerebral artery blood velocity (MCAv) which was continuously recorded. In addition, continuous beat-to-beat blood pressure (BP) and heart rate were collected. Mean arterial pressure (MAP) and cerebrovascular conductance index (CVCi) were also calculated. MCAv increased in response to the Stroop test from BSL in both GWI- (BSL: 49 ± 10 vs Stroop: 52 ± 11 cm/s; P < 0.05) and GWI+ (BSL: 48 ± 10 vs Stroop: 52 ± 11 cm/s; P < 0.01). MAP also increased from BSL in both GWI- (BSL: 94 ± 12 vs Stroop: 98 ± 12 mmHg; P < 0.01) and GWI+ (BSL: 98 ± 10 vs Stroop: 102 ± 12 mmHg; P < 0.01), while CVCi was unchanged from BSL in GWI- (BSL: 0.54 ± 0.14 vs Stroop: 0.54 ± 0.12 cm/s/mmHg; P = 0.68) but increased in GWI+ (BSL: 0.50 ± 0.12 vs Stroop: 0.52 ± 0.13 cm/s/mmHg; P < 0.05). There was, however, no difference in MCAv percent change with the Stroop test between GWI- and GWI+ (6 ± 7% vs 8 ± 6%, respectively; P = 0.55). Similarly, no group differences were observed for percent change in MAP (GWI-: 5 ± 4% vs GWI+: 4 ± 6%; P = 0.83) or CVCi (GWI-: 2 ± 7% vs GWI+: 4 ± 7%; P=0.42). The N-back test increased MCAv from BSL in both GWI- (BSL: 50 ± 9 vs N-back: 54 ± 12 cm/s; P < 0.01) and GWI+ (BSL: 49 ± 10 vs N-back: 53 ± 11 cm/s; P < 0.01). MAP increased from BSL in GWI- (BSL: 95 ± 10 vs N-back: 99 ± 10 mmHg; P <0.01) as well as GWI+ (BSL: 98 ± 9 vs N-back: 100 ± 10 mmHg; P < 0.01). CVCi also increased from BSL in GWI- (BSL: 0.53 ± 0.12 vs N-back: 0.55 ± 0.14 cm/s/mmHg; P < 0.05) and in GWI+ (BSL: 0.51 ± 0.12 vs N-back: 0.54 ± 0.13 cm/s/mmHg; P < 0.01). There was no difference in MCAv percent change to the N-back test between GWI- and GWI+ (9 ± 7% vs 8 ± 5%, respectively; P = 0.72) and no group differences were observed for percent change in MAP (GWI-: 5 ± 3% vs GWI+: 3 ± 3%; P = 0.23) or CVCi (GWI-: 4 ± 4% vs GWI+: 5 ± 5%; P = 0.65). GWI classification was not associated with reduced NVC or altered hemodynamic responses during acute cognitive challenges. These results suggest that, even though cognitive complaints are common in GWI, the blood velocity responses to acute cognitive challenges do not seem to be impaired in GWI+ Veterans. Future studies could address other potential mechanisms underlying the cognitive complaints in GWI. Department of Defense 19-1-0381, National Institutes of Health T32HL007936 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.