Patrick G. A. Oomen, Charlotte S. Hakkers, Joop E. Arends, Guido E. L. van der Berk, Pascal Pas, Andy I. M. Hoepelman, Berend J. van Welzen, Stefan du Plessis
{"title":"艾滋病病毒感染者停用依非韦伦后前纹状体反应抑制认知改善的潜在神经机制：随机对照 BOLD fMRI 试验","authors":"Patrick G. A. Oomen, Charlotte S. Hakkers, Joop E. Arends, Guido E. L. van der Berk, Pascal Pas, Andy I. M. Hoepelman, Berend J. van Welzen, Stefan du Plessis","doi":"10.1007/s40121-024-00966-7","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>It is unclear whether neurotoxicity due to the antiretroviral drug efavirenz (EFV) results in neurocognitive impairment in people living with HIV (PLWH). Previously, we found that discontinuing EFV was associated with improved processing speed and attention on neuropsychological assessment. In this imaging study, we investigate potential neural mechanisms underlying this cognitive improvement using a BOLD fMRI task assessing cortical and subcortical functioning.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Asymptomatic adult PLWH stable on emtricitabine/tenofovirdisoproxil/efavirenz were randomly (1:2) assigned to continue their regimen (<i>n</i> = 12) or to switch to emtricitabine/tenofovirdisoproxil/rilpivirine (<i>n</i> = 28). At baseline and after 12 weeks, both groups performed the Stop-Signal Anticipation Task, which tests reactive and proactive inhibition (indicative of subcortical and cortical functioning, respectively), involving executive functioning, working memory, and attention. Behavior and BOLD fMRI activation levels related to processing speed and attention Z-scores were assessed in 17 pre-defined brain regions.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Both groups had comparable patient and clinical characteristics. Reactive inhibition behavioral responses improved for both groups on week 12, with other responses unchanged. Between-group activation did not differ significantly. For reactive inhibition, positive Pearson coefficients were observed for the change in BOLD fMRI activation levels and change in processing speed and attention Z-scores in all 17 regions in participants switched to emtricitabine/tenofovir disoproxil/rilpivirine, whereas in the control group, negative correlation coefficients were observed in 10/17 and 13/17 regions, respectively. No differential pattern was observed for proactive inhibition.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Potential neural mechanisms underlying cognitive improvement after discontinuing EFV in PLWH were found in subcortical functioning, with our findings suggesting that EFV’s effect on attention and processing speed is, at least partially, mediated by reactive inhibition.</p><h3 data-test=\"abstract-sub-heading\">Trial Registration</h3><p>Clinicaltrials.gov identifier [NCT02308332].</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Underlying Neural Mechanisms of Cognitive Improvement in Fronto-striatal Response Inhibition in People Living with HIV Switching Off Efavirenz: A Randomized Controlled BOLD fMRI Trial\",\"authors\":\"Patrick G. 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In this imaging study, we investigate potential neural mechanisms underlying this cognitive improvement using a BOLD fMRI task assessing cortical and subcortical functioning.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>Asymptomatic adult PLWH stable on emtricitabine/tenofovirdisoproxil/efavirenz were randomly (1:2) assigned to continue their regimen (<i>n</i> = 12) or to switch to emtricitabine/tenofovirdisoproxil/rilpivirine (<i>n</i> = 28). At baseline and after 12 weeks, both groups performed the Stop-Signal Anticipation Task, which tests reactive and proactive inhibition (indicative of subcortical and cortical functioning, respectively), involving executive functioning, working memory, and attention. Behavior and BOLD fMRI activation levels related to processing speed and attention Z-scores were assessed in 17 pre-defined brain regions.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>Both groups had comparable patient and clinical characteristics. Reactive inhibition behavioral responses improved for both groups on week 12, with other responses unchanged. Between-group activation did not differ significantly. For reactive inhibition, positive Pearson coefficients were observed for the change in BOLD fMRI activation levels and change in processing speed and attention Z-scores in all 17 regions in participants switched to emtricitabine/tenofovir disoproxil/rilpivirine, whereas in the control group, negative correlation coefficients were observed in 10/17 and 13/17 regions, respectively. 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Underlying Neural Mechanisms of Cognitive Improvement in Fronto-striatal Response Inhibition in People Living with HIV Switching Off Efavirenz: A Randomized Controlled BOLD fMRI Trial
Introduction
It is unclear whether neurotoxicity due to the antiretroviral drug efavirenz (EFV) results in neurocognitive impairment in people living with HIV (PLWH). Previously, we found that discontinuing EFV was associated with improved processing speed and attention on neuropsychological assessment. In this imaging study, we investigate potential neural mechanisms underlying this cognitive improvement using a BOLD fMRI task assessing cortical and subcortical functioning.
Methods
Asymptomatic adult PLWH stable on emtricitabine/tenofovirdisoproxil/efavirenz were randomly (1:2) assigned to continue their regimen (n = 12) or to switch to emtricitabine/tenofovirdisoproxil/rilpivirine (n = 28). At baseline and after 12 weeks, both groups performed the Stop-Signal Anticipation Task, which tests reactive and proactive inhibition (indicative of subcortical and cortical functioning, respectively), involving executive functioning, working memory, and attention. Behavior and BOLD fMRI activation levels related to processing speed and attention Z-scores were assessed in 17 pre-defined brain regions.
Results
Both groups had comparable patient and clinical characteristics. Reactive inhibition behavioral responses improved for both groups on week 12, with other responses unchanged. Between-group activation did not differ significantly. For reactive inhibition, positive Pearson coefficients were observed for the change in BOLD fMRI activation levels and change in processing speed and attention Z-scores in all 17 regions in participants switched to emtricitabine/tenofovir disoproxil/rilpivirine, whereas in the control group, negative correlation coefficients were observed in 10/17 and 13/17 regions, respectively. No differential pattern was observed for proactive inhibition.
Conclusion
Potential neural mechanisms underlying cognitive improvement after discontinuing EFV in PLWH were found in subcortical functioning, with our findings suggesting that EFV’s effect on attention and processing speed is, at least partially, mediated by reactive inhibition.
期刊介绍：
Infectious Diseases and Therapy is an international, open access, peer-reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of infectious disease therapies and interventions, including vaccines and devices. Studies relating to diagnostic products and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
Areas of focus include, but are not limited to, bacterial and fungal infections, viral infections (including HIV/AIDS and hepatitis), parasitological diseases, tuberculosis and other mycobacterial diseases, vaccinations and other interventions, and drug-resistance, chronic infections, epidemiology and tropical, emergent, pediatric, dermal and sexually-transmitted diseases.
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