30.2 Network Connectivity Changes Underlying Responses to Trigeminal Nerve Stimulation in ADHD: RCT Results

ObjectivesExternal trigeminal nerve stimulation (TNS) is a noninvasive method of brain modulation that received FDA device clearance in 2019 for treatment of children aged 7 to 12 years with ADHD. Children randomized to active TNS exhibited significantly greater improvements in ADHD symptoms (p < .005) than sham and increased EEG power in the right frontal (F4) and frontal midline (Fz) brain regions. This presentation examines changes in resting-state functional connectivity to more fully characterize the neural mechanisms underlying TNS treatment–related improvements in ADHD.MethodsSixty-two children aged 8 to 12 years with K-SADS–diagnosed ADHD were randomly assigned to 4 weeks of nightly active or sham TNS treatment. The primary outcomes were the clinician-rated ADHD Rating Scale (ADHD-RS) and the Clinical Global Impression (CGI) scales. The secondary outcomes included cognitive measures, weekly ratings of behavioral executive functions (Behavior Rating Inventory of Executive Function [BRIEF]), and EEG measures at pretreatment and posttreatment. Cortical source–level resting-state functional connectivity was estimated from 128-channel EEGs using the groupSIFT program within the EEGLAB data analysis platform.ResultsAfter 4 weeks of treatment, the active TNS group exhibited stronger connectivity between the anterior and posterior nodes of the default mode network (DMN) and lower connectivity between the frontal and medial nodes of the salience and executive control networks than the sham group (p’s range = .004-.008). Lower connectivity among edges involving the right frontal nodes (right insula, right lateral prefrontal cortex) were significantly associated with improved ADHD symptomatology (r’s range = .29-.35; p = .02-.05) at the end of treatment. TNS responders trended toward stronger connectivity within the DMN (p = .06), which correlated with greater improvement in ADHD symptoms (r = .33; p = .03) and better parent-rated executive function (BRIEF working memory [WM] r = -.30; p = .05).ConclusionsThe neural mechanisms underlying the TNS treatment effects in ADHD involve normalization of connectivity within several resting-state networks (DMN, salience, executive control), particularly those involving mid- and right-frontal connections.ADHD, NM, TREAT ObjectivesExternal trigeminal nerve stimulation (TNS) is a noninvasive method of brain modulation that received FDA device clearance in 2019 for treatment of children aged 7 to 12 years with ADHD. Children randomized to active TNS exhibited significantly greater improvements in ADHD symptoms (p < .005) than sham and increased EEG power in the right frontal (F4) and frontal midline (Fz) brain regions. This presentation examines changes in resting-state functional connectivity to more fully characterize the neural mechanisms underlying TNS treatment–related improvements in ADHD. External trigeminal nerve stimulation (TNS) is a noninvasive method of brain modulation that received FDA device clearance in 2019 for treatment of children aged 7 to 12 years with ADHD. Children randomized to active TNS exhibited significantly greater improvements in ADHD symptoms (p < .005) than sham and increased EEG power in the right frontal (F4) and frontal midline (Fz) brain regions. This presentation examines changes in resting-state functional connectivity to more fully characterize the neural mechanisms underlying TNS treatment–related improvements in ADHD. MethodsSixty-two children aged 8 to 12 years with K-SADS–diagnosed ADHD were randomly assigned to 4 weeks of nightly active or sham TNS treatment. The primary outcomes were the clinician-rated ADHD Rating Scale (ADHD-RS) and the Clinical Global Impression (CGI) scales. The secondary outcomes included cognitive measures, weekly ratings of behavioral executive functions (Behavior Rating Inventory of Executive Function [BRIEF]), and EEG measures at pretreatment and posttreatment. Cortical source–level resting-state functional connectivity was estimated from 128-channel EEGs using the groupSIFT program within the EEGLAB data analysis platform. Sixty-two children aged 8 to 12 years with K-SADS–diagnosed ADHD were randomly assigned to 4 weeks of nightly active or sham TNS treatment. The primary outcomes were the clinician-rated ADHD Rating Scale (ADHD-RS) and the Clinical Global Impression (CGI) scales. The secondary outcomes included cognitive measures, weekly ratings of behavioral executive functions (Behavior Rating Inventory of Executive Function [BRIEF]), and EEG measures at pretreatment and posttreatment. Cortical source–level resting-state functional connectivity was estimated from 128-channel EEGs using the groupSIFT program within the EEGLAB data analysis platform. ResultsAfter 4 weeks of treatment, the active TNS group exhibited stronger connectivity between the anterior and posterior nodes of the default mode network (DMN) and lower connectivity between the frontal and medial nodes of the salience and executive control networks than the sham group (p’s range = .004-.008). Lower connectivity among edges involving the right frontal nodes (right insula, right lateral prefrontal cortex) were significantly associated with improved ADHD symptomatology (r’s range = .29-.35; p = .02-.05) at the end of treatment. TNS responders trended toward stronger connectivity within the DMN (p = .06), which correlated with greater improvement in ADHD symptoms (r = .33; p = .03) and better parent-rated executive function (BRIEF working memory [WM] r = -.30; p = .05). After 4 weeks of treatment, the active TNS group exhibited stronger connectivity between the anterior and posterior nodes of the default mode network (DMN) and lower connectivity between the frontal and medial nodes of the salience and executive control networks than the sham group (p’s range = .004-.008). Lower connectivity among edges involving the right frontal nodes (right insula, right lateral prefrontal cortex) were significantly associated with improved ADHD symptomatology (r’s range = .29-.35; p = .02-.05) at the end of treatment. TNS responders trended toward stronger connectivity within the DMN (p = .06), which correlated with greater improvement in ADHD symptoms (r = .33; p = .03) and better parent-rated executive function (BRIEF working memory [WM] r = -.30; p = .05). ConclusionsThe neural mechanisms underlying the TNS treatment effects in ADHD involve normalization of connectivity within several resting-state networks (DMN, salience, executive control), particularly those involving mid- and right-frontal connections.ADHD, NM, TREAT The neural mechanisms underlying the TNS treatment effects in ADHD involve normalization of connectivity within several resting-state networks (DMN, salience, executive control), particularly those involving mid- and right-frontal connections.