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OBJECTIVE Report pilot findings of neurobehavioral gains and network changes observed in persons with disordered consciousness (DoC) who received repetitive transcranial magnetic stimulation (rTMS) or amantadine (AMA), and then rTMS+AMA. PARTICIPANTS Four persons with DoC 1 to 15 years after traumatic brain injury (TBI). DESIGN Alternate treatment-order, within-subject, baseline-controlled trial. MAIN MEASURES For group and individual neurobehavioral analyses, predetermined thresholds, based on mixed linear-effects models and conditional minimally detectable change, were used to define meaningful neurobehavioral change for the Disorders of Consciousness Scale-25 (DOCS) total and Auditory-Language measures. Resting-state functional connectivity (rsFC) of the default mode and 6 other networks was examined. RESULTS Meaningful gains in DOCS total measures were observed for 75% of treatment segments and auditory-language gains were observed after rTMS, which doubled when rTMS preceded rTMS+AMA. Neurobehavioral changes were reflected in rsFC for language, salience, and sensorimotor networks. Between networks interactions were modulated, globally, after all treatments. CONCLUSIONS For persons with DoC 1 to 15 years after TBI, meaningful neurobehavioral gains were observed after provision of rTMS, AMA, and rTMS+AMA. Sequencing and combining of treatments to modulate broad-scale neural activity, via differing mechanisms, merits investigation in a future study powered to determine efficacy of this approach to enabling neurobehavioral recovery.

Optimizing transcranial magnetic stimulation (TMS) treatments in traumatic brain injury (TBI) and co-occurring conditions may benefit from neuroimaging-based customization. PARTICIPANTS Our total sample (N = 97) included 58 individuals with TBI (49 mild, 8 moderate, and 1 severe in a state of disordered consciousness), of which 24 had co-occurring conditions (depression in 14 and alcohol use disorder in 10). Of those without TBI, 6 individuals had alcohol use disorder and 33 were healthy controls. Of our total sample, 54 were veterans and 43 were civilians. DESIGN Proof-of-concept study incorporating data from 5 analyses/studies that used multimodal approaches to integrate neuroimaging with TMS. MAIN MEASURES Multimodal neuroimaging methods including structural magnetic resonance imaging (MRI), MRI-guided TMS navigation, functional MRI, diffusion MRI, and TMS-induced electric fields. Outcomes included symptom scales, neuropsychological tests, and physiological measures. RESULTS It is feasible to use multimodal neuroimaging data to customize TMS targets and understand brain-based changes in targeted networks among people with TBI. CONCLUSIONS TBI is an anatomically heterogeneous disorder. Preliminary evidence from the 5 studies suggests that using multimodal neuroimaging approaches to customize TMS treatment is feasible. To test whether this will lead to increased clinical efficacy, studies that integrate neuroimaging and TMS targeting data with outcomes are needed.

Research Objectives To explore the relationship between attention/working memory (WM) performance and grey matter volume in the dorsal attention network (DAN), a neural network in the brain that supports encoding and maintenance of external information. Design Observational. Setting Data obtained from the Parkinson's Progression Marker Initiative (PPMI; www.ppmi-info.org ), an international longitudinal multisite study. Participants Participants with persistent WM impairment (n= 10) and persistent normal WM performance (n=10) were compared. WM was measured using the Letter Number Sequencing (LNS) test. Persistent impairment was defined by a standardized test score of 8 or less for 4 consecutive years since baseline imaging. Normal WM performance was defined by a standardized test score of 10 or more for 4 consecutive years since baseline imaging. Groups were matched on sex, age, years of education, and disease duration. Interventions Not Applicable. Main Outcome Measures Grey matter volume was measured using voxel-based morphometry (VBM) through SPM12 and CAT12. Region of interest analysis within the DAN (Schaeffer et al., 2018 100-parcel atlas), was conducted. Whole brain cluster analysis was conducted for confirmatory evidence. Significant clusters within a DAN mask (Schaeffer et al., 2018 100-parcel atlas) are reported with a FDR (p=0.05). Results For ROI analysis, grey matter atrophy in the bilateral visuomotor cortex (p=0.005), bilateral intraparietal sulcus (p=0.04), and right superior parietal lobule (p=0.021) was found in the impaired WM group compared to the normal WM group. Between groups, differences in several clusters within the DAN masks were observed. Conclusions These promising preliminary findings support the notion that changes in grey matter volume within cognitive neural networks, such as the DAN, can be a biomarker for decline in cognitive function, as well as treatment responsiveness in people living with PD. Author(s) Disclosures None.