Medial Femoral Trochlea Osteochondral Flap Reconstruction of the Previously Unsalvageable Kienbock-Associated Lunate With a Coronal Split.

PURPOSE: Patients with Kienbock disease can present with coronal fracture and collapse of the proximal lunate (Unified B2/Bain grade 1, 2B). Traditionally, this was considered unsalvageable. However, medial femoral trochlea (MFT) osteochondral reconstruction, used to recreate the proximal lunate surface, can be paired with reduction and repair of the coronal plane fracture, thus restoring midcarpal congruity. The purpose of this study was to report radiographic and clinical outcomes following lunate coronal fracture fixation at the time of MFT osteochondral reconstruction. METHODS: This was a retrospective study performed at a single institution. We identified patients with Kienbock disease who underwent MFT osteochondral reconstruction from 2014 to 2023. Patients were included if they had a coronal fracture of the lunate distal articular surface fixed at the time of surgery. Radiographic and clinical parameters were evaluated, including carpal height ratio, union rate, presence of heterotopic ossification, need for revision surgery, and patient-reported outcome measures. RESULTS: Thirty-three patients were included, with a mean age of 27.5 years (range: 15-41); 19 (58%) were women. Mean radiographic follow-up time was 5.8 months, and mean clinical follow-up time was 22.6 months. Union was achieved in 30/33 patients (91%). Carpal height ratio improved from 1.32 to 1.4. Two patients (6%) required reoperation, one for removal of heterotopic ossification and another for conversion to proximal row carpectomy. Patients demonstrated meaningful improvement in brief Michigan Hand Questionnaire and Patient-Reported Outcomes Measurement Information Upper Extremity scores. Range of motion before and after surgery was similar. CONCLUSIONS: Lunate coronal fracture fixation with MFT osteochondral reconstruction represents an additional management option in select patients with Kienbock disease. This technique restores the midcarpal joint during lunate reconstruction and may allow patients to avoid salvage procedures. Early radiographic and clinical outcomes are promising. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Vascularized Medial Femoral Condyle Flap Reconstruction for Osseous Defects of the Hand and Wrist.

Vascularized bone flaps from the descending genicular artery system are versatile and effective for the use of recalcitrant nonunions from the tubular bones of the hand to the long bones of the upper extremity. Familiarity with the vascular pedicle, various techniques of harvest and inset, and skin paddle harvest and application are essential for the reconstructive surgeon.

Use of Treatments after Recovery from Thumb Carpometacarpal Arthritis Surgery.

BACKGROUND: Which treatments patients continue to use more than 1 year after primary thumb carpometacarpal arthritis surgery, and how such use relates to patient-reported outcomes, is largely unknown. METHODS: The authors identified patients who had isolated primary trapeziectomy alone or with ligament reconstruction ± tendon interposition and were 1 to 4 years postoperative. Participants completed a surgical site-focused electronic questionnaire about what treatments they still used. Patient-reported outcome measures were the Quick Disability of the Arm, Shoulder, and Hand questionnaire and visual analog/numerical rating scales for current pain, pain with activities, and typical worst pain. RESULTS: A total of 112 patients met inclusion and exclusion criteria and participated. At a median of 3 years after surgery, over 40% reported current use of at least one treatment for their thumb carpometacarpal surgical site, with 22% using more than one treatment. Of those who still used treatments, 48% used over-the-counter medications, 34% used home or office-based hand therapy, 29% used splinting, 25% used prescription medications, and 4% used corticosteroid injections. A total of 108 participants completed all patient-reported outcome measures. With bivariate analyses, the authors found that use of any treatment after recovering from surgery was associated with statistically and clinically significantly worse scores for all measures. CONCLUSIONS: Clinically relevant proportions of patients continue to use various treatments a median of 3 years after primary thumb carpometacarpal arthritis surgery. Continued use of any treatment is associated with significantly worse patient-reported outcomes for function and pain.

Patient-Reported Lower Extremity Outcomes Following Fibula or Medial Femoral Condyle Free Flaps for Upper Extremity Defects.

BACKGROUND: Free fibula flap (FFF) and medial femoral condyle (MFC) flap are commonly used for upper extremity osseous reconstruction, yet donor-site morbidity has never been systematically compared. METHODS: Patients who underwent an FFF or MFC for upper extremity extra-carpal osseous reconstruction at 3 academic hand centers were retrospectively identified. Only patients who underwent reconstruction for a defect in which either flap type is routinely used or has been described in the literature were deemed eligible. Patients who agreed to participate were asked to complete the Lower Extremity Functional Scale (LEFS) and Lower Limb Core Scale (LLCS). The reported population norm median score of LEFS is 77 points. The LLCS population norm mean score is 90.52 points. RESULTS: Twenty-one patients (10 MFC, 11 FFF) were enrolled. The median LEFS score for patients after MFC was 76 (interquartile range [IQR], 49-80) points and 75 (IQR, 56-79) points after FFF. The median LLCS score for patients after MFC was 96.4 (IQR, 87.9-100) points and 100 (IQR, 91-100) points after FFF. Median LEFS scores were slightly below the population norm, whereas median LLCS scores were above the norm for both FFF and MFC. All patients stated they would have the surgery again and that any dysfunction or pain in the leg was justified by the benefit in the arm. CONCLUSIONS: When considering whether to use an MFC or FFF for upper extremity reconstruction, both flap types appear to result in modest and comparable donor-site morbidity.

Lateral Femoral Trochlea Flap Reconstruction of the Proximal Capitate: An Assessment of Congruity and Description of Technique.

PURPOSE: We examined morphologic similarities of the medial lateral femoral trochlea (MFT) and lateral femoral trochlea (LFT) osteochondral flaps for reconstruction of the proximal capitate. METHODS: Magnetic resonance imaging scans of the wrists and ipsilateral knees of 10 young healthy volunteers were obtained. Three morphologic parameters were investigated, comparing the MFT and LFT harvest sites to the capitate proximal pole. The correspondingly relevant surgical planes were compared. The coronal plane radius of curvature (ROC) of the capitate was compared with the sagittal planes of the MFT and LFT. The sagittal plane ROC of the capitate was compared to the axial planes of the MFT and LFT. The angular relationship between the dorsal cortical surface of the capitate and the proximal pole cartilage (proximal dorsal capitate pitch) was compared to the corresponding angles between the cortical bone and convex cartilage on the LFT and MFT. RESULTS: The average ratios of ROC for the coronal planes of the capitate to the MFT (0.61) and LFT (0.58) were similar. The average ratios of ROC for the sagittal planes of the capitate to the MFT (0.57) and LFT (0.86) were also similar. The proximal dorsal capitate pitch demonstrated greater similarity to the corresponding shape of the LFT (angular ratio, 1.01) than to that of the MFT (angular ratio, 0.74). CONCLUSIONS: The LFT and MFT demonstrate similar congruity to the proximal capitate in the sagittal and coronal planes of the wrist. The LFT dorsal pitch closely approximates the relationship of the proximal capitate pole to its dorsal cortical surface. CLINICAL RELEVANCE: In capitate fracture, fracture nonunion, or avascular necrosis, both the MFT and LFT demonstrate similarity to the proximal convex capitate morphology. The relationship between the cortical and chondral surfaces of the LFT is morphologically very similar to that of the proximal capitate.

Magnetic Resonance Imaging to Investigate the Clinical Applicability of the Medial Femoral Trochlea Osteochondral Flap Within the Wrist.

BACKGROUND: The medial femoral trochlea (MFT) osteochondral flap is employed for reconstruction of unsalvageable scaphoid proximal pole nonunions. The convex surface of the cartilage-bearing proximal trochlea is used to replace the similarly contoured proximal scaphoid and articulate with the concave scaphoid fossa of the radius. A magnetic resonance imaging (MRI) comparison of the shape of the MFT as it relates to the native proximal scaphoid has not been previously performed. Our study aimed to quantifiably compare the shape of the MFT, proximal scaphoid, and scaphoid fossa. METHODS: Using imaging processing software, we measured radius of curvature of the articular segments in MRI scans of 10 healthy subjects' wrists and knees. RESULTS: Compared with the scaphoid fossa, average ratio of the radius of circumference of the proximal scaphoid was 0.79 and 0.78 in the coronal and sagittal planes, respectively. Compared with the scaphoid fossa, average ratio of the radius of circumference of the MFT was 0.98 and 1.31 in the coronal and sagittal planes, respectively. The radius of curvature of the MFT was larger than the proximal scaphoid, in the coronal and sagittal planes. In the coronal plane, the MFT radius of curvature is nearly identical to the scaphoid fossa, a closer match than the scaphoid itself. In the sagittal plane, the radius of curvature of the MFT was larger than the radius of curvature of the scaphoid fossa. CONCLUSIONS: Our data suggest that the radius of curvature, in the sagittal and coronal planes, of the MFT and proximal scaphoid is disparate.

Arterial Perfusion of the Proximal Phalanx Revisited: New Insights Based on Micro-Computed Tomography.

PURPOSE: To characterize the periosteal and endosteal arterial perfusion of the proximal phalanx using micro-computed tomography angiography (micro-CTA). METHODS: Cadaveric upper extremities were injected with a barium sulfate/gelatin suspension. Phalanges were imaged using micro-CTA and analyzed with a focus on osseous arterial anatomy. Periosteal and endosteal perfusion was characterized by number of vessels, length, anatomic course, and caliber. RESULTS: The base of the proximal phalanx had a significantly greater number (8.0 ± 3.5) of periosteal vessels than those of the shaft (4.1 ± 1.6) and head (1.3 ± 1.1). One-third (34.4%) of the specimens demonstrated a complete absence of periosteal vessels in the head. A nutrient endosteal vessel was noted in 100% of the specimens. Entering at the junction of the middle and distal third of the bone (25.8 ± 3.9 mm from base), the nutrient vessel entered the proximal phalanx of the index finger along its ulnar aspect (8 of 8 specimens), the middle finger along its radial aspect (6 of 8), the ring finger along its ulnar aspect (5 of 8), and the little finger along its radial aspect (7 of 8). The nutrient vessel branched into proximal and distal extensions toward the shaft and head, respectively, with an average endosteal length of 10.7 ± 5.2 mm and average diameter of 0.36 ± 0.11 mm. CONCLUSIONS: Periosteal contributions to the perfusion of the proximal phalanx appear to diminish distally. The endosteal arterial anatomy remains consistent, with a single nutrient vessel entering the intramedullary canal with reliable laterality on each digit. This is often the only vessel supplying the head of the proximal phalanx, making this area particularly susceptible to vascular compromise. CLINICAL RELEVANCE: An understanding of the patterns of perfusion of the proximal phalanx provides some insight into clinically observed pathology, as well as guidance for operative management.

Lateral Femoral Trochlea Osteochondral Flap Reconstruction of Proximal Pole Scaphoid Nonunions.

PURPOSE: The medial femoral trochlea flap has been described as a method of scaphoid proximal pole nonunion reconstruction when the proximal pole is deemed nonsalvageable. The lateral femoral trochlea (LFT) is an alternative donor site providing a comparable vascularized convex osteochondral flap. We describe the technique and outcomes of our first 17 cases of LFT flap reconstruction of the proximal scaphoid pole with a minimum follow-up of 14 months. METHODS: Seventeen of the first 24 patients who underwent LFT scaphoid reconstruction at 3 institutions were able to be contacted for clinical follow-up and chart reviews. We recorded patient age and sex, duration of nonunion, number of previous surgical procedures, details of surgical technique, achievement of osseous union, complications, additional postoperative procedures, preoperative and postoperative pain, and range of motion. Preoperative and postoperative scapholunate and radiolunate angles were analyzed on x-rays and achievement of osseous union on computerized tomography scans. RESULTS: The average age of patients included was 35 years (range, 16-55 years). Follow-up data were recorded at an average of 33 months (range, 14-62 months). Ten patients had previous procedures (average, 1; range, 0-2). Median duration from trauma to LFT was 3.4 years (range, 8 months-12 years) among patients who had a recognized date of injury. Osseous healing was achieved in 16 of 17 patients and confirmed by computerized tomograpy scan. Twelve patients reported complete pain relief, while 5 reported partial pain relief. Final postoperative range of motion was 59°extension (range, 30°-85°) and 50° flexion (range, 10°-80°), which was comparable to preoperative values. Preoperative (59°) and postoperative (55°) scapholunate angles were similar to normal wrists. CONCLUSION: Vascularized LFT flaps provide an alternative donor site for vascularized osteochondral reconstruction of proximal pole scaphoid nonunion. Rate of union, range of motion, and pain relief are similar to reported results with medial femoral trochlea flap reconstruction. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

An Algorithmic Approach to the Treatment of Kienböck Disease.

The algorithm and rationale described is a reflection of our own surgical experience for this challenging disorder and can be compared with other publications. Our algorithm has evolved from treatment of a large volume of patients with Kienböck disease in a referral practice. However, it is limited to the management that we have found logical, effective, and within our scope of experience. The treatment guidelines for our specialty as a whole will evolve as our understanding of the etiology and our ability to quantify efficacy improves.

Could salt intake directly affect the cerebral microvasculature in hypertension?

OBJECTIVES: Excess dietary salt and chronic kidney disease (CKD) are acknowledged stroke risk factors. The development of small vessel disease, similarly affecting the cerebral and renal microvasculatures, may be an important mechanistic link underlying this interaction. Therefore, we aimed to evaluate if the dietary salt intake and markers of CKD (estimated glomerular filtration rate, albuminuria) relate to transcranial Doppler (TCD) markers of cerebral small vessel disease (CSVD) in hypertensive patients. MATERIALS AND METHODS: Fifty-six hypertensive patients (57% with diabetes) underwent TCD monitoring in the middle (MCA) and posterior (PCA) cerebral arteries for evaluating neurovascular coupling (NVC), dynamic cerebral autoregulation (dCA), and vasoreactivity to carbon dioxide (VRCO2). We investigated the relation between renal parameters and TCD studies using Pearson's correlation coefficient and linear regression analyses. RESULTS: There were no associations between dCA, VRCO2, NVC, and renal function tests. However, there was a negative association between the daily salt intake and the natural frequency during visual stimulation (r2=0.101, ß=-0.340, p=0.035), indicative of increased rigidity of the cerebral resistance vessels that react to cognitive activation. CONCLUSIONS: In this cross-sectional study, we found an association between excess dietary salt consumption and CSVD in hypertensive patients. Future research is needed to evaluate whether the natural frequency could be an early, non-invasive, surrogate marker for microvascular dysfunction in hypertension.

Achieving Functional Outcomes after Surgical Management of Catastrophic Vasopressor-induced Limb Ischemia.

Vasopressor-induced limb ischemia is an unfortunate complication that can occur in patients treated for septic shock. Current literature lacks surgical treatment recommendations for this condition, besides amputation. We describe various reconstructive surgeries and functional outcomes in patients treated surgically for vasopressor-induced limb ischemia. Methods: We retrospectively reviewed patients who were treated for septic shock and developed vasopressor-induced limb ischemia at our tertiary referral academic medical center. We reviewed presentation, treatment, surgical outcomes, and long-term functional outcomes. Results: We present three previously healthy patients who developed gangrene of multiple limbs following the use of vasopressors to treat septic shock. Each patient underwent amputations or limb salvage procedures. Conclusions: Limb ischemia is a devastating complication that can occur after prolonged vasopressor use. The decision to proceed with limb salvage versus amputation of ischemic extremities should be tailored to the individual patient. The main objective should be for the patient to obtain optimal function and quality of life, regardless of the type of surgery.

Neurovascular Coupling Is Impaired in Hypertensive and Diabetic Subjects Without Symptomatic Cerebrovascular Disease.

The mechanistic link between hypertension, diabetes and cerebral small vessel disease (CSVD) is still poorly understood. We hypothesized that hypertension and diabetes could impair cerebrovascular regulation prior to irreversibly established cerebrovascular disease. In this study, 52 hypertensive patients [54% males; age 64 ± 11 years; 58% with comorbid diabetes mellitus (DM)] without symptomatic cerebrovascular disease underwent transcranial Doppler (TCD) monitoring in the middle (MCA) and posterior (PCA) cerebral arteries, to assess vasoreactivity to carbon dioxide (VRCO2) and neurovascular coupling (NVC). 1.5T magnetic resonance imaging was also performed and white matter hyperintensity volume was automatically segmented from FLAIR sequences. TCD data from 17 healthy controls were obtained for comparison (47% males; age 60 ± 16 years). Hypertensive patients showed significant impairment of NVC in the PCA, with reduced increment in cerebral blood flow velocity during visual stimulation (22.4 ± 9.2 vs. 31.6 ± 5.7, p < 0.001), as well as disturbed NVC time-varying properties, with slower response (lower rate time: 0.00 ± 0.02 vs. 0.03 ± 6.81, p = 0.001), and reduced system oscillation (reduced natural frequency: 0.18 ± 0.08 vs. 0.22 ± 0.06, p < 0.001), when compared to controls. VRCO2 remained relatively preserved in MCA and PCA. These results were worse in hypertensive diabetic patients, with lower natural frequency (p = 0.043) than non-diabetic patients. White matter disease burden did not predict worse NVC. These findings suggest that hypertensive diabetic patients may have a precocious impairment of NVC, already occurring without symptomatic CSVD. Future research is warranted to evaluate whether NVC assessment could be useful as an early, non-invasive, surrogate marker for CSVD.

Long-Term Patency and Fluid Dynamics of Recipient Artery after End-to-Side Anastomosis for Free Tissue Transfer.

BACKGROUND: End-to-end microvascular anastomoses sacrifice downstream inline perfusion of the recipient vessels. End-to-side anastomoses, in theory, maintain distal inline flow of the recipient vessel. The proposed benefit of the end-to-side technique depends on patency of the distal vessels and subsequent flow parameters, but maintenance of distal perfusion has not been conclusively demonstrated. METHODS: Fifteen patients who underwent a successful extremity free flap procedure via end-to-side anastomoses to a noncritical vessel between 2003 and 2017 were enrolled. Recipient artery patency distal to the anastomosis was assessed using pulse volume recordings and duplex ultrasound imaging. Resistance indices, flow velocities, vessel diameters, volumetric flow, and turbulent flow dimensionless number (Reynolds number) were measured. Comparisons were made to the ipsilateral collateral vessel as well as to the vessels on the nonoperative contralateral limb using paired t tests. RESULTS: Downstream flow was identified in 14 of 15 patients (93 percent patency). There was no statistical difference in resistive indices comparing the anastomotic vessel (0.859 ± 0.300) and the collateral vessel (0.853 ± 0.179) of the ipsilateral extremity. Ultrasound flows were similar; the anastomotic vessel demonstrated downstream volumetric flows of 139 ± 92.0 cm3/min versus 137 ± 41.6 cm3/min within the same vessel of the nonoperative contralateral limb. The anastomotic vessel had Reynolds numbers well below the turbulent threshold (448 ± 202 and 493 ± 127 for the anastomotic and nonoperative contralateral limb, respectively). CONCLUSION: End-to-side anastomosis to noncritical vessels resulted in a 93 percent long-term recipient vessel patency rate, with no statistically significant changes in volumetric flows, resistive indices, or fluid dynamics in the vessels that remained patent.

Thumb Carpometacarpal Arthritis Surgery: The Patient Experience.

BACKGROUND: Patients with symptomatic recalcitrant thumb carpometacarpal arthritis often undergo surgery. Although most surgical patients do well, the authors anticipated that a substantial portion of their thumb carpometacarpal surgery patients would have unsatisfactory experiences and express unmet expectations, dissatisfaction, and regret, regardless of surgical procedure performed. The authors hypothesized those experiences would correlate with patient-reported outcomes scores. METHODS: The authors identified patients who had undergone trapeziectomy alone or with ligament reconstruction 1 to 4 years previously for primary thumb carpometacarpal arthritis. One hundred twelve patients completed Quick Disabilities of the Arm, Shoulder and Hand and visual analogue scale pain, expectations, satisfaction, and regret questionnaires. RESULTS: More than 40 percent of patients expected to "return to normal" after surgery for pain, strength, and/or function. Including all patients, 7, 19, and 11 percent had unmet expectations for improvement in pain, strength, and function, respectively. Twelve percent expressed dissatisfaction with their outcome. Although just 4 percent regretted undergoing surgery, 13 percent would likely not recommend the procedure to someone they care about. There were no statistically significant differences for any patient-reported outcomes between trapeziectomy-alone (n = 20) and trapeziectomy with ligament reconstruction (n = 92). Visual analogue scale and Quick Disabilities of the Arm, Shoulder and Hand questionnaire scores were both moderately correlated with expectations being met for pain, strength, and function and for satisfaction with surgical outcome. CONCLUSIONS: Patients' thumb carpometacarpal surgical experiences vary considerably. Many express dissatisfaction or a lack of expectations met with the two most common procedures. A thorough understanding and review of expectations preoperatively may be uniquely pertinent for these patients. Further research should determine predictors and potentially modifiable factors for unsatisfactory outcomes.

Medial femoral trochlea flap reconstruction versus proximal row carpectomy for Kienböck's disease: a morphometric comparison.

Surgical options for advanced Kienböck's disease include proximal row carpectomy or lunate reconstruction with a medial femoral trochlea osteochondral flap. This study compares morphology of the proximal capitate and the medial femoral trochlear surfaces to the proximal lunate using three-dimensional geometric morphometric analysis. Virtual articular surfaces were extracted from MRI studies of ten healthy volunteers. Distances between corresponding points on the proximal lunate and proximal capitate or medial femoral trochlear surfaces were measured. In seven subjects, mean inter-surface distance for the medial femoral trochlea-proximal lunate pair was significantly lower than the proximal capitate-proximal lunate pairing. In three subjects, mean proximal capitate-proximal lunate distance was significantly lower. We conclude that the medial femoral trochlear flap was anatomically closer to the shape of the proximal lunate in the majority of the examined subjects. However, we found that in three out of ten cases, the proximal capitate was a better match.

Scaphoid Nonunion Vascularized Bone Grafting in 2021: Is Avascular Necrosis the Sole Determinant?

The decision regarding the use of vascularized bone grafting (VBG) or nonvascularized bone grafting for the treatment of scaphoid nonunion (SNU) needs guidelines based on patient- and fracture-specific risk factors. Historically, the presence of avascular necrosis was viewed as the primary indication for VBG; however, avascular necrosis is not the only indicator to determine whether VBG can improve our treatment of difficult SNU cases. The methods of detecting scaphoid avascular necrosis lack consensus and accuracy, limiting their use as decision-making tools. Additionally, many other preoperative risk factors for SNU surgery failure have been reported and require careful and standardized study, including the location of nonunion in the scaphoid proximal pole, the duration of nonunion, previous failed nonunion surgery, smoking, and fracture nonunion displacement or collapse. An appropriate study size and design are needed to determine the factors that guide the use of VBG or nonvascularized bone grafting to optimize the outcomes of SNU surgery.

Attention and Default Mode Network Assessments of Meditation Experience during Active Cognition and Rest.

Meditation experience has previously been shown to improve performance on behavioral assessments of attention, but the neural bases of this improvement are unknown. Two prominent, strongly competing networks exist in the human cortex: a dorsal attention network, that is activated during focused attention, and a default mode network, that is suppressed during attentionally demanding tasks. Prior studies suggest that strong anti-correlations between these networks indicate good brain health. In addition, a third network, a ventral attention network, serves as a "circuit-breaker" that transiently disrupts and redirects focused attention to permit salient stimuli to capture attention. Here, we used functional magnetic resonance imaging to contrast cortical network activation between experienced focused attention Vipassana meditators and matched controls. Participants performed two attention tasks during scanning: a sustained attention task and an attention-capture task. Meditators demonstrated increased magnitude of differential activation in the dorsal attention vs. default mode network in a sustained attention task, relative to controls. In contrast, there were no evident attention network differences between meditators and controls in an attentional reorienting paradigm. A resting state functional connectivity analysis revealed a greater magnitude of anticorrelation between dorsal attention and default mode networks in the meditators as compared to both our local control group and a n = 168 Human Connectome Project dataset. These results demonstrate, with both task- and rest-based fMRI data, increased stability in sustained attention processes without an associated attentional capture cost in meditators. Task and resting-state results, which revealed stronger anticorrelations between dorsal attention and default mode networks in experienced mediators than in controls, are consistent with a brain health benefit of long-term meditation practice.

Customizing TMS Applications in Traumatic Brain Injury Using Neuroimaging.

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.

A Pilot Trial Examining the Merits of Combining Amantadine and Repetitive Transcranial Magnetic Stimulation as an Intervention for Persons With Disordered Consciousness After TBI.

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.

Neural Connectivity Changes Facilitated by Familiar Auditory Sensory Training in Disordered Consciousness: A TBI Pilot Study.

For people with disordered consciousness (DoC) after traumatic brain injury (TBI), relationships between treatment-induced changes in neural connectivity and neurobehavioral recovery have not been explored. To begin building a body of evidence regarding the unique contributions of treatments to changes in neural network connectivity relative to neurobehavioral recovery, we conducted a pilot study to identify relationships meriting additional examination in future research. To address this objective, we examined previously unpublished neural connectivity data derived from a randomized clinical trial (RCT). We leveraged these data because treatment efficacy, in the RCT, was based on a comparison of a placebo control with a specific intervention, the familiar auditory sensory training (FAST) intervention, consisting of autobiographical auditory-linguistic stimuli. We selected a subgroup of RCT participants with high-quality imaging data (FAST n = 4 and placebo n = 4) to examine treatment-related changes in brain network connectivity and how and if these changes relate to neurobehavioral recovery. To discover promising relationships among the FAST intervention, changes in neural connectivity, and neurobehavioral recovery, we examined 26 brain regions and 19 white matter tracts associated with default mode, salience, attention, and language networks, as well as three neurobehavioral measures. Of the relationships discovered, the systematic filtering process yielded evidence supporting further investigation of the relationship among the FAST intervention, connectivity of the left inferior longitudinal fasciculus, and auditory-language skills. Evidence also suggests that future mechanistic research should focus on examining the possibility that the FAST supports connectivity changes by facilitating redistribution of brain resources. For a patient population with limited treatment options, the reported findings suggest that a simple, yet targeted, passive sensory stimulation treatment may have altered functional and structural connectivity. If replicated in future research, then these findings provide the foundation for characterizing the unique contributions of the FAST intervention and could inform development of new treatment strategies. For persons with severely damaged brain networks, this report represents a first step toward advancing understanding of the unique contributions of treatments to changing brain network connectivity and how these changes relate to neurobehavioral recovery for persons with DoC after TBI. Clinical Trial Registry: NCT00557076, The Efficacy of Familiar Voice Stimulation During Coma Recovery (http://www.clinicaltrials.gov).