rTMS/iTBS and Cognitive Rehabilitation for Deficits Associated With TBI and PTSD: A Theoretical Framework and Review.

Rehabilitation of cognitive and psychosocial deficits resulting from traumatic brain injury (TBI) continues to be an area of concern in health care. Commonly co-occurring psychiatric disorders, such as major depressive disorder and posttraumatic stress disorder, create additional hurdles when attempting to remediate cognitive sequelae. There is increased need for procedures that will yield consistent gains indicative of recovery of function. Intermittent theta-burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation, has potential as an instrument that can be tailored to aid cognitive processes and support functional gains. The use of iTBS enables direct stimulation of desired neural systems. iTBS, performed in conjunction with behavioral interventions (e.g., cognitive rehabilitation, psychotherapy), may result in additive success in facilitating cognitive restoration and adaptation. The purpose of this theoretical review is to illustrate how the technical and physiological aspects of iTBS may enhance other forms of neurorehabilitation for individuals with TBI. Future research on combinatorial iTBS interventions has the potential to translate to other complex neuropsychiatric conditions.

An Initial miRNA Profile of Persons With Persisting Neurobehavioral Impairments and States of Disordered Consciousness After Severe Traumatic Brain Injury.

OBJECTIVE: To examine the merits of using microRNAs (miRNAs) as biomarkers of disorders of consciousness (DoC) due to traumatic brain injury (TBI). SETTINGS: Acute and subacute beds. PARTICIPANTS: Patients remaining in vegetative and minimally conscious states (VS, MCS), an average of 1.5 years after TBI, and enrolled in a randomized clinical trial ( n = 6). Persons without a diagnosed central nervous system disorder, neurotypical controls ( n = 5). DESIGN: Comparison of whole blood miRNA profiles between patients and age/gender-matched controls. For patients, correlational analyses between miRNA profiles and measures of neurobehavioral function. MAIN MEASURES: Baseline measures of whole blood miRNAs isolated from the cellular and fluid components of blood and measured using miRNA-seq and real-time polymerase chain reaction (RT-PCR). Baseline neurobehavioral measures derived from 7 tests. RESULTS: For patients, relative to controls, 48 miRNA were significantly ( P < .05)/differentially expressed. Cluster analysis showed that neurotypical controls were most similar to each other and with 2 patients (VS: n = 1; and MCS: n = 1). Three patients, all in MCS, clustered separately. The only female in the sample, also in MCS, formed an independent group. For the 48 miRNAs, the enriched pathways identified are implicated in secondary brain damage and 26 miRNAs were significantly ( P < .05) correlated with measures of neurobehavioral function. CONCLUSIONS: Patients remaining in states of DoC an average of 1.5 years after TBI showed a different and reproducible pattern of miRNA expression relative to age/gender-matched neurotypical controls. The phenotypes, defined by miRNA profiles relative to persisting neurobehavioral impairments, provide the basis for future research to determine the miRNA profiles differentiating states of DoC and the basis for future research using miRNA to detect treatment effects, predict treatment responsiveness, and developing targeted interventions. If future research confirms and advances reported findings, then miRNA profiles will provide the foundation for patient-centric DoC neurorehabilitation.

The diagnostic intersection of cognitive-communication disorders and aphasia secondary to TBI.

BACKGROUND & AIMS: The present retrospective study examines veterans and military personnel who have sustained a cognitive-communication deficit/disorder (CCD) and/or aphasia secondary to traumatic brain injury (TBI). The prevalence of each disorder secondary to TBI is identified and demographic factors are analysed to determine whether specific characteristics (age, gender, race and/or ethnicity) differentially influenced diagnosis (CCD or aphasia). METHODS & PROCEDURES: A retrospective analysis examining the prevalence of CCD and aphasia among US service personnel with a complicated mild-to-severe TBI treated over a 4-year period (1 January 2016-31 December 2019) was conducted. Medical diagnoses and demographic factors were obtained from administrative data repositories and a logistic regression was performed to identify the relationship between demographic factors and diagnoses. OUTCOMES & RESULTS: Analyses revealed that 8.8% of individuals studied had a secondary diagnosis of CCD (6.9%), aphasia (1.5%) or both (0.4%). This signifies 6863 cases of CCD, 1516 cases of aphasia and 396 cases of CCD and aphasia (dual diagnosis) per 100,000 individuals who have sustained a complicated mild-to-severe TBI. The proportion of cases observed with these diagnoses was consistent with the racial, gender and ethnic demographics of those diagnosed with TBI. Statistical modelling revealed that increased age is predictive of a diagnosis of aphasia relative to CCD. CONCLUSIONS & IMPLICATIONS: Service personnel sustaining TBIs are at increased risk of communication impairments with deficits observed across all gender, racial and ethnic demographics. CCD is more commonly observed than aphasia, though clinicians should be cognisant of both when performing assessments. Age is a factor that can influence diagnosis. WHAT THIS PAPER ADDS: What is already known on the subject Military personnel are at increased risk of communication disorders (CCDs) with TBI associated with multiple types of communication impairments including CCD, aphasia, dysarthria and apraxia of speech. What this paper adds to existing knowledge This paper examines CCD and aphasia occurring following TBI. The proportion of observed cases of CCD and aphasia secondary to TBI are calculated over a 4-year period and the prevalence of these disorders is provided. Additionally, statistical modelling is used to identify differences in the diagnosis of CCD relative to aphasia using the demographic factors of age, racial identity and ethnicity. What are the potential or actual clinical implications of this work? CCD is a frequently occurring issue following TBI, and the findings of this study demonstrate that it is a concern observed across gender, racial and ethnic lines. Advanced age is linked with the diagnosis of aphasia relative to CCD following TBI and should be a consideration during evaluation of patients who have sustained significant head trauma.

Factors that Influence Follow-Up Care for Families of Children with Acquired Brain Injury: A Scoping Review.

PURPOSE: To describe factors that contribute to medical/rehabilitation service access following pediatric acquired brain injury (ABI) and identify gaps in the literature to guide future research. MATERIALS & METHODS: The PRISMA framework for scoping reviews guided this process. Peer-reviewed journal databases were searched for articles published between 1/2008 and 12/2020, identifying 400 unique articles. For full inclusion, articles had to examine a variable related to the receipt or initiation of medical/rehabilitative services for children with ABI. Review articles and non-English articles were excluded. RESULTS: Nine studies met full inclusion criteria. Included studies identified factors focused on four primary areas: understanding brain injury education/recommendations and ease of implementing recommendations, ease of scheduling and attending appointments, age/injury factors, and sociocultural factors. Well-scheduled appointments and simple strategies facilitated families' access to care and implementation of recommendations. An overwhelming number of recommendations, socioeconomic variables, and transportation challenges served as barriers for families and schools. CONCLUSIONS: This scoping review offers several directions on which researchers can build to improve access to care and recommendation-implementation for families who have a child with an ABI. Enhanced understanding of these factors may lead to better service access, reduction of unmet needs, and enhanced long-term outcomes for children with ABI.

Psychometric Properties of the Coma Near-Coma Scale for Adults in Disordered States of Consciousness: A Rasch Analysis.

OBJECTIVES: To examine the construct validity and measurement precision of the Coma Near-Coma scale (CNC) in measuring neurobehavioral function (NBF) in patients with disorders of consciousness receiving postacute care rehabilitation. DESIGN: Rasch analysis of retrospective data. PARTICIPANTS: Participants (N=48) with disordered consciousness who were admitted to postacute care rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: CNC. RESULTS: Assessment with CNC repeated weekly until the participant was conscious or discharged from the postacute care facility (451 participant records). Rating scale steps were ordered for all items. Eight of the 10 CNC items evaluated in this study fit the measurement model (χ2=5332.58; df=11; P=.17); pain items formed a distinct construct. The ordering of the 8 items from most to least challenging makes clinical sense and compares favorably with other published hierarchies of NBF. Tactile items are more easily responded to. Visual and auditory items requiring higher cognitive processing were more challenging. In the full sample, the CNC achieved good measurement precision, with a person separation reliability of 0.87. CONCLUSIONS: The items of the CNC reflect good construct validity and acceptable interrater reliability. The measurement precision achieved indicates that the CNC may be used to make decisions about groups of individuals but that these items may not be sufficiently precise for individual patient treatment decision-making.

Safety Considerations for the Use of Transcranial Magnetic Stimulation as Treatment for Coma Recovery in People With Severe Traumatic Brain Injury.

OBJECTIVE: For persons in states of disordered consciousness (DoC) after severe traumatic brain injury (sTBI), we report cumulative findings from safety examinations, including serious adverse events (AEs) of a repetitive transcranial magnetic stimulation (rTMS) parameter protocol in 2 different studies. PARTICIPANTS: Seven persons in states of DoC after sTBI with widespread neuropathology, but no large lesions in proximity to the site of rTMS. One participant had a ventriculoperitoneal shunt with programmable valve. METHODS: Two clinical trials each providing 30 rTMS sessions to the right or left dorsolateral prefrontal cortex, involving 300 to 600 pulses over 1 or 2 sessions daily. One study provided concomitant amantadine. Safety indicators monitored related to sleep, temperature, blood pressure, skin integrity, sweating, weight loss, infections, and seizure. RESULTS: Average changes for monitored indicators were of mild severity, with 75 nonserious AEs and 1 serious AE (seizure). The participant incurring a seizure resumed rTMS while taking antieplieptics without further seizure activity. CONCLUSIONS: Considering elevated risks for this patient population and conservative patient selection, findings indicate a relatively safe profile for the specified rTMS protocols; however, potential for seizure induction must be monitored. Future research for this population can be broadened to include patients previously excluded on the basis of profiles raising safety concerns.

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.

Responsiveness, Minimal Detectable Change, and Minimally Clinically Important Differences for the Disorders of Consciousness Scale.

OBJECTIVES: To determine the responsiveness, minimal detectable change (MDC95), and minimally clinically important difference (MCID) of the Disorders of Consciousness Scale (DOCS-25) in patients with severe traumatic brain injury (TBI) and to report the percentages of patients' change scores exceeding MDC and MCID after 3 weeks of inpatient rehabilitation. SETTING: Post-acute rehabilitation hospitals. PARTICIPANTS: One hundred seventy-two patients with severe TBI. Ninety-two were included in the DOCS-25 3-week analysis. DESIGN: Retrospective cohort study. MAIN MEASURE(S): Disorders of Consciousness Scale, Glasgow Coma Scale. RESULTS: The effect size and standardized response mean of the DOCS-25 for those who improved were 0.45 and 1.3, respectively-moderate to large by Cohen criteria. The MDC95 (95% confidence interval) was 5.6. Distribution-based MCIDs for small (0.20 SD), moderate (0.33 SD), and large (0.50 SD) differences were 2.6 units, 4.4 units, and 6.6 units, respectively. The anchor-based MCID was 8.6 units. On average, patients who improved (n = 57) gained 14.5 units by week 3, exceeding the anchor-based MCID. On average, patients who did not improve (n = 35) declined by 7.2 units, which exceeds both the MDC95 and the largest distribution-based MCID. CONCLUSION(S): The DOCS-25 is a responsive, clinician-observed assessment tool for capturing change in neurobehavioral function in adults recovering from severe TBI. This is the first study to provide evidence for the size of neurobehavioral function change that might indicate meaningful recovery in patients with severe TBI. Results from this study may support future research by better informing sample size calculations for clinical trials and also assist clinicians in identifying when variation in level of consciousness is consequential enough to warrant changes in intervention.

Validation Study of the Marianjoy Fall Risk Assessment Tool.

Evaluation of fall risk in acute inpatient rehabilitation poses unique challenges. The purpose of this study was to validate an assessment tool for inpatient rehabilitation fall risk identification. This retrospective, descriptive study used a cohort of inpatient rehabilitation patients to evaluate the Marianjoy Fall Risk Assessment Tool reliability and validity. Following implementation of this Tool, fall rates steadily decreased to 49% over 6 years.

Psychometric properties of the disorders of consciousness scale.

OBJECTIVE: To provide evidence for psychometric properties of the Disorders of Consciousness Scale (DOCS). DESIGN: Prospective observational cohort. SETTINGS: Seven rehabilitation facilities. PARTICIPANTS: Patients (N=174) with severe brain injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE DOCS RESULTS: Initial analyses suggested eliminating 6 items to maximize psychometrics, resulting in the DOCS-25. The 25 items form a unidimensional hierarchy, rating scale categories are ordered, there are no misfitting items, and differential item functioning was not found according to sex, type of brain injury, veteran status, and days from onset. Person separation reliability (.91) indicates that the DOCS-25 is appropriate for individual patient measurement. Items are well targeted to the sample, with the difference between mean person and item calibrations less than 1 logit. DOCS-25 Rasch measures result in a 62% gain in relative precision over total raw scores. Internal consistency is very good (Cronbach α=.86); interrater agreement is excellent (intracIass correlation coefficient=.90) for both the DOCS-25 and the sensory subscales. The DOCS-25 total measure, but not subscale measures, correlates with the Glasgow Coma Scale and the Coma/Near-Coma Scales and distinguishes significantly between vegetative and minimally conscious states, indicating concurrent validity. CONCLUSIONS: The DOCS-25 is psychometrically strong. It has excellent measurement precision and captures a broad range of patient function, which is critical for capturing recovery of consciousness. The sensory subscales are clinically informative but should not be reported as separate measures. The Keyform synthesizes clinical observations to visualize response patterns with potential for informing clinical decision-making. Future studies should determine sensitivity to change, examine issues of rater severity, and explore the usefulness of the Keyform in clinical practice.

Prescribing multiple neurostimulants during rehabilitation for severe brain injury.

BACKGROUND: Despite a lack of clear evidence, multiple neurostimulants are commonly provided after severe brain injury (BI). The purpose of this study is to determine if the number of neurostimulants received during rehabilitation was associated with recovery of full consciousness or improved neurobehavioral function after severe BI. METHOD: Data from 115 participants were extracted from a neurobehavioral observational study database for this exploratory, retrospective analysis. Univariate optimal data analysis was conducted to determine if the number of neurostimulants influenced classification of four outcomes: recovery of full consciousness during rehabilitation, recovery of full consciousness within one year of injury, and meaningful neurobehavioral improvement during rehabilitation defined as either at least a 4.7 unit (minimal detectable change) or 2.58 unit (minimal clinically important difference) gain on the Disorders of Consciousness Scale-25 (DOCS-25). RESULTS: Number of neurostimulants was not significantly (P > 0.05) associated with recovery of full consciousness during rehabilitation, within one year of injury, or meaningful neurobehavioral improvement using the DOCS-25. CONCLUSIONS: Receiving multiple neurostimulants during rehabilitation may not influence recovery of full consciousness or meaningful neurobehavioral improvement. Given costs associated with additional medication, future research is needed to guide physicians about the merits of prescribing multiple neurostimulants during rehabilitation after severe BI.

Medical comorbidities in disorders of consciousness patients and their association with functional outcomes.

OBJECTIVE: To identify, for patients in states of seriously impaired consciousness, comorbid conditions present during inpatient rehabilitation and their association with function at 1 year. DESIGN: Abstracted data from a prospective cross-sectional observational study with data collection occurring January 1996 through December 2007. SETTING: Four inpatient rehabilitation facilities in metropolitan areas. PARTICIPANTS: The study sample of 68 participants is abstracted from a database of 157 patients remaining in states of seriously impaired consciousness for at least 28 days. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: One-year cognitive, motor, and total FIM score. RESULTS: The most common medical complications during inpatient rehabilitation for the study sample are active seizures (46%), spasticity (57%), urinary tract infections (47%), and hydrocephalus with and without shunt (38%). Presence of ≥3 medical complications during inpatient rehabilitation, controlling for injury severity, is significantly (P<.05) associated with poorer total FIM and FIM motor scores 1 year after injury. The presence of hydrocephalus with and without shunt (r=-.20, -.21, -.18; P ≤.15), active seizures (r=-.31, -.22, -.42), spasticity (r=-.38, -.28, -.40), and urinary tract infections (r=-.25, -.24, -.26) were significantly (P<.10) associated with total FIM, FIM cognitive, and FIM motor scores, respectively. CONCLUSIONS: Reported findings indicate that persons in states of seriously impaired consciousness with higher numbers of medical complications during inpatient rehabilitation are more likely to have lower functional levels 1-year postinjury. The findings indicate that persons with ≥3 medical complications during inpatient rehabilitation are at a higher risk for poorer functional outcomes at 1 year. It is, therefore, prudent to evaluate these patients for indications of these complications during inpatient rehabilitation.

Comparing indices of responsiveness for the Coma Near-Coma Scale with and without pain items: An Exploratory study.

INTRODUCTION: This study aimed to establish the indices of responsiveness for the Coma/Near-Coma (CNC) scale without (8 items) and with (10 items) pain test stimuli. A secondary purpose was to examine whether the CNC 8 items and 10 items differ when detecting change in neurobehavioral function. METHODS: We analyzed CNC data from three studies of participants with disorders of consciousness: one observational study and two intervention studies. We generated Rasch person measures using the CNC 8 items and CNC 10 items for each participant at two time points 14 ± 2 days apart using Rasch Measurement Theory. We calculated the distribution-based minimal clinically important difference (MCID) and minimal detectable change using 95% confidence intervals (MDC95 ). RESULTS: We used the Rasch transformed equal-interval scale person measures in logits. For the CNC 8 items: Distribution-based MCID 0.33 SD = 0.41 logits and MDC95  = 1.25 logits. For the CNC 10 items: Distribution-based MCID 0.33 SD = 0.37 logits and MDC95  = 1.03 logits. Twelve and 13 participants made a change beyond measurement error (MDC95 ) using the CNC 8-item and 10-item scales, respectively. CONCLUSION: Our preliminary evidence supports the clinical and research utility of the CNC 8-item scale for measuring the responsiveness of neurobehavioral function, and that it demonstrates comparable responsiveness to the CNC 10-item scale without administering the two pain items. The distribution-based MCID can be used to evaluate group-level changes while the MDC95 can support clinical, data-driven decisions about an individual patient.

"Fluctuation is the norm": Rehabilitation practitioner perspectives on ambiguity and uncertainty in their work with persons in disordered states of consciousness after traumatic brain injury.

The purpose of this study is to describe the clinical lifeworld of rehabilitation practitioners who work with patients in disordered states of consciousness (DoC) after severe traumatic brain injury (TBI). We interviewed 21 practitioners using narrative interviewing methods from two specialty health systems that admit patients in DoC to inpatient rehabilitation. The overarching theme arising from the interview data is "Experiencing ambiguity and uncertainty in clinical reasoning about consciousness" when treating persons in DoC. We describe practitioners' practices of looking for consistency, making sense of ambiguous and hard to explain patient responses, and using trial and error or "tinkering" to care for patients. Due to scientific uncertainty about diagnosis and prognosis in DoC and ambiguity about interpretation of patient responses, working in the field of DoC disrupts the canonical meaning-making processes that practitioners have been trained in. Studying the lifeworld of rehabilitation practitioners through their story-making and story-telling uncovers taken-for-granted assumptions and normative structures that may exist in rehabilitation medical and scientific culture, including practitioner training. We are interested in understanding these canonical breaches in order to make visible how practitioners make meaning while treating patients.

Mapping outcomes for recovery of consciousness in studies from 1986 to 2020: a scoping review protocol.

INTRODUCTION: Historically, heterogeneous outcome assessments have been used to measure recovery of consciousness in patients with disorders of consciousness (DoC) following traumatic brain injury (TBI), making it difficult to compare across studies. To date, however, there is no comprehensive review of clinical outcome assessments that are used in intervention studies of adults with DoC. The objective of this scoping review is to develop a comprehensive inventory of clinical outcome assessments for recovery of consciousness that have been used in clinical studies of adults with DoC following TBI. METHODS AND ANALYSIS: The methodological framework for this review is: (1) identify the research questions, (2) identify relevant studies, (3) select studies, (4) chart the data, (5) collate, summarise and report results and (6) consult stakeholders to drive knowledge translation. We will identify relevant studies by searching the following electronic bibliographic databases: PubMed, Scopus, EMBASE, PsycINFO and The Cochrane Library (including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and Cochrane Methodology Register). Criteria for article inclusion are published in the English-language, peer-reviewed studies of interventions aimed at facilitating recovery of consciousness among adults (> 18 years) with DoC following a severe TBI, published from January 1986 to December 2020. Articles meeting inclusion criteria at this stage will undergo a full text review. We will chart the data by applying the WHO International Classification of Functioning, Disability and Health Framework to identify the content areas of clinical outcome assessments. To support knowledge translation efforts, we will involve clinicians and researchers experienced in TBI care throughout the project from conceptualisation of the study through dissemination of results. ETHICS AND DISSEMINATION: No ethical approval is required for this study as it is not determined to be human subjects research. Results will be presented at national conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: CRD42017058383.

Psychometric measurement properties of the world health organization disability assessment schedule 2.0 (WHODAS) evaluated among veterans with mild traumatic brain injury and behavioral health conditions.

PURPOSE: Examine the psychometric properties of the World Health Organization Disability Assessment Schedule 2.0 among U.S. Iraq/Afghanistan Veterans with a combination of mild traumatic brain injury and behavioral health conditions using Rasch analysis. METHODS: 307 Veterans were classified as either combat control (n = 141), or one of three clinical groups: mild traumatic brain injury (n = 10), behavioral health conditions (n = 24), or both (n = 128). Data from the three clinical groups were used to establish step and item calibrations serving as anchors when including the control group. RESULTS: Measurement precision was excellent (person separation reliability = 0.93). Ordering of item calibrations formed a logical hierarchy. Test items were off-target (too easy) for the clinical groups. Principal component analysis indicated unidimensionality although 4/36 items misfit the measurement model. No meaningful differential item functioning was detected. There was a moderate effect size (Hedge's g = 1.64) between the control and clinical groups. CONCLUSIONS: The World Health Organization Disability Assessment Schedule was suitable for our study sample, distinguishing 4 levels of functional ability. Although items may be easy for some Veterans with mild traumatic brain injury and/or behavioral health conditions, the World Health Organization Disability Assessment Schedule can be used to capture disability information for those with moderate to severe disability.Implications for rehabilitationPersistent functional disability is seen in military and civilian populations with mild traumatic brain injury which often co-occurs with behavioral health conditions.A comprehensive measure of disability is needed to distinguish between levels of disability to inform clinical decisions for individual patients and to detect treatment effects between groups in research.Results of this analysis indicate the World Health Organization Disability Assessment Schedule items are sufficiently unidimensional to evaluate level of disability in the moderate and severe range among persons with mild traumatic brain injury with and without behavioral health conditions.Further examination of the psychometric properties of the World Health Organization.Disability Assessment Schedule is necessary before measurement of disability is recommended for those with less than moderate levels of disability.

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).

Familiar auditory sensory training in chronic traumatic brain injury: a case study.

PURPOSE: The evaluation and treatment for patients with prolonged periods of seriously impaired consciousness following traumatic brain injury (TBI), such as a vegetative or minimally conscious state, poses considerable challenges, particularly in the chronic phases of recovery. METHOD: This blinded crossover study explored the effects of familiar auditory sensory training (FAST) compared with a sham stimulation in a patient seven years post severe TBI. Baseline data were collected over 4 weeks to account for variability in status with neurobehavioral measures, including the Disorders of Consciousness scale (DOCS), Coma Near Coma scale (CNC), and Consciousness Screening Algorithm. Pre-stimulation neurophysiological assessments were completed as well, namely Brainstem Auditory Evoked Potentials (BAEP) and Somatosensory Evoked Potentials (SSEP). RESULTS: Results revealed that a significant improvement in the DOCS neurobehavioral findings after FAST, which was not maintained during the sham. BAEP findings also improved with maintenance of these improvements following sham stimulation as evidenced by repeat testing. CONCLUSIONS: The results emphasize the importance for continued evaluation and treatment of individuals in chronic states of seriously impaired consciousness with a variety of tools. Further study of auditory stimulation as a passive treatment paradigm for this population is warranted. Implications for Rehabilitation Clinicians should be equipped with treatment options to enhance neurobehavioral improvements when traditional treatment methods fail to deliver or maintain functional behavioral changes. Routine assessment is crucial to detect subtle changes in neurobehavioral function even in chronic states of disordered consciousness and determine potential preserved cognitive abilities that may not be evident due to unreliable motor responses given motoric impairments. Familiar Auditory Stimulation Training (FAST) is an ideal passive stimulation that can be supplied by families, allied health clinicians and nursing staff of all levels.