Development and Evaluation of a Pragmatic Measure of Adherence to Dialectical Behavior Therapy: The DBT Adherence Checklist for Individual Therapy.

This paper presents two studies conducted to develop and evaluate a new pragmatic measure of therapist adherence to Dialectical Behavior Therapy (DBT): the DBT Adherence Checklist for Individual Therapy (DBT AC-I). Study 1 used item response analysis to select items from the gold standard DBT Adherence Coding Scale (DBT ACS) using archival data from 1271 DBT sessions. Items were then iteratively refined based on feedback from 33 target end-users to ensure relevance, usability, and understandability. Study 2 examined the psychometric properties of the DBT AC-I as a therapist self-report and observer-rated measure in 100 sessions from 50 therapist-client dyads, while also evaluating predictors of therapist accuracy in self-rated adherence. When used as a therapist self-report measure, concordance between therapist and observer ratings was at least moderate (AC1 ≥ 0.41) for all DBT AC-I items but overall concordance (ICC = 0.09) as well as convergent (r = 0.05) and criterion validity (AUC = 0.54) with the DBT ACS were poor. Higher therapist accuracy was predicted by greater DBT knowledge and adherence as well as more severe client suicidal ideation. When used by trained observers, the DBT AC-I had excellent interrater reliability (ICC = 0.93), convergent validity (r = 0.90), and criterion validity (AUC = 0.94). While therapists' self-rated adherence on the DBT AC-I should not be assumed to reflect their actual adherence, some therapists may self-rate accurately. The DBT AC-I offers an effective and relatively efficient method of evaluating adherence to DBT when used by trained observers.

Incidence and risk factors for graft failure in the modern era of cord blood transplantation.

BACKGROUND AND OBJECTIVES: Graft failure (GF) after cord blood transplant (CBT) has decreased with improved supportive care and cord selection strategies. We aimed to evaluate cord blood selection and factors associated with retransplantation on the incidence of GF, determine risk factors for GF including host antibodies to Kell antigen and evaluate survival after GF. MATERIALS AND METHODS: We retrospectively reviewed 84 patients who underwent CBT at the University of Oklahoma between 2000 and 2016 and compared outcomes in patients with/without engraftment by Day 28. The nonengraftment cohort was further divided into patients who underwent retransplantation. Kaplan-Meier curves with log-rank tests were calculated to assess the association between mortality and engraftment. RESULTS: Engraftment following CBT was high at 81%, with 52% engrafting by Day 28 and an additional 29% engrafting by a median of 36 days. Retransplantation led to 88% engraftment at a median of 53 days. Overall, 75% of the 40 patients who did not engraft by Day 28 died. Female sex and total nucleated cell count < 3.5/kg were significantly associated with lack of engraftment and higher mortality. Antibodies to Kell fetal antigen were not identified. Retransplantation by Day 28 for primary GF conferred a survival advantage. CONCLUSION: This study demonstrates that failure to engraft by 28 days was associated with increased mortality, and risk was mitigated with early retransplantation. Female sex and low total cell dose were associated with increased mortality. Early identification of GF coupled with early retransplantation can reduce mortality in CBT.

Effects of Workshop Training in the Dialectical Behavior Therapy Prolonged Exposure Protocol on Clinician Beliefs, Adoption, and Perceived Clinical Outcomes.

Although extensive efforts have been made to train clinicians in evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD), relatively few PTSD patients are considered appropriate for and therefore receive these treatments. The dialectical behavior therapy prolonged exposure (DBT PE) protocol was developed to expand the reach of EBPs for PTSD to suicidal patients with severe comorbidities, but methods of training clinicians to deliver this treatment have not been evaluated. We examined the impact of DBT PE workshops on clinician beliefs, adoption, and perceived patient outcomes. Clinicians (N = 266) attended 2- or 4-day workshops and completed surveys at pretraining, posttraining, and 3- and 6-month follow-ups. From pretraining to 6-month follow-up, there were significant improvements in clinician concerns regarding worsening, perceived treatment credibility, and self-efficacy that did not differ by workshop length, R2 s = .20-.45. At 6-months posttraining, 53.5% of clinicians (38.8% 2-day, 66.3% 4-day) reported using DBT PE with 241 patients. Higher posttraining ratings of self-efficacy and perceived treatment credibility predicted later DBT PE use, R2 = .28. Among adopting clinicians, 81.3% reported that, on average, their patients' PTSD improved and 66.7% reported that patients were much to very much improved on average. Most clinicians reported that their patients' comorbid problems did not worsen during DBT PE and if worsening occurred, it typically involved temporary increases in distress. Workshops may be an effective method of changing clinician beliefs and promoting the use of DBT PE in a manner that clinicians experience as effective and safe for their patients.

Identifying Change Targets for Posttraumatic Stress Disorder Among Suicidal and Self-Injuring Women With Borderline Personality Disorder.

Research on psychotherapies for posttraumatic stress disorder (PTSD) is increasingly focused on understanding not only which treatments work but why and for whom they work. The present pilot study evaluated the temporal relations between five hypothesized change targets-posttraumatic cognitions, guilt, shame, general emotion dysregulation, and experiential avoidance-and PTSD severity among women with PTSD, borderline personality disorder, and recent suicidal and/or self-injurious behaviors. Participants (N = 26) were randomized to receive 1 year of dialectical behavior therapy (DBT) with or without the DBT prolonged exposure (DBT PE) protocol for PTSD. Potential change targets and PTSD were assessed at 4-month intervals during treatment and at 3-month posttreatment follow-up. Time-lagged mixed-effects models indicated that between-person differences in all change targets except guilt were associated with more severe PTSD, η2 s = .32-.55, and, except for general emotion dysregulation, slowed the rate of change in PTSD severity over time, η2 s = .20-.39. In DBT but not in DBT + DBT PE, individuals with higher levels of guilt and experiential avoidance relative to their own average had more severe PTSD at the next assessment point, η2 s = .12-.25. The associations between the proposed change targets and PTSD severity were not bidirectional, except for general emotion dysregulation, η2 = .50; and posttraumatic cognitions, η2 = .06. These preliminary findings suggest that trauma-related cognitions, shame, and guilt, as well as problems regulating them, may be important change targets for improving PTSD in this patient population.

Workflow Analysis Driven Recommendations for Integration of Electronically-Enhanced Sexually Transmitted Infection Screening Tools in Pediatric Emergency Departments.

Adolescents are disproportionately affected by sexually transmitted infections (STIs). Failure to diagnose and treat STIs in a timely manner may result in serious sequelae. Adolescents frequently access the emergency department (ED) for care. Although ED-based STI screening is acceptable to both patients and clinicians, understanding how best to implement STI screening processes into the ED clinical workflow without compromising patient safety or efficiency is critical. The objective of this study was to conduct direct observations documenting current workflow processes and tasks during patient visits at six Pediatric Emergency Care Applied Research Network (PECARN) EDs for site-specific integration of STI electronically-enhanced screening processes. Workflow observations were captured via TaskTracker, a time and motion electronic data collection application that allows researchers to categorize general work processes and record multitasking by providing a timestamp of when tasks began and ended. Workflow was captured during 118 patient visits across six PECARN EDs. The average time to initial assessment by the most senior provider was 76 min (range 59-106 min, SD = 43 min). Care teams were consistent across sites, and included attending physicians, advanced practice providers, nurses, registration clerks, technicians, and students. A timeline belt comparison was performed. Across most sites, the most promising implementation of a STI screening tool was in the patient examination room following the initial patient assessment by the nurse.

Perspectives on a Stage-Based Treatment for Posttraumatic Stress Disorder Among Dialectical Behavior Therapy Consumers in Public Mental Health Settings.

Difficulties with consumer engagement are a common barrier to implementing trauma-focused evidence-based psychotherapies (TF-EBPs). Potential methods of increasing engagement include utilizing a stage-based treatment approach, and involving consumers in implementation efforts. This mixed method study explored consumers' perspectives on a stage-based TF-EBP, Dialectical Behavior Therapy (DBT) with the DBT Prolonged Exposure (DBT PE) protocol. Nineteen DBT consumers in two public mental health agencies targeted for implementation of DBT + DBT PE participated in focus groups and completed questionnaires assessing treatment preferences and expectancies. Consumers reported positive treatment expectancies and a strong preference for DBT with DBT PE (89.5%) over DBT alone (5.3%) or PE alone (5.3%). This was primarily due to beliefs about the treatment's efficacy, a perceived need for PTSD treatment, and the stage-based approach. Consumer-focused strategies for increasing uptake and reach of TF-EBPs are discussed.

Neural Plasticity of Mild Tinnitus: An fMRI Investigation Comparing Those Recently Diagnosed with Tinnitus to Those That Had Tinnitus for a Long Period of Time.

Objectives. The aim of the study was to compare differences in neural correlates of tinnitus in adults with recent onset and others who had the disorder for longer than a year. Design. A total of 25 individuals with tinnitus were divided into groups based on the amount of time for which they had experienced tinnitus: <1 year (RTIN) or >1 year (LTIN). Subjects underwent an fMRI scan while listening to affective sounds from the International Affective Digital Sounds database. Resting state functional connectivity data were also collected. Results. The RTIN group recruited the posterior cingulate and insula to a greater extent than the LTIN group when processing affective sounds. In addition, we found that the LTIN group engaged more frontal regions when listening to the stimuli compared to the RTIN group. Lastly, we found increased correlations between the default mode network and the precuneus in RTIN patients compared to LTIN at rest. Conclusion. Our results suggest that the posterior cingulate and insula may be associated with an early emotional reaction to tinnitus in both task and resting states. Over time, tinnitus patients may recruit more frontal regions to better control their emotional response and exhibit altered connectivity in the default mode network.

Microscopic clusters feature the composition of biochemical tetraspanin-assemblies and constitute building-blocks of tetraspanin enriched domains.

Biochemical approaches revealed that tetraspanins are multi-regulatory proteins forming a web, where they act in tetraspanin-enriched-microdomains (TEMs). A microscopic criterion differentiating between web and TEMs is lacking. Using super-resolution microcopy, we identify co-assemblies between the tetraspanins CD9 and CD81 and CD151 and CD81. CD9 assemblies contain as well the CD9/CD81-interaction partner EWI-2. Moreover, CD9 clusters are proximal to clusters of the CD81-interaction partner CD44 and CD81-/EWI-2-interacting ezrin-radixin-moesin proteins. Assemblies scatter unorganized across the cell membrane; yet, upon EWI-2 elevation, they agglomerate into densely packed arranged-crowds in a process independent from actin dynamics. In conclusion, microscopic clusters are equivalent to biochemical tetraspanin-assemblies, defining in their entirety the tetraspanin web. Cluster-agglomeration enriches tetraspanins, which makes agglomerations to a microscopic complement of TEMs. The microscopic classification of tetraspanin assemblies advances our understanding of this enigmatic protein family, whose members play roles in a plethora of cellular functions, diseases, and pathogen infections.

Plasma membrane potential oscillations in insulin secreting Ins-1 832/13 cells do not require glycolysis and are not initiated by fluctuations in mitochondrial bioenergetics.

Oscillations in plasma membrane potential play a central role in glucose-induced insulin secretion from pancreatic ß-cells and related insulinoma cell lines. We have employed a novel fluorescent plasma membrane potential (Δψ(p)) indicator in combination with indicators of cytoplasmic free Ca(2+) ([Ca(2+)](c)), mitochondrial membrane potential (Δψ(m)), matrix ATP concentration, and NAD(P)H fluorescence to investigate the role of mitochondria in the generation of plasma membrane potential oscillations in clonal INS-1 832/13 ß-cells. Elevated glucose caused oscillations in plasma membrane potential and cytoplasmic free Ca(2+) concentration over the same concentration range required for insulin release, although considerable cell-to-cell heterogeneity was observed. Exogenous pyruvate was as effective as glucose in inducing oscillations, both in the presence and absence of 2.8 mM glucose. Increased glucose and pyruvate each produced a concentration-dependent mitochondrial hyperpolarization. The causal relationships between pairs of parameters (Δψ(p) and [Ca(2+)](c), Δψ(p) and NAD(P)H, matrix ATP and [Ca(2+)](c), and Δψ(m) and [Ca(2+)](c)) were investigated at single cell level. It is concluded that, in these ß-cells, depolarizing oscillations in Δψ(p) are not initiated by mitochondrial bioenergetic changes. Instead, regardless of substrate, it appears that the mitochondria may simply be required to exceed a critical bioenergetic threshold to allow release of insulin. Once this threshold is exceeded, an autonomous Δψ(p) oscillatory mechanism is initiated.

An Inverse Relationship Between Gray Matter Volume and Speech-in-Noise Performance in Tinnitus Patients with Normal Hearing Sensitivity.

Speech-in-noise (SiN) recognition difficulties are often reported in patients with tinnitus. Although brain structural changes such as reduced gray matter (GM) volume in auditory and cognitive processing regions have been reported in the tinnitus population, it remains unclear how such changes influence speech understanding, such as SiN performance. In this study, pure-tone audiometry and Quick Speech-in-Noise test were conducted on individuals with tinnitus and normal hearing and hearing-matched controls. T1-weighted structural MRI images were obtained from all participants. After preprocessing, GM volumes were compared between tinnitus and control groups using whole-brain and region-of-interest analyses. Further, regression analyses were performed to examine the correlation between regional GM volume and SiN scores in each group. The results showed decreased GM volume in the right inferior frontal gyrus in the tinnitus group relative to the control group. In the tinnitus group, SiN performance showed a negative correlation with GM volume in the left cerebellum (Crus I/II) and the left superior temporal gyrus; no significant correlation between SiN performance and regional GM volume was found in the control group. Even with clinically defined normal hearing and comparable SiN performance relative to controls, tinnitus appears to change the association between SiN recognition and regional GM volume. This change may reflect compensatory mechanisms utilized by individuals with tinnitus who maintain behavioral performance.

Effectiveness of and processes related to internet-delivered acceptance and commitment therapy for adolescents with anxiety disorders: a randomized controlled trial.

Early access to evidence-based help is crucial for adolescents with anxiety disorders. Internet-delivered acceptance and commitment therapy (iACT) may offer adolescents increased access to care and more flexibility in engaging with treatment when and how they prefer. Process-based therapies, such as ACT, focus on theoretically derived and empirically tested key mechanisms in treatment that enable change. This study aimed to investigate the effectiveness of iACT for adolescents with anxiety disorders. The study also assessed the relationship between psychological flexibility and treatment outcomes and the relationship between participating adolescents' and therapists' perceived alliance and treatment outcomes. This was a randomized controlled trial comparing a 10-week intervention group with a wait-list control group. The 52 participants, aged 15 to 19, were recruited from all over Sweden. The treatment was effective in increasing quality of life and psychological flexibility, with moderate between-group effect sizes based on observed values. Changes in psychological flexibility was associated with changes in anxiety symptoms. The results further showed a statistically significant between-group difference in post-treatment diagnoses. No significant time per group interaction was found for anxiety symptoms, as both groups improved. Working alliance was rated as high by both participating adolescents and therapists but showed no significant relationship with treatment outcomes. Participants found the treatment an acceptable intervention. This study shows promising results for iACT in treating adolescents with anxiety disorders. The results suggest the model of psychological flexibility as an important process of change in treatment outcomes. Future research should validate these findings in larger samples and clinical contexts.

The temporal relationships between therapist adherence and patient outcomes in dialectical behavior therapy.

OBJECTIVE: Although Dialectical Behavior Therapy (DBT) is a well-established evidence-based psychotherapy, little is known about the role of therapist adherence in promoting positive outcomes. This study evaluated the temporal relationships between therapist adherence to DBT and patient outcomes, as well as potential moderators of these relationships. METHOD: Data were from six clinical trials conducted in research and community settings with a variety of patient populations. In these trials, trained observers rated 83 therapists for adherence during 1,262 DBT individual therapy sessions with 288 patients. Patient outcomes included suicide attempts, nonsuicidal self-injury (NSSI), treatment dropout, psychiatric hospitalizations, and global functioning. Longitudinal mixed-effects models evaluated the time-ordered, bidirectional relationships between adherence and outcomes. RESULTS: Higher therapist adherence significantly predicted fewer subsequent suicide attempts (p = .002, η = 0.32) and a lower risk of dropout (p = .002, η = 0.33), and the latter relationship was strongest among patients with comorbid opioid dependence. Higher therapist adherence predicted fewer subsequent hospitalizations among community therapists (p = .001, η = 0.35) and patients that were not exclusively suicidal/self-injuring (p < .001, η = 0.41). Conversely, more frequent NSSI (p = .03, η = 0.22) and worse global functioning (p = .01, η = 0.26) predicted higher subsequent therapist adherence, and the latter relationship was moderated by patient population. CONCLUSIONS: Therapist adherence improves several key patient outcomes and retention, highlighting the importance of delivering DBT with adherence to the manual. Therapists may find it easier to deliver DBT adherently to more severely impaired patients. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Does Adding the Dialectical Behavior Therapy Prolonged Exposure (DBT PE) Protocol for PTSD to DBT Improve Outcomes in Public Mental Health Settings? A Pilot Nonrandomized Effectiveness Trial With Benchmarking.

The Dialectical Behavior Therapy Prolonged Exposure (DBT PE) protocol improves DBT's effects on PTSD in research settings, but its effectiveness in community settings is largely unknown. This pilot nonrandomized controlled trial examined DBT with and without DBT PE in four public mental health agencies. Patients (N = 35, 12-56 years old, 80.0% female, 64.7% racial/ethnic minorities, 44.1% sexual minorities) had PTSD, were receiving DBT, and completed assessments every four months over one year. Sixteen patients (45.7%) initiated DBT PE, 19 (54.3%) did not, and dropout did not differ between groups (31.3% vs. 26.3%). The primary barrier to initiating DBT PE was clinician turnover (57.9% of non-initiators). After adjusting for confounds, DBT PE initiators (g = 1.1) and completers (g = 1.4) showed a greater reduction in PTSD than patients who received DBT only (g = 0.5; p's < .05). Rates of reliable improvement in PTSD were 71.4% (DBT PE completers), 53.8% (DBT PE initiators), and 31.3% (DBT). Similar patterns were observed for posttraumatic cognitions, emotion dysregulation, general psychological distress, and limited activity days. There was no worsening of self-injurious behavior or crisis service use among patients who received DBT PE. Benchmarking analyses indicated comparable feasibility, acceptability, and safety, but a smaller magnitude of clinical change, than in efficacy studies. Results require replication in a randomized trial but suggest that DBT PE can be transported effectively to community settings.

The Dialectical Behavior Therapy Adherence Coding Scale (DBT ACS): Psychometric properties.

The Dialectical Behavior Therapy Adherence Coding Scale (DBT ACS) is an observer-rated measure used to evaluate the extent to which therapists deliver individual and group DBT with adherence to the manual. Despite its frequent use in clinical trials of DBT, relatively little is known about its psychometric properties. The present study utilized data from six clinical trials conducted in research and community settings with a variety of patient populations. Across these studies, the DBT ACS was used to code a total of 1,271 DBT individual therapy sessions and 180 DBT group sessions. Results indicate the DBT ACS computed global score has good internal consistency (α = .81) and excellent interrater reliability (ICC = .93). A confirmatory factor analysis found that a single factor yielded acceptable goodness of fit indices. The DBT ACS discriminated between DBT and another treatment and between research and community therapists. Across studies, variability in adherence scores was attributable more to therapists (33%) than to patients (15%). Both therapist and patient variability were higher in effectiveness than efficacy trials. Generalizability coefficients indicated that 5 sessions are needed to estimate a dependable adherence score at the patient level, whereas 9-15 sessions are needed to achieve adequate generalizability at the therapist level. Fewer sessions were needed to yield dependable scores for community therapists compared to research therapists. The DBT ACS appears to be a reliable, valid, and dependable method of assessing therapist adherence to individual and group DBT across diverse treatment settings, therapist types, and patient populations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Salience, emotion, and attention: The neural networks underlying tinnitus distress revealed using music and rest.

In the present study, we used an innovative music-rest interleaved fMRI paradigm to investigate the neural correlates of tinnitus distress. Tinnitus is a poorly-understood hearing disorder where individuals perceive sounds, in the absence of an external source. Although the great majority of individuals habituate to chronic tinnitus and report few symptoms, a minority report debilitating distress and annoyance. Prior research suggests that a diverse set of brain regions, including the attention, the salience, and the limbic networks, play key roles in mediating both the perception of tinnitus and its impact on the individual; however, evidence of the degree and extent of their involvement has been inconsistent. Here, we minimally modified the conventional resting state fMRI by interleaving it with segments of jazz music. We found that the functional connectivity between a set of brain regions-including cerebellum, precuneus, superior/middle frontal gyrus, and primary visual cortex-and seeds in the dorsal attention network, the salience network, and the amygdala, were effective in fractionating the tinnitus patients into two subgroups, characterized by the severity of tinnitus-related distress. Further, our findings revealed cross-modal modulation of the attention and salience networks by the visual modality during the music segments. On average, the more bothersome the reported tinnitus, the stronger was the exhibited inter-network functional connectivity. This study substantiates the essential role of the attention, salience, and limbic networks in tinnitus habituation, and suggests modulation of the attention and salience networks across the auditory and visual modalities as a possible compensatory mechanism for bothersome tinnitus.

Decreased resting perfusion in precuneus and posterior cingulate cortex predicts tinnitus severity.

Functional magnetic resonance imaging has been increasingly used to understand the mechanisms involved in subjective tinnitus; however, researchers have struggled to reach a consensus about a primary mechanistic model to explain tinnitus. While many studies have used functional connectivity of the BOLD signal to understand how patterns of activity change with tinnitus severity, there is much less research on whether there are differences in more fundamental physiology, including cerebral blood flow, which may help inform the BOLD measures. Here, arterial spin labeling was used to measure perfusion in four regions-of-interest, guided by current models of tinnitus, in a sample of 60 tinnitus patients and 31 control subjects. We found global reductions in cerebral perfusion in tinnitus compared with controls. Additionally, we observed a significant negative correlation between tinnitus severity and perfusion. These results demonstrate that examining perfusion from the whole brain may present a complementary tool for studying tinnitus. More research will help better understand the physiology underlying these differences in perfusion.

A large-scale diffusion imaging study of tinnitus and hearing loss.

Subjective, chronic tinnitus, the perception of sound in the absence of an external source, commonly occurs with many comorbidities, making it a difficult condition to study. Hearing loss, often believed to be the driver for tinnitus, is perhaps one of the most significant comorbidities. In the present study, white matter correlates of tinnitus and hearing loss were examined. Diffusion imaging data were collected from 96 participants-43 with tinnitus and hearing loss (TINHL), 17 with tinnitus and normal hearing thresholds (TINNH), 17 controls with hearing loss (CONHL) and 19 controls with normal hearing (CONNH). Fractional anisotropy (FA), mean diffusivity and probabilistic tractography analyses were conducted on the diffusion imaging data. Analyses revealed differences in FA and structural connectivity specific to tinnitus, hearing loss, and both conditions when comorbid, suggesting the existence of tinnitus-specific neural networks. These findings also suggest that age plays an important role in neural plasticity, and thus may account for some of the variability of results in the literature. However, this effect is not seen in tractography results, where a sensitivity analysis revealed that age did not impact measures of network integration or segregation. Based on these results and previously reported findings, we propose an updated model of tinnitus, wherein the internal capsule and corpus callosum play important roles in the evaluation of, and neural plasticity in response to tinnitus.

Poly-Epsilon-Lysine Hydrogels with Dynamic Crosslinking Facilitates Cell Proliferation.

The extracellular matrix (ECM) is a three-dimensional network within which fundamental cell processes such as cell attachment, proliferation, and differentiation occur driven by its inherent biological and structural cues. Hydrogels have been used as biomaterials as they possess many of the ECM characteristics that control cellular processes. However, the permanent crosslinking often found in hydrogels fails to recapitulate the dynamic nature of the natural ECM. This not only hinders natural cellular migration but must also limit cellular expansion and growth. Moreover, there is an increased interest in the use of new biopolymers to create biomimetic materials that can be used for biomedical applications. Here we report on the natural polymer poly-ε-lysine in forming dynamic hydrogels via reversible imine bond formation, with cell attachment promoted by arginine-glycine-aspartic acid (RGD) incorporation. Together, the mechanical properties and cell behavior of the dynamic hydrogels with low poly-ε-lysine quantities indicated good cell viability and high metabolic activity.

Dissociating tinnitus patients from healthy controls using resting-state cyclicity analysis and clustering.

Chronic tinnitus is a common and sometimes debilitating condition that lacks scientific consensus on physiological models of how the condition arises as well as any known cure. In this study, we applied a novel cyclicity analysis, which studies patterns of leader-follower relationships between two signals, to resting-state functional magnetic resonance imaging (rs-fMRI) data of brain regions acquired from subjects with and without tinnitus. Using the output from the cyclicity analysis, we were able to differentiate between these two groups with 58-67% accuracy by using a partial least squares discriminant analysis. Stability testing yielded a 70% classification accuracy for identifying individual subjects' data across sessions 1 week apart. Additional analysis revealed that the pairs of brain regions that contributed most to the dissociation between tinnitus and controls were those connected to the amygdala. In the controls, there were consistent temporal patterns across frontal, parietal, and limbic regions and amygdalar activity, whereas in tinnitus subjects, this pattern was much more variable. Our findings demonstrate a proof-of-principle for the use of cyclicity analysis of rs-fMRI data to better understand functional brain connectivity and to use it as a tool for the differentiation of patients and controls who may differ on specific traits.

Functional Brain Changes During Mindfulness-Based Cognitive Therapy Associated With Tinnitus Severity.

Mindfulness-based therapies have been introduced as a treatment option to reduce the psychological severity of tinnitus, a currently incurable chronic condition. This pilot study of twelve subjects with chronic tinnitus investigates the relationship between measures of both task-based and resting state functional magnetic resonance imaging (fMRI) and measures of tinnitus severity, assessed with the Tinnitus Functional Index (TFI). MRI was measured at three time points: before, after, and at follow-up of an 8-week long mindfulness-based cognitive therapy intervention. During the task-based fMRI with affective sounds, no significant changes were observed between sessions, nor was the activation to emotionally salient compared to neutral stimuli significantly predictive of TFI. Significant results were found using resting state fMRI. There were significant decreases in functional connectivity among the default mode network, cingulo-opercular network, and amygdala across the intervention, but no differences were seen in connectivity with seeds in the dorsal attention network (DAN) or fronto-parietal network and the rest of the brain. Further, only resting state connectivity between the brain and the amygdala, DAN, and fronto-parietal network significantly predicted TFI. These results point to a mostly differentiated landscape of functional brain measures related to tinnitus severity on one hand and mindfulness-based therapy on the other. However, overlapping results of decreased amygdala connectivity with parietal areas and the negative correlation between amygdala-parietal connectivity and TFI is suggestive of a brain imaging marker of successful treatment.