Joyce Nicklaus

Altered networks in bothersome tinnitus: a functional connectivity study

BackgroundThe objective was to examine functional connectivity linked to the auditory system in patients with bothersome tinnitus. Activity was low frequency (< 0.1 Hz), spontaneous blood oxygenation level-dependent (BOLD) responses at rest. The question was whether the experience of chronic bothersome tinnitus induced changes in synaptic efficacy between co-activated components. Functional connectivity for seed regions in auditory, visual, attention, and control networks was computed across all 2 mm3 brain volumes in 17 patients with moderate-severe bothersome tinnitus (Tinnitus Handicap Index: average 53.5 ± 3.6 (range 38-76)) and 17 age-matched controls.ResultsIn bothersome tinnitus, negative correlations reciprocally characterized functional connectivity between auditory and occipital/visual cortex. Negative correlations indicate that when BOLD response magnitudes increased in auditory or visual cortex they decreased in the linked visual or auditory cortex, suggesting reciprocally phase reversed activity between functionally connected locations in tinnitus. Both groups showed similar connectivity with positive correlations within the auditory network. Connectivity for primary visual cortex in tinnitus included extensive negative correlations in the ventral attention temporoparietal junction and in the inferior frontal gyrus and rostral insula - executive control network components. Rostral insula and inferior frontal gyrus connectivity in tinnitus also showed greater negative correlations in occipital cortex.ConclusionsThese results imply that in bothersome tinnitus there is dissociation between activity in auditory cortex and visual, attention and control networks. The reciprocal negative correlations in connectivity between these networks might be maladaptive or reflect adaptations to reduce phantom noise salience and conflict with attention to non-auditory tasks.

Ecological Momentary Assessment of Tinnitus Using Smartphone Technology A Pilot Study

Objective To explore the feasibility of ecological momentary assessments (EMAs) as a tool to more accurately assess the level of bother from tinnitus. Study Design Longitudinal observational study. Setting Washington University Department of Otolaryngology–Head and Neck Surgery faculty practice plan. Subjects and Methods Twenty participants with moderately to severely bothersome tinnitus were enrolled. All participants owned a smartphone device, and all communications were conducted via email, phone, and text messaging. Participants received 4 EMAs per day for 2 weeks via text message and a final survey on the 15th day. In each survey, participants recorded their level of tinnitus bother, their location at the time of response, their stress level, how they were feeling, and what they were doing. Response rates as a proxy for the feasibility of the program. Results There were a total of 1120 surveys sent to 20 participants (56 surveys per participant), and 889 (79.4%) of the surveys were completed and returned. The median time to response from the moment of receiving the text message was 7 minutes. The distribution of responses to the EMA question, “In the last 5 minutes, how bothered have you been by your tinnitus?” displayed both high between- and within-subject variability. At the end of 2 weeks, the median score on the Tinnitus Handicap Inventory was 37, with a range of 10 to 82 points; the median Tinnitus Functional Index score was 43, with a range of 10 to 82 points. Conclusion This study suggests bothered tinnitus patients will use smartphones as part of EMA.

Effects of severe bothersome tinnitus on cognitive function measured with standardized tests

Neurocognitive tests compared abilities in people with bothersome tinnitus against an age-, gender-, and education-matched normative population. Participants between 18 and 60 years had subjective, unilateral or bilateral, nonpulsatile tinnitus for >6 months and a Tinnitus Handicap Inventory score of ≥38. Results from a first testing session showed deficits in learning, learning rates, immediate recall of heard words, and use of a serial order encoding strategy. Initial reliance on serial order encoding and, later, increased intrusion of incorrect words towards normal levels might indicate a less demanding strategy to compensate for weakness in associative memory for semantic categories.

Effects of mindfulness based stress reduction therapy on subjective bother and neural connectivity in chronic tinnitus.

Objective To evaluate the impact of a Mindfulness Based Stress Reduction (MBSR) program in patients with chronic bothersome tinnitus on the (1) severity of symptoms of tinnitus and (2) functional connectivity in neural attention networks. Study Design Open-label interventional pilot study. Setting Outpatient academic medical center. Subjects A total of 13 adult participants with a median age of 55 years, suffering from bothersome tinnitus. Methods An 8-week MBSR program was conducted by a trained MBSR instructor. The primary outcome measure was the difference in patient-reported tinnitus symptoms using the Tinnitus Handicap Index (THI) and Tinnitus Functional Index (TFI) between pre-intervention, post-MBSR, and 4-week post-MBSR assessments. Secondary outcomes included change in measurements of depression, anxiety, mindfulness, and cognitive abilities. Functional connectivity magnetic resonance imaging (MRI) was performed at pre- and post-MBSR intervention time points to serve as a neuroimaging biomarker of critical cortical networks. Results Scores on the THI and TFI showed statistically significant and clinically meaningful improvement over the course of the study with a median ΔTHI of −16 and median ΔTFI of −14.8 between baseline and 4-week follow-up scores. Except for depression, there was no significant change in any of the secondary outcome measures. Analysis of the resting state functional connectivity MRI (rs-fcMRI) data showed increased connectivity in the post-MBSR group in attention networks but not the default network. Conclusion Participation in an MBSR program is associated with decreased severity in tinnitus symptoms and depression and connectivity changes in neural attention networks. MBSR is a promising treatment option for chronic bothersome tinnitus that is both noninvasive and inexpensive.

Cognitive Impairment after Chemotherapy Related to Atypical Network Architecture for Executive Control

Objectives: A common complaint of cancer patients is the experience of cognitive difficulty during and after chemotherapy. We hypothesized that cognitive impairment may result from dysfunction in large-scale brain networks, particularly those involved in attentional control. Methods: Using a case-control design, this study includes women with a history of invasive ductal or lobular triple-negative breast cancer who completed standard adjuvant chemotherapy within 2 years of study entry. Women who reported cognitive impairment by the Global Rating of Cognition question were considered to be cases (n = 15). Women who reported no cognitive impairment were considered to be controls (n = 13). All enrolled participants were eligible for MRI investigation and underwent resting-state functional connectivity MRI. Results: Women who self-reported cognitive impairment were found to have disrupted resting-state functional connectivity, as measured by MRI, when compared to women who did not self-report cognitive impairment. These findings suggest that some women may be more sensitive to the standard treatments for breast cancer and that this increased sensitivity may result in functional connectivity alterations in the brain networks supporting attention and executive function. Conclusions: Neuroimaging analyses confirmed self-reported cognitive deficits in women with breast cancer treated with chemotherapy.

The effect of noninvasive brain stimulation on neural connectivity in Tinnitus: A randomized trial

To explore neural connectivity changes associated with repetitive transcranial magnetic stimulation (rTMS) to the temporoparietal junction for patients with bothersome tinnitus.

The Feasibility of Using Metacognitive Strategy Training to Improve Cognitive Performance and Neural Connectivity in Women with Chemotherapy-Induced Cognitive Impairment

Objective: To evaluate the feasibility and preliminary effect of metacognitive strategy training (MCST) on cognitive performance and on neural connectivity in the frontoparietal network in women with chemotherapy-induced cognitive impairment (CICI) following treatment for breast cancer. Methods: A single-group pre/post study was conducted. After completing the baseline assessment battery and neuroimaging, the participants completed a 12-session MCST intervention. Following the completion of the intervention, the subjects completed the same assessment battery and neuroimaging as was completed at baseline within 4 weeks after the intervention. The key inclusion/exclusion criteria for this study were: completed chemotherapy for treatment of breast cancer, no other neurological or psychiatric diagnoses, self-reported CICI, and no contraindications to the use of MRI. Results: MCST had a small-to-large positive effect on all primary (cognitive) and secondary (quality of life and psychosocial) behavioral outcome measures (r = -0.12 to -0.88). There was also a positive change in functional connectivity in a frontoparietal cognitive control network connection in 6 of the 10 subjects, which was correlated to changes in the behavioral measures. Conclusions: This study found that MCST was associated with a positive effect on cognitive performance and neural connectivity in women with CICI following treatment for breast cancer.

Functional Connectivity during Modulation of Tinnitus with Orofacial Maneuvers

Objective To determine changes in cortical neural networks as defined by resting-state functional connectivity magnetic resonance imaging during voluntary modulation of tinnitus with orofacial maneuvers. Study Design Cross-sectional study. Setting Academic medical center. Subjects and Methods Participants were scanned during the maneuver and also at baseline to serve as their own control. The authors chose, a priori, 58 seed regions to evaluate previously described cortical neural networks by computing temporal correlations between all seed region pairs. Seed regions whose correlations significantly differed between rest and maneuver (P < .05, uncorrected) entered into a second-stage analysis of computing the correlation coefficient between the seed region and time courses in each of the remaining brain voxels. A threshold-free cluster enhancement permutation analysis evaluated the distribution of these correlation coefficients after transformation to Fisher z scores and registration to a surface-based reconstruction using Freesurfer. Results The median age for the 16 subjects was 54 years (range, 27-72 years), and all had subjective, unilateral or bilateral, nonpulsatile tinnitus for 6 months or longer. In 9 subjects who could voluntarily increase the loudness of their tinnitus, there were no significant differences in functional connectivity in any cortical networks. A separate analysis evaluated results from 3 patients who decreased the loudness of their tinnitus. Four subjects were excluded because of excessive motion in the scanner. Conclusion The absence of significant differences in functional connectivity due to voluntary orofacial maneuvers that increased tinnitus loudness failed to confirm prior reports of altered cerebral blood flows during somatomotor behaviors.

Cognitive Training for Adults With Bothersome Tinnitus: A Randomized Clinical Trial

Importance Individuals with tinnitus have poorer working memory, slower processing speeds and reaction times, and deficiencies in selective attention, all of which interfere with readiness and performance. Brain Fitness Program–Tinnitus (BFP-T) is a cognitive training program specially designed to exploit neuroplasticity for preservation and expansion of cognitive health in adults with tinnitus. Objective To evaluate the effect of the BFP-T on tinnitus. Design, Setting, and Participants This open-label, intention-to-treat randomized clinical trial prescreened 191 patients with tinnitus and 64 healthy controls (HCs) from June 1, 2012, through October 31, 2013. Participants were 40 adults with bothersome tinnitus for more than 6 months and 20 age-matched HCs. Patients with tinnitus were randomized to a BFP-T or non–BFP-T control group. The BFP-T was completed online, and assessments were completed at Washington University School of Medicine. Interventions Participants in the intervention group were required to complete the BFP-T online 1 hour per day 5 days per week for 8 weeks. Tinnitus assessment, neuroimaging, and cognitive testing were completed at baseline and 8 weeks later. The HCs underwent neuroimaging and cognitive assessments. Main Outcomes and Measures The primary outcome measure was the change in Tinnitus Handicap Inventory (THI) score. Behavioral measures, neuroimaging, and cognitive tests were performed before and after the intervention. Results A total of 40 patients with tinnitus and 20 HCs participated in the study (median [range] age, 56 [35-64] years in the BFP-T group, 52 [24-64] years in the non–BFP-T group, and 50 [30-64] years in the HC group; 13 [65%] in the BFP-T group, 14 [70%] in the non–BFP-T group, and 13 [65%] in the HC group were males; and 16 [80%] in the BFP-T group, 16 [80%] in the non–BFP-T group, and 15 [75%] in the HC group were white). There was a reduction in the THI score in the BFP-T group (median, 7; range, −16 to 64) and non–BFP-T group (median, 11; range, −6 to 26), but this reduction was not significantly different between the 2 groups (median difference, 0; 95% CI, −10 to 8). There was no difference in cognitive test scores and other behavioral measures. There was a significant difference between baseline and follow-up in functional connectivity in cognitive control regions in the BFP-T group but not in HCs or individuals with untreated tinnitus. Of the 20 patients in the BFP-T group, 10 (50%) self-reported improvement attributable to the intervention, and 6 (30%) reported to be much improved in the domains of tinnitus, memory, attention, and concentration. Conclusions and Relevance These findings suggest that the computer-based cognitive training program is associated with self-reported changes in attention, memory, and perception of tinnitus. A possible mechanistic explanation for these changes could be neuroplastic changes in key brain systems involved in cognitive control. Cognitive training programs might have a role in the future treatment of patients with tinnitus. Trial Registration clinicaltrials.gov Identifier: NCT01458821

Evaluation of Ecological Momentary Assessment for Tinnitus Severity

Importance Existing patient-reported outcome measures of tinnitus assess the severity and disability retrospectively, which may result in adequate reliability, but cannot capture the fluctuating and individualized nature of tinnitus. Experience sampling may provide an alternative. Objective To use an ecological momentary assessment (EMA) to measure tinnitus disability and associated constructs. Design, Setting, and Participants Forty adults with tinnitus provided self-report of their tinnitus bother using 5 questions measured by EMA, as well as standard retrospective outcome measures. In this 6-week longitudinal observational study conducted from July 15 to December 22, 2014, participants provided EMA data for 2 weeks (part 1); then after a 2-week break, they provided EMA data for an additional 2 weeks (part 2). A text message with a link to the EMA survey was sent for a total of 56 assessments during each 2-week assessment period. Ecological momentary assessment responses were evaluated using multilevel confirmatory factor analysis to assess the fluctuating nature of bothersome tinnitus across the group and within the pool of individuals over time. Main Outcomes and Measures Ecological momentary assessment questions measured tinnitus disability and associated constructs. Compliance in each study part was assessed based on response rates. The Tinnitus Functional Index and the Overall Global Rating of Bother Scale were assessed at the beginning and end of each 2-week assessment period to explore the effect of the frequent EMAs on the perceived level of bother from tinnitus. Results Of the 40 participants in the study (10 women and 30 men; mean [SD] age, 60.0 [10.5] years), the median survey response rate was high (49 responses to 56 surveys sent [88%] for part 1 and 47 responses of 56 surveys sent [84%] for part 2). The latent factor identified by the 2-level confirmatory factor analysis models demonstrates that within-individual tinnitus bother, loudness, and stress vary together over time. In addition, tinnitus bother, feeling, and stress symptoms all vary together across individuals, which means that bother and stress covary strongly both across time and across individuals. Conclusions and Relevance Ecological momentary assessment evaluates the moment-to-moment perception of tinnitus and the effect of emotional and environmental factors, which suggests that it is a superior tool to measure tinnitus outcomes compared with standard retrospective self-reports. Taken together, information from emotional and environmental factors can be summarized in an underlying (latent) factor that represents a vulnerability to bothersome tinnitus and that can be used to comprehensively describe the tinnitus experience. Momentary variability in tinnitus bother is strongly associated with levels of perceived stress.