Individual differences in the evaluation of ambiguous visual and auditory threat-related expressions.

This study investigated the neural correlates of the judgement of auditory and visual ambiguous threat-related information, and the influence of state anxiety on this process. Healthy subjects were scanned using a fast, high-resolution functional magnetic resonance imaging (fMRI) multiband sequence while they performed a two-alternative forced-choice emotion judgement task on faces and vocal utterances conveying explicit anger or fear, as well as ambiguous ones. Critically, the latter was specific to each subject, obtained through a morphing procedure and selected prior to scanning following a perceptual decision-making task. Behavioural results confirmed a greater task-difficulty for subject-specific ambiguous stimuli and also revealed a judgement bias for visual fear, and, to a lesser extent, for auditory anger. Imaging results showed increased activity in regions of the salience and frontoparietal control networks (FPCNs) and deactivation in areas of the default mode network for ambiguous, relative to explicit, expressions. In contrast, the right amygdala (AMG) responded more strongly to explicit stimuli. Interestingly, its response to the same ambiguous stimulus depended on the subjective judgement of the expression. Finally, we found that behavioural and neural differences between ambiguous and explicit expressions decreased as a function of state anxiety scores. Taken together, our results show that behavioural and brain responses to emotional expressions are determined not only by emotional clarity but also modality and the subjects' subjective perception of the emotion expressed, and that some of these responses are modulated by state anxiety levels.

Multivariate fMRI pattern analysis of fear perception across modalities.

The emotional expression of fear can be processed through a number of modalities, and of varying forms, however, much of the functional imaging literature has centered on investigating fear as expressed through faces. Findings point to an active involvement of the amygdala, and remain fairly consistent in other studies of unimodal fear perception; however, few studies have looked at within-subject cross-modal responses to fear. Thus, we approached this inquiry by testing 30 healthy young adults with fast, high-resolution fMRI, recording the neural responses of fear perception, as expressed through faces, bodies, prosody, and vocalizations. The study was analyzed using a multivariate approach (multi-voxel pattern analysis) and yielded a significant distinction in the responses associated with the perception of fearful vs. neutral emotions. Calculated weights highlighted areas in the amygdala and surrounding subcortical structures as contributing the greatest to the discrimination; however, a whole-brain analysis was necessary to obtain above-chance classification accuracy, suggesting that processing fear across modalities likely involves a broad, distributed network. Thus, our findings support a multivariate approach to studying a highly complex construct such as emotion, as it accounts for multiple voxels simultaneously and can accommodate the high subject-level variability that oftentimes comes with studying emotion perception.

Singing in the brain: Neural representation of music and voice as revealed by fMRI.

The ubiquity of music across cultures as a means of emotional expression, and its proposed evolutionary relation to speech, motivated researchers to attempt a characterization of its neural representation. Several neuroimaging studies have reported that specific regions in the anterior temporal lobe respond more strongly to music than to other auditory stimuli, including spoken voice. Nonetheless, because most studies have employed instrumental music, which has important acoustic distinctions from human voice, questions still exist as to the specificity of the observed "music-preferred" areas. Here, we sought to address this issue by testing 24 healthy young adults with fast, high-resolution fMRI, to record neural responses to a large and varied set of musical stimuli, which, critically, included a capella singing, as well as purely instrumental excerpts. Our results confirmed that music; vocal or instrumental, preferentially engaged regions in the superior STG, particularly in the anterior planum polare, bilaterally. In contrast, human voice, either spoken or sung, activated more strongly a large area along the superior temporal sulcus. Findings were consistent between univariate and multivariate analyses, as well as with the use of a "silent" sparse acquisition sequence that minimizes any potential influence of scanner noise on the resulting activations. Activity in music-preferred regions could not be accounted for by any basic acoustic parameter tested, suggesting these areas integrate, likely in a nonlinear fashion, a combination of acoustic attributes that, together, result in the perceived musicality of the stimuli, consistent with proposed hierarchical processing of complex auditory information within the temporal lobes.

Emotion regulation in bipolar disorder type-I: multivariate analysis of fMRI data.

BACKGROUND: Bipolar disorder type-I (BD-I) patients are known to show emotion regulation abnormalities. In a previous fMRI study using an explicit emotion regulation paradigm, we compared responses from 19 BD-I patients and 17 matched healthy controls (HC). A standard general linear model-based univariate analysis revealed that BD patients showed increased activations in inferior frontal gyrus when instructed to decrease their emotional response as elicited by neutral images. We implemented multivariate pattern recognition analyses on the same data to examine if we could classify conditions within-group as well as HC versus BD. METHODS: We reanalyzed explicit emotion regulation data using a multivariate pattern recognition approach, as implemented in PRONTO software. The original experimental paradigm consisted of a full 2 × 2 factorial design, with valence (Negative/Neutral) and instruction (Look/Decrease) as within subject factors. RESULTS: The multivariate models were able to accurately classify different task conditions when HC and BD were analyzed separately (63.24%-75.00%, p = 0.001-0.012). In addition, the models were able to correctly classify HC versus BD with significant accuracy in conditions where subjects were instructed to downregulate their felt emotion (59.60%-60.84%, p = 0.014-0.018). The results for HC versus BD classification demonstrated contributions from the salience network, several occipital and frontal regions, inferior parietal lobes, as well as other cortical regions, to achieve above-chance classifications. CONCLUSIONS: Our multivariate analysis successfully reproduced some of the main results obtained in the previous univariate analysis, confirming that these findings are not dependent on the analysis approach. In particular, both types of analyses suggest that there is a significant difference of neural patterns between conditions within each subject group. The multivariate approach also revealed that reappraisal conditions provide the most informative activity for differentiating HC versus BD, irrespective of emotional valence (negative or neutral). The current results illustrate the importance of investigating the cognitive control of emotion in BD. We also propose a set of candidate regions for further study of emotional control in BD.

Preliminary Real-World Evidence Supporting the Efficacy of a Remote Neurofeedback System in Improving Mental Health: Retrospective Single-Group Pretest-Posttest Study.

BACKGROUND: Neurofeedback training (NFT) has been shown to be effective in treating several disorders (eg, attention-deficit/hyperactivity disorder [ADHD], anxiety, and depression); however, little is currently known regarding the effectiveness of remote NFT systems. OBJECTIVE: This retrospective study provides real-world data (N=593) to assess the efficacy of app-based remote NFT in improving brain health and cognitive performance. METHODS: Improvement was measured from pre- to postintervention of in-app assessments that included validated symptom questionnaires (the 12-item General Health Questionnaire, the ADHD Rating Scale IV, the Adult ADHD Self-Report Scale, the 7-item Generalized Anxiety Disorder scale, and the 9-item Patient Health Questionnaire), a cognitive test of attention and executive functioning (ie, continuous performance task), and resting electroencephalography (EEG) markers. Clinically significant improvement was evaluated using standard approaches. RESULTS: The greatest improvement was reported for the anxiety questionnaire, for which 69% (68/99) of participants moved from abnormal to healthy score ranges. Overall, adult and child participants who engaged in neurofeedback to improve attention and executive functions demonstrated improved ADHD scores and enhanced performance on a cognitive (ie, response inhibition) task. Adults with ADHD additionally demonstrated elevated delta/alpha and theta/alpha ratios at baseline and a reduction in the delta/alpha ratio indicator following neurofeedback. CONCLUSIONS: Preliminary findings suggest the efficacy of app-based remote neurofeedback in improving mental health, given the reduced symptom severity from pre- to postassessment for general psychological health, ADHD, anxiety, and depression, as well as adjusted resting EEG neural markers for individuals with symptoms of ADHD. Collectively, this supports the utility of the in-app assessment in monitoring behavioral and neural indices of mental health.

Intra-individual Reliability of Voice- and Music-elicited Responses and their Modulation by Expertise.

A growing number of functional neuroimaging studies have identified regions within the temporal lobe, particularly along the planum polare and planum temporale, that respond more strongly to music than other types of acoustic stimuli, including voice. This "music preferred" regions have been reported using a variety of stimulus sets, paradigms and analysis approaches and their consistency across studies confirmed through meta-analyses. However, the critical question of intra-subject reliability of these responses has received less attention. Here, we directly assessed this important issue by contrasting brain responses to musical vs. vocal stimuli in the same subjects across three consecutive fMRI runs, using different types of stimuli. Moreover, we investigated whether these music- and voice-preferred responses were reliably modulated by expertise. Results demonstrated that music-preferred activity previously reported in temporal regions, and its modulation by expertise, exhibits a high intra-subject reliability. However, we also found that activity in some extra-temporal regions, such as the precentral and middle frontal gyri, did depend on the particular stimuli employed, which may explain why these are less consistently reported in the literature. Taken together, our findings confirm and extend the notion that specific regions in the brain consistently respond more strongly to certain socially-relevant stimulus categories, such as faces, voices and music, but that some of these responses appear to depend, at least to some extent, on the specific features of the paradigm employed.

Portable eyetracking-based assessment of memory decline.

INTRODUCTION: Preferential viewing of novel stimuli in the Visual Paired Comparison task has provided a useful marker of memory and medial temporal lobe function. We created a portable version of the VPC (P-VPC) and contrasted P-VPC metrics against the Montreal Cognitive Assessment (MoCA) in healthy adults, to assess the validity and reliability of the P-VPC as an indicator of memory function across age. A supplementary case series was conducted with individuals diagnosed with Alzheimer's disease (AD) and other dementias, to provide a preliminary illustration of the P-VPC's use as a measure in clinical populations. METHOD: Participants (n = 207) were tested using the P-VPC. Individuals were familiarized with a set of objects, which were each presented alongside a novel object in the test phase. Novelty viewing scores were compared to MoCA scores to index concurrent validity. Item analyses were conducted as a test of internal reliability of the P-VPC. A complementary clinical case series was conducted with AD (n = 4) and dementia (n = 5) participants, who were tested using the P-VPC and further compared to healthy age-matched participants. RESULTS: Preferential viewing decreased with age in healthy participants, and was positively correlated with MoCA scores. Compared to the MoCA, P-VPC scores did not differ based on education and/or whether English was spoken as the native language. Item analyses revealed acceptable internal consistency. P-VPC viewing percentiles of healthy participants were modeled as a function of age, and illustrated that individuals of the clinical case series diagnosed with AD scored in below-average percentiles, while those with dementia did not score below-average. CONCLUSION: Good concurrent validity and acceptable internal reliability were observed, and P-VPC scores were not confounded by education or language experience. Low performance was observed in individuals with clinically diagnosed AD, suggesting that the P-VPC may be a potential tool for screening memory decline.

Focus group reflections on the current and future state of cognitive assessment tools in geriatric health care.

OBJECTIVE: This study provides insight into the thoughts and opinions of geriatric health-care professionals toward cognitive assessments and the use of emerging technologies, such as eye-tracking, to supplement current tools. METHODS: Two focus group sessions were conducted with nurses and physicians who routinely administer neurocognitive assessments to geriatric populations. Video recordings of the focus group sessions were transcribed and a thematic analysis was performed. RESULTS: Participants reported the need for assessment and diagnostic tools that are accessible and efficient, and that are capable of accommodating the rapid growth in the aging population. The prevalence of more complex ailments experienced by older adults has had repercussions in the quality of care that the clients receive, and has contributed to lengthy wait times and resource shortages. Health-care professionals stated that they are hampered by the disjointed structure of the health-care system and that they would benefit from a more efficient allocation of responsibilities made possible through tools that did not require extensive training or certification. Eyetracking-based cognitive assessments were thought to strongly complement this system, yet it was thought that difficulty would be faced in gaining the support and increased uptake by health-care professionals due to the nonintuitive relationship between eyetracking and cognition. CONCLUSION: The findings suggest that health-care professionals are receptive to the use of eyetracking technology to assess for cognitive health as it would conserve resources by allowing frontline staff to administer assessments with minimal training.

A clinical frailty index in aging mice: comparisons with frailty index data in humans.

We previously quantified frailty in aged mice with frailty index (FI) that used specialized equipment to measure health parameters. Here we developed a simplified, noninvasive method to quantify frailty through clinical assessment of C57BL/6J mice (5-28 months) and compared the relationship between FI scores and age in mice and humans. FIs calculated with the original performance-based eight-item FI increased from 0.06 ± 0.01 at 5 months to 0.36 ± 0.06 at 19 months and 0.38 ± 0.04 at 28 months (n = 14). By contrast, the increase was graded with a 31-item clinical FI (0.02 ± 0.005 at 5 months; 0.12 ± 0.008 at 19 months; 0.33 ± 0.02 at 28 months; n = 14). FI scores calculated from 70 self-report items from the first wave of the Survey of Health, Ageing and Retirement in Europe were plotted as function of age (n = 30,025 people). The exponential relationship between FI scores and age (normalized to 90% mortality) was similar in mice and humans for the clinical FI but not the eight-item FI. This noninvasive FI based on clinical measures can be used in longitudinal studies to quantify frailty in mice. Unlike the performance-based eight-item mouse FI, the clinical FI exhibits key features of the FI established for use in humans.