The physiological processes underlying the segregation of concurrent sounds were investigated through the use of event-related brain potentials. The stimuli were complex sounds containing multiple ...harmonics, one of which could be mistuned so that it was no longer an integer multiple of the fundamental. Perception of concurrent auditory objects increased with degree of mistuning and was accompanied by negative and positive waves that peaked at 180 and 400 ms poststimulus, respectively. The negative wave, referred to as
object-related negativity,
was present during passive listening, but the positive wave was not. These findings indicate bottom-up and top-down influences during auditory scene analysis. Brain electrical source analyses showed that distinguishing simultaneous auditory objects involved a widely distributed neural network that included auditory cortices, the medial temporal lobe, and posterior association cortices.
•16 MDD 8-Week remitters, 12 MDD 16-week remitters and 14 MDD non-remitters, and 30 healthy controls underwent fMRI during the performance of an emotional conflict task.•MDD participants were scanned ...at baseline, prior to treatment initiation and after 8 weeks treatment with the SSRI escitalopram. HC were scanned in the same intervals.•All groups demonstrated an emotional Stroop effect in reaction time, at Baseline and Week 8.•All MDD groups showed lower task related activation compared to HC at Baseline.•By Week 8, task-related activation was not significantly different between MDD groups and HC.•Findings suggest that escitalopram ameliorates differences in neural activity between HC and MDD groups, while differences in degree of mood symptom alleviation across MDD groups remain.
Identifying objective biomarkers can assist in predicting remission/non-remission to treatment, improving remission rates, and reducing illness burden in major depressive disorder (MDD).
Sixteen MDD 8-week remitters (MDD-8), twelve 16-week remitters (MDD-16), 14 non-remitters (MDD-NR) and 30 healthy comparison participants (HC) completed a functional magnetic resonance imaging emotional conflict task at baseline, prior to treatment with escitalopram, and 8 weeks after treatment initiation. Patients were followed 16 weeks to assess remitter status.
All groups demonstrated emotional Stroop in reaction time (RT) at baseline and Week 8. There were no baseline differences between HC and MDD-8, MDD-16, or MDD-NR in RT or accuracy. By Week 8, MDD-8 demonstrated poorer accuracy compared to HC. Compared to HC, the baseline blood-oxygen level dependent (BOLD) signal was decreased in MDD-8 in brain-stem and thalamus; in MDD-16 in lateral occipital cortex, middle temporal gyrus, and cuneal cortex; in MDD-NR in lingual and occipital fusiform gyri, thalamus, putamen, caudate, cingulate gyrus, insula, cuneal cortex, and middle temporal gyrus. By Week 8, there were no BOLD activity differences between MDD groups and HC.
The Emotional Conflict Task lacks a neutral (non-emotional) condition, restricting interpretation of how mood may influence perception of non-emotionally valenced stimuli.
The Emotional Conflict Task is not an objective biomarker for remission trajectory in patients with MDD receiving escitalopram treatment. Escitalopram may have influenced emotion recognition in MDD groups in terms of augmented accuracy and BOLD signal in response to an Emotional Conflict Task, following 8 weeks of escitalopram treatment.
Task‐based functional neuroimaging methods are increasingly being used to identify biomarkers of treatment response in psychiatric disorders. To facilitate meaningful interpretation of neural ...correlates of tasks and their potential changes with treatment over time, understanding the reliability of the blood‐oxygen‐level dependent (BOLD) signal of such tasks is essential. We assessed test–retest reliability of an emotional conflict task in healthy participants collected as part of the Canadian Biomarker Integration Network in Depression. Data for 36 participants, scanned at three time points (weeks 0, 2, and 8) were analyzed, and intra‐class correlation coefficients (ICC) were used to quantify reliability. We observed moderate reliability (median ICC values between 0.5 and 0.6), within occipital, parietal, and temporal regions, specifically for conditions of lower cognitive complexity, that is, face, congruent or incongruent trials. For these conditions, activation was also observed within frontal and sub‐cortical regions, however, their reliability was poor (median ICC < 0.2). Clinically relevant prognostic markers based on task‐based fMRI require high predictive accuracy at an individual level. For this to be achieved, reliability of BOLD responses needs to be high. We have shown that reliability of the BOLD response to an emotional conflict task in healthy individuals is moderate. Implications of these findings to further inform studies of treatment effects and biomarker discovery are discussed.
Social and economic costs of depression are exacerbated by prolonged periods spent identifying treatments that would be effective for a particular patient. Thus, a tool that reliably predicts an ...individual patient's response to treatment could significantly reduce the burden of depression.
To estimate how accurately an outcome of escitalopram treatment can be predicted from electroencephalographic (EEG) data on patients with depression.
This prognostic study used a support vector machine classifier to predict treatment outcome using data from the first Canadian Biomarker Integration Network in Depression (CAN-BIND-1) study. The CAN-BIND-1 study comprised 180 patients (aged 18-60 years) diagnosed with major depressive disorder who had completed 8 weeks of treatment. Of this group, 122 patients had EEG data recorded before the treatment; 115 also had EEG data recorded after the first 2 weeks of treatment.
All participants completed 8 weeks of open-label escitalopram (10-20 mg) treatment.
The ability of EEG data to predict treatment outcome, measured as accuracy, specificity, and sensitivity of the classifier at baseline and after the first 2 weeks of treatment. The treatment outcome was defined in terms of change in symptom severity, measured by the Montgomery-Åsberg Depression Rating Scale, before and after 8 weeks of treatment. A patient was designated as a responder if the Montgomery-Åsberg Depression Rating Scale score decreased by at least 50% during the 8 weeks and as a nonresponder if the score decrease was less than 50%.
Of the 122 participants who completed a baseline EEG recording (mean SD age, 36.3 12.7 years; 76 62.3% female), the classifier was able to identify responders with an estimated accuracy of 79.2% (sensitivity, 67.3%; specificity, 91.0%) when using only the baseline EEG data. For a subset of 115 participants who had additional EEG data recorded after the first 2 weeks of treatment, use of these data increased the accuracy to 82.4% (sensitivity, 79.2%; specificity, 85.5%).
These findings demonstrate the potential utility of EEG as a treatment planning tool for escitalopram therapy. Further development of the classification tools presented in this study holds the promise of expediting the search for optimal treatment for each patient.
Background
Acute change in gait speed while performing a mental task dual-task gait cost (DTC), and hyperintensity magnetic resonance imaging signals in white matter are both important disability ...predictors in older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC is associated with overall hyperintensity volume from specific major brain regions in poststroke.
Methods
This is a cohort study with a total of 123 older (69 ± 7 years of age) participants with history of stroke were included from the Ontario Neurodegenerative Disease Research Initiative. Participants were clinically assessed and had gait performance assessed under single- and dual-task conditions. Structural neuroimaging data were analyzed to measure both, white matter hyperintensity (WMH) and normal appearing volumes. Percentage of WMH volume in frontal, parietal, occipital, and temporal lobes as well as subcortical hyperintensities in basal ganglia + thalamus were the main outcomes. Multivariate models investigated associations between DTC and hyperintensity volumes, adjusted for age, sex, years of education, global cognition, vascular risk factors, APOE4 genotype, residual sensorimotor symptoms from previous stroke and brain volume.
Results
There was a significant positive global linear association between DTC and hyperintensity burden (adjusted Wilks’ λ = .87, P = .01). Amongst all WMH volumes, hyperintensity burden from basal ganglia + thalamus provided the most significant contribution to the global association (adjusted β = .008, η2 = .03; P = .04), independently of brain atrophy.
Conclusions
In poststroke, increased DTC may be an indicator of larger white matter damages, specifically in subcortical regions, which can potentially affect the overall cognitive processing and decrease gait automaticity by increasing the cortical control over patients’ locomotion.
•Patients with major depression underwent two-stage 16-week antidepressant trial.•Whole-brain cortical thickness (CT) was measured in patients and healthy controls.•Site (N = 6) differences were ...corrected at each vertex using ComBat.•Patients exhibited thinner cortex in left rostral middle frontal cortex at baseline.•There were no baseline CT features associated with antidepressant response.
Major depressive disorder (MDD) is considered a highly heterogeneous clinical and neurobiological mental disorder. We employed a novel layered treatment design to investigate whether cortical thickness features at baseline differentiated treatment responders from non-responders after 8 and 16 weeks of a standardized sequential antidepressant treatment. Secondary analyses examined baseline differences between MDD and controls as a replication analysis and longitudinal changes in thickness after 8 weeks of escitalopram treatment. 181 MDD and 95 healthy comparison (HC) participants were studied. After 8 weeks of escitalopram treatment (10–20 mg/d, flexible dosage), responders (>50% decrease in Montgomery-Åsberg Depression Scale score) were continued on escitalopram; non-responders received adjunctive aripiprazole (2–10 mg/d, flexible dosage). MDD participants were classified into subgroups according to their response profiles at weeks 8 and 16. Baseline group differences in cortical thickness were analyzed with FreeSurfer between HC and MDD groups as well as between response groups. Two-stage longitudinal processing was used to investigate 8-week escitalopram treatment-related changes in cortical thickness. Compared to HC, the MDD group exhibited thinner cortex in the left rostral middle frontal cortex MNI(X,Y,Z=−29,9,54.5,−7.7); CWP=0.0002. No baseline differences in cortical thickness were observed between responders and non-responders based on week-8 or week-16 response profile. No changes in cortical thickness was observed after 8 weeks of escitalopram monotherapy. In a two-step 16-week sequential clinical trial we found that baseline cortical thickness does not appear to be associated to clinical response to pharmacotherapy at 8 or 16 weeks.
Spatial and nonspatial auditory tasks preferentially recruit dorsal and ventral brain areas, respectively. However, the extent to which these auditory differences reflect specific aspects of mental ...processing has not been directly studied. In the present functional magnetic resonance imaging experiment, participants encoded and maintained either the location or the identity of a sound for a delay period of several seconds and then subsequently compared that information with a second sound. Relative to sound localization, sound identification was associated with greater hemodynamic activity in the left rostral superior temporal gyrus. In contrast, localizing sounds recruited greater activity in the parietal cortex, posterior temporal lobe, and superior frontal sulcus. The identification differences were most prominent during the early stage of the trial, whereas the location differences were most evident during the late (i.e., comparison) stage. Accordingly, our results suggest that auditory spatial and identity dissociations as revealed by functional imaging may be dependent to some degree on the type of processing being carried out. In addition, dorsolateral prefrontal and lateral superior parietal areas showed greater activity during the comparison as opposed to the earlier stage of the trial, regardless of the type of auditory task, consistent with results from visual working memory studies.
•White matter changes in transdiagnostic risk was compared to discrete disorder.•Discrete disorder group had lower fractional anisotropy compared to other groups.•Attenuated syndromes group had ...higher fractional anisotropy compared to controls.•White matter changes in discrete disorder are most evident after illness onset.•Few changes in white matter were observed in the transdiagnostic risk phase.
Identifying biomarkers of serious mental illness, such as altered white matter microstructure, can aid in early diagnosis and treatment. White matter microstructure was assessed using constrained spherical deconvolution of diffusion imaging data in a sample of 219 youth (age 12–25 years, 64.84% female) across 8 sites. Participants were classified as healthy controls (HC; n = 47), familial risk for serious mental illness (n = 31), mild-symptoms (n = 37), attenuated syndromes (n = 66), or discrete disorder (n = 38) based on clinical assessments. Fractional anisotropy (FA) and mean diffusivity (MD) values were derived for the whole brain white matter, forceps minor, anterior cingulate, anterior thalamic radiations (ATR), inferior fronto-occipital fasciculus, superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF). Linear mixed effects models showed a significant effect of age on MD of the left ATR, left SLF, and left UF, and a significant effect of group on FA for all tracts examined. For most tracts, the discrete disorder group had significantly lower FA than other groups, and the attenuated syndromes group had higher FA compared to HC, with few differences between the remaining groups. White matter differences in MDD are most evident in individuals following illness onset, as few significant differences were observed in the risk phase.
Behavioral improvement within the first hour of training is commonly explained as procedural learning (i.e., strategy changes resulting from task familiarization). However, it may additionally ...reflect a rapid adjustment of the perceptual and/or attentional system in a goal-directed task. In support of this latter hypothesis, we show feature-specific gains in performance for groups of participants briefly trained to use either a spectral or spatial difference between 2 vowels presented simultaneously during a vowel identification task. In both groups, the neuromagnetic activity measured during the vowel identification task following training revealed source activity in auditory cortices, prefrontal, inferior parietal, and motor areas. More importantly, the contrast between the 2 groups revealed a striking double dissociation in which listeners trained on spectral or spatial cues showed higher source activity in ventral ("what") and dorsal ("where") brain areas, respectively. These feature-specific effects indicate that brief training can implicitly bias top-down processing to a trained acoustic cue and induce a rapid recalibration of the ventral and dorsal auditory streams during speech segregation and identification.
Purpose
Tauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect
in vivo
. This ...study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate
in vivo
the difference in peripapillary retinal nerve fibre layer (pRNFL) thickness and macular retinal thickness between participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP-43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia).
Study design
Prospective, multi-centre, observational study.
Materials and methods
pRNFL and macular SD-OCT images were acquired in both eyes of each participant using Heidelberg Spectralis SD-OCT. Global and pRNFL thickness in 6 sectors were analyzed, as well as macular thickness in a central 1 mm diameter zone and 4 surrounding sectors. Linear mixed model methods adjusting for baseline differences between groups were used to compare the two groups with respect to pRNFL and macular thickness.
Results
A significant difference was found in mean pRNFL thickness between groups, with the TDP-43 group (
n
= 28 eyes) having a significantly thinner pRNFL in the temporal sector than the tauopathy group (
n
= 9 eyes; mean difference = 15.46 μm, SE = 6.98,
p
= 0.046), which was not significant after adjusting for multiple comparisons. No other significant differences were found between groups for pRNFL or macular thickness.
Conclusion
The finding that the temporal pRNFL in the TDP-43 group was on average 15.46 μm thinner could potentially have clinical significance. Future work with larger sample sizes, longitudinal studies, and at the level of retinal sublayers will help to determine the utility of SD-OCT to differentiate between these two proteinopathies.
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