T1 relaxation time is prolonged in healthy aging: a whole brain study.

BACKGROUND: : Measurement of tissue characteristics such as the longitudinal relaxation time (T1) provides complementary information to the volumetric and surface based structural analyses. We aimed to investigate T1 relaxation time characteristics in healthy aging via an exploratory design in the whole brain. The data processing pipeline was designed to minimize errors related to aging effects such as atrophy. METHODS: Sixty healthy participants underwent MRI scanning (28 F, 32 M, age range: 18-78, 30 young and 30 old) in November 2017-March 2018 at the Bilkent University UMRAM Center. Four images with varying flip angles with FLASH (fast low angle shot magnetic resonance imaging) sequence and a high-resolution structural image with MP-RAGE (Magnetization Prepared - RApid Gradient Echo) were acquired. T1 relaxation times of the entire brain were mapped by using the region of interest (ROI) based method on 134 brain areas in young and old populations. RESULTS: T1 prolongation was observed in various subcortical (bilateral hippocampus, caudate and thalamus) and cortical brain structures (bilateral precentral gyrus, bilateral middle frontal gyrus, bilateral supplementary motor area (SMA), left middle occipital gyrus, bilateral postcentral gyrus and bilateral Heschl's gyrus) as well as cerebellar regions (GM regions of cerebellum: bilateral cerebellum III, cerebellum IV V, cerebellum X, cerebellar vermis u 4 5, cerebellar vermis u 9 and WM cerebellar regions: left cerebellum IX, bilateral cerebellum X and cerebellar vermis u 4 5). DISCUSSION: T1 mapping provides a practical quantitative MRI (qMRI) methodology for studying the tissue characteristics in healthy aging. T1 values are significantly increased in the aging group among half of the studied ROIs (57 ROIs out of 134).

A Pilot Trial of Dopamine Replacement for Dynamic Facial Expressions in Parkinson's Disease.

Background: Current conflict exists regarding the potential beneficial effects of dopamine medications on facial expressivity in Parkinson's disease. Via digital video analysis software, we previously found reduced facial movement (entropy) and slower time to reach peak entropy in individuals with Parkinson's disease compared to controls. Objectives: We aimed to determine whether levodopa medications improved parameters of dynamic facial expressions (amplitude, speed). Methods: A total of 34 individuals with idiopathic Parkinson's disease were videotaped making voluntary facial expressions (happy, fear, anger, disgust) when "on" and "off" levodopa. Participants were 52 to 80 years old, early to mid-stage disease, non-demented, and included more men (65%). Expressions were digitized and analyzed using software that extracted three variables: two indices of movement change (total entropy, percent entropy change) and time to reach peak expression. Results: Indices of facial movement (total entropy, peak entropy) and timing were significantly improved when patients were "on" vs "off" medication (all F's ≥ 3.00, P < 0.05). For total movement and time to reach peak entropy, levodopa-related improvements were emotion nonspecific. Levodopa-related improvement for peak entropy was driven primarily by happy expressions. There was no relationship between quantitative indices and clinical measures of mood (depression, anxiety) and motor disease severity. Conclusion: The effects of levodopa on Parkinson's disease voluntary facial movement and on timing were robust and consistent with those of levodopa on other intentional movements in Parkinson's disease. This improvement possibly occurred because of levodopa enhanced activation of face representation areas in fronto-cortical regions or because of less movement-based suppression.

Hand Pronation-Supination Movement as a Proxy for Remotely Monitoring Gait and Posture Stability in Parkinson's Disease.

The Unified Parkinson's Disease Rating Scale (UPDRS) is a subjective Parkinson's Disease (PD) physician scoring/monitoring system. To date, there is no single upper limb wearable/non-contact system that can be used objectively to assess all UPDRS-III motor system subgroups (i.e., tremor (T), rigidity (R), bradykinesia (B), gait and posture (GP), and bulbar anomalies (BA)). We evaluated the use of a non-contact hand motion tracking system for potential extraction of GP information using forearm pronation-supination (P/S) motion parameters (speed, acceleration, and frequency). Twenty-four patients with idiopathic PD participated, and their UPDRS data were recorded bilaterally by physicians. Pearson's correlation, regression analyses, and Monte Carlo validation was conducted for all combinations of UPDRS subgroups versus motion parameters. In the 262,125 regression models that were trained and tested, the models within 1% of the lowest error showed that the frequency of P/S contributes to approximately one third of all models; while speed and acceleration also contribute significantly to the prediction of GP from the left-hand motion of right handed patients. In short, the P/S better indicated GP when performed with the non-dominant hand. There was also a significant negative correlation (with medium to large effect size, range: 0.3-0.58) between the P/S speed and the single BA score for both forearms and combined UPDRS score for the dominant hand. This study highlights the potential use of wearable or non-contact systems for forearm P/S to remotely monitor and predict the GP information in PD.

Laterality of motor symptom onset and facial expressivity in Parkinson disease using face digitization.

The onset of motor symptoms in Parkinson disease (PD) is typically unilateral. Previous work has suggested that laterality of motor symptoms may also influence non-motor symptoms including cognition and emotion perception. In line with hemispheric differences in emotion processing, we tested whether left side/right brain motor onset was associated with worse expression of facial affect when compared to right side/left brain motor onset. We evaluated movement changes associated with facial affect in 30 patients with idiopathic PD (15 left-sided motor onset, 15 right-sided motor onset) and 20 healthy controls. Participants were videotaped while posing three facial expressions: fear, anger, and happiness. Expressions were digitized and analyzed using software that extracted three variables: two measures of dynamic movement change (total entropy and entropy percent change) and a measure of time to initiate facial expression (latency). The groups did not differ in overall amount of movement change or percentchange. However, left-sided onset PD patients were significantly slower in initiating anger and happiness facial expressions than were right-sided onset PD patients and controls. Our results indicated PD patients with left-sided symptom onset had greater latency in initiating two of three facial expressions, which may reflect laterality effects in intentional behaviour.

Diffusion Tensor Imaging Group Analysis Using Tract Profiling and Directional Statistics.

Group analysis in diffusion tensor imaging is challenging. Comparisons of tensor morphology across groups have typically been performed on scalar measures of diffusivity, such as fractional anisotropy (FA), disregarding the complex three-dimensional morphologies of diffusion tensors. Scalar measures consider only the magnitude of the diffusion but not directions. In the present study, we have introduced a new approach based on directional statistics to use directional information of diffusion tensors in statistical group analysis based on Bingham distribution. We have investigated different directional statistical models to find the best fit. During the experiments, we confirmed that carrying out directional statistical analysis along the tract is much more effective than voxel- or skeleton-guided directional statistics. Hence, we propose a new method called tract profiling and directional statistics (TPDS) applicable to fiber bundles. As a case study, the method has been applied to identify connectivity differences of patients with major depressive disorder. The results obtained with the directional statistic-based analysis are consistent with those of NBS, but additionally, we found significant changes in the right hemisphere striatum, ACC, and prefrontal, parietal, temporal, and occipital connections as well as left hemispheric differences in the limbic areas such as the thalamus, amygdala, and hippocampus. The results are also evaluated with respect to fiber lengths. Comparison with the output of the network-based statistical toolbox indicated that the benefit of the proposed method becomes much more distinctive as the tract length increases. The likelihood of finding clusters of voxels that differ in long tracts is higher in TPDS, while that relationship is not clearly established in NBS.

Dimensionality of the system usability scale among professionals using internet-based interventions for depression: a confirmatory factor analysis.

BACKGROUND: The System Usability Scale (SUS) is used to measure usability of internet-based Cognitive Behavioural Therapy (iCBT). However, whether the SUS is a valid instrument to measure usability in this context is unclear. The aim of this study is to assess the factor structure of the SUS, measuring usability of iCBT for depression in a sample of professionals. In addition, the psychometric properties (reliability, convergent validity) of the SUS were tested. METHODS: A sample of 242 professionals using iCBT for depression from 6 European countries completed the SUS. Confirmatory Factor Analysis (CFA) was conducted to test whether a one-factor, two-factor, tone-model or bi-direct model would fit the data best. Reliability was assessed using complementary statistical indices (e.g. omega). To assess convergent validity, the SUS total score was correlated with an adapted Client Satisfaction Questionnaire (CSQ-3). RESULTS: CFA supported the one-factor, two-factor and tone-model, but the bi-factor model fitted the data best (Comparative Fit Index = 0.992, Tucker Lewis Index = 0.985, Root Mean Square Error of Approximation = 0.055, Standardized Root Mean Square Residual = 0.042 (respectively χ2diff (9) = 69.82, p < 0.001; χ2diff (8) = 33.04, p < 0.001). Reliability of the SUS was good (ω = 0.91). The total SUS score correlated moderately with the CSQ-3 (CSQ1 rs = .49, p < 0.001; CSQ2 rs = .46, p < 0.001; CSQ3 rs = .38, p < 0.001), indicating convergent validity. CONCLUSIONS: Although the SUS seems to have a multidimensional structure, the best model showed that the total sumscore of the SUS appears to be a valid and interpretable measure to assess the usability of internet-based interventions when used by professionals in mental healthcare.

Effectiveness of a Web- and Mobile-Guided Psychological Intervention for Depressive Symptoms in Turkey: Protocol for a Randomized Controlled Trial.

BACKGROUND: In Turkey, there are serious deficiencies in mental health care. Although depression is highly prevalent, only a small number of people seek professional help. Innovative solutions are needed to overcome this treatment gap. Web-based problem-solving therapy (PST) is an intervention proven to be effective in the treatment of depression, although little is known about its clinical effects in Turkey. OBJECTIVE: This study aims to test the clinical effects of a Web and mobile app of an adapted PST for depressive symptoms among the general population in Turkey. METHODS: Participants will be recruited through announcements in social media and the Middle East Technical University. Adults (18-55 years) with mild to moderate depressive symptoms (Beck Depression Inventory-II [BDI-II] score between 10-29) will be included in the study. Participants with a medium-to-high suicidal risk (according to the Mini-International Neuropsychiatric Interview) will be excluded. A 3-armed randomized controlled trial with a waiting control group will be utilized. A sample size of 444 participants will be randomized across 3 groups. The first experimental group will receive direct access to the Web version of the intervention; the second experimental group will receive direct access to the mobile app of the intervention as well as automated supportive short message service text messages based on PST. The control group consists of a wait-list and will gain access to the intervention 4 months after the baseline. The intervention is based on an existing PST for the Turkish population, Her Sey Kontrol Altinda (HSKA), consisting of 5 modules each with a duration of 1 week and is guided by a clinical psychologist. The primary outcome is change in depressive symptoms measured by the BDI-II. Secondary outcomes include symptoms of anxiety, stress, worry, self-efficacy, and quality of life. Furthermore, satisfaction with, usability and acceptability of the intervention are important features that will be evaluated. All outcomes will take place online through self-assessment at posttest (6-8 weeks after baseline) and at follow-up (4 months after baseline). RESULTS: We will recruit a total of 444 participants with mild to moderate depressive symptoms from March 2018 to February 2019 or until the recruitment is complete. We expect the final trial results to be available by the end of May 2019. This trial is funded by the Scientific and Technological Research Council of Turkey (National Postdoctoral Research Fellowship Programme 2016/1). CONCLUSIONS: Results from this study will reveal more information about the clinical effects of HSKA as well as its applicability in a Turkish setting through the Web and mobile platforms. On the basis of the results, a guided Web- and mobile-based PST intervention might become an appropriate alternative for treating mild to moderate depressive symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT03754829; https://clinicaltrials.gov/ct2/show/NCT03754829 (Archived by WebCite at http://www.webcitation.org/74HugwLo7). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13239.

Binary Classification Using Neural and Clinical Features: An Application in Fibromyalgia With Likelihood-Based Decision Level Fusion.

Among several features used for clinical binary classification, behavioral performance, questionnaire scores, test results, and physical exam reports can be counted. Attempts to include neuroimaging findings to support clinical diagnosis are scarce due to difficulties in collecting such data, as well as problems in integration of neuroimaging findings with other features. The binary classification method proposed here aims to merge small samples from multiple sites so that a large cohort, which better describes the features of the disease can be built. We implemented a simple and robust framework for detection of fibromyalgia, using likelihood during decision level fusion. This framework supports sharing of classifier applications across clinical sites and arrives at a decision by fusing results from multiple classifiers. If there are missing opinions from some classifiers due to inability to collect their input features, such degradation in information is tolerated. We implemented this method using functional near infrared spectroscopy (fNIRS) data collected from fibromyalgia patients across three different tasks. Functional connectivity maps are derived from these tasks as features. In addition, self-reported clinical features are also used. Five classifiers are trained using k nearest neighborhood (kNN), linear discriminant analysis (LDA), and support vector machine (SVM). Fusion of classification opinions from multiple classifiers based on likelihood ratios outperformed individual classifier performances. When 2, 3, 4, and 5 different classifiers are fused, sensitivity, and specificity figures of 100% could be obtained based on the choice of the classifier set.

Association of Fine Motor Loss and Allodynia in Fibromyalgia: An fNIRS Study.

Recent studies showed that fine motor control dysfunction was observed in fibromyalgia (FM) syndrome as well as allodynia. However, brain signatures of this association still remain unclear. In this study, finger tapping task (FTT) and median nerve stimulation (MNS) were applied to both hands of 15 FM patients and healthy controls (HC) to understand this relationship. Hemodynamic activity was measured simultaneously using functional near-infrared spectroscopy (fNIRS). Experiments were analyzed separately by using 2x2 repeated measures ANOVA. Results for the FTT experiment revealed that HC showed higher activity than FM patients in bilateral superior parietal gyrus (SPG), left supramarginal gyrus (SMG) and right somatosensory cortex (SI). Furthermore, right-hand FTT resulted in higher activity than left-hand FTT in left SPG, left SI and right motor cortex (MI). In the MNS experiment, FM patients showed higher activity than HC in bilateral SPG, right SMG, right SI and right middle frontal gyrus (MFG). Negative correlation was observed in left SPG between FTT and MNS activities. Besides, MNS activity in left SPG was negatively correlated with left-hand pain threshold.This study revealed that left SPG might be an important indicator to associate fine motor loss and allodynia in FM.

Differential efficiency of transcutaneous electrical nerve stimulation in dominant versus nondominant hands in fibromyalgia: placebo-controlled functional near-infrared spectroscopy study.

Using functional near-infrared spectroscopy (fNIRS), modulation of hemodynamic responses by transcutaneous electrical nerve stimulation (TENS) during delivery of nociceptive stimulation was investigated in fibromyalgia (FM) patients and healthy controls for both hands. Two experiments were conducted: (1) median nerve stimulation with TENS and (2) painful stimulation using electronic von Frey filaments with TENS/placebo TENS. Mean [Formula: see text] brain activity was compared across groups and conditions using factorial ANOVA. Dominant (right) hand stimulation indicated significant interactions between group and condition in both hemispheres. Post hoc results revealed that FM patients showed an increased activation in "pain + TENS" condition compared to the "pain + placebo TENS" condition while the brain activity patterns for these conditions in controls were reversed. Left-hand stimulation resulted in similar TENS effects (reduced activation for "pain + TENS" than "pain + placebo TENS") in both groups. TENS effects in FM patients might be manipulated by the stimulation side. While the nondominant hand was responsive to TENS treatment, the dominant hand was not. These results indicate that stimulation side might be an effective factor in FM treatment by using TENS. Future studies are needed to clarify the underlying mechanism for these findings.

Valence-based Word-Face Stroop task reveals differential emotional interference in patients with major depression.

Word-Face Stroop task creates emotional conflict between affective words and affective faces. In this task, healthy participants consistently slow down while responding to incongruent cases. Such interference related slowdown is associated with recruitment of inhibitory processes to eliminate task-irrelevant information. We created a valence-based Word-Face Stroop task, in which participants were asked to indicate whether the words in the foreground are positive, negative or neutral. Healthy participants were faster and more accurate than un-medicated patients with major depression disorder (MDD). In addition, a significant congruence by group interaction is observed: healthy participants slowed down for incongruent cases, but MDD patients did not. Furthermore, for the negative words, healthy individuals made more errors while responding to incongruent cases but MDD patients made the lowest number of errors for this category. The emotional percepts of the patients were intact, because correct response rates in word valence judgments for positive/negative words, and reaction times for happy/sad faces had similar patterns with those of controls. These findings are supported by the analytical rumination interpretation of depression: patients lose speed/accuracy in laboratory tasks due to processing load spent during continuous rumination. However, for tasks in line with their preoccupation, continual practice makes the patients more vigilant and adept.

Quantification of the effects of transcutaneous electrical nerve stimulation with functional magnetic resonance imaging: a double-blind randomized placebo-controlled study.

OBJECTIVE: To evaluate the effects of transcutaneous electric nerve stimulation (TENS) by using functional magnetic resonance imaging (fMRI) in patients with carpal tunnel syndrome (CTS). DESIGN: Randomized controlled trial. SETTINGS: University medical center and an outpatient imaging center. PARTICIPANTS: Female patients with CTS (n=20) were randomized into 2 groups receiving either TENS (n=10) or sham TENS (n=10). In both groups, an initial baseline fMRI session was performed via stimulating digits 2, 5, and 3 in turn, 1 scan run for each. TENS versus sham TENS treatment was given, and a repeat imaging was performed starting 20 minutes after the treatment as follows: second finger on the 20th minute, fifth finger on the 25th minute (ulnar nerve innervated control finger), and third finger on the 30th min. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Differences in fMRI activation between the 2 groups were evaluated. RESULTS: Our results demonstrated that 20 to 25 minutes after TENS treatment-but not in the sham TENS group-a significant fMRI signal decrease for digit 2 (post-TENS vs baseline) was observed in the secondary somatosensory regions, ipsilateral primary motor cortex (M1), contralateral supplementary motor cortex (SMA), contralateral parahippocampal gyrus, contralateral lingual gyrus, and bilateral superior temporal gyrus. Measurements on the 25th to 30th minutes for digit 5 were similar between the groups, with presence of activities in areas other than generally activated regions because of painful stimuli. Thirty to 35 minutes after TENS treatment, a significant fMRI signal decrease for digit 3 was detected in the contralateral M1 and contralateral SMA only in the TENS group. CONCLUSIONS: Our findings showed that TENS treatment significantly decreased the pain-related cortical activations caused by stimulation of the median nerve-innervated fingers up to 35 minutes after treatment.

Faces of emotion in Parkinsons disease: micro-expressivity and bradykinesia during voluntary facial expressions.

In humans, the neural circuitry underlying facial expressions differs, depending on whether facial expressions are spontaneously (i.e., limbic, subcortical) or voluntarily initiated (i.e., frontal cortex). Previous investigators have suggested that the "masked face" of Parkinson's disease involves spontaneous, but not intentional, facial expressions. In contrast, we hypothesized that intentional facial expressions may be slowed (bradykinetic) and involve less movement, in much the same way that other intentional movements are affected by Parkinson's disease. To test this hypothesis, we used sophisticated computer imaging techniques to quantify dynamic facial movement. Relative to controls, Parkinson patients had reduced facial movement (entropy) and were significantly slowed in reaching a peak expression (i.e., bradykinesia). These findings are consistent with the view that the basal ganglia play a role in affecting intentional facial movements. This possibly occurs because of diminished efficiency and/or activation of face representation areas in the frontal cortical regions (i.e., motor, premotor, and supplementary motor area) or because of movement-based suppression secondary to dopaminergic reduction in frontostriatal pathways. Taken together, the characterization of Parkinson's disease as a model system for the neuroanatomic dissociation between voluntary and spontaneous expressions may be unjustified.

Processing words with emotional connotation: an FMRI study of time course and laterality in rostral frontal and retrosplenial cortices.

Responses of rostral frontal and retrosplenial cortices to the emotional significance of words were measured using functional magnetic resonance imaging (fMRI). Twenty-six strongly right-handed participants engaged in a language task that alternated between silent word generation to categories with positive, negative, or neutral emotional connotation and a baseline task of silent repetition of emotionally neutral words. Activation uniquely associated with word generation to categories with positive or negative versus neutral emotional connotation occurred bilaterally in rostral frontal and retrosplenial cortices. Furthermore, the time courses of activity in these areas differed, indicating that they subserve different functions in processing the emotional connotation of words. Namely, the retrosplenial cortex appears to be involved in evaluating the emotional salience of information from external sources, whereas the rostral frontal cortex also plays a role in internal generation of words with emotional connotation. In both areas, activity associated with positive or negative emotional connotation was more extensive in the left hemisphere than the right, regardless of valence, presumably due to the language demands of word generation. The present findings localize specific areas in the brain that are involved in processing emotional meaning of words within the brain's distributed semantic system. In addition, time course analysis reveals diverging mechanisms in anterior and posterior cortical areas during processing of words with emotional significance.

Left and right basal ganglia and frontal activity during language generation: contributions to lexical, semantic, and phonological processes.

fMRI was used to determine the frontal, basal ganglia, and thalamic structures engaged by three facets of language generation: lexical status of generated items, the use of semantic vs. phonological information during language generation, and rate of generation. During fMRI, 21 neurologically normal subjects performed four tasks: generation of nonsense syllables given beginning and ending consonant blends, generation of words given a rhyming word, generation of words given a semantic category at a fast rate (matched to the rate of nonsense syllable generation), and generation of words given a semantic category at a slow rate (matched to the rate of generating of rhyming words). Components of a left pre-SMA-dorsal caudate nucleus-ventral anterior thalamic loop were active during word generation from rhyming or category cues but not during nonsense syllable generation. Findings indicate that this loop is involved in retrieving words from pre-existing lexical stores. Relatively diffuse activity in the right basal ganglia (caudate nucleus and putamen) also was found during word-generation tasks but not during nonsense syllable generation. Given the relative absence of right frontal activity during the word generation tasks, we suggest that the right basal ganglia activity serves to suppress right frontal activity, preventing right frontal structures from interfering with language production. Current findings establish roles for the left and the right basal ganglia in word generation. Hypotheses are discussed for future research to help refine our understanding of basal ganglia functions in language generation.

Semantic monitoring of words with emotional connotation during fMRI: contribution of anterior left frontal cortex.

Previous studies showed that cortex in the anterior portions of the left frontal and temporal lobes participates in generating words with emotional connotations and processing pictures with emotional content. If these cortices process the semantic attribute of emotional connotation, they should be active whenever processing emotional connotation, without respect to modality of input or mode of output. Thus, we hypothesized that they would activate during monitoring of words with emotional connotations. Sixteen normal subjects performed semantic monitoring of words with emotional connotations, animal names, and implement names during fMRI. Cortex in the anterior left frontal lobe demonstrated significant activity for monitoring words with emotional connotations compared to monitoring tone sequences, animal names, or implement names. Together, the current and previous results implicate cortex in the anterior left frontal lobe in semantic processing of emotional connotation, consistent with connections of this cortex to paralimbic association areas. Current findings also indicate that neural substrates for processing emotional connotation are independent of substrates for processing the categories of living and nonliving things.