Moderators of Sexual Recidivism as Indicator of Treatment Effectiveness in Persons With Sexual Offense Histories: An Updated Meta-analysis.

The present meta-analysis is an update of the meta-analysis by Schmucker and Lösel [Campbell Syst. Rev. 2017; 13: 1-75], which synthesized evidence on sexual recidivism as an indicator of treatment effectiveness in persons with sexual offense histories. The updated meta-analysis includes 37 samples comprising a total of 30,394 individuals with sexual offense histories, which is nearly three times the sample size reported by Schmucker and Lösel (2017: 28 samples, N = 9781). In line with Schmucker and Lösel (2017), the mean treatment effect was small with an odds ratio of 1.54 [95% CI 1.22, 1.95] (p < .001). A moderator analysis suggested three predictors of importance, i.e., risk level, treatment specialization, and author confounding. Greater treatment effectiveness was suggested in high- and medium-compared to low-risk individuals and in specialized compared to non-specialized treatments. Authors affiliated with treatment programs reported larger effectiveness than independent authors. These findings were overall in line with Schmucker and Lösel (2017), though the effects of risk level and treatment specialization were stronger in the current meta-analysis. The findings of the updated meta-analysis reinforce the evidence for the first and second principle of the Risk-Need-Responsivity model. The results may support researchers and decision-makers in interpreting the current evidence on sexual recidivism as an indicator of treatment effectiveness, and, based on that, implement and carry out informative, methodologically sound evaluations of ongoing treatment programs in persons with sexual offense histories.

Conditional power of antidepressant network meta-analysis.

BACKGROUND: Conditional power of network meta-analysis (NMA) can support the planning of randomized controlled trials (RCTs) assessing medical interventions. Conditional power is the probability that updating existing inconclusive evidence in NMA with additional trial(s) will result in conclusive evidence, given assumptions regarding trial design, anticipated effect sizes, or event probabilities. METHODS: The present work aimed to estimate conditional power for potential future trials on antidepressant treatments. Existing evidence was based on a published network of 502 RCTs conducted between 1979-2018 assessing acute antidepressant treatment in major depressive disorder (MDD). Primary outcomes were efficacy in terms of the symptom change on the Hamilton Depression Scale (HAMD) and tolerability in terms of the dropout rate due to adverse events. The network compares 21 antidepressants consisting of 231 relative treatment comparisons, 164 (efficacy) and 127 (tolerability) of which are currently assumed to have inconclusive evidence. RESULTS: Required sample sizes to achieve new conclusive evidence with at least 80% conditional power were estimated to range between N = 894 - 4190 (efficacy) and N = 521 - 1246 (tolerability). Otherwise, sample sizes ranging between N = 49 - 485 (efficacy) and N = 40 - 320 (tolerability) may require stopping for futility based on a boundary at 20% conditional power. Optimizing trial designs by considering multiple trials that contribute both direct and indirect evidence, anticipating alternative effect sizes or alternative event probabilities, may increase conditional power but required sample sizes remain high. Antidepressants having the greatest conditional power associated with smallest required sample sizes were identified as those on which current evidence is low, i.e., clomipramine, levomilnacipran, milnacipran, nefazodone, and vilazodone, with respect to both outcomes. CONCLUSIONS: The present results suggest that conditional power to achieve new conclusive evidence in ongoing or future trials on antidepressant treatments is low. Limiting the use of the presented conditional power analysis are primarily due to the estimated large sample sizes which would be required in future trials as well as due to the well-known small effect sizes in antidepressant treatments. These findings may inform researchers and decision-makers regarding the clinical relevance and justification of research in ongoing or future antidepressant RCTs in MDD.

No substantial change in the balance between model-free and model-based control via training on the two-step task.

Human decisions can be habitual or goal-directed, also known as model-free (MF) or model-based (MB) control. Previous work suggests that the balance between the two decision systems is impaired in psychiatric disorders such as compulsion and addiction, via overreliance on MF control. However, little is known whether the balance can be altered through task training. Here, 20 healthy participants performed a well-established two-step task that differentiates MB from MF control, across five training sessions. We used computational modelling and functional near-infrared spectroscopy to assess changes in decision-making and brain hemodynamic over time. Mixed-effects modelling revealed overall no substantial changes in MF and MB behavior across training. Although our behavioral and brain findings show task-induced changes in learning rates, these parameters have no direct relation to either MF or MB control or the balance between the two systems, and thus do not support the assumption of training effects on MF or MB strategies. Our findings indicate that training on the two-step paradigm in its current form does not support a shift in the balance between MF and MB control. We discuss these results with respect to implications for restoring the balance between MF and MB control in psychiatric conditions.

Comparative efficacy of placebos in short-term antidepressant trials for major depression: a secondary meta-analysis of placebo-controlled trials.

BACKGROUND: The issue of unblinded outcome-assessors and patients has repeatedly been stressed as a flaw in allegedly double-blind antidepressant trials. Unblinding bias can for example result from a drug's marked side effects. If such unblinding bias is present for a given drug, then it might be expected that the placebos of that drug are rated significantly less effective than that of other antidepressants. METHODS: To test this hypothesis, the present exploratory analysis conducted a Bayesian network meta-analysis (NMA) comparing the efficacy of 19 different placebos in placebo-controlled trials provided in the dataset by Cipriani et al. (Lancet 2018; 391: 1357-66). Primary outcome was efficacy (continuous) estimated on the standardized mean difference (SMD) scale and defined as the pre-post change on the Hamilton Depression scale (HAMD-17), on which information was available in N = 258 trials. RESULTS: Comparative placebo ranking suggested mirtazapine-placebo (SMD -2.0 [- 5.0-1.0 95% CrI]) to be the most, and amitriptyline- (SMD 1.2 [- 1.6-3.9 95% CrI]) and trazodone- (SMD 2.1 [- 0.9-5.2 95% CrI]) placebos to be the least effective placebos. Other placebos suggested to be more effective than amitriptyline- and trazodone-placebos (based on 95% CrIs excluding zero) were citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, and venlafaxine placebos. These NMA results were corroborated by the observation that the relative efficacy between drug and placebo was considerably larger for amitriptyline and trazodone than for instance mirtazapine, duloxetine, and venlafaxine, supported by a small and insignificant correlation between drug-efficacy and placebo-efficacy (r = - 0.202, p = 0.408). DISCUSSION: The present exploratory NMA indicates that distinguishable side effects of older drugs may unblind outcome-assessors thus resulting in overestimation of the average drug-placebo difference and underrating bias in placebo-arms, particularly for the older antidepressant drugs amitriptyline and trazodone. If confirmed in prospective studies, these findings suggest that efficacy rankings for antidepressants are susceptible to bias and should be considered unreliable or misleading. The analysis is limited by the focus on the single-comparison placebos (76%, i.e., placebos assessed in two-arm trials), since double-comparison placebos (25%, i.e., placebos assessed in three-arm trials) are hard to interpret and therefore not included in the present interpretation. Another limitation is the problem of multiplicity, which was only approximately accounted for in the Bayesian NMA by modelling treatment effects as exchangeable.

Brain cytochrome-c-oxidase as a marker of mitochondrial function: A pilot study in major depression using NIRS.

BACKGROUND: Brain mitochondrial dysfunction is implicated in the pathophysiology of mood disorders. Brain cytochrome-c-oxidase (COX) activity is associated with the mitochondrial function. Near-infrared spectroscopy (NIRS) noninvasively measures oxidized COX (oxCOX) and tissue oxygenation index (TOI) reflecting cerebral blood flow and oxygenation. METHODS: oxCOX and TOI were assessed in prefrontal cortex (Fp1/2, Brodmann area 10) in patients in a major depressive episode (N = 13) with major depressive disorder (MDD; N = 7) and bipolar disorder (BD; N = 6) compared with the controls (N = 10). One patient with MDD and all the patients with BD were taking medications. Computational modeling estimated oxCOX and TOI related indices of mitochondrial function and cerebral blood flow, respectively. RESULTS: oxCOX was lower in patients than controls (p = .014) correlating inversely with depression severity (r = -.72; p = .006), driven primarily by lower oxCOX in BD compared with the controls. Computationally modeled mitochondrial parameters of the electron transport chain, such as the nicotinamide adenine dinucleotide ratio (NAD+ /NADH; p = .001) and the proton leak rate across the inner mitochondrial membrane (klk2 ; p = .008), were also lower in patients and correlated inversely with depression severity. No such effects were found for TOI. CONCLUSIONS: In this pilot study, oxCOX and related mitochondrial parameters assessed by NIRS indicate an abnormal cerebral metabolic state in mood disorders proportional to depression severity, potentially providing a biomarker of antidepressant effect. Because the effect was driven by the medicated BD group, findings need to be evaluated in a larger, medication-free population.

Comparison of functional near-infrared spectroscopy and electrodermal activity in assessing objective versus subjective risk during risky financial decisions.

Risk is an important factor impacting financial decisions. Risk can be processed objectively, e.g. as variance across possible outcomes of a choice option or subjectively, e.g. as value of that variance to a given individual. The aim of the present study was to test the potential of functional near-infrared spectroscopy (fNIRS) in assessing these different ways of processing risk while subjects decided between either high or low risk financial options or a safe (risk-free) option. For comparison we simultaneously measured electrodermal activity (EDA), a well-established method in decision-making research and a core measure of affective processes. FNIRS showed that lateral prefrontal cortex responses to high risk were enhanced relative to low risk only in risk-seeking individuals but reduced relative to low risk in risk-averse individuals. This is in-line with individual-specific risk processing reflecting the subjective value of risk. By contrast, EDA showed enhanced responses to high risk, independent of individual risk attitude, in-line with the notion of objective risk processing. The dissociation between the two measures arose even though they overall were equally sensitive to detect individual risk-related differences and even though there was an increased, risk attitude-independent, temporal coherence between the two measures during high-risk conditions. Our results suggest that hemodynamic responses in lateral prefrontal cortex as measured by fNIRS reflect the subjective value of risk, whereas EDA may index the objective amount of risk people are presented with. The findings suggest that fNIRS could be a useful method for studying risk behavior in financial decisions.

Physiological effects of mechanical pain stimulation at the lower back measured by functional near-infrared spectroscopy and capnography.

The aim was to investigate the effect of mechanical pain stimulation at the lower back on hemodynamic and oxygenation changes in the prefrontal cortex (PFC) assessed by functional near-infrared spectroscopy (fNIRS) and on the partial pressure of end-tidal carbon dioxide ( PetCO 2) measured by capnography. 13 healthy subjects underwent three measurements (M) during pain stimulation using pressure pain threshold (PPT) at three locations, i.e., the processus spinosus at the level of L4 (M1) and the lumbar paravertebral muscles at the level of L1 on the left (M2) and the right (M3) side. Results showed that only in the M2 condition the pain stimulation elicited characteristic patterns consisting of (1) a fNIRS-derived decrease in oxy- and total hemoglobin concentration and tissue oxygen saturation, an increase in deoxy-hemoglobin concentration, (2) a decrease in the PetCO 2 response and (3) a decrease in coherence between fNIRS parameters and PetCO 2 responses in the respiratory frequency band (0.2-0.5 Hz). We discuss the comparison between M2 vs. M1 and M3, suggesting that the non-significant findings in the two latter measurements were most likely subject to effects of the different stimulated tissues, the stimulated locations and the stimulation order. We highlight that PetCO 2 is a crucial parameter for proper interpretation of fNIRS data in experimental protocols involving pain stimulation. Together, our data suggest that the combined fNIRS-capnography approach has potential for further development as pain monitoring method, such as for evaluating clinical pain treatment.

Predictive and incremental validity of the Static-99, Static-99R, and STABLE-2007 for sexual recidivism: A diagnostic test accuracy network meta-analysis (DTA-NMA).

The Static-99, Static-99R, and STABLE-2007 are internationally well-established instruments for predicting static and dynamic risks of sexual recidivism in individuals convicted of sexual offenses. Previous meta-analyses assessed their predictive and incremental validity, but none has yet compared the two Static versions and the Static-STABLE combinations. Here, we implemented diagnostic test accuracy network meta-analysis (DTA-NMA) to compare all tests and identify optimal cutoffs in one comprehensive analysis. The DTA-NMA included 32 samples comprising 45,224 adult male individuals. More information was available on the Static-99 (22 samples; 34,316 individuals) and the Static-99R (13 samples; 27,243 individuals), compared to the Static-99/STABLE-2007 (three samples; 762 individuals), the Static-99R/STABLE-2007 (two samples; 2,972 individuals), and the STABLE-2007 (three samples; 816 individuals). The primary outcome was the area under the receiver operating characteristic curve (AUC). The secondary outcomes were sensitivity and specificity. Optimal cutoffs were determined using the Youden index. The AUC suggested moderate predictive validity for Static-99 and Static-99R, whereas STABLE-2007 had no predictive value. The optimal cutoff of Static-99R was suggested to have higher specificity than that of Static-99, whereas sensitivity was comparable between instruments. The notion of incremental validity for STABLE-2007 could not be confirmed. This work represents the first meta-analysis to compare Static-99, Static-99R, STABLE-2007, and their combinations in one analysis. Static-99R demonstrated the highest specificity in predicting the risk of sexual recidivism, indicating a potential advantage in detecting true nonrecidivists. The findings are discussed, considering the current recommendations for assessing the risk of sexual recidivism in the criminal justice system. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The effect of sudden depressurization on pilots at cruising altitude.

The standard flight level for commercial airliners is ∼12 km (40 kft; air pressure: ∼ 200 hPa), the maximum certification altitude of modern airliners may be as high as 43-45 kft. Loss of structural integrity of an airplane may result in sudden depressurization of the cabin potentially leading to hypoxia with loss of consciousness of the pilots. Specialized breathing masks supply the pilots with oxygen. The aim of this study was to experimentally simulate such sudden depressurization to maximum design altitude in a pressure chamber while measuring the arterial and brain oxygenation saturation (SaO(2) and StO(2)) of the pilots. Ten healthy subjects with a median age of 50 (range 29-70) years were placed in a pressure chamber, breathing air from a cockpit mask. Pressure was reduced from 753 to 148 hPa within 20 s, and the test mask was switched to pure O(2) within 2 s after initiation of depressurization. During the whole procedure SaO(2) and StO(2) were measured by pulse oximetry, respectively near-infrared spectroscopy (NIRS; in-house built prototype) of the left frontal cortex. During the depressurization the SaO(2) dropped from median 93% (range 91-98%) to 78% (62-92%) by 16% (6-30%), while StO(2) decreased from 62% (47-67%) to 57% (43-62%) by 5% (3-14%). Considerable drops in oxygenation were observed during sudden depressurization. The inter-subject variability was high, for SaO(2) depending on the subjects' ability to preoxygenate before the depressurization. The drop in StO(2) was lower than the one in SaO(2) maybe due to compensation in blood flow.

Error detection and error memory in spatial navigation as reflected by electrodermal activity.

The study investigated spatial navigation by means of electrodermal activity (EDA). Two groups of healthy subjects (group 1, age <38; group 2, age ≥ 38) were recorded during navigation through two 3-D virtual mazes differing in difficulty, that is, Maze Simple (MazeS) and Maze Complex (MazeC). Our results show (1) an effect of difficulty, that is, larger skin conductance responses (SCRs) and slower velocity profiles while navigating through MazeC as compared to MazeS. (2) An effect of age, that is, larger SCRs and faster velocity profiles in younger subjects (group 1) compared to older subjects (group 2). (3) An effect of maze region, that is, SCRs increased when subjects entered dead ends with group 1 (young group) decreasing in velocity, whereas group 2 (old group) increased in velocity. (4) And an error memory effect, that is, subjects who remembered an error at a given decision point (crossroads preceding dead ends in MazeC) from previous trials, and then if they did not repeat that error, elicited decreased SCRs as compared to subjects who did not remember and subsequently repeated an error. The latter aspect is the most impactful as it shows that EDA is able to reflect error detection and memory during spatial navigation. Our data designate EDA as suitable monitoring tool for identification and differentiation of the affective correlates underlying spatial navigation, which has recently attracted researchers' attention due to its increased use in 3-D virtual environments.

Between-brain connectivity during imitation measured by fNIRS.

The present study aimed to step into two-person neuroscience by investigating the hemodynamic correlates of between-brain connectivity involved in imitation and its dependency on pacing stimuli. To test this approach, we used wireless functional near-infrared spectroscopy (fNIRS) to record simultaneously during imitation performance of a paced finger-tapping task (PFT) in two subjects over premotor cortices (PMC). During the imitation (IM) condition, a model and an imitator were recorded while tapping in synchrony with auditory stimuli separated by a constant interval (stimulus-paced mode, St-P), followed by tapping without the pacing stimulus (self-paced mode, Se-P). During the control (CO) condition, each subject (single 1 and 2) performed the PFT task with the same pacing mode pattern, but alone without reference to each other. Using wavelet transform coherence (WTC) analysis evaluating functional connectivity between brains, we found (1) that IM revealed a larger coherence increase between the model and the imitator as compared to the CO condition. (2) Within the IM condition, a larger coherence increase was found during Se-P as compared to St-P mode. Using Granger-causality (G-causality) analysis evaluating effective connectivity between brains, we found (3) that IM revealed larger G-causality as compared to the CO condition and (4) that within the IM condition, the signal of the model G-caused that of the imitator to a greater extent as compared to vice versa. Our findings designate fNIRS as suitable tool for monitoring between-brain connectivity during dynamic interactions between two subjects and that those measurements might thereby provide insight into activation patterns not detectable using typical single-person experiments. Overall, the results of the present study demonstrate the potential of simultaneously assessing brain hemodynamics in interacting subjects in several research areas where social interactions are involved.

Enhancement of motor imagery-related cortical activation during first-person observation measured by functional near-infrared spectroscopy.

It is known that activity in secondary motor areas during observation of human limbs performing actions is affected by the observer's viewpoint, with first-person views generally leading to stronger activation. However, previous neuroimaging studies have displayed limbs in front of the observer, providing an offset view of the limbs without a truly first-person viewpoint. It is unknown to what extent these pseudo-first-person viewpoints have affected the results published to date. In this experiment, we used a horizontal two-dimensional mirrored display that places virtual limbs at the correct egocentric position relative to the observer. We compared subjects using the mirrored and conventional displays while recording over the premotor cortex with functional near-infrared spectroscopy. Subjects watched a first-person view of virtual arms grasping incoming balls on-screen; they were instructed to either imagine the virtual arm as their own [motor imagery during observation (MIO)] or to execute the movements [motor execution (ME)]. With repeated-measures anova, the hemoglobin difference as a direct index of cortical oxygenation revealed significant main effects of the factors hemisphere (P = 0.005) and condition (P ≤ 0.001) with significant post hoc differences between MIO-mirror and MIO-conventional (P = 0.024). These results suggest that the horizontal mirrored display provides a more accurate first-person view, enhancing subjects' ability to perform motor imagery during observation. Our results may have implications for future experimental designs involving motor imagery, and may also have applications in video gaming and virtual reality therapy, such as for patients following stroke.

Understanding inverse oxygenation responses during motor imagery: a functional near-infrared spectroscopy study.

Motor imagery (MI) is described as the mental rehearsal of voluntary movements. We used wireless functional near-infrared spectroscopy (fNIRS) recorded over secondary motor areas during performance of MI and motor execution (ME) in 11 healthy subjects, who either executed or imagined two drawing tasks differing in shape and frequency, i.e. simple (circle, 0.2 Hz) and complex (curved shape, 0.333 Hz). At the group level, results showed that fNIRS is capable of discriminating between the task mode, i.e. MI vs. ME, and the task complexity, i.e. simple vs. complex. At the single-subject level, we observed inverse oxygenation responses, i.e. a decrease in Δ[O(2) Hb] and/or increase in Δ[HHb]. These inverse responses only occurred during MI tasks and were highly correlated, in the first place, with task mode, and secondly with task complexity. Inverse Δ[O(2) Hb] responses are likely to reflect individual differences in performance-related signals and may contribute to the commonly observed inter-subject variability in fNIRS measurements. As MI is now widely used as a mental task in neurorehabilitative applications, the resulting oxygenation pattern may be of use for future developments. For this programme to be successful it is crucial to determine the sources of inter-subject variability. Our study presents a first effort in this direction, indicating that MI-related inverse Δ[O(2) Hb] responses are correlated, first, with task mode and, secondly, with task complexity.

Single-trial classification of motor imagery differing in task complexity: a functional near-infrared spectroscopy study.

BACKGROUND: For brain computer interfaces (BCIs), which may be valuable in neurorehabilitation, brain signals derived from mental activation can be monitored by non-invasive methods, such as functional near-infrared spectroscopy (fNIRS). Single-trial classification is important for this purpose and this was the aim of the presented study. In particular, we aimed to investigate a combined approach: 1) offline single-trial classification of brain signals derived from a novel wireless fNIRS instrument; 2) to use motor imagery (MI) as mental task thereby discriminating between MI signals in response to different tasks complexities, i.e. simple and complex MI tasks. METHODS: 12 subjects were asked to imagine either a simple finger-tapping task using their right thumb or a complex sequential finger-tapping task using all fingers of their right hand. fNIRS was recorded over secondary motor areas of the contralateral hemisphere. Using Fisher's linear discriminant analysis (FLDA) and cross validation, we selected for each subject a best-performing feature combination consisting of 1) one out of three channel, 2) an analysis time interval ranging from 5-15 s after stimulation onset and 3) up to four Δ[O2Hb] signal features (Δ[O2Hb] mean signal amplitudes, variance, skewness and kurtosis). RESULTS: The results of our single-trial classification showed that using the simple combination set of channels, time intervals and up to four Δ[O2Hb] signal features comprising Δ[O2Hb] mean signal amplitudes, variance, skewness and kurtosis, it was possible to discriminate single-trials of MI tasks differing in complexity, i.e. simple versus complex tasks (inter-task paired t-test p ≤ 0.001), over secondary motor areas with an average classification accuracy of 81%. CONCLUSIONS: Although the classification accuracies look promising they are nevertheless subject of considerable subject-to-subject variability. In the discussion we address each of these aspects, their limitations for future approaches in single-trial classification and their relevance for neurorehabilitation.

Motor imagery in response to fake feedback measured by functional near-infrared spectroscopy.

The objective of this study was to describe brain oxygenation patterns during motor imagery (MI) in response to feedback using functional near-infrared spectroscopy (fNIRS). fNIRS was recorded over the primary motor cortex in 15 healthy subjects using a right hand motor task during four fake feedback conditions: MI without feedback (MI(0)), MI with positive (MI(+)) and negative feedback (MI(-)) and during actual movement execution (ME) as control task. Behavioral data were collected using the Edinburgh Handedness Inventory (EHI) and The Kinesthetic and Visual Imagery Questionnaire (KVIQ-10). We observed inter-condition differences and inter-subject variability in signal amplitude with larger O(2)Hb concentration changes both in response to MI(+) (0.154+/-0.067 microM) and MI(-) (0.129+/-0.074 microM) as compared to MI(0) (0.109+/-0.024 microM) and ME (0.210+/-0.013 microM). We present fNIRS data of MI performance in response to different feedback conditions indicating that there exist distinct oxygenation patterns. These data may contribute to the development of fNIRS controlled feedback systems.

Testing the potential of a virtual reality neurorehabilitation system during performance of observation, imagery and imitation of motor actions recorded by wireless functional near-infrared spectroscopy (fNIRS).

BACKGROUND: Several neurorehabilitation strategies have been introduced over the last decade based on the so-called simulation hypothesis. This hypothesis states that a neural network located in primary and secondary motor areas is activated not only during overt motor execution, but also during observation or imagery of the same motor action. Based on this hypothesis, we investigated the combination of a virtual reality (VR) based neurorehabilitation system together with a wireless functional near infrared spectroscopy (fNIRS) instrument. This combination is particularly appealing from a rehabilitation perspective as it may allow minimally constrained monitoring during neurorehabilitative training. METHODS: fNIRS was applied over F3 of healthy subjects during task performance in a virtual reality (VR) environment: 1) 'unilateral' group (N = 15), contralateral recording during observation, motor imagery, observation & motor imagery, and imitation of a grasping task performed by a virtual limb (first-person perspective view) using the right hand; 2) 'bilateral' group (N = 8), bilateral recording during observation and imitation of the same task using the right and left hand alternately. RESULTS: In the unilateral group, significant within-condition oxy-hemoglobin concentration Δ[O2Hb] changes (mean ± SD µmol/l) were found for motor imagery (0.0868 ± 0.5201 µmol/l) and imitation (0.1715 ± 0.4567 µmol/l). In addition, the bilateral group showed a significant within-condition Δ[O2Hb] change for observation (0.0924 ± 0.3369 µmol/l) as well as between-conditions with lower Δ[O2Hb] amplitudes during observation compared to imitation, especially in the ipsilateral hemisphere (p < 0.001). Further, in the bilateral group, imitation using the non-dominant (left) hand resulted in larger Δ[O2Hb] changes in both the ipsi- and contralateral hemispheres as compared to using the dominant (right) hand. CONCLUSIONS: This study shows that our combined VR-fNIRS based neurorehabilitation system can activate the action-observation system as described by the simulation hypothesis during performance of observation, motor imagery and imitation of hand actions elicited by a VR environment. Further, in accordance with previous studies, the findings of this study revealed that both inter-subject variability and handedness need to be taken into account when recording in untrained subjects. These findings are of relevance for demonstrating the potential of the VR-fNIRS instrument in neurofeedback applications.

Raising Placebo Efficacy in Antidepressant Trials Across Decades Explained by Small-Study Effects: A Meta-Reanalysis.

BACKGROUND: Recent meta-analyses reported placebo response rate in antidepressant trials to be stable since the 1970s. These meta-analyses however were limited in considering only linear time trends, assessed trial-level covariates based on single-model hypothesis testing only, and did not adjust for small-study effects (SSE), a well-known but not yet formally assessed bias in antidepressant trials. METHODS: This secondary meta-analysis extends previous work by modeling nonlinear time trends, assessing the relative importance of trial-level covariates using a multimodel approach, and rigorously adjusting for SSE. Outcomes were placebo efficacy (continuous), based on the Hamilton Depression Scale, and placebo response rate. RESULTS: Results suggested that any nonlinear time trends in both placebo efficacy (continuous) and response rate were best explained by SSE. Adjusting for SSE revealed a significant gradual increase in placebo efficacy (continuous) from 1979 to 2014. A similar observation was made for placebo response rate, but did not reach significance due higher susceptibility to SSE. By contrast, trial-level covariates alone were found to be insufficient in explaining time trends. CONCLUSION: The present findings contribute to the ongoing debate on antidepressant placebo outcomes and highlight the need to adjust for bias introduced by SSE. The results are of clinical relevance because SSE may affect the evaluation of success or failure in antidepressant trials.

Task complexity relates to activation of cortical motor areas during uni- and bimanual performance: a functional NIRS study.

Hand motor tasks are frequently used to assess impaired motor function in neurology and neurorehabilitation. Assessments can be varied by means of hand laterality, i.e. unimanual or bimanual performance, as well as by means of task complexity, i.e. different degrees ranging from simple to complex sequence tasks. The resulting functional activation in human primary motor cortex (M1) has been studied intensively by traditional neuroimaging methods. Previous studies using functional near-infrared spectroscopy (fNIRS) investigated simple hand motor tasks. However, it is unknown whether fNIRS can also detect changes in response to increasing task complexity. Our hypothesis was to show that fNIRS could detect activation changes in relation to task complexity in uni- and bimanual tasks. Sixteen healthy right-handed subjects performed five finger-tapping tasks: unimanual left and right, simple and complex tasks as well as bimanual complex tasks. We found significant differences in oxy-hemoglobin (O(2)Hb) and deoxy-hemoglobin (HHb) concentration in the right hemisphere over M1. Largest O(2)Hb concentration changes were found during complex (0.351+/-0.051 micromol/l) and simple (0.275+/-0.054 micromol/l) right hand tasks followed by bimanual (0.249+/-0.047 micromol/l), complex (0.154+/-0.034 micromol/l) and simple (0.110+/-0.034 micromol/l) left hand tasks. Largest HHb concentration changes were found during bimanual (-0.138+/-0.006 micromol/l) tasks, followed by simple right hand (-0.12+/-0.016 micromol/l), complex left (-0.0875+/-0.007 micromol/l), complex right (-0.0863+/-0.005 micromol/l) and simple left (-0.0674+/-0.005 micromol/l) hand tasks. We report for the first time that fNIRS detects oxygenation changes in relation to task complexity during finger-tapping. The study aims to contribute to the establishment of fNIRS as a neuroimaging method to assess hand motor function in clinical settings where traditional neuroimaging methods cannot be applied.

An extended drawing test for the assessment of arm and hand function with a performance invariant for healthy subjects.

Impaired hand motor function resulting from neurological, psychiatric or orthopaedic disorders affects patients of all ages. Existing hand function assessment methods, e.g. rating scales, accelerometers and electromyographical devices, are often time-consuming to administer, subjective in interpretation and/or expensive. Graphonomic tests are gaining popularity as a way of avoiding these drawbacks while relating directly to writing and drawing. Here we present a computerized Extended Drawing Test (EDT), which improves on an earlier Drawing Test for stroke patients in three ways. First, it assesses isolated proximal arm movement using a graphics pen in a puck-like pen holder, and in addition combined arm and finger dexterity in movements using a normal writing grip. Secondly, we calibrated our test against 186 healthy subjects (3-70 years), finding significant age- and handedness-related differences in both speed and accuracy of drawing. Thirdly, to simplify assessment we devised an overall performance measure using a variant of Fitts' Law combining speed and accuracy, which we found to be age-independent for healthy subjects above 3 years of age. This result enables us to provide age-independent performance norms using both hands, with and without the pen holder. These norms may assist quantification of specific arm dysfunction by comparing patient performance with the healthy norms, and also by comparing within-patient performance in the dominant and non-dominant hands with and without the pen holder. Using our freely available software, this new test will allow clinicians to rapidly assess arm and hand function across a wide range of patient categories and ages.

Test-retest reliability of brain mitochondrial cytochrome-c-oxidase assessed by functional near-infrared spectroscopy.

Functional near-infrared spectroscopy (fNIRS) is a noninvasive method for measuring in vivo both hemodynamic and mitochondrial metabolic activities in brain cortical structures. Although the test-retest reliability of the hemodynamic measures, such as reflected by oxygenated (HbO2), deoxygenated (HHb) hemoglobin, and the tissue oxygenation index (TOI), has been previously reported to be good to excellent, the reliability of the metabolic signal indexed by oxidized cytochrome-c-oxidase (oxCCO) has not been reported. The present test-retest study compared the reliability of the metabolic and hemodynamic signals in 10 healthy participants undergoing hypo- and hypercapnia challenges. The primary reliability measure was the intraclass correlation coefficient (ICC). Results of both hypo- and hypercapnia showed that the oxCCO signal (ICC = 0.876 / 0.757) had robust reliability comparable with that of the HbO2 (ICC = 0.841 / 0.801), HHb (ICC = 0.804 / 0.571), and TOI (ICC = 0.574 / 0.614) signals. These findings show that the oxCCO signal can be assessed by fNIRS with comparable reliability to the hemodynamic measures. We discuss the results in light of current interest in a mitochondrial metabolic marker derived from fNIRS.