The delayed reproduction of long time intervals defined by innocuous thermal sensation.

The presence of discrete events during an interval to be estimated generally causes a dilation of perceived duration (event-filling effect). Here, we investigated this phenomenon in the thermal modality using multi-seconds (19 s) innocuous cool stimuli that were either constant (continuous interval) or fluctuating to create three discrete sensory events (segmented interval). Moreover, we introduced a delay following stimulus offset, before the reproduction phase, to allow for a direct comparison with our recent study showing an underestimation of duration in a delayed reproduction task of heat pain sensations (Khoshnejad et al. in Pain 155:581-590, 2014. doi: 10.1016/j.pain.2013.12.015 ). The event-filling effect was tested by comparing the delayed reproduction of the segmented and the continuous stimuli in experimental conditions asking participants to (1) reproduce the dynamics of the sensation (i.e., changes in sensory intensity over time) or (2) reproduce only the interval duration (i.e., sensation onset-to-offset). A perceptual (control) condition required participants to report changes in sensation concurrently with the stimulus. Results of the dynamic task confirmed the underestimation of duration in the delayed reproduction task, but this effect was only found with the continuous and not with the segmented stimulus. This implies that the dilation of duration produced by segmentation might compensate for the underestimation of duration in this delayed reproduction task. However, this temporal dilation effect was only observed when participants were required to attend and reproduce the dynamics of sensation. These results suggest that the event-filling effect can be observed in the thermal sensory modality and that attention directed toward changes in sensory intensity might contribute to this effect.

Maturation of EEG power spectra in early adolescence: a longitudinal study.

This study investigated the fine-grained development of the EEG power spectra in early adolescence, and the extent to which it is reflected in changes in peak frequency. It also sought to determine whether sex differences in the EEG power spectra reflect differential patterns of maturation. A group of 56 adolescents were tested at age 10 years and then at two further time-points approximately 18 months apart. The EEG was recorded during both eyes-closed and eyes-open conditions and Fourier transformed to provide estimates of absolute and relative spectral power at 0.5 Hz intervals from 0.5 to 40 Hz. The peak alpha frequency for each individual at each time-point was also determined for relative spectral power. Partial Least Squares (PLS) analysis was used to determine the combination of electrodes and frequencies that showed developmental change, or differed between the sexes. As a function of age, absolute delta and theta frequencies power decreased, and relative alpha2 and beta frequencies increased, replicating the standard findings of a decrease in lower, and increase in higher, frequencies with age. A small but significant increase in peak alpha frequency with age was detected. Moreover PLS analysis performed with individual alpha frequencies aligned to 10 Hz suggested that the age-related increase seen in alpha2 relative power was driven by changes in the peak frequency. Although males demonstrated higher alpha power than females, there were no sex differences in peak frequency, suggesting that there may be more to sex differences in EEG power than simply different rates of maturation between the two sexes.

Effects of Brief Mindfulness Interventions on the Interference Induced by Experimental Heat Pain on Cognition in Healthy Individuals.

Background: Pain captures attention and interferes with competing tasks demanding cognitive effort. Brief mindfulness interventions involving both conceptual learning and meditation exercises have been shown to improve attention and reduce pain sensitivity, and could potentially reduce pain interference. This study assesses the effect of a 5-day mindfulness intervention (20 min/day) on the interference produced by thermal pain on working memory performance using a 2-back task. Methods: Healthy participants were randomized into three groups exposed to mindfulness meditation training (n = 15), an active educational control intervention comprising only conceptual information on mindfulness (n = 15), or no intervention (n = 15). The two active interventions were administered in a dual-blind fashion and outcomes were assessed by research personnel blind to this allocation. Evaluation sessions were conducted before and after the interventions to assess the effect of pain on 2-back performance (pain interference). Importantly, both pain stimuli and the 2-back task were calibrated individually and in each session before assessing pain interference, thereby controlling for possible changes in baseline pain sensitivity and cognitive performance. Secondary outcomes included heat pain sensitivity, cold pain tolerance, cognitive inhibition, cognitive flexibility, and divided attention. Results: Manipulation checks confirmed that heat pain interferes with the performance of the working-memory task. Compared to the no-intervention control group, pain interference was significantly reduced following the conceptual intervention but not the meditation intervention, although a corollary analysis suggests the effect might be due to regression toward the mean caused by baseline imbalance in pain interference. Secondary outcomes also suggested an increase in pain tolerance in the conceptual learning group only. Discussion: A short mindfulness meditation intervention was insufficient to reduce pain interference but conceptual learning about mindfulness produced some unexpected benefits. Although the generalization of experimental findings to clinical pain conditions may be premature, these results highlight the importance of distinguishing the contribution of mindfulness education and meditation training in future studies. Understanding the effects of mindfulness training on pain regulation and management must take into consideration the multiple factors underlying this complex intervention.

Expected value and sensitivity to punishment modulate insular cortex activity during risky decision making.

The exact contribution of the insula to risky decision making remains unclear, as are the specific outcome parameters and inter-individual characteristics that modulate insular activity prior to a risky choice. This fMRI study examines the contributions of outcome valence, magnitude, probability, and expected value (EV) to insular activity during risky decision making, and explores the influence of sensitivity to reward and to punishment, and anxiety, to insular activity. Participants (N = 31) performed a gambling task requiring choice between two roulettes with different outcome magnitude, probability and EV, under gain and loss conditions separately, and filled questionnaires assessing sensitivity to punishment/reward, and state/trait anxiety. Parametric analyses were conducted to examine the modulation of brain activity during decision making in relation to each task parameter. Correlations were examined between insular activity and psychometric questionnaires. EV of the selected roulette was associated with right posterior insula activation during decision making. Higher sensitivity to punishment was associated with lower bilateral insular activation. These findings suggest that the right posterior insula is involved in tracking the EV of a risky option during decision making. The involvement of the insula when making risky decisions also appears to be influenced by inter-individual differences in sensitivity to punishment.

Basal ganglia and frontal involvement in self-generated and externally-triggered finger movements in the dominant and non-dominant hand.

Although there are a number of functional neuroimaging studies that have investigated self-initiated and externally-triggered movements, data directly comparing right and left hands in this context are very scarce. The goal of this study was to further understand the role of the basal ganglia and prefrontal cortex in the realm of self-initiated and externally-triggered right and left hand movements. Young healthy right-handed adults performed random, follow and repeat conditions of a finger moving task with their right and left hands, while being scanned with functional magnetic resonance imaging. Significant activation of the dorsolateral prefrontal cortex was observed when comparing the self-initiated movements with the repeated control and externally-triggered movements when using either hand in agreement with its role in monitoring. The caudate nucleus activation was found during self-initiated conditions compared with the control condition when either hand was used, showing that it is particularly involved when a new movement needs to be planned. Significant putamen activation was observed in all within-hand contrasts except for the externally-triggered vs. control condition when using the left hand. Furthermore, greater putaminal activation was found for the left vs. the right hand during the control condition, but for the right vs. the left hand subtraction for the self-initiated condition. Our results show that the putamen is particularly involved in the execution of non-routine movements, especially if those are self-initiated. Furthermore, we propose that, for right-handed people performing fine movements, as far as putamen involvement is concerned, the lack of proficiency of the non-dominant hand may prevail over other task demands.

Correction: Test-retest reliability of myelin imaging in the human spinal cord: Measurement errors versus region- and aging-induced variations.

[This corrects the article DOI: 10.1371/journal.pone.0189944.].

Test-retest reliability of myelin imaging in the human spinal cord: Measurement errors versus region- and aging-induced variations.

PURPOSE: To implement a statistical framework for assessing the precision of several quantitative MRI metrics sensitive to myelin in the human spinal cord: T1, Magnetization Transfer Ratio (MTR), saturation imposed by an off-resonance pulse (MTsat) and Macromolecular Tissue Volume (MTV). METHODS: Thirty-three healthy subjects within two age groups (young, elderly) were scanned at 3T. Among them, 16 underwent the protocol twice to assess repeatability. Statistical reliability indexes such as the Minimal Detectable Change (MDC) were compared across metrics quantified within different cervical levels and white matter (WM) sub-regions. The differences between pathways and age groups were quantified and interpreted in context of the test-retest repeatability of the measurements. RESULTS: The MDC was respectively 105.7ms, 2.77%, 0.37% and 4.08% for T1, MTR, MTsat and MTV when quantified over all WM, while the standard-deviation across subjects was 70.5ms, 1.34%, 0.20% and 2.44%. Even though particular WM regions did exhibit significant differences, these differences were on the same order as test-retest errors. No significant difference was found between age groups for all metrics. CONCLUSION: While T1-based metrics (T1 and MTV) exhibited better reliability than MT-based measurements (MTR and MTsat), the observed differences between subjects or WM regions were comparable to (and often smaller than) the MDC. This makes it difficult to determine if observed changes are due to variations in myelin content, or simply due to measurement error. Measurement error remains a challenge in spinal cord myelin imaging, but this study provides statistical guidelines to standardize the field and make it possible to conduct large-scale multi-center studies.

Brain processing of the temporal dimension of acute pain in short-term memory.

The dynamics of noxious sensation shapes pain perception, yet the memory of the temporal dimension of pain remains almost completely unexplored. Here, brain activity during the memory of pain duration was contrasted with that associated with the memory of pain intensity using functional magnetic resonance imaging and a delayed reproduction task. Participants encoded, maintained during a short delay, and reproduced (1) the "duration" of pain (ie, onset-to-offset), (2) the "dynamics" of pain (ie, evolution of pain over time), or (3) the intensity of pain (ie, control with no explicit temporal processing required). Results show that the inferior frontal gyrus/insula and adjacent striatal structures as well as the supramarginal and middle temporal gyri are activated in the duration task compared to the control intensity task. Specific examination of the memory delay of the duration task further revealed activation in the supramarginal gyrus extending to the parietal operculum (possibly SII) and primary somatosensory cortex (SI). In contrast, the memory delay of the dynamic task involved the bilateral supplementary motor area and the frontoparietal attentional network. Although SI, SII, and insula may contribute to the memory trace of pain sensation, other areas less commonly reported in pain studies are associated with time processing and may therefore contribute to the processing of temporal aspects of pain. Results further suggest a differential role of core timing regions of the brain depending on specific task instructions and attentional allocations to the single dimension of time, as compared to the joint processing of both time and intensity.

Function of basal ganglia in bridging cognitive and motor modules to perform an action.

The basal ganglia (BG) are thought to be involved in the integration of multiple sources of information, and their dysfunction can lead to disorders such as Parkinson's disease (PD). PD patients show motor and cognitive dysfunction with specific impairments in the internal generation of motor actions and executive deficits, respectively. The role of the BG, then, would be to integrate information from several sources in order to make a decision on a resulting action adequate for the required task. Reanalyzing the data set from our previous study (Martinu et al., 2012), we investigated this hypothesis by applying a graph theory method to a series of fMRI data during the performance of self-initiated (SI) finger movement tasks obtained in healthy volunteers (HV) and early stage PD patients. Dorsally, connectivity strength between the medial prefrontal areas (mPFC) and cortical regions including the primary motor area (M1), the extrastriate visual cortex, and the associative cortex, was reduced in the PD patients. The connectivity strengths were positively correlated to activity in the striatum in both groups. Ventrally, all connectivity between the striatum, the thalamus, and the extrastriate visual cortex decreased in strength in the PD, as did the connectivity between the striatum and the ventrolateral PFC (VLPFC). Individual response time (RT) was negatively correlated to connectivity strength between the dorsolateral PFC (DLPFC) and the striatum and positively correlated to connectivity between the VLPFC and the striatum in the HV. These results indicate that the BG, with the mPFC and thalamus, are involved in integrating multiple sources of information from areas such as DLPFC, and VLPFC, connecting to M1, thereby determining a network that leads to the adequate decision and performance of the resulting action.

Asymmetrical effect of levodopa on the neural activity of motor regions in PD.

Parkinson's disease (PD) is a neurodegenerative illness often characterized by asymmetrical symptoms. However, the reason for this asymmetry and the cerebral correlates underlying symptom asymmetry are still not well understood. Furthermore, the effects of levodopa on the cerebral correlates of disease asymmetry have not been investigated. In this study, right-handed PD patients performed self-initiated, externally triggered and repetitive control finger movements with both their right and left hands during functional magnetic resonance imaging (fMRI) to investigate asymmetrical effects of levodopa on the hemodynamic correlates of finger movements. Patients completed two experimental sessions OFF and ON medication after a minimum of 12 hours medication withdrawal. We compared the effect of levodopa on the neural activation patterns underlying the execution of both the more affected and less affected hand for self-initiated and externally triggered movements. Our results show that levodopa led to larger differences in cerebral activity for movements of the more affected, left side: there were significant differences in activity after levodopa administration in regions of the motor cortico-striatal network when patients performed self-initiated and externally triggered movements with their left hand. By contrast, when patients used their right hand, levodopa led to differences in cerebellar activity only. As our patients were affected more severely on their left side, we propose that levodopa may help provide additional dopaminergic input, improving movements for the more severely affected side. These results suggest that the impact of reduced dopamine in the cortico-striatal system and the action of levodopa is not symmetrical.

Cortico-basal ganglia and cortico-cerebellar circuits in Parkinson's disease: pathophysiology or compensation?

The basal ganglia and the cerebellum are anatomically and functionally linked to the cerebral cortex through a series of well-established circuits. The disruption of dopaminergic projections in Parkinson's disease (PD) leads to an imbalance within these circuits, leading to motor and cognitive symptoms. The cortico-cerebellar (CC) network has often been viewed as a compensatory network, helping the dysfunction of the cortico-basal ganglia (CBG) circuits in PD. However, evidence for this compensatory role is scarce; most changes in cerebellar activity could equally be attributed to pathophysiological changes underlying PD. This paper will review the anatomy, interaction and function of the CBG and CC circuits, the pathophysiological, metabolic, and functional changes observed in PD, as well as the effect of levodopa and deep brain stimulation on these changes. We will use this framework to discuss the pathophysiological and compensatory mechanisms behind CBG and CC circuit activity in PD.

Exploring age-related changes in dynamical non-stationarity in electroencephalographic signals during early adolescence.

Dynamics of brain signals such as electroencephalogram (EEG) can be characterized as a sequence of quasi-stable patterns. Such patterns in the brain signals can be associated with coordinated neural oscillations, which can be modeled by non-linear systems. Further, these patterns can be quantified through dynamical non-stationarity based on detection of qualitative changes in the state of the systems underlying the observed brain signals. This study explored age-related changes in dynamical non-stationarity of the brain signals recorded at rest, longitudinally with 128-channel EEG during early adolescence (10 to 13 years of age, 56 participants). Dynamical non-stationarity was analyzed based on segmentation of the time series with subsequent grouping of the segments into clusters with similar dynamics. Age-related changes in dynamical non-stationarity were described in terms of the number of stationary states and the duration of the stationary segments. We found that the EEG signal became more non-stationary with age. Specifically, the number of states increased whereas the mean duration of the stationary segment decreased with age. These two effects had global and parieto-occipital distribution, respectively, with the later effect being most dominant in the alpha (around 10 Hz) frequency band.

The contribution of neuroimaging for the study of cognitive deficits in Parkinson's disease.

The last few years have seen an increase in the number of studies using functional Magnetic Resonance Imaging (fMRI) along with receptor imaging and regional cerebral blood flow Positron Emission Tomography (PET) to understand the neurobiological underpinnings of cognitive deficits in Parkinson's disease (PD). These studies have shown evidence that the nigrostriatal degeneration solely cannot account for these deficits and that involvement of other neural systems such as the mesocortical dopamine may also play an important role. In this article, we provide a review of neuroimaging results regarding the role of possible compensatory activity, L-Dopa medication, and difference in genotypes on the cognitive deficits observed in PD. Finally, some future avenues for research are proposed.