Neuroimaging Paradigms Research Articles

NEURAL CORRELATES OF KNEE MOTOR CONTROL FOR YOUNG FEMALES WITH PATELLOFEMORAL PAIN

Background: Patellofemoral pain (PFP) is a common knee pain condition that affects up to 30% of adolescents and is disproportionately distributed between sexes, affecting females 2-10 times more frequently than male counterparts (Fulkerson, 2002). PFP, characterized by retro- or peripatellar pain, can be debilitating, leading to cessation of physical activity in 74% of adolescents (Fairbank, Pynsent, van Poortvliet, & Phillips, 1984). Aberrant lower-extremity biomechanics for those with PFP has been identified (Souza & Powers, 2009; Willson & Davis, 2008), but the underlying brain activation patterns contributing to pain-disrupted knee motor control is unknown. Patients with knee ligament deficiency demonstrate decreased sensorimotor activity and increased prelimbic activity in response to knee pain, compared with matched controls (Kadowaki, Tadenuma, Kumahashi, & Uchio, 2017), and those with knee ligament reconstruction demonstrate a disrupted sensory-motor brain activation strategy to control the knee (Grooms et al., 2017; Grooms, Page, & Onate, 2015). As PFP has been identified as a contributing factor to knee osteoarthritis later in life (Utting, Davies, & Newman, 2005), identifying the neural mechanisms driving pain-disrupted motor control could guide innovative neural-targeted interventions to treat and reduce knee pain. We hypothesized that patients with PFP, like those with knee ligament deficiencies and reconstruction, would demonstrate decreased sensorimotor brain activation and increased medial pain network brain activation to control the knee. We used our previously established knee motor control neuroimaging paradigm that simulates knee flexion and extension movements (Grooms et al., 2015) to identify altered neural activation patterns for those with PFP and compared those with matched controls. Methods: Four adolescent girls with patellofemoral pain (PFP: n = 4, 15.4 ± 2.2yrs, 158.5 ± 5.4 cm, 61.5 ± 15.6 kg) were matched with four adolescent girls with no history of knee pain (controls) based on age, height, and weight (Con: n =4, 16.4 ± 1.8yrs, 161.8 ± 5.1 cm, 54.9 ± 6.9 kg). Participants were positioned supine in a magnetic resonance imaging (MRI) scanner and completed a series of unilateral 45° knee extension/flexion movements at a velocity of 1.2 Hz (Figure 1; Left Panel). Various torso straps and head packing procedures were utilized to restrict excessive head motion. A second level mixed-effects (FLAME 1+2) independent samples t-test contrasted brain activation between the PFP and controls using a significance level set a priori at p < .05; Gaussian random field cluster corrected and z threshold set at z > 1.5. Results: Results revealed significantly depressed brain activation in the right parietal operculum cortex (z = 5.99, p < .001) and left Heschl’s gyrus (z = 3.83, p < .001) for the PFP compared to the controls (Figure 1; Right Panel). Discussion: The present study revealed significant differences in the neural activation patterns to control the knee between adolescent girls with PFP and those with no knee pain. Patients with PFP demonstrated less activation in sensorimotor cortices, seen in the parietal operculum, and sensory integration, seen in Heschl’s gyrus, when compared to healthy controls (Grooms et al., 2017; Kadowaki et al., 2017). These results indicate that pain may be suppressing sensory integration to control the knee for those with PFP. Congruent with previous neuroimaging investigations assessing those with knee injury (Grooms et al., 2017; Kadowaki et al., 2017), PFP appears to also induce neuroplastic effects identifiable using fMRI. These results provide a potential neural target for interventions that aim to restore sensorimotor integration in those with PFP, reduce pain, and restore an active lifestyle in young females. [Figure: see text]

Preliminary development of a neuroimaging paradigm to examine neural correlates of relationship conflict

Social stress in the form of conflict between romantic partners is a salient correlate of substance use disorders (SUD), and also plays an integral role in SUD treatment outcomes. Neuroimaging has advanced the study of social stress on SUD etiology, course, and treatment. However, no neuroimaging paradigms have yet been developed to examine neural responses to conflict among romantic couples. In order to fill this gap in the literature, the goal of this exploratory study was to examine the preliminary feasibility of a novel relationship conflict fMRI paradigm. We compared the effects of an auditory relationship conflict versus a neutral cue on functional connectivity in corticolimbic brain regions, and the associations between neural activities and self-report ratings of relationship adjustment, substance use problems, and intimate partner violence. We also explored sex differences in neural correlates of relationship conflict versus neutral cues. Participants demonstrated increased functional connectivity between the amygdala and the prefrontal cortex during the relationship conflict cue compared to the neutral cue. Intimate partner violence was associated with functional connectivity. Sex differences emerged in neural responses to the relationship conflict cue compared to the neutral cue. Collectively, the findings demonstrate preliminary validity of this novel neuroimaging paradigm for couples.

Communication of emotion via drumming: dual-brain imaging with functional near-infrared spectroscopy.

Nonverbal communication of emotion is essential to human interaction and relevant to many clinical applications, yet it is an understudied topic in social neuroscience. Drumming is an ancient nonverbal communication modality for expression of emotion that has not been previously investigated in this context. We investigate the neural response to live, natural communication of emotion via drumming using a novel dual-brain neuroimaging paradigm. Hemodynamic signals were acquired using whole-head functional near-infrared spectroscopy (fNIRS). Dyads of 36 subjects participated in two conditions, drumming and talking, alternating between ‘sending’ (drumming or talking to partner) and ‘receiving’ (listening to partner) in response to emotionally salient images from the International Affective Picture System. Increased frequency and amplitude of drum strikes was behaviorally correlated with higher arousal and lower valence measures and neurally correlated with temporoparietal junction (TPJ) activation in the listener. Contrast comparisons of drumming greater than talking also revealed neural activity in right TPJ. Together, findings suggest that emotional content communicated by drumming engages right TPJ mechanisms in an emotionally and behaviorally sensitive fashion. Drumming may provide novel, effective clinical approaches for treating social–emotional psychopathology.

Disentangling the Neural Basis of Cognitive Behavioral Therapy in Psychiatric Disorders: A Focus on Depression

Background: Major depressive disorder (MDD) stands among the most frequent psychiatric disorders. Cognitive behavioral therapy (CBT) has been shown to be effective for treating depression, yet its neural mechanisms of action are not well elucidated. The objective of this work is to assess the available neuroimaging studies exploring CBT’s effects in adult patients with MDD. Methods: Computerized databases were consulted till April 2018 and a research was conducted according to PRISMA guidelines in order to identify original research articles published at any time in English and French languages on this topic. Results: Seventeen studies were identified. Only one study was randomized comparing CBT to pharmacological interventions, and none included an effective control. Following CBT, changes occurred in cerebral areas that are part of the fronto-limbic system, namely the cingulate cortex, prefrontal cortex and amygdala-hippocampal complex. However, the pattern of activation and connectivity in these areas varied across the studies. Conclusion: A considerable heterogeneity exists with regard to study design, adapted CBT type and intensity, and employed neuroimaging paradigms, all of which may partly explain the difference in studies’ outcomes. The lack of randomization and effective controls in most of them makes it difficult to draw formal conclusion whether the observed effects are CBT mediated or due to spontaneous recovery. Despite the observed inconsistencies and dearth of data, CBT appears to exert its anti-depressant effects mainly by modulating the function of affective and cognitive networks devoted to emotions generation and control, respectively. This concept remains to be validated in large scale randomized controlled trials.

Neuromodulation of reinforced skill learning reveals the causal function of prefrontal cortex.

Accumulating evidence has suggested functional interactions between prefrontal cortex (PFC) and dissociable large-scale networks. However, how these networks interact in the human brain to enable complex behaviors is not well-understood. Here, using a combination of behavioral, brain stimulation and neuroimaging paradigms, we tested the hypothesis that human PFC is required for successful reinforced skill formation. We additionally tested the extent to which PFC-dependent skill formation is related to intrinsic functional communication with this region. We report that inhibitory noninvasive transcranial magnetic stimulation over lateral PFC, a hub region with a diverse connectivity profile, causally modulated effective reinforcement-based motor skill acquisition. Furthermore, PFC-dependent skill formation was strongly related to the strength of functional connectivity between the PFC and regions in the sensorimotor network. These results point to the involvement of lateral PFC in the neural architecture that underlies the acquisition of complex skills, and suggest that, in relation to skill acquisition, this region may be involved in functional interactions with sensorimotor networks.

The Complex Nature of Hippocampal-Striatal Interactions in Spatial Navigation.

Decades of research have established the importance of the hippocampus for episodic and spatial memory. In spatial navigation tasks, the role of the hippocampus has been classically juxtaposed with the role of the dorsal striatum, the latter of which has been characterized as a system important for implementing stimulus-response and action-outcome associations. In many neuroimaging paradigms, this has been explored through contrasting way finding and route-following behavior. The distinction between the contributions of the hippocampus and striatum to spatial navigation has been supported by extensive literature. Convergent research has also underscored the fact that these different memory systems can interact in dynamic ways and contribute to a broad range of navigational scenarios. For example, although familiar routes may often be navigable based on stimulus-response associations, hippocampal episodic memory mechanisms can also contribute to egocentric route-oriented memory, enabling recall of context-dependent sequences of landmarks or the actions to be made at decision points. Additionally, the literature has stressed the importance of subdividing the striatum into functional gradients—with more ventral and medial components being important for the behavioral expression of hippocampal-dependent spatial memories. More research is needed to reveal how networks involving these regions process and respond to dynamic changes in memory and control demands over the course of navigational events. In this Perspective article, we suggest that a critical direction for navigation research is to further characterize how hippocampal and striatal subdivisions interact in different navigational contexts.

A Multitude of Neural Representations Behind Multisensory "Social Norm" Processing.

Humans show a unique capacity to process complex information from multiple sources. Social perception in natural environment provides a good example of such capacity as it typically requires the integration of information from different sensory systems, and also from different levels of sensory processing. Here, instead of studying one isolate system and level of representation, we focused upon a neuroimaging paradigm which allows to capture multiple brain representations simultaneously, i.e., low and high-level processing in two different sensory systems, as well as abstract cognitive processing of congruency. Subjects performed social decisions based on the congruency between auditory and visual processing. Using multivoxel pattern analysis (MVPA) of functional magnetic resonance imaging (fMRI) data, we probed a wide variety of representations. Our results confirmed the expected representations at each level and system according to the literature. Further, beyond the hierarchical organization of the visual, auditory and higher order neural systems, we provide a more nuanced picture of the brain functional architecture. Indeed, brain regions of the same neural system show similarity in their representations, but they also share information with regions from other systems. Further, the strength of neural information varied considerably across domains in a way that was not obviously related to task relevance. For instance, selectivity for task-irrelevant animacy of visual input was very strong. The present approach represents a new way to explore the richness of co-activated brain representations underlying the natural complexity in human cognition.

Assessing Top-Down and Bottom-Up Contributions to Auditory Stream Segregation and Integration With Polyphonic Music.

Polyphonic music listening well exemplifies processes typically involved in daily auditory scene analysis situations, relying on an interactive interplay between bottom-up and top-down processes. Most studies investigating scene analysis have used elementary auditory scenes, however real-world scene analysis is far more complex. In particular, music, contrary to most other natural auditory scenes, can be perceived by either integrating or, under attentive control, segregating sound streams, often carried by different instruments. One of the prominent bottom-up cues contributing to multi-instrument music perception is their timbre difference. In this work, we introduce and validate a novel paradigm designed to investigate, within naturalistic musical auditory scenes, attentive modulation as well as its interaction with bottom-up processes. Two psychophysical experiments are described, employing custom-composed two-voice polyphonic music pieces within a framework implementing a behavioral performance metric to validate listener instructions requiring either integration or segregation of scene elements. In Experiment 1, the listeners' locus of attention was switched between individual instruments or the aggregate (i.e., both instruments together), via a task requiring the detection of temporal modulations (i.e., triplets) incorporated within or across instruments. Subjects responded post-stimulus whether triplets were present in the to-be-attended instrument(s). Experiment 2 introduced the bottom-up manipulation by adding a three-level morphing of instrument timbre distance to the attentional framework. The task was designed to be used within neuroimaging paradigms; Experiment 2 was additionally validated behaviorally in the functional Magnetic Resonance Imaging (fMRI) environment. Experiment 1 subjects (N = 29, non-musicians) completed the task at high levels of accuracy, showing no group differences between any experimental conditions. Nineteen listeners also participated in Experiment 2, showing a main effect of instrument timbre distance, even though within attention-condition timbre-distance contrasts did not demonstrate any timbre effect. Correlation of overall scores with morph-distance effects, computed by subtracting the largest from the smallest timbre distance scores, showed an influence of general task difficulty on the timbre distance effect. Comparison of laboratory and fMRI data showed scanner noise had no adverse effect on task performance. These Experimental paradigms enable to study both bottom-up and top-down contributions to auditory stream segregation and integration within psychophysical and neuroimaging experiments.

Sparse coding reveals greater functional connectivity in female brains during naturalistic emotional experience.

Functional neuroimaging is widely used to examine changes in brain function associated with age, gender or neuropsychiatric conditions. FMRI (functional magnetic resonance imaging) studies employ either laboratory-designed tasks that engage the brain with abstracted and repeated stimuli, or resting state paradigms with little behavioral constraint. Recently, novel neuroimaging paradigms using naturalistic stimuli are gaining increasing attraction, as they offer an ecologically-valid condition to approximate brain function in real life. Wider application of naturalistic paradigms in exploring individual differences in brain function, however, awaits further advances in statistical methods for modeling dynamic and complex dataset. Here, we developed a novel data-driven strategy that employs group sparse representation to assess gender differences in brain responses during naturalistic emotional experience. Comparing to independent component analysis (ICA), sparse coding algorithm considers the intrinsic sparsity of neural coding and thus could be more suitable in modeling dynamic whole-brain fMRI signals. An online dictionary learning and sparse coding algorithm was applied to the aggregated fMRI signals from both groups, which was subsequently factorized into a common time series signal dictionary matrix and the associated weight coefficient matrix. Our results demonstrate that group sparse representation can effectively identify gender differences in functional brain network during natural viewing, with improved sensitivity and reliability over ICA-based method. Group sparse representation hence offers a superior data-driven strategy for examining brain function during naturalistic conditions, with great potential for clinical application in neuropsychiatric disorders.

Taking tests in the magnet: Brain mapping standardized tests.

Standardized psychometric tests are sophisticated, well-developed, and consequential instruments; test outcomes are taken as facts about people that impact their lives in important ways. As part of an initial demonstration that human brain mapping techniques can add converging neural-level evidence to understanding standardized tests, our participants completed items from standardized tests during an fMRI scan. We compared tests for diagnosing posttraumatic stress disorder (PTSD) and the correlated measures of Neuroticism, Attachment, and Centrality of Event to a general-knowledge baseline test. Twenty-three trauma-exposed participants answered 20 items for each of our five tests in each of the three runs for a total of 60 items per test. The tests engaged different neural processes; which test a participant was taking was accurately predicted from other participants' brain activity. The novelty of the application precluded specific anatomical predictions; however, the interpretation of activated regions using meta-analyses produced encouraging results. For instance, items on the Attachment test engaged regions shown to be more active for tasks involving judgments of others than judgments of the self. The results are an initial demonstration of a theoretically and practically important test-taking neuroimaging paradigm and suggest specific neural processes in answering PTSD-related tests. Hum Brain Mapp 38:5706-5725, 2017. © 2017 Wiley Periodicals, Inc.

Understanding principles of integration and segregation using whole-brain computational connectomics: implications for neuropsychiatric disorders.

To survive in an ever-changing environment, the brain must seamlessly integrate a rich stream of incoming information into coherent internal representations that can then be used to efficiently plan for action. The brain must, however, balance its ability to integrate information from various sources with a complementary capacity to segregate information into modules which perform specialized computations in local circuits. Importantly, evidence suggests that imbalances in the brain's ability to bind together and/or segregate information over both space and time is a common feature of several neuropsychiatric disorders. Most studies have, however, until recently strictly attempted to characterize the principles of integration and segregation in static (i.e. time-invariant) representations of human brain networks, hence disregarding the complex spatio-temporal nature of these processes. In the present Review, we describe how the emerging discipline of whole-brain computational connectomics may be used to study the causal mechanisms of the integration and segregation of information on behaviourally relevant timescales. We emphasize how novel methods from network science and whole-brain computational modelling can expand beyond traditional neuroimaging paradigms and help to uncover the neurobiological determinants of the abnormal integration and segregation of information in neuropsychiatric disorders.This article is part of the themed issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.

Patterns of Default Mode Network Deactivation in Obsessive Compulsive Disorder

The objective of the present study was to research the patterns of Default Mode Network (DMN) deactivation in Obsessive Compulsive Disorder (OCD) in the transition between a resting and a non-rest emotional condition. Twenty-seven participants, 15 diagnosed with OCD and 12 healthy controls (HC), underwent a functional neuroimaging paradigm in which DMN brain activation in a resting condition was contrasted with activity during a non-rest condition consisting in the presentation of emotionally pleasant and unpleasant images. Results showed that HC, when compared with OCD, had a significant deactivation in two anterior nodes of the DMN (medial frontal and superior frontal) in the non-rest pleasant stimuli condition. Additional analysis for the whole brain, contrasting the resting condition with all the non-rest conditions grouped together, showed that, compared with OCD, HC had a significantly deactivation of a widespread brain network (superior frontal, insula, middle and superior temporal, putamen, lingual, cuneus, and cerebellum). Concluding, the present study found that OCD patients had difficulties with the deactivation of DMN even when the non-rest condition includes the presentation of emotional provoking stimuli, particularly evident for images with pleasant content.

Recent theoretical, neural, and clinical advances in sustained attention research.

Models of attention often distinguish among attention subtypes, with classic models separating orienting, switching, and sustaining functions. Compared with other forms of attention, the neurophysiological basis of sustaining attention has received far less notice, yet it is known that momentary failures of sustained attention can have far-ranging negative effects in healthy individuals, and lasting sustained attention deficits are pervasive in clinical populations. In recent years, however, there has been increased interest in characterizing moment-to-moment fluctuations in sustained attention, in addition to the overall vigilance decrement, and understanding how these neurocognitive systems change over the life span and across various clinical populations. The use of novel neuroimaging paradigms and statistical approaches has allowed for better characterization of the neural networks supporting sustained attention and has highlighted dynamic interactions within and across multiple distributed networks that predict behavioral performance. These advances have also provided potential biomarkers to identify individuals with sustained attention deficits. These findings have led to new theoretical models explaining why sustaining focused attention is a challenge for individuals and form the basis for the next generation of sustained attention research, which seeks to accurately diagnose and develop theoretically driven treatments for sustained attention deficits that affect a variety of clinical populations.

Test-retest reliability of functional connectivity networks during naturalistic fMRI paradigms.

Functional connectivity analysis has become a powerful tool for probing the human brain function and its breakdown in neuropsychiatry disorders. So far, most studies adopted resting-state paradigm to examine functional connectivity networks in the brain, thanks to its low demand and high tolerance that are essential for clinical studies. However, the test-retest reliability of resting-state connectivity measures is moderate, potentially due to its low behavioral constraint. On the other hand, naturalistic neuroimaging paradigms, an emerging approach for cognitive neuroscience with high ecological validity, could potentially improve the reliability of functional connectivity measures. To test this hypothesis, we characterized the test-retest reliability of functional connectivity measures during a natural viewing condition, and benchmarked it against resting-state connectivity measures acquired within the same functional magnetic resonance imaging (fMRI) session. We found that the reliability of connectivity and graph theoretical measures of brain networks is significantly improved during natural viewing conditions over resting-state conditions, with an average increase of almost 50% across various connectivity measures. Not only sensory networks for audio-visual processing become more reliable, higher order brain networks, such as default mode and attention networks, but also appear to show higher reliability during natural viewing. Our results support the use of natural viewing paradigms in estimating functional connectivity of brain networks, and have important implications for clinical application of fMRI. Hum Brain Mapp 38:2226-2241, 2017. © 2017 Wiley Periodicals, Inc.

How emotion context modulates unconscious goal activation during motor force exertion

Priming participants with emotional or action-related concepts influences goal formation and motor force output during effort exertion tasks, even without awareness of priming information. However, little is known about neural processes underpinning how emotional cues interact with action (or inaction) goals to motivate (or demotivate) motor behaviour. In a novel functional neuroimaging paradigm, visible emotional images followed by subliminal action or inaction word primes were presented before participants performed a maximal force exertion. In neutral emotional contexts, maximum force was lower following inaction than action primes. However, arousing emotional images had interactive motivational effects on the motor system: Unpleasant images prior to inaction primes increased force output (enhanced effort exertion) relative to control primes, and engaged a motivation-related network involving ventral striatum, extended amygdala, as well as right inferior frontal cortex. Conversely, pleasant images presented before action (versus control) primes decreased force and activated regions of the default-mode network, including inferior parietal lobule and medial prefrontal cortex. These findings show that emotional context can determine how unconscious goal representations influence motivational processes and are transformed into actual motor output, without direct rewarding contingencies. Furthermore, they provide insight into altered motor behaviour in psychopathological disorders with dysfunctional motivational processes.

Cognitive and neural consequences of memory suppression in major depressive disorder

Negative biases in cognition have been documented consistently in major depressive disorder (MDD), including difficulties in the ability to control the processing of negative material. Although negative information-processing biases have been studied using both behavioral and neuroimaging paradigms, relatively little research has been conducted examining the difficulties of depressed persons with inhibiting the retrieval of negative information from long-term memory. In this study, we used the think/no-think paradigm and functional magnetic resonance imaging to assess the cognitive and neural consequences of memory suppression in individuals diagnosed with depression and in healthy controls. The participants showed typical behavioral forgetting effects, but contrary to our hypotheses, there were no differences between the depressed and nondepressed participants or between neutral and negative memories. Relative to controls, depressed individuals exhibited greater activity in right middle frontal gyrus during memory suppression, regardless of the valence of the suppressed stimuli, and differential activity in the amygdala and hippocampus during memory suppression involving negatively valenced stimuli. These findings indicate that depressed individuals are characterized by neural anomalies during the suppression of long-term memories, increasing our understanding of the brain bases of negative cognitive biases in MDD.

Emotional prosody processing in autism spectrum disorder.

Individuals with Autism Spectrum Disorder (ASD) are characterized by severe deficits in social communication, whereby the nature of their impairments in emotional prosody processing have yet to be specified. Here, we investigated emotional prosody processing in individuals with ASD and controls with novel, lifelike behavioral and neuroimaging paradigms. Compared to controls, individuals with ASD showed reduced emotional prosody recognition accuracy on a behavioral task. On the neural level, individuals with ASD displayed reduced activity of the STS, insula and amygdala for complex vs basic emotions compared to controls. Moreover, the coupling between the STS and amygdala for complex vs basic emotions was reduced in the ASD group. Finally, groups differed with respect to the relationship between brain activity and behavioral performance. Brain activity during emotional prosody processing was more strongly related to prosody recognition accuracy in ASD participants. In contrast, the coupling between STS and anterior cingulate cortex (ACC) activity predicted behavioral task performance more strongly in the control group. These results provide evidence for aberrant emotional prosody processing of individuals with ASD. They suggest that the differences in the relationship between the neural and behavioral level of individuals with ASD may account for their observed deficits in social communication.

Validation of the Pittsburgh Infant Brain Injury Score for Abusive Head Trauma.

Abusive head trauma is the leading cause of death from physical abuse. Misdiagnosis of abusive head trauma as well as other types of brain abnormalities in infants is common and contributes to increased morbidity and mortality. We previously derived the Pittsburgh Infant Brain Injury Score (PIBIS), a clinical prediction rule to assist physicians deciding which high-risk infants should undergo computed tomography of the head. Well-appearing infants 30 to 364 days of age with temperature <38.3°C, no history of trauma, and a symptom associated with an increased risk of having a brain abnormality were eligible for enrollment in this prospective, multicenter clinical prediction rule validation. By using a predefined neuroimaging paradigm, subjects were classified as cases or controls. The sensitivity, specificity, and negative and positive predictive values of the rule for prediction of brain injury were calculated. A total of 1040 infants were enrolled: 214 cases and 826 controls. The 5-point PIBIS included abnormality on dermatologic examination (2 points), age ≥3.0 months (1 point), head circumference >85th percentile (1 point), and serum hemoglobin <11.2g/dL (1 point). At a score of 2, the sensitivity and specificity for abnormal neuroimaging was 93.3% (95% confidence interval 89.0%-96.3%) and 53% (95% confidence interval 49.3%-57.1%), respectively. Our data suggest that the PIBIS accurately identifies infants who would benefit from neuroimaging to evaluate for brain injury. An implementation analysis is needed before the PIBIS can be integrated into clinical practice.

EEG ultradian rhythmicity differences in disorders of consciousness during wakefulness.

Temporal fluctuations of cognitively-mediated behaviors in minimally conscious state (MCS) have been linked to changes of awareness, but the time-pattern of these variations remains ill-described. We analyzed 4-h EEG recordings from 12 patients with disorders of consciousness (6 MCS and 6 vegetative state/unresponsive wakefulness syndrome, VS/UWS). Relative powers (delta, theta, alpha, beta1 and beta2 bands) and spectral entropy were estimated (Fz, Cz and Pz derivations). Spectral entropy time-courses were then analyzed. MCS patients had higher theta and alpha and lower delta power when compared to VS/UWS. They showed higher spectral entropy mean value and higher time variability. MCS patients were characterized by spectral entropy fluctuations with periodicities of 70min (range 57-80 min). Notably, these periodicities closely resemble those described in awake healthy subjects, which were hypothesized to be related to fluctuation in vigilance/attention. No significant periodicity was observed for VS/UWS. The spectral entropy periodicity found in MCS patients could reflect the fluctuation of awareness responsible for the inconsistency of MCS manifestation of cognitively-mediated behaviors. The presence of a 70min periodicity in spectral entropy could permit clinicians to better choose their time-window when performing a clinical assessment of consciousness. It could also permit to monitor fluctuations in cognitive performance (i.e., response to command) during complementary testing by passive or active electrophysiological or functional neuroimaging paradigms or in resting state conditions.

Chronic cigarette smoking is linked with structural alterations in brain regions showing acute nicotinic drug-induced functional modulations.

BackgroundWhereas acute nicotine administration alters brain function which may, in turn, contribute to enhanced attention and performance, chronic cigarette smoking is linked with regional brain atrophy and poorer cognition. However, results from structural magnetic resonance imaging (MRI) studies comparing smokers versus nonsmokers have been inconsistent and measures of gray matter possess limited ability to inform functional relations or behavioral implications. The purpose of this study was to address these interpretational challenges through meta-analytic techniques in the service of clarifying the impact of chronic smoking on gray matter integrity and more fully contextualizing such structural alterations.MethodsWe first conducted a coordinate-based meta-analysis of structural MRI studies to identify consistent structural alterations associated with chronic smoking. Subsequently, we conducted two additional meta-analytic assessments to enhance insight into potential functional and behavioral relations. Specifically, we performed a multimodal meta-analytic assessment to test the structural–functional hypothesis that smoking-related structural alterations overlapped those same regions showing acute nicotinic drug-induced functional modulations. Finally, we employed database driven tools to identify pairs of structurally impacted regions that were also functionally related via meta-analytic connectivity modeling, and then delineated behavioral phenomena associated with such functional interactions via behavioral decoding.ResultsAcross studies, smoking was associated with convergent structural decreases in the left insula, right cerebellum, parahippocampus, multiple prefrontal cortex (PFC) regions, and the thalamus. Indicating a structural–functional relation, we observed that smoking-related gray matter decreases overlapped with the acute functional effects of nicotinic agonist administration in the left insula, ventromedial PFC, and mediodorsal thalamus. Suggesting structural-behavioral implications, we observed that the left insula’s task-based, functional interactions with multiple other structurally impacted regions were linked with pain perception, the right cerebellum’s interactions with other regions were associated with overt body movements, interactions between the parahippocampus and thalamus were linked with memory processes, and interactions between medial PFC regions were associated with face processing.ConclusionsCollectively, these findings emphasize brain regions (e.g., ventromedial PFC, insula, thalamus) critically linked with cigarette smoking, suggest neuroimaging paradigms warranting additional consideration among smokers (e.g., pain processing), and highlight regions in need of further elucidation in addiction (e.g., cerebellum).Electronic supplementary materialThe online version of this article (doi:10.1186/s12993-016-0100-5) contains supplementary material, which is available to authorized users.