Changes In Regional Activity Research Articles

Normalization of Fronto-Parietal Activation by Cognitive-Behavioral Therapy in Unmedicated Pediatric Patients With Anxiety Disorders.

Anxiety disorders are prevalent among youths and are often highly impairing. Cognitive-behavioral therapy (CBT) is an effective first-line treatment. The authors investigated the brain mechanisms associated with symptom change following CBT. Unmedicated youths diagnosed with an anxiety disorder underwent 12 weeks of CBT as part of two randomized clinical trials testing the efficacy of adjunctive computerized cognitive training. Across both trials, participants completed a threat-processing task during functional MRI before and after treatment. Age-matched healthy comparison youths completed two scans over the same time span. The mean age of the samples was 13.20 years (SD=2.68); 41% were male (youths with anxiety disorders, N=69; healthy comparison youths, N=62). An additional sample including youths at temperamental risk for anxiety (N=87; mean age, 10.51 years [SD=0.43]; 41% male) was utilized to test the stability of anxiety-related neural differences in the absence of treatment. Whole-brain regional activation changes (thresholded at p<0.001) were examined using task-based blood-oxygen-level-dependent response. Before treatment, patients with an anxiety disorder exhibited altered activation in fronto-parietal attention networks and limbic regions relative to healthy comparison children across all task conditions. Fronto-parietal hyperactivation normalized over the course of treatment, whereas limbic responses remained elevated after treatment. In the at-risk sample, overlapping clusters emerged between regions showing stable associations with anxiety over time and regions showing treatment-related changes. Activation in fronto-parietal networks may normalize after CBT in unmedicated pediatric anxiety patients. Limbic regions may be less amenable to acute CBT effects. Findings from the at-risk sample suggest that treatment-related changes may not be attributed solely to the passage of time.

Regional activity and effective connectivity within the frontoparietal network during precision walking with visual cueing: an fNIRS study.

Precision walking (PW) incorporates precise step adjustments into regular walking patterns to navigate challenging surroundings. However, the brain processes involved in PW control, which encompass cortical regions and interregional interactions, are not fully understood. This study aimed to investigate the changes in regional activity and effective connectivity within the frontoparietal network associated with PW. Functional near-infrared spectroscopy data were recorded from adult subjects during treadmill walking tasks, including normal walking (NOR) and PW with visual cues, wherein the intercue distance was either fixed (FIX) or randomly varied (VAR) across steps. The superior parietal lobule (SPL), dorsal premotor area (PMd), supplementary motor area (SMA), and dorsolateral prefrontal cortex (dlPFC) were specifically targeted. The results revealed higher activities in SMA and left PMd, as well as left-to-right SPL connectivity, in VAR than in FIX. Activities in SMA and right dlPFC, along with dlPFC-to-SPL connectivity, were higher in VAR than in NOR. Overall, these findings provide insights into the roles of different brain regions and connectivity patterns within the frontoparietal network in facilitating gait control during PW, providing a useful baseline for further investigations into brain networks involved in locomotion.

Remote spatial memory processing in the juvenile brain and contribution of the hippocampus

A majority of research into memory formation and consolidation is commonly focused on adult brains and organisms. Our work focuses on the mechanisms of memory within the developing, juvenile brain in an attempt to provide a more full understanding of the underlying neural mechanisms of memory formation, consolidation and storage. During juvenile development, the brain undergoes important remodeling and synaptic pruning towards shaping the adult brain. Thus, during this time, memories may be lost through the remodeling of hippocampal-neocortical connections. The significance of comparing juvenile and adult memory processes is critical in understanding the structural changes that occur within memory-specific circuits associated with long-term memory formation. To provide a comparison of the neurobehavioral aspects of long-term memory formation in juveniles and adults, we trained Long Evan’s rats on a spatial task on postnatal days 16, 18, 20, 25, 30 or 50 (adults). Each age group was then tested for memory recall 24 hours or 3 weeks later. We noted that memory recall showed a dramatic change at postnatal day 20 such that memory recall at postnatal day 25 was similar to adult levels. We then used immunohistochemistry to quantify and analyze neural activity patterns in brain regions thought to underlie the short- and long-term storage of spatial memories. Identification of these regional activity changes during juvenile periods and comparison with adults allows us to explore the function and organization of interacting brain regions in long-term spatial memory storage during development.

Defensive behaviors and brain regional activation changes in rats confronting a snake

In the present study, we examined behavioral and brain regional activation changes of rats). To a nonmammalian predator, a wild rattler snake (Crotalus durissus terrificus). Accordingly, during snake threat, rat subjects showed a striking and highly significant behavioral response of freezing, stretch attend, and, especially, spatial avoidance of this threat. The brain regional activation patterns for these rats were in broad outline similar to those of rats encountering other predator threats, showing Fos activation of sites in the amygdala, hypothalamus, and periaqueductal gray matter. In the amygdala, only the lateral nucleus showed significant activation, although the medial nucleus, highly responsive to olfaction, also showed higher activation. Importantly, the hypothalamus, in particular, was somewhat different, with significant Fos increases in the anterior and central parts of the ventromedial hypothalamic nucleus (VMH), in contrast to patterns of enhanced Fos expression in the dorsomedial VMH to cat predators, and in the ventrolateral VMH to an attacking conspecific. In addition, the juxtodorsalmedial region of the lateral hypothalamus showed enhanced Fos activation, where inputs from the septo-hippocampal system may suggest the potential involvement of hippocampal boundary cells in the very strong spatial avoidance of the snake and the area it occupied. Notably, these two hypothalamic paths appear to merge into the dorsomedial part of the dorsal premammillary nucleus and dorsomedial and lateral parts of the periaqueductal gray, all of which present significant increases in Fos expression and are likely to be critical for the expression of defensive behaviors in responses to the snake threat.

Capturing the spatiotemporal dynamics of self-generated, task-initiated thoughts with EEG and fMRI

The temporal structure of self-generated cognition is a key attribute to the formation of a meaningful stream of consciousness. When at rest, our mind wanders from thought to thought in distinct mental states. Despite the marked importance of ongoing mental processes, it is challenging to capture and relate these states to specific cognitive contents. In this work, we employed ultra-high field functional magnetic resonance imaging (fMRI) and high-density electroencephalography (EEG) to study the ongoing thoughts of participants instructed to retrieve self-relevant past episodes for periods of 22sec. These task-initiated, participant-driven activity patterns were compared to a distinct condition where participants performed serial mental arithmetic operations, thereby shifting from self-related to self-unrelated thoughts. BOLD activity mapping revealed selective enhanced activity in temporal, parietal and occipital areas during the memory compared to the mental arithmetic condition, evincing their role in integrating the re-experienced past events into conscious representations during memory retrieval. Functional connectivity analysis showed that these regions were organized in two major subparts, previously associated to “scene-reconstruction” and “self-experience” subsystems. EEG microstate analysis allowed studying these participant-driven thoughts in the millisecond range by determining the temporal dynamics of brief periods of stable scalp potential fields. This analysis revealed selective modulation of occurrence and duration of specific microstates in the memory and in the mental arithmetic condition, respectively. EEG source analysis revealed similar spatial distributions of the sources of these microstates and the regions identified with fMRI. These findings imply a functional link between BOLD activity changes in regions related to a certain mental activity and the temporal dynamics of mentation, and support growing evidence that specific fMRI networks can be captured with EEG as repeatedly occurring brief periods of integrated coherent neuronal activity, lasting only fractions of seconds.

Activity and Connectivity Differences Underlying Inhibitory Control Across the Adult Life Span.

Inhibitory control requires precise regulation of activity and connectivity within multiple brain networks. Previous studies have typically evaluated age-related changes in regional activity or changes in interregional interactions. Instead, we test the hypothesis that activity and connectivity make distinct, complementary contributions to performance across the life span and the maintenance of successful inhibitory control systems. A representative sample of healthy human adults in a large, population-based life span cohort performed an integrated Stop-Signal (SS)/No-Go task during functional magnetic resonance imaging (n = 119; age range, 18–88 years). Individual differences in inhibitory control were measured in terms of the SS reaction time (SSRT), using the blocked integration method. Linear models and independent components analysis revealed that individual differences in SSRT correlated with both activity and connectivity in a distributed inhibition network, comprising prefrontal, premotor, and motor regions. Importantly, this pattern was moderated by age, such that the association between inhibitory control and connectivity, but not activity, differed with age. Multivariate statistics and out-of-sample validation tests of multifactorial functional organization identified differential roles of activity and connectivity in determining an individual's SSRT across the life span. We propose that age-related differences in adaptive cognitive control are best characterized by the joint consideration of multifocal activity and connectivity within distributed brain networks. These insights may facilitate the development of new strategies to support cognitive ability in old age.SIGNIFICANCE STATEMENT The preservation of cognitive and motor control is crucial for maintaining well being across the life span. We show that such control is determined by both activity and connectivity within distributed brain networks. In a large, population-based cohort, we used a novel whole-brain multivariate approach to estimate the functional components of inhibitory control, in terms of their activity and connectivity. Both activity and connectivity in the inhibition network changed with age. But only the association between performance and connectivity, not activity, differed with age. The results suggest that adaptive control is best characterized by the joint consideration of multifocal activity and connectivity. These insights may facilitate the development of new strategies to maintain cognitive ability across the life span in health and disease.

State-Independent and Dependent Neural Responses to Psychosocial Stress in Current and Remitted Depression.

Stress is a strong risk factor for major depressive disorder, while sensitization to stress in remitted individuals plays a key role in depression recurrence. The present study explored the state-independent (trait) and dependent (state) neural responses to psychosocial stress in major depressive disorder. Thirty-six patients with medication-naive first-episode current depression, 33 patients with remitted depression, and 36 demographically matched healthy control participants were administered the Montreal Imaging Stress Task during functional MRI. One-way analyses of variance were used to assess differences in stress responses in the three groups. Both currently depressed and remitted patients exhibited higher stress levels and cortisol responses than control subjects. Compared with control subjects, both depressed and remitted patients exhibited reduced activation in the ventromedial prefrontal cortex and increased activation in the precuneus. The stress-induced ventromedial prefrontal cortex activation changes negatively correlated with cortisol increases in all three groups. Additional increased activations were found in the dorsolateral prefrontal cortex and bilateral striatum in remitted patients compared with control subjects, and activation in these regions correlated inversely with depressive symptoms in the remitted group. These findings provide novel evidence regarding the trait and state markers of depression on neural responses to psychosocial stress. Regional activation changes in the ventromedial prefrontal cortex and precuneus may reflect the trait markers of depression. Hyperactivation in the dorsolateral prefrontal cortex and striatum may represent a state-dependent compensatory mechanism during depression remission.

Adaptive Adolescent Flexibility: Neurodevelopment of Decision-making and Learning in a Risky Context.

Research on adolescence has largely focused on the particular biological and neural changes that place teens at risk for negative outcomes linked to increases in sensation-seeking and risky behavior. However, there is a growing interest in the adaptive function of adolescence, with work highlighting the dual nature of adolescence as a period of potential risk and opportunity. We examined how behavioral and neural sensitivity to risk and reward varies as a function of age using the Balloon Analog Risk Task. Seventy-seven children and adolescents (ages 8-17 years) completed the Balloon Analog Risk Task during an fMRI session. Results indicate that adolescents show greater learning throughout the task. Furthermore, older participants showed increased neural responses to reward in the OFC and ventral striatum, increased activation to risk in the mid-cingulate cortex, as well as increased functional OFC-medial PFC coupling in both risk and reward contexts. Age-related changes in regional activity and interregional connectivity explain the link between age and increases in flexible learning. These results support the idea that adolescents' sensitivity to risk and reward supports adaptive learning and behavioral approaches for reward acquisition.

Tonic Local Brain Blood Flow Control by Astrocytes Independent of Phasic Neurovascular Coupling.

According to the current model of neurovascular coupling, blood flow is controlled regionally through phasic changes in the activity of neurons and astrocytes that signal to alter arteriole diameter. Absent in this model, however, is how brain blood flow is tonically regulated independent of regional changes in activity. This is important because a large fraction of brain blood flow is required to maintain basal metabolic needs. Using two-photon fluorescence imaging combined with patch-clamp in acute rat brain slices of sensory-motor cortex, we demonstrate that reducing resting Ca(2+) in astrocytes with intracellular BAPTA causes vasoconstriction in adjacent arterioles. BAPTA-induced vasoconstriction was eliminated by a general COX blocker and the effect is mimicked by a COX-1, but not COX-2, antagonist, suggesting that astrocytes provide tonic, steady-state vasodilation by releasing prostaglandin messengers. Tonic vasodilation was insensitive to TTX, as well as a variety of synaptic and extrasynaptic receptor antagonists, indicating that the phenomenon operates largely independent of neural activity. Using in vivo two-photon fluorescence imaging of the barrel cortex in fully awake mice, we reveal that acute COX-1 inhibition reduces resting arteriole diameter but fails to affect vasodilation in response to vibrissae stimulation. Our findings demonstrate that astrocytes provide tonic regulation of arterioles using resting intracellular Ca(2+) in a manner that is independent of phasic, neuronal-evoked vasodilation. Significance statement: The brain requires both phasic and tonic regulation of its blood supply to service energy needs over various temporal windows. While many mechanisms have been described for phasic blood flow regulation, how the brain accomplishes tonic control is largely unknown. Here we describe a way in which astrocytes contribute to the management of basal brain blood flow by providing steady-state vasodilation to arterioles via resting astrocyte Ca(2+) and the continuous release of prostaglandin messengers. This phenomenon may be important for understanding the declines in basal brain blood flow that occur in aging and dementia, as well as for the interpretation of fMRI data.

Neuroimaging of Fear-Associated Learning.

Fear conditioning has been commonly used as a model of emotional learning in animals and, with the introduction of functional neuroimaging techniques, has proven useful in establishing the neurocircuitry of emotional learning in humans. Studies of fear acquisition suggest that regions such as amygdala, insula, anterior cingulate cortex, and hippocampus play an important role in acquisition of fear, whereas studies of fear extinction suggest that the amygdala is also crucial for safety learning. Extinction retention testing points to the ventromedial prefrontal cortex as an essential region in the recall of the safety trace, and explicit learning of fear and safety associations recruits additional cortical and subcortical regions. Importantly, many of these findings have implications in our understanding of the pathophysiology of psychiatric disease. Recent studies using clinical populations have lent insight into the changes in regional activity in specific disorders, and treatment studies have shown how pharmaceutical and other therapeutic interventions modulate brain activation during emotional learning. Finally, research investigating individual differences in neurotransmitter receptor genotypes has highlighted the contribution of these systems in fear-associated learning.

Association between longitudinal changes in prefrontal hemodynamic responses and social adaptation in patients with bipolar disorder and major depressive disorder

BackgroundPatients with affective disorders exhibit changes in regional brain function and show abnormal social adaptation. However, to our knowledge, no near-infrared spectroscopy (NIRS) study has examined the relationship between these two phenomena longitudinally. This study examined the region-specific functional abnormality associated with bipolar disorder (BD) and major depressive disorder (MDD), and the association between particular longitudinal changes in regional activation and social adaptation. MethodsWe evaluated frontotemporal functioning during a verbal fluency test (VFT) for patients with BD (N=18), those with MDD (N=10), and healthy controls (HCs; N=14) using NIRS. NIRS measurements and the Social Adaptation Self-evaluation Scale (SASS) were administered twice with an interval of approximately 6 months. ResultsThe BD and MDD groups showed lesser activation than the HCs in the bilateral ventro-lateral prefrontal cortex and the anterior part of the temporal cortex (VLPFC/aTC). Longitudinal changes in SASS scores were positively associated with the extent of change in left VLPFC/aTC activation in the BD group and with right VLPFC/aTC activation in the MDD group. LimitationsOur small sample size limited statistical power, and the effect of medication and multiple comparisons cannot be excluded, although these effects were considered in the interpretation of the present results. ConclusionLongitudinal increases of VLPFC/aTC activation were associated with improvement in social adaptation in patients with BD and those with MDD. NIRS measurement could be a useful tool for objective evaluation of changes in social adaptation in BD and MDD.

Independent Modulation of Engagement and Connectivity of the Facial Network During Affect Processing byCACNA1CandANK3Risk Genes for Bipolar Disorder

Genome-wide association studies (GWASs) indicate that single-nucleotide polymorphisms in the CACNA1C and ANK3 genes increase the risk for bipolar disorder (BD). The genes influence neuronal firing by modulating calcium and sodium channel functions, respectively. Both genes modulate γ-aminobutyric acid-transmitting interneuron function and can thus affect brain regional activation and interregional connectivity. To determine whether the genetic risk for BD associated with 2 GWAS-supported risk single-nucleotide polymorphisms at CACNA1C rs1006737 and ANK3 rs10994336 is mediated through changes in regional activation and interregional connectivity of the facial affect-processing network. Cross-sectional functional magnetic resonance imaging study at a research institute of 41 euthymic patients with BD and 46 healthy participants, all of British white descent. Blood oxygen level-dependent signal and effective connectivity measures during the facial affect-processing task. In healthy carriers, both genetic risk variants were independently associated with increased regional engagement throughout the facial affect-processing network and increased effective connectivity between the visual and ventral prefrontal cortical regions. In contrast, BD carriers of either genetic risk variant exhibited pronounced reduction in ventral prefrontal cortical activation and visual-prefrontal effective connectivity. Our data demonstrate that the effect of CACNA1C rs1006737 and ANK3 rs10994336 (or genetic variants in linkage disequilibrium) on the brain converges on the neural circuitry involved in affect processing and provides a mechanism linking BD to genome-wide genetic risk variants.

Neural Correlates of Impulsive Buying Tendencies during Perception of Product Packaging

Research has shown that people differ in their susceptibility to impulsive buying. The appeal of product packaging has the potential to trigger impulsive buying even for consumers with no intention to make a purchase. The aim of the present study was to investigate whether individual differences in consumers' impulsive buying tendencies affect unconscious neural responses during the perception of product packaging. Functional magnetic resonance imaging (fMRI) was applied to measure neural responses to the perception of product packages in participants with different impulsive buying tendencies. The results of the study support and expand prior research in impulsive and reflective information processing and behavior. First, attractive versus neutral packages evoked more intensive activity changes in brain regions associated with an impulsive system. Second, attractive and unattractive versus neutral packages led to less intensive activity changes in regions associated with a reflective system. Third, attractive packages activated regions associated with reward, whereas unattractive packages activated regions associated with negative emotions. The results suggest that there is indeed a corresponding relationship between stronger impulsive buying tendencies and activity in brain areas associated with impulsive and reflective processes.

Adult age-dependent differences in resting-state connectivity within and between visual-attention and sensorimotor networks

Healthy aging is accompanied by structural and functional changes in the brain, among which a loss of neural specificity (i.e., dedifferentiation) is one of the most consistent findings. Little is known, however, about changes in interregional integration underlying a dedifferentiation across different functional systems. In a large sample (n = 399) of healthy adults aged from 18 to 85 years, we analyzed age-dependent differences in resting-state (RS) (task-independent) functional connectivity (FC) of a set of brain regions derived from a previous fMRI study. In that study, these regions had shown an age-related loss of activation specificity in visual-attention (superior parietal area 7A and dorsal premotor cortex) or sensorimotor (area OP4 of the parietal operculum) tasks. In addition to these dedifferentiated regions, the FC analysis of the present study included “task-general” regions associated with both attention and sensorimotor systems (rostral supplementary motor area and bilateral anterior insula) as defined via meta-analytical co-activation mapping. Within this network, we observed both selective increases and decreases in RS-FC with age. In line with regional activation changes reported previously, we found diminished anti-correlated FC for inter-system connections (i.e., between sensorimotor-related and visual attention-related regions). Our analysis also revealed reduced FC between system-specific and task-general regions, which might reflect age-related deficits in top-down control possibly leading to dedifferentiation of task-specific brain activity. Together, our results underpin the notion that RS-FC changes concur with regional activity changes in the healthy aging brain, presumably contributing jointly to age-related behavioral changes.

Changes in Regional Activity of the Psoas Major and Quadratus Lumborum With Voluntary Trunk and Hip Tasks and Different Spinal Curvatures in Sitting

Cross-sectional controlled laboratory study. To investigate the function of discrete regions of psoas major (PM) and quadratus lumborum (QL) with changes in spinal curvature and hip position. Anatomically discrete regions of PM and QL may have differential function on the lumbar spine, based on anatomical and biomechanical differences in their moment arms between fascicles within each muscle. Fine-wire electrodes were inserted with ultrasound guidance into PM fascicles arising from the transverse process (PM-t) and vertebral body (PM-v) and anterior (QL-a) and posterior (QL-p) layers of QL. Recordings were made on 9 healthy participants, who performed 7 tasks with maximal voluntary efforts and adopted 3 sitting postures that involved different spinal curvatures and hip angles. Activity of PM-t was greater during trunk extension than flexion, whereas activity of PM-v was greater during hip flexion than trunk efforts. Activity of QL-p was greater during trunk extension and lateral flexion, whereas QL-a showed greater activity during lateral flexion. During sitting tasks, PM-t was more active when sitting with a short lordosis than a flat (less extended) lumbar spine posture, whereas PM-v was similarly active in both sitting postures. Activity of PM-t was more affected by changes in position of the lumbar spine than the hip, whereas PM-v was more actively involved in the movement of the hip rather than that of the lumbar spine. Moreover, from its anatomy, PM-t has a combined potential to extend/lordose the lumbar spine and flex the hip, at least in a flexed-hip position.

Source Space Analysis of Event-Related Dynamic Reorganization of Brain Networks

How the brain works is nowadays synonymous with how different parts of the brain work together and the derivation of mathematical descriptions for the functional connectivity patterns that can be objectively derived from data of different neuroimaging techniques. In most cases static networks are studied, often relying on resting state recordings. Here, we present a quantitative study of dynamic reconfiguration of connectivity for event-related experiments. Our motivation is the development of a methodology that can be used for personalized monitoring of brain activity. In line with this motivation, we use data with visual stimuli from a typical subject that participated in different experiments that were previously analyzed with traditional methods. The earlier studies identified well-defined changes in specific brain areas at specific latencies related to attention, properties of stimuli, and tasks demands. Using a recently introduced methodology, we track the event-related changes in network organization, at source space level, thus providing a more global and complete view of the stages of processing associated with the regional changes in activity. The results suggest the time evolving modularity as an additional brain code that is accessible with noninvasive means and hence available for personalized monitoring and clinical applications.

Graph Theoretical Approaches in Brain Networks

In the last decade network theory has proved an effective tool for modeling and describing the complex topology emerging either from anatomical or functional brain connectivity patterns. From a graph theoretical perspective, the brain can be conceived as a networked system composed of nodes coincident with different brain sites and links which in the current view can either represent anatomical tracts between brain regions or measures of statistical dependencies between their electrical activity. One of the most intriguing, and now well known, examples of the application of network theory to neuroimaging data unveiled that the way brain regions are connected is typically neither regular nor random. Instead brain networks, like other real networked systems, tend to exhibit a complex structure theoretically consistent with the capability of processing information within regional clusters and avoiding excessive connections between clusters. While the simplest instantiation of this configuration showed similar characteristics to mathematically defined “small-world” networks, it has become clear that additional topological structures including hierarchical modularity can nuance our expectations of the brain's underlying architecture and dynamics. An important goal in these research endeavors is to identify how brain network organization can inform our understanding of the brain's intuitive need to balance the two competing principles of integration and segregation and how alterations in brain structure and dynamics can lead to alterations in human behavior and cognitive function. The present special issue collects a series of selected contributions related to the methodological and practical applications of network theory to anatomical and functional brain connectivity patterns. The contribution entitled “Voxel scale complex networks of functional connectivity in the rat brain: neurochemical state dependence of global and local topological properties” addresses the dependence of the functional connectivity estimated from the fMRI signals of the rat brain in response to alterations of the neurotransmitter system as induced by the administration of specific pharmaceutical drugs such as d-amphetamine, fluoxetine, and nicotine. The contribution entitled “A signal-processing-based approach to time-varying graph analysis for dynamic brain network identification” proposes a dynamic network summarization approach to describe the time-varying evolution of connectivity patterns in functional brain activity. The proposed method is evaluated on event-related potential (ERP) data, which demonstrates the dynamic nature of functional connectivity. The contribution entitled “how the statistical validation of functional connectivity patterns can prevent erroneous definition of small-world properties of a brain connectivity network” addresses important methodological choices that are often made in the construction of functional brain network from EEG data, including the choice of statistical thresholds to determine the presence or absence of network links and the role of spatial correlations in determining graph properties. The contribution entitled “weighted phase lag index and graph analysis: preliminary investigation of functional connectivity during resting state in children” presents original results concerning the application of small-world parameters and betweenness centrality measures to characterize the topological structure of the functional network in the children's brain from noninvasive MEG recordings. The contribution entitled “source space analysis of event-related dynamic reorganization of brain networks” conducts a quantitative study of the dynamic reconfiguration of connectivity for event-related experiments at source space level, which provides a global and complete view of the stages of processing associated with the regional changes in activity. The contribution entitled “Redundancy as a Graph-Based Index of Frequency Specific MEG Functional Connectivity” focuses on quantifying the differential role that paths of different lengths potentially play in brain connectivity and demonstrates that a redundancy-based measure captures unique information not accessible via approaches that only examine the shortest paths through a network. The contribution entitled “A computationally efficient, exploratory approach to brain connectivity incorporating false discovery rate control, a priori knowledge, and group inference” proposes a multisubject, exploratory brain connectivity modeling approach. The proposed method allows for the incorporation of prior knowledge of connectivity and the determination of the dominant brain connectivity pattern among a group of subjects. Fabrizio De Vico Fallani Danielle Bassett Tianzi Jiang

Glucose administration enhances fMRI brain activation and connectivity related to episodic memory encoding for neutral and emotional stimuli

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with episodic memory encoding and whether these effects would differ depending on the emotional valence of the material. We used a double-blind, within-participants, crossover design in which either glucose (50g) or a saccharin placebo were administered before scanning, on days approximately 1 week apart. We scanned healthy young male participants with fMRI as they viewed emotionally arousing negative pictures and emotionally neutral pictures, intermixed with baseline fixation. Free recall was tested at 5min after scanning and again after 1 day. Glucose administration increased activation in brain regions associated with successful episodic memory encoding. Glucose also enhanced activation in regions whose activity was correlated with subsequent successful recall, including the hippocampus, prefrontal cortex, and other regions, and these effects differed for negative vs. neutral stimuli. Finally, glucose substantially increased functional connectivity between the hippocampus and amygdala and a network of regions previously implicated in successful episodic memory encoding. These findings fit with evidence from nonhuman animals indicating glucose modulates memory by selectively enhancing neural activity in brain regions engaged during memory tasks. Our results highlight the modulatory effects of glucose and the importance of examining both regional changes in activity and functional connectivity to fully characterize the effects of glucose on brain function and memory.

Changes in regional activity are accompanied with changes in inter-regional connectivity during 4 weeks motor learning

Structural equation modeling (SEM) and fMRI were used to test whether changes in the regional activity are accompanied by changes in the inter-regional connectivity as motor practice progresses. Ten healthy subjects were trained to perform finger movement task daily for 4 weeks. Three sessions of fMRI images were acquired within 4 weeks. The changes in inter-regional connectivity were evaluated by measuring the effective connectivity between the primary motor area (M1), supplementary motor area (SMA), dorsal premotor cortex (PMd), basal ganglia (BG), cerebellum (CB), and posterior ventrolateral prefrontal cortex (pVLPFC). The regional activities in M1 and SMA increased from pre-training to week 2 and decreased from week 2 to week 4. The inter-regional connectivity generally increased in strength (with SEM path coefficients becoming more positive or negative) as practice progressed. The increases in the strength of the inter-regional connectivity may reflect long-term reorganization of the skilled motor network. We suggest that the performance gain was achieved by dynamically tuning the inter-regional connectivity in the motor network.

Regional brain activation changes and abnormal functional connectivity of the ventrolateral prefrontal cortex during working memory processing in adults with attention‐deficit/hyperactivity disorder

Previous studies on working memory (WM) function in adults with attention-deficit/hyperactivity disorder (ADHD) suggested aberrant activation of the prefrontal cortex and the cerebellum. Although it has been hypothesized that activation differences in these regions most likely reflect aberrant frontocerebellar circuits, the functional coupling of these brain networks during cognitive performance has not been investigated so far. In this study, functional magnetic resonance imaging (fMRI) and both univariate and multivariate analytic techniques were used to investigate regional activation changes and functional connectivity differences during cognitive processing in healthy controls (n = 12) and ADHD adults (n = 12). Behavioral performance during a parametric verbal WM paradigm did not significantly differ between adults with ADHD and healthy controls. During the delay period of the activation task, however, ADHD patients showed significantly less activation in the left ventrolateral prefrontal cortex (VLPFC), as well as in cerebellar and occipital regions compared with healthy control subjects. In both groups, independent component analyses revealed a functional network comprising bilateral lateral prefrontal, striatal, and cingulate regions. ADHD adults had significantly lower connectivity in the bilateral VLPFC, the anterior cingulate cortex, the superior parietal lobule, and the cerebellum compared with healthy controls. Increased connectivity in ADHD adults was found in right prefrontal regions, the left dorsal cingulate cortex and the left cuneus. These findings suggest both regional brain activation deficits and functional connectivity changes of the VLPFC and the cerebellum as well as functional connectivity abnormalities of the anterior cingulate and the parietal cortex in ADHD adults during WM processing.