Network Of Brain Regions Research Articles

Comment: Coma-causing brainstem lesions.

Arousal, or wakefulness, is an integral component of consciousness and prerequisite for other brain functions, yet its neuroanatomy in humans is poorly understood. Classically, the brainstem “reticular formation” has been considered important for wakefulness.1 Experiments in rodents suggest this brainstem area can be subdivided into functionally discrete regions, and that injury to one region in the pontine tegmentum reliably disrupts arousal and produces coma.2 A homologous brainstem region is likely present in humans, based on analysis of coma-causing lesions.3 However, it remains unclear whether there is a human brainstem site significantly more associated with coma-causing lesions than with non–coma-causing lesions, and exactly where this site is located. Such a brainstem site would likely maintain arousal through ascending projections to other brain regions (originally termed the ascending reticular activating system, or ARAS),1,4 but this network of brain regions in humans is also unclear.

Distinct neural mechanisms underlie the success, precision, and vividness of episodic memory.

A network of brain regions have been linked with episodic memory retrieval, but limited progress has been made in identifying the contributions of distinct parts of the network. Here, we utilized continuous measures of retrieval to dissociate three components of episodic memory: retrieval success, precision, and vividness. In the fMRI scanner, participants encoded objects that varied continuously on three features: color, orientation, and location. Participants' memory was tested by having them recreate the appearance of the object features using a continuous dial, and continuous vividness judgments were recorded. Retrieval success, precision, and vividness were dissociable both behaviorally and neurally: successful versus unsuccessful retrieval was associated with hippocampal activity, retrieval precision scaled with activity in the angular gyrus, and vividness judgments tracked activity in the precuneus. The ability to dissociate these components of episodic memory reveals the benefit afforded by measuring memory on a continuous scale, allowing functional parcellation of the retrieval network.

Brain network connectivity in women exposed to intimate partner violence: a graph theory analysis study.

Evidence suggests that women who suffer from intimate partner violence (IPV) and posttraumatic stress disorder (PTSD) have structural and functional alterations in specific brain regions. Yet, little is known about how brain connectivity may be altered in individuals with IPV, but without PTSD. Women exposed to IPV (n=18) and healthy controls (n=18) underwent structural brain imaging using a Siemens 3T MRI. Global and regional brain network connectivity measures were determined, using graph theory analyses. Structural covariance networks were created using volumetric and cortical thickness data after controlling for intracranial volume, age and alcohol use. Nonparametric permutation tests were used to investigate group differences. Findings revealed altered connectivity on a global and regional level in the IPV group of regions involved in cognitive-emotional control, with principal involvement of the caudal anterior cingulate, the middle temporal gyrus, left amygdala and ventral diencephalon that includes the thalamus. To our knowledge, this is the first evidence showing different brain network connectivity in global and regional networks in women exposed to IPV, and without PTSD. Altered cognitive-emotional control in IPV may underlie adaptive neural mechanisms in environments characterized by potentially dangerous cues.

The effect of age on relational encoding as revealed by hippocampal functional connectivity

The neural processes mediating cognition occur in networks distributed throughout the brain. The encoding and retrieval of relational memories, memories for multiple items or multifeatural events, is supported by a network of brain regions, particularly the hippocampus. The hippocampal coupling hypothesis suggests that the hippocampus is functionally connected with the default mode network (DMN) during retrieval, but during encoding, decouples from the DMN. Based on prior research suggesting that older adults are less able to modulate between brain network states, we tested the hypothesis that older adults’ hippocampus would show functional connectivity with the DMN during relational encoding. The results suggest that, while the hippocampus is functionally connected to some regions of the DMN during relational encoding in both younger and older adults, older adults show additional DMN connectivity. Such age-related changes in network modulation appear not to be mediated by compensatory processes, but rather to reflect a form of neural inefficiency, most likely due to reduced inhibition.

Changing Balance of Spinal Cord Excitability and Nociceptive Brain Activity in Early Human Development

SummaryIn adults, nociceptive reflexes and behavioral responses are modulated by a network of brain regions via descending projections to the spinal dorsal horn [1]. Coordinated responses to noxious inputs manifest from a balance of descending facilitation and inhibition. In contrast, young infants display exaggerated and uncoordinated limb reflexes [2]. Our understanding of nociceptive processing in the infant brain has been advanced by the use of electrophysiological and hemodynamic imaging [3, 4, 5, 6]. From approximately 35 weeks’ gestation, nociceptive-specific patterns of brain activity emerge [7], whereas prior to this, non-specific bursts of activity occur in response to noxious, tactile, visual, and auditory stimulation [7, 8, 9, 10]. During the preterm period, refinement of spinal cord excitability is also observed: reflex duration shortens, response threshold increases, and improved discrimination between tactile and noxious events occurs [2, 11, 12]. However, the development of descending modulation in human infants remains relatively unexplored. In 40 infants aged 28–42 weeks’ gestation, we examined the relationship between nociceptive brain activity and spinal reflex withdrawal activity in response to a clinically essential noxious procedure. Nociceptive-specific brain activity increases in magnitude with gestational age, whereas reflex withdrawal activity decreases in magnitude, duration, and latency across the same developmental period. By recording brain and spinal cord activity in the same infants, we demonstrate that the maturation of nociceptive brain activity is concomitant with the refinement of noxious-evoked limb reflexes. We postulate that, consistent with studies in animals, infant reflexes are influenced by the development of top-down inhibitory modulation from maturing subcortical and cortical brain networks.

Acute stress and episodic memory retrieval: neurobiological mechanisms and behavioral consequences.

Episodic retrieval allows people to access memories from the past to guide current thoughts and decisions. In many real-world situations, retrieval occurs under conditions of acute stress, either elicited by the retrieval task or driven by other, unrelated concerns. Memory under such conditions may be hindered, as acute stress initiates a cascade of neuromodulatory changes that can impair episodic retrieval. Here, we review emerging evidence showing that dissociable stress systems interact over time, influencing neural function. In addition to the adverse effects of stress on hippocampal-dependent retrieval, we consider how stress biases attention and prefrontal cortical function, which could further affect controlled retrieval processes. Finally, we consider recent data indicating that stress at retrieval increases activity in a network of brain regions that enable reflexive, rapid responding to upcoming threats, while transiently taking offline regions supporting flexible, goal-directed thinking. Given the ubiquity of episodic memory retrieval in everyday life, it is critical to understand the theoretical and applied implications of acute stress. The present review highlights the progress that has been made, along with important open questions.

Design and Application of a New Automated Fluidic Visceral Stimulation Device for Human fMRI Studies of Interoception.

Mapping the brain centers that mediate the sensory-perceptual processing of visceral afferent signals arising from the body (i.e., interoception) is useful both for characterizing normal brain activity and for understanding clinical disorders related to abnormal processing of visceral sensation. Here, we report a novel closed-system, electrohydrostatically driven master–slave device that was designed and constructed for delivering controlled fluidic stimulations of visceral organs and inner cavities of the human body within the confines of a 3T magnetic resonance imaging (MRI) scanner. The design concept and performance of the device in the MRI environment are described. In addition, the device was applied during a functional MRI (fMRI) investigation of visceral stimulation related to detrusor distention in two representative subjects to verify its feasibility in humans. System evaluation tests demonstrate that the device is MR-compatible with negligible impact on imaging quality [static signal-to-noise ratio (SNR) loss <2.5% and temporal SNR loss <3.5%], and has an accuracy of 99.68% for flow rate and 99.27% for volume delivery. A precise synchronization of the stimulus delivery with fMRI slice acquisition was achieved by programming the proposed device to detect the 5 V transistor–transistor logic (TTL) trigger signals generated by the MRI scanner. The fMRI data analysis using the general linear model analysis with the standard hemodynamic response function showed increased activations in the network of brain regions that included the insula, anterior and mid-cingulate and lateral prefrontal cortices, and thalamus in response to increased distension pressure on viscera. The translation from manually operated devices to an MR-compatible and MR-synchronized device under automatic control represents a useful innovation for clinical neuroimaging studies of human interoception.

Commentary: Tractography-Activation Models Applied to Subcallosal Cingulate Deep Brain Stimulation.

Commentary: Tractography-Activation Models Applied to Subcallosal Cingulate Deep Brain Stimulation.

Consolidation of Complex Events via Reinstatement in Posterior Cingulate Cortex.

It is well-established that active rehearsal increases the efficacy of memory consolidation. It is also known that complex events are interpreted with reference to prior knowledge. However, comparatively little attention has been given to the neural underpinnings of these effects. In healthy adults humans, we investigated the impact of effortful, active rehearsal on memory for events by showing people several short video clips and then asking them to recall these clips, either aloud (Experiment 1) or silently while in an MRI scanner (Experiment 2). In both experiments, actively rehearsed clips were remembered in far greater detail than unrehearsed clips when tested a week later. In Experiment 1, highly similar descriptions of events were produced across retrieval trials, suggesting a degree of semanticization of the memories had taken place. In Experiment 2, spatial patterns of BOLD signal in medial temporal and posterior midline regions were correlated when encoding and rehearsing the same video. Moreover, the strength of this correlation in the posterior cingulate predicted the amount of information subsequently recalled. This is likely to reflect a strengthening of the representation of the video's content. We argue that these representations combine both new episodic information and stored semantic knowledge (or "schemas"). We therefore suggest that posterior midline structures aid consolidation by reinstating and strengthening the associations between episodic details and more generic schematic information. This leads to the creation of coherent memory representations of lifelike, complex events that are resistant to forgetting, but somewhat inflexible and semantic-like in nature.

Subclinical depression severity is associated with distinct patterns of functional connectivity for subregions of anterior cingulate cortex

Depression is a prevalent psychiatric condition characterized by sad mood and anhedonia. Neuroscientific research has consistently identified abnormalities in a network of brain regions in major depression, including subregions of the anterior cingulate cortex (ACC). However, few studies have investigated whether the same neural correlates of depression symptom severity are apparent in subclinical or healthy subjects. In the current study, we used resting-state fMRI to examine functional connectivity for subregions of the ACC in N = 28 participants with subclinical levels of depression. In regression analyses, we examined relationships between depression severity and functional connectivity for pregenual ACC (pgACC), anterior subgenual ACC (sgACC), and posterior sgACC seed regions. Additionally, we examined relationships between ACC subregion connectivity and trait levels of positive and negative affect. We found distinct associations between depression severity and functional connectivity of ACC subregions. Higher depression severity was associated with reduced pgACC-striatum connectivity and reduced anterior sgACC-anterior insula connectivity. Consistent with resting-state findings in major depression, higher depression severity was also related to greater anterior sgACC-posterior cingulate connectivity and greater posterior sgACC-dorsolateral prefrontal connectivity. Lastly, there were distinct correlations between connectivity for anterior versus posterior ACC subregions and positive and negative affective traits. These findings provide novel support linking subclinical depression to the same neural substrates associated with major depression. More broadly, these results contribute to an emerging literature on dimensional approaches to psychiatric illness.

Amplitude-modulated stimuli reveal auditory-visual interactions in brain activity and brain connectivity.

The temporal congruence between auditory and visual signals coming from the same source can be a powerful means by which the brain integrates information from different senses. To investigate how the brain uses temporal information to integrate auditory and visual information from continuous yet unfamiliar stimuli, we used amplitude-modulated tones and size-modulated shapes with which we could manipulate the temporal congruence between the sensory signals. These signals were independently modulated at a slow or a fast rate. Participants were presented with auditory-only, visual-only, or auditory-visual (AV) trials in the fMRI scanner. On AV trials, the auditory and visual signal could have the same (AV congruent) or different modulation rates (AV incongruent). Using psychophysiological interaction analyses, we found that auditory regions showed increased functional connectivity predominantly with frontal regions for AV incongruent relative to AV congruent stimuli. We further found that superior temporal regions, shown previously to integrate auditory and visual signals, showed increased connectivity with frontal and parietal regions for the same contrast. Our findings provide evidence that both activity in a network of brain regions and their connectivity are important for AV integration, and help to bridge the gap between transient and familiar AV stimuli used in previous studies.

Global motion perception is independent from contrast sensitivity for coherent motion direction discrimination and visual acuity in 4.5-year-old children

Global motion processing depends on a network of brain regions that includes extrastriate area V5 in the dorsal visual stream. For this reason, psychophysical measures of global motion perception have been used to provide a behavioral measure of dorsal stream function. This approach assumes that global motion is relatively independent of visual functions that arise earlier in the visual processing hierarchy such as contrast sensitivity and visual acuity. We tested this assumption by assessing the relationships between global motion perception, contrast sensitivity for coherent motion direction discrimination (henceforth referred to as contrast sensitivity) and habitual visual acuity in a large group of 4.5-year-old children (n=117). The children were born at risk of abnormal neurodevelopment because of prenatal drug exposure or risk factors for neonatal hypoglycemia. Motion coherence thresholds, a measure of global motion perception, were assessed using random dot kinematograms. The contrast of the stimuli was fixed at 100% and coherence was varied. Contrast sensitivity was measured using the same stimuli by fixing motion coherence at 100% and varying dot contrast. Stereoacuity was also measured. Motion coherence thresholds were not correlated with contrast sensitivity or visual acuity. However, lower (better) motion coherence thresholds were correlated with finer stereoacuity (ρ=0.38, p=0.004). Contrast sensitivity and visual acuity were also correlated (ρ=−0.26, p=0.004) with each other. These results indicate that global motion perception for high contrast stimuli is independent of contrast sensitivity and visual acuity and can be used to assess motion integration mechanisms in children.

Investigating virtual reality navigation in amnestic mild cognitive impairment using fMRI

ABSTRACTSpatial navigation requires a well-established network of brain regions, including the hippocampus, caudate nucleus, and retrosplenial cortex. Amnestic Mild Cognitive Impairment (aMCI) is a condition with predominantly memory impairment, conferring a high predictive risk factor for dementia. aMCI is associated with hippocampal atrophy and subtle deficits in spatial navigation. We present the first use of a functional Magnetic Resonance Imaging (fMRI) navigation task in aMCI, using a virtual reality analog of the Radial Arm Maze. Compared with controls, aMCI patients showed reduced activity in the hippocampus bilaterally, retrosplenial cortex, and left dorsolateral prefrontal cortex. Reduced activation in key areas for successful navigation, as well as additional regions, was found alongside relatively normal task performance. Results also revealed increased activity in the right dorsolateral prefrontal cortex in aMCI patients, which may reflect compensation for reduced activations elsewhere. These data support suggestions that fMRI spatial navigation tasks may be useful for staging of progression in MCI.

The effect of observers on behavior and the brain during aggressive encounters

What effect does an audience have on an animal’s behavior and where is this influence registered in the brain? To answer these questions, we analyzed male cichlid fish fighting in the presence of audiences of various compositions and measured expression of immediate early genes in the brain as a proxy for neural activity. We hypothesized their behavior would change depending on who was watching them. We measured behavioral responses from both the “watchers” and the “watched” during aggressive encounters and found that males fighting in the presence of an audience were more aggressive than males fighting without an audience. Depending on the nature of the audience, immediate early gene expression in key brain nuclei was differentially influenced. Both when an audience of larger males watched fighting males, and when they were watching larger males fighting, nuclei in the brain considered homologous with mammalian nuclei known to be associated with anxiety showed increased activity. When males were in the presence of any audience or when males saw any other males fighting, nuclei in the brain known to be involved in reproduction and aggression were differentially activated relative to control animals. In all cases, there was a close relationship between patterns of brain gene expression between fighters and observers. This suggests that the network of brain regions known as the social behavior network, common across vertebrates, are activated not only in association with the expression of social behavior but also by the reception of social information.

Brain Mechanisms for Processing Affective (and Nonaffective) Touch Are Atypical in Autism.

C-tactile (CT) afferents encode caress-like touch that supports social-emotional development, and stimulation of the CT system engages the insula and cortical circuitry involved in social-emotional processing. Very few neuroimaging studies have investigated the neural mechanisms of touch processing in people with autism spectrum disorder (ASD), who often exhibit atypical responses to touch. Using functional magnetic resonance imaging, we evaluated the hypothesis that children and adolescents with ASD would exhibit atypical brain responses to CT-targeted touch. Children and adolescents with ASD, relative to typically developing (TD) participants, exhibited reduced activity in response to CT-targeted (arm) versus non-CT-targeted (palm) touch in a network of brain regions known to be involved in social-emotional information processing including bilateral insula and insular operculum, the right posterior superior temporal sulcus, bilateral temporoparietal junction extending into the inferior parietal lobule, right fusiform gyrus, right amygdala, and bilateral ventrolateral prefrontal cortex including the inferior frontal and precentral gyri, suggesting atypical social brain hypoactivation. Individuals with ASD (vs. TD) showed an enhanced response to non-CT-targeted versus CT-targeted touch in the primary somatosensory cortex, suggesting atypical sensory cortical hyper-reactivity.

Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex

Reward-guided decision-making depends on a network of brain regions. Among these are the orbitofrontal and the anterior cingulate cortex. However, it is difficult to ascertain if these areas constitute anatomical and functional unities, and how these areas correspond between monkeys and humans. To address these questions we looked at connectivity profiles of these areas using resting-state functional MRI in 38 humans and 25 macaque monkeys. We sought brain regions in the macaque that resembled 10 human areas identified with decision making and brain regions in the human that resembled six macaque areas identified with decision making. We also used diffusion-weighted MRI to delineate key human orbital and medial frontal brain regions. We identified 21 different regions, many of which could be linked to particular aspects of reward-guided learning, valuation, and decision making, and in many cases we identified areas in the macaque with similar coupling profiles.

This is your brain on Scrabble: Neural correlates of visual word recognition in competitive Scrabble players as measured during task and resting-state

Competitive Scrabble players devote considerable time to studying words and practicing Scrabble-related skills (e.g., anagramming). This training is associated with extraordinary performance in lexical decision, the standard visual word recognition task (Hargreaves, Pexman, Zdrazilova & Sargious, 2012). In the present study we investigated the neural consequences of this lexical expertise. Using both event-related and resting-state fMRI, we compared brain activity and connectivity in 12 competitive Scrabble experts with 12 matched non-expert controls. Results showed that when engaged in the lexical decision task (LDT), Scrabble experts made use of brain regions not generally associated with meaning retrieval in visual word recognition, but rather those associated with working memory and visual perception. The analysis of resting-state data also showed group differences, such that a different network of brain regions was associated with higher levels of Scrabble-related skill in experts than in controls.

Functional Connectivity Changes and Executive and Social Problems in Neurofibromatosis Type I.

Neurofibromatosis type 1 (NF1) has regularly been associated with cognitive, social, and behavioral problems. The fact that many different cognitive and behavioral impairments have been observed in NF1 suggests that networks of brain regions are involved rather than specific brain regions. Here, we examined whether functional connectivity was different in NF1 and, if so, whether associations were present with cognitive, social, and behavioral outcomes. Fourteen NF1 patients (8 male, age: M=12.49, SD=2.65) and 30 healthy controls (HC; 23 male, age: M=12.30, SD=2.94; p=0.835) were included. Functional connectivity was assessed using functional resting-state scanning. We analyzed brain regions that have been associated with cognitive and social functions: the bilateral ventral anterior cingulate cortex (vACC), the bilateral amygdala, the bilateral orbitofrontal cortex (OFC), and the posterior cingulate cortex (PCC). For NF1 patients, connection strengths between brain regions showing HC-NF1 differences were correlated with parent reports of cognitive, social, and behavioral functioning. Compared to HC, patients showed differences in functional connectivity between the left vACC and the frontal cortex, insula, and subcortical areas (caudate, putamen), between the left amygdala and the frontal cortex, insula, supramarginal gyrus, and PCC/precuneus, and between the left OFC and frontal and subcortical areas (caudate, pallidum). In patients, indications were found for associations between increased frontofrontal and temporofrontal functional connectivity with cognitive, social, and behavioral deficits (r-range=0.536-0.851). NF1 patients showed differences in functional connectivity between areas associated with cognitive and social functioning when compared to controls. This, plus the fact that connectivity strengths in these networks were associated with worse cognitive, social, and behavioral outcomes, suggests a neuropathological basis for the widespread deficits observed in NF1.

Effects of transcranial direct current stimulation on naming and cortical excitability in stroke patients with aphasia

This study aimed to investigate the effects of anodal transcranial direct current stimulation (A-tDCS) over the left posterior perisylvian region (PPR) on picture naming and cortical excitability measured with electroencephalography (EEG) nonlinear dynamics analysis (NDA) in aphasic patients. Twelve aphasic patients received 20 sessions of speech-language therapy during each of three phases: sham tDCS (Phase A1); A-tDCS to the left PPR (Phase B); and sham tDCS (Phase A2). Picture naming and auditory word-picture identification were measured before and after each phase. The EEG nonlinear index of approximate entropy (ApEn) was calculated for all subjects and 12 normal controls. Picture naming and auditory word-picture identification was significantly improved after phase B. The EEG ApEn analysis indicated that improved picture naming correlated with a higher activation level in wide areas of the left hemisphere and in isolated areas of the right hemisphere after phase B. These results revealed that A-tDCS over the left PPR coupled with speech-language therapy can improve picture naming and auditory comprehension in aphasic patients. tDCS not only modulates activity in the brain region directly underlying the stimulating electrode but also in a network of brain regions that are function-related.

Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding.

Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy.Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network.Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls.Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications.