Cognitive behavioral training reverses the effect of pain exposure on brain-network activity

Repeated sensory exposures shape the brain's function and its responses to environmental stimuli. An important clinical and scientific question is how exposure to pain affects brain network activity and whether that activity is modifiable with training. We sought to determine whether repeated pain exposure would impact brain-network activity and whether these effects can be reversed by cognitive behavioral training (CBT). Healthy subjects underwent 8 experimental sessions on separate days where they received painful thermal stimuli. They were randomly assigned to groups receiving either CBT (Regulate group, n=17) or a non-pain-focused treatment (Control group, n=13). Before and after these sessions, participants underwent functional MRI (fMRI) during painful stimulation and at rest. The effect of repeated pain over time in the Control group was a decrease in the neurotypical pain-evoked default mode network (DMN) deactivation. The Regulate group did not show these DMN effects but rather had decreased deactivation of the right ventrolateral prefrontal cortex (R vlPFC) of the executive control network. In the Regulate group, reduced pain-evoked DMN deactivation was associated with greater individual reduction in pain intensity and unpleasantness over time. Finally, the Regulate group showed enhanced resting functional connectivity between areas of the DMN and executive control network over time, compared to the Control group. Our study demonstrates that trainable cognitive states can alter the effect of repeated sensory exposure on the brain. The findings point to the potential utility of cognitive training to prevent changes in brain network connectivity that occur with repeated pain experience

Spontaneous migraine attack causes alterations in default mode network connectivity

BACKGROUND: Although migraine is one of the most investigated neurologic disorders, we do not have a perfect neuroimaging biomarker for its pathophysiology. One option to improve our knowledge is to study resting-state functional connectivity in and out of headache pain. However, our understanding of the functional connectivity changes during spontaneous migraine attack is partial and incomplete. CASE PRESENTATION: Using resting-state functional magnetic resonance imaging we assessed a 24-year old woman affected by migraine without aura at two different times: during a spontaneous migraine attack and in interictal phase. Seed-to-voxel whole brain analysis was carried out using the posterior cingulate cortex as a seed, representing the default mode network (DMN). Our results showed decreased intrinsic connectivity within core regions of the DMN with an exception of a subsystem including the dorsal medial and superior frontal gyri, and the mid-temporal gyrus which is responsible for pain interpretation and control. In addition, increased connectivity between the DMN and pain and specific migraine-related areas, such as the pons and hypothalamus, developed during the spontaneous migraine attack. CONCLUSION: Our preliminary results provide further support for the hypothesis that alterations of the DMN functional connectivity during migraine headache may lead to maladaptive top-down modulation of migraine pain-related areas which might be a specific biomarker for migraine

Distinct patterns of temporal and directional connectivity among intrinsic networks in the human brain

To determine the spatiotemporal relationships among intrinsic networks of the human brain, we recruited seven neurosurgical patients (four males and three females) who were implanted with intracranial depth electrodes. We first identified canonical resting-state networks at the individual subject level using an iterative matching procedure on each subject's resting-state fMRI data. We then introduced single electrical pulses to fMRI pre-identified nodes of the default network (DN), frontoparietal network (FPN), and salience network (SN) while recording evoked responses in other recording sites within the same networks. We found bidirectional signal flow across the three networks, albeit with distinct patterns of evoked responses within different time windows. We used a data-driven clustering approach to show that stimulation of the FPN and SN evoked a rapid (&lt;70 ms) response that was predominantly higher within the SN sites, whereas stimulation of the DN led to sustained responses in later time windows (85–200 ms). Stimulations in the medial temporal lobe components of the DN evoked relatively late effects (&gt;130 ms) in other nodes of the DN, as well as FPN and SN. Our results provide temporal information about the patterns of signal flow between intrinsic networks that provide insights into the spatiotemporal dynamics that are likely to constrain the architecture of the brain networks supporting human cognition and behavior.SIGNIFICANCE STATEMENTDespite great progress in the functional neuroimaging of the human brain, we still do not know the precise set of rules that define the patterns of temporal organization between large-scale networks of the brain. In this study, we stimulated and then recorded electrical evoked potentials within and between three large-scale networks of the brain, the default network (DN), frontoparietal network (FPN), and salience network (SN), in seven subjects undergoing invasive neurosurgery. Using a data-driven clustering approach, we observed distinct temporal and directional patterns between the three networks, with FPN and SN activity predominant in early windows and DN stimulation affecting the network in later windows. These results provide important temporal information about the interactions between brain networks supporting human cognition and behavior.</jats:p

Integration and segregation across large-scale intrinsic brain networks as a marker of sustained attention and task-unrelated thought

Sustained attention is a fundamental cognitive process that can be decoupled from distinct external events, and instead emerges from ongoing intrinsic large-scale network interdependencies fluctuating over seconds to minutes. Lapses of sustained attention are commonly associated with the subjective experience of mind wandering and task-unrelated thoughts. Little is known about how fluctuations in information processing underpin sustained attention, nor how mind wandering undermines this information processing. To overcome this, we used fMRI to investigate brain activity during subjects’ performance (n=29) of a cognitive task that was optimized to detect and isolate continuous fluctuations in both sustained attention (via motor responses) and task-unrelated thought (via subjective reports). We then investigated sustained attention with respect to global attributes of communication throughout the functional architecture, i.e., by the segregation and integration of information processing across large scale-networks. Further, we determined how task-unrelated thoughts related to these global information processing markers of sustained attention. The results show that optimal states of sustained attention favor both enhanced segregation and reduced integration of information processing in several task-related large-scale cortical systems with concurrent reduced segregation and enhanced integration in the auditory and sensorimotor systems. Higher degree of mind wandering was associated with losses of the favored segregation and integration of specific subsystems in our sustained attention model. Taken together, we demonstrate that intrinsic ongoing neural fluctuations are characterized by two converging communication modes throughout the global functional architecture, which give rise to optimal and suboptimal attention states. We discuss how these results might potentially serve as neural markers for clinically abnormal attention

Functional network antagonism and consciousness

Spontaneous brain activity changes across states of consciousness. A particular consciousness-mediated configuration is the anticorrelations between the default mode network and other brain regions. What this antagonistic organization implies about consciousness to date remains inconclusive. In this Perspective Article, we propose that anticorrelations are the physiological expression of the concept of segregation, namely the brain’s capacity to show selectivity in the way areas will be functionally connected. We postulate that this effect is mediated by the process of neural inhibition, by regulating global and local inhibitory activity. While recognizing that this effect can also result from other mechanisms, neural inhibition helps the understanding of how network metastability is affected after disrupting local and global neural balance. In combination with relevant theories of consciousness, we suggest that anticorrelations are a physiological prior that can work as a marker of preserved consciousness. We predict that if the brain is not in a state to host anticorrelations, then most likely the individual does not entertain subjective experience. We believe that this link between anticorrelations and the underlying physiology will help not only to comprehend how consciousness happens, but also conceptualize effective interventions for treating consciousness disorders in which anticorrelations seem particularly affected

Pharmacological Modulation of Noradrenergic Arousal Circuitry Disrupts Functional Connectivity of the Locus Ceruleus in Humans

State-dependent activity of locus ceruleus (LC) neurons has long suggested a role for noradrenergic modulation of arousal. However, in vivo insights into noradrenergic arousal circuitry have been constrained by the fundamental inaccessibility of the human brain for invasive studies. Functional magnetic resonance imaging (fMRI) studies performed during site-specific pharmacological manipulations of arousal levels may be used to study brain arousal circuitry. Dexmedetomidine is an anesthetic that alters the level of arousal by selectively targeting α2 adrenergic receptors on LC neurons, resulting in reduced firing rate and norepinephrine release. Thus, we hypothesized that dexmedetomidine-induced altered arousal would manifest with reduced functional connectivity between the LC and key brain regions involved in the regulation of arousal. To test this hypothesis, we acquired resting-state fMRI data in right-handed healthy volunteers 18–36 years of age (n = 15, 6 males) at baseline, during dexmedetomidine-induced altered arousal, and recovery states. As previously reported, seed-based resting-state fMRI analyses revealed that the LC was functionally connected to a broad network of regions including the reticular formation, basal ganglia, thalamus, posterior cingulate cortex (PCC), precuneus, and cerebellum. Functional connectivity of the LC to only a subset of these regions (PCC, thalamus, and caudate nucleus) covaried with the level of arousal. Functional connectivity of the PCC to the ventral tegmental area/pontine reticular formation and thalamus, in addition to the LC, also covaried with the level of arousal. We propose a framework in which the LC, PCC, thalamus, and basal ganglia comprise a functional arousal circuitry

Spontaneous cognitive processes and the behavioral validation of time-varying brain connectivity

In cognitive neuroscience, focus is commonly placed on associating brain function with changes in objectively measured external stimuli or with actively generated cognitive processes. In everyday life, however, many forms of cognitive processes are initiated spontaneously, without an individual’s active effort and without explicit manipulation of behavioral state. Recently, there has been increased emphasis, especially in functional neuroimaging research, on spontaneous correlated activity among spatially segregated brain regions (intrinsic functional connectivity) and, more specifically, on intraindividual fluctuations of such correlated activity on various time scales (time-varying functional connectivity). In this Perspective, we propose that certain subtypes of spontaneous cognitive processes are detectable in time-varying functional connectivity measurements. We define these subtypes of spontaneous cognitive processes and review evidence of their representations in time-varying functional connectivity from studies of attentional fluctuations, memory reactivation, and effects of baseline states on subsequent perception. Moreover, we describe how these studies are critical to validating the use of neuroimaging tools (e.g., fMRI) for assessing ongoing brain network dynamics. We conclude that continued investigation of the behavioral relevance of time-varying functional connectivity will be beneficial both in the development of comprehensive neural models of cognition, and in informing on best practices for studying brain network dynamics