Dante R. Chialvo

Scale-free brain functional networks

Functional magnetic resonance imaging is used to extract functional networks connecting correlated human brain sites. Analysis of the resulting networks in different tasks shows that (a) the distribution of functional connections, and the probability of finding a link versus distance are both scale-free, (b) the characteristic path length is small and comparable with those of equivalent random networks, and (c) the clustering coefficient is orders of magnitude larger than those of equivalent random networks. All these properties, typical of scale-free small-world networks, reflect important functional information about brain states.

Beyond Feeling: Chronic Pain Hurts the Brain, Disrupting the Default-Mode Network Dynamics

Chronic pain patients suffer from more than just pain; depression and anxiety, sleep disturbances, and decision-making abnormalities (Apkarian et al., 2004a) also significantly diminish their quality of life. Recent studies have demonstrated that chronic pain harms cortical areas unrelated to pain (Apkarian et al., 2004b; Acerra and Moseley, 2005), but whether these structural impairments and behavioral deficits are connected by a single mechanism is as of yet unknown. Here we propose that long-term pain alters the functional connectivity of cortical regions known to be active at rest, i.e., the components of the “default mode network” (DMN). This DMN (Raichle et al., 2001; Greicius et al., 2003; Vincent et al., 2007) is marked by balanced positive and negative correlations between activity in component brain regions. In several disorders, however this balance is disrupted (Fox and Raichle, 2007). Using well validated functional magnetic resonance imaging (fMRI) paradigms to study the DMN (Fox et al., 2005), we investigated whether the impairments of chronic pain patients could be rooted in disturbed DMN dynamics. Studying with fMRI a group of chronic back pain (CBP) patients and healthy controls while executing a simple visual attention task, we discovered that CBP patients, despite performing the task equally well as controls, displayed reduced deactivation in several key DMN regions. These findings demonstrate that chronic pain has a widespread impact on overall brain function, and suggest that disruptions of the DMN may underlie the cognitive and behavioral impairments accompanying chronic pain.

Chronic pain and the emotional brain : Specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain

Living with unrelenting pain (chronic pain) is maladaptive and is thought to be associated with physiological and psychological modifications, yet there is a lack of knowledge regarding brain elements involved in such conditions. Here, we identify brain regions involved in spontaneous pain of chronic back pain (CBP) in two separate groups of patients (n = 13 and n = 11), and contrast brain activity between spontaneous pain and thermal pain (CBP and healthy subjects, n = 11 each). Continuous ratings of fluctuations of spontaneous pain during functional magnetic resonance imaging were separated into two components: high sustained pain and increasing pain. Sustained high pain of CBP resulted in increased activity in the medial prefrontal cortex (mPFC; including rostral anterior cingulate). This mPFC activity was strongly related to intensity of CBP, and the region is known to be involved in negative emotions, response conflict, and detection of unfavorable outcomes, especially in relation to the self. In contrast, the increasing phase of CBP transiently activated brain regions commonly observed for acute pain, best exemplified by the insula, which tightly reflected duration of CBP. When spontaneous pain of CBP was contrasted to thermal stimulation, we observe a double-dissociation between mPFC and insula with the former correlating only to intensity of spontaneous pain and the latter correlating only to pain intensity for thermal stimulation. These findings suggest that subjective spontaneous pain of CBP involves specific spatiotemporal neuronal mechanisms, distinct from those observed for acute experimental pain, implicating a salient role for emotional brain concerning the self.

Chronic pain patients are impaired on an emotional decision-making task

&NA; Chronic pain can result in anxiety, depression and reduced quality of life. However, its effects on cognitive abilities have remained unclear although many studies attempted to psychologically profile chronic pain. We hypothesized that performance on an emotional decision‐making task may be impaired in chronic pain since human brain imaging studies show that brain regions critical for this ability are also involved in chronic pain. Chronic back pain (CBP) patients, chronic complex regional pain syndrome (CRPS) patients, and normal volunteers (matched for age, sex, and education) were studied on the Iowa Gambling Task, a card game developed to study emotional decision‐making. Outcomes on the gambling task were contrasted to performance on other cognitive tasks. The net number of choices made from advantageous decks after subtracting choices made from disadvantageous decks on average was 22.6 in normal subjects (n=26), 13.4 in CBP patients (n=26), and −9.5 in CRPS patients (n=12), indicating poor performance in the patient groups as compared to the normal controls (P<0.004). Only pain intensity assessed during the gambling task was correlated with task outcome and only in CBP patients (r=−0.75, P<0.003). Other cognitive abilities, such as attention, short‐term memory, and general intelligence tested normal in the chronic pain patients. Our evidence indicates that chronic pain is associated with a specific cognitive deficit, which may impact everyday behavior especially in risky, emotionally laden, situations.

Spontaneous cortical activity in awake monkeys composed of neuronal avalanches

Spontaneous neuronal activity is an important property of the cerebral cortex but its spatiotemporal organization and dynamical framework remain poorly understood. Studies in reduced systems—tissue cultures, acute slices, and anesthetized rats—show that spontaneous activity forms characteristic clusters in space and time, called neuronal avalanches. Modeling studies suggest that networks with this property are poised at a critical state that optimizes input processing, information storage, and transfer, but the relevance of avalanches for fully functional cerebral systems has been controversial. Here we show that ongoing cortical synchronization in awake rhesus monkeys carries the signature of neuronal avalanches. Negative LFP deflections (nLFPs) correlate with neuronal spiking and increase in amplitude with increases in local population spike rate and synchrony. These nLFPs form neuronal avalanches that are scale-invariant in space and time and with respect to the threshold of nLFP detection. This dimension, threshold invariance, describes a fractal organization: smaller nLFPs are embedded in clusters of larger ones without destroying the spatial and temporal scale-invariance of the dynamics. These findings suggest an organization of ongoing cortical synchronization that is scale-invariant in its three fundamental dimensions—time, space, and local neuronal group size. Such scale-invariance has ontogenetic and phylogenetic implications because it allows large increases in network capacity without a fundamental reorganization of the system.

Learning from Mistakes

We re-examine the commonly held view that learning and memory necessarily require potentiation of synapses. A simple neuronal model of self-organized learning with no positive reinforcement is presented. The strongest synapses are selected for propagation of activity. Active synaptic connections are temporarily tagged and subsequently depressed if the resulting output turns out to be unsuccessful. Thus, all learning occurs by mistakes. The model operates at a highly adaptive state with low activity. Previously stored patterns may be swiftly retrieved when the environment and the demands of the brain change. The combined process of: (i) activity selection by extremal winner-take-all dynamics; and (ii) the subsequent weeding out of synapses may be viewed as synaptic Darwinism. We argue that all the features of the model are biologically plausible and discuss our results in light of recent experiments by Fitzsimonds et al. on back-propagation of long-term depression, by Xu et al. on facilitation of long-term depression in the hippocampus by behavioural stress, and by Frey and Morris on synaptic tagging.

The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.

Critical brain networks

Highly correlated brain dynamics produces synchronized states with no behavioral value, while weakly correlated dynamics prevents information flow. We discuss the idea put forward by Per Bak that the working brain stays at an intermediate (critical) regime characterized by power-law correlations.

Supernormal excitability as a mechanism of chaotic dynamics of activation in cardiac Purkinje fibers.

Supernormality, which can be defined as greater than normal excitability during or immediately after action potential repolarization, has been observed in a variety of cardiac preparations. However, as yet, no description of the dynamics of tissue response to repetitive stimulation in the presence of supernormal or relatively supernormal excitability has appeared. Isolated sheep cardiac Purkinje fibers (2-5 mm in length) were superfused with Tyrodes solution and stimulated with depolarizing current pulses through a suction pipette. Recovery of excitability, restitution of the action potential duration, and response patterns were measured in each fiber for a wide range of current amplitudes and stimulation frequencies. When the potassium chloride concentration of the Tyrodes solution was decreased from 7 to 4 mM, the excitability recovery function consistently changed from monophasic (normal) to triphasic (supernormal). During repetitive stimulation at increasing rates, normal preparations responded only with gradual changes in the activation ratio, expressed as periodic phase-locked responses (i.e., Wenckebach-like patterns, etc.). Supernormal preparations showed a nonmonotonic change in the activation ratio, as well as complex aperiodic response patterns. Numerical results from an analytical model gave a quantitative basis for the relation between nonmonotonicity in the excitability function and the development of complex rhythms in cardiac Purkinje fibers. Both our experimental and theoretical results indicate that the presence of supernormality and the slope of the action potential duration restitution curve at short diastolic intervals are responsible for the development of chaotic dynamics. Moreover, our results give an accurate description of the supernormality phenomenon, predict the behavior expected under such conditions, and provide insight about the role of membrane recovery in determining regular and irregular frequency-dependent rhythm and conduction disturbances.

Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy

Abstract Postherpetic neuralgia (PHN) is a debilitating chronic pain condition, yet there is a lack of knowledge regarding underlying brain activity. Here we identify brain regions involved in spontaneous pain of PHN (n = 11) and determine its modulation with Lidoderm therapy (patches of 5% lidocaine applied to the PHN affected body part). Continuous ratings of fluctuations of spontaneous pain during fMRI were contrasted to ratings of fluctuations of a bar observed during scanning, at three sessions: (1) pre‐treatment baseline, (2) after 6 h of Lidoderm treatment, and (3) after 2 weeks of Lidoderm use. Overall brain activity for spontaneous pain of PHN involved affective and sensory‐discriminative areas: thalamus, primary and secondary somatosensory, insula and anterior cingulate cortices, as well as areas involved in emotion, hedonics, reward, and punishment: ventral striatum, amygdala, orbital frontal cortex, and ventral tegmental area. Generally, these activations decreased at sessions 2 and 3, except right anterior insular activity which increased with treatment. The sensory and affective activations only responded to the short‐term treatment (6 h of Lidoderm); while the ventral striatum and amygdala (reward‐related regions) decreased mainly with longer‐term treatment (2 weeks of Lidoderm). Pain properties: average magnitude of spontaneous pain, and responses on Neuropathic Pain Scale (NPS), decreased with treatment. The ventral striatal and amygdala activity best reflected changes in NPS, which was modulated only with longer‐term treatment. The results show a specific brain activity pattern for PHN spontaneous pain, and implicate areas involved in emotions and reward as best reflecting changes in pain with treatment.