On the Relationship between MRI and Local Field Potential Measurements of Spatial and Temporal Variations in Functional Connectivity.

Correlations between fluctuations in resting state BOLD fMRI signals are interpreted as measures of functional connectivity (FC), but the neural basis of their origins and their relationships to specific features of underlying electrophysiologic activity, have not been fully established. In particular, the dependence of FC metrics on different frequency bands of local field potentials (LFPs), and the relationship of dynamic changes in BOLD FC to underlying temporal variations of LFP correlations, are not known. We compared the spatial profiles of resting state coherences of different frequency bands of LFP signals, with high resolution resting state BOLD FC measurements. We also compared the probability distributions of temporal variations of connectivity in both modalities using a Markov chain model-based approach. We analyzed data obtained from the primary somatosensory (S1) cortex of monkeys. We found that in areas 3b and 1 of S1 cortex, low frequency LFP signal fluctuations were the main contributions to resting state LFP coherence. Additionally, the dynamic changes of BOLD FC behaved most similarly to the LFP low frequency signal coherence. These results indicate that, within the S1 cortex meso-scale circuit studied, resting state FC measures from BOLD fMRI mainly reflect contributions from low frequency LFP signals and their dynamic changes.

Cry presence and amplitude do not reflect cortical processing of painful stimuli in newborns with distinct responses to touch or cold.

OBJECTIVE: Newborns requiring hospitalisation frequently undergo painful procedures. Prevention of pain in infants is of prime concern because of adverse associations with physiological and neurological development. However, pain mitigation is currently guided by behavioural observation assessments that have not been validated against direct evidence of pain processing in the brain. The aim of this study was to determine whether cry presence or amplitude is a valid indicator of pain processing in newborns. DESIGN: Prospective observational cohort. SETTING: Newborn nursery. PATIENTS: Healthy infants born at >37 weeks and <42 weeks gestation. INTERVENTIONS: We prospectively studied newborn cortical responses to light touch, cold and heel stick, and the amplitude of associated infant vocalisations using our previously published paradigms of time-locked electroencephalogram (EEG) with simultaneous audio recordings. RESULTS: Latencies of cortical peak responses to each of the three stimuli type were significantly different from each other. Of 54 infants, 13 (24%), 19 (35%) and 35 (65%) had cries in response to light touch, cold and heel stick, respectively. Cry in response to non-painful stimuli did not predict cry in response to heel stick. All infants with EEG data had measurable pain responses to heel stick, whether they cried or not. There was no association between presence or amplitude of cries and cortical nociceptive amplitudes. CONCLUSIONS: In newborns with distinct brain responses to light touch, cold and pain, cry presence or amplitude characteristics do not provide adequate behavioural markers of pain signalling in the brain. New bedside assessments of newborn pain may need to be developed using brain-based methodologies as benchmarks in order to provide optimal pain mitigation.

Realistic models of apparent dynamic changes in resting-state connectivity in somatosensory cortex.

Variations over time in resting-state correlations in blood oxygenation level-dependent (BOLD) signals from different cortical areas may indicate changes in brain functional connectivity. However, apparent variations over time may also arise from stationary signals when the sample duration is finite. Recently, a vector autoregressive (VAR) null model has been proposed to simulate real functional magnetic resonance imaging (fMRI) data, which provides a robust stationary model for identifying possible temporal dynamic changes in functional connectivity. In this work, we propose a simpler model that uses a filtered stationary dataset. The filtered stationary model generates statistically stationary time series from random data with a single prescribed correlation coefficient that is calculated as the average over the entire time series. In addition, we propose a dynamic model, which is better able to replicate real fMRI connectivity, estimated from monkey brain studies, than the two stationary models. We compare simulated results using these three models with the behavior of primary somatosensory cortex (S1) networks in anesthetized squirrel monkeys at high field (9.4 T), using a sliding window correlation analysis. We found that at short window sizes, both stationary models reproduced the distribution of correlations of real signals well, but at longer window sizes, a dynamic model reproduced the distribution of correlations of real signals better than the stationary models. While stationary models replicate several features of real data, a close representation of the behavior of resting-state data acquired from somatosensory cortex of non-human primates is obtained only when a dynamic correlation is introduced, suggesting dynamic variations in connectivity are real. Hum Brain Mapp 37:3897-3910, 2016. © 2016 Wiley Periodicals, Inc.

The Caenorhabditis elegans choline transporter CHO-1 sustains acetylcholine synthesis and motor function in an activity-dependent manner.

Cholinergic neurotransmission supports motor, autonomic, and cognitive function and is compromised in myasthenias, cardiovascular diseases, and neurodegenerative disorders. Presynaptic uptake of choline via the sodium-dependent, hemicholinium-3-sensitive choline transporter (CHT) is believed to sustain acetylcholine (ACh) synthesis and release. Analysis of this hypothesis in vivo is limited in mammals because of the toxicity of CHT antagonists and the early postnatal lethality of CHT-/- mice (Ferguson et al., 2004). In Caenorhabditis elegans, in which cholinergic signaling supports motor activity and mutant alleles impacting ACh secretion and response can be propagated, we investigated the contribution of CHT (CHO-1) to facets of cholinergic neurobiology. Using the cho-1 promoter to drive expression of a translational, green fluorescent protein-CHO-1 fusion (CHO-1:GFP) in wild-type and kinesin (unc-104) mutant backgrounds, we establish in the living nematode that the transporter localizes to cholinergic synapses, and likely traffics on synaptic vesicles. Using embryonic primary cultures, we demonstrate that CHO-1 mediates hemicholinium-3-sensitive, high-affinity choline uptake that can be enhanced with depolarization in a Ca(2+)-dependent manner supporting ACh synthesis. Although homozygous cho-1 null mutants are viable, they possess 40% less ACh than wild-type animals and display stress-dependent defects in motor activity. In a choline-free liquid environment, cho-1 mutants demonstrate premature paralysis relative to wild-type animals. Our findings establish a requirement for presynaptic choline transport activity in vivo in a model amenable to a genetic dissection of CHO-1 regulation.