Dual-Energy Computed Tomography Collagen Density Mapping of the Cranio-Cervical Ligaments-A Retrospective Feasibility Study.

The objectives of this study were to investigate the mean collagen content of the atlanto-axial joint (AAJ) ligaments in a cohort without inflammatory disease and to analyze clinical confounders such as age, sex, and presence of ligamentous calcifications. A total of 153 patients who underwent dual-energy computed tomography (DECT) due to various reasons (e.g., suspected cancer or infection) were included in this retrospective study. Reconstruction of collagen density maps from the DECT dataset was performed. Region of interest (ROI) analysis was performed to assess densities in the following regions: ligamentum transversum atlantis (LTA), ligamenta alaria, fasciculi longitudinales, ligamentum nuchae, and retro-odontoid soft tissue (RDS). Osteoarthritis (OA) and the presence of calcifications were assessed by two experienced readers blinded to clinical data. Subgroup comparisons were performed using unpaired t-tests. The correlation of collagen density and clinical factors was investigated using Pearson's correlation coefficient. Mean LTA collagen density was 141.7 (SD 35.7). Ligamentous calcifications were rare (14.4 %). OA of the AAJ was common (91.5 %). LTA collagen density was not associated with age (Pearson's r of 0.109; p = 0.180) and was not significantly higher in patients with OA (p = 0.070). No correlations between RDS thickness, collagen density or calcifications were found. Our results show collagen density mapping of the cranio-cervical joint ligaments to be feasible; collagen densities are not significantly associated with age, sex, AAJ degeneration, or asymptomatic ligamentous calcification.

Alterations of distributed neuronal network oscillations during acute pain in freely-moving mice.

The experience of pain involves the activation of multiple brain areas. Pain-specific activity patterns within and between these local networks remain, however, largely unknown. We measured neuronal network oscillations in different relevant regions of the mouse brain during acute pain, induced by subcutaneous injection of capsaicin into the left hind paw. Field potentials were recorded from primary somatosensory cortex, anterior cingulate cortex (ACC), posterior insula, ventral posterolateral thalamic nucleus, parietal cortex, central nucleus of the amygdala and olfactory bulb. Analysis included power spectra of local signals as well as interregional coherences and cross-frequency coupling (CFC). Capsaicin injection caused hypersensitivity to mechanical stimuli for at least one hour. At the same time, CFC between low (1-12 Hz) and fast frequencies (80-120 Hz) was increased in the ACC, as well as interregional coherence of low frequency oscillations (< 30 Hz) between several networks. However, these changes were not significant anymore after multiple comparison corrections. Using a variable selection method (elastic net) and a logistic regression classifier, however, the pain state was reliably predicted by combining parameters of power and coherence from various regions. Distinction between capsaicin and saline injection was also possible when data were restricted to frequencies <30 Hz, as used in clinical electroencephalography (EEG). Our findings indicate that changes of distributed brain oscillations may provide a functional signature of acute pain or pain-related alterations in activity.

Parallel detection of theta and respiration-coupled oscillations throughout the mouse brain.

Slow brain oscillations are usually coherent over long distances and thought to link distributed cell assemblies. In mice, theta (5-10 Hz) stands as one of the most studied slow rhythms. However, mice often breathe at theta frequency, and we recently reported that nasal respiration leads to local field potential (LFP) oscillations that are independent of theta. Namely, we showed respiration-coupled oscillations in the hippocampus, prelimbic cortex, and parietal cortex, suggesting that respiration could impose a global brain rhythm. Here we extend these findings by analyzing LFPs from 15 brain regions recorded simultaneously with respiration during exploration and REM sleep. We find that respiration-coupled oscillations can be detected in parallel with theta in several neocortical regions, from prefrontal to visual areas, and also in subcortical structures such as the thalamus, amygdala and ventral hippocampus. They might have escaped attention in previous studies due to the absence of respiration monitoring, the similarity with theta oscillations, and the highly variable peak frequency. We hypothesize that respiration-coupled oscillations constitute a global brain rhythm suited to entrain distributed networks into a common regime. However, whether their widespread presence reflects local network activity or is due to volume conduction remains to be determined.

Selective entrainment of gamma subbands by different slow network oscillations.

Theta oscillations (4-12 Hz) are thought to provide a common temporal reference for the exchange of information among distant brain networks. On the other hand, faster gamma-frequency oscillations (30-160 Hz) nested within theta cycles are believed to underlie local information processing. Whether oscillatory coupling between global and local oscillations, as showcased by theta-gamma coupling, is a general coding mechanism remains unknown. Here, we investigated two different patterns of oscillatory network activity, theta and respiration-induced network rhythms, in four brain regions of freely moving mice: olfactory bulb (OB), prelimbic cortex (PLC), parietal cortex (PAC), and dorsal hippocampus [cornu ammonis 1 (CA1)]. We report differential state- and region-specific coupling between the slow large-scale rhythms and superimposed fast oscillations. During awake immobility, all four regions displayed a respiration-entrained rhythm (RR) with decreasing power from OB to CA1, which coupled exclusively to the 80- to 120-Hz gamma subband (γ2). During exploration, when theta activity was prevailing, OB and PLC still showed exclusive coupling of RR with γ2 and no theta-gamma coupling, whereas PAC and CA1 switched to selective coupling of theta with 40- to 80-Hz (γ1) and 120- to 160-Hz (γ3) gamma subbands. Our data illustrate a strong, specific interaction between neuronal activity patterns and respiration. Moreover, our results suggest that the coupling between slow and fast oscillations is a general brain mechanism not limited to the theta rhythm.