Structural basis of envelope and phase intrinsic coupling modes in the cerebral cortex.

Intrinsic coupling modes (ICMs) can be observed in ongoing brain activity at multiple spatial and temporal scales. Two families of ICMs can be distinguished: phase and envelope ICMs. The principles that shape these ICMs remain partly elusive, in particular their relation to the underlying brain structure. Here we explored structure-function relationships in the ferret brain between ICMs quantified from ongoing brain activity recorded with chronically implanted micro-ECoG arrays and structural connectivity (SC) obtained from high-resolution diffusion MRI tractography. Large-scale computational models were used to explore the ability to predict both types of ICMs. Importantly, all investigations were conducted with ICM measures that are sensitive or insensitive to volume conduction effects. The results show that both types of ICMs are significantly related to SC, except for phase ICMs when using measures removing zero-lag coupling. The correlation between SC and ICMs increases with increasing frequency which is accompanied by reduced delays. Computational models produced results that were highly dependent on the specific parameter settings. The most consistent predictions were derived from measures solely based on SC. Overall, the results demonstrate that patterns of cortical functional coupling as reflected in both phase and envelope ICMs are both related, albeit to different degrees, to the underlying structural connectivity in the cerebral cortex.

Dynamic reconfiguration of cortical functional connectivity across brain states.

Throughout each day, the brain displays transient changes in state, as evidenced by shifts in behavior and vigilance. While the electrophysiological correlates of brain states have been studied for some time, it remains unclear how large-scale cortico-cortical functional connectivity systematically reconfigures across states. Here, we investigate state-dependent shifts in cortical functional connectivity by recording local field potentials (LFPs) during spontaneous behavioral transitions in the ferret using chronically implanted micro-electrocorticographic (µECoG) arrays positioned over occipital, parietal, and temporal cortical regions. To objectively classify brain state, we describe a data-driven approach that projects time-varying LFP spectral properties into brain state space. Distinct brain states displayed markedly different patterns of cross-frequency phase-amplitude coupling and inter-electrode phase synchronization across several LFP frequency bands. The largest across-state differences in functional connectivity were observed between periods of presumed slow-wave and rapid-eye-movement-sleep/active-state, which were characterized by the contrasting phenomena of cortical network fragmentation and global synchronization, respectively. Collectively, our data provide strong evidence that large-scale functional interactions in the brain dynamically reconfigure across behavioral states.

Crossmodal integration improves sensory detection thresholds in the ferret.

During the last two decades ferrets (Mustela putorius) have been established as a highly efficient animal model in different fields in neuroscience. Here we asked whether ferrets integrate sensory information according to the same principles established for other species. Since only few methods and protocols are available for behaving ferrets we developed a head-free, body-restrained approach allowing a standardized stimulation position and the utilization of the ferret's natural response behavior. We established a behavioral paradigm to test audiovisual integration in the ferret. Animals had to detect a brief auditory and/or visual stimulus presented either left or right from their midline. We first determined detection thresholds for auditory amplitude and visual contrast. In a second step, we combined both modalities and compared psychometric fits and the reaction times between all conditions. We employed Maximum Likelihood Estimation (MLE) to model bimodal psychometric curves and to investigate whether ferrets integrate modalities in an optimal manner. Furthermore, to test for a redundant signal effect we pooled the reaction times of all animals to calculate a race model. We observed that bimodal detection thresholds were reduced and reaction times were faster in the bimodal compared to unimodal conditions. The race model and MLE modeling showed that ferrets integrate modalities in a statistically optimal fashion. Taken together, the data indicate that principles of multisensory integration previously demonstrated in other species also apply to crossmodal processing in the ferret.

Auditory and visual interactions between the superior and inferior colliculi in the ferret.

The integration of visual and auditory spatial information is important for building an accurate perception of the external world, but the fundamental mechanisms governing such audiovisual interaction have only partially been resolved. The earliest interface between auditory and visual processing pathways is in the midbrain, where the superior (SC) and inferior colliculi (IC) are reciprocally connected in an audiovisual loop. Here, we investigate the mechanisms of audiovisual interaction in the midbrain by recording neural signals from the SC and IC simultaneously in anesthetized ferrets. Visual stimuli reliably produced band-limited phase locking of IC local field potentials (LFPs) in two distinct frequency bands: 6-10 and 15-30 Hz. These visual LFP responses co-localized with robust auditory responses that were characteristic of the IC. Imaginary coherence analysis confirmed that visual responses in the IC were not volume-conducted signals from the neighboring SC. Visual responses in the IC occurred later than retinally driven superficial SC layers and earlier than deep SC layers that receive indirect visual inputs, suggesting that retinal inputs do not drive visually evoked responses in the IC. In addition, SC and IC recording sites with overlapping visual spatial receptive fields displayed stronger functional connectivity than sites with separate receptive fields, indicating that visual spatial maps are aligned across both midbrain structures. Reciprocal coupling between the IC and SC therefore probably serves the dynamic integration of visual and auditory representations of space.

Impulsive behaviour in rats induced by intracortical DOI infusions is antagonized by co-administration of an mGlu2/3 receptor agonist.

The orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC) modulate impulsive behaviours. Serotonin [5-hydroxytryptamine (5-HT)] 2A receptors have also been implicated in impulsivity and govern antagonistic interactions with metabotropic glutamate (mGlu)2/3 receptors. This study examined the interactions between 5-HT2A and mGlu2/3 receptors in the OFC and mPFC with relevance to impulsive choice and impulsive action. Impulsive choice was assessed in Lister Hooded rats, trained in a delay-discounting T-maze task, after bilateral intra-OFC infusions of the 5-HT2A/C receptor agonist DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride; 5 µg/0.5 µl] and the mGlu2/3 receptor agonist LY379268 (1 µg/0.5 µl). Impulsive action was assessed in a second group of rats trained in a five-choice serial reaction time task (5-CSRTT) and receiving bilateral intra-mPFC infusions of DOI (5 µg/0.5 µl) and LY379268 (1 µg/0.5 µl). Intra-OFC DOI increased impulsive choice, which was not seen when DOI was co-administered with LY379268. LY379268 itself had no effect on choice behaviour. Intra-mPFC DOI caused impulsive over-responding in the 5-CSRTT that was attenuated when DOI and LY379268 were co-injected. Local mPFC-infusions of LY379268 had no effect on 5-CSRTT performance. This study suggests a differential involvement of OFC and mPFC 5-HT2A receptors in impulsive choice and impulsive action. Moreover, compounds acting at mGlu2/3 receptors might have the potential to improve impulsivity-related impairments.