Decreased homotopic functional connectivity in traumatic brain injury.

INTRODUCTION: Homotopic functional connectivity (HoFC), the synchrony in activity patterns between homologous brain regions, is a fundamental characteristic of resting-state functional connectivity (RsFC). METHODS: We examined the difference in HoFC, computed as the correlation between atlas-based regions and their counterpart on the opposite hemisphere, in 16 moderate-severe traumatic brain injury patients (msTBI) and 36 healthy controls. Regions of decreased HoFC in msTBI patients were further used as seeds for examining differences between groups in correlations with other brain regions. Finally, we computed logistic regression models of regional HoFC and fractional anisotropy (FA) of the corpus callosum (CC). RESULTS: TBI patients exhibited decreased HoFC in the middle and posterior cingulate cortex, thalamus, superior temporal pole, and cerebellum III. Furthermore, decreased RsFC was found between left cerebellum III and right parahippocampal cortex and vermis, between superior temporal pole and left caudate and medial left and right frontal orbital gyri. Thalamic HoFC and FA of the CC discriminate patients as msTBI with a high accuracy of 96%. CONCLUSION: TBI is associated with regionally decreased HoFC. Moreover, a multimodality model of interhemispheric connectivity allowed for a high degree of accuracy in disease discrimination and enabled a deeper understanding of TBI effects on brain interhemispheric reorganization post-TBI.

Lateralisation of subcortical functional connectivity during and after general anaesthesia.

BACKGROUND: Arousal and awareness are two important components of consciousness states. Functional neuroimaging has furthered our understanding of cortical and thalamocortical mechanisms of awareness. Investigating the relationship between subcortical functional connectivity and arousal has been challenging owing to the relatively small size of brainstem structures and thalamic nuclei, and their depth in the brain. METHODS: Resting state functional MRI scans of 72 healthy volunteers were acquired before, during, 1 h after, and 1 day after sevoflurane general anaesthesia. Functional connectivity of subcortical regions of interest vs whole brain and homotopic functional connectivity for assessment of left-right symmetry analyses of both cortical and subcortical regions of interest were performed. Both analyses used high resolution atlases generated from deep brain stimulation applications. RESULTS: Functional connectivity in subcortical loci within the thalamus and of the ascending reticular activating system was sharply restricted under anaesthesia, featuring a general lateralisation of connectivity. Similarly, left-right homology was sharply reduced under anaesthesia. Subcortical bilateral functional connectivity was not fully restored after emergence from anaesthesia, although greater restoration was seen between ascending reticular activating system loci and specific thalamic nuclei thought to be involved in promoting and maintaining arousal. Functional connectivity was fully restored to baseline by the following day. CONCLUSIONS: Functional connectivity in the subcortex is sharply restricted and lateralised under general anaesthesia. This restriction may play a part in loss and return of consciousness. CLINICAL TRIAL REGISTRATION: NCT02275026.

Alterations in Network Connectivity after Traumatic Brain Injury in Mice.

Victims of mild traumatic brain injury (mTBI) usually do not display clear morphological brain defects, but frequently have long-lasting cognitive deficits, emotional difficulties, and behavioral disturbances. In the present study we used diffusion magnetic resonance imaging (dMRI) combined with graph theory measurements to investigate the effects of mTBI on brain network connectivity. We employed a non-invasive closed-head weight-drop mouse model to produce mTBI. Mice were scanned at two time points, 24 h before the injury and either 7 or 30 days following the injury. Connectivity matrices were computed for each animal at each time point, and these were subsequently used to extract graph theory measures reflecting network integration and segregation, on both the global (i.e., whole brain) and local (i.e., single regions) levels. We found that cluster coefficient, reflecting network segregation, decreased 7 days post-injury and then returned to baseline level 30 days following the injury. Global efficiency, reflecting network integration, demonstrated opposite patterns in the left and right hemispheres, with an increase of right hemisphere efficiency at 7 days and then a decrease in efficiency following 30 days, and vice versa in the left hemisphere. These findings suggest a possible compensation mechanism acting to moderate the influence of mTBI on the global network. Moreover, these results highlight the importance of tracking the dynamic changes in mTBI over time, and the potential of structural connectivity as a promising approach for studying network integrity and pathology progression in mTBI.

Functional effects of synthetic cannabinoids versus Δ9 -THC in mice on body temperature, nociceptive threshold, anxiety, cognition, locomotor/exploratory parameters and depression.

Synthetic cannabinoids are psychoactive substances designed to mimic the euphorigenic effects of the natural cannabis. Novel unregulated compounds appear once older compounds become illegal. It has been previously reported that synthetic cannabinoids are different than Δ9 -tetrahydrocannabinol (Δ9 -THC) as they have chemical structures unrelated to Δ9 -THC, different metabolism and, often, greater toxicity. This study aimed to investigate the effects of three novel synthetic cannabinoids and pure Δ9 -THC on body temperature, nociceptive threshold, anxiety, memory function, locomotor and exploratory parameters, and depression. We performed a battery of behavioural and motor tests starting 50 minutes post i.p. injection of each drug to adult ICR mice. The synthetic cannabinoids that were used are AB-FUBINACA, AB-CHMINACA and PB-22. All synthetic cannabinoids and Δ9 -THC caused hypothermia, but only Δ9 -THC induced a clear antinociceptive effect. All synthetic cannabinoids and Δ9 -THC caused decreased anxiety levels, spatial memory deficits and decreased exploratory behaviour as measured in the elevated plus maze, Y-maze and staircase paradigm, respectively. However, all synthetic cannabinoids but not Δ9 -THC demonstrated decreased locomotor activity in the staircase test. Moreover, only AB-FUBINACA and Δ9 -THC affected the gait balance and grip strength of the mice as was assessed by the latency time to fall from a rod. In the forced swimming test, PB-22 caused elevated depression-like behaviour while AB-FUBINACA induced a reversed effect. These results suggest varied effects among different synthetic cannabinoids and Δ9 -THC. Further studies are needed to characterize the overall effects and differences between these synthetic cannabinoids and Δ9 -THC.