Brain functional connectivity in children with a mild traumatic brain injury: A scoping review.

INTRODUCTION: The occurrence of mild traumatic brain injury(mTBI) is estimated at 0,2-0,3% cases annually. Following a mTBI, some children experience persistent symptoms, and functional connectivity(FC) changes may be implicated. However, characteristics of FC have not been widely described in this population. This scoping review aimed to identify and understand the impacts of mTBI on EEG-measured FC in children, provide an overview of the available literature, detail analysis techniques, and describe gaps in the research. METHODS: PubMed, Web of Science, Medline, Embase, ProQuest and CINAHL were searched up to June 25, 2023, with the terms child, mTBI, EEG, FC, and their synonyms. Ten studies were identified. RESULTS: Five studies reported significant differences between the mTBI group and controls. In addition to group differences, six studies reported significant variation over time. Brain Network Analysis(BNA), utilized in seven studies, was the primary FC analysis recorded. Two of the five studies that reported significant differences following mTBI utilized the BNA. The other three applied alternative analysis methods. DISCUSSION: FC assessment based on EEG can identify some differences in children with mTBI. BNA was more useful in following changes over time. Further research is suggested, considering the limited age range and number of retrieved studies.

Mesocortical dopamine depletion and anxiety-related behavior in the rat: sex and hemisphere differences.

The mesocortical dopamine (DA) system of the rat plays an important role in prefrontal cortex (PFC) regulation of stress and emotion and exhibits functional hemispheric asymmetry for such processing. Since few studies examine sex differences in this context, we compared the effects of left vs. right unilateral PFC DA depletion in males and females in several behavioral situations associated with anxiety or aversion. Adult rats received unilateral injections of 6-hydroxydopamine (6-OHDA) or vehicle in the ventromedial (vm) PFC. Behavioral tests included a predator odor burying test, elevated plus maze and sucrose consumption with simple taste aversion. Tissue analysis confirmed that vmPFCs injected with 6-OHDA were depleted of DA (75-85%) compared to controls. Burying behavior and sucrose consumption were affected only by left lesions, similarly in both sexes. However, risk assessment behaviors were affected by right lesions in opposite directions in males and females. Behaviors modified preferentially by the left cortex thus showed less evidence of sex differences than those modulated by the right. While mesocortical DA depletion effects are lateralized, the nature of these effects can vary with sex and specific behavior. Such findings may be clinically significant, given the large gender differences in the incidence of mood and anxiety disorders, which also show many lateralized prefrontal abnormalities.

Role of sex in the neurochemical and neuroendocrine correlates of paw preference in the rat.

Handedness in humans and paw preference (PP) in rodents have been associated with neural and physiological correlates, which frequently appear to be sex-specific. The present study examines sex differences in the effects of differential PP on post mortem measures of regional monoamine activity in adult Long-Evans rats. The effects of PP on neuroendocrine function were also assessed by measuring plasma adrenocorticotropic hormone (ACTH) in response to a 30-min restraint stress. Most rats showed strong individual PP. Males (n=27) and females (n=26) did not differ in the direction or strength of their PP with nearly equal numbers of left and right-pawed rats. However, many Sex×PP interactions were noted in regional neurochemical measures, and most effects of PP were bilateral in nature and sex-specific. In males, Left PP (relative to Right PP) was associated with reduced striatal dopamine (DA) levels and amygdala DA metabolism bilaterally. In females, Left PP was associated with a bilateral upregulation of DAergic metabolism in both prefrontal cortex and nucleus accumbens, increased amygdala serotonin metabolism, and a (right) unilateral increase in amygdala DA. As in previous studies, some correlations were also noted between PP and asymmetrical or unilateral monoamine measures. As well, rats with strong PP, independent of direction or sex, had lower basal ACTH and more robust stress responses than rats with weak PP, suggesting a possible adaptive advantage to strong lateralization. Overall, sex differences were found only regarding effects of the direction of PP, not its magnitude. The findings suggest that the direction of PP affects distinct bilateral networks of structures sex-dependently. Such fundamental influences of PP on functional brain organization have implications for a wide array of processes under monoaminergic modulation in these brain regions, and may further our understanding of the numerous human examples of gender and handedness interactions across several modalities.

Effects of unilateral amygdala dopamine depletion on behaviour in the elevated plus maze: role of sex, hemisphere and retesting.

A growing body of literature suggests that sex differences exist in both rodents and humans in terms of the central processing of stress and emotion, and an important factor in this regard may involve differential hemispheric specialization. The amygdala has been shown to be functionally asymmetrical in both rats and humans and its involvement in stress and emotion processing is well documented. Given that amygdala function is importantly modulated by dopamine (DA), the present study examined the effects of left vs. right unilateral DAergic depletion targeting the basolateral amygdala in male and female rats. We examined behaviour in the elevated plus maze over two consecutive days, and plasma adrenocorticotropic hormone (ACTH) levels in response to a separate 30min restraint stress. Overall, females showed significantly more exploration of open arms of the plus maze than males, while not differing in general activity reflected in closed arm entries. Significant SexxHemisphere interactions were observed for all measures related to open arm exploration, as right amygdala DA depletion produced an anxiolytic effect in males, increasing open arm exploration, but reduced this behaviour in females. Moreover, open arm exploration was greatly reduced on the second maze exposure in males, but unchanged in females. A SexxHemisphere interaction was also found for plasma ACTH levels. It is suggested that the role of amygdala DA on stress-related behaviour and physiology reflects inherent differences in amygdala function dependent on both sex and hemisphere.

Acetylcholine release is elicited in the visual cortex, but not in the prefrontal cortex, by patterned visual stimulation: a dual in vivo microdialysis study with functional correlates in the rat brain.

By its projections to the primary visual and the prefrontal cortices, the basal forebrain cholinergic system is involved in cognitive processing of sensory stimuli. It has been suggested that visual stimulus-induced cholinergic activation of the visual cortex may exert a permissive role on thalamocortical inputs. However, it is not known if visual stimulation elicits cholinergic activation of high-order brain areas in the absence of attentional need. In the present study, we measured the effects of patterned visual stimulation (horizontal grating) on the release of acetylcholine with dual-probe in vivo microdialysis in the visual and the prefrontal cortices of anesthetized rats. We also used retrograde tracing to determine the anatomical relationships of cholinergic neurons with neurons of the visual system and the prefrontal cortex. Finally, we evaluated a functional correlate of this stimulation, namely c-fos immunolabeling. Patterned visual stimulation elicited significant increases in acetylcholine release in the visual cortex, accompanied by an increased number of c-fos immunoreactive neurons in this brain area. In contrast, in the prefrontal cortex, neither the level of acetylcholine release nor the number of c-fos immunoreactive neurons was significantly changed because of the stimulation. Cholinergic basal forebrain neurons projecting to the visual or the prefrontal cortices were both localized within the horizontal limb of the diagonal band of Broca but were not immunoreactive for c-fos during visual stimulation. No parts of the visual system were found to directly project to these basal forebrain neurons. These results suggest the differential involvement of cholinergic projections in the integration of sensory stimuli, depending on the level of activity of the targeted cortical area.

Distinct electrophysiological properties of glutamatergic, cholinergic and GABAergic rat septohippocampal neurons: novel implications for hippocampal rhythmicity.

The medial septum-diagonal band complex (MSDB) contains cholinergic and non-cholinergic neurons known to play key roles in learning and memory processing, and in the generation of hippocampal theta rhythm. Electrophysiologically, several classes of neurons have been described in the MSDB, but their chemical identity remains to be fully established. By combining electrophysiology with single-cell RT-PCR, we have identified four classes of neurons in the MSDB in vitro. The first class displayed slow-firing and little or no Ih, and expressed choline acetyl-transferase mRNA (ChAT). The second class was fast-firing, had a substantial Ih and expressed glutamic acid decarboxylase 67 mRNA (GAD67), sometimes co-localized with ChAT mRNAs. A third class exhibited fast- and burst-firing, had an important Ih and expressed GAD67 mRNA also occasionally co-localized with ChAT mRNAs. The ionic mechanism underlying the bursts involved a low-threshold spike and a prominent Ih current, conductances often associated with pacemaker activity. Interestingly, we identified a fourth class that expressed transcripts solely for one or two of the vesicular glutamate transporters (VGLUT1 and VGLUT2), but not ChAT or GAD. Some putative glutamatergic neurons displayed electrophysiological properties similar to ChAT-positive slow-firing neurons such as the occurrence of a very small Ih, but nearly half of glutamatergic neurons exhibited cluster firing with intrinsically generated voltage-dependent subthreshold membrane oscillations. Neurons belonging to each of the four described classes were found among septohippocampal neurons by retrograde labelling. We provide results suggesting that slow-firing cholinergic, fast-firing and burst-firing GABAergic, and cluster-firing glutamatergic neurons, may each uniquely contribute to hippocampal rhythmicity in vivo.

Alteration in the production of free oxygen radicals and proinflammatory cytokines by peritoneal and alveolar macrophages in old mice and immunomodulatory effect of RU 41740 administration. Part I: Effect of short and repetitive noise stress.

The aim of this study was to analyze the effects of stress on natural immunity in old mice, and the potential of an immunomodulating drug to correct stress-induced immune abnormalities. We analyzed both the alveolar (ALM) and peritoneal macrophage (PerM) oxidative responses and cytokine productions of TNF-alpha and IL-1alpha, in old mice after exposure to 3 days of noise stress, with and without treatment with RU 41740, an immunomodulating compound. Production of Free Oxygen Radicals (FOR) by ALM and PerM macrophages was evaluated using a luminol-dependent chemiluminescence method at the basal state and after stimulation. Serum corticosterone was also measured. Three groups of 22-24 month-old C57BL/6 mice were studied. Seven mice were treated with RU 41740 (10 mg kg(-1)) every day for 5 days and then exposed to sound stress (110 dB, 1000 Hz, for 3 nights). Ten mice were treated with saline, then submitted to a sham stress. Eight animals received neither treatment nor stress. There was no difference in corticosterone level between the three groups and between these groups and a control group nonstressed, noncannulated. After stimulation by fMetLeuPhe, production of FOR by ALM and PerM significantly increased after stress and returned to normal values after RU 41740 treatment (p < 0.001). The cytokine levels (TNF-alpha and IL-1alpha) decreased after stress and returned to normal levels after RU 41740 treatment. This study shows that, in aged mice, auditory stress is associated with modifications of macrophage functions which are different, depending on their localization and on the function under study. It confirms the immunomodulatory capacities of RU 41740 that was shown to counteract these effects of stress in elderly animals.