Cross-hemispheric communication: Insights on lateralized brain functions.

On the surface, the two hemispheres of vertebrate brains look almost perfectly symmetrical, but several motor, sensory, and cognitive systems show a deeply lateralized organization. Importantly, the two hemispheres are connected by various commissures, white matter tracts that cross the brain's midline and enable cross-hemispheric communication. Cross-hemispheric communication has been suggested to play an important role in the emergence of lateralized brain functions. Here, we review current advances in understanding cross-hemispheric communication that have been made using modern neuroscientific tools in rodents and other model species, such as genetic labeling, large-scale recordings of neuronal activity, spatiotemporally precise perturbation, and quantitative behavior analyses. These findings suggest that the emergence of lateralized brain functions cannot be fully explained by largely static factors such as genetic variation and differences in structural brain asymmetries. In addition, learning-dependent asymmetric interactions between the left and right hemispheres shape lateralized brain functions.

Alterations in a cross-hemispheric circuit associates with novelty discrimination deficits in mouse models of neurodegeneration.

A major pathological hallmark of neurodegenerative diseases, including Alzheimer's, is a significant reduction in the white matter connecting the two cerebral hemispheres, as well as in the correlated activity between anatomically corresponding bilateral brain areas. However, the underlying circuit mechanisms and the cognitive relevance of cross-hemispheric (CH) communication remain poorly understood. Here, we show that novelty discrimination behavior activates CH neurons and enhances homotopic synchronized neural oscillations in the visual cortex. CH neurons provide excitatory drive required for synchronous neural oscillations between hemispheres, and unilateral inhibition of the CH circuit is sufficient to impair synchronous oscillations and novelty discrimination behavior. In the 5XFAD and Tau P301S mouse models, CH communication is altered, and novelty discrimination is impaired. These data reveal a hitherto uncharacterized CH circuit in the visual cortex, establishing a causal link between this circuit and novelty discrimination behavior and highlighting its impairment in mouse models of neurodegeneration.

Medullary Norepinephrine Projections Release Norepinephrine into the Contralateral Bed Nucleus of the Stria Terminalis.

Central norepinephrine signaling influences a wide range of behavioral and physiological processes, and the ventral bed nucleus of the stria terminalis (vBNST) receives some of the densest norepinephrine innervation in the brain. Previous work describes norepinephrine neurons as projecting primarily unilaterally; however, recent evidence for cross-hemispheric catecholamine signaling challenges this idea. Here, we use fast-scan cyclic voltammetry and retrograde tracing to characterize cross-hemispheric norepinephrine signaling in the vBNST. We delivered stimulations to noradrenergic pathways originating in the A1/A2 and locus coeruleus and found hemispherically equivalent norepinephrine release in the vBNST regardless of stimulated hemisphere. Unilateral retrograde tracing revealed that medullary, but not locus coeruleus norepinephrine neurons send cross-hemispheric projections to the vBNST. Further characterization with pharmacological lesions revealed that stimulations of the locus coeruleus and its axon bundles likely elicit vBNST norepinephrine release through indirect activation. These experiments are the first to demonstrate contralateral norepinephrine release and establish that medullary, but not coerulean neurons are responsible for norepinephrine release in the vBNST.

The effects of cross-hemispheric dorsolateral prefrontal cortex transcranial direct current stimulation (tDCS) on task switching.

BACKGROUND: Task switching, defined as the ability to flexibly switch between tasks in the face of goal shifting, is a central mechanism in cognitive control. Task switching is thought to involve both prefrontal cortex (PFC) and parietal regions. Our previous work has shown that it is possible to modulate set shifting tasks using 1 mA tDCS on both the left dorsolateral prefrontal cortex and the left primary motor area. However, it remains unclear whether the effects of PFC tDCS on task switching are hemisphere-dependent. OBJECTIVES: We aimed to test the effects of three types of cross-hemispheric tDCS over the PFC (left anode-right cathode [LA-RC], left cathode-right anode [LC-RA] and sham stimulation) on participants' performance (reaction time) and accuracy (correct responses) in two task-switching paradigms (i.e., letter/digit naming and vowel-consonant/parity tasks). METHODS: Sixteen participants received cross-hemispheric tDCS over the PFC in two task-switching paradigms. RESULTS: The results show that cross-hemispheric tDCS over the PFC modulates task-switching ability in both paradigms. Our results were task and hemisphere-specific, such that in the letter/digit naming task, LA-RC tDCS increased switching performance, whereas LC-RA tDCS improved accuracy. On the other hand, in the vowel-consonant/parity task, LA-RC improved accuracy, and decreased switching performance. CONCLUSIONS: Our findings confirm the notion that involvement of the PFC on task switching depends critically on laterality, implying the existence of different roles for the left hemisphere and the right hemisphere in task switching.