Cerebellar Functional Lateralization From the Perspective of Clinical Neuropsychology

Objective: The cerebellar functional laterality, with its right hemisphere predominantly involved in verbal performance and the left one engaged in visuospatial processes, has strong empirical support. However, the clinical observation and single research results show that the damage to the right cerebellar hemisphere may cause extralinguistic and more global cognitive decline. The aim of our research was to assess the pattern of cognitive functioning, depending on the cerebellar lesion side, with particular emphasis on the damage to the right cerebellar hemisphere.Method: The study sample consisted of 31 patients with focal cerebellar lesions and 31 controls, free of organic brain damage. The Addenbrooke’s Cognitive Examination ACE III and the Trail Making Test TMT were used to assess patients’ cognitive functioning.Results: Left-sided cerebellar lesion patients scored lower than controls in attention and visuospatial domain, but not in language, fluency, and memory functions. Participants with right-sided cerebellar lesion demonstrated a general deficit of cognitive functioning, with impairments not only in language and verbal fluency subscales but also in all ACE III domains, including memory, attention, and visuospatial functions. The TMT results proved that cerebellar damage is associated with executive function impairment, regardless of the lesion side.Conclusion: The cognitive profiles of patients with cerebellum lesions differ with regard to the lesion side. Left-sided cerebellar lesions are associated with selective visuospatial and attention impairments, whereas the right-sided ones may result in a more global cognitive decline, which is likely secondary to language deficiencies, associated with this lateral cerebellar injury.

Functional Connectivity Lateralisation Shift of Resting State Networks is Linked to Visuospatial Memory and White Matter Microstructure in Relapsing–Remitting Multiple Sclerosis

Laterality patterns of resting state networks (RSN) change in various neuropsychiatric conditions. Multiple sclerosis (MS) causes neuro-cognitive symptoms involving dysfunctional large-scale brain networks. Yet, whether healthy laterality patterns of RSNs are maintained in MS and whether altered laterality patterns explain disease symptoms has not been explicitly investigated. We analysed functional MRI and diffusion tensor imaging data from 24 relapsing–remitting MS patients and 25 healthy participants. We performed group-level independent component analysis and used dual regression to estimate individual versions of well-established RSNs. Voxelwise laterality indices were calculated for each RSN. Group differences were assessed via a general linear model-based approach. The relationship between functional laterality and white matter microstructural asymmetry was assessed using Tract-Based Spatial Statistics. Spearman’s correlation was calculated between laterality indices and Brief International Cognitive Assessment for Multiple Sclerosis scores. Functional laterality of the dorsal attention network showed a significant leftward shift in the MS group in the posterior intraparietal sulcus (p < 0.033). Default-mode network laterality showed a significant leftward shift in the MS group in the angular gyrus (p < 0.005). Diminished dorsal attention network laterality was associated with increased fractional anisotropy asymmetry in the superior longitudinal fasciculus (p < 0.02). In the default-mode network, leftward laterality of the angular gyrus was associated with higher BVMT-R scores (R = − 0.52, p < 0.023). Our results confirm previous descriptions of RSN dysfunction in relapsing–remitting MS and show that altered functional connectivity lateralisation patterns of RSNs might contibute to cognitive performance and structural remodellation even in patients with mild clinical symptoms.

White matter variability, cognition, and disorders: a systematic review

Inter-individual differences can inform treatment procedures and—if accounted for—have the potential to significantly improve patient outcomes. However, when studying brain anatomy, these inter-individual variations are commonly unaccounted for, despite reports of differences in gross anatomical features, cross-sectional, and connectional anatomy. Brain connections are essential to facilitate functional organization and, when severed, cause impairments or complete loss of function. Hence, the study of cerebral white matter may be an ideal compromise to capture inter-individual variability in structure and function. We reviewed the wealth of studies that associate cognitive functions and clinical symptoms with individual tracts using diffusion tractography. Our systematic review indicates that tractography has proven to be a sensitive method in neurology, psychiatry, and healthy populations to identify variability and its functional correlates. However, the literature may be biased, as the most commonly studied tracts are not necessarily those with the highest sensitivity to cognitive functions and pathologies. Additionally, the hemisphere of the studied tract is often unreported, thus neglecting functional laterality and asymmetries. Finally, we demonstrate that tracts, as we define them, are not correlated with one, but multiple cognitive domains or pathologies. While our systematic review identified some methodological caveats, it also suggests that tract–function correlations might still be a promising tool in identifying biomarkers for precision medicine. They can characterize variations in brain anatomy, differences in functional organization, and predicts resilience and recovery in patients.

Glutamatergic Neurotransmission Controls the Functional Lateralization of the mPFC in the Modulation of Anxiety Induced by Social Defeat Stress in Male Mice

The rodent medial prefrontal cortex (mPFC) is anatomically divided into cingulate (Cg1), prelimbic (PrL), and infralimbic (IL) subareas. The left and right mPFC (L and RmPFC) process emotional responses induced by stress-related stimuli, and LmPFC and RmPFC inhibition elicit anxiogenesis and anxiolysis, respectively. Here we sought to investigate (i) the mPFC functional laterality on social avoidance/anxiogenic-like behaviors in male mice subjected to chronic social defeat stress (SDS), (ii) the effects of left prelimbic (PrL) inhibition (with local injection of CoCl2) on the RmPFC glutamatergic neuronal activation pattern (immunofluorescence assay), and (iii) the effects of the dorsal right mPFC (Cg1 + PrL) NMDA receptor blockade (with local injection of AP7) on the anxiety induced by left dorsal mPFC inhibition in mice exposed to the elevated plus maze (EPM). Results showed that chronic SDS induced anxiogenic-like behaviors followed by the rise of ΔFosB labeling and by ΔFosB + CaMKII double-labeling bilaterally in the Cg1 and IL subareas of the mPFC. Chronic SDS also increased ΔFosB and by ΔFosB + CaMKII labeling only on the right PrL. Also, the left PrL inhibition increased cFos + CaMKII labeling in the contralateral PrL and IL. Moreover, anxiogenesis induced by the left PrL inhibition was blocked by NMDA receptor antagonist AP7 injected into the right PrL. These findings suggest the lateralized control of the glutamatergic neurotransmission in the modulation of emotional-like responses in mice subjected to chronic SDS.

Atypical Brain Asymmetry in Human Situs Inversus: Gut Feeling or Real Evidence?

The alignment of visceral and brain asymmetry observed in some vertebrate species raises the question of whether this association also exists in humans. While the visceral and brain systems may have developed asymmetry for different reasons, basic visceral left–right differentiation mechanisms could have been duplicated to establish brain asymmetry. We describe the main phenotypical anomalies and the general mechanism of left–right differentiation of vertebrate visceral and brain laterality. Next, we systematically review the available human studies that explored the prevalence of atypical behavioral and brain asymmetry in visceral situs anomalies, which almost exclusively involved participants with the mirrored visceral organization (situs inversus). The data show no direct link between human visceral and brain functional laterality as most participants with situs inversus show the typical population bias for handedness and brain functional asymmetry, although an increased prevalence of functional crowding may be present. At the same time, several independent studies present evidence for a possible relation between situs inversus and the gross morphological asymmetry of the brain torque with potential differences between subtypes of situs inversus with ciliary and non-ciliary etiologies.

White matter variability, cognition, and disorders: a systematic review.

Inter-individual differences can inform treatment procedures and - if accounted for - have the potential to significantly improve patient outcomes. However, when studying brain anatomy, these inter-individual variations are commonly unaccounted for, despite reports of differences in gross anatomical features, cross-sectional and connectional anatomy. Brain connections are essential to facilitate functional organisation and, when severed, cause impairments or complete loss of function. Hence the study of cerebral white matter may be an ideal compromise to capture inter-individual variability in structure and function. We reviewed the wealth of studies that associate functions and clinical symptoms with individual tracts using diffusion tractography. Our systematic review indicates that tractography has proven to be a sensitive method in neurology, psychiatry and healthy populations to identify variability and its functional correlates. However, the literature may be biased, as we determined that the most commonly studied tracts are not necessarily those with the highest sensitivity to cognitive functions and pathologies. Additionally, the side of the studied tract is often unreported, thus neglecting functional laterality and hemispheric asymmetries. Finally, we demonstrate that tracts, as we define them, are not usually correlated with only one, but rather multiple cognitive domains or pathologies. While our systematic review identified some methodological caveats, it also suggests that tract-function correlations might be a promising biomarker for precision medicine. It characterises variations in brain anatomy, differences in functional organisation, and predicting resilience or recovery in patients.

A modality selective effect of functional laterality in pain detection sensitivity

The ability to detect environmental changes is essential to determine the appropriate reaction when facing potential threats. Both detection and reaction functions are critical to survival, and the superior performance of motor reaction for the dominant hand is well recognized in humans. However, it is not clear whether there exists laterality in sensitivity to detect external changes and whether the possible laterality is associated with sensory modality and stimulus intensity. Here, we tested whether the perceptual sensitivity and electrophysiological responses elicited by graded sensory stimuli (i.e., nociceptive somatosensory, non-nociceptive somatosensory, auditory, and visual) that were delivered on/near the left and right hands would be different for right-handed individuals. We observed that perceived intensities and most brain responses were significantly larger when nociceptive stimuli were delivered to the left side (i.e., the non-dominant hand) than to the right side (i.e., the dominant hand). No significant difference was observed between the two sides for other modalities. The higher sensitivity to detect nociceptive stimuli for the non-dominant hand would be important to provide a prompt reaction to noxious events, thus compensating for its worse motor performance. This laterality phenomenon should be considered when designing experiments for pain laboratory studies and evaluating regional sensory abnormalities for pain patients.

Lateralized sound production in the beluga whale (Delphinapterus leucas)

ABSTRACTLike other toothed whales, belugas produce sound through pneumatic actuation of two phonic lip pairs, but it is unclear whether both pairs are actuated concurrently to generate a single sound (the dual actuation hypothesis) or laterally in the production of their rich vocal repertoires. Here, using suction cup hydrophones on the head of a trained beluga whale, we measured seven different communication signal types and echolocation clicks in order to test the hypothesis that belugas produce distinct sounds unilaterally. We show that, like other delphinoids, belugas produce echolocation clicks with the right phonic lips and tonal sounds from the left. We also demonstrate for the first time that the left phonic lips are responsible for generating communication signals other than tonal sounds. Thus, our findings provide empirical support for functionalized laterality in delphinoid sound production, in keeping with the functional laterality hypothesis of vocal-motor control in toothed whales.

Voluntary Actions Modulate Perception and Neural Representation of Action-Consequences in a Hand-Dependent Manner

Evoked neural activity in sensory regions and perception of sensory stimuli are modulated when the stimuli are the consequence of voluntary movement, as opposed to an external source. It has been suggested that such modulations are due to motor commands that are sent to relevant sensory regions during voluntary movement. However, given the anatomical-functional laterality bias of the motor system, it is plausible that the pattern of such behavioral and neural modulations will also exhibit a similar bias, depending on the effector triggering the stimulus (e.g., right/left hand). Here, we examined this issue in the visual domain using behavioral and neural measures (fMRI). Healthy participants judged the relative brightness of identical visual stimuli that were either self-triggered (using right/left hand button presses), or triggered by the computer. Stimuli were presented either in the right or left visual field. Despite identical physical properties of the visual consequences, we found stronger perceptual modulations when the triggering hand was ipsi- (rather than contra-) lateral to the stimulated visual field. Additionally, fMRI responses in visual cortices differentiated between stimuli triggered by right/left hand. Our findings support a model in which voluntary actions induce sensory modulations that follow the anatomical-functional bias of the motor system.

Cutting of the rat hippocampal commissure impairs short-term memory but not long-term memory

Split-brain experiments, which have been actively conducted since the twentieth century, have provided a great deal of insight into inter-hemispheric functional laterality and interactions. However, how communication between the left and right hippocampi directly contributes to memory formation is still poorly understood. To address this issue, we cut the rat hippocampal commissure (HC) connecting the left and right hippocampi prior to behavioral tests, which comprised of four memory tasks. The result showed that cutting the HC impairs short-term memory but not long-term memory. This suggests that the HC contributes mainly to the appropriate formation of short-term memory by mediating communication between the left and right hippocampi. Our findings would help to elucidate dynamic memory formation in the hippocampus and contribute to the development of therapeutics for some neurological diseases which cause a reduction in the inter-hemispheric interaction.