Compensation or Preservation? Different Roles of Functional Lateralization in Speech Perception of Older Non-musicians and Musicians.

Musical training can counteract age-related decline in speech perception in noisy environments. However, it remains unclear whether older non-musicians and musicians rely on functional compensation or functional preservation to counteract the adverse effects of aging. This study utilized resting-state functional connectivity (FC) to investigate functional lateralization, a fundamental organization feature, in older musicians (OM), older non-musicians (ONM), and young non-musicians (YNM). Results showed that OM outperformed ONM and achieved comparable performance to YNM in speech-in-noise and speech-in-speech tasks. ONM exhibited reduced lateralization than YNM in lateralization index (LI) of intrahemispheric FC (LI_intra) in the cingulo-opercular network (CON) and LI of interhemispheric heterotopic FC (LI_he) in the language network (LAN). Conversely, OM showed higher neural alignment to YNM (i.e., a more similar lateralization pattern) compared to ONM in CON, LAN, frontoparietal network (FPN), dorsal attention network (DAN), and default mode network (DMN), indicating preservation of youth-like lateralization patterns due to musical experience. Furthermore, in ONM, stronger left-lateralized and lower alignment-to-young of LI_intra in the somatomotor network (SMN) and DAN and LI_he in DMN correlated with better speech performance, indicating a functional compensation mechanism. In contrast, stronger right-lateralized LI_intra in FPN and DAN and higher alignment-to-young of LI_he in LAN correlated with better performance in OM, suggesting a functional preservation mechanism. These findings highlight the differential roles of functional preservation and compensation of lateralization in speech perception in noise among elderly individuals with and without musical expertise, offering insights into successful aging theories from the lens of functional lateralization and speech perception.

A new approach to quantify asymmetry in human movement.

In this perspective paper, we propose a new approach to quantify the asymmetries in human movement. Before describing this approach, we delve into the asymmetry in human movement, often defined as the opposite of symmetry, and its implications for studying human movement. We critically examine the various methods available to quantify and describe bilateral differences, from arbitrary thresholds (such as the commonly employed 10-15% difference) to the measure of the smallest meaningful changes, and we stress the need for consideration of interindividual variability in the analysis. Our proposal centers on a straightforward metric, the probability of agreement, and a corresponding plot summarizing the agreement between measures from two limbs. Critically, the agreement between two limbs depends on the value of the clinically acceptable difference. The agreement will increase with larger values of clinically acceptable difference and decrease with smaller values of clinically acceptable difference. Data from various movements and conditions in athletes' sports training and rehabilitation are used to illustrate this approach. Our perspective provides valuable insights into the nature of asymmetry in human movement, considering that a rational understanding of asymmetry in human movement requires a thoughtful approach encompassing both statistical and clinical significance. The data and codes employed in our research are openly accessible in the supplementary materials, enabling others in the field to replicate and build upon our findings.

Modeling the association between functional connectivity and lateralization with the activity flow framework.

The human brain is localized and distributed. On the one hand, each cognitive function tends to involve one hemisphere more than the other, also known as the principle of lateralization. On the other hand, interactions among brain regions in the form of functional connectivity (FC) are indispensable for intact function. Recent years have seen growing interest in the association between lateralization and FC. However, FC metrics vary from spurious correlation to causal associations. If lateralization manifests local processing and causal network interactions, more causally valid FC metrics should predict lateralization index (LI) better than FC based on simple correlations. The present study directly investigates this hypothesis within the activity flow framework to compare the association between lateralization and four brain connectivity metrics: correlation-based FC, multiple-regression FC, partial-correlation FC, and combinedFC. We propose two modeling approaches: the one-step approach, which models the relationship between LI and FC directly, and the two-step approach, which predicts the brain activation and calculates the LI. Our results indicated that multiple-regression FC, partial-correlation FC, and combinedFC could significantly improve the model prediction compared to correlation-based FC, which was consistent in a spatial working memory task (typically right-lateralized) and a language task (typically left-lateralized). The one-step and two-step approach yielded similar conclusions. In addition, the finding was replicated in a clinical sample of schizophrenia (SZ), bipolar disorder (BP), and attention deficit hyperactivity disorder (ADHD). The present study suggests that the causal interactions among brain regions help shape the lateralization pattern.

Visual feedback decoding during bimanual circle drawing.

The between-hand interference during bimanual tasks is a consequence of the connection between the neural controllers of movement. Previous studies showed the existence of an asymmetric between-hand interference (caused by neural cross talk) when different kinematics plans were to be executed by each hand or when only one was visually guided and received perturbed visual feedback. Here, in continuous bimanual circle drawing tasks, we investigated if the central nervous system (CNS) can benefit from visual composite feedback, i.e., a weighted sum of hands' positions presented for the visually guided hand, to control the nonvisible hand. Our results demonstrated improvement in the nonvisible nondominant hand (NDH) performance in the presence of the composite feedback. When NDH was visually guided, the dominant hand's (DH) performance during asymmetric drawing deteriorated, whereas its performance during symmetric drawing improved. This indicates that the CNS's ability to leverage composite feedback, which can be the result of decoding the nonvisible hand positional information from the composite feedback, is task-dependent and can be asymmetric. Also, the nonvisible hand's performance degraded when DH or NDH was visually guided with amplified error feedback. The results of the amplified feedback condition do not strongly support the asymmetry of the interference during asymmetric circle drawing. Comparing muscle activations in the asymmetric experiment, we concluded that the observed kinematic differences were not due to alternation in muscle co-contractions.NEW & NOTEWORTHY Many daily activities involve bimanual coordination while simultaneous movement of the hands may result in interference with their movements. Here, we studied whether the central nervous system could use the relevant information in composite feedback, i.e., a weighted sum of positional information of nonvisible and visible hands, to improve the movement of the nonvisible hand. Our results suggest the ability to decode and associate task-relevant information from the composite feedback.

Functional MRI Lateralization [M1] of dlPFC and Implications for Transcranial Magnetic Stimulation (TMS) Targeting.

The present study investigates a potential method of optimizing effective strategies for the functional lateralization of the dorsolateral prefrontal cortex (dlPFC) while in a scanner. Effective hemisphere lateralization of the dlPFC is crucial for lowering the functional risks connected to specific interventions (such as neurosurgery and transcranial magnetic stimulation (TMS), as well as increasing the effectiveness of a given intervention by figuring out the optimal location. This task combines elements of creative problem solving, executive decision making based on an internal rule set, and working memory. A retrospective analysis was performed on a total of 58 unique participants (34 males, 24 females, Mage = 42.93 years, SDage = 16.38). Of these participants, 47 were classified as right-handed, 7 were classified as left-handed, and 4 were classified as ambidextrous, according to the Edinburgh Handedness Inventory. The imaging data were qualitatively judged by two trained, blinded investigators (neurologist and neuropsychologist) for dominant handedness (primary motor cortex) and dominant dorsolateral prefrontal cortex (dlPFC). The results demonstrated that 21.4% of right-handed individuals showed a dominant dlPFC localized to the right hemisphere rather than the assumed left, and 16.7% of left-handers were dominant in their left hemisphere. The task completed in the scanner might be an efficient method for localizing a potential dlPFC target for the purpose of brain stimulation (e.g., TMS), though further study replications are needed to extend and validate these findings.

Characteristics of cognitive function in patients with cerebellar infarction and its association with lesion location.

Objective: This study aimed to explore the characteristics of cognitive function in patients with cerebellar infarction and its association with lesion location. Methods: Forty-five patients with isolated cerebellar infarction were collected in the Department of Neurology, Beijing Tiantan Hospital. Thirty healthy controls were recruited matched by age and education. Global cognitive function was evaluated by using Addenbrooke's Cognitive Examination version III (ACE-III). An extensive neuropsychological assessment battery was also tested to evaluate the characteristics of each cognitive domain. 3D slicer software was used to draw the lesion, and evaluate the lesions' volume, side, and location. Group analysis was used to compare the differences in cognitive performance between patients and healthy controls, and patients with left and right cerebellar hemisphere infarction. Spearman analysis was used to explore the correlation between cognitive function and lesion volume. We also subdivided each patient's lesions according to the cerebellar atlas to identify the specific cerebellar location related to cognitive decline. Results: Patients with cerebellar infarction had a lower ACE-III score compared with the healthy group (87.9 ± 6.2 vs. 93.7 ± 2.9, p < 0.001), and 22 (48.9%) patients were diagnosed with cognitive impairment. The z-transformed score of attention and executive function in the patients' group was -0.9 ± 1.4 and -0.8 ± 1.0 respectively, with 19 (43.2%) and 23 (56.4%) patients impaired. Compared with healthy controls, the relative risk ratio with 95% confidence interval (CI) for impairment in attention and executive function were 3.24 (1.22-8.57) and 3.39 (1.45-7.89). However, only 10 (22.1%) patients showed impairment in more than two cognitive domains. Compared with the left lesion group, patients with right cerebellar infarction showed significantly impaired executive function (-1.1 ± 0.3 vs. -0.5 ± 0.2, p = 0.01). And the cerebellar posterior lobe regions, especially lobules VI, VIII, and IX, were explored to have lower cognitive performance. Furthermore, lesion volume was identified to be associated with the ACE-III score (r = -0.37, p = 0.04). Conclusion: We identified that cerebellar involvement in cognition, especially in attention processing and executive function. Cerebellar right-sided lateralization of cognition and functional topography were also revealed in the current study.

Lateralization of short-term memory in the frontal cortex.

Despite essentially symmetric structures in mammalian brains, the left and right hemispheres do not contribute equally to certain cognitive functions. How both hemispheres interact to cause this asymmetry remains unclear. Here, we study this question in the anterior lateral motor cortex (ALM) of mice performing five versions of a tactile-based decision-making task with a short-term memory (STM) component. Unilateral inhibition of ALM produces variable behavioral deficits across tasks, with the left, right, or both ALMs playing critical roles in STM. Neural activity and its encoding capability are similar across hemispheres, despite that only one hemisphere dominates in behavior. Inhibition of the dominant ALM disrupts encoding capability in the non-dominant ALM, but not vice versa. Variable behavioral deficits are predicted by the influence on contralateral activity across sessions, mice, and tasks. Together, these results reveal that the left and right ALM interact asymmetrically, leading to their differential contributions to STM.

Analysis of lateral orbitofrontal cortex activation on acquisition of fear extinction and neuronal activities in fear circuit.

Inappropriate fear expression and failure of fear extinction are commonly seen in patients with post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD). Among the patients, aberrant and asymmetric activation of the lateral orbitofrontal cortex (lOFC) is reported in some clinical cases. In this study, we aimed to examine the role of lOFC activation in extinction acquisition and explore the potential functional lateralization of lOFC on extinction. We bilaterally or unilaterally activated the lOFC with N-methyl-D-aspartate (NMDA) before fear extinction acquisition in rats. Our data suggested that both left and bilateral lOFC activation interfered with the in-session expression of conditioned fear, whereas activation of the right lOFC did not. In addition, pre-extinction unilateral or bilateral activation of the lOFC, regardless of the side, impaired the acquisition of fear extinction. We also quantified the neuronal activities during the late phase of extinction with immunohistochemical approach. Our data showed that activation of the lOFC increased the neuronal activities on the injection side(s) in the medial prefrontal cortex (mPFC), the lateral amygdala (LA), the basolateral amygdala (BLA; preferentially the non-GABAergic neurons), and the medial intercalated cells (mITC; preferentially the right side). To conclude, aberrant activation of the lOFC during extinction disturbed the excitatory/inhibitory balance of neuronal activities in fear-related brain regions, which interfered with the expression of conditioned fear and impaired the acquisition of fear extinction.

Comparative Analysis of Lateral Preferences in Patients With Resistant Schizophrenia.

Background: Schizophrenia is a chronic brain disorder of diverse etiology and clinical presentation. Despite the expansion of treatment methods, between 30 and 50% of cases remain resistant to treatment. In patients with schizophrenia, specifics in the dominant lateralization in the brain function have been discovered. This gave a reason to seek the relation between functional lateralization and the effect of treatment. Methods: Of the 105 people observed with schizophrenia, 45 (42.9%) were treatment resistant, and 60 (57.1%) were considered responders. We compared functional lateralization (hand, foot, and eye) between the two groups. Handedness was ascertained by using the Edinburgh Handedness Inventory. The assessment was made at 12 weeks of treatment. Results: Of all patients with schizophrenia, 41.89% have mixed lateralization, 53.34% are right winged, and 4.76% of the patients are left winged. Resistance of the symptoms shows that 26 (57.78%) are cross-dominated, 18 (40%) are right winged, and 1 (2.22%) is left winged. In patients with clinical remission, 18 (30%) are of mixed dominance, 38 (63.33%) are right winged, and 4 (6.66%) are left winged. From the results for the separate lateralization of the hand, foot, and eye, we found a significant difference only in terms of the dominance of the eye. In 44 (41.9%) of the patients, we found dominance of the left eye. In patients with resistance, the percentage established by us is higher-at 26 (57.8%). These results indicate that the increased percentage of mixed dominance in patients with schizophrenia is mainly due to left-sided lateralization of the eye, especially in those with resistance to treatment. Conclusion: We find an increased number of patients with cross-dominance left eye dominance in patients with schizophrenia. Cross-dominance and left eye dominance are associated with a higher probability of symptom resistance than other forms of lateralization (left-handed or right-handed). The high percentage of cross-dominance is due to the high percentage of left-sided dominance of the eye.

Callosal Fiber Length Scales with Brain Size According to Functional Lateralization, Evolution, and Development.

Brain size significantly impacts the organization of white matter fibers. Fiber length scaling, the degree to which fiber length varies according to brain size, was overlooked. We investigated how fiber lengths within the corpus callosum, the most prominent white matter tract, vary according to brain size. The results showed substantial variation in length scaling among callosal fibers, replicated in two large healthy cohorts (∼2000 human subjects, including both sexes). The underscaled callosal fibers mainly connected the precentral gyrus and parietal cortices, whereas the overscaled callosal fibers mainly connected the prefrontal cortices. The variation in such length scaling was biologically meaningful: larger scaling corresponded to larger neurite density index but smaller fractional anisotropy values; cortical regions connected by the callosal fibers with larger scaling were more lateralized functionally as well as phylogenetically and ontogenetically more recent than their counterparts. These findings highlight an interaction between interhemispheric communication and organizational and adaptive principles underlying brain development and evolution.SIGNIFICANCE STATEMENT Brain size varies across evolution, development, and individuals. Relative to small brains, the neural fiber length in large brains is inevitably increased, but the degree of such increase may differ between fiber tracts. Such a difference, if it exists, is valuable for understanding adaptive neural principles in large versus small brains during evolution and development. The present study showed a substantial difference in the length increase between the callosal fibers that connect the two hemispheres, replicated in two large healthy cohorts. Together, our study demonstrates that reorganization of interhemispheric fibers length according to brain size is intrinsically related to fiber composition, functional lateralization, cortical myelin content, and evolutionary and developmental expansion.

Do spatial and recognition memories have a lateralized processing by the dorsal hippocampus CA3?

The present study evaluated the function of the right and left CA3 of the dorsal hippocampus (dHPC) in the processing of (i) recognition memory, (ii) recent and remote spatial memory, (iii) working memory and (iv) navigation strategy. Wistar rats were divided into four experimental groups: vehicle group (VG), animals received a bilateral injection of phosphate-saline buffer (PBS) in both right and left dorsal CA3; dHPC-R group, animals received an injection of ibotenic acid (IBO) in the right dorsal CA3; dHPC-L group, animals received an IBO injection in left dorsal CA3; and dHPC-Bi group, animals received bilateral injections of IBO in both dorsal CA3. Rats were submitted to a sequence of behavioral tests: Morris water maze (MWM), object recognition test (ORT), forced T-maze and MWM 30 days after the first exposure. The results showed no evidence of functional lateralization and the dorsal CA3 does not seem to be essential for learning and memory (recent and remote) processing and allocentric navigation analyzed in the MWM and T-maze, respectively. However, rats with right or bilateral lesions in the dorsal CA3 failed to recognize the familiar object in the ORT, suggesting a lateralized processing of recognition memory. That result is unprecedented and contributes to the knowledge about the compartmentalization of HPC functions.

A novel virtual reality approach for functional lateralization in healthy adults.

Functional lateralization relates to a natural asymmetry in the dominance right or left body side, and is a fundamental principle of the brain. The hemispheres of the brain control the contralateral body side, and show subtle, yet striking, anatomical asymmetries and functional lateralization. Innovative technologies, including Virtual Reality (VR), are entering the areas of experimental research, modeling and simulation related to the study of lateralization, with new perspectives of different applications in modern medical practice. Researchers/clinicians note that there are fewer VR studies with healthy participants, and which are important in evaluating/interpreting clinical outcomes, and testing the usefulness, limitations, and sensitivity of VR. The presented influence of the domination of upper/lower limbs on the performance of VR exercises was studied in healthy right-handed adults. Virtual testing sessions were performed independently with both/ dominant/ non-dominant hands, and the similar VR sessions were conduced on a Wii Balance Board (WBB) with the choice of body side, at different levels of the difficulty. The obtained results are consistent with other studies which show that cognitive-motor training in VR with the WBB platform is a very sensitive and promising tool for recognizing/assessing functional asymmetries of the right-left body side not only in disturbed lateralization, but also in the test training of healthy subjects.

Fronto-temporal cortical atrophy in 'nyaope' combination heroin and cannabis use disorder.

Sub-Saharan Africa is one of the top three regions with the highest rates of opioid-related premature mortality. Nyaope is the street name for what is believed to be a drug cocktail in South Africa although recent research suggests that it is predominantly heroin. Nyaope powder is most commonly smoked together with cannabis, a drug-use pattern unique to the region. Due to the increasing burden of this drug in low-income communities and the absence of human structural neuroimaging data of combination heroin and cannabis use disorder, we initiated an important cohort study in order to identify neuroanatomical sequelae. Twenty-eight male nyaope users and thirty healthy, matched controls were recruited from drug rehabilitation centers and the community, respectively. T1-weighted MRI images were obtained using a 3 T General Electric Discovery and cortical thickness was examined and compared. Nyaope users displayed extensive grey matter atrophy in the right hemispheric medial orbitofrontal, rostral middle frontal, superior temporal, superior frontal, and supramarginal gyri (two-sided t-test, p < 0.05, corrected for multiple comparisons). Our findings indicate cortical abnormality in nyaope users in regions involved in impulse control, decision making, social- and self-perception, and working memory. Importantly, affected brain regions show large overlap with the pattern of cortical abnormalities shown in heroin use disorder.

Hemispheric Lateralization of Visuospatial Attention Is Independent of Language Production on Right-Handers: Evidence From Functional Near-Infrared Spectroscopy.

It is well-established that visuospatial attention is mainly lateralized to the right hemisphere, whereas language production is mainly left-lateralized. However, there is a significant controversy regarding how these two kinds of lateralization interact with each other. The present research used functional near-infrared spectroscopy (fNIRS) to examine whether visuospatial attention is indeed right-lateralized, whereas language production is left-lateralized, and more importantly, whether the extent of lateralization in the visuospatial task is correlated with that in the task involving language. Specifically, fifty-two healthy right-handed participants participated in this study. Multiple-channel fNIRS technique was utilized to record the cerebral hemodynamic changes when participants were engaged in naming objects depicted in pictures (the picture naming task) or judging whether a presented line was bisected correctly (the landmark task). The degree of hemispheric lateralization was quantified according to the activation difference between the left and right hemispheres. We found that the picture-naming task predominantly activated the inferior frontal gyrus (IFG) of the left hemisphere. In contrast, the landmark task predominantly activated the inferior parietal sulcus (IPS) and superior parietal lobule (SPL) of the right hemisphere. The quantitative calculation of the laterality index also showed a left-lateralized distribution for the picture-naming task and a right-lateralized distribution for the landmark task. Intriguingly, the correlation analysis revealed no significant correlation between the laterality indices of these two tasks. Our findings support the independent hypothesis, suggesting that different cognitive tasks may engender lateralized processing in the brain, but these lateralized activities may be independent of each other. Meanwhile, we stress the importance of handedness in understanding the relationship between functional asymmetries. Methodologically, we demonstrated the effectiveness of using the multichannel fNIRS technique to investigate the hemispheric specialization of different cognitive tasks and their lateralization relations between different tasks. Our findings and methods may have important implications for future research to explore lateralization-related issues in individuals with neural pathologies.

Left and right hemispheric lateralization of the amygdala in pain.

Hemispheric asymmetries within the brain have been identified across taxa and have been extensively studied since the early 19th century. Here, we discuss lateralization of a brain structure, the amygdala, and how this lateralization is reshaping how we understand the role of the amygdala in pain processing. The amygdala is an almond-shaped, bilateral brain structure located within the limbic system. Historically, the amygdala was known to have a role in the processing of emotions and attaching emotional valence to memories and other experiences. The amygdala has been extensively studied in fear conditioning and affect but recently has been shown to have an important role in processing noxious information and impacting pain. The amygdala is composed of multiple nuclei; of special interest is the central nucleus of the amygdala (CeA). The CeA receives direct nociceptive inputs from the parabrachial nucleus (PBN) through the spino-parabrachio-amygdaloid pathway as well as more highly processed cortical and thalamic input via the lateral and basolateral amygdala. Although the amygdala is a bilateral brain region, most data investigating the amygdala's role in pain have been generated from the right CeA, which has an overwhelmingly pro-nociceptive function across pain models. The left CeA has often been characterized to have no effect on pain modulation, a dampened pro-nociceptive function, or most recently an anti-nociceptive function. This review explores the current literature on CeA lateralization and the hemispheres' respective roles in the processing and modulation of different forms of pain.

Mental Shopping Calculations: A Transcranial Magnetic Stimulation Study.

One of the most critical skills behind consumer's behavior is the ability to assess whether a price after a discount is a real bargain. Yet, the neural underpinnings and cognitive mechanisms associated with such a skill are largely unknown. While there is general agreement that the posterior parietal cortex (PPC) on the left is critical for mental calculations, and there is also recent repetitive transcranial magnetic stimulation (rTMS) evidence pointing to the supramarginal gyrus (SMG) of the right PPC as crucial for consumer-like arithmetic (e.g., multi-digit mental addition or subtraction), it is still unknown whether SMG is involved in calculations of sale prices. Here, we show that the neural mechanisms underlying discount arithmetic characteristic for shopping are different from complex addition or subtraction, with discount calculations engaging left SMG more. We obtained these outcomes by remodeling our laboratory to resemble a shop and asking participants to calculate prices after discounts (e.g., $8.80-25 or $4.80-75%), while stimulating left and right SMG with neuronavigated rTMS. Our results indicate that such complex shopping calculations as establishing the price after a discount involve SMG asymmetrically, whereas simpler calculations such as price addition do not. These findings have some consequences for neural models of mathematical cognition and shed some preliminary light on potential consumer's behavior in natural settings.

Phenotypes in hemispheric functional segregation? Perspectives and challenges.

Directional hemispheric dominance has been established for numerous cognitive functions in the human brain. Strong population biases with some functions favoring the left and others the right hemisphere generated the popular idea of an advantageous prototypical division of labor between both halves of the brain, molded by evolution and genetically blueprinted. As most empirical studies on functional lateralization focused on a single function at a time, little is known about the relation between different asymmetric functions and the consequences of atypical functional segregation in healthy individuals. Recent investigations suggest the existence of at least three different phenotypes in human functional segregation relevant for future neuroscientific and genetic research. Using atypical language dominance as a starting point, I summarize the existing literature about its behavioral and neural consequences and explore the evidence for intermediate phenotypes in brain functional segregation that could bridge behavioral and genetic data.