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Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We resampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers compared to right-handers showed average differences of surface area asymmetry within the fusiform cortex, the anterior insula, the anterior middle cingulate cortex, and the precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries. Implicated genes included six encoding microtubule-related proteins: TUBB, TUBA1B, TUBB3, TUBB4A, MAP2, and NME7—mutations in the latter can cause left to right reversal of the visceral organs. There were also two cortical regions where average thickness asymmetry was altered in lef-thandedness: on the postcentral gyrus and the inferior occipital cortex, functionally annotated with hand sensorimotor and visual roles. These cortical thickness asymmetries were not heritable. Heritable surface area asymmetries of language-related regions may link the etiologies of hand preference and language, whereas nonheritable asymmetries of sensorimotor cortex may manifest as consequences of hand preference.

The valuation of food is a fundamental component of our decision-making. Yet little is known about how value signals for food and other rewards are constructed by the brain. Using a food-based decision task in human participants, we found that subjective values can be predicted from beliefs about constituent nutritive attributes of food: protein, fat, carbohydrates and vitamin content. Multivariate analyses of functional MRI data demonstrated that, while food value is represented in patterns of neural activity in both medial and lateral parts of the orbitofrontal cortex (OFC), only the lateral OFC represents the elemental nutritive attributes. Effective connectivity analyses further indicate that information about the nutritive attributes represented in the lateral OFC is integrated within the medial OFC to compute an overall value. These findings provide a mechanistic account for the construction of food value from its constituent nutrients. Suzuki et al. found that food valuation is related to beliefs about nutritive attributes. Functional MRI revealed these attribute codes in lateral orbitofrontal cortex, suggesting a mechanism by which value signals are constructed from constituent attributes.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Previous research has associated alpha-band [8–12 Hz] oscillations with inhibitory functions: for instance, several studies showed that visual attention increases alpha-band power in the hemisphere ipsilateral to the attended location. However, other studies demonstrated that alpha oscillations positively correlate with visual perception, hinting at different processes underlying their dynamics. Here, using an approach based on traveling waves, we demonstrate that there are two functionally distinct alpha-band oscillations propagating in different directions. We analyzed EEG recordings from three datasets of human participants performing a covert visual attention task (one new dataset with N = 16, two previously published datasets with N = 16 and N = 31). Participants were instructed to detect a brief target by covertly attending to the screen’s left or right side. Our analysis reveals two distinct processes: allocating attention to one hemifield increases top-down alpha-band waves propagating from frontal to occipital regions ipsilateral to the attended location, both with and without visual stimulation. These top-down oscillatory waves correlate positively with alpha-band power in frontal and occipital regions. Yet, different alpha-band waves propagate from occipital to frontal regions and contralateral to the attended location. Crucially, these forward waves were present only during visual stimulation, suggesting a separate mechanism related to visual processing. Together, these results reveal two distinct processes reflected by different propagation directions, demonstrating the importance of considering oscillations as traveling waves when characterizing their functional role.

A group of transcriptionally defined spinal neurons, V0 neurons, are identified as necessary for the control of normal alternation of left and right limbs in mice. Locomotion step change derives from V0 neurons Locomotion involves coordinated and sequential activation of neurons and muscles on both sides of the body. Ole Kiehn and colleagues identify a group of transcriptionally defined spinal neurons, the V0 neurons derived from the p0 progenitor domain of the ventral spinal chord, as being responsible for controlling alternation of left and right limbs in mouse. Both excitatory and inhibitory V0 neurons exist, and ablation of individual populations selectively impairs alternation at different locomotion speeds. All forms of locomotion are repetitive motor activities that require coordinated bilateral activation of muscles. The executive elements of locomotor control are networks of spinal neurons that determine gait pattern through the sequential activation of motor-neuron pools on either side of the body axis 1 , 2 , 3 , 4 . However, little is known about the constraints that link left–right coordination to locomotor speed. Recent advances have indicated that both excitatory and inhibitory commissural neurons may be involved in left–right coordination 5 , 6 , 7 . But the neural underpinnings of this, and a possible causal link between these different groups of commissural neurons and left–right alternation, are lacking. Here we show, using intersectional mouse genetics, that ablation of a group of transcriptionally defined commissural neurons—the V0 population—leads to a quadrupedal hopping at all frequencies of locomotion. The selective ablation of inhibitory V0 neurons leads to a lack of left–right pattern at low frequencies, mixed coordination at medium frequencies, and alternation at high locomotor frequencies. When ablation is targeted to excitatory V0 neurons, left–right alternation is present at low frequencies, and hopping is restricted to medium and high locomotor frequencies. Therefore, the intrinsic logic of the central control of locomotion incorporates a modular organization, with two subgroups of V0 neurons required for the existence of left–right alternating modes at different speeds of locomotion. The two molecularly distinct sets of commissural neurons may constrain species-related naturally occurring frequency-dependent coordination and be involved in the evolution of different gaits.

Genetically identical individuals display variability in their physiology, morphology, and behaviors, even when reared in essentially identical environments, but there is little mechanistic understanding of the basis of such variation. Here, we investigated whether Drosophila melanogaster displays individual-to-individual variation in locomotor behaviors. We developed a new high-throughout platform capable of measuring the exploratory behavior of hundreds of individual flies simultaneously. With this approach, we find that, during exploratory walking, individual flies exhibit significant bias in their left vs. right locomotor choices, with some flies being strongly left biased or right biased. This idiosyncrasy was present in all genotypes examined, including wild-derived populations and inbred isogenic laboratory strains. The biases of individual flies persist for their lifetime and are nonheritable: i.e., mating two left-biased individuals does not yield left-biased progeny. This locomotor handedness is uncorrelated with other asymmetries, such as the handedness of gut twisting, leg-length asymmetry, and wing-folding preference. Using transgenics and mutants, we find that the magnitude of locomotor handedness is under the control of columnar neurons within the central complex, a brain region implicated in motor planning and execution. When these neurons are silenced, exploratory laterality increases, with more extreme leftiness and rightiness. This observation intriguingly implies that the brain may be able to dynamically regulate behavioral individuality. Significance Genetically identical individuals display variability in their behaviors even when reared in essentially identical environments. This variation underlies both personality and individuality, but there is little mechanistic understanding of how such differences arise. Here, we investigated individual-to-individual variation in locomotor behaviors of fruit flies. Surprisingly, individual flies exhibit significant bias in their left vs. right locomotor choices during exploratory locomotion, with some flies being strongly left biased or right biased. Using the Drosophila genetic toolkit, we find that the magnitude of locomotor handedness is under the control of neurons within a brain region implicated in motor planning and execution. This observation intriguingly implies that the brain may be able to dynamically regulate behavioral individuality.

Knowledge of amygdalar and hippocampal development as they pertain to sex differences and laterality would help to understand not only brain development but also the relationship between brain volume and brain functions. However, few studies investigated development of these two regions, especially during infancy. The purpose of this study was to examine typical volumetric trajectories of amygdala and hippocampus from infancy to early adulthood by predicting sexual dimorphism and laterality. We performed a cross-sectional morphometric MRI study of amygdalar and hippocampal growth from 1 month to 25 years old, using 109 healthy individuals. The findings indicated significant non-linear age-related volume changes, especially during the first few years of life, in both the amygdala and hippocampus regardless of sex. The peak ages of amygdalar and hippocampal volumes came at the timing of preadolescence (9-11 years old). The female amygdala reached its peak age about one year and a half earlier than the male amygdala did. In addition, its rate of growth change decreased earlier in the females. Furthermore, both females and males displayed rightward laterality in the hippocampus, but only the males in the amygdala. The robust growth of the amygdala and hippocampus during infancy highlight the importance of this period for neural and functional development. The sex differences and laterality during development of these two regions suggest that sex-related factors such as sex hormones and functional laterality might affect brain development.

Oligodendrocytes form myelin sheaths and provide metabolic support to axons. Using in vivo genetic fate tracing in a mouse model of amyotrophic lateral sclerosis (ALS), this study shows that there is extensive degeneration of oligodendrocytes near motor neurons prior to behavioral manifestation of disease. Although oligodendrocytes were regenerated from resident progenitors, they failed to mature and restore myelin, a feature also observed in brain and spinal cord tissue from ALS patients. Selective deletion of ALS-linked mutant SOD1 from the oligodendrocyte lineage greatly delayed disease onset, suggesting that this mutant protein impairs their ability to support motor neurons. Oligodendrocytes associate with axons to establish myelin and provide metabolic support to neurons. In the spinal cord of amyotrophic lateral sclerosis (ALS) mice, oligodendrocytes downregulate transporters that transfer glycolytic substrates to neurons and oligodendrocyte progenitors (NG2 + cells) exhibit enhanced proliferation and differentiation, although the cause of these changes in oligodendroglia is unknown. We found extensive degeneration of gray matter oligodendrocytes in the spinal cord of SOD1 (G93A) ALS mice prior to disease onset. Although new oligodendrocytes were formed, they failed to mature, resulting in progressive demyelination. Oligodendrocyte dysfunction was also prevalent in human ALS, as gray matter demyelination and reactive changes in NG2 + cells were observed in motor cortex and spinal cord of ALS patients. Selective removal of mutant SOD1 from oligodendroglia substantially delayed disease onset and prolonged survival in ALS mice, suggesting that ALS-linked genes enhance the vulnerability of motor neurons and accelerate disease by directly impairing the function of oligodendrocytes.

Hand preference is a prominent behavioural trait linked to human brain asymmetry. A handful of genetic variants have been reported to associate with hand preference or quantitative measures related to it. Most of these reports were on the basis of limited sample sizes, by current standards for genetic analysis of complex traits. Here we performed a genome-wide association analysis of hand preference in the large, population-based UK Biobank cohort (N = 331,037). We used gene-set enrichment analysis to investigate whether genes involved in visceral asymmetry are particularly relevant to hand preference, following one previous report. We found no evidence supporting any of the previously suggested variants or genes, nor that genes involved in visceral laterality have a role in hand preference. It remains possible that some of the previously reported genes or pathways are relevant to hand preference as assessed in other ways, or else are relevant within specific disorder populations. However, some or all of the earlier findings are likely to be false positives, and none of them appear relevant to hand preference as defined categorically in the general population. Our analysis did produce a small number of novel, significant associations, including one implicating the microtubule-associated gene MAP2 in handedness.

In most people, language is processed predominantly by the left hemisphere of the brain, but we do not know how or why. A popular view is that developmental language disorders result from a poorly lateralized brain, but until recently, evidence has been weak and indirect. Modern neuroimaging methods have made it possible to study normal and abnormal development of lateralized function in the developing brain and have confirmed links with language and literacy impairments. However, there is little evidence that weak cerebral lateralization has common genetic origins with language and literacy impairments. Our understanding of the association between atypical language lateralization and developmental disorders may benefit if we reconceptualize the nature of cerebral asymmetry to recognize its multidimensionality and consider variation in lateralization over developmental time. Contrary to popular belief, cerebral lateralization may not be a highly heritable, stable characteristic of individuals; rather, weak lateralization may be a consequence of impaired language learning.