The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
Inter-individual variability in perception, thought and action is frequently treated as a source of 'noise' in scientific investigations of the neural mechanisms that underlie these processes, and discarded by averaging data from a group of participants. However, recent MRI studies in the human brain show that inter-individual variability in a wide range of basic and higher cognitive functions - including perception, motor control, memory, aspects of consciousness and the ability to introspect - can be predicted from the local structure of grey and white matter as assessed by voxel-based morphometry or diffusion tensor imaging. We propose that inter-individual differences can be used as a source of information to link human behaviour and cognition to brain anatomy.
Noninvasive cortical stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have proved to be powerful tools for establishing causal relationships between brain regions and their functions. In the present study, we demonstrate that a new technique called transcranial alternating current stimulation (tACS) can interact with ongoing rhythmic activities in the visual cortex in a frequency-specific fashion and induce visual experiences (phosphenes). We delivered an oscillatory current over the occipital cortex with tACS. In order to observe interactions with ongoing cortical rhythms, we compared the effects of delivering tACS under conditions of light ("Light" condition) or darkness ("Dark" condition). Stimulation over the occipital cortex induced perception of continuously flickering light most effectively when the beta frequency range was applied in an illuminated room, whereas the most effective stimulation frequency shifted to the alpha frequency range during testing in darkness. Stimulation with theta or gamma frequencies did not produce any visual phenomena. The shift of the effective stimulation frequency indicates that the frequency dependency is caused by interactions with ongoing oscillatory activity in the stimulated cortex. Our results suggest that tACS can be used as a noninvasive tool for establishing a causal link between rhythmic cortical activities and their functions.
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