Epilepsy is a common neurological disorder, and mutations in genes encoding ion channels or neurotransmitter receptors are frequent causes of monogenic forms of epilepsy. Here we show that abnormal expansions of TTTCA and TTTTA repeats in intron 4 of SAMD12 cause benign adult familial myoclonic epilepsy (BAFME). Single-molecule, real-time sequencing of BAC clones and nanopore sequencing of genomic DNA identified two repeat configurations in SAMD12. Intriguingly, in two families with a clinical diagnosis of BAFME in which no repeat expansions in SAMD12 were observed, we identified similar expansions of TTTCA and TTTTA repeats in introns of TNRC6A and RAPGEF2, indicating that expansions of the same repeat motifs are involved in the pathogenesis of BAFME regardless of the genes in which the expanded repeats are located. This discovery that expansions of noncoding repeats lead to neuronal dysfunction responsible for myoclonic tremor and epilepsy extends the understanding of diseases with such repeat expansion.

Functional brain organization of macaque monkeys and humans was directly compared by functional magnetic resonance imaging. Subjects of both species performed a modified Wisconsin Card Sorting Test that required behavioral flexibility in the form of cognitive set shifting. Equivalent visual stimuli and task sequence were used for the two species. We found transient activation related to cognitive set shifting in focal regions of prefrontal cortex in both monkeys and humans. These functional homologs were located in cytoarchitectonically equivalent regions in the posterior part of ventrolateral prefrontal cortex. This comparative imaging provides insights into the evolution of cognition in primates.

Functional organization of human cerebral hemispheres is asymmetrically specialized, most typically along a verbal͞nonverbal axis. In this event-related functional MRI study, we report another example of the asymmetrical specialization. Set-shifting paradigms derived from the Wisconsin card sorting test were used, where subjects update one behavior to another on the basis of environmental feedback. The cognitive requirements constituting the paradigms were decomposed into two components according to temporal stages of task events. Double dissociation of the component brain activity was found in the three bilateral pairs of regions in the lateral frontal cortex, the right regions being activated during exposure to negative feedback and the corresponding left regions being activated during updating of behavior, to suggest that both hemispheres contribute to cognitive set shifting but in different ways. The asymmetrical hemispheric specialization within the same paradigms further implies an interhemispheric interaction of these task components that achieve a common goal.