Brain Pathways in LIS1-Associated Lissencephaly Revealed by Diffusion MRI Tractography.

Lissencephaly (LIS) is a rare neurodevelopmental disorder with severe symptoms caused by abnormal neuronal migration during cortical development. It is caused by both genetic and non-genetic factors. Despite frequent studies about the cortex, comprehensive elucidation of structural abnormalities and their effects on the white matter is limited. The main objective of this study is to analyze abnormal neuronal migration pathways and white matter fiber organization in LIS1-associated LIS using diffusion MRI (dMRI) tractography. For this purpose, slabs of brain specimens with LIS (n = 3) and age and sex-matched controls (n = 4) were scanned with 3T dMRI. Our high-resolution ex vivo dMRI successfully identified common abnormalities across the samples. The results revealed an abnormal increase in radially oriented subcortical fibers likely associated with radial migration pathways and u-fibers and a decrease in association fibers in all LIS specimens.

Striatum-projecting prefrontal cortex neurons support working memory maintenance.

Neurons in the medial prefrontal cortex (mPFC) are functionally linked to working memory (WM) but how distinct projection pathways contribute to WM remains unclear. Based on optical recordings, optogenetic perturbations, and pharmacological interventions in male mice, we report here that dorsomedial striatum (dmStr)-projecting mPFC neurons are essential for WM maintenance, but not encoding or retrieval, in a T-maze spatial memory task. Fiber photometry of GCaMP6m-labeled mPFC→dmStr neurons revealed strongest activity during the maintenance period, and optogenetic inhibition of these neurons impaired performance only when applied during this period. Conversely, enhancing mPFC→dmStr pathway activity-via pharmacological suppression of HCN1 or by optogenetic activation during the maintenance period-alleviated WM impairment induced by NMDA receptor blockade. Moreover, cellular-resolution miniscope imaging revealed that >50% of mPFC→dmStr neurons are active during WM maintenance and that this subpopulation is distinct from neurons active during encoding and retrieval. In all task periods, neuronal sequences were evident. Striatum-projecting mPFC neurons thus critically contribute to spatial WM maintenance.

The primitive brain of early Homo.

The brains of modern humans differ from those of great apes in size, shape, and cortical organization, notably in frontal lobe areas involved in complex cognitive tasks, such as social cognition, tool use, and language. When these differences arose during human evolution is a question of ongoing debate. Here, we show that the brains of early Homo from Africa and Western Asia (Dmanisi) retained a primitive, great ape-like organization of the frontal lobe. By contrast, African Homo younger than 1.5 million years ago, as well as all Southeast Asian Homo erectus, exhibited a more derived, humanlike brain organization. Frontal lobe reorganization, once considered a hallmark of earliest Homo in Africa, thus evolved comparatively late, and long after Homo first dispersed from Africa.

Evidence for independent brain and neurocranial reorganization during hominin evolution.

Throughout hominin evolution, the brain of our ancestors underwent a 3-fold increase in size and substantial structural reorganization. However, inferring brain reorganization from fossil hominin neurocrania (=braincases) remains a challenge, above all because comparative data relating brain to neurocranial structures in living humans and great apes are still scarce. Here we use MRI and same-subject spatially aligned computed tomography (CT) and MRI data of humans and chimpanzees to quantify the spatial relationships between these structures, both within and across species. Results indicate that evolutionary changes in brain and neurocranial structures are largely independent of each other. The brains of humans compared to chimpanzees exhibit a characteristic posterior shift of the inferior pre- and postcentral gyri, indicative of reorganization of the frontal opercular region. Changes in human neurocranial structure do not reflect cortical reorganization. Rather, they reflect constraints related to increased encephalization and obligate bipedalism, resulting in relative enlargement of the parietal bones and anterior displacement of the cerebellar fossa. This implies that the relative position and size of neurocranial bones, as well as overall endocranial shape (e.g., globularity), should not be used to make inferences about evolutionary changes in the relative size or reorganization of adjacent cortical regions of fossil hominins.

Identification of in vivo Sulci on the External Surface of Eight Adult Chimpanzee Brains: Implications for Interpreting Early Hominin Endocasts.

The only direct source of information about hominin brain evolution comes from the fossil record of endocranial casts (endocasts) that reproduce details of the external morphology of the brain imprinted on the walls of the braincase during life. Surface traces of sulci that separate the brain's convolutions (gyri) are reproduced sporadically on early hominin endocasts. Paleoneurologists rely heavily on published descriptions of sulci on brains of great apes, especially chimpanzees (humans' phylogenetically closest living relatives), to guide their identifications of sulci on ape-sized hominin endocasts. However, the few comprehensive descriptions of cortical sulci published for chimpanzees usually relied on post mortem brains, (now) antiquated terminology for some sulci, and photographs or line drawings from limited perspectives (typically right or left lateral views). The shortage of adequate descriptions of chimpanzee sulcal patterns partly explains why the identities of certain sulci on australopithecine endocasts (e.g., the inferior frontal and middle frontal sulci) have been controversial. Here, we provide images of lateral and dorsal surfaces of 16 hemispheres from 4 male and 4 female adult chimpanzee brains that were obtained using in vivo magnetic resonance imaging. Sulci on the exposed surfaces of the frontal, parietal, temporal, and occipital lobes are identified on the images based on their locations, positions relative to each other, and homologies known from comparative studies of cytoarchitecture in primates. These images and sulcal identifications exceed the quantity and quality of previously published illustrations of chimpanzee brains with comprehensively labeled sulci and, thus, provide a larger number of examples for identifying sulci on hominin endocasts than hitherto available. Our findings, even in a small sample like the present one, overturn published claims that australopithecine endocasts reproduce derived configurations of certain sulci in their frontal lobes that never appear on chimpanzee brains. The sulcal patterns in these new images also suggest that changes in two gyri that bridge between the parietal and occipital lobes may have contributed to cortical reorganization in early hominins. It is our hope that these labeled in vivo chimpanzee brains will assist future researchers in identifying sulci on hominin endocasts, which is a necessary first step in the quest to learn how and when the external morphology of the human cerebral cortex evolved from apelike precursors.