S. C. Vance

. Here we report a comprehensive and high-resolution transcriptomic and spatial cell-type atlas for the whole adult mouse brain. The cell-type atlas was created by combining a single-cell RNA-sequencing (scRNA-seq) dataset of around 7 million cells profiled (approximately 4.0 million cells passing quality control), and a spatial transcriptomic dataset of approximately 4.3 million cells using multiplexed error-robust fluorescence in situ hybridization (MERFISH). The atlas is hierarchically organized into 4 nested levels of classification: 34 classes, 338 subclasses, 1,201 supertypes and 5,322 clusters. We present an online platform, Allen Brain Cell Atlas, to visualize the mouse whole-brain cell-type atlas along with the single-cell RNA-sequencing and MERFISH datasets. We systematically analysed the neuronal and non-neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The results reveal unique features of cell-type organization in different brain regions-in particular, a dichotomy between the dorsal and ventral parts of the brain. The dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other. Our study also uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types. Finally, we found that transcription factors are major determinants of cell-type classification and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. The whole mouse brain transcriptomic and spatial cell-type atlas establishes a benchmark reference atlas and a foundational resource for integrative investigations of cellular and circuit function, development and evolution of the mammalian brain.

Using data derived from a 15-year follow-up study of 520 veterans surviving penetrating brain wounds received in the Vietnam war, we have developed a predictive formula and tables for posttraumatic epilepsy based on time elapsed postinjury and presence of specific clinical and computed tomographic scan risk factors. Such patients remain at some increased risk for epilepsy even ten to 15 years postinjury, although most can be 95% certain of avoiding epilepsy if they have been seizure free for three years posttrauma. Epilepsy onset latency was independent of any risk factors identified.

We examined the relationship of preinjury intelligence, a lesion-severity variable (brain-tissue loss volume), and lesion location to the persistence of cognitive deficits in Vietnam veterans with penetrating brain wounds. Using stepwise multiple linear regression procedures, we found that preinjury intelligence predicted a significant amount of the variance on postinjury cognitive testing, being a better predictor for tests requiring a number of complementary cognitive processes (e.g., intelligence tests) than for tests measuring a specific cognitive process (e.g., face recognition). Brain-tissue volume loss was found to play a larger role when a global cognitive measure was used, but a smaller role when a specific cognitive process was measured. Finally, lesion location was shown to be a significant predictor of performance only for specific cognitive processes. Nevertheless, preinjury intelligence/education appears to play an even larger role in postinjury performance than either brain-tissue loss volume or a particular structural loss.

We compared the neurologic and cognitive performance of 15 young veterans who suffered unilateral penetrating missile wounds to the basal forebrain 15 years ago in the Vietnam War with uninjured controls and patients with lesions elsewhere in the brain. The subjects performed worse on tests of episodic memory, reasoning, and arithmetic and had more prolonged unconsciousness after injury; but their performance usually compared favorably with that of uninjured controls on tests of intelligence, attention, and language and was not consistent with that of a demented patient. The data suggest that the basal forebrain is functionally related to the reticular formation and to the basal forebrain is functionally related to the reticular formation and to the limbic-hippocampal memory system.

Persistent memory problems were reported by a 39-year-old man who suffered a penetrating brain wound while serving in Vietnam 15 years earlier. Neuropsychological testing indicated an unusually isolated memory impairment. Computed tomography revealed transection of the columns of the fornix cerebri with no temporal-lobe involvement and minimal thalamic damage. We suggest that the fornix cerebri has a role in the maintenance of information accessibility to both encoding and recall during post-working memory processing and in the organization of verbal information during encoding and/or retrieval for declarative (recall) purposes. These processes are not essential for verbal recognition but can result in decrements on specific laboratory tasks and in social adjustment.