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Here we present an annotation of speech in the audio-visual movie “Forrest Gump” and its audio-description for a visually impaired audience, as an addition to a large public functional brain imaging dataset ( studyforrest.org). The annotation provides information about the exact timing of each of the more than 2500 spoken sentences, 16,000 words (including 202 non-speech vocalizations), 66,000 phonemes, and their corresponding speaker. Additionally, for every word, we provide lemmatization, a simple part-of-speech-tagging (15 grammatical categories), a detailed part-of-speech tagging (43 grammatical categories), syntactic dependencies, and a semantic analysis based on word embedding which represents each word in a 300-dimensional semantic space. To validate the dataset’s quality, we build a model of hemodynamic brain activity based on information drawn from the annotation. Results suggest that the annotation’s content and quality enable independent researchers to create models of brain activity correlating with a variety of linguistic aspects under conditions of near-real-life complexity.

Background: Stroke is a devastating neurological injury, which can result in significant cognitive and behavioural deficits. Modelling the disease processes associated with stroke in animals is key to the development of novel therapeutic approaches. However, some aspects of stroke pathophysiology, including neuropsychiatric symptoms, do not translate well from humans to animals. Here, we aimed to investigate the development of post-stroke depression in a rodent model of stroke. Methods: The distal middle cerebral artery (MCA) was permanently occluded by electrocoagulation in adult male C57/Bl6/J mice. Animals were allowed to survive for 6 hours, 24 hours, 2 days, 5 days or 7 days prior to behavioural testing. Brains were taken to confirm lesion volumes at the above times. Behavioural tests studied basic exploration and motivation (open field and marble burying) as well as depression-like behaviours (tail suspension and sucrose preference). Results: Animals developed robust and reproducible lesions in the cortex but whilst stroke reduced activity in the open field, animals showed no associated behavioural deficits in any of the tests used for depression-like behaviours. Conclusions: The distal middle cerebral artery occlusion (MCAO) model results in a small cortical lesion which produces no depression-like behaviours. These negative data are important for those wishing to investigate the more cognitive and behavioural aspects of stroke.

Vascular tumors are neoplasms of endothelial cells, a significant number of which present in childhood. Recent studies have examined the mutational landscape of many subtypes of vascular tumors, identifying mutations primarily within the Ras–mitogen-activated protein kinase (MAPK) pathway and providing a unique opportunity to consider targeted therapeutics. This review will summarize the current understanding of childhood vascular tumor pathobiology.

Background: Stroke is a devastating neurological injury, which can result in significant cognitive and behavioural deficits. Modelling the disease processes associated with stroke in animals is key to the development of novel therapeutic approaches. However, some aspects of stroke pathophysiology, including neuropsychiatric symptoms, do not translate well from humans to animals. Here, we aimed to investigate the development of post-stroke depression in a rodent model of stroke. Methods: The distal middle cerebral artery (MCA) was permanently occluded by electrocoagulation in adult male C57/Bl6/J mice. Animals were allowed to survive for 6 hours, 24 hours, 2 days, 5 days or 7 days prior to behavioural testing. Brains were taken to confirm lesion volumes at the above times. Behavioural tests studied basic exploration and motivation (open field and marble burying) as well as depression-like behaviours (tail suspension and sucrose preference). Results: Animals developed robust and reproducible lesions in the cortex but whilst stroke reduced activity in the open field, animals showed no associated behavioural deficits in any of the tests used for depression-like behaviours. Conclusions: The distal middle cerebral artery occlusion (MCAO) model results in a small cortical lesion which produces no depression-like behaviours. These negative data are important for those wishing to investigate the more cognitive and behavioural aspects of stroke.

Language is key for human interactions and relies on a well-known set of brain cortical areas linked by large-scale white-matter fasciculi. However, very little is known about the ontogeny of the language network, how it is affected by very preterm birth, or how structural connectivity profiles observable before language acquisition may predispose distinct computational mechanisms associated with later language processing. Recent advances in diffusion-weighted magnetic resonance imaging and tractography are allowing researchers to provide novel, insightful understanding of the human language brain network through in vivo non-invasive investigations across the whole lifespan. Here, we propose a commentary on a series of papers which aimed to summarise the latest technological advances in neuroimaging research in order to provide future directions to study language development following very preterm birth.

In the brain of primates, the auditory cortex connects with the frontal lobe via the temporal pole (auditory ventral stream; AVS) and via the inferior parietal lobe (auditory dorsal stream; ADS). The AVS is responsible for sound recognition, and the ADS for sound-localization, voice detection and integration of calls with faces. I propose that the primary role of the ADS in non-human primates is the detection and response to contact calls. These calls are exchanged between tribe members (e.g., mother-offspring) and are used for monitoring location. Detection of contact calls occurs by the ADS identifying a voice, localizing it, and verifying that the corresponding face is out of sight. Once a contact call is detected, the primate produces a contact call in return via descending connections from the frontal lobe to a network of limbic and brainstem regions. Because the ADS of present day humans also performs speech production, I further propose an evolutionary course for the transition from contact call exchange to an early form of speech. In accordance with this model, structural changes to the ADS endowed early members of the genus Homo with partial vocal control. This development was beneficial as it enabled offspring to modify their contact calls with intonations for signaling high or low levels of distress to their mother. Eventually, individuals were capable of participating in yes-no question-answer conversations. In these conversations the offspring emitted a low-level distress call for inquiring about the safety of objects (e.g., food), and his/her mother responded with a high- or low-level distress call to signal approval or disapproval of the interaction. Gradually, the ADS and its connections with brainstem motor regions became more robust and vocal control became more volitional. Speech emerged once vocal control was sufficient for inventing novel calls.

The sequelae of post-stroke aphasia are considerable, necessitating an understanding of the functional neuroanatomy of language, cognitive processes underlying various language tasks, and the mechanisms of recovery after stroke. This knowledge is vital in providing optimal care of individuals with aphasia and counseling to their families and caregivers. The standard of care in the rehabilitation of aphasia dictates that treatment be evidence-based and person-centered. Promising techniques, such as cortical stimulation as an adjunct to behavioral therapy, are just beginning to be explored. These topics are discussed in this review.

Barrier mechanisms in the brain are important for its normal functioning and development. Stability of the brain’s internal environment, particularly with respect to its ionic composition, is a prerequisite for the fundamental basis of its function, namely transmission of nerve impulses. In addition, the appropriate and controlled supply of a wide range of nutrients such as glucose, amino acids, monocarboxylates, and vitamins is also essential for normal development and function. These are all cellular functions across the interfaces that separate the brain from the rest of the internal environment of the body. An essential morphological component of all but one of the barriers is the presence of specialized intercellular tight junctions between the cells comprising the interface: endothelial cells in the blood-brain barrier itself, cells of the arachnoid membrane, choroid plexus epithelial cells, and tanycytes (specialized glial cells) in the circumventricular organs. In the ependyma lining the cerebral ventricles in the adult brain, the cells are joined by gap junctions, which are not restrictive for intercellular movement of molecules. But in the developing brain, the forerunners of these cells form the neuroepithelium, which restricts exchange of all but the smallest molecules between cerebrospinal fluid and brain interstitial fluid because of the presence of strap junctions between the cells. The intercellular junctions in all these interfaces are the physical basis for their barrier properties. In the blood-brain barrier proper, this is combined with a paucity of vesicular transport that is a characteristic of other vascular beds. Without such a diffusional restrain, the cellular transport mechanisms in the barrier interfaces would be ineffective. Superimposed on these physical structures are physiological mechanisms as the cells of the interfaces contain various metabolic transporters and efflux pumps, often ATP-binding cassette (ABC) transporters, that provide an important component of the barrier functions by either preventing entry of or expelling numerous molecules including toxins, drugs, and other xenobiotics. In this review, we summarize these influx and efflux mechanisms in normal developing and adult brain, as well as indicating their likely involvement in a wide range of neuropathologies. There have been extensive attempts to overcome the barrier mechanisms that prevent the entry of many drugs of therapeutic potential into the brain. We outline those that have been tried and discuss why they may so far have been largely unsuccessful. Currently, a promising approach appears to be focal, reversible disruption of the blood-brain barrier using focused ultrasound, but more work is required to evaluate the method before it can be tried in patients. Overall, our view is that much more fundamental knowledge of barrier mechanisms and development of new experimental methods will be required before drug targeting to the brain is likely to be a successful endeavor. In addition, such studies, if applied to brain pathologies such as stroke, trauma, or multiple sclerosis, will aid in defining the contribution of brain barrier pathology to these conditions, either causative or secondary.

In the brain of primates, the auditory cortex connects with the frontal lobe via the temporal pole (auditory ventral stream; AVS) and via the inferior parietal lobe (auditory dorsal stream; ADS). The AVS is responsible for sound recognition, and the ADS for sound-localization, voice detection and integration of calls with faces. I propose that the primary role of the ADS in non-human primates is the detection and response to contact calls. These calls are exchanged between tribe members (e.g., mother-offspring) and are used for monitoring location. Detection of contact calls occurs by the ADS identifying a voice, localizing it, and verifying that the corresponding face is out of sight. Once a contact call is detected, the primate produces a contact call in return via descending connections from the frontal lobe to a network of limbic and brainstem regions. Because the ADS of present day humans also performs speech production, I further propose an evolutionary course for the transition from contact call exchange to an early form of speech. In accordance with this model, structural changes to the ADS endowed early members of the genus Homo with partial vocal control. This development was beneficial as it enabled offspring to modify their contact calls with intonations for signaling high or low levels of distress to their mother. Eventually, individuals were capable of participating in yes-no question-answer conversations. In these conversations the offspring emitted a low-level distress call for inquiring about the safety of objects (e.g., food), and his/her mother responded with a high- or low-level distress call to signal approval or disapproval of the interaction. Gradually, the ADS and its connections with brainstem motor regions became more robust and vocal control became more volitional. Speech emerged once vocal control was sufficient for inventing novel calls.

In the brain of primates, the auditory cortex connects with the frontal lobe via the temporal pole (auditory ventral stream; AVS) and via the inferior parietal lobule (auditory dorsal stream; ADS). The AVS is responsible for sound recognition, and the ADS for sound-localization, voice detection and audio-visual integration. I propose that the primary role of the ADS in monkeys/apes is the perception and response to contact calls. These calls are exchanged between tribe members (e.g., mother-offspring) and are used for monitoring location. Perception of contact calls occurs by the ADS detecting a voice, localizing it, and verifying that the corresponding face is out of sight. The auditory cortex then projects to parieto-frontal visuospatial regions (visual dorsal stream) for searching the caller, and via a series of frontal lobe-brainstem connections, a contact call is produced in return. Because the human ADS processes also speech production and repetition, I further describe a course for the development of speech in humans. I propose that, due to duplication of a parietal region and its frontal projections, and strengthening of direct frontal-brainstem connections, the ADS converted auditory input directly to vocal regions in the frontal lobe, which endowed early Hominans with partial vocal control. This enabled offspring to modify their contact calls with intonations for signaling different distress levels to their mother. Vocal control could then enable question-answer conversations, by offspring emitting a low-level distress call for inquiring about the safety of objects, and mothers responding with high- or low-level distress calls. Gradually, the ADS and the direct frontal-brainstem connections became more robust and vocal control became more volitional. Eventually, individuals were capable of inventing new words and offspring were capable of inquiring about objects in their environment and learning their names via mimicry.