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Humans have the remarkable cognitive capacity to rapidly adapt to changing environments. Central to this capacity is the ability to form high-level, abstract representations that take advantage of regularities in the world to support generalization1. However, little is known about how these representations are encoded in populations of neurons, how they emerge through learning and how they relate to behaviour2,3. Here we characterized the representational geometry of populations of neurons (single units) recorded in the hippocampus, amygdala, medial frontal cortex and ventral temporal cortex of neurosurgical patients performing an inferential reasoning task. We found that only the neural representations formed in the hippocampus simultaneously encode several task variables in an abstract, or disentangled, format. This representational geometry is uniquely observed after patients learn to perform inference, and consists of disentangled directly observable and discovered latent task variables. Learning to perform inference by trial and error or through verbal instructions led to the formation of hippocampal representations with similar geometric properties. The observed relation between representational format and inference behaviour suggests that abstract and disentangled representational geometries are important for complex cognition.
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PURPOSE OF REVIEW: Convergent evidence from a number of neuroscience disciplines supports the hypothesis that Alzheimer's disease and other neurodegenerative disorders progress along brain networks. This review considers the role of neuroimaging in strengthening the case for network-based neurodegeneration and elucidating potential mechanisms. RECENT FINDINGS: Advances in functional and structural MRI have recently enabled the delineation of multiple large-scale distributed brain networks. The application of these network-imaging modalities to neurodegenerative disease has shown that specific disorders appear to progress along specific networks. Recent work applying theoretical measures of network efficiency to in-vivo network imaging has allowed for the development and evaluation of models of disease spread along networks. Novel MRI acquisition and analysis methods are paving the way for in-vivo assessment of the layer-specific microcircuits first targeted by neurodegenerative diseases. These methodological advances coupled with large, longitudinal studies of subjects progressing from healthy aging into dementia will enable a detailed understanding of the seeding and spread of these disorders. SUMMARY: Neuroimaging has provided ample evidence that neurodegenerative disorders progress along brain networks, and is now beginning to elucidate how they do so.
Assuntos
Encéfalo , Vias Neurais , Doenças Neurodegenerativas , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Imagem de Tensor de Difusão , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/metabolismo , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia , NeuroimagemRESUMO
Value-based decision-making requires different variables-including offer value, choice, expected outcome, and recent history-at different times in the decision process. Orbitofrontal cortex (OFC) is implicated in value-based decision-making, but it is unclear how downstream circuits read out complex OFC responses into separate representations of the relevant variables to support distinct functions at specific times. We recorded from single OFC neurons while macaque monkeys made cost-benefit decisions. Using a novel analysis, we find separable neural dimensions that selectively represent the value, choice, and expected reward of the present and previous offers. The representations are generally stable during periods of behavioral relevance, then transition abruptly at key task events and between trials. Applying new statistical methods, we show that the sensitivity, specificity and stability of the representations are greater than expected from the population's low-level features-dimensionality and temporal smoothness-alone. The separability and stability suggest a mechanism-linear summation over static synaptic weights-by which downstream circuits can select for specific variables at specific times.
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Tomada de Decisões/fisiologia , Macaca/fisiologia , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/fisiologia , Animais , Comportamento de Escolha/fisiologia , Análise Custo-Benefício , Masculino , Neurônios/fisiologiaRESUMO
Electrical microstimulation is used widely in experimental neurophysiology to examine causal links between specific brain areas and their behavioral functions and is used clinically to treat neurological and psychiatric disorders in patients. Typically, microstimulation is applied to local brain regions as a train of equally spaced current pulses. We were interested in the sensitivity of a neural circuit to a train of variably spaced pulses, as is observed in physiological spike trains. We compared the effect of fixed, decelerating, accelerating, and randomly varying microstimulation patterns on the likelihood and metrics of eye movements evoked from the frontal eye field of monkeys, while holding the mean interpulse interval constant. Our results demonstrate that the pattern of microstimulation pulses strongly influences the probability of evoking a saccade, as well as the metrics of the saccades themselves. Specifically, the pattern most closely resembling physiological spike trains (accelerating pattern) was most effective at evoking a saccade, three times more so than the least effective decelerating pattern. A saccade-triggered average of effective random trains confirmed the positive relationship between accelerating rate and efficacy. These results have important implications for the use of electrical microstimulation in both experimental and clinical settings and suggest a means to study the role of temporal pattern in the encoding of behavioral and cognitive functions.
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Mapeamento Encefálico , Estimulação Elétrica , Movimentos Sacádicos/fisiologia , Movimentos Sacádicos/efeitos da radiação , Análise de Variância , Animais , Comportamento Animal , Relação Dose-Resposta à Radiação , Macaca mulatta , Probabilidade , Tempo de Reação/efeitos da radiação , Análise de Regressão , Fatores de TempoRESUMO
From human perception to primate neurophysiology, monitoring eye position is critical to the study of vision, attention, oculomotor control, and behavior. Two principal techniques for the precise measurement of eye position-the long-standing sclera-embedded search coil and more recent optical tracking techniques-are in use in various laboratories, but no published study compares the performance of the two methods simultaneously in the same primates. Here we compare two popular systems-a sclera-embedded search coil from C-N-C Engineering and the EyeLink 1000 optical system from SR Research-by recording simultaneously from the same eye in the macaque monkey while the animal performed a simple oculomotor task. We found broad agreement between the two systems, particularly in positional accuracy during fixation, measurement of saccade amplitude, detection of fixational saccades, and sensitivity to subtle changes in eye position from trial to trial. Nonetheless, certain discrepancies persist, particularly elevated saccade peak velocities, post-saccadic ringing, influence of luminance change on reported position, and greater sample-to-sample variation in the optical system. Our study shows that optical performance now rivals that of the search coil, rendering optical systems appropriate for many if not most applications. This finding is consequential, especially for animal subjects, because the optical systems do not require invasive surgery for implantation and repair of search coils around the eye. Our data also allow laboratories using the optical system in human subjects to assess the strengths and limitations of the technique for their own applications.