Venture capitalist's early diagnosis led her to study the brain.

Humans deftly parse statistics from sequences. Some theories posit that humans learn these statistics by forming cognitive maps, or underlying representations of the latent space which links items in the sequence. Here, an item in the sequence is a node, and the probability of transitioning between two items is an edge. Sequences can then be generated from walks through the latent space, with different spaces giving rise to different sequence statistics. Individual or group differences in sequence learning can be modeled by changing the time scale over which estimates of transition probabilities are built, or in other words, by changing the amount of temporal discounting. Latent space models with temporal discounting bear a resemblance to models of navigation through Euclidean spaces. However, few explicit links have been made between predictions from Euclidean spatial navigation and neural activity during human sequence learning. Here, we use a combination of behavioral modeling and intracranial encephalo...

A fundamental challenge for the nervous system is to encode signals spanning many orders of magnitude with neurons of limited bandwidth. To meet this challenge, perceptual systems use gain control. However, whether the motor system uses an analogous mechanism is essentially unknown. Neuromodulators, such as serotonin, are prime candidates for gain control signals during force production. Serotonergic neurons project diffusely to motor pools, and, therefore, force production by one muscle should change the gain of others. Here we present behavioral and pharmaceutical evidence that serotonin modulates the input–output gain of motoneurons in humans. By selectively changing the efficacy of serotonin with drugs, we systematically modulated the amplitude of spinal reflexes. More importantly, force production in different limbs interacts systematically, as predicted by a spinal gain control mechanism. Psychophysics and pharmacology suggest that the motor system adopts gain control mechanisms, and serotonin is a p...

Nepalese in Neuroscience cofounder shares her path to the field

Semantic priming in schizophrenia is of interest because semantic memory abnormalities may play a role in numerous cognitive deficits apparent in this population (especially language processing). Behavioral investigations of semantic priming in schizophrenics have yielded mixed results, however; and brain imaging experiments have typically concentrated on sensory processes in schizophrenic brains, including preattentional auditory processing, sensory gating & correlates of sensory hallucination. We present preliminary results from a magnetoencephalography study of semantic priming in six schizophrenic adults, using a cross-modal lexical decision paradigm. Behavioral results showed normal effects of prime relatedness on reaction times, with priming for words preceded by semantically related items, and inhibition for words preceded by unrelated items. Brain data were collected at 1kHz from a 156-channel axial gradiometer system, and subjected to standard noise-reduction and averaging techniques, before being...

During rest, the cerebral cortex displays rich, coordinated patterns of spontaneous activity. The mechanism that shapes these patterns is largely unknown. Here we demonstrate that a Hebbian-like, sustained process plays a role in focusing these coherent patterns. Human subjects used an fMRI-based neurofeedback (NF) paradigm to intensely activate the dorsal anterior cingulate cortex for a single epoch (30 min). Resting-state correlations between all of the cortical voxels' BOLD time courses (functional connectivity) were mapped before, immediately after, and one day after the NF session. We found that the single epoch of cortical activation induced a lasting restructuring of the functional connections according to a Hebbian-like rule. Therefore, the change (increase and decrease) in functional connectivity strength of cortical voxels during rest reflected the level of their prior coactivation during the NF epoch. Interestingly, the effect was significantly enhanced 1 d after the NF activation epoch. The eff...

Downregulation of oligodendrocyte-related genes, referred to as oligodendrocyte dysfunction, in schizophrenia has been revealed by DNA microarray studies. Because oligodendrocyte-specific transcription factors regulate the differentiation of oligodendrocytes, genes encoding them are prime candidates for oligodendrocyte dysfunction in schizophrenia. We found that the cytosine-guanine dinucleotide (CpG) island of sex-determining region Y-box containing gene 10 ( SOX10 ), an oligodendrocyte-specific transcription factor, tended to be highly methylated in brains of patients with schizophrenia, correlated with reduced expression of SOX10 . We also found that DNA methylation status of SOX10 also was associated with other oligodendrocyte gene expressions in schizophrenia. This may be specific to SOX10 , because the CpG island of OLIG2 , which encodes another oligodendrocyte-specific transcription factor, was rarely methylated in brains, and the methylation status of myelin-associated oligodendrocytic basic protei...

CNS myelination by oligodendrocytes requires directed transport of myelin membrane components and a timely and spatially controlled membrane expansion. In this study, we show the functional involvement of the R-soluble N -ethylmaleimide-sensitive factor attachment protein receptor (R-SNARE) proteins VAMP3/cellubrevin and VAMP7/TI-VAMP in myelin membrane trafficking. VAMP3 and VAMP7 colocalize with the major myelin proteolipid protein (PLP) in recycling endosomes and late endosomes/lysosomes, respectively. Interference with VAMP3 or VAMP7 function using small interfering RNA-mediated silencing and exogenous expression of dominant-negative proteins diminished transport of PLP to the oligodendroglial cell surface. In addition, the association of PLP with myelin-like membranes produced by oligodendrocytes cocultured with cortical neurons was reduced. We furthermore identified Syntaxin-4 and Syntaxin-3 as prime acceptor Q-SNAREs of VAMP3 and VAMP7, respectively. Analysis of VAMP3-deficient mice revealed no myel...

Graduate student's research uncovers a truth about himself.

Working memory (WM) is an important cognitive domain for everyday life functioning and is often disturbed in neuropsychiatric disorders. Functional magnetic resonance imaging (fMRI) studies in humans show that distributed brain areas typically described as fronto-parietal regions are implicated in WM tasks. Based on data from a large sample of healthy young adults ( N = 1369), we applied independent component analysis (ICA) to the WM-fMRI signal and identified two distinct networks that were relevant for differences in individual WM task performance. A parietally-centered network was particularly relevant for individual differences in task measures related to WM performance (“WM dependent”) and a frontally-centered network was relevant for differences in attention-dependent task performance. Importantly, frontal areas that are typically considered as key regions for WM were either involved in both WM-dependent and attention-dependent performance, or in attention-dependent performance only. The networks ide...