@article {123, title = {Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke.}, journal = {Brain}, volume = {139}, year = {2016}, month = {2016 Jan}, pages = {259-75}, abstract = {

There is an urgent need for a therapy that reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. We show here that intramuscular delivery of neurotrophin-3 (NT3, encoded by NTF3) can induce sensorimotor recovery when treatment is initiated 24 h after stroke. Specifically, in two randomized, blinded preclinical trials, we show improved sensory and locomotor function in adult (6 months) and elderly (18 months) rats treated 24 h following cortical ischaemic stroke with human NT3 delivered using a clinically approved serotype of adeno-associated viral vector (AAV1). Importantly, AAV1-hNT3 was given in a clinically-feasible timeframe using a straightforward, targeted route (injections into disabled forelimb muscles). Magnetic resonance imaging and histology showed that recovery was not due to neuroprotection, as expected given the delayed treatment. Rather, treatment caused corticospinal axons from the less affected hemisphere to sprout in the spinal cord. This treatment is the first gene therapy that reverses disability after stroke when administered intramuscularly in an elderly body. Importantly, phase I and II clinical trials by others show that repeated, peripherally administered high doses of recombinant NT3 are safe and well tolerated in humans with other conditions. This paves the way for NT3 as a therapy for stroke.

}, keywords = {Adenoviridae, Age Factors, Animals, Endothelin-1, Female, Genetic Vectors, Humans, Injections, Intramuscular, Locomotion, Magnetic Resonance Imaging, Microinjections, Muscle, Skeletal, Neuroimaging, Neurotrophin 3, Pyramidal Tracts, Rats, Recovery of Function, Spinal Cord, Stroke, Time Factors}, issn = {1460-2156}, doi = {10.1093/brain/awv341}, author = {Duricki, Denise A and Hutson, Thomas H and Kathe, Claudia and Soleman, Sara and Gonzalez-Carter, Daniel and Petruska, Jeffrey C and Shine, H David and Chen, Qin and Wood, Tobias C and Bernanos, Michel and Cash, Diana and Williams, Steven C R and Gage, Fred H and Moon, Lawrence D F} } @article {183, title = {Selection of distinct populations of dentate granule cells in response to inputs as a mechanism for pattern separation in mice.}, journal = {Elife}, volume = {2}, year = {2013}, month = {2013}, pages = {e00312}, abstract = {

The hippocampus is critical for episodic memory and computational studies have predicted specific functions for each hippocampal subregion. Particularly, the dentate gyrus (DG) is hypothesized to perform pattern separation by forming distinct representations of similar inputs. How pattern separation is achieved by the DG remains largely unclear. By examining neuronal activities at a population level, we revealed that, unlike CA1 neuron populations, dentate granule cell (DGC) ensembles activated by learning were not preferentially reactivated by memory recall. Moreover, when mice encountered an environment to which they had not been previously exposed, a novel DGC population-rather than the previously activated DGC ensembles that responded to past events-was selected to represent the new environmental inputs. This selection of a novel responsive DGC population could be triggered by small changes in environmental inputs. Therefore, selecting distinct DGC populations to represent similar but not identical inputs is a mechanism for pattern separation. DOI:http://dx.doi.org/10.7554/eLife.00312.001.

}, keywords = {Animals, Behavior, Animal, Brain Mapping, CA1 Region, Hippocampal, Conditioning (Psychology), Cues, Dentate Gyrus, Environment, Fear, Gene Expression Regulation, Genes, Reporter, Memory, Memory, Episodic, Mental Recall, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Neural Pathways, Neurons, Pattern Recognition, Physiological, Time Factors}, issn = {2050-084X}, doi = {10.7554/eLife.00312}, author = {Deng, Wei and Mayford, Mark and Gage, Fred H} } @article {190, title = {Signed words in the congenitally deaf evoke typical late lexicosemantic responses with no early visual responses in left superior temporal cortex.}, journal = {J Neurosci}, volume = {32}, year = {2012}, month = {2012 Jul 11}, pages = {9700-5}, abstract = {

Congenitally deaf individuals receive little or no auditory input, and when raised by deaf parents, they acquire sign as their native and primary language. We asked two questions regarding how the deaf brain in humans adapts to sensory deprivation: (1) is meaning extracted and integrated from signs using the same classical left hemisphere frontotemporal network used for speech in hearing individuals, and (2) in deafness, is superior temporal cortex encompassing primary and secondary auditory regions reorganized to receive and process visual sensory information at short latencies? Using MEG constrained by individual cortical anatomy obtained with MRI, we examined an early time window associated with sensory processing and a late time window associated with lexicosemantic integration. We found that sign in deaf individuals and speech in hearing individuals activate a highly similar left frontotemporal network (including superior temporal regions surrounding auditory cortex) during lexicosemantic processing, but only speech in hearing individuals activates auditory regions during sensory processing. Thus, neural systems dedicated to processing high-level linguistic information are used for processing language regardless of modality or hearing status, and we do not find evidence for rewiring of afferent connections from visual systems to auditory cortex.

}, keywords = {Adolescent, Adult, Brain Mapping, Deafness, Evoked Potentials, Female, Functional Laterality, Humans, Magnetic Fields, Magnetic Resonance Imaging, Magnetoencephalography, Male, Photic Stimulation, Semantics, Sign Language, Temporal Lobe, Time Factors, Young Adult}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.1002-12.2012}, author = {Leonard, Matthew K and Ferjan Ramirez, Naja and Torres, Christina and Travis, Katherine E and Hatrak, Marla and Mayberry, Rachel I and Halgren, Eric} } @article {212, title = {Neural substrates of time perception and impulsivity.}, journal = {Brain Res}, volume = {1406}, year = {2011}, month = {2011 Aug 11}, pages = {43-58}, abstract = {

Several studies provide empirical evidence for the association between impulsivity and time perception. However, little is known about the neural substrates underlying this function. This investigation examined the influence of impulsivity on neural activation patterns during the encoding and reproduction of intervals with durations of 3, 9 and 18s using event-related functional magnetic resonance imaging (fMRI). Twenty-seven subjects participated in this study, including 15 high impulsive subjects that were classified based on their self-rating. FMRI activation during the duration reproduction task was correlated with measures of two self-report questionnaires related to the concept of impulsivity (Barratt Impulsiveness Scale, BIS; Zimbardo Time Perspective Inventory, ZTPI). Behaviorally, those individuals who under-reproduced temporal intervals also showed lower scores on the ZTPI future perspective subscale and higher scores on the BIS. FMRI activation revealed an accumulating pattern of neural activity peaking at the end of the 9- and 18-s intervals within right posterior insula. Activations of brain regions during the reproduction phase of the timing task, such as those related to motor execution as well as to the {\textquoteright}core control network{\textquoteright} - encompassing the inferior frontal and medial frontal cortices, the anterior insula as well as the inferior parietal cortex - were significantly correlated with reproduced duration, as well as with BIS and ZTPI subscales. In particular, the greater activation in these regions the shorter were the reproduced intervals, the more impulsive was an individual and the less pronounced the future perspective. Activation in the core control network, thus, may form a biological marker for cognitive time management and for impulsiveness.

}, keywords = {Adolescent, Brain, Brain Mapping, Female, Humans, Image Processing, Computer-Assisted, Impulsive Behavior, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Oxygen, Personality Inventory, Reaction Time, Self Report, Surveys and Questionnaires, Time Factors, Time Perception, Young Adult}, issn = {1872-6240}, doi = {10.1016/j.brainres.2011.06.048}, author = {Wittmann, Marc and Simmons, Alan N and Flagan, Taru and Lane, Scott D and Wackermann, Ji{\v r}{\'\i} and Paulus, Martin P} } @article {211, title = {Accumulation of neural activity in the posterior insula encodes the passage of time.}, journal = {Neuropsychologia}, volume = {48}, year = {2010}, month = {2010 Aug}, pages = {3110-20}, abstract = {

A number of studies have examined the perception of time with durations ranging from milliseconds to a few seconds, however the neural basis of these processes are still poorly understood and the neural substrates underlying the perception of multiple-second intervals are unknown. Here we present evidence of neural systems activity in circumscribed areas of the human brain involved in the encoding of intervals with durations of 9 and 18s in a temporal reproduction task using event-related functional magnetic resonance imaging (fMRI). During the encoding there was greater activation in more posterior parts of the medial frontal and insular cortex whereas the reproduction phase involved more anterior parts of these brain structures. Intriguingly, activation curves over time show an accumulating pattern of neural activity, which peaks at the end of the interval within bilateral posterior insula and superior temporal cortex when individuals are presented with 9- and 18-s tone intervals. This is consistent with an accumulator-type activity, which encodes duration in the multiple seconds range. Given the close connection between the dorsal posterior insula and ascending internal body signals, we suggest that the accumulation of physiological changes in body states constitutes our experience of time. This is the first time that an accumulation function in the posterior insula is detected that might be correlated with the encoding of time intervals.

}, keywords = {Adult, Analysis of Variance, Brain Mapping, Cerebral Cortex, Factor Analysis, Statistical, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Oxygen, Reaction Time, Time Factors, Time Perception, Young Adult}, issn = {1873-3514}, doi = {10.1016/j.neuropsychologia.2010.06.023}, author = {Wittmann, Marc and Simmons, Alan N and Aron, Jennifer L and Paulus, Martin P} }