Duke Institute for Brain science

Durham, NC, United States

Duke Institute for Brain science

Durham, NC, United States
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Van Hooser S.D.,Duke University | Van Hooser S.D.,Brandeis University | Roy A.,Brandeis University | Rhodes H.J.,Duke University | And 6 more authors.
Journal of Neuroscience | Year: 2013

Tree shrew primary visual cortex (V1) exhibits a pronounced laminar segregation of inputs from different classes of relay neurons in the lateral geniculate nucleus (LGN). We examined how several receptive field (RF) properties were transformed from LGN to V1 layer 4 to V1 layer 2/3. The progression of RF properties across these stages differed markedly from that found in the cat. V1 layer 4 cells are largely similar to the the LGN cells that provide their input, being dominated by a single sign (ON or OFF) and being strongly modulated by sinusoidal gratings. Some layer 4 neurons, notably those near the edges of layer 4, exhibited increased orientation selectivity, and most layer 4 neurons exhibited a preference for lower temporal frequencies. Neurons in cortical layer 2/3 differ significantly from those in the LGN; most exhibited strong orientation tuning and both ON and OFF responses. The strength of orientation selectivity exhibited a notable sublaminar organization, with the strongest orientation tuned neurons in the most superficial parts of layer 2/3. Modulation indexes provide evidence for simple and complex cells in both layer 4 and layer 2/3. However, neurons with high modulation indexes were heterogenous in the spatial organization of ON and OFF responses, with many of them exhibiting unbalanced ON and OFF responses rather than well-segregated ON and OFF subunits. When compared to the laminar organization of V1 in other mammals, these data show that the process of natural selection can result in significantly altered structure/function relationships in homologous cortical circuits. © 2013 the authors.


De Brigard F.,Duke University | De Brigard F.,Duke Institute for Brain science | Nathan Spreng R.,Cornell University | Mitchell J.P.,Harvard University | Schacter D.L.,Harvard University
NeuroImage | Year: 2015

Previous research has shown that autobiographical episodic counterfactual thinking-i.e., mental simulations about alternative ways in which one's life experiences could have occurred-engages the brain's default network (DN). However, it remains unknown whether or not the DN is also engaged during impersonal counterfactual thoughts, specifically those involving other people or objects. The current study compares brain activity during counterfactual simulations involving the self, others and objects. In addition, counterfactual thoughts involving others were manipulated in terms of similarity and familiarity with the simulated characters. The results indicate greater involvement of DN during person-based (i.e., self and other) as opposed to object-based counterfactual simulations. However, the involvement of different regions of the DN during other-based counterfactual simulations was modulated by how close and/or similar the simulated character was perceived to be by the participant. Simulations involving unfamiliar characters preferentially recruited dorsomedial prefrontal cortex. Simulations involving unfamiliar similar characters, characters with whom participants identified personality traits, recruited lateral temporal gyrus. Finally, our results also revealed differential coupling of right hippocampus with lateral prefrontal and temporal cortex during counterfactual simulations involving familiar similar others, but with left transverse temporal gyrus and medial frontal and inferior temporal gyri during counterfactual simulations involving either oneself or unfamiliar dissimilar others. These results suggest that different brain mechanisms are involved in the simulation of personal and impersonal counterfactual thoughts, and that the extent to which regions associated with autobiographical memory are recruited during the simulation of counterfactuals involving others depends on the perceived similarity and familiarity with the simulated individuals. © 2015 Elsevier Inc.


Huang X.,Max Planck Florida Institute for Neuroscience | Huang X.,Duke University | Elyada Y.M.,Max Planck Florida Institute for Neuroscience | Elyada Y.M.,Duke University | And 5 more authors.
Journal of Neuroscience | Year: 2014

Columnar organization of orientation selectivity and clustered horizontal connections linking orientation columns are two of the distinctive organizational features of primary visual cortex in many mammalian species. However, the functional role of these connections has been harder to characterize. Here we examine the extent and nature of horizontal interactions in V1 of the tree shrew using optical imaging of intrinsic signals, optogenetic stimulation, and multi-unit recording. Surprisingly, we find the effects of optogenetic stimulation depend primarily on distance and not on the specific orientation domains or axes in the cortex, which are stimulated. In addition, across a wide range of variation in both visual and optogenetic stimulation we find linear addition of the two inputs. These results emphasize that the cortex provides a rich substrate for functional interactions that are not limited to the orientation-specific interactions predicted by the monosynaptic distribution of horizontal connections. © 2014 the authors.


van Hooser S.D.,Duke University | van Hooser S.D.,Brandeis University | Li Y.,Duke University | Christensson M.,Duke University | And 6 more authors.
Journal of Neuroscience | Year: 2012

Visual experience plays a critical role in the development of direction-selective responses in ferret visual cortex. In visually naive animals, presentation of a bidirectional "training" stimulus induces rapid increases in the direction-selective responses of single neurons that can be predicted by small but significant direction biases that are present in neighboring neurons at the onset of stimulation. In this study we used in vivo two-photon imaging of calcium signals to further explore the contribution of visual experience to the emergence of directionselective responses in ferret visual cortex. The first set of experiments was designed to determine whether visual experience is required for the development of the initial neighborhood bias. In animals that were dark-reared until the time of eye opening, we found that individual neurons exhibited weak direction-selective responses accompanied by a reduced but statistically significant neighborhood bias, indicating that both features arise without the need for visual experience. The second set of experiments used a unidirectional training stimulus to assess the relative roles of the neighborhood bias and visual experience in determining the direction preference that cortical neurons acquire during direction training. We found that neurons became more responsive to the trained direction even when they were located in regions of the cortex with an initial neighborhood bias for the direction opposite the training stimulus. Together, these results suggest an adaptive developmental strategy for the elaboration of direction-selective responses, one in which experience-independent mechanisms provide a symmetry-breaking seed for the instructive effects of visual experience. © 2012 the authors.


McKinstry S.U.,Duke University | Karadeniz Y.B.,Duke University | Worthington A.K.,Duke University | Hayrapetyan V.Y.,Duke University | And 10 more authors.
Journal of Neuroscience | Year: 2014

Huntington's disease (HD) is a neurodegenerative disease caused by the expansion of a poly-glutamine (poly-Q) stretch in the huntingtin (Htt) protein. Gain-of-function effects of mutant Htt have been extensively investigated as the major driver of neurodegeneration in HD. However, loss-of-function effects of poly-Q mutations recently emerged as potential drivers of disease pathophysiology. Early synaptic problems in the excitatory cortical and striatal connections have been reported in HD, but the role of Htt protein in synaptic connectivity was unknown. Therefore, we investigated the role of Htt in synaptic connectivity in vivo by conditionally silencing Htt in the developing mouse cortex. When cortical Htt function was silenced, cortical and striatal excitatory synapses formed and matured at an accelerated pace through postnatal day 21 (P21). This exuberant synaptic connectivity was lost over time in the cortex, resulting in the deterioration of synapses by 5 weeks. Synaptic decline in the cortex was accompanied with layer- and region-specific reactive gliosis without cell loss. To determine whether the disease-causing poly-Q mutation in Htt affects synapse development, we next investigated the synaptic connectivity in a full-length knock-in mouse model of HD, the zQ175 mouse. Similar to the cortical conditional knock-outs, we found excessive excitatory synapse formation and maturation in the cortices of P21 zQ175, which was lost by 5 weeks. Together, our findings reveal that cortical Htt is required for the correct establishment of cortical and striatal excitatory circuits, and this function of Htt is lost when the mutant Htt is present. © 2014 the authors.


Chituc V.,Duke University | Henne P.,Duke University | Sinnott-Armstrong W.,Duke University | Sinnott-Armstrong W.,Duke Institute for Brain science | And 2 more authors.
Cognition | Year: 2016

Recently, psychologists have explored moral concepts including obligation, blame, and ability. While little empirical work has studied the relationships among these concepts, philosophers have widely assumed such a relationship in the principle that "ought" implies "can," which states that if someone ought to do something, then they must be able to do it. The cognitive underpinnings of these concepts are tested in the three experiments reported here. In Experiment 1, most participants judge that an agent ought to keep a promise that he is unable to keep, but only when he is to blame for the inability. Experiment 2 shows that such "ought" judgments correlate with judgments of blame, rather than with judgments of the agent's ability. Experiment 3 replicates these findings for moral "ought" judgments and finds that they do not hold for nonmoral "ought" judgments, such as what someone ought to do to fulfill their desires. These results together show that folk moral judgments do not conform to a widely assumed philosophical principle that "ought" implies "can." Instead, judgments of blame play a modulatory role in some judgments of obligation. © 2016 Elsevier B.V.


Balasubramaniam M.,Duke University | Telles S.,Indian Council of Medical Research Center for Advanced Research | Doraiswamy P.M.,Duke University | Doraiswamy P.M.,Duke Institute for Brain science
Frontiers in Psychiatry | Year: 2013

Background: The demand for clinically efficacious, safe, patient acceptable, and cost-effective forms of treatment for mental illness is growing. Several studies have demonstrated benefit from yoga in specific psychiatric symptoms and a general sense of well-being. Objective: To systematically examine the evidence for efficacy of yoga in the treatment of selected major psychiatric disorders. Methods: Electronic searches of The Cochrane Central Register of Controlled Trials and the standard bibliographic databases, MEDLINE, EMBASE, and PsycINFO, were performed through April 2011 and an updated in June 2011 using the keywords yoga AND psychiatry OR depression OR anxiety OR schizophrenia OR cognition OR memory OR attention AND randomized controlled trial (RCT). Studies with yoga as the independent variable and one of the above mentioned terms as the dependent variable were included and exclusion criteria were applied. Results:The search yielded a total of 124 trials, of which 16 met rigorous criteria for the final review. Grade B evidence supporting a potential acute benefit for yoga exists in depression (four RCTs), as an adjunct to pharmacotherapy in schizophrenia (three RCTs), in children with ADHD (two RCTs), and Grade C evidence in sleep complaints (three RCTs). RCTs in cognitive disorders and eating disorders yielded conflicting results. No studies looked at primary prevention, relapse prevention, or comparative effectiveness versus pharmacotherapy. Conclusion:There is emerging evidence from randomized trials to support popular beliefs about yoga for depression, sleep disorders, and as an augmentation therapy. Limitations of literature include inability to do double-blind studies, multiplicity of comparisons within small studies, and lack of replication. Biomarker and neuroimaging studies, those comparing yoga with standard pharmaco and psychotherapies, and studies of long-term efficacy are needed to fully translate the promise of yoga for enhancing mental health. © 2013 Balasubramaniam, Telles and Doraiswamy.


Zannas A.S.,Duke University | Okuno Y.,Kyoto University | Doraiswamy P.M.,Duke University | Doraiswamy P.M.,Duke Institute for Brain science
Pharmacotherapy | Year: 2014

Study Objectives: Case reports suggest a relationship between cholinesterase inhibitors (ChEIs) and Pisa syndrome (PS), also known as pleurothotonus, a form of dystonia, but this relationship has not been systematically examined. Our objective was to estimate the adjusted reporting ratios of PS with donepezil, rivastigmine, and galantamine in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. DESIGN: Retrospective analysis of adverse event reports in the FAERS database. PATIENTS: Patients with drug-related adverse events in the FAERS database. MEASUREMENTS AND MAIN RESULTS: The Gamma Poisson Shrinker algorithm was used to estimate the empirical Bayes geometric mean (EBGM) along with the lower and upper 90% confidence interval (CI) limits (EB05 and EB95, respectively), as measures of the adjusted reporting ratio of PS in patients taking ChEIs. EB05 < 2.0 was used as the cutoff for significance for the signals. The EBGM (EB05) was 37.9 (30) for all ChEIs, 25.6 (17.6) for donepezil, 76.4 (50.3) for galantamine, and 33.7 (21.2) for rivastigmine. All adverse event signals were strongly significant based on the a priori set EB05 cutoff. The female:male ratio in the reported cases was 2:1. No significant signals were found between ChEIs and other dystonias. About half of the ChEI users were also taking concomitant antipsychotics. CONCLUSION: Although FAERS data cannot establish causality due to reporting biases, our findings support a potential dopaminergic-cholinergic imbalance as an underlying mechanism for PS and may help increase clinician awareness, early identification, and treatment of ChEI-related dystonias. KEY WORDS cholinesterase inhibitors, dystonia, Pisa syndrome, pleurothotonus. © 2013 Pharmacotherapy Publications, Inc.


Boyd J.L.,Duke University | Skove S.L.,Duke University | Rouanet J.P.,Duke University | Pilaz L.-J.,Duke University | And 5 more authors.
Current Biology | Year: 2015

The human neocortex differs from that of other great apes in several notable regards, including altered cell cycle, prolonged corticogenesis, and increased size [1-5]. Although these evolutionary changes most likely contributed to the origin of distinctively human cognitive faculties, their genetic basis remains almost entirely unknown. Highly conserved non-coding regions showing rapid sequence changes along the human lineage are candidate loci for the development and evolution of uniquely human traits. Several studies have identified human-accelerated enhancers [6-14], but none have linked an expression difference to a specific organismal trait. Here we report the discovery of a human-accelerated regulatory enhancer (HARE5) of FZD8, a receptor of the Wnt pathway implicated in brain development and size [15, 16]. Using transgenic mice, we demonstrate dramatic differences in human and chimpanzee HARE5 activity, with human HARE5 driving early and robust expression at the onset of corticogenesis. Similar to HARE5 activity, FZD8 is expressed in neural progenitors of the developing neocortex [17-19]. Chromosome conformation capture assays reveal that HARE5 physically and specifically contacts the core Fzd8 promoter in the mouse embryonic neocortex. To assess the phenotypic consequences of HARE5 activity, we generated transgenic mice in which Fzd8 expression is under control of orthologous enhancers (Pt-HARE5::Fzd8 and Hs-HARE5::Fzd8). In comparison to Pt-HARE5::Fzd8, Hs-HARE5::Fzd8 mice showed marked acceleration of neural progenitor cell cycle and increased brain size. Changes in HARE5 function unique to humans thus alter the cell-cycle dynamics of a critical population of stem cells during corticogenesis and may underlie some distinctive anatomical features of the human brain. © 2015 Elsevier Ltd All rights reserved.


Tur-Kaspa I.,Institute for Human Reproduction | Tur-Kaspa I.,University of Chicago | Jeelani R.,Wayne State University | Doraiswamy P.M.,Duke Institute for Brain science
Nature Reviews Neurology | Year: 2014

Preimplantation genetic diagnosis (PGD) is an option for couples at risk of having offspring with an inherited debilitating or fatal neurological disorder who wish to conceive a healthy child. PGD has been carried out for conditions with various modes of inheritance, including spinal muscular atrophy, Huntington disease, fragile X syndrome, and chromosomal or mitochondrial disorders, and for susceptibility genes for cancers with nervous system involvement. Most couples at risk of transmitting a genetic mutation would opt for PGD over prenatal testing and possible termination of a pregnancy. The aim of this Perspectives article is to assist neurologists in counselling and treating patients who wish to explore the option of PGD to enable conception of an unaffected child. PGD can be accomplished for most disorders in which the genetic basis is known, and we argue that it is time for clinicians and neurological societies to consider the evidence and to formulate guidelines for the responsible integration of PGD into modern preventative neurology. © 2014 Macmillan Publishers Limited.

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