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Showing papers in "Frontiers in Neuroscience in 2012"


Journal ArticleDOI
TL;DR: The FBCSP algorithm performed relatively the best among the other submitted algorithms and yielded a mean kappa value of 0.569 and 0.600 across all subjects in Datasets 2a and 2b of the BCI Competition IV.
Abstract: The Common Spatial Pattern (CSP) algorithm is an effective and popular method for classifying 2-class motor imagery electroencephalogram (EEG) data, but its effectiveness depends on the subject-specific frequency band. This paper presents the Filter Bank Common Spatial Pattern (FBCSP) algorithm to optimize the subject-specific frequency band for CSP on Datasets 2a and 2b of the Brain-Computer Interface (BCI) Competition IV. Dataset 2a comprised 4 classes of 22 channels EEG data from 9 subjects, and Dataset 2b comprised 2 classes of 3 bipolar channels EEG data from 9 subjects. Multi-class extensions to FBCSP are also presented to handle the 4-class EEG data in Dataset 2a, namely, Divide-and-Conquer (DC), Pair-Wise (PW), and One-Versus-Rest (OVR) approaches. Two feature selection algorithms are also presented to select discriminative CSP features on Dataset 2b, namely, the Mutual Information-based Best Individual Feature (MIBIF) algorithm, and the Mutual Information-based Rough Set Reduction (MIRSR) algorithm. The single-trial classification accuracies were presented using 10x10-fold cross-validations on the training data and session-to-session transfer on the evaluation data from both datasets. Disclosure of the test data labels after the BCI Competition IV showed that the FBCSP algorithm performed relatively the best among the other submitted algorithms and yielded a mean kappa value of 0.569 and 0.600 across all subjects in Datasets 2a and 2b respectively.

862 citations


Journal ArticleDOI
TL;DR: The Mindboggle-101 dataset is introduced, the largest and most complete set of free, publicly accessible, manually labeled human brain images, and a new cortical labeling protocol that relies on robust anatomical landmarks and minimal manual edits after initialization with automated labels is created.
Abstract: We introduce the Mindboggle-101 dataset, the largest and most complete set of free, publicly accessible, manually labeled human brain images. To manually label the macroscopic anatomy in magnetic resonance images of 101 healthy participants, we created a new cortical labeling protocol that relies on robust anatomical landmarks and minimal manual edits after initialization with automated labels. The “Desikan-Killiany-Tourville” (DKT) protocol is intended to improve the ease, consistency, and accuracy of labeling human cortical areas. Given how difficult it is to label brains, the Mindboggle-101 dataset is intended to serve as brain atlases for use in labeling other brains, as a normative dataset to establish morphometric variation in a healthy population for comparison against clinical populations, and contribute to the development, training, testing, and evaluation of automated registration and labeling algorithms. To this end, we also introduce benchmarks for the evaluation of such algorithms by comparing our manual labels with labels automatically generated by probabilistic and multi-atlas registration-based approaches. All data and related software and updated information are available on the http://www.mindboggle.info/data/ website.

806 citations


Journal ArticleDOI
TL;DR: The BCI competition IV stands in the tradition of prior BCI competitions that aim to provide high quality neuroscientific data for open access to the scientific community and it is the hope that winning entries may enhance the analysis methods of future BCIs.
Abstract: The BCI competition IV stands in the tradition of prior BCI competitions that aim to provide high quality neuroscientific data for open access to the scientific community. As experienced already in prior competitions not only scientists from the narrow field of BCI compete, but scholars with a broad variety of backgrounds and nationalities. They include high specialists as well as students. The goals of all BCI competitions have always been to challenge with respect to novel paradigms and complex data. We report on the following challenges: (1) asynchronous data, (2) synthetic, (3) multi-class continuous data, (4) session-to-session transfer, (5) directionally modulated MEG, (6) finger movements recorded by ECoG. As after past competitions, our hope is that winning entries may enhance the analysis methods of future BCIs.

747 citations


Journal ArticleDOI
TL;DR: The conceptual basis of the NKI-RS is described, including study design, sampling considerations, and steps to synchronize phenotypic and neuroimaging assessment, and it is hoped that familiarity with the conceptual underpinnings will facilitate harmonization with future data collection efforts aimed at advancing psychiatric neuroscience and nosology.
Abstract: The National Institute of Mental Health strategic plan for advancing psychiatric neuroscience calls for an acceleration of discovery and the delineation of developmental trajectories for risk and resilience across the lifespan. To attain these objectives, sufficiently powered datasets with broad and deep phenotypic characterization, state-of-the-art neuroimaging, and genetic samples must be generated and made openly available to the scientific community. The enhanced Nathan Kline Institute Rockland Sample (NKI-RS) is a response to this need. NKI-RS is an ongoing, institutionally-centered endeavor aimed at creating a large-scale (N>1000), deeply phenotyped, community-ascertained, lifespan sample (ages 6-85 years old) with advanced neuroimaging and genetics. These data will be publically shared, openly and prospectively (i.e., on a weekly basis). Herein, we describe the conceptual basis of the NKI-RS, including study design, sampling considerations, and steps to synchronize phenotypic and neuroimaging assessment. Additionally, we describe our process for sharing the data with the scientific community while protecting participant confidentiality, maintaining an adequate database, and certifying data integrity. The pilot phase of the NKI-RS, including challenges in recruiting, characterizing, imaging, and sharing data, is discussed while also explaining how this experience informed the final design of the enhanced NKI-RS. It is our hope that familiarity with the conceptual underpinnings of the enhanced NKI-RS will facilitate harmonization with future data collection efforts aimed at advancing psychiatric neuroscience and nosology.

693 citations


Journal ArticleDOI
TL;DR: It is found that the slope of frequency distortions decreases with the sample size, which is echoed by findings in decision from experience and previous models of the representation of uncertainty can be found that none can account for the empirical findings.
Abstract: In decision from experience, the source of probability information affects how probability is distorted in the decision task. Understanding how and why probability is distorted is a key issue in understanding the peculiar character of experience-based decision. We consider how probability information is used not just in decision-making but also in a wide variety of cognitive, perceptual, and motor tasks. Very similar patterns of distortion of probability/frequency information have been found in visual frequency estimation, frequency estimation based on memory, signal detection theory, and in the use of probability information in decision-making under risk and uncertainty. We show that distortion of probability in all cases is well captured as linear transformations of the log odds of frequency and/or probability, a model with a slope parameter, and an intercept parameter. We then consider how task and experience influence these two parameters and the resulting distortion of probability. We review how the probability distortions change in systematic ways with task and report three experiments on frequency distortion where the distortions change systematically in the same task. We found that the slope of frequency distortions decreases with the sample size, which is echoed by findings in decision from experience. We review previous models of the representation of uncertainty and find that none can account for the empirical findings.

635 citations


Journal ArticleDOI
TL;DR: Estimating the flexibility of neuroimaging analysis by submitting a single event-related fMRI experiment to a large number of unique analysis procedures reveals considerable flexibility, which suggests that false positive results may be more prevalent than expected in the literature.
Abstract: How likely are published findings in the functional neuroimaging literature to be false? According to a recent mathematical model, the potential for false positives increases with the flexibility of analysis methods. Functional MRI (fMRI) experiments can be analyzed using a large number of commonly used tools, with little consensus on how, when, or whether to apply each one. This situation may lead to substantial variability in analysis outcomes. Thus, the present study sought to estimate the flexibility of neuroimaging analysis by submitting a single event-related fMRI experiment to a large number of unique analysis procedures. Ten analysis steps for which multiple strategies appear in the literature were identified, and two to four strategies were enumerated for each step. Considering all possible combinations of these strategies yielded 6,912 unique analysis pipelines. Activation maps from each pipeline were corrected for multiple comparisons using five thresholding approaches, yielding 34,560 significance maps. While some outcomes were relatively consistent across pipelines, others showed substantial methods-related variability in activation strength, location, and extent. Some analysis decisions contributed to this variability more than others, and different decisions were associated with distinct patterns of variability across the brain. Qualitative outcomes also varied with analysis parameters: many contrasts yielded significant activation under some pipelines but not others. Altogether, these results reveal considerable flexibility in the analysis of fMRI experiments. This observation, when combined with mathematical simulations linking analytic flexibility with elevated false positive rates, suggests that false positive results may be more prevalent than expected in the literature. This risk of inflated false positive rates may be mitigated by constraining the flexibility of analytic choices or by abstaining from selective analysis reporting.

321 citations


Journal ArticleDOI
TL;DR: Overall, the studies suggest that CC circuits may indeed influence the descending commands associated with navigational decisions, thereby making them more context dependent.
Abstract: Animals must routinely deal with barriers as they move through their natural environment. These challenges require directed changes in leg movements and posture performed in the context of ever changing internal and external conditions. In particular, cockroaches use a combination of tactile and visual information to evaluate objects in their path in order to effectively guide their movements in complex terrain. When encountering a large block, the insect uses its antennae to evaluate the object’s height then rears upward accordingly before climbing. A shelf presents a choice between climbing and tunneling that depends on how the antennae strike the shelf; tapping from above yields climbing, while tapping from below causes tunneling. However, ambient light conditions detected by the ocelli can bias that decision. Similarly, in a T-maze turning is determined by antennal contact but influenced by visual cues. These multi-sensory behaviors led us to look at the central complex as a center for sensori-motor integration within the insect brain. Visual and antennal tactile cues are processed within the central complex and, in tethered preparations, several central complex units changed firing rates in tandem with or prior to altered step frequency or turning, while stimulation through the implanted electrodes evoked these same behavioral changes. To further test for a central complex role in these decisions, we examined behavioral effects of brain lesions. Electrolytic lesions in restricted regions of the central complex generated site specific behavioral deficits. Similar changes were also found in reversible effects of procaine injections in the brain. Finally, we are examining these kinds of decisions made in a large arena that more closely matches the conditions under which cockroaches forage. Overall, our studies suggest that CC circuits may indeed influence the descending commands associated with navigational decisions, thereby making them more context dependent.

287 citations


Journal ArticleDOI
TL;DR: In this article, the authors compare the utility of a variety of motion correction techniques using a simulated functional activation signal added to 20 real NIRS datasets which contain motion artifacts, including spline interpolation, wavelet analysis, and Kalman filtering.
Abstract: Near-infrared spectroscopy (NIRS) is susceptible to signal artifacts caused by relative motion between NIRS optical fibers and the scalp. These artifacts can be very damaging to the utility of functional NIRS, particularly in challenging subject groups where motion can be unavoidable. A number of approaches to the removal of motion artifacts from NIRS data have been suggested. In this paper we systematically compare the utility of a variety of published NIRS motion correction techniques using a simulated functional activation signal added to 20 real NIRS datasets which contain motion artifacts. Principle component analysis, spline interpolation, wavelet analysis, and Kalman filtering approaches are compared to one another and to standard approaches using the accuracy of the recovered, simulated hemodynamic response function (HRF). Each of the four motion correction techniques we tested yields a significant reduction in the mean-squared error (MSE) and significant increase in the contrast-to-noise ratio (CNR) of the recovered HRF when compared to no correction and compared to a process of rejecting motion-contaminated trials. Spline interpolation produces the largest average reduction in MSE (55%) while wavelet analysis produces the highest average increase in CNR (39%). On the basis of this analysis, we recommend the routine application of motion correction techniques (particularly spline interpolation or wavelet analysis) to minimize the impact of motion artifacts on functional NIRS data.

283 citations


Journal ArticleDOI
TL;DR: A simple, compact, tailor-made clustering algorithm, QuickBundles (QB), that overcomes the complexity of these large data sets and provides informative clusters in seconds and can help in the search for similarities across several subjects.
Abstract: Diffusion MR data sets produce large numbers of streamlines which are hard to visualize, interact with, and interpret in a clinically acceptable time scale, despite numerous proposed approaches. As a solution we present a simple, compact, tailor-made clustering algorithm, QuickBundles (QB), that overcomes the complexity of these large data sets and provides informative clusters in seconds. Each QB cluster can be represented by a single centroid streamline; collectively these centroid streamlines can be taken as an effective representation of the tractography. We provide a number of tests to show how the QB reduction has good consistency and robustness. We show how the QB reduction can help in the search for similarities across several subjects.

260 citations


Journal ArticleDOI
TL;DR: These models support the hypothesis that changes in tonic dopamine within the striatum can alter the exploration-exploitation trade-off by modulating the output of the basal ganglia.
Abstract: We continuously face the dilemma of choosing between actions that gather new information or actions that exploit existing knowledge. This “exploration-exploitation” trade-off depends on the environment: stability favors exploiting knowledge to maximize gains; volatility favors exploring new options and discovering new outcomes. Here we set out to reconcile recent evidence for dopamine’s involvement in the exploration-exploitation trade-off with the existing evidence for basal ganglia control of action selection, by testing the hypothesis that tonic dopamine in the striatum, the basal ganglia’s input nucleus, sets the current exploration-exploitation trade-off. We first advance the idea of interpreting the basal ganglia output as a probability distribution function for action selection. Using computational models of the full basal ganglia circuit, we showed that, under this interpretation, the actions of dopamine within the striatum change the basal ganglia’s output to favor the level of exploration or exploitation encoded in the probability distribution. We also found that our models predict striatal dopamine controls the exploration-exploitation trade-off if we instead read-out the probability distribution from the target nuclei of the basal ganglia, where their inhibitory input shapes the cortical input to these nuclei. Finally, by integrating the basal ganglia within a reinforcement learning model, we showed how dopamine’s effect on the exploration-exploitation trade-off could be measurable in a forced two-choice task. These simulations also showed how tonic dopamine can appear to affect learning while only directly altering the trade-off. Thus, our models support the hypothesis that changes in tonic dopamine within the striatum can alter the exploration-exploitation trade-off by modulating the output of the basal ganglia.

180 citations


Journal ArticleDOI
TL;DR: How evolutionary conserved and newly acquired features of the developing and adult zebrafish thalamus can be compared to the mammalian situation is discussed.
Abstract: Current research on the thalamus and related structures in the zebrafish diencephalon identifies an increasing number of both neurological structures and ontogenetic processes as evolutionary conserved between teleosts and mammals. The patterning processes, for example, which during the embryonic development of zebrafish form the thalamus proper appear largely conserved. Yet also striking differences between zebrafish and other vertebrates have been observed, particularly when we look at mature and histologically differentiated brains. A case in point is the migrated preglomerular complex of zebrafish which evolved only within the lineage of ray-finned fish and has no counterpart in mammals or tetrapod vertebrates. Based on its function as a sensory relay station with projections to pallial zones, the preglomerular complex has been compared to specific thalamic nuclei in mammals. However, no thalamic projections to the zebrafish dorsal pallium, which corresponds topologically to the mammalian isocortex, have been identified. Merely one teleostean thalamic nucleus proper, the auditory nucleus, projects to a part of the dorsal telencephalon, the pallial amygdala. Studies on patterning mechanisms identify a rostral and caudal domain in the embryonic thalamus proper. In both, teleosts and mammals, the rostral domain gives rise to GABAergic neurons, whereas glutamatergic neurons originate in the caudal domain of the zebrafish thalamus. The distribution of GABAergic derivatives in the adult zebrafish brain, furthermore, revealed previously overlooked thalamic nuclei and redefined already established ones. These findings require some reconsideration regarding the topological origin of these adult structures. In what follows, I discuss how evolutionary conserved and newly acquired features of the developing and adult zebrafish thalamus can be compared to the mammalian situation.

Journal ArticleDOI
TL;DR: The identification of the classical intracellular progesterone receptors as therapeutic targets for myelin repair suggests new health benefits for synthetic progestins, specifically designed for contraceptive use and hormone replacement therapies.
Abstract: Progesterone is well known as a female reproductive hormone and in particular for its role in uterine receptivity, implantation, and the maintenance of pregnancy. However, neuroendocrine research over the past decades has established that progesterone has multiple functions beyond reproduction. Within the nervous system, its neuromodulatory and neuroprotective effects are much studied. Although progesterone has been shown to also promote myelin repair, its influence and that of other steroids on myelination and remyelination is relatively neglected. Reasons for this are that hormonal influences are still not considered as a central problem by most myelin biologists, and that neuroendocrinologists are not sufficiently concerned with the importance of myelin in neuron functions and viability. The effects of progesterone in the nervous system involve a variety of signaling mechanisms. The identification of the classical intracellular progesterone receptors as therapeutic targets for myelin repair suggests new health benefits for synthetic progestins, specifically designed for contraceptive use and hormone replacement therapies. There are also major advantages to use natural progesterone in neuroprotective and myelin repair strategies, because progesterone is converted to biologically active metabolites in nervous tissues and interacts with multiple target proteins. The delivery of progesterone however represents a challenge because of its first-pass metabolism in digestive tract and liver. Recently, the intranasal route of progesterone administration has received attention for easy and efficient targeting of the brain. Progesterone in the brain is derived from the steroidogenic endocrine glands or from local synthesis by neural cells. Stimulating the formation of endogenous progesterone is currently explored as an alternative strategy for neuroprotection, axonal regeneration, and myelin repair.

Journal ArticleDOI
TL;DR: This is the first field validation of a dry electrode P300 BCI system, and paves the way for new research and development with EEG recording systems that are much more practical and convenient in field settings than conventional systems.
Abstract: Most brain-computer interfaces (BCI) rely on one of three types of signals in the electroencephalogram (EEG): P300s, steady-state visually evoked potentials (SSVEP), and event-related desynchronization (ERD). EEG is typically recorded non-invasively with electrodes mounted on the human scalp using conductive electrode gel for optimal impedance and data quality. The use of electrode gel entails serious problems that are especially pronounced in real-world settings when experts are not available. Some recent work has introduced dry electrode systems that do not require gel, but often introduce new problems such as comfort and signal quality. The principal goal of this study was to assess a new dry electrode BCI system in a very common task: spelling with a P300 BCI. A total of 23 subjects used a P300 BCI to spell the word “LUCAS” while receiving realtime, closed-loop feedback. The dry system yielded classification accuracies that were similar to those obtained with gel systems. All subjects completed a questionnaire after data recording, and all subjects stated that the dry system was not uncomfortable. This is the first field validation of a dry electrode P300 BCI system, and paves the way for new research and development with EEG recording systems that are much more practical and convenient in field settings than conventional systems.

Journal ArticleDOI
TL;DR: Emerging evidence indicates epigenetic mechanisms maintain sex differences in the POA that are organized perinatally and thereby produce permanent behavioral changes, and emerging strategies to better elucidate the mechanisms through which genetics and epigenetics contribute to brain and behavioral sex differences are reviewed.
Abstract: Steroid hormones of gonadal origin act on the neonatal brain to produce sex differences that underlie adult reproductive physiology and behavior. Neuronal sex differences occur on a variety of levels, including differences in regional volume and/or cell number, morphology, physiology, molecular signaling, and gene expression. In the rodent, many of these sex differences are determined by steroid hormones, particularly estradiol, and are established by diverse downstream effects. One brain region that is potently organized by estradiol is the preoptic area (POA), a region critically involved in many behaviors that show sex differences, including copulatory and maternal behaviors. This review focuses on the POA as a case study exemplifying the depth and breath of our knowledge as well as the gaps in understanding the mechanisms through which gonadal hormones produce lasting neural and behavioral sex differences. In the POA, multiple cell types, including neurons, astrocytes, and microglia are masculinized by estradiol. Multiple downstream molecular mediators are involved, including prostaglandins, various glutamate receptors, protein kinase A, and several immune signaling molecules. Moreover, emerging evidence indicates epigenetic mechanisms maintain sex differences in the POA that are organized perinatally and thereby produce permanent behavioral changes. We also review emerging strategies to better elucidate the mechanisms through which genetics and epigenetics contribute to brain and behavioral sex differences.

Journal ArticleDOI
TL;DR: It is argued that there is a common framework for understanding decisions made in both perceptual and economic decision-making, under which an agent has to combine sensory information with value information, and computational models of the decision process typically used in PDM are reviewed.
Abstract: Investigation into the neural and computational bases of decision-making has proceeded in two parallel but distinct streams. Perceptual decision-making (PDM) is concerned with how observers detect, discriminate, and categorize noisy sensory information. Economic decision-making (EDM) explores how options are selected on the basis of their reinforcement history. Traditionally, the sub-fields of PDM and EDM have employed different paradigms, proposed different mechanistic models, explored different brain regions, disagreed about whether decisions approach optimality. Nevertheless, we argue that there is a common framework for understanding decisions made in both tasks, under which an agent has to combine sensory information (what is the stimulus) with value information (what is it worth). We review computational models of the decision process typically used in PDM, based around the idea that decisions involve a serial integration of evidence, and assess their applicability to decisions between good and gambles. Subsequently, we consider the contribution of three key brain regions – the parietal cortex, the basal ganglia, and the orbitofrontal cortex (OFC) – to perceptual and EDM, with a focus on the mechanisms by which sensory and reward information are integrated during choice. We find that although the parietal cortex is often implicated in the integration of sensory evidence, there is evidence for its role in encoding the expected value of a decision. Similarly, although much research has emphasized the role of the striatum and OFC in value-guided choices, they may play an important role in categorization of perceptual information. In conclusion, we consider how findings from the two fields might be brought together, in order to move toward a general framework for understanding decision-making in humans and other primates.

Journal ArticleDOI
TL;DR: This study showed that SSVEP based BCI systems can reach very high accuracies after only a very short training period, and shows thatSSVEP BCIs could provide communication for some users when other approaches might not work for them.
Abstract: Brain-computer interfaces (BCI) are communication systems that allow people to send messages or commands without movement. BCIs rely on different types of signals in the electroencephalogram (EEG), typically P300s, steady-state visually evoked potentials (SSVEP), or event-related desynchronization (ERD). Early BCI systems were often evaluated with a selected group of subjects. Also, many articles do not mention data from subjects who performed poorly. These and other factors have made it difficult to estimate how many people could use different BCIs. The present study explored how many subjects could use an SSVEP BCI. We recorded data from 53 subjects while they participated in 1 to 4 runs that were each 4 minutes long. During these runs, the subjects focused on one of four LEDs that each flickered at a different frequency. The 8 channel EEG data were analyzed with a minimum energy parameter estimation algorithm and classified with linear discriminant analysis into one of the four classes. On-line results showed that SSVEP BCIs could provide effective communication for all 53 subjects, resulting in a grand average accuracy of 95.5%. 96.2% of the subjects reached an accuracy above 80%, and nobody was below 60%. This study showed that SSVEP based BCI systems can reach very high accuracies after only a very short training period. The SSVEP approach worked for all participating subjects, who attained accuracy well above chance level. This is important because it shows that SSVEP BCIs could provide communication for some users when other approaches might not work for them.

Journal ArticleDOI
TL;DR: Interestingly, it is found that ventromedial prefrontal cortex (vmPFC) activity decreased as participants further expanded balloons, which suggests that escalating risk-taking in the task might be perceived as exposure to increasing possible losses rather than the increasing potential total reward relative to the starting point of the trial.
Abstract: Functional imaging studies examining the neural correlates of risk have mainly relied on paradigms involving exposure to simple chance gambles and an economic definition of risk as variance in the probability distribution over possible outcomes. However, there is little evidence that choices made during gambling tasks predict naturalistic risk-taking behaviors such as drug use, extreme sports, or even equity investing. To better understand the neural basis of naturalistic risk-taking, we scanned participants using fMRI while they completed the Balloon Analog Risk Task, an experimental measure that includes an active decision/choice component and that has been found to correlate with a number of naturalistic risk-taking behaviors. In the task, as in many naturalistic settings, escalating risk-taking occurs under uncertainty and might be experienced either as the accumulation of greater potential rewards, or as exposure to increasing possible losses (and decreasing expected value). We found that areas previously linked to risk and risk-taking (bilateral anterior insula, anterior cingulate cortex, and right dorsolateral prefrontal cortex) were activated as participants continued to inflate balloons. Interestingly, we found that ventromedial prefrontal cortex (vmPFC) activity decreased as participants further expanded balloons. In light of previous findings implicating the vmPFC in value calculation, this result suggests that escalating risk-taking in the task might be perceived as exposure to increasing possible losses (and decreasing expected value) rather than the increasing potential total reward relative to the starting point of the trial. A better understanding of how neural activity changes with risk-taking behavior in the task offers insight into the potential neural mechanisms driving naturalistic risk-taking.

Journal ArticleDOI
TL;DR: Insight is provided into how neural circuits may process rewards and punishments associated with simple decisions under acutely stressful conditions by examining how it may modulate responses to Rewards and punishments within reward-processing neural circuitry.
Abstract: People often make decisions under aversive conditions such as acute stress. Yet, less is known about the process in which acute stress can influence decision-making. A growing body of research has established that reward-related information associated with the outcomes of decisions exerts a powerful influence over the choices people make and that an extensive network of brain regions, prominently featuring the striatum, is involved in the processing of this reward-related information. Thus, an important step in research on the nature of acute stress’ influence over decision-making is to examine how it may modulate responses to rewards and punishments within reward-processing neural circuitry. In the current experiment, we employed a simple reward processing paradigm – where participants received monetary rewards and punishments – known to evoke robust striatal responses. Immediately prior to performing each of two task runs, participants were exposed to acute stress (i.e., cold pressor) or a no stress control procedure in a between-subjects fashion. No stress group participants exhibited a pattern of activity within the dorsal striatum and orbitofrontal cortex consistent with past research on outcome processing – specifically, differential responses for monetary rewards over punishments. In contrast, acute stress group participants’ dorsal striatum and orbitofrontal cortex demonstrated decreased sensitivity to monetary outcomes and a lack of differential activity. These findings provide insight into how neural circuits may process rewards and punishments associated with simple decisions under acutely stressful conditions.

Journal ArticleDOI
TL;DR: The increase of oxytocin levels for at least 7 h shows how effective intranasal administration of oxycoetocin is, and may raise ethical questions about potentially persisting behavioral effects after participants have left the lab setting.
Abstract: We addressed the question how long salivary oxytocin levels remain elevated after intranasal administration, and whether it makes a difference when 16 IU or 24 IU of oxytocin administration is used. Oxytocin levels were measured in saliva samples collected from 46 female participants right before intranasal administration (at 9:30 AM) of 16 IU (n = 18) or 24 IU (n = 10) of oxytocin, or a placebo (n = 18), and each hour after administration, for 7h in total. Oxytocin levels did not differ among conditions before use of the nasal spray. Salivary oxytocin levels in the placebo group showed high stability across the day. After oxytocin administration oxytocin levels markedly increased, they peaked around 1h after administration, and were still significantly elevated 7h after administration. The amount of oxytocin (16 IU or 24 IU) did not make a difference for oxytocin levels. The increase of oxytocin levels for at least 7h shows how effective intranasal administration of oxytocin is. Our findings may raise ethical questions about potentially persisting behavioral effects after participants have left the lab setting. More research into the long-term neurological and behavioral effects of sniffs of oxytocin is urgently needed.

Journal ArticleDOI
TL;DR: Novel findings showing that the same stimulus – intra-oral infusion of sucrose – has differing effects on NAc shell dopamine release depending on the prior experience are presented and the emerging literature suggests an important role for differential phasic dopamine signaling in aversion vs. reward.
Abstract: Adaptive motivated behavior requires rapid discrimination between beneficial and harmful stimuli. Such discrimination leads to the generation of either an approach or rejection response, as appropriate, and enables organisms to maximize reward and minimize punishment. Classically, the nucleus accumbens (NAc) and the dopamine projection to it are considered an integral part of the brain’s reward circuit, i.e., they direct approach and consumption behaviors and underlie positive reinforcement. This reward-centered framing ignores important evidence about the role of this system in encoding aversive events. One reason for bias towards reward is the difficulty in designing experiments in which animals repeatedly experience punishments; another is the challenge in dissociating the response to an aversive stimulus itself from the reward/relief experienced when an aversive stimulus is terminated. Here, we review studies that employ techniques with sufficient time resolution to measure responses in ventral tegmental area (VTA) and NAc to aversive stimuli as they are delivered. We also present novel findings showing that the same stimulus – intraoral infusion of sucrose – has differing effects on NAc shell dopamine release depending on the prior experience. Here, for some rats, sucrose was rendered aversive by explicitly pairing it with malaise in a conditioned taste aversion paradigm. Thereafter, sucrose infusions led to a suppression of dopamine with a similar magnitude and time course to intra-oral infusions of a bitter quinine solution. The results are discussed in the context of regional differences in dopamine signaling and the implications of a pause in phasic dopamine release within the NAc shell. Together with our data, the emerging literature suggests an important role for differential phasic dopamine signaling in aversion versus reward.

Journal ArticleDOI
TL;DR: A computer-based experiment on human subjects found that only when many demonstrators were available and subjects were uncertain was subject behavior conformist, and a further analysis found that the underlying response to social information alone was generally conformist.
Abstract: Humans are characterized by an extreme dependence on culturally transmitted information and recent formal theory predicts that natural selection should favour adaptive learning strategies that facilitate effective use of social information in decision making. One strategy that has attracted particular attention is conformist transmission, defined as the disproportionately likely adoption of the most common variant. Conformity has historically been emphasized as significant in the social psychology literature, and recently there have also been reports of conformist behaviour in nonhuman animals. However, mathematical analyses differ in how important and widespread they expect conformity to be, and relevant experimental work is scarce, and generates findings that are both mutually contradictory and inconsistent with the predictions of the models. We review the relevant literature considering the causation, function, history and ontogeny of conformity and describe a computer-based experiment on human subjects that we carried out in order to resolve ambiguities. We found that only when many demonstrators were available and subjects were uncertain was subject behaviour conformist. A further analysis found that the underlying response to social information alone was generally conformist. Thus, our data are consistent with a conformist use of social information, but as subject’s behaviour is the result of both social and asocial influences, the resultant behaviour may not be conformist. We end by relating these findings to an embryonic cognitive neuroscience literature that has recently begun to explore the neural bases of social learning. Here conformist transmission may be a particularly useful case study, not only because there are well-defined and tractable opportunities to characterize the biological underpinnings of this form of social learning, but also because early findings imply that humans may possess specific cognitive adaptations for effective social learning.

Journal ArticleDOI
TL;DR: The mechanisms of synaptic inhibition of interneurons are reviewed and their role in the operation of hippocampal inhibitory circuits is discussed.
Abstract: Information processing within neuronal networks is determined by a dynamic partnership between principal neurons and local circuit inhibitory interneurons. The population of GABAergic interneurons is extremely heterogeneous and comprises, in many brain regions, cells with divergent morphological and physiological properties, distinct molecular expression profiles, and highly specialized functions. GABAergic interneurons have been studied extensively during the past two decades, especially in the hippocampus, which is a relatively simple cortical structure. Different types of hippocampal inhibitory interneurons control spike initiation (e.g., axo-axonic and basket cells) and synaptic integration (e.g., bistratified and oriens–lacunosum moleculare interneurons) within pyramidal neurons and synchronize local network activity, providing a means for functional segregation of neuronal ensembles and proper routing of hippocampal information. Thus, it is thought that, at least in the hippocampus, GABAergic inhibitory interneurons represent critical regulating elements at all stages of information processing, from synaptic integration and spike generation to large-scale network activity. However, this raises an important question: if inhibitory interneurons are fundamental for network computations, what are the mechanisms that control the activity of the interneurons themselves? Given the essential role of synaptic inhibition in the regulation of neuronal activity, it would be logical to expect that specific inhibitory mechanisms have evolved to control the operation of interneurons. Here, we review the mechanisms of synaptic inhibition of interneurons and discuss their role in the operation of hippocampal inhibitory circuits.

Journal ArticleDOI
TL;DR: The emerging roles of epigenetic mechanisms particularly microRNAs, element-1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF), polycomb proteins, and methyl-CpG bindings proteins, in regulating the entire process of postnatal and adult neurogenesis are explored.
Abstract: The process of neurogenesis includes neural stem cell proliferation, fate specification, young neuron migration, neuronal maturation, and functional integration into existing circuits. Although neurogenesis occurs largely during embryonic development, low levels but functionally important neurogenesis persists in restricted regions of the postnatal brain, including the subgranular zone of the dentate gyrus in the hippocampus and the subventricular zone of the lateral ventricles. This review will cover both embryonic and adult neurogenesis with an emphasis on the latter. Of the many endogenous mediators of postnatal neurogenesis, epigenetic pathways, such as mediators of DNA methylation, chromatin remodeling systems, and non-coding RNA modulators, appear to play an integral role. Mounting evidence shows that such epigenetic factors form regulatory networks, which govern each step of postnatal neurogenesis. In this review, we explore the emerging roles of epigenetic mechanisms particularly microRNAs, element-1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF), polycomb proteins, and methyl-CpG bindings proteins, in regulating the entire process of postnatal and adult neurogenesis. We further summarize recent data regarding how the crosstalk among these different epigenetic proteins forms the critical regulatory network that regulates neuronal development. We finally discuss how crosstalk between these pathways may serve to translate environmental cues into control of the neurogenic process.

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TL;DR: This work extensively searched the scientific literature for all original reports describing reconstructions of neuronal morphology since the advent of this technique three decades ago and identified 902 publications describing ∼44,000 digital reconstructions.
Abstract: The importance of neuronal morphology has been recognized from the early days of neuroscience. Elucidating the functional roles of axonal and dendritic arbors in synaptic integration, signal transmission, network connectivity, and circuit dynamics requires quantitative analyses of digital three-dimensional reconstructions.We extensively searched the scientific literature for all original reports describing reconstructions of neuronal morphology since the advent of this technique three decades ago. From almost 50,000 titles, 30,000 abstracts, and more than 10,000 full-text articles, we identified 902 publications describing approximately 44,000 digital reconstructions. Reviewing the growth of this field exposed general research trends on specific animal species, brain regions, neuron types, and experimental approaches. The entire bibliography, annotated with relevant metadata and (wherever available) direct links to the underlying digital data, is accessible at NeuroMorpho.Org.

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TL;DR: It is argued that the cognitive processes for making decisions in a world of risk are not the same as those for dealing with uncertainty, and it is unlikely that the authors' brains are adapted to them.
Abstract: We deal with risk versus uncertainty, a distinction that is of fundamental importance for cognitive neuroscience yet largely neglected. In a world of risk (“small world”), all alternatives, consequences, and probabilities are known. In uncertain (“large”) worlds, some of this information is unknown or unknowable. Most of cognitive neuroscience studies exclusively study the neural correlates for decisions under risk (e.g., lotteries), with the tacit implication that understanding these would lead to an understanding of decision making in general. First, we show that normative strategies for decisions under risk do not generalize to uncertain worlds, where simple heuristics are often the more accurate strategies. Second, we argue that the cognitive processes for making decisions in a world of risk are not the same as those for dealing with uncertainty. Because situations with known risks are the exception rather than the rule in human evolution, it is unlikely that our brains are adapted to them. We therefore suggest a paradigm shift towards studying decision processes in uncertain worlds and provide first examples.

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TL;DR: The performance showed that multi-class MI tasks can be reliably discriminated using artifact-contaminated EEG recordings from a few channels, and may be a promising avenue for online robust EEG-based BCI applications.
Abstract: Recent studies show that scalp electroencephalography (EEG) as a non-invasive interface has great potential for brain-computer interfaces (BCIs). However, one factor that has limited practical applications for EEG-based BCI so far is the difficulty to decode brain signals in a reliable and efficient way. This paper proposes a new robust processing framework for decoding of multi-class motor imagery (MI) that is based on five main processing steps. (i) Raw EEG segmentation without the need of visual artifact inspection. (ii) Considering that EEG recordings are often contaminated not just by electrooculography (EOG) but also other types of artifacts, we propose to first implement an automatic artifact correction method that combines regression analysis with independent component analysis (ICA) for recovering the original source signals. (iii) The significant difference between frequency components based on event-related (de-) synchronization and sample entropy is then used to find non-continuous discriminating rhythms. After spectral filtering using the discriminating rhythms, a channel selection algorithm is used to select only relevant channels. (iv) Feature vectors are extracted based on the inter-class diversity and time-varying dynamic characteristics of the signals. (v) Finally, a support vector machine (SVM) is employed for four-class classification. We tested our proposed algorithm on experimental data that was obtained from dataset 2a of BCI competition IV (2008). The overall four-class kappa values (between 0.41 and 0.80) were comparable to other models but without requiring any artifact-contaminated trial removal. The performance showed that multi-class MI tasks can be reliably discriminated using artifact-contaminated EEG recordings from a few channels. This may be a promising avenue for online robust EEG-based BCI applications.

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TL;DR: The hypothesis that theta-band oscillatory balance between right and left frontal and prefrontal regions, with a predominance role to the right hemisphere (RH), is crucial for regulatory control during decision-making under risk is investigated.
Abstract: The process of evaluating risks and benefits involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC). It has been proposed that in conflict and reward situations, theta-band (4–8 Hz) oscillatory activity in the frontal cortex may reflect an electrophysiological mechanism for coordinating neural networks monitoring behavior, as well as facilitating task-specific adaptive changes. The goal of the present study was to investigate the hypothesis that theta-band oscillatory balance between right and left frontal and prefrontal regions, with a predominance role to the right hemisphere, is crucial for regulatory control during decision-making under risk. In order to explore this hypothesis, we used transcranial Alternating Current Stimulation (tACS), a novel technique that provides the opportunity to explore the functional role of neuronal oscillatory activities and to establish a causal link between specific oscillations and functional lateralization in risky decision-making situations. For this aim, healthy participants were randomly allocated to one of three stimulation groups (LH stimulation / RH stimulation / Sham stimulation), with active AC stimulation delivered in a frequency-dependent manner (at 6.5 Hz; 1mA peak to-peak). During the AC stimulation, participants performed the Balloon Analog Risk Task. This experiment revealed that participants receiving LH stimulation displayed riskier decision-making style compared to sham and RH stimulation groups. However, there was no difference in decision-making behaviors between sham and RH stimulation groups. The current study extends the notion that DLPFC activity is critical for adaptive decision-making in the context of risk-taking and emphasis the role of theta-band oscillatory activity during risky decision-making situations.

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TL;DR: The proposition of a good hardware verification practice may rise synergy effects between hardware developers and neuroscientists, and how weight discretization could be considered for other backends dedicated to large-scale simulations is suggested.
Abstract: Large-scale neuromorphic hardware systems typically bear the trade-off between detail level and required chip resources. Especially when implementing spike-timing dependent plasticity, reduction in resources leads to limitations as compared to floating point precision. By design, a natural modification that saves resources would be reducing synaptic weight resolution. In this study, we give an estimate for the impact of synaptic weight discretization on different levels, ranging from random walks of individual weights to computer simulations of spiking neural networks. The FACETS wafer-scale hardware system offers a 4-bit resolution of synaptic weights, which is shown to be sufficient within the scope of our network benchmark. Our findings indicate that increasing the resolution may not even be useful in light of further restrictions of customized mixed-signal synapses. In addition, variations due to production imperfections are investigated and shown to be uncritical in the context of the presented study. Our results represent a general framework for setting up and configuring hardware-constrained synapses. We suggest how weight discretization could be considered for other backends dedicated to large-scale simulations. Thus, our proposition of a good hardware verification practice may rise synergy effects between hardware developers and neuroscientists.

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TL;DR: It is demonstrated that targeting inflammasome-IL-1β signaling can normalize ethanol-impaired hippocampal neurogenesis, which may have therapeutic implications for treatment of cognitive impairment associated with hippocampal dysfunction in alcoholics.
Abstract: Regulation of hippocampal neurogenesis is poorly understood, but appears to contribute to mood and cognition. Ethanol and neuroinflammation are known to reduce neurogenesis. We have found that ethanol induces neuroinflammation supporting the hypothesis that ethanol induction of neuroinflammation contributes to ethanol inhibition of neurogenesis. To identify the key proinflammatory molecule that may be responsible for ethanol-impaired neurogenesis we used an ex vivo model of organotypic hippocampal-entorhinal cortex (HEC) brain slice cultures. Here, we demonstrated a key role of proinflammatory cytokine IL-1β signaling in mediating ethanol inhibition of neurogenesis. Ethanol inhibition of neurogenesis was reversed by neutralizing antibody to IL-1β or blockade of the IL-1β receptor with antagonist IL-1RIa. Ethanol-impaired neurogenesis is associated with strong induction of IL-1β and inflammasome proteins NALP1 and NALP3 in both neurons and astrocytes. Blockade of IL-1β synthesis with inflammasome inhibitors Parthenolide and Bay11708 significantly reversed ethanol inhibited neurogenesis. Furthermore, we also found that IL-1β and inflammasome proteins NALP1 and NALP3 are increased in hippocampal neurons and astrocytes in postmortem alcoholic human brain. Together, these novel findings demonstrate that targeting inflammasome-IL-1β signaling can normalize ethanol-impaired hippocampal neurogenesis, which may have therapeutic implications for treatment of cognitive impairment associated with hippocampal dysfunction in alcoholics.

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TL;DR: This paper used LASSO regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI).
Abstract: We implemented LASSO (least absolute shrinkage and selection operator) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4 and CDH13. The top genes we identified with this method also displayed significant and widespread post-hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8±2.2 SD years). In exploratory analyses, three selected SNPs in the MACROD2 gene were also significantly associated with performance intelligence quotient (PIQ). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.