Neural Control of the Lower Urinary Tract

PubMed Central

de Groat, William C.; Griffiths, Derek; Yoshimura, Naoki

2015-01-01

This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed. PMID:25589273

Genetic Influences on the Neural and Physiological Bases of Acute Threat: A Research Domain Criteria (RDoC) Perspective

PubMed Central

Sumner, Jennifer A.; Powers, Abigail; Jovanovic, Tanja; Koenen, Karestan C.

2015-01-01

The NIMH Research Domain Criteria (RDoC) initiative aims to describe key dimensional constructs underlying mental function across multiple units of analysis—from genes to observable behaviors—in order to better understand psychopathology. The acute threat (“fear”) construct of the RDoC Negative Valence System has been studied extensively from a translational perspective, and is highly pertinent to numerous psychiatric conditions, including anxiety and trauma-related disorders. We examined genetic contributions to the construct of acute threat at two units of analysis within the RDoC framework: 1) neural circuits and 2) physiology. Specifically, we focused on genetic influences on activation patterns of frontolimbic neural circuitry and on startle, skin conductance, and heart rate responses. Research on the heritability of activation in threat-related frontolimbic neural circuitry is lacking, but physiological indicators of acute threat have been found to be moderately heritable (35-50%). Genetic studies of the neural circuitry and physiology of acute threat have almost exclusively relied on the candidate gene method and, as in the broader psychiatric genetics literature, most findings have failed to replicate. The most robust support has been demonstrated for associations between variation in the serotonin transporter (SLC6A4) and catechol-O-methyltransferase (COMT) genes with threat-related neural activation and physiological responses. However, unbiased genome-wide approaches using very large samples are needed for gene discovery, and these can be accomplished with collaborative consortium-based research efforts, such as those of the Psychiatric Genomics Consortium (PGC) and Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium. PMID:26377804

A neural circuitry that emphasizes spinal feedback generates diverse behaviours of human locomotion

PubMed Central

Song, Seungmoon; Geyer, Hartmut

2015-01-01

Neural networks along the spinal cord contribute substantially to generating locomotion behaviours in humans and other legged animals. However, the neural circuitry involved in this spinal control remains unclear. We here propose a specific circuitry that emphasizes feedback integration over central pattern generation. The circuitry is based on neurophysiologically plausible muscle-reflex pathways that are organized in 10 spinal modules realizing limb functions essential to legged systems in stance and swing. These modules are combined with a supraspinal control layer that adjusts the desired foot placements and selects the leg that is to transition into swing control during double support. Using physics-based simulation, we test the proposed circuitry in a neuromuscular human model that includes neural transmission delays, musculotendon dynamics and compliant foot–ground contacts. We find that the control network is sufficient to compose steady and transitional 3-D locomotion behaviours including walking and running, acceleration and deceleration, slope and stair negotiation, turning, and deliberate obstacle avoidance. The results suggest feedback integration to be functionally more important than central pattern generation in human locomotion across behaviours. In addition, the proposed control architecture may serve as a guide in the search for the neurophysiological origin and circuitry of spinal control in humans. PMID:25920414

Technologies for imaging neural activity in large volumes

PubMed Central

Ji, Na; Freeman, Jeremy; Smith, Spencer L.

2017-01-01

Neural circuitry has evolved to form distributed networks that act dynamically across large volumes. Collecting data from individual planes, conventional microscopy cannot sample circuitry across large volumes at the temporal resolution relevant to neural circuit function and behaviors. Here, we review emerging technologies for rapid volume imaging of neural circuitry. We focus on two critical challenges: the inertia of optical systems, which limits image speed, and aberrations, which restrict the image volume. Optical sampling time must be long enough to ensure high-fidelity measurements, but optimized sampling strategies and point spread function engineering can facilitate rapid volume imaging of neural activity within this constraint. We also discuss new computational strategies for the processing and analysis of volume imaging data of increasing size and complexity. Together, optical and computational advances are providing a broader view of neural circuit dynamics, and help elucidate how brain regions work in concert to support behavior. PMID:27571194

Animal, but Not Human, Faces Engage the Distributed Face Network in Adolescents with Autism

ERIC Educational Resources Information Center

Whyte, Elisabeth M.; Behrmann, Marlene; Minshew, Nancy J.; Garcia, Natalie V.; Scherf, K. Suzanne

2016-01-01

Multiple hypotheses have been offered to explain the impaired face-processing behavior and the accompanying underlying disruptions in neural circuitry among individuals with autism. We explored the specificity of atypical face-processing activation and potential alterations to fusiform gyrus (FG) morphology as potential underlying mechanisms.…

Functional mapping of the neural circuitry of rat maternal motivation: effects of site-specific transient neural inactivation

PubMed Central

Pereira, Mariana; Morrell, Joan I.

2011-01-01

The present review focuses on recent studies from our laboratory examining the neural circuitry subserving rat maternal motivation across postpartum. We employed a site-specific neural inactivation method by infusion of bupivacaine to map the maternal motivation circuitry using two complementary behavioral approaches: unconditioned maternal responsiveness and choice of pup- over cocaine-conditioned incentives in a concurrent pup/cocaine choice conditioned place preference task. Our findings revealed that during the early postpartum period, distinct brain structures, including the medial preoptic area, ventral tegmental area and medial prefrontal cortex infralimbic and anterior cingulate subregions, contribute a pup-specific bias to the motivational circuitry. As the postpartum period progresses and the pups grow older, our findings further revealed that maternal responsiveness becomes progressively less dependent on medial preoptic area and medial prefrontal cortex infralimbic activity, and more distributed in the maternal circuitry, such that additional network components, including the medial prefrontal cortex prelimbic subregion, are recruited with maternal experience, and contribute to the expression of late postpartum maternal behavior. Collectively, our findings provide strong evidence that the remarkable ability of postpartum females to successfully care for their developing infants is subserved by a distributed neural network that carries out efficient and dynamic processing of complex, constantly changing incoming environmental and pup-related stimuli, ultimately allowing the progression of appropriate expression and waning of maternal responsiveness across the postpartum period. PMID:21815954

Neural systems and hormones mediating attraction to infant and child faces

PubMed Central

Luo, Lizhu; Ma, Xiaole; Zheng, Xiaoxiao; Zhao, Weihua; Xu, Lei; Becker, Benjamin; Kendrick, Keith M.

2015-01-01

We find infant faces highly attractive as a result of specific features which Konrad Lorenz termed “Kindchenschema” or “baby schema,” and this is considered to be an important adaptive trait for promoting protective and caregiving behaviors in adults, thereby increasing the chances of infant survival. This review first examines the behavioral support for this effect and physical and behavioral factors which can influence it. It then provides details of the increasing number of neuroimaging and electrophysiological studies investigating the neural circuitry underlying this baby schema effect in parents and non-parents of both sexes. Next it considers potential hormonal contributions to the baby schema effect in both sexes and the neural effects associated with reduced responses to infant cues in post-partum depression, anxiety and drug taking. Overall the findings reviewed reveal a very extensive neural circuitry involved in our perception of cuteness in infant faces, with enhanced activation compared to adult faces being found in brain regions involved in face perception, attention, emotion, empathy, memory, reward and attachment, theory of mind and also control of motor responses. Both mothers and fathers also show evidence for enhanced responses in these same neural systems when viewing their own as opposed to another child. Furthermore, responses to infant cues in many of these neural systems are reduced in mothers with post-partum depression or anxiety or have taken addictive drugs throughout pregnancy. In general reproductively active women tend to rate infant faces as cuter than men, which may reflect both heightened attention to relevant cues and a stronger activation in their brain reward circuitry. Perception of infant cuteness may also be influenced by reproductive hormones with the hypothalamic neuropeptide oxytocin being most strongly associated to date with increased attention and attraction to infant cues in both sexes. PMID:26236256

Neural systems and hormones mediating attraction to infant and child faces.

PubMed

Luo, Lizhu; Ma, Xiaole; Zheng, Xiaoxiao; Zhao, Weihua; Xu, Lei; Becker, Benjamin; Kendrick, Keith M

2015-01-01

We find infant faces highly attractive as a result of specific features which Konrad Lorenz termed "Kindchenschema" or "baby schema," and this is considered to be an important adaptive trait for promoting protective and caregiving behaviors in adults, thereby increasing the chances of infant survival. This review first examines the behavioral support for this effect and physical and behavioral factors which can influence it. It then provides details of the increasing number of neuroimaging and electrophysiological studies investigating the neural circuitry underlying this baby schema effect in parents and non-parents of both sexes. Next it considers potential hormonal contributions to the baby schema effect in both sexes and the neural effects associated with reduced responses to infant cues in post-partum depression, anxiety and drug taking. Overall the findings reviewed reveal a very extensive neural circuitry involved in our perception of cuteness in infant faces, with enhanced activation compared to adult faces being found in brain regions involved in face perception, attention, emotion, empathy, memory, reward and attachment, theory of mind and also control of motor responses. Both mothers and fathers also show evidence for enhanced responses in these same neural systems when viewing their own as opposed to another child. Furthermore, responses to infant cues in many of these neural systems are reduced in mothers with post-partum depression or anxiety or have taken addictive drugs throughout pregnancy. In general reproductively active women tend to rate infant faces as cuter than men, which may reflect both heightened attention to relevant cues and a stronger activation in their brain reward circuitry. Perception of infant cuteness may also be influenced by reproductive hormones with the hypothalamic neuropeptide oxytocin being most strongly associated to date with increased attention and attraction to infant cues in both sexes.

Neuroimaging and Anxiety: the Neural Substrates of Pathological and Non-pathological Anxiety.

PubMed

Taylor, James M; Whalen, Paul J

2015-06-01

Advances in the use of noninvasive neuroimaging to study the neural correlates of pathological and non-pathological anxiety have shone new light on the underlying neural bases for both the development and manifestation of anxiety. This review summarizes the most commonly observed neural substrates of the phenotype of anxiety. We focus on the neuroimaging paradigms that have shown promise in exposing this relevant brain circuitry. In this way, we offer a broad overview of how anxiety is studied in the neuroimaging laboratory and the key findings that offer promise for future research and a clearer understanding of anxiety.

Bilateral primary motor cortex circuitry is modulated due to theta burst stimulation to left dorsal premotor cortex and bimanual training.

PubMed

Neva, Jason L; Vesia, Michael; Singh, Amaya M; Staines, W Richard

2015-08-27

Motor preparatory and execution activity is enhanced after a single session of bimanual visuomotor training (BMT). Recently, we have shown that increased primary motor cortex (M1) excitability occurs when BMT involves simultaneous activation of homologous muscles and these effects are enhanced when BMT is preceded by intermittent theta burst stimulation (iTBS) to the left dorsal premotor cortex (lPMd). The neural mechanisms underlying these modulations are unclear, but may include interhemispheric interactions between homologous M1s and connectivity with premotor regions. The purpose of this study was to investigate the possible intracortical and interhemispheric modulations of the extensor carpi radials (ECR) representation in M1 bilaterally due to: (1) BMT, (2) iTBS to lPMd, and (3) iTBS to lPMd followed by BMT. This study tests three related hypotheses: (1) BMT will enhance excitability within and between M1 bilaterally, (2) iTBS to lPMd will primarily enhance left M1 (lM1) excitability, and (3) the combination of these interventions will cause a greater enhancement of bilateral M1 excitability. We used single and paired-pulse transcranial magnetic stimulation (TMS) to quantify M1 circuitry bilaterally. The results demonstrate the neural mechanisms underlying the early markers of rapid functional plasticity associated with BMT and iTBS to lPMd primarily relate to modulations of long-interval inhibitory (i.e. GABAB-mediated) circuitry within and between M1s. This work provides novel insight into the underlying neural mechanisms involved in M1 excitability changes associated with BMT and iTBS to lPMd. Critically, this work may inform rehabilitation training and stimulation techniques that modulate cortical plasticity after brain injury. Copyright © 2015. Published by Elsevier B.V.

Reward from bugs to bipeds: a comparative approach to understanding how reward circuits function

PubMed Central

Scaplen, Kristin M.; Kaun, Karla R.

2016-01-01

Abstract In a complex environment, animals learn from their responses to stimuli and events. Appropriate response to reward and punishment can promote survival, reproduction and increase evolutionary fitness. Interestingly, the neural processes underlying these responses are remarkably similar across phyla. In all species, dopamine is central to encoding reward and directing motivated behaviors, however, a comprehensive understanding of how circuits encode reward and direct motivated behaviors is still lacking. In part, this is a result of the sheer diversity of neurons, the heterogeneity of their responses and the complexity of neural circuits within which they are found. We argue that general features of reward circuitry are common across model organisms, and thus principles learned from invertebrate model organisms can inform research across species. In particular, we discuss circuit motifs that appear to be functionally equivalent from flies to primates. We argue that a comparative approach to studying and understanding reward circuit function provides a more comprehensive understanding of reward circuitry, and informs disorders that affect the brain’s reward circuitry. PMID:27328845

Functional Neuroanatomy of "Drosophila" Olfactory Memory Formation

ERIC Educational Resources Information Center

Guven-Ozkan, Tugba; Davis, Ronald L.

2014-01-01

New approaches, techniques and tools invented over the last decade and a half have revolutionized the functional dissection of neural circuitry underlying "Drosophila" learning. The new methodologies have been used aggressively by researchers attempting to answer three critical questions about olfactory memories formed with appetitive…

Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder.

PubMed

Schreiter, S; Spengler, S; Willert, A; Mohnke, S; Herold, D; Erk, S; Romanczuk-Seiferth, N; Quinlivan, E; Hindi-Attar, C; Banzhaf, C; Wackerhagen, C; Romund, L; Garbusow, M; Stamm, T; Heinz, A; Walter, H; Bermpohl, F

2016-11-01

Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses. During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately. BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation. This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders.

Lighting up the brain's reward circuitry.

PubMed

Lobo, Mary Kay

2012-07-01

The brain's reward circuit is critical for mediating natural reward behaviors including food, sex, and social interaction. Drugs of abuse take over this circuit and produce persistent molecular and cellular alterations in the brain regions and their neural circuitry that make up the reward pathway. Recent use of optogenetic technologies has provided novel insights into the functional and molecular role of the circuitry and cell subtypes within these circuits that constitute this pathway. This perspective will address the current and future use of light-activated proteins, including those involved in modulating neuronal activity, cellular signaling, and molecular properties in the neural circuitry mediating rewarding stimuli and maladaptive responses to drugs of abuse. © 2012 New York Academy of Sciences.

A Developmental Neuroscience of Borderline Pathology: Emotion Dysregulation and Social Baseline Theory

ERIC Educational Resources Information Center

Hughes, Amy E.; Crowell, Sheila E.; Uyeji, Lauren; Coan, James A.

2012-01-01

Theoretical and empirical research has linked poor emotion regulation abilities with dysfunctional frontolimbic circuitry. Consistent with this, research on borderline personality disorder (BPD) finds that frontolimbic dysfunction is a predominant neural substrate underlying the disorder. Emotion regulation is profoundly compromised in BPD.…

Neuroanatomical Substrates of Social Cognition Dysfunction in Autism

ERIC Educational Resources Information Center

Pelphrey, Kevin; Adolphs, Ralph; Morris, James P.

2004-01-01

In this review article, we summarize recent progress toward understanding the neural structures and circuitry underlying dysfunctional social cognition in autism. We review selected studies from the growing literature that has used the functional neuroimaging techniques of cognitive neuroscience to map out the neuroanatomical substrates of social…

The Neural Basis of and a Common Neural Circuitry in Different Types of Pro-social Behavior

PubMed Central

Luo, Jun

2018-01-01

Pro-social behaviors are voluntary behaviors that benefit other people or society as a whole, such as charitable donations, cooperation, trust, altruistic punishment, and fairness. These behaviors have been widely described through non self-interest decision-making in behavioral experimental studies and are thought to be increased by social preference motives. Importantly, recent studies using a combination of neuroimaging and brain stimulation, designed to reveal the neural mechanisms of pro-social behaviors, have found that a wide range of brain areas, specifically the prefrontal cortex, anterior insula, anterior cingulate cortex, and amygdala, are correlated or causally related with pro-social behaviors. In this review, we summarize the research on the neural basis of various kinds of pro-social behaviors and describe a common shared neural circuitry of these pro-social behaviors. We introduce several general ways in which experimental economics and neuroscience can be combined to develop important contributions to understanding social decision-making and pro-social behaviors. Future research should attempt to explore the neural circuitry between the frontal lobes and deeper brain areas. PMID:29922197

Tbr2 Deficiency in Mitral and Tufted Cells Disrupts Excitatory–Inhibitory Balance of Neural Circuitry in the Mouse Olfactory Bulb

PubMed Central

Mizuguchi, Rumiko; Naritsuka, Hiromi; Mori, Kensaku; Mao, Chai-An; Klein, William H.; Yoshihara, Yoshihiro

2013-01-01

The olfactory bulb (OB) is the first relay station in the brain where odor information from the olfactory epithelium is integrated, processed through its intrinsic neural circuitry, and conveyed to higher olfactory centers. Compared with profound mechanistic insights into olfactory axon wiring from the nose to the OB, little is known about the molecular mechanisms underlying the formation of functional neural circuitry among various types of neurons inside the OB. T-box transcription factor Tbr2 is expressed in various types of glutamatergic excitatory neurons in the brain including the OB projection neurons, mitral and tufted cells. Here we generated conditional knockout mice in which the Tbr2 gene is inactivated specifically in mitral and tufted cells from late embryonic stages. Tbr2 deficiency caused cell-autonomous changes in molecular expression including a compensatory increase of another T-box member, Tbr1, and a concomitant shift of vesicular glutamate transporter (VGluT) subtypes from VGluT1 to VGluT2. Tbr2-deficient mitral and tufted cells also exhibited anatomical abnormalities in their dendritic morphology and projection patterns. Additionally, several non-cell-autonomous phenotypes were observed in parvalbumin-, calbindin-, and 5T4-positive GABAergic interneurons. Furthermore, the number of dendrodendritic reciprocal synapses between mitral/tufted cells and GABAergic interneurons was significantly reduced. Upon stimulation with odorants, larger numbers of mitral and tufted cells were activated in Tbr2 conditional knockout mice. These results suggest that Tbr2 is required for not only the proper differentiation of mitral and tufted cells, but also for the establishment of functional neuronal circuitry in the OB and maintenance of excitatory–inhibitory balance crucial for odor information processing. PMID:22745484

Tbr2 deficiency in mitral and tufted cells disrupts excitatory-inhibitory balance of neural circuitry in the mouse olfactory bulb.

PubMed

Mizuguchi, Rumiko; Naritsuka, Hiromi; Mori, Kensaku; Mao, Chai-An; Klein, William H; Yoshihara, Yoshihiro

2012-06-27

The olfactory bulb (OB) is the first relay station in the brain where odor information from the olfactory epithelium is integrated, processed through its intrinsic neural circuitry, and conveyed to higher olfactory centers. Compared with profound mechanistic insights into olfactory axon wiring from the nose to the OB, little is known about the molecular mechanisms underlying the formation of functional neural circuitry among various types of neurons inside the OB. T-box transcription factor Tbr2 is expressed in various types of glutamatergic excitatory neurons in the brain including the OB projection neurons, mitral and tufted cells. Here we generated conditional knockout mice in which the Tbr2 gene is inactivated specifically in mitral and tufted cells from late embryonic stages. Tbr2 deficiency caused cell-autonomous changes in molecular expression including a compensatory increase of another T-box member, Tbr1, and a concomitant shift of vesicular glutamate transporter (VGluT) subtypes from VGluT1 to VGluT2. Tbr2-deficient mitral and tufted cells also exhibited anatomical abnormalities in their dendritic morphology and projection patterns. Additionally, several non-cell-autonomous phenotypes were observed in parvalbumin-, calbindin-, and 5T4-positive GABAergic interneurons. Furthermore, the number of dendrodendritic reciprocal synapses between mitral/tufted cells and GABAergic interneurons was significantly reduced. Upon stimulation with odorants, larger numbers of mitral and tufted cells were activated in Tbr2 conditional knockout mice. These results suggest that Tbr2 is required for not only the proper differentiation of mitral and tufted cells, but also for the establishment of functional neuronal circuitry in the OB and maintenance of excitatory-inhibitory balance crucial for odor information processing.

The emotional power of poetry: neural circuitry, psychophysiology and compositional principles

PubMed Central

Koelsch, Stefan; Wagner, Valentin; Jacobsen, Thomas; Menninghaus, Winfried

2017-01-01

Abstract It is a common experience—and well established experimentally—that music can engage us emotionally in a compelling manner. The mechanisms underlying these experiences are receiving increasing scrutiny. However, the extent to which other domains of aesthetic experience can similarly elicit strong emotions is unknown. Using psychophysiology, neuroimaging and behavioral responses, we show that recited poetry can act as a powerful stimulus for eliciting peak emotional responses, including chills and objectively measurable goosebumps that engage the primary reward circuitry. Importantly, while these responses to poetry are largely analogous to those found for music, their neural underpinnings show important differences, specifically with regard to the crucial role of the nucleus accumbens. We also go beyond replicating previous music-related studies by showing that peak aesthetic pleasure can co-occur with physiological markers of negative affect. Finally, the distribution of chills across the trajectory of poems provides insight into compositional principles of poetry. PMID:28460078

Linking ADHD to the Neural Circuitry of Attention

PubMed Central

Mueller, Adrienne; Hong, David S.; Shepard, Steven; Moore, Tirin

2017-01-01

ADHD is a complex condition with a heterogeneous presentation. Current diagnosis is primarily based on subjective experience and observer reports of behavioral symptoms – an approach that has significant limitations. Many studies show that individuals with ADHD exhibit poorer performance on cognitive tasks than neurotypical controls, and at least seven main functional domains appear implicated in ADHD. We discuss the underlying neural mechanisms of cognitive functions associated with ADHD with emphasis on the neural basis of selective attention, demonstrating the feasibility of basic research approaches for further understanding cognitive behavioral processes as they relate to human psychopathology. The study of circuit-level mechanisms underlying executive functions in nonhuman primates holds promise for advancing our understanding, and ultimately the treatment, of ADHD. PMID:28483638

Disturbance in the neural circuitry underlying positive emotional processing in post-traumatic stress disorder (PTSD). An fMRI study.

PubMed

Jatzko, Alexander; Schmitt, Andrea; Demirakca, Traute; Weimer, Erik; Braus, Dieter F

2006-03-01

This study was designed to investigate the circuitry underlying movie-induced positive emotional processing in subjects with chronic PTSD. Ten male subjects with chronic PTSD and ten matched controls were studied. In an fMRI-paradigm a sequence of a wellknown Walt Disney cartoon with positive emotional valence was shown. PTSD subjects showed an increased activation in the right posterior temporal, precentral and superior frontal cortex. Controls recruited more emotion-related regions bilateral in the temporal pole and areas of the left fusiform and parahippocampal gyrus. This pilot study is the first to reveal alterations in the processing of positive emotions in PTSD possibly reflecting a neuronal correlate of the symptom of emotional numbness in PTSD.

Games in the Brain: Neural Substrates of Gambling Addiction.

PubMed

Murch, W Spencer; Clark, Luke

2016-10-01

As a popular form of recreational risk taking, gambling games offer a paradigm for decision neuroscience research. As an individual behavior, gambling becomes dysfunctional in a subset of the population, with debilitating consequences. Gambling disorder has been recently reconceptualized as a "behavioral addiction" in the DSM-5, based on emerging parallels with substance use disorders. Why do some individuals undergo this transition from recreational to disordered gambling? The biomedical model of problem gambling is a "brain disorder" account that posits an underlying neurobiological abnormality. This article first delineates the neural circuitry that underpins gambling-related decision making, comprising ventral striatum, ventromedial prefrontal cortex, dopaminergic midbrain, and insula, and presents evidence for pathophysiology in this circuitry in gambling disorder. These biological dispositions become translated into clinical disorder through the effects of gambling games. This influence is better articulated in a public health approach that describes the interplay between the player and the (gambling) product. Certain forms of gambling, including electronic gambling machines, appear to be overrepresented in problem gamblers. These games harness psychological features, including variable ratio schedules, near-misses, "losses disguised as wins," and the illusion of control, which modulate the core decision-making circuitry that is perturbed in gambling disorder. © The Author(s) 2015.

Neural overlap in processing music and speech.

PubMed

Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L

2015-03-19

Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Neural overlap in processing music and speech

PubMed Central

Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L.

2015-01-01

Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. PMID:25646513

Neuronal Substrates of Relapse to Cocaine-Seeking Behavior: Role of Prefrontal Cortex

ERIC Educational Resources Information Center

Rebec, George V.; Sun, WenLin

2005-01-01

The return to drug seeking, even after prolonged periods of abstinence, is a defining feature of cocaine addiction. The neural circuitry underlying relapse has been identified in neuropharmacological studies of experimental animals, typically rats, and supported in brain imaging studies of human addicts. Although the nucleus accumbens (NAcc),…

Cannabis Use and Memory Brain Function in Adolescent Boys: A Cross-Sectional Multicenter Functional Magnetic Resonance Imaging Study

ERIC Educational Resources Information Center

Jager, Gerry; Block, Robert I.; Luijten, Maartje; Ramsey, Nick F.

2010-01-01

Objective: Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and…

Differential Effects of Insular and Ventromedial Prefrontal Cortex Lesions on Risky Decision-Making

ERIC Educational Resources Information Center

Clark, L.; Bechara, A.; Damasio, H.; Aitken, M. R. F.; Sahakian, B. J.; Robbins, T. W.

2008-01-01

The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear…

A cortical neural prosthesis for restoring and enhancing memory

NASA Astrophysics Data System (ADS)

Berger, Theodore W.; Hampson, Robert E.; Song, Dong; Goonawardena, Anushka; Marmarelis, Vasilis Z.; Deadwyler, Sam A.

2011-08-01

A primary objective in developing a neural prosthesis is to replace neural circuitry in the brain that no longer functions appropriately. Such a goal requires artificial reconstruction of neuron-to-neuron connections in a way that can be recognized by the remaining normal circuitry, and that promotes appropriate interaction. In this study, the application of a specially designed neural prosthesis using a multi-input/multi-output (MIMO) nonlinear model is demonstrated by using trains of electrical stimulation pulses to substitute for MIMO model derived ensemble firing patterns. Ensembles of CA3 and CA1 hippocampal neurons, recorded from rats performing a delayed-nonmatch-to-sample (DNMS) memory task, exhibited successful encoding of trial-specific sample lever information in the form of different spatiotemporal firing patterns. MIMO patterns, identified online and in real-time, were employed within a closed-loop behavioral paradigm. Results showed that the model was able to predict successful performance on the same trial. Also, MIMO model-derived patterns, delivered as electrical stimulation to the same electrodes, improved performance under normal testing conditions and, more importantly, were capable of recovering performance when delivered to animals with ensemble hippocampal activity compromised by pharmacologic blockade of synaptic transmission. These integrated experimental-modeling studies show for the first time that, with sufficient information about the neural coding of memories, a neural prosthesis capable of real-time diagnosis and manipulation of the encoding process can restore and even enhance cognitive, mnemonic processes.

Reciprocal Patterns of c-Fos Expression in the Medial Prefrontal Cortex and Amygdala after Extinction and Renewal of Conditioned Fear

ERIC Educational Resources Information Center

Knapska, Ewelina; Maren, Stephen

2009-01-01

After extinction of conditioned fear, memory for the conditioning and extinction experiences becomes context dependent. Fear is suppressed in the extinction context, but renews in other contexts. This study characterizes the neural circuitry underlying the context-dependent retrieval of extinguished fear memories using c-Fos immunohistochemistry.…

Gustatory Habituation in "Drosophila" Relies on "Rutabaga" (Adenylate Cyclase)-Dependent Plasticity of GABAergic Inhibitory Neurons

ERIC Educational Resources Information Center

Paranjpe, Pushkar; Rodrigues, Veronica; VijayRaghavan, K.; Ramaswami, Mani

2012-01-01

In some situations, animals seem to ignore stimuli which in other contexts elicit a robust response. This attenuation in behavior, which enables animals to ignore a familiar, unreinforced stimulus, is called habituation. Despite the ubiquity of this phenomenon, it is generally poorly understood in terms of the underlying neural circuitry. Hungry…

Establishing neural crest identity: a gene regulatory recipe

PubMed Central

Simões-Costa, Marcos; Bronner, Marianne E.

2015-01-01

The neural crest is a stem/progenitor cell population that contributes to a wide variety of derivatives, including sensory and autonomic ganglia, cartilage and bone of the face and pigment cells of the skin. Unique to vertebrate embryos, it has served as an excellent model system for the study of cell behavior and identity owing to its multipotency, motility and ability to form a broad array of cell types. Neural crest development is thought to be controlled by a suite of transcriptional and epigenetic inputs arranged hierarchically in a gene regulatory network. Here, we examine neural crest development from a gene regulatory perspective and discuss how the underlying genetic circuitry results in the features that define this unique cell population. PMID:25564621

Vulnerability of the neural circuitry underlying sexual behavior to chronic adult exposure to oral bisphenol a in male mice.

PubMed

Picot, Marie; Naulé, Lydie; Marie-Luce, Clarisse; Martini, Mariangela; Raskin, Kalina; Grange-Messent, Valérie; Franceschini, Isabelle; Keller, Matthieu; Mhaouty-Kodja, Sakina

2014-02-01

There are human reproduction concerns associated with extensive use of bisphenol A (BPA)-containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone. We evaluated the developmental and adult exposure to oral BPA at doses equivalent to the no-observed-adverse-effect-level (5 mg/kg body weight per day) and tolerable daily intake (TDI) (50 μg/kg body weight per day) on mouse sexual behavior and the potential mechanisms underlying BPA effects. Adult exposure to BPA reduced sexual motivation and performance at TDI dose only. Exposed males took longer to initiate mating and reach ejaculation despite normal olfactory chemoinvestigation. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. By contrast, developmental exposure to BPA at TDI or no-observed-adverse-effect-level dose did not reduce sexual behavior or alter the neuroanatomical organization of the preoptic area. Disrupting the neural androgen receptor resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and neural androgen receptor mutation share a common mechanism of action. This shows, for the first time, that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA and suggests that BPA could act in vivo as an antiandrogenic compound.

Neurostimulation and neuromodulation: a guide to selecting the right urologic patient.

PubMed

Schmidt, R A; Doggweiler, R

1998-01-01

Sensory input has an important influence on the integrity of neural circuitry. Central nervous system circuitry is programmed and reinforced by everyday experience. Even the simplest of behaviors participate in this process. A balance between inhibition and facilitation must be maintained for the CNS to function normally. For example, the bladder stores urine because of the inhibition from a closed sphincter, and relaxation of the sphincter disinhibits the bladder to permit voiding. This synergistic 'seesaw' in reflex neural activity preserves the functional and anatomical integrity of the lower urinary tract. Dysfunction and anatomical change results when an unnatural bias develops between inhibitory and facilitatory neural activity. Neurostimulation has an inherent conditioning effect on neural excitability and can restore the neural equilibrium. Voiding diaries are very useful in documenting these changes.

Neural circuitry coordinating male copulation

PubMed Central

Pavlou, Hania J; Lin, Andrew C; Neville, Megan C; Nojima, Tetsuya; Diao, Fengqiu; Chen, Brian E; White, Benjamin H; Goodwin, Stephen F

2016-01-01

Copulation is the goal of the courtship process, crucial to reproductive success and evolutionary fitness. Identifying the circuitry underlying copulation is a necessary step towards understanding universal principles of circuit operation, and how circuit elements are recruited into the production of ordered action sequences. Here, we identify key sex-specific neurons that mediate copulation in Drosophila, and define a sexually dimorphic motor circuit in the male abdominal ganglion that mediates the action sequence of initiating and terminating copulation. This sexually dimorphic circuit composed of three neuronal classes – motor neurons, interneurons and mechanosensory neurons – controls the mechanics of copulation. By correlating the connectivity, function and activity of these neurons we have determined the logic for how this circuitry is coordinated to generate this male-specific behavior, and sets the stage for a circuit-level dissection of active sensing and modulation of copulatory behavior. DOI: http://dx.doi.org/10.7554/eLife.20713.001 PMID:27855059

Review of thalamocortical resting-state fMRI studies in schizophrenia

PubMed Central

Giraldo-Chica, Monica; Woodward, Neil D.

2017-01-01

Brain circuitry underlying cognition, emotion, and perception is abnormal in schizophrenia. There is considerable evidence that the neuropathology of schizophrenia includes the thalamus, a key hub of cortical-subcortical circuitry and an important regulator of cortical activity. However, the thalamus is a heterogeneous structure composed of several nuclei with distinct inputs and cortical connections. Limitations of conventional neuroimaging methods and conflicting findings from post-mortem investigations have made it difficult to determine if thalamic pathology in schizophrenia is widespread or limited to specific thalamocortical circuits. Resting-state fMRI has proven invaluable for understanding the large-scale functional organization of the brain and investigating neural circuitry relevant to psychiatric disorders. This article summarizes resting-state fMRI investigations of thalamocortical functional connectivity in schizophrenia. Particular attention is paid to the course, diagnostic specificity, and clinical correlates of thalamocortical network dysfunction. PMID:27531067

Neural substrates of approach-avoidance conflict decision-making

PubMed Central

Aupperle, Robin L.; Melrose, Andrew J.; Francisco, Alex; Paulus, Martin P.; Stein, Murray B.

2014-01-01

Animal approach-avoidance conflict paradigms have been used extensively to operationalize anxiety, quantify the effects of anxiolytic agents, and probe the neural basis of fear and anxiety. Results from human neuroimaging studies support that a frontal-striatal-amygdala neural circuitry is important for approach-avoidance learning. However, the neural basis of decision-making is much less clear in this context. Thus, we combined a recently developed human approach-avoidance paradigm with functional magnetic resonance imaging (fMRI) to identify neural substrates underlying approach-avoidance conflict decision-making. Fifteen healthy adults completed the approach-avoidance conflict (AAC) paradigm during fMRI. Analyses of variance were used to compare conflict to non-conflict (avoid-threat and approach-reward) conditions and to compare level of reward points offered during the decision phase. Trial-by-trial amplitude modulation analyses were used to delineate brain areas underlying decision-making in the context of approach/avoidance behavior. Conflict trials as compared to the non-conflict trials elicited greater activation within bilateral anterior cingulate cortex (ACC), anterior insula, and caudate, as well as right dorsolateral prefrontal cortex. Right caudate and lateral PFC activation was modulated by level of reward offered. Individuals who showed greater caudate activation exhibited less approach behavior. On a trial-by-trial basis, greater right lateral PFC activation related to less approach behavior. Taken together, results suggest that the degree of activation within prefrontal-striatal-insula circuitry determines the degree of approach versus avoidance decision-making. Moreover, the degree of caudate and lateral PFC activation is related to individual differences in approach-avoidance decision-making. Therefore, the AAC paradigm is ideally suited to probe anxiety-related processing differences during approach-avoidance decision-making. PMID:25224633

Neural substrates of approach-avoidance conflict decision-making.

PubMed

Aupperle, Robin L; Melrose, Andrew J; Francisco, Alex; Paulus, Martin P; Stein, Murray B

2015-02-01

Animal approach-avoidance conflict paradigms have been used extensively to operationalize anxiety, quantify the effects of anxiolytic agents, and probe the neural basis of fear and anxiety. Results from human neuroimaging studies support that a frontal-striatal-amygdala neural circuitry is important for approach-avoidance learning. However, the neural basis of decision-making is much less clear in this context. Thus, we combined a recently developed human approach-avoidance paradigm with functional magnetic resonance imaging (fMRI) to identify neural substrates underlying approach-avoidance conflict decision-making. Fifteen healthy adults completed the approach-avoidance conflict (AAC) paradigm during fMRI. Analyses of variance were used to compare conflict to nonconflict (avoid-threat and approach-reward) conditions and to compare level of reward points offered during the decision phase. Trial-by-trial amplitude modulation analyses were used to delineate brain areas underlying decision-making in the context of approach/avoidance behavior. Conflict trials as compared to the nonconflict trials elicited greater activation within bilateral anterior cingulate cortex, anterior insula, and caudate, as well as right dorsolateral prefrontal cortex (PFC). Right caudate and lateral PFC activation was modulated by level of reward offered. Individuals who showed greater caudate activation exhibited less approach behavior. On a trial-by-trial basis, greater right lateral PFC activation related to less approach behavior. Taken together, results suggest that the degree of activation within prefrontal-striatal-insula circuitry determines the degree of approach versus avoidance decision-making. Moreover, the degree of caudate and lateral PFC activation related to individual differences in approach-avoidance decision-making. Therefore, the approach-avoidance conflict paradigm is ideally suited to probe anxiety-related processing differences during approach-avoidance decision-making. © 2014 Wiley Periodicals, Inc.

The Role of the Lateral Hypothalamus in Violent Intraspecific Aggression—The Glucocorticoid Deficit Hypothesis

PubMed Central

Haller, József

2018-01-01

This review argues for a central role of the lateral hypothalamus in those deviant forms of aggression, which result from chronic glucocorticoid deficiency. Currently, this nucleus is considered a key region of the mechanisms that control predatory aggression. However, recent findings demonstrate that it is strongly activated by aggression in subjects with a chronically downregulated hypothalamus-pituitary-adrenocortical (HPA) axis; moreover, this activation is causally involved in the emergence of violent aggression. The review has two parts. In the first part, we review human findings demonstrating that under certain conditions, strong stressors downregulate the HPA-axis on the long run, and that the resulting glucocorticoid deficiency is associated with violent aggression including aggressive delinquency and aggression-related psychopathologies. The second part addresses neural mechanisms in animals. We show that the experimental downregulation of HPA-axis function elicits violent aggression in rodents, and the activation of the brain circuitry that originally subserves predatory aggression accompanies this change. The lateral hypothalamus is not only an integral part of this circuitry, but can elicit deviant and violent forms of aggression. Finally, we formulate a hypothesis on the pathway that connects unfavorable social conditions to violent aggression via the neural circuitry that includes the lateral hypothalamus.

Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury.

PubMed

Minassian, Karen; McKay, W Barry; Binder, Heinrich; Hofstoetter, Ursula S

2016-04-01

Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries.

Aggression is associated with greater subsequent alcohol consumption: A shared neural basis in the ventral striatum.

PubMed

Chester, David S; DeWall, C Nathan

2018-05-01

Alcohol use and abuse (e.g., binge drinking) are among the most reliable causes of aggressive behavior. Conversely, people with aggressive dispositions (e.g., intermittent explosive disorder) are at greater risk for subsequent substance abuse. Yet it remains unknown why aggression might promote subsequent alcohol use. Both aggressive acts and alcohol use are rewarding and linked to greater activity in neural reward circuitry. Through this shared instantiation of reward, aggression may then increase subsequent alcohol consumption. Supporting this mechanistic hypothesis, participants' aggressive behavior directed at someone who had recently rejected them, was associated with more subsequent beer consumption on an ad-lib drinking task. Using functional MRI, both aggressive behavior and beer consumption were associated with greater activity in the bilateral ventral striatum during acts of retaliatory aggression. These results imply that aggression is linked to subsequent alcohol abuse, and that a mechanism underlying this effect is likely to be the activation of the brain's reward circuitry during aggressive acts. © 2018 Wiley Periodicals, Inc.

Brain pathways for cognitive-emotional decision making in the human animal.

PubMed

Levine, Daniel S

2009-04-01

As roles for different brain regions become clearer, a picture emerges of how primate prefrontal cortex executive circuitry influences subcortical decision making pathways inherited from other mammals. The human's basic needs or drives can be interpreted as residing in an on-center off-surround network in motivational regions of the hypothalamus and brain stem. Such a network has multiple attractors that, in this case, represent the amount of satisfaction of these needs, and we consider and interpret neurally a continuous-time simulated annealing algorithm for moving between attractors under the influence of noise that represents "discontent" combined with "initiative." For decision making on specific tasks, we employ a variety of rules whose neural circuitry appears to involve the amygdala and the orbital, cingulate, and dorsolateral regions of prefrontal cortex. These areas can be interpreted as connected in a three-layer adaptive resonance network. The vigilance of the network, which is influenced by the state of the hypothalamic needs network, determines the level of sophistication of the rule being utilized.

Discrete Circuits Support Generalized versus Context-Specific Vocal Learning in the Songbird.

PubMed

Tian, Lucas Y; Brainard, Michael S

2017-12-06

Motor skills depend on the reuse of individual gestures in multiple sequential contexts (e.g., a single phoneme in different words). Yet optimal performance requires that a given gesture be modified appropriately depending on the sequence in which it occurs. To investigate the neural architecture underlying such context-dependent modifications, we studied Bengalese finch song, which, like speech, consists of variable sequences of "syllables." We found that when birds are instructed to modify a syllable in one sequential context, learning generalizes across contexts; however, if unique instruction is provided in different contexts, learning is specific for each context. Using localized inactivation of a cortical-basal ganglia circuit specialized for song, we show that this balance between generalization and specificity reflects a hierarchical organization of neural substrates. Primary motor circuitry encodes a core syllable representation that contributes to generalization, while top-down input from cortical-basal ganglia circuitry biases this representation to enable context-specific learning. Copyright © 2017 Elsevier Inc. All rights reserved.

Untangling the neurobiology of coping styles in rodents: Towards neural mechanisms underlying individual differences in disease susceptibility.

PubMed

de Boer, Sietse F; Buwalda, Bauke; Koolhaas, Jaap M

2017-03-01

Considerable individual differences exist in trait-like patterns of behavioral and physiological responses to salient environmental challenges. This individual variation in stress coping styles has an important functional role in terms of health and fitness. Hence, understanding the neural embedding of coping style variation is fundamental for biobehavioral neurosciences in probing individual disease susceptibility. This review outlines individual differences in trait-aggressiveness as an adaptive component of the natural sociobiology of rats and mice, and highlights that these reflect the general style of coping that varies from proactive (aggressive) to reactive (docile). We propose that this qualitative coping style can be disentangled into multiple quantitative behavioral domains, e.g., flexibility/impulse control, emotional reactivity and harm avoidance/reward processing, that each are encoded into selective neural circuitries. Since functioning of all these brain circuitries rely on fine-tuned serotonin signaling, autoinhibitory control mechanisms of serotonergic neuron (re)activity are crucial in orchestrating general coping style. Untangling the precise neuromolecular mechanisms of different coping styles will provide a roadmap for developing better therapeutic strategies of stress-related diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks.

PubMed

Dodds, Chris M; Henson, Richard N; Suckling, John; Miskowiak, Kamilla W; Ooi, Cinly; Tait, Roger; Soltesz, Fruzsina; Lawrence, Phil; Bentley, Graham; Maltby, Kay; Skeggs, Andrew; Miller, Sam R; McHugh, Simon; Bullmore, Edward T; Nathan, Pradeep J

2013-01-01

It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.

The relationship of neurogenesis and growth of brain regions to song learning

PubMed Central

Kirn, John R.

2009-01-01

Song learning, maintenance and production require coordinated activity across multiple auditory, sensory-motor, and neuromuscular structures. Telencephalic components of the sensory-motor circuitry are unique to avian species that engage in song learning. The song system shows protracted development that begins prior to hatching but continues well into adulthood. The staggered developmental timetable for construction of the song system provides clues of subsystems involved in specific stages of song learning and maintenance. Progressive events, including neurogenesis and song system growth, as well as regressive events such as apoptosis and synapse elimination, occur during periods of song learning and the transitions between stereotyped and variable song during both development and adulthood. There is clear evidence that gonadal steroids influence the development of song attributes and shape the underlying neural circuitry. Some aspects of song system development are influenced by sensory, motor and social experience, while other aspects of neural development appear to be experience-independent. Although there are species differences in the extent to which song learning continues into adulthood, growing evidence suggests that despite differences in learning trajectories, adult refinement of song motor control and song maintenance can require remarkable behavioral and neural flexibility reminiscent of sensory-motor learning. PMID:19853905

Conservatism and the neural circuitry of threat: economic conservatism predicts greater amygdala–BNST connectivity during periods of threat vs safety

PubMed Central

Muftuler, L Tugan; Larson, Christine L

2018-01-01

Abstract Political conservatism is associated with an increased negativity bias, including increased attention and reactivity toward negative and threatening stimuli. Although the human amygdala has been implicated in the response to threatening stimuli, no studies to date have investigated whether conservatism is associated with altered amygdala function toward threat. Furthermore, although an influential theory posits that connectivity between the amygdala and bed nucleus of the stria terminalis (BNST) is important in initiating the response to sustained or uncertain threat, whether individual differences in conservatism modulate this connectivity is unknown. To test whether conservatism is associated with increased reactivity in neural threat circuitry, we measured participants’ self-reported social and economic conservatism and asked them to complete high-resolution fMRI scans while under threat of an unpredictable shock and while safe. We found that economic conservatism predicted greater connectivity between the BNST and a cluster of voxels in the left amygdala during threat vs safety. These results suggest that increased amygdala–BNST connectivity during threat may be a key neural correlate of the enhanced negativity bias found in conservatism. PMID:29126127

Conservatism and the neural circuitry of threat: economic conservatism predicts greater amygdala-BNST connectivity during periods of threat vs safety.

PubMed

Pedersen, Walker S; Muftuler, L Tugan; Larson, Christine L

2018-01-01

Political conservatism is associated with an increased negativity bias, including increased attention and reactivity toward negative and threatening stimuli. Although the human amygdala has been implicated in the response to threatening stimuli, no studies to date have investigated whether conservatism is associated with altered amygdala function toward threat. Furthermore, although an influential theory posits that connectivity between the amygdala and bed nucleus of the stria terminalis (BNST) is important in initiating the response to sustained or uncertain threat, whether individual differences in conservatism modulate this connectivity is unknown. To test whether conservatism is associated with increased reactivity in neural threat circuitry, we measured participants' self-reported social and economic conservatism and asked them to complete high-resolution fMRI scans while under threat of an unpredictable shock and while safe. We found that economic conservatism predicted greater connectivity between the BNST and a cluster of voxels in the left amygdala during threat vs safety. These results suggest that increased amygdala-BNST connectivity during threat may be a key neural correlate of the enhanced negativity bias found in conservatism. © The Author (2017). Published by Oxford University Press.

Modality specificity in the cerebro-cerebellar neurocircuitry during working memory.

PubMed

Ng, H B Tommy; Kao, K-L Cathy; Chan, Y C; Chew, Effie; Chuang, K H; Chen, S H Annabel

2016-05-15

Previous studies have suggested cerebro-cerebellar circuitry in working memory. The present fMRI study aims to distinguish differential cerebro-cerebellar activation patterns in verbal and visual working memory, and employs a quantitative analysis to deterimine lateralization of the activation patterns observed. Consistent with Chen and Desmond (2005a,b) predictions, verbal working memory activated a cerebro-cerebellar circuitry that comprised left-lateralized language-related brain regions including the inferior frontal and posterior parietal areas, and subcortically, right-lateralized superior (lobule VI) and inferior cerebellar (lobule VIIIA/VIIB) areas. In contrast, a distributed network of bilateral inferior frontal and inferior temporal areas, and bilateral superior (lobule VI) and inferior (lobule VIIB) cerebellar areas, was recruited during visual working memory. Results of the study verified that a distinct cross cerebro-cerebellar circuitry underlies verbal working memory. However, a neural circuitry involving specialized brain areas in bilateral neocortical and bilateral cerebellar hemispheres subserving visual working memory is observed. Findings are discussed in the light of current models of working memory and data from related neuroimaging studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Modeling neural circuits in Parkinson's disease.

PubMed

Psiha, Maria; Vlamos, Panayiotis

2015-01-01

Parkinson's disease (PD) is caused by abnormal neural activity of the basal ganglia which are connected to the cerebral cortex in the brain surface through complex neural circuits. For a better understanding of the pathophysiological mechanisms of PD, it is important to identify the underlying PD neural circuits, and to pinpoint the precise nature of the crucial aberrations in these circuits. In this paper, the general architecture of a hybrid Multilayer Perceptron (MLP) network for modeling the neural circuits in PD is presented. The main idea of the proposed approach is to divide the parkinsonian neural circuitry system into three discrete subsystems: the external stimuli subsystem, the life-threatening events subsystem, and the basal ganglia subsystem. The proposed model, which includes the key roles of brain neural circuit in PD, is based on both feed-back and feed-forward neural networks. Specifically, a three-layer MLP neural network with feedback in the second layer was designed. The feedback in the second layer of this model simulates the dopamine modulatory effect of compacta on striatum.

Imaging genetics and the neurobiological basis of individual differences in vulnerability to addiction.

PubMed

Sweitzer, Maggie M; Donny, Eric C; Hariri, Ahmad R

2012-06-01

Addictive disorders are heritable, but the search for candidate functional polymorphisms playing an etiological role in addiction is hindered by complexity of the phenotype and the variety of factors interacting to impact behavior. Advances in human genome sequencing and neuroimaging technology provide an unprecedented opportunity to explore the impact of functional genetic variants on variability in behaviorally relevant neural circuitry. Here, we present a model for merging these technologies to trace the links between genes, brain, and addictive behavior. We describe imaging genetics and discuss the utility of its application to addiction. We then review data pertaining to impulsivity and reward circuitry as an example of how genetic variation may lead to variation in behavioral phenotype. Finally, we present preliminary data relating the neural basis of reward processing to individual differences in nicotine dependence. Complex human behaviors such as addiction can be traced to their basic genetic building blocks by identifying intermediate behavioral phenotypes, associated neural circuitry, and underlying molecular signaling pathways. Impulsivity has been linked with variation in reward-related activation in the ventral striatum (VS), altered dopamine signaling, and functional polymorphisms of DRD2 and DAT1 genes. In smokers, changes in reward-related VS activation induced by smoking abstinence may be associated with severity of nicotine dependence. Variation in genes related to dopamine signaling may contribute to heterogeneity in VS sensitivity to reward and, ultimately, to addiction. These findings illustrate the utility of the imaging genetics approach for investigating the neurobiological basis for vulnerability to addiction. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Alternative neural circuitry that might be impaired in the development of Alzheimer disease.

PubMed

Avila, Jesus; Perry, George; Strange, Bryan A; Hernandez, Felix

2015-01-01

It is well established that some individuals with normal cognitive capacity have abundant senile plaques in their brains. It has been proposed that those individuals are resilient or have compensation factors to prevent cognitive decline. In this comment, we explore an alternative mechanism through which cognitive capacity is maintained. This mechanism could involve the impairment of alternative neural circuitry. Also, the proportion of molecules such as Aβ or tau protein present in different areas of the brain could be important.

What does the fruitless gene tell us about nature vs. nurture in the sex life of Drosophila?

PubMed

Yamamoto, Daisuke; Kohatsu, Soh

2017-04-03

The fruitless (fru) gene in Drosophila has been proposed to play a master regulator role in the formation of neural circuitries for male courtship behavior, which is typically considered to be an innate behavior composed of a fixed action pattern as generated by the central pattern generator. However, recent studies have shed light on experience-dependent changes and sensory-input-guided plasticity in courtship behavior. For example, enhanced male-male courtship, a fru mutant "hallmark," disappears when fru-mutant males are raised in isolation. The fact that neural fru expression is induced by neural activities in the adult invites the supposition that Fru as a chromatin regulator mediates experience-dependent epigenetic modification, which underlies the neural and behavioral plasticity.

A GPU-accelerated cortical neural network model for visually guided robot navigation.

PubMed

Beyeler, Michael; Oros, Nicolas; Dutt, Nikil; Krichmar, Jeffrey L

2015-12-01

Humans and other terrestrial animals use vision to traverse novel cluttered environments with apparent ease. On one hand, although much is known about the behavioral dynamics of steering in humans, it remains unclear how relevant perceptual variables might be represented in the brain. On the other hand, although a wealth of data exists about the neural circuitry that is concerned with the perception of self-motion variables such as the current direction of travel, little research has been devoted to investigating how this neural circuitry may relate to active steering control. Here we present a cortical neural network model for visually guided navigation that has been embodied on a physical robot exploring a real-world environment. The model includes a rate based motion energy model for area V1, and a spiking neural network model for cortical area MT. The model generates a cortical representation of optic flow, determines the position of objects based on motion discontinuities, and combines these signals with the representation of a goal location to produce motor commands that successfully steer the robot around obstacles toward the goal. The model produces robot trajectories that closely match human behavioral data. This study demonstrates how neural signals in a model of cortical area MT might provide sufficient motion information to steer a physical robot on human-like paths around obstacles in a real-world environment, and exemplifies the importance of embodiment, as behavior is deeply coupled not only with the underlying model of brain function, but also with the anatomical constraints of the physical body it controls. Copyright © 2015 Elsevier Ltd. All rights reserved.

Longitudinal relationships among activity in attention redirection neural circuitry and symptom severity in youth.

PubMed

Bertocci, Michele A; Bebko, Genna; Dwojak, Amanda; Iyengar, Satish; Ladouceur, Cecile D; Fournier, Jay C; Versace, Amelia; Perlman, Susan B; Almeida, Jorge R C; Travis, Michael J; Gill, Mary Kay; Bonar, Lisa; Schirda, Claudiu; Diwadkar, Vaibhav A; Sunshine, Jeffrey L; Holland, Scott K; Kowatch, Robert A; Birmaher, Boris; Axelson, David; Horwitz, Sarah M; Frazier, Thomas; Arnold, L Eugene; Fristad, Mary A; Youngstrom, Eric A; Findling, Robert L; Phillips, Mary L

2017-05-01

Changes in neural circuitry function may be associated with longitudinal changes in psychiatric symptom severity. Identification of these relationships may aid in elucidating the neural basis of psychiatric symptom evolution over time. We aimed to distinguish these relationships using data from the Longitudinal Assessment of Manic Symptoms (LAMS) cohort. Forty-one youth completed two study visits (mean=21.3 months). Elastic-net regression (Multiple response Gaussian family) identified emotional regulation neural circuitry that changed in association with changes in depression, mania, anxiety, affect lability, and positive mood and energy dysregulation, accounting for clinical and demographic variables. Non-zero coefficients between change in the above symptom measures and change in activity over the inter-scan interval were identified in right amygdala and left ventrolateral prefrontal cortex. Differing patterns of neural activity change were associated with changes in each of the above symptoms over time. Specifically, from Scan1 to Scan2, worsening affective lability and depression severity were associated with increased right amygdala and left ventrolateral prefrontal cortical activity. Worsening anxiety and positive mood and energy dysregulation were associated with decreased right amygdala and increased left ventrolateral prefrontal cortical activity. Worsening mania was associated with increased right amygdala and decreased left ventrolateral prefrontal cortical activity. These changes in neural activity between scans accounted for 13.6% of the variance; that is 25% of the total explained variance (39.6%) in these measures. Distinct neural mechanisms underlie changes in different mood and anxiety symptoms overtime.

Understanding the Role of TSC1/2 in Cerebellar Purkinje Neurons

DTIC Science & Technology

2016-09-01

development of new pharmacotherapy for TSC-patients with autism . 15. SUBJECT TERMS autism , tuberous sclerosis, cerebellum 16. SECURITY CLASSIFICATION...patients with TSC display symptoms of autism spectrum disorder (ASD). Although much research has been conducted, the neural circuitry and molecular...mechanism underlying autism remain unclear. Specific cerebellar defects have been seen in TSC patients, suggesting a crucial role for the cerebellum

Interactions between Medial Prefrontal Cortex and Dorsomedial Striatum Are Necessary for Odor Span Capacity in Rats: Role of GluN2B-Containing NMDA Receptors

ERIC Educational Resources Information Center

Davies, Don A.; Greba, Quentin; Selk, Jantz C.; Catton, Jillian K.; Baillie, Landon D.; Mulligan, Sean J.; Howland, John G.

2017-01-01

Working memory is involved in the maintenance and manipulation of information essential for complex cognition. While the neural substrates underlying working memory capacity have been studied in humans, considerably less is known about the circuitry mediating working memory capacity in rodents. Therefore, the present experiments tested the…

Gender development and the human brain.

PubMed

Hines, Melissa

2011-01-01

Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones.

Neural Circuits Underlying Crying and Cry Responding in Mammals

PubMed Central

Newman, John D.

2007-01-01

Crying is a universal vocalization in human infants, as well as in the infants of other mammals. Little is known about the neural structures underlying cry production, or the circuitry that mediates a caregiver’s response to cry sounds. In this review, the specific structures known or suspected to be involved in this circuit are identified, along with neurochemical systems and hormones for which evidence suggests a role in responding to infants and infant cries. In addition, evidence that crying elicits parental responses in different mammals is presented. An argument is made for including ‘crying’ as a functional category in the vocal repertoire of all mammalian infants (and the adults of some species). The prevailing neural model for crying production considers forebrain structures to be dispensable. However, evidence for the anterior cingulate gyrus in cry production, and this structure along with the amygdala and some other forebrain areas in responding to cries is presented. PMID:17363076

Thinking outside the cortex: social motivation in the evolution and development of language.

PubMed

Syal, Supriya; Finlay, Barbara L

2011-03-01

Alteration of the organization of social and motivational neuroanatomical circuitry must have been an essential step in the evolution of human language. Development of vocal communication across species, particularly birdsong, and new research on the neural organization and evolution of social and motivational circuitry, together suggest that human language is the result of an obligatory link of a powerful cortico-striatal learning system, and subcortical socio-motivational circuitry.

The relationship of neurogenesis and growth of brain regions to song learning.

PubMed

Kirn, John R

2010-10-01

Song learning, maintenance and production require coordinated activity across multiple auditory, sensory-motor, and neuromuscular structures. Telencephalic components of the sensory-motor circuitry are unique to avian species that engage in song learning. The song system shows protracted development that begins prior to hatching but continues well into adulthood. The staggered developmental timetable for construction of the song system provides clues of subsystems involved in specific stages of song learning and maintenance. Progressive events, including neurogenesis and song system growth, as well as regressive events such as apoptosis and synapse elimination, occur during periods of song learning and the transitions between variable and stereotyped song during both development and adulthood. There is clear evidence that gonadal steroids influence the development of song attributes and shape the underlying neural circuitry. Some aspects of song system development are influenced by sensory, motor and social experience, while other aspects of neural development appear to be experience-independent. Although there are species differences in the extent to which song learning continues into adulthood, growing evidence suggests that despite differences in learning trajectories, adult refinement of song motor control and song maintenance can require remarkable behavioral and neural flexibility reminiscent of sensory-motor learning. Copyright © 2009 Elsevier Inc. All rights reserved.

Facing changes and changing faces in adolescence: A new model for investigating adolescent-specific interactions between pubertal, brain and behavioral development

PubMed Central

Scherf, K. Suzanne; Behrmann, Marlene; Dahl, Ronald E.

2015-01-01

Adolescence is a time of dramatic physical, cognitive, emotional, and social changes as well as a time for the development of many social-emotional problems. These characteristics raise compelling questions about accompanying neural changes that are unique to this period of development. Here, we propose that studying adolescent-specific changes in face processing and its underlying neural circuitry provides an ideal model for addressing these questions. We also use this model to formulate new hypotheses. Specifically, pubertal hormones are likely to increase motivation to master new peer-oriented developmental tasks, which will in turn, instigate the emergence of new social/affective components of face processing. We also predict that pubertal hormones have a fundamental impact on the reorganization of neural circuitry supporting face processing and propose, in particular, that, the functional connectivity, or temporal synchrony, between regions of the face-processing network will change with the emergence of these new components of face processing in adolescence. Finally, we show how this approach will help reveal why adolescence may be a period of vulnerability in brain development and suggest how it could lead to prevention and intervention strategies that facilitate more adaptive functional interactions between regions within the broader social information processing network. PMID:22483070

Preliminary investigation of the relationships between sleep duration, reward circuitry function, and mood dysregulation in youth offspring of parents with bipolar disorder.

PubMed

Soehner, Adriane M; Bertocci, Michele A; Manelis, Anna; Bebko, Genna; Ladouceur, Cecile D; Graur, Simona; Monk, Kelly; Bonar, Lisa K; Hickey, Mary Beth; Axelson, David; Goldstein, Benjamin I; Goldstein, Tina R; Birmaher, Boris; Phillips, Mary L

2016-11-15

Altered reward circuitry function is observed in individuals with bipolar disorder (BD) and their unaffected offspring (OBP). While OBP are at elevated risk for BD, modifiable risk factors that may exacerbate neural vulnerabilities in OBP remain under-characterized. As sleep loss is strongly linked to mania in BD, this study tested associations between sleep duration, reward circuitry function, and mood dysregulation in OBP. Two groups of youth unaffected with BD (9-17yr) completed a number-guessing fMRI reward paradigm: 25 OBP and 21 age-sex-IQ-matched offspring of control parents with non-BD psychopathology (OCP), to differentiate risk for BD from risk for psychopathology more broadly. Regressions tested effects of group status, self-reported past-week sleep duration, and their interaction on neural activity and bilateral ventral striatum (VS) functional connectivity to win>control. Correlations with parent-reported mood dysregulation were assessed. Group effects were observed for right posterior insula activity (OCP>OBP) and VS-left posterior insula connectivity (OBP>OCP). Group ⁎ sleep duration interactions were observed for left dorsal anterior-mid-cingulate (daMCC) activity and VS-left anterior insula/ventrolateral prefrontal cortex (VLPFC) connectivity. Specifically, sleep duration and daMCC activity were positively related in OBP, but negatively related in OCP and sleep duration and VS-left anterior insula/VLPFC connectivity were negatively related in OBP, but positively in OCP. Additionally, increased VS-left posterior insula connectivity and VS-left anterior insula/VLPFC connectivity were associated with greater mood dysregulation in OBP only. Cross-sectional design and small sample size. Altered reward-related VS-insula connectivity could represent a neural pathway underpinning mood dysregulation in OBP, and may be modulated by shortened sleep duration. Copyright © 2016 Elsevier B.V. All rights reserved.

Lifelong Bilingualism and Neural Reserve against Alzheimer’s disease: A Review of Findings and Potential Mechanisms

PubMed Central

Gold, Brian T.

2014-01-01

Alzheimer’s disease (AD) is a progressive brain disorder that initially affects medial temporal lobe circuitry and memory functions. Current drug treatments have only modest effects on the symptomatic course of the disease. In contrast, a growing body of evidence suggests that lifelong bilingualism may delay the onset of clinical AD symptoms by several years. The purpose of the present review is to summarize evidence for bilingualism as a reserve variable against AD and discuss potential underlying neurocognitive mechanisms. Evidence is reviewed suggesting that bilingualism may delay clinical AD symptoms by protecting frontostriatal and frontoparietal executive control circuitry rather than medial temporal lobe memory circuitry. Cellular and molecular mechanisms that may contribute to bilingual cognitive reserve effects are discussed, including those that may affect neuronal metabolic functions, dynamic neuronal-glial interactions, vascular factors, myelin structure and neurochemical signaling. Future studies that may test some of these potential mechanisms of bilingual CR effects are proposed. PMID:25496781

Lifelong bilingualism and neural reserve against Alzheimer's disease: a review of findings and potential mechanisms.

PubMed

Gold, Brian T

2015-03-15

Alzheimer's disease (AD) is a progressive brain disorder that initially affects medial temporal lobe circuitry and memory functions. Current drug treatments have only modest effects on the symptomatic course of the disease. In contrast, a growing body of evidence suggests that lifelong bilingualism may delay the onset of clinical AD symptoms by several years. The purpose of the present review is to summarize evidence for bilingualism as a reserve variable against AD and discuss potential underlying neurocognitive mechanisms. Evidence is reviewed suggesting that bilingualism may delay clinical AD symptoms by protecting frontostriatal and frontoparietal executive control circuitry rather than medial temporal lobe memory circuitry. Cellular and molecular mechanisms that may contribute to bilingual cognitive reserve effects are discussed, including those that may affect neuronal metabolic functions, dynamic neuronal-glial interactions, vascular factors, myelin structure and neurochemical signaling. Future studies that may test some of these potential mechanisms of bilingual CR effects are proposed. Copyright © 2014 Elsevier B.V. All rights reserved.

The hippocampus and dorsal raphe nucleus are key brain areas associated with the antidepressant effects of lithium augmentation of desipramine.

PubMed

Cussotto, Sofia; Cryan, John F; O'Leary, Olivia F

2017-05-01

Approximately 50% of depressed individuals fail to achieve remission with first-line antidepressant drugs and a third remain treatment-resistant. When first-line antidepressant treatment is unsuccessful, second-line strategies include dose optimisation, switching to another antidepressant, combination with another antidepressant, or augmentation with a non-antidepressant medication. Much of the evidence for the efficacy of augmentation strategies comes from studies using lithium to augment the effects of tricyclic antidepressants. The neural circuitry underlying the therapeutic effects of lithium augmentation is not yet fully understood. Recently, we reported that chronic treatment with a combination of lithium and the antidepressant desipramine, exerted antidepressant-like behavioural effects in a mouse strain (BALB/cOLaHsd) that did not exhibit an antidepressant-like behavioural response to either drug alone. In the present study, we used this model in combination with ΔFosB/FosB immunohistochemistry to identify brain regions chronically affected by lithium augmentation of desipramine when compared to either treatment alone. The data suggest that the dorsal raphe nucleus and the CA3 regions of the dorsal hippocampus are key nodes in the neural circuitry underlying antidepressant action of lithium augmentation of desipramine. These data give new insight into the neurobiology underlying the mechanism of lithium augmentation in the context of treatment-resistant depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-Disturbances as a Possible Premorbid Indicator of Schizophrenia Risk: A Neurodevelopmental Perspective

PubMed Central

Brent, Benjamin K.; Seidman, Larry J.; Thermenos, Heidi W.; Holt, Daphne J.; Keshavan, Matcheri S.

2013-01-01

Self-disturbances (SDs) are increasingly identified in schizophrenia and are theorized to confer vulnerability to psychosis. Neuroimaging research has shed some light on the neural correlates of SDs in schizophrenia. But, the onset and trajectory of the neural alterations underlying SDs in schizophrenia remain incompletely understood. We hypothesize that the aberrant structure and function of brain areas (e.g., prefrontal, lateral temporal, and parietal cortical structures) comprising the “neural circuitry of self” may represent an early, premorbid (i.e., pre-prodromal) indicator of schizophrenia risk. Consistent with neurodevelopmental models, we argue that “early” (i.e., perinatal) dysmaturational processes (e.g., abnormal cortical neural cell migration and mini-columnar formation) affecting key prefrontal (e.g., medial prefrontal cortex), lateral temporal cortical (e.g., superior temporal sulcus), parietal (e.g., inferior parietal lobule) structures involved in self-processing may lead to subtle disruptions of “self” during childhood in persons at risk for schizophrenia. During adolescence, progressive neurodevelopmental alterations (e.g., aberrant synaptic pruning) affecting the neural circuitry of self may contribute to worsening of SDs. This could result in the emergence of prodromal symptoms and, eventually, full-blown psychosis. To highlight why adolescence may be a period of heightened risk for SDs, we first summarize the literature regarding the neural correlates of self in typically developing children. Next, we present evidence from neuroimaging studies in genetic high-risk youth suggesting that fronto-temporal-parietal structures mediating self-reflection may be abnormal in the premorbid period. Our goal is that the ideas presented here might provide future directions for research into the neurobiology of SDs during the pre-psychosis development of youth at risk for schizophrenia. PMID:23932148

Functional Specialization within the Striatum along Both the Dorsal/Ventral and Anterior/Posterior Axes during Associative Learning via Reward and Punishment

ERIC Educational Resources Information Center

Mattfeld, Aaron T.; Gluck, Mark A.; Stark, Craig E. L.

2011-01-01

The goal of the present study was to elucidate the role of the human striatum in learning via reward and punishment during an associative learning task. Previous studies have identified the striatum as a critical component in the neural circuitry of reward-related learning. It remains unclear, however, under what task conditions, and to what…

Dissociable Frontostriatal White Matter Connectivity Underlies Reward and Motor Impulsivity

PubMed Central

Hampton, William H.; Alm, Kylie H.; Venkatraman, Vinod; Nugiel, Tehila; Olson, Ingrid R.

2017-01-01

Dysfunction of cognitive control often leads to impulsive decision-making in clinical and healthy populations. Some research suggests that a generalized cognitive control mechanism underlies the ability to modulate various types of impulsive behavior, while other evidence suggests different forms of impulsivity are dissociable, and rely on distinct neural circuitry. Past research consistently implicates several brain regions, such as the striatum and portions of the prefrontal cortex, in impulsive behavior. However the ventral and dorsal striatum are distinct in regards to function and connectivity. Nascent evidence points to the importance of frontostriatal white matter connectivity in impulsivity, yet it remains unclear whether particular tracts relate to different control behaviors. Here we used probabilistic tractography of diffusion imaging data to relate ventral and dorsal frontostriatal connectivity to reward and motor impulsivity measures. We found a double dissociation such that individual differences in white matter connectivity between the ventral striatum and the ventromedial prefrontal cortex and dorsolateral prefrontal cortex was associated with reward impulsivity, as measured by delay discounting, whereas connectivity between dorsal striatum and supplementary motor area was associated with motor impulsivity, but not vice versa. Our findings suggest that (a) structural connectivity can is associated with a large amount of behavioral variation; (b) different types of impulsivity are driven by dissociable frontostriatal neural circuitry. PMID:28189592

Border-ownership-dependent tilt aftereffect in incomplete figures

NASA Astrophysics Data System (ADS)

Sugihara, Tadashi; Tsuji, Yoshihisa; Sakai, Ko

2007-01-01

A recent physiological finding of neural coding for border ownership (BO) that defines the direction of a figure with respect to the border has provided a possible basis for figure-ground segregation. To explore the underlying neural mechanisms of BO, we investigated stimulus configurations that activate BO circuitry through psychophysical investigation of the BO-dependent tilt aftereffect (BO-TAE). Specifically, we examined robustness of the border ownership signal by determining whether the BO-TAE is observed when gestalt factors are broken. The results showed significant BO-TAEs even when a global shape was not explicitly given due to the ambiguity of the contour, suggesting a contour-independent mechanism for BO coding.

Border-ownership-dependent tilt aftereffect in incomplete figures.

PubMed

Sugihara, Tadashi; Tsuji, Yoshihisa; Sakai, Ko

2007-01-01

A recent physiological finding of neural coding for border ownership (BO) that defines the direction of a figure with respect to the border has provided a possible basis for figure-ground segregation. To explore the underlying neural mechanisms of BO, we investigated stimulus configurations that activate BO circuitry through psychophysical investigation of the BO-dependent tilt aftereffect (BO-TAE). Specifically, we examined robustness of the border ownership signal by determining whether the BO-TAE is observed when gestalt factors are broken. The results showed significant BO-TAEs even when a global shape was not explicitly given due to the ambiguity of the contour, suggesting a contour-independent mechanism for BO coding.

Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species.

PubMed

Gee, Dylan G; Fetcho, Robert N; Jing, Deqiang; Li, Anfei; Glatt, Charles E; Drysdale, Andrew T; Cohen, Alexandra O; Dellarco, Danielle V; Yang, Rui R; Dale, Anders M; Jernigan, Terry L; Lee, Francis S; Casey, B J

2016-04-19

Anxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in gene expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) levels, would impact the development of frontolimbic circuitry implicated in anxiety disorders. In a pediatric imaging sample of over 1,000 3- to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that emerge by ∼12 y of age and are paralleled by changes in anxiety-related behavior. Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environmental backgrounds, we confirm phenotypic differences in frontoamygdala circuitry and anxiety-related behavior by postnatal day 45 (P45), when AEA levels begin to decrease, and also, at P75 but not before. These results, which converge across species and level of analysis, highlight the importance of underlying developmental neurobiology in the emergence of genetic effects on brain circuitry and function. Moreover, the results have important implications for the identification of risk for disease and precise targeting of treatments to the biological state of the developing brain as a function of developmental changes in gene expression and neural circuit maturation.

Neural evidence that human emotions share core affective properties.

PubMed

Wilson-Mendenhall, Christine D; Barrett, Lisa Feldman; Barsalou, Lawrence W

2013-06-01

Research on the "emotional brain" remains centered around the idea that emotions like fear, happiness, and sadness result from specialized and distinct neural circuitry. Accumulating behavioral and physiological evidence suggests, instead, that emotions are grounded in core affect--a person's fluctuating level of pleasant or unpleasant arousal. A neuroimaging study revealed that participants' subjective ratings of valence (i.e., pleasure/displeasure) and of arousal evoked by various fear, happiness, and sadness experiences correlated with neural activity in specific brain regions (orbitofrontal cortex and amygdala, respectively). We observed these correlations across diverse instances within each emotion category, as well as across instances from all three categories. Consistent with a psychological construction approach to emotion, the results suggest that neural circuitry realizes more basic processes across discrete emotions. The implicated brain regions regulate the body to deal with the world, producing the affective changes at the core of emotions and many other psychological phenomena.

Neural Evidence that Human Emotions Share Core Affective Properties

PubMed Central

Wilson-Mendenhall, Christine D.; Barrett, Lisa Feldman; Barsalou, Lawrence W.

2014-01-01

Research on the “emotional brain” remains centered around the idea that emotions like fear, happiness, and sadness result from specialized and distinct neural circuitry. Accumulating behavioral and physiological evidence suggests, instead, that emotions are grounded in core affect – a person's fluctuating level of pleasant or unpleasant arousal. A neuroimaging study revealed that participants' subjective ratings of valence (i.e., pleasure/displeasure) and of arousal evoked by various fear, happiness, and sadness experiences correlated with neural activity in specific brain regions (orbitofrontal cortex and amygdala, respectively). We observed these correlations across diverse instances within each emotion category, as well as across instances from all three categories. Consistent with a psychological construction approach to emotion, the results suggest that neural circuitry realizes more basic processes across discrete emotions. The implicated brain regions regulate the body to deal with the world, producing the affective changes at the core of emotions and many other psychological phenomena. PMID:23603916

Thinking outside the Cortex: Social Motivation in the Evolution and Development of Language

ERIC Educational Resources Information Center

Syal, Supriya; Finlay, Barbara L.

2011-01-01

Alteration of the organization of social and motivational neuroanatomical circuitry must have been an essential step in the evolution of human language. Development of vocal communication across species, particularly birdsong, and new research on the neural organization and evolution of social and motivational circuitry, together suggest that…

Cell-type Specific Optogenetic Mice for Dissecting Neural Circuitry Function

PubMed Central

Zhao, Shengli; Ting, Jonathan T.; Atallah, Hisham E.; Qiu, Li; Tan, Jie; Gloss, Bernd; Augustine, George J.; Deisseroth, Karl; Luo, Minmin; Graybiel, Ann M.; Feng, Guoping

2011-01-01

Optogenetic methods have emerged as powerful tools for dissecting neural circuit connectivity, function, and dysfunction. We used a Bacterial Artificial Chromosome (BAC) transgenic strategy to express Channelrhodopsin2 (ChR2) under the control of cell-type specific promoter elements. We provide a detailed functional characterization of the newly established VGAT-ChR2-EYFP, ChAT-ChR2-EYFP, TPH2-ChR2-EYFP and Pvalb-ChR2-EYFP BAC transgenic mouse lines and demonstrate the utility of these lines for precisely controlling action potential firing of GABAergic, cholinergic, serotonergic, and parvalbumin+ neuron subsets using blue light. This resource of cell type-specific ChR2 mouse lines will facilitate the precise mapping of neuronal connectivity and the dissection of the neural basis of behavior. PMID:21985008

Associations Among Pubertal Development, Empathic Ability, and Neural Responses While Witnessing Peer Rejection in Adolescence

PubMed Central

Masten, Carrie L.; Eisenberger, Naomi I.; Pfeifer, Jennifer H.; Colich, Natalie L.; Dapretto, Mirella

2012-01-01

Links among concurrent and longitudinal changes in pubertal development and empathic ability from age 10 to 13 and neural responses while witnessing peer rejection at age 13 were examined in 16 participants. More advanced pubertal development at age 13, and greater longitudinal increases in pubertal development, related to increased activity in regions underlying cognitive aspects of empathy. Likewise, at age 13 greater perspective taking related to activity in cognitive empathy-related regions; however, affective components of empathy (empathic concern and personal distress) were additionally associated with activity in affective pain-related regions. Longitudinal increases in empathic ability related to cognitive and affective empathy-related circuitry. Findings provide preliminary evidence that physical and cognitive-emotional development relate to adolescents’ neural responses when witnessing peer rejection. PMID:23379360

The ventral hippocampus, but not the dorsal hippocampus is critical for learned approach-avoidance decision making.

PubMed

Schumacher, Anett; Vlassov, Ekaterina; Ito, Rutsuko

2016-04-01

The resolution of an approach-avoidance conflict induced by ambivalent information involves the appraisal of the incentive value of the outcomes and associated stimuli to orchestrate an appropriate behavioral response. Much research has been directed at delineating the neural circuitry underlying approach motivation and avoidance motivation separately. Very little research, however, has examined the neural substrates engaged at the point of decision making when opposing incentive motivations are experienced simultaneously. We hereby examine the role of the dorsal and ventral hippocampus (HPC) in a novel approach-avoidance decision making paradigm, revisiting a once popular theory of HPC function, which posited the HPC to be the driving force of a behavioral inhibition system that is activated in situations of imminent threat. Rats received pre-training excitotoxic lesions of the dorsal or ventral HPC, and were trained to associate different non-spatial cues with appetitive, aversive and neutral outcomes in three separate arms of the radial maze. On the final day of testing, a state of approach-avoidance conflict was induced by simultaneously presenting two cues of opposite valences, and comparing the time the rats spent interacting with the superimposed 'conflict' cue, and the neutral cue. The ventral HPC-lesioned group showed significant preference for the conflict cue over the neutral cue, compared to the dorsal HPC-lesioned, and control groups. Thus, we provide evidence that the ventral, but not dorsal HPC, is a crucial component of the neural circuitry concerned with exerting inhibitory control over approach tendencies under circumstances in which motivational conflict is experienced. © 2015 Wiley Periodicals, Inc.

Neural Correlates of the Perception for Novel Objects

PubMed Central

Zhang, Hao; Liu, Jia; Zhang, Qinglin

2013-01-01

Perception of novel objects is of enormous importance in our lives. People have to perceive or understand novel objects when seeing an original painting, admiring an unconventional construction, and using an inventive device. However, very little is known about neural mechanisms underlying the perception for novel objects. Perception of novel objects relies on the integration of unusual features of novel objects in order to identify what such objects are. In the present study, functional Magnetic Resonance Imaging (MRI) was employed to investigate neural correlates of perception of novel objects. The neuroimaging data on participants engaged in novel object viewing versus ordinary object viewing revealed that perception of novel objects involves significant activation in the left precuneus (Brodmann area 7) and the right visual cortex. The results suggest that the left precuneus is associated with the integration of unusual features of novel objects, while the right visual cortex is sensitive to the detection of such features. Our findings highlight the left precuneus as a crucial component of the neural circuitry underlying perception of novel objects. PMID:23646167

SMAD7 directly converts human embryonic stem cells to telencephalic fate by a default mechanism

PubMed Central

Ozair, Mohammad Zeeshan; Noggle, Scott; Warmflash, Aryeh; Krzyspiak, Joanna Ela; Brivanlou, Ali H.

2013-01-01

Human embryonic stem cells (hESCs) provide a valuable window into the dissection of the molecular circuitry underlying the early formation of the human forebrain. However, dissection of signaling events in forebrain development using current protocols is complicated by non-neural contamination and fluctuation of extrinsic influences. Here we show that SMAD7, a cell-intrinsic inhibitor of TGFβ signaling, is sufficient to directly convert pluripotent hESCs to an anterior neural fate. Time-course gene expression revealed down-regulation of MAPK components, and combining MEK1/2 inhibition with SMAD7-mediated TGFβ inhibition promoted telencephalic conversion. FGF-MEK and TGFβ-SMAD signaling maintain hESCs by promoting pluripotency genes and repressing neural genes. Our findings suggest that in the absence of these cues, pluripotent cells simply revert to a program of neural conversion. Hence the “primed” state of hESCs requires inhibition of the “default” state of neural fate acquisition. This has parallels in amphibians, suggesting an evolutionarily conserved mechanism. PMID:23034881

Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders.

PubMed

O'Donnell, Cian; Gonçalves, J Tiago; Portera-Cailliau, Carlos; Sejnowski, Terrence J

2017-10-11

A leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this one-dimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here, we combined computational simulations with analysis of in vivo two-photon Ca 2+ imaging data from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: (1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; (2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; (3) The direction of circuit alterations in Fmr1 KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher dimensional models that can better capture the multidimensional computational functions of neural circuits.

Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders

PubMed Central

Gonçalves, J Tiago; Portera-Cailliau, Carlos

2017-01-01

A leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this one-dimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here, we combined computational simulations with analysis of in vivo two-photon Ca2+ imaging data from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: (1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; (2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; (3) The direction of circuit alterations in Fmr1 KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher dimensional models that can better capture the multidimensional computational functions of neural circuits. PMID:29019321

Plasticity of reward neurocircuitry and the 'dark side' of drug addiction.

PubMed

Koob, George F; Le Moal, Michel

2005-11-01

Drug seeking is associated with activation of reward neural circuitry. Here we argue that drug addiction also involves a 'dark side'--a decrease in the function of normal reward-related neurocircuitry and persistent recruitment of anti-reward systems. Understanding the neuroplasticity of the dark side of this circuitry is the key to understanding vulnerability to addiction.

Facing changes and changing faces in adolescence: a new model for investigating adolescent-specific interactions between pubertal, brain and behavioral development.

PubMed

Scherf, K Suzanne; Behrmann, Marlene; Dahl, Ronald E

2012-04-01

Adolescence is a time of dramatic physical, cognitive, emotional, and social changes as well as a time for the development of many social-emotional problems. These characteristics raise compelling questions about accompanying neural changes that are unique to this period of development. Here, we propose that studying adolescent-specific changes in face processing and its underlying neural circuitry provides an ideal model for addressing these questions. We also use this model to formulate new hypotheses. Specifically, pubertal hormones are likely to increase motivation to master new peer-oriented developmental tasks, which will in turn, instigate the emergence of new social/affective components of face processing. We also predict that pubertal hormones have a fundamental impact on the re-organization of neural circuitry supporting face processing and propose, in particular, that, the functional connectivity, or temporal synchrony, between regions of the face-processing network will change with the emergence of these new components of face processing in adolescence. Finally, we show how this approach will help reveal why adolescence may be a period of vulnerability in brain development and suggest how it could lead to prevention and intervention strategies that facilitate more adaptive functional interactions between regions within the broader social information processing network. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neural Circuitry of the Bilingual Mental Lexicon: Effect of Age of Second Language Acquisition

ERIC Educational Resources Information Center

Isel, Frederic; Baumgaertner, Annette; Thran, Johannes; Meisel, Jurgen M.; Buchel, Christian

2010-01-01

Numerous studies have proposed that changes of the human language faculty caused by neural maturation can explain the substantial differences in ultimate attainment of grammatical competences between first language (L1) acquirers and second language (L2) learners. However, little evidence on the effect of neural maturation on the attainment of…

Neural Correlates of Moral Sensitivity and Moral Judgment Associated with Brain Circuitries of Selfhood: A Meta-Analysis

ERIC Educational Resources Information Center

Han, Hyemin

2017-01-01

The present study meta-analyzed 45 experiments with 959 subjects and 463 activation foci reported in 43 published articles that investigated the neural mechanism of moral functions by comparing neural activity between the moral task conditions and non-moral task conditions with the Activation Likelihood Estimation method. The present study…

Analog Processor To Solve Optimization Problems

NASA Technical Reports Server (NTRS)

Duong, Tuan A.; Eberhardt, Silvio P.; Thakoor, Anil P.

1993-01-01

Proposed analog processor solves "traveling-salesman" problem, considered paradigm of global-optimization problems involving routing or allocation of resources. Includes electronic neural network and auxiliary circuitry based partly on concepts described in "Neural-Network Processor Would Allocate Resources" (NPO-17781) and "Neural Network Solves 'Traveling-Salesman' Problem" (NPO-17807). Processor based on highly parallel computing solves problem in significantly less time.

Prefrontal contributions to visual selective attention.

PubMed

Squire, Ryan F; Noudoost, Behrad; Schafer, Robert J; Moore, Tirin

2013-07-08

The faculty of attention endows us with the capacity to process important sensory information selectively while disregarding information that is potentially distracting. Much of our understanding of the neural circuitry underlying this fundamental cognitive function comes from neurophysiological studies within the visual modality. Past evidence suggests that a principal function of the prefrontal cortex (PFC) is selective attention and that this function involves the modulation of sensory signals within posterior cortices. In this review, we discuss recent progress in identifying the specific prefrontal circuits controlling visual attention and its neural correlates within the primate visual system. In addition, we examine the persisting challenge of precisely defining how behavior should be affected when attentional function is lost.

The neuropsychology of self-reflection in psychiatric illness.

PubMed

Philippi, Carissa L; Koenigs, Michael

2014-07-01

The development of robust neuropsychological measures of social and affective function-which link critical dimensions of mental health to their underlying neural circuitry-could be a key step in achieving a more pathophysiologically-based approach to psychiatric medicine. In this article, we summarize research indicating that self-reflection (the inward attention to personal thoughts, memories, feelings, and actions) may be a useful model for developing such a paradigm, as there is evidence that self-reflection is (1) measurable with self-report scales and performance-based tests, (2) linked to the activity of a specific neural circuit, and (3) dimensionally related to mental health and various forms of psychopathology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Converging models of schizophrenia - Network alterations of prefrontal cortex underlying cognitive impairments

PubMed Central

Sakurai, Takeshi; Gamo, Nao J; Hikida, Takatoshi; Kim, Sun-Hong; Murai, Toshiya; Tomoda, Toshifumi; Sawa, Akira

2015-01-01

The prefrontal cortex (PFC) and its connections with other brain areas are crucial for cognitive function. Cognitive impairments are one of the core symptoms associated with schizophrenia, and manifest even before the onset of the disorder. Altered neural networks involving PFC contribute to cognitive impairments in schizophrenia. Both genetic and environmental risk factors affect the development of the local circuitry within PFC as well as development of broader brain networks, and make the system vulnerable to further insults during adolescence, leading to the onset of the disorder in young adulthood. Since spared cognitive functions correlate with functional outcome and prognosis, a better understanding of the mechanisms underlying cognitive impairments will have important implications for novel therapeutics for schizophrenia focusing on cognitive functions. Multidisciplinary approaches, from basic neuroscience to clinical studies, are required to link molecules, circuitry, networks, and behavioral phenotypes. Close interactions among such fields by sharing a common language on connectomes, behavioral readouts, and other concepts are crucial for this goal. PMID:26408506

Reading acceleration training changes brain circuitry in children with reading difficulties

PubMed Central

Horowitz-Kraus, Tzipi; Vannest, Jennifer J; Kadis, Darren; Cicchino, Nicole; Wang, Yingying Y; Holland, Scott K

2014-01-01

Introduction Dyslexia is characterized by slow, inaccurate reading. Previous studies have shown that the Reading Acceleration Program (RAP) improves reading speed and accuracy in children and adults with dyslexia and in typical readers across different orthographies. However, the effect of the RAP on the neural circuitry of reading has not been established. In the current study, we examined the effect of the RAP training on regions of interest in the neural circuitry for reading using a lexical decision task during fMRI in children with reading difficulties and typical readers. Methods Children (8–12 years old) with reading difficulties and typical readers were studied before and after 4 weeks of training with the RAP in both groups. Results In addition to improvements in oral and silent contextual reading speed, training-related gains were associated with increased activation of the left hemisphere in both children with reading difficulties and typical readers. However, only children with reading difficulties showed improvements in reading comprehension, which were associated with significant increases in right frontal lobe activation. Conclusions Our results demonstrate differential effects of the RAP on neural circuits supporting reading in both children with reading difficulties and typical readers and suggest that the intervention may stimulate use of typical neural circuits for reading and engage compensatory pathways to support reading in the developing brain of children with reading difficulties. PMID:25365797

Dissociable frontostriatal white matter connectivity underlies reward and motor impulsivity.

PubMed

Hampton, William H; Alm, Kylie H; Venkatraman, Vinod; Nugiel, Tehila; Olson, Ingrid R

2017-04-15

Dysfunction of cognitive control often leads to impulsive decision-making in clinical and healthy populations. Some research suggests that a generalized cognitive control mechanism underlies the ability to modulate various types of impulsive behavior, while other evidence suggests different forms of impulsivity are dissociable, and rely on distinct neural circuitry. Past research consistently implicates several brain regions, such as the striatum and portions of the prefrontal cortex, in impulsive behavior. However the ventral and dorsal striatum are distinct in regards to function and connectivity. Nascent evidence points to the importance of frontostriatal white matter connectivity in impulsivity, yet it remains unclear whether particular tracts relate to different control behaviors. Here we used probabilistic tractography of diffusion imaging data to relate ventral and dorsal frontostriatal connectivity to reward and motor impulsivity measures. We found a double dissociation such that individual differences in white matter connectivity between the ventral striatum and the ventromedial prefrontal cortex and dorsolateral prefrontal cortex was associated with reward impulsivity, as measured by delay discounting, whereas connectivity between dorsal striatum and supplementary motor area was associated with motor impulsivity, but not vice versa. Our findings suggest that (a) structural connectivity can is associated with a large amount of behavioral variation; (b) different types of impulsivity are driven by dissociable frontostriatal neural circuitry. Copyright © 2017 Elsevier Inc. All rights reserved.

Recovery of biological motion perception and network plasticity after cerebellar tumor removal.

PubMed

Sokolov, Arseny A; Erb, Michael; Grodd, Wolfgang; Tatagiba, Marcos S; Frackowiak, Richard S J; Pavlova, Marina A

2014-10-01

Visual perception of body motion is vital for everyday activities such as social interaction, motor learning or car driving. Tumors to the left lateral cerebellum impair visual perception of body motion. However, compensatory potential after cerebellar damage and underlying neural mechanisms remain unknown. In the present study, visual sensitivity to point-light body motion was psychophysically assessed in patient SL with dysplastic gangliocytoma (Lhermitte-Duclos disease) to the left cerebellum before and after neurosurgery, and in a group of healthy matched controls. Brain activity during processing of body motion was assessed by functional magnetic resonance imaging (MRI). Alterations in underlying cerebro-cerebellar circuitry were studied by psychophysiological interaction (PPI) analysis. Visual sensitivity to body motion in patient SL before neurosurgery was substantially lower than in controls, with significant improvement after neurosurgery. Functional MRI in patient SL revealed a similar pattern of cerebellar activation during biological motion processing as in healthy participants, but located more medially, in the left cerebellar lobules III and IX. As in normalcy, PPI analysis showed cerebellar communication with a region in the superior temporal sulcus, but located more anteriorly. The findings demonstrate a potential for recovery of visual body motion processing after cerebellar damage, likely mediated by topographic shifts within the corresponding cerebro-cerebellar circuitry induced by cerebellar reorganization. The outcome is of importance for further understanding of cerebellar plasticity and neural circuits underpinning visual social cognition.

Neural systems underlying reward and approach behaviors in childhood and adolescence.

PubMed

Galván, Adriana

2014-01-01

Transitions into and out of adolescence are critical developmental periods of reward-seeking and approach behaviors. Converging evidence suggests that intriguing reward-related behavioral shifts are mediated by developmental changes in frontostriatal circuitry. This chapter explores how the conceptual frameworks and empirical studies in the field of developmental cognitive neuroscience have contributed to understanding reward-related behavior across development.The chapter concludes with some implications for adaptive and maladaptive behaviors that arise from these behaviors as children transition from childhood to adolescence.

Neuronal Circuitry Mechanisms Regulating Adult Mammalian Neurogenesis

PubMed Central

Song, Juan; Olsen, Reid H.J.; Sun, Jiaqi; Ming, Guo-li; Song, Hongjun

2017-01-01

The adult mammalian brain is a dynamic structure, capable of remodeling in response to various physiological and pathological stimuli. One dramatic example of brain plasticity is the birth and subsequent integration of newborn neurons into the existing circuitry. This process, termed adult neurogenesis, recapitulates neural developmental events in two specialized adult brain regions: the lateral ventricles of the forebrain. Recent studies have begun to delineate how the existing neuronal circuits influence the dynamic process of adult neurogenesis, from activation of quiescent neural stem cells (NSCs) to the integration and survival of newborn neurons. Here, we review recent progress toward understanding the circuit-based regulation of adult neurogenesis in the hippocampus and olfactory bulb. PMID:27143698

Impulsivity and Aggression in Schizophrenia: A Neural Circuitry Perspective with Implications for Treatment

PubMed Central

Hoptman, Matthew J.

2015-01-01

Elevations of impulsive behavior have been observed in a number of serious mental illnesses. These phenomena can lead to harmful behaviors, including violence, and thus represent a serious public health concern. Such violence is often a reason for psychiatric hospitalization, and it often leads to prolonged hospital stays, suffering by patients and their victims, and increased stigmatization. Despite the attention paid to violence, little is understood about its neural basis in schizophrenia. On a psychological level, aggression in schizophrenia has been primarily attributed to psychotic symptoms, desires for instrumental gain, or impulsive responses to perceived personal slights. Often multiple attributions can coexist during a single aggressive incident. In this review, I will discuss the neural circuitry associated with impulsivity and aggression in schizophrenia, with an emphasis on implications for treatment. Impulsivity appears to account for a great deal of aggression in schizophrenia, especially in inpatient settings. Urgency, defined as impulsivity in the context of strong emotion, is the primary focus of this article. It is elevated in several psychiatric disorders, and in schizophrenia, it has been related to aggression. Many studies have implicated dysfunctional frontotemporal circuitry in impulsivity and aggression in schizophrenia, and pharmacological treatments may act via that circuitry to reduce urgency and aggressive behaviors, but more mechanistic studies are critically needed. Recent studies point toward manipulable neurobehavioral targets and suggest that cognitive, pharmacological, neuromodulatory, and neurofeedback treatment approaches can be developed to ameliorate urgency and aggression in schizophrenia. It is hoped that these approaches will improve treatment efficacy. PMID:25900066

The roles of cannabinoid and dopamine receptor systems in neural emotional learning circuits: implications for schizophrenia and addiction.

PubMed

Laviolette, S R; Grace, A A

2006-07-01

Cannabinoids represent one of the most widely used hallucinogenic drugs and induce profound alterations in sensory perception and emotional processing. Similarly, the dopamine (DA) neurotransmitter system is critical for the central processing of emotion and motivation. Functional disturbances in either of these neurotransmitter systems are well-established correlates of the psychopathological symptoms and behavioral manifestations observed in addiction and schizophrenia. Increasing evidence from the anatomical, pharmacological and behavioral neuroscience fields points to complex functional interactions between these receptor systems at the anatomical, pharmacological and neural systems levels. An important question relates to whether these systems act in an orchestrated manner to produce the emotional processing and sensory perception deficits underlying addiction and schizophrenia. This review describes evidence for functional neural interactions between cannabinoid and DA receptor systems and how disturbances in this neural circuitry may underlie the aberrant emotional learning and processing observed in disorders such as addiction and schizophrenia.

Neural Correlates of Odor Learning in the Presynaptic Microglomerular Circuitry in the Honeybee Mushroom Body Calyx.

PubMed

Haenicke, Joachim; Yamagata, Nobuhiro; Zwaka, Hanna; Nawrot, Martin; Menzel, Randolf

2018-01-01

The mushroom body (MB) in insects is known as a major center for associative learning and memory, although exact locations for the correlating memory traces remain to be elucidated. Here, we asked whether presynaptic boutons of olfactory projection neurons (PNs) in the main input site of the MB undergo neuronal plasticity during classical odor-reward conditioning and correlate with the conditioned behavior. We simultaneously measured Ca 2+ responses in the boutons and conditioned behavioral responses to learned odors in honeybees. We found that the absolute amount of the neural change for the rewarded but not for the unrewarded odor was correlated with the behavioral learning rate across individuals. The temporal profile of the induced changes matched with odor response dynamics of the MB-associated inhibitory neurons, suggestive of activity modulation of boutons by this neural class. We hypothesize the circuit-specific neural plasticity relates to the learned value of the stimulus and underlies the conditioned behavior of the bees.

Development switch in neural circuitry underlying odor-malaise learning.

PubMed

Shionoya, Kiseko; Moriceau, Stephanie; Lunday, Lauren; Miner, Cathrine; Roth, Tania L; Sullivan, Regina M

2006-01-01

Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.

Sex differences in the development of brain mechanisms for processing biological motion.

PubMed

Anderson, L C; Bolling, D Z; Schelinski, S; Coffman, M C; Pelphrey, K A; Kaiser, M D

2013-12-01

Disorders related to social functioning including autism and schizophrenia differ drastically in incidence and severity between males and females. Little is known about the neural systems underlying these sex-linked differences in risk and resiliency. Using functional magnetic resonance imaging and a task involving the visual perception of point-light displays of coherent and scrambled biological motion, we discovered sex differences in the development of neural systems for basic social perception. In adults, we identified enhanced activity during coherent biological motion perception in females relative to males in a network of brain regions previously implicated in social perception including amygdala, medial temporal gyrus, and temporal pole. These sex differences were less pronounced in our sample of school-age youth. We hypothesize that the robust neural circuitry supporting social perception in females, which diverges from males beginning in childhood, may underlie sex differences in disorders related to social processing. © 2013 Elsevier Inc. All rights reserved.

Sex Differences in the Development of Brain Mechanisms for Processing Biological Motion

PubMed Central

Anderson, L.C.; Bolling, D.Z.; Schelinski, S.; Coffman, M.C.; Pelphrey, K.A.; Kaiser, M.D.

2013-01-01

Disorders related to social functioning including autism and schizophrenia differ drastically in incidence and severity between males and females. Little is known about the neural systems underlying these sex-linked differences in risk and resiliency. Using functional magnetic resonance imaging and a task involving the visual perception of point-light displays of coherent and scrambled biological motion, we discovered sex differences in the development of neural systems for basic social perception. In adults, we identified enhanced activity during coherent biological motion perception in females relative to males in a network of brain regions previously implicated in social perception including amygdala, medial temporal gyrus, and temporal pole. These sex differences were less pronounced in our sample of school-age youth. We hypothesize that the robust neural circuitry supporting social perception in females, which diverges from males beginning in childhood, may underlie sex differences in disorders related to social processing. PMID:23876243

Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner.

PubMed

Mitew, Stanislaw; Gobius, Ilan; Fenlon, Laura R; McDougall, Stuart J; Hawkes, David; Xing, Yao Lulu; Bujalka, Helena; Gundlach, Andrew L; Richards, Linda J; Kilpatrick, Trevor J; Merson, Tobias D; Emery, Ben

2018-01-22

Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which neuronal activity is capable of regulating myelination at the individual axon level is unclear. Here we demonstrate that stimulation of somatosensory axons in the mouse brain increases proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) within the underlying white matter. Stimulated axons display an increased probability of being myelinated compared to neighboring non-stimulated axons, in addition to being ensheathed with thicker myelin. Conversely, attenuating neuronal firing reduces axonal myelination in a selective activity-dependent manner. Our findings reveal that the process of selecting axons for myelination is strongly influenced by the relative activity of individual axons within a population. These observed cellular changes are consistent with the emerging concept that adaptive myelination is a key mechanism for the fine-tuning of neuronal circuitry in the mammalian CNS.

Dissociation of neural mechanisms underlying orientation processing in humans

PubMed Central

Ling, Sam; Pearson, Joel; Blake, Randolph

2009-01-01

Summary Orientation selectivity is a fundamental, emergent property of neurons in early visual cortex, and discovery of that property [1, 2] dramatically shaped how we conceptualize visual processing [3–6]. However, much remains unknown about the neural substrates of these basic building blocks of perception, and what is known primarily stems from animal physiology studies. To probe the neural concomitants of orientation processing in humans, we employed repetitive transcranial magnetic stimulation (rTMS) to attenuate neural responses evoked by stimuli presented within a local region of the visual field. Previous physiological studies have shown that rTMS can significantly suppress the neuronal spiking activity, hemodynamic responses, and local field potentials within a focused cortical region [7, 8]. By suppressing neural activity with rTMS, we were able to dissociate components of the neural circuitry underlying two distinct aspects of orientation processing: selectivity and contextual effects. Orientation selectivity gauged by masking was unchanged by rTMS, whereas an otherwise robust orientation repulsion illusion was weakened following rTMS. This dissociation implies that orientation processing relies on distinct mechanisms, only one of which was impacted by rTMS. These results are consistent with models positing that orientation selectivity is largely governed by the patterns of convergence of thalamic afferents onto cortical neurons, with intracortical activity then shaping population responses contained within those orientation-selective cortical neurons. PMID:19682905

Abnormalities of neural circuitry in Alzheimer's disease: hippocampus and cortical cholinergic innervation.

PubMed

Geula, C

1998-07-01

Severe pathology in Alzheimer's disease (AD) results in marked disruption of cortical circuitry. Formation of neurofibrillary tangles, neuronal loss, decrease in dendritic extent, and synaptic depletion combine to halt communication among various cortical areas, resulting in anatomic isolation and fragmentation of many cortical zones. The clinical manifestation of this disruption is severe and debilitating cognitive dysfunction, often accompanied by psychiatric and behavioral disturbances and a diminished ability to perform activities of daily living. However, different cortical circuits are not equally vulnerable to AD pathology. In particular, two cortical systems that appear to be involved in the neural processing of memory are selectively vulnerable to degeneration in AD. One consists of connections between the hippocampus and its neighboring cortical structures within the temporal lobe. The second is the cortical cholinergic system that originates in neurons within the basal forebrain and innervates the entire cortical mantle. The circuitry in these systems shows early and severe degenerative changes in the course of AD. The selective vulnerability of these circuits is the probable reason for the early and marked loss of memory observed in these patients. This review presents current knowledge of the general pattern of cortical circuitry, followed by a summary of abnormalities of this circuitry in AD. The cortical circuits that exhibit selective pathology in AD are described in greater detail. Therapeutic implications of the abnormal circuitry in AD are also discussed. For therapies to be effective, early diagnosis of AD is necessary. Future efforts at AD therapy must be combined with an equally intense effort to develop tools capable of early diagnosis of AD, preferably at a preclinical stage before the onset of cognitive symptoms.

Spatial working memory in neurofibromatosis 1: Altered neural activity and functional connectivity.

PubMed

Ibrahim, Amira F A; Montojo, Caroline A; Haut, Kristen M; Karlsgodt, Katherine H; Hansen, Laura; Congdon, Eliza; Rosser, Tena; Bilder, Robert M; Silva, Alcino J; Bearden, Carrie E

2017-01-01

Neurofibromatosis Type 1 (NF1) is a genetic disorder that disrupts central nervous system development and neuronal function. Cognitively, NF1 is characterized by difficulties with executive control and visuospatial abilities. Little is known about the neural substrates underlying these deficits. The current study utilized Blood-Oxygen-Level-Dependent (BOLD) functional MRI (fMRI) to explore the neural correlates of spatial working memory (WM) deficits in patients with NF1. BOLD images were acquired from 23 adults with NF1 (age M  = 32.69; 61% male) and 25 matched healthy controls (age M  = 33.08; 64% male) during an in-scanner visuo-spatial WM task. Whole brain functional and psycho-physiological interaction analyses were utilized to investigate neural activity and functional connectivity, respectively, during visuo-spatial WM performance. Participants also completed behavioral measures of spatial reasoning and verbal WM. Relative to healthy controls, participants with NF1 showed reduced recruitment of key components of WM circuitry, the left dorsolateral prefrontal cortex and right parietal cortex. In addition, healthy controls exhibited greater simultaneous deactivation between the posterior cingulate cortex (PCC) and temporal regions than NF1 patients. In contrast, NF1 patients showed greater PCC and bilateral parietal connectivity with visual cortices as well as between the PCC and the cerebellum. In NF1 participants, increased functional coupling of the PCC with frontal and parietal regions was associated with better spatial reasoning and WM performance, respectively; these relationships were not observed in controls. Dysfunctional engagement of WM circuitry, and aberrant functional connectivity of 'task-negative' regions in NF1 patients may underlie spatial WM difficulties characteristic of the disorder.

A Physiological Neural Controller of a Muscle Fiber Oculomotor Plant in Horizontal Monkey Saccades

PubMed Central

Enderle, John D.

2014-01-01

A neural network model of biophysical neurons in the midbrain is presented to drive a muscle fiber oculomotor plant during horizontal monkey saccades. Neural circuitry, including omnipause neuron, premotor excitatory and inhibitory burst neurons, long lead burst neuron, tonic neuron, interneuron, abducens nucleus, and oculomotor nucleus, is developed to examine saccade dynamics. The time-optimal control strategy by realization of agonist and antagonist controller models is investigated. In consequence, each agonist muscle fiber is stimulated by an agonist neuron, while an antagonist muscle fiber is unstimulated by a pause and step from the antagonist neuron. It is concluded that the neural network is constrained by a minimum duration of the agonist pulse and that the most dominant factor in determining the saccade magnitude is the number of active neurons for the small saccades. For the large saccades, however, the duration of agonist burst firing significantly affects the control of saccades. The proposed saccadic circuitry establishes a complete model of saccade generation since it not only includes the neural circuits at both the premotor and motor stages of the saccade generator, but also uses a time-optimal controller to yield the desired saccade magnitude. PMID:24944832

The Neural Circuit Mechanisms Underlying the Retinal Response to Motion Reversal

PubMed Central

Chen, Eric Y.; Chou, Janice; Park, Jeongsook; Schwartz, Greg

2014-01-01

To make up for delays in visual processing, retinal circuitry effectively predicts that a moving object will continue moving in a straight line, allowing retinal ganglion cells to anticipate the object's position. However, a sudden reversal of motion triggers a synchronous burst of firing from a large group of ganglion cells, possibly signaling a violation of the retina's motion prediction. To investigate the neural circuitry underlying this response, we used a combination of multielectrode array and whole-cell patch recordings to measure the responses of individual retinal ganglion cells in the tiger salamander to reversing stimuli. We found that different populations of ganglion cells were responsible for responding to the reversal of different kinds of objects, such as bright versus dark objects. Using pharmacology and designed stimuli, we concluded that ON and OFF bipolar cells both contributed to the reversal response, but that amacrine cells had, at best, a minor role. This allowed us to formulate an adaptive cascade model (ACM), similar to the one previously used to describe ganglion cell responses to motion onset. By incorporating the ON pathway into the ACM, we were able to reproduce the time-varying firing rate of fast OFF ganglion cells for all experimentally tested stimuli. Analysis of the ACM demonstrates that bipolar cell gain control is primarily responsible for generating the synchronized retinal response, as individual bipolar cells require a constant time delay before recovering from gain control. PMID:25411485

The Impact of Ecological Niche on Adaptive Flexibility of Sensory Circuitry

PubMed Central

Pallas, Sarah L.

2017-01-01

Evolution and development are interdependent, particularly with regard to the construction of the nervous system and its position as the machine that produces behavior. On the one hand, the processes directing development and plasticity of the brain provide avenues through which natural selection can sculpt neural cell fate and connectivity, and on the other hand, they are themselves subject to selection pressure. For example, mutations that produce heritable perturbations in neuronal birth and death rates, transcription factor expression, or availability of axon guidance factors within sensory pathways can markedly affect the development of form and thus the function of stimulus decoding circuitry. This evolvability of flexible circuits makes them more adaptable to environmental variation. Although there is general agreement on this point, whether the sensitivity of circuits to environmental influence and the mechanisms underlying development and plasticity of sensory pathways are similar across species from different ecological niches has received almost no attention. Neural circuits are generally more sensitive to environmental influences during an early critical period, but not all niches afford the same access to stimuli in early life. Furthermore, depending on predictability of the habitat and ecological niche, sensory coding circuits might be more susceptible to sensory experience in some species than in others. Despite decades of work on understanding the mechanisms underlying critical period plasticity, the importance of ecological niche in visual pathway development has received little attention. Here, I will explore the relationship between critical period plasticity and ecological niche in mammalian sensory pathways. PMID:28701910

The Impact of Ecological Niche on Adaptive Flexibility of Sensory Circuitry.

PubMed

Pallas, Sarah L

2017-01-01

Evolution and development are interdependent, particularly with regard to the construction of the nervous system and its position as the machine that produces behavior. On the one hand, the processes directing development and plasticity of the brain provide avenues through which natural selection can sculpt neural cell fate and connectivity, and on the other hand, they are themselves subject to selection pressure. For example, mutations that produce heritable perturbations in neuronal birth and death rates, transcription factor expression, or availability of axon guidance factors within sensory pathways can markedly affect the development of form and thus the function of stimulus decoding circuitry. This evolvability of flexible circuits makes them more adaptable to environmental variation. Although there is general agreement on this point, whether the sensitivity of circuits to environmental influence and the mechanisms underlying development and plasticity of sensory pathways are similar across species from different ecological niches has received almost no attention. Neural circuits are generally more sensitive to environmental influences during an early critical period, but not all niches afford the same access to stimuli in early life. Furthermore, depending on predictability of the habitat and ecological niche, sensory coding circuits might be more susceptible to sensory experience in some species than in others. Despite decades of work on understanding the mechanisms underlying critical period plasticity, the importance of ecological niche in visual pathway development has received little attention. Here, I will explore the relationship between critical period plasticity and ecological niche in mammalian sensory pathways.

Dissociable Patterns of Neural Activity during Response Inhibition in Depressed Adolescents with and without Suicidal Behavior

ERIC Educational Resources Information Center

Pan, Lisa A.; Batezati-Alves, Silvia C.; Almeida, Jorge R. C.; Segreti, AnnaMaria; Akkal, Dalila; Hassel, Stefanie; Lakdawala, Sara; Brent, David A.; Phillips, Mary L.

2011-01-01

Objectives: Impaired attentional control and behavioral control are implicated in adult suicidal behavior. Little is known about the functional integrity of neural circuitry supporting these processes in suicidal behavior in adolescence. Method: Functional magnetic resonance imaging was used in 15 adolescent suicide attempters with a history of…

Neural sex modifies the function of a C. elegans sensory circuit.

PubMed

Lee, Kyunghwa; Portman, Douglas S

2007-11-06

Though sex differences in animal behavior are ubiquitous, their neural and genetic underpinnings remain poorly understood. In particular, the role of functional differences in the neural circuitry that is shared by both sexes has not been extensively investigated. We have addressed these issues with C. elegans olfaction, a simple innate behavior mediated by sexually isomorphic neurons. Though males respond to the same olfactory attractants as do hermaphrodites, we find that each sex has a characteristic repertoire of olfactory preferences. These are not secondary to other sex-specific behaviors and do not require signaling from the gonad. Sex-specific olfactory preferences are controlled by tra-1, the master regulator of C. elegans sexual differentiation. Moreover, the genetic masculinization of neurons in an otherwise wild-type hermaphrodite is sufficient to switch the sexual phenotype of olfactory preference behavior. These studies reveal novel and unexpected sex differences in a C. elegans sensory behavior that is exhibited by both sexes. Our results indicate that these differences are a function of the chromosomally determined sexual identity of shared neural circuitry.

Beautiful friendship: Social sharing of emotions improves subjective feelings and activates the neural reward circuitry

PubMed Central

Galli, Lisa; Schott, Björn H.; Wold, Andrew; van der Schalk, Job; Manstead, Antony S. R.; Scherer, Klaus; Walter, Henrik

2015-01-01

Humans have a strong tendency to affiliate with other people, especially in emotional situations. Here, we suggest that a critical mechanism underlying this tendency is that socially sharing emotional experiences is in itself perceived as hedonically positive and thereby contributes to the regulation of individual emotions. We investigated the effect of social sharing of emotions on subjective feelings and neural activity by having pairs of friends view emotional (negative and positive) and neutral pictures either alone or with the friend. While the two friends remained physically separated throughout the experiment—with one undergoing functional magnetic resonance imaging and the other performing the task in an adjacent room—they were made aware on a trial-by-trial basis whether they were seeing pictures simultaneously with their friend (shared) or alone (unshared). Ratings of subjective feelings were improved significantly when participants viewed emotional pictures together than alone, an effect that was accompanied by activity increase in ventral striatum and medial orbitofrontal cortex, two important components of the reward circuitry. Because these effects occurred without any communication or interaction between the friends, they point to an important proximate explanation for the basic human motivation to affiliate with others, particularly in emotional situations. PMID:25298009

Beautiful friendship: Social sharing of emotions improves subjective feelings and activates the neural reward circuitry.

PubMed

Wagner, Ullrich; Galli, Lisa; Schott, Björn H; Wold, Andrew; van der Schalk, Job; Manstead, Antony S R; Scherer, Klaus; Walter, Henrik

2015-06-01

Humans have a strong tendency to affiliate with other people, especially in emotional situations. Here, we suggest that a critical mechanism underlying this tendency is that socially sharing emotional experiences is in itself perceived as hedonically positive and thereby contributes to the regulation of individual emotions. We investigated the effect of social sharing of emotions on subjective feelings and neural activity by having pairs of friends view emotional (negative and positive) and neutral pictures either alone or with the friend. While the two friends remained physically separated throughout the experiment-with one undergoing functional magnetic resonance imaging and the other performing the task in an adjacent room-they were made aware on a trial-by-trial basis whether they were seeing pictures simultaneously with their friend (shared) or alone (unshared). Ratings of subjective feelings were improved significantly when participants viewed emotional pictures together than alone, an effect that was accompanied by activity increase in ventral striatum and medial orbitofrontal cortex, two important components of the reward circuitry. Because these effects occurred without any communication or interaction between the friends, they point to an important proximate explanation for the basic human motivation to affiliate with others, particularly in emotional situations. © The Author (2014). Published by Oxford University Press.

Singing modulates parvalbumin interneurons throughout songbird forebrain vocal control circuitry

PubMed Central

Zengin-Toktas, Yildiz

2017-01-01

Across species, the performance of vocal signals can be modulated by the social environment. Zebra finches, for example, adjust their song performance when singing to females (‘female-directed’ or FD song) compared to when singing in isolation (‘undirected’ or UD song). These changes are salient, as females prefer the FD song over the UD song. Despite the importance of these performance changes, the neural mechanisms underlying this social modulation remain poorly understood. Previous work in finches has established that expression of the immediate early gene EGR1 is increased during singing and modulated by social context within the vocal control circuitry. Here, we examined whether particular neural subpopulations within those vocal control regions exhibit similar modulations of EGR1 expression. We compared EGR1 expression in neurons expressing parvalbumin (PV), a calcium buffer that modulates network plasticity and homeostasis, among males that performed FD song, males that produced UD song, or males that did not sing. We found that, overall, singing but not social context significantly affected EGR1 expression in PV neurons throughout the vocal control nuclei. We observed differences in EGR1 expression between two classes of PV interneurons in the basal ganglia nucleus Area X. Additionally, we found that singing altered the amount of PV expression in neurons in HVC and Area X and that distinct PV interneuron types in Area X exhibited different patterns of modulation by singing. These data indicate that throughout the vocal control circuitry the singing-related regulation of EGR1 expression in PV neurons may be less influenced by social context than in other neuron types and raise the possibility of cell-type specific differences in plasticity and calcium buffering. PMID:28235074

Association of Resting Metabolism in the Fear Neural Network With Extinction Recall Activations and Clinical Measures in Trauma-Exposed Individuals.

PubMed

Marin, Marie-France; Song, Huijin; VanElzakker, Michael B; Staples-Bradley, Lindsay K; Linnman, Clas; Pace-Schott, Edward F; Lasko, Natasha B; Shin, Lisa M; Milad, Mohammed R

2016-09-01

Exposure-based therapy, an effective treatment for posttraumatic stress disorder (PTSD), relies on extinction learning principles. In PTSD patients, dysfunctional patterns in the neural circuitry underlying fear extinction have been observed using resting-state or functional activation measures. It remains undetermined whether resting activity predicts activations during extinction recall or PTSD symptom severity. Moreover, it remains unclear whether trauma exposure per se affects resting activity in this circuitry. The authors employed a multimodal approach to examine the relationships among resting metabolism, clinical symptoms, and activations during extinction recall. Three cohorts were recruited: PTSD patients (N=24), trauma-exposed individuals with no PTSD (TENP) (N=20), and trauma-unexposed healthy comparison subjects (N=21). Participants underwent a resting positron emission tomography scan 4 days before a functional MRI fear conditioning and extinction paradigm. Amygdala resting metabolism negatively correlated with clinical functioning (as measured by the Global Assessment of Functioning Scale) in the TENP group, and hippocampal resting metabolism negatively correlated with clinical functioning in the PTSD group. In the PTSD group, dorsal anterior cingulate cortex (dACC) resting metabolism positively correlated with PTSD symptom severity, and it predicted increased dACC activations but decreased hippocampal and ventromedial prefrontal cortex activations during extinction recall. The TENP group had lower amygdala resting metabolism compared with the PTSD and healthy comparison groups, and it exhibited lower hippocampus resting metabolism relative to the healthy comparison group. Resting metabolism in the fear circuitry correlated with functioning, PTSD symptoms, and extinction recall activations, further supporting the relevance of this network to the pathophysiology of PTSD. The study findings also highlight the fact that chronic dysfunction in the amygdala and hippocampus is demonstrable in PTSD and other trauma-exposed individuals, even without exposure to an evocative stimulus.

Effects of Nerve Injury and Segmental Regeneration on the Cellular Correlates of Neural Morphallaxis

PubMed Central

Martinez, Veronica G.; Manson, Josiah M.B.; Zoran, Mark J.

2009-01-01

Functional recovery of neural networks after injury requires a series of signaling events similar to the embryonic processes that governed initial network construction. Neural morphallaxis, a form of nervous system regeneration, involves reorganization of adult neural connectivity patterns. Neural morphallaxis in the worm, Lumbriculus variegatus, occurs during asexual reproduction and segmental regeneration, as body fragments acquire new positional identities along the anterior–posterior axis. Ectopic head (EH) formation, induced by ventral nerve cord lesion, generated morphallactic plasticity including the reorganization of interneuronal sensory fields and the induction of a molecular marker of neural morphallaxis. Morphallactic changes occurred only in segments posterior to an EH. Neither EH formation, nor neural morphallaxis was observed after dorsal body lesions, indicating a role for nerve cord injury in morphallaxis induction. Furthermore, a hierarchical system of neurobehavioral control was observed, where anterior heads were dominant and an EH controlled body movements only in the absence of the anterior head. Both suppression of segmental regeneration and blockade of asexual fission, after treatment with boric acid, disrupted the maintenance of neural morphallaxis, but did not block its induction. Therefore, segmental regeneration (i.e., epimorphosis) may not be required for the induction of morphallactic remodeling of neural networks. However, on-going epimorphosis appears necessary for the long-term consolidation of cellular and molecular mechanisms underlying the morphallaxis of neural circuitry. PMID:18561185

Neuronal Control of Swimming Behavior: Comparison of Vertebrate and Invertebrate Model Systems

PubMed Central

Mullins, Olivia J.; Hackett, John T.; Buchanan, James T.; Friesen, W. Otto

2010-01-01

Swimming movements in the leech and lamprey are highly analogous, and lack homology. Thus, similarities in mechanisms must arise from convergent evolution rather than from common ancestry. Despite over forty years of parallel investigations into this annelid and primitive vertebrate, a close comparison of the approaches and results of this research is lacking. The present review evaluates the neural mechanisms underlying swimming in these two animals and describes the many similarities that provide intriguing examples of convergent evolution. Specifically, we discuss swim initiation, maintenance and termination, isolated nervous system preparations, neural-circuitry, central oscillators, intersegmental coupling, phase lags, cycle periods and sensory feedback. Comparative studies between species highlight mechanisms that optimize behavior and allow us a broader understanding of nervous system function. PMID:21093529

New modules are added to vibrissal premotor circuitry with the emergence of exploratory whisking

PubMed Central

Takatoh, Jun; Nelson, Anders; Zhou, Xiang; Bolton, M. McLean; Ehlers, Michael D.; Arenkiel, Benjamin R.; Mooney, Richard; Wang, Fan

2012-01-01

SUMMARY Rodents begin to use bilaterally coordinated, rhythmic sweeping of their vibrissae (“whisking”) for environmental exploration around two weeks after birth. Whether and how vibrissal control circuitry changes after birth is unknown, and relevant premotor circuitry remains poorly characterized. Using a modified rabies virus transsynaptic tracing strategy, we labeled neurons synapsing directly onto vibrissa facial motor neurons (vFMNs). Sources of potential excitatory, inhibitory, and modulatory vFMN premotor neurons, and differences between the premotor circuitry for vFMNs innervating intrinsic versus extrinsic vibrissal muscles, were systematically characterized. The emergence of whisking is accompanied by the addition of “new” sets of bilateral excitatory inputs to vFMNs from neurons in the lateral paragigantocellularis (LPGi). Furthermore, descending axons from the motor cortex directly innervate LPGi premotor neurons. Thus, neural modules well suited to facilitate the bilateral coordination and cortical control of whisking are added to premotor circuitry in parallel with the emergence of this exploratory behavior. PMID:23352170

Food-Related Neural Circuitry in Prader-Willi Syndrome: Response to High- versus Low-Calorie Foods

ERIC Educational Resources Information Center

Dimitropoulos, Anastasia; Schultz, Robert T.

2008-01-01

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hyperphagia and food preoccupations. Although dysfunction of the hypothalamus likely has a critical role in hyperphagia, it is only one of several regions involved in the regulation of eating. The purpose of this research was to examine food-related neural circuitry…

Neural mechanisms controlling seasonal reproduction: principles derived from the sheep model and its comparison with hamsters.

PubMed

Weems, Peyton W; Goodman, Robert L; Lehman, Michael N

2015-04-01

Seasonal reproduction is a common adaptive strategy among mammals that allows for breeding to occur at times of the year when it is most advantageous for the subsequent survival and growth of offspring. A major mechanism responsible for seasonal reproduction is a striking increase in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the negative feedback effects of estradiol. The neural and neuroendocrine circuitry responsible for mammalian seasonal reproduction has been primarily studied in three animal models: the sheep, and two species of hamsters. In this review, we first describe the afferent signals, neural circuitry and transmitters/peptides responsible for seasonal reproductive transitions in sheep, and then compare these mechanisms with those derived from studies in hamsters. The results suggest common principles as well as differences in the role of specific brain nuclei and neuropeptides, including that of kisspeptin cells of the hypothalamic arcuate nucleus, in regulating seasonal reproduction among mammals. Copyright © 2014 Elsevier Inc. All rights reserved.

Liking, wanting, and the incentive-sensitization theory of addiction.

PubMed

Berridge, Kent C; Robinson, Terry E

2016-11-01

Rewards are both "liked" and "wanted," and those 2 words seem almost interchangeable. However, the brain circuitry that mediates the psychological process of "wanting" a particular reward is dissociable from circuitry that mediates the degree to which it is "liked." Incentive salience or "wanting," a form of motivation, is generated by large and robust neural systems that include mesolimbic dopamine. By comparison, "liking," or the actual pleasurable impact of reward consumption, is mediated by smaller and fragile neural systems, and is not dependent on dopamine. The incentive-sensitization theory posits the essence of drug addiction to be excessive amplification specifically of psychological "wanting," especially triggered by cues, without necessarily an amplification of "liking." This is because of long-lasting changes in dopamine-related motivation systems of susceptible individuals, called "neural sensitization." A quarter-century after its proposal, evidence has continued to grow in support the incentive-sensitization theory. Further, its scope is now expanding to include diverse behavioral addictions and other psychopathologies. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Liking, Wanting and the Incentive-Sensitization Theory of Addiction

PubMed Central

Berridge, Kent C.; Robinson, Terry E.

2016-01-01

Rewards are both ‘liked’ and ‘wanted’, and those two words seem almost interchangeable. However, the brain circuitry that mediates the psychological process of ‘wanting’ a particular reward is dissociable from circuitry that mediates the degree to which it is ‘liked’. Incentive salience or ‘wanting’, a form of motivation, is generated by large and robust neural systems that include mesolimbic dopamine. By comparison, ‘liking’, or the actual pleasurable impact of reward consumption, is mediated by smaller and fragile neural systems, and is not dependent on dopamine. The incentive-sensitization theory posits the essence of drug addiction to be excessive amplification specifically of psychological ‘wanting’, especially triggered by cues, without necessarily an amplification of ‘liking’. This is due to long-lasting changes in dopamine-related motivation systems of susceptible individuals, called neural sensitization. A quarter-century after its proposal, evidence has continued to grow in support the incentive-sensitization theory. Further, its scope is now expanding to include diverse behavioral addictions and other psychopathologies. PMID:27977239

Associations Between Daily Mood States and Brain Gray Matter Volume, Resting-State Functional Connectivity and Task-Based Activity in Healthy Adults.

PubMed

Ismaylova, Elmira; Di Sante, Jessica; Gouin, Jean-Philippe; Pomares, Florence B; Vitaro, Frank; Tremblay, Richard E; Booij, Linda

2018-01-01

Numerous studies have shown differences in the functioning in the areas of the frontal-limbic circuitry between depressed patients and controls. However, current knowledge on frontal-limbic neural substrates of individual differences in mood states in everyday life in healthy individuals is scarce. The present study investigates anatomical, resting-state, and functional neural correlates of daily mood states in healthy individuals. We expected to observe associations between mood and the frontal-limbic circuitry and the default-mode network (DMN). A total of 42 healthy adults (19 men, 23 women; 34 ± 1.2 years) regularly followed for behavior and psychosocial functioning since age of 6, underwent a functional magnetic resonance imaging scan, and completed a daily diary of mood states and related cognitions for 5 consecutive days. Results showed that individuals with smaller left hippocampal gray matter volumes experienced more negative mood and rumination in their daily life. Greater resting-state functional connectivity (rsFC) within the DMN, namely between posterior cingulate cortex (PCC) and medial prefrontal cortex regions as well as between PCC and precuneus, was associated with both greater negative and positive mood states in daily life. These rsFC results could be indicative of the role of the DMN regional functioning in emotional arousal, irrespective of valence. Lastly, greater daily positive mood was associated with greater activation in response to negative emotional stimuli in the precentral gyri, previously linked to emotional interference on cognitive control. Altogether, present findings might reflect neural mechanisms underlying daily affect and cognition among healthy individuals.

Regulating Critical Period Plasticity: Insight from the Visual System to Fear Circuitry for Therapeutic Interventions

PubMed Central

Nabel, Elisa M.; Morishita, Hirofumi

2013-01-01

Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development – the preeminent model of experience-dependent critical period plasticity-actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins – endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions. PMID:24273519

Neural responses during the anticipation and receipt of olfactory reward and punishment in human.

PubMed

Zou, Lai-Quan; Zhou, Han-Yu; Zhuang, Yuan; van Hartevelt, Tim J; Lui, Simon S Y; Cheung, Eric F C; Møller, Arne; Kringelbach, Morten L; Chan, Raymond C K

2018-03-01

Pleasure experience is an important part of normal healthy life and is essential for general and mental well-being. Many neuroimaging studies have investigated the underlying neural processing of verbal and visual modalities of reward. However, how the brain processes rewards in the olfactory modality is not fully understood. This study aimed to examine the neural basis of olfactory rewards in 25 healthy participants using functional magnetic resonance imaging (fMRI). We developed an Olfactory Incentive Delay (OLID) imaging task distinguishing between the anticipation and receipt of olfactory rewards and punishments. We found that the pallidum was activated during the anticipation of both olfactory rewards and punishments. The bilateral insula was activated independently from the odours' hedonic valence during the receipt phase. In addition, right caudate activation during the anticipation of unpleasant odours was correlated with self-reported anticipatory hedonic traits, whereas bilateral insular activation during the receipt of pleasant odours was correlated with self-reported consummatory hedonic traits. These findings suggest that activity in the insula and the caudate may be biomarkers of anhedonia. These findings also highlight a useful and valid paradigm to study the neural circuitry underlying reward processing in people with anhedonia. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neural circuitry and immunity

PubMed Central

Pavlov, Valentin A.; Tracey, Kevin J.

2015-01-01

Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine. PMID:26512000

Amigo adhesion protein regulates development of neural circuits in zebrafish brain.

PubMed

Zhao, Xiang; Kuja-Panula, Juha; Sundvik, Maria; Chen, Yu-Chia; Aho, Vilma; Peltola, Marjaana A; Porkka-Heiskanen, Tarja; Panula, Pertti; Rauvala, Heikki

2014-07-18

The Amigo protein family consists of three transmembrane proteins characterized by six leucine-rich repeat domains and one immunoglobulin-like domain in their extracellular moieties. Previous in vitro studies have suggested a role as homophilic adhesion molecules in brain neurons, but the in vivo functions remain unknown. Here we have cloned all three zebrafish amigos and show that amigo1 is the predominant family member expressed during nervous system development in zebrafish. Knockdown of amigo1 expression using morpholino oligonucleotides impairs the formation of fasciculated tracts in early fiber scaffolds of brain. A similar defect in fiber tract development is caused by mRNA-mediated expression of the Amigo1 ectodomain that inhibits adhesion mediated by the full-length protein. Analysis of differentiated neural circuits reveals defects in the catecholaminergic system. At the behavioral level, the disturbed formation of neural circuitry is reflected in enhanced locomotor activity and in the inability of the larvae to perform normal escape responses. We suggest that Amigo1 is essential for the development of neural circuits of zebrafish, where its mechanism involves homophilic interactions within the developing fiber tracts and regulation of the Kv2.1 potassium channel to form functional neural circuitry that controls locomotion. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Neural Systems Involved in Fear and Anxiety Measured with Fear-Potentiated Startle

ERIC Educational Resources Information Center

Davis, Michael

2006-01-01

A good deal is now known about the neural circuitry involved in how conditioned fear can augment a simple reflex (fear-potentiated startle). This involves visual or auditory as well as shock pathways that project via the thalamus and perirhinal or insular cortex to the basolateral amygdala (BLA). The BLA projects to the central (CeA) and medial…

Frontolimbic Neural Circuitry at 6 Months Predicts Individual Differences in Joint Attention at 9 Months

ERIC Educational Resources Information Center

Elison, Jed T.; Wolff, Jason J.; Heimer, Debra C.; Paterson, Sarah J.; Gu, Hongbin; Hazlett, Heather C.; Styner, Martin; Gerig, Guido; Piven, Joseph

2013-01-01

Elucidating the neural basis of joint attention in infancy promises to yield important insights into the development of language and social cognition, and directly informs developmental models of autism. We describe a new method for evaluating responding to joint attention performance in infancy that highlights the 9- to 10-month period as a time…

Altered Neural Circuits Accompany Lower Performance during Narrative Comprehension in Children with Reading Difficulties: An fMRI Study

ERIC Educational Resources Information Center

Horowitz-Kraus, Tzipi; Buck, Catherine; Dorrmann, Dana

2016-01-01

Narrative comprehension is a linguistic ability that is foundational for future reading ability. The aim of the current study was to examine the neural circuitry of children with reading difficulties (RD) compared to typical readers during a narrative-comprehension task. We hypothesized that due to deficient executive functions, which support…

Social domain based modulation of neural responses to threat: The different roles of romantic partners versus friends.

PubMed

Morriss, Jayne; Bell, Tiffany; Johnstone, Tom; van Reekum, Carien M; Hill, Jonathan

2018-06-21

The neural circuitry associated with threat regulation in the absence of other people is well established. An examination of threat regulatory processes with people from different domains of an individual's social world is key to understanding social emotion regulation and personality functioning conceptualised as social domain organisation. In this study, 42 healthy female participants completed functional magnetic imaging sessions in which they underwent a scan in the presence of a romantic partner or friend, whilst completing a threat of shock task. In the presence of a romantic partner vs. friend, we found a reduction in amygdala activation to threat vs. safe trials over time. Furthermore, in the presence of a romantic partner vs. friend we observed greater subgenual anterior cingulate cortex and ventromedial prefrontal cortex activation to threat vs. safe trials overall. The results support the hypothesis that recruitment of threat regulation circuitry is modulated by romantic partner relative to another person well-known to the individual. Future work needs to examine neural responses to a wider range of stimuli across more social domains, and implications of failures of this neural organisation for psychopathology.

Differential neural contributions to native- and foreign-language talker identification

PubMed Central

Perrachione, Tyler K.; Pierrehumbert, Janet B.; Wong, Patrick C.M.

2009-01-01

Humans are remarkably adept at identifying individuals by the sound of their voice, a behavior supported by the nervous system’s ability to integrate information from voice and speech perception. Talker-identification abilities are significantly impaired when listeners are unfamiliar with the language being spoken. Recent behavioral studies describing the language-familiarity effect implicate functionally integrated neural systems for speech and voice perception, yet specific neuroscientific evidence demonstrating the basis for such integration has not yet been shown. Listeners in the present study learned to identify voices speaking a familiar (native) or unfamiliar (foreign) language. The talker-identification performance of neural circuitry in each cerebral hemisphere was assessed using dichotic listening. To determine the relative contribution of circuitry in each hemisphere to ecological (binaural) talker identification abilities, we compared the predictive capacity of dichotic performance on binaural performance across languages. We found listeners’ right-ear (left hemisphere) performance to be a better predictor of overall accuracy in their native language than a foreign one. The enhanced predictive capacity of the classically language-dominant left-hemisphere on overall talker-identification accuracy demonstrates functionally integrated neural systems for speech and voice perception during natural talker identification. PMID:19968445

Well-being and Anticipation for Future Positive Events: Evidences from an fMRI Study.

PubMed

Luo, Yangmei; Chen, Xuhai; Qi, Senqing; You, Xuqun; Huang, Xiting

2017-01-01

Anticipation for future confers great benefits to human well-being and mental health. However, previous work focus on how people's well-being correlate with brain activities during perception of emotional stimuli, rather than anticipation for the future events. Here, the current study investigated how well-being relates to neural circuitry underlying the anticipating process of future desired events. Using event-related functional magnetic resonance imaging, 40 participants were scanned while they were performing an emotion anticipation task, in which they were instructed to anticipate the positive or neutral events. The results showed that bilateral medial prefrontal cortex (MPFC) were activated during anticipation for positive events relative to neutral events, and the enhanced brain activation in MPFC was associated with higher level of well-being. The findings suggest a neural mechanism by which the anticipation process to future desired events correlates to human well-being, which provide a future-oriented view on the neural sources of well-being.

Well-being and Anticipation for Future Positive Events: Evidences from an fMRI Study

PubMed Central

Luo, Yangmei; Chen, Xuhai; Qi, Senqing; You, Xuqun; Huang, Xiting

2018-01-01

Anticipation for future confers great benefits to human well-being and mental health. However, previous work focus on how people’s well-being correlate with brain activities during perception of emotional stimuli, rather than anticipation for the future events. Here, the current study investigated how well-being relates to neural circuitry underlying the anticipating process of future desired events. Using event-related functional magnetic resonance imaging, 40 participants were scanned while they were performing an emotion anticipation task, in which they were instructed to anticipate the positive or neutral events. The results showed that bilateral medial prefrontal cortex (MPFC) were activated during anticipation for positive events relative to neutral events, and the enhanced brain activation in MPFC was associated with higher level of well-being. The findings suggest a neural mechanism by which the anticipation process to future desired events correlates to human well-being, which provide a future-oriented view on the neural sources of well-being. PMID:29375415

Psychopathy to Altruism: Neurobiology of the Selfish-Selfless Spectrum.

PubMed

Sonne, James W H; Gash, Don M

2018-01-01

The age-old philosophical, biological, and social debate over the basic nature of humans as being "universally selfish" or "universally good" continues today highlighting sharply divergent views of natural social order. Here we analyze advances in biology, genetics and neuroscience increasing our understanding of the evolution, features and neurocircuitry of the human brain underlying behavior in the selfish-selfless spectrum. First, we examine evolutionary pressures for selection of altruistic traits in species with protracted periods of dependence on parents and communities for subsistence and acquisition of learned behaviors. Evidence supporting the concept that altruistic potential is a common feature in human populations is developed. To go into greater depth in assessing critical features of the social brain, the two extremes of selfish-selfless behavior, callous unemotional psychopaths and zealous altruists who take extreme measures to help others, are compared on behavioral traits, structural/functional neural features, and the relative contributions of genetic inheritance versus acquired cognitive learning to their mindsets. Evidence from population groups ranging from newborns, adopted children, incarcerated juveniles, twins and mindfulness meditators point to the important role of neuroplasticity and the dopaminergic reward systems in forming and reforming neural circuitry in response to personal experience and cultural influences in determining behavior in the selfish-selfless spectrum. The underlying neural circuitry differs between psychopaths and altruists with emotional processing being profoundly muted in psychopaths and significantly enhanced in altruists. But both groups are characterized by the reward system of the brain shaping behavior. Instead of rigid assignment of human nature as being "universally selfish" or "universally good," both characterizations are partial truths based on the segments of the selfish-selfless spectrum being examined. In addition, individuals and populations can shift in the behavioral spectrum in response to cognitive therapy and social and cultural experience, and approaches such as mindfulness training for introspection and reward-activating compassion are entering the mainstream of clinical care for managing pain, depression, and stress.

Psychopathy to Altruism: Neurobiology of the Selfish–Selfless Spectrum

PubMed Central

Sonne, James W. H.; Gash, Don M.

2018-01-01

The age-old philosophical, biological, and social debate over the basic nature of humans as being “universally selfish” or “universally good” continues today highlighting sharply divergent views of natural social order. Here we analyze advances in biology, genetics and neuroscience increasing our understanding of the evolution, features and neurocircuitry of the human brain underlying behavior in the selfish–selfless spectrum. First, we examine evolutionary pressures for selection of altruistic traits in species with protracted periods of dependence on parents and communities for subsistence and acquisition of learned behaviors. Evidence supporting the concept that altruistic potential is a common feature in human populations is developed. To go into greater depth in assessing critical features of the social brain, the two extremes of selfish–selfless behavior, callous unemotional psychopaths and zealous altruists who take extreme measures to help others, are compared on behavioral traits, structural/functional neural features, and the relative contributions of genetic inheritance versus acquired cognitive learning to their mindsets. Evidence from population groups ranging from newborns, adopted children, incarcerated juveniles, twins and mindfulness meditators point to the important role of neuroplasticity and the dopaminergic reward systems in forming and reforming neural circuitry in response to personal experience and cultural influences in determining behavior in the selfish–selfless spectrum. The underlying neural circuitry differs between psychopaths and altruists with emotional processing being profoundly muted in psychopaths and significantly enhanced in altruists. But both groups are characterized by the reward system of the brain shaping behavior. Instead of rigid assignment of human nature as being “universally selfish” or “universally good,” both characterizations are partial truths based on the segments of the selfish–selfless spectrum being examined. In addition, individuals and populations can shift in the behavioral spectrum in response to cognitive therapy and social and cultural experience, and approaches such as mindfulness training for introspection and reward-activating compassion are entering the mainstream of clinical care for managing pain, depression, and stress. PMID:29725317

Pain perception and hypnosis: findings from recent functional neuroimaging studies.

PubMed

Del Casale, Antonio; Ferracuti, Stefano; Rapinesi, Chiara; Serata, Daniele; Caltagirone, Saverio Simone; Savoja, Valeria; Piacentino, Daria; Callovini, Gemma; Manfredi, Giovanni; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

2015-01-01

Hypnosis modulates pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. By reviewing functional neuroimaging studies focusing on pain perception under hypnosis, the authors aimed to identify brain activation-deactivation patterns occurring in hypnosis-modulated pain conditions. Different changes in brain functionality occurred throughout all components of the pain network and other brain areas. The anterior cingulate cortex appears to be central in modulating pain circuitry activity under hypnosis. Most studies also showed that the neural functions of the prefrontal, insular, and somatosensory cortices are consistently modified during hypnosis-modulated pain conditions. Functional neuroimaging studies support the clinical use of hypnosis in the management of pain conditions.

Shared neurocircuitry underlying feeding and drugs of abuse in Drosophila.

PubMed

Landayan, Dan; Wolf, Fred W

2015-12-01

The neural circuitry and molecules that control the rewarding properties of food and drugs of abuse appear to partially overlap in the mammalian brain. This has raised questions about the extent of the overlap and the precise role of specific circuit elements in reward and in other behaviors associated with feeding regulation and drug responses. The much simpler brain of invertebrates including the fruit fly Drosophila, offers an opportunity to make high-resolution maps of the circuits and molecules that govern behavior. Recent progress in Drosophila has revealed not only some common substrates for the actions of drugs of abuse and for the regulation of feeding, but also a remarkable level of conservation with vertebrates for key neuromodulatory transmitters. We speculate that Drosophila may serve as a model for distinguishing the neural mechanisms underlying normal and pathological motivational states that will be applicable to mammals. Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.

Spinal Locomotor Circuits Develop Using Hierarchical Rules Based on Motorneuron Position and Identity.

PubMed

Hinckley, Christopher A; Alaynick, William A; Gallarda, Benjamin W; Hayashi, Marito; Hilde, Kathryn L; Driscoll, Shawn P; Dekker, Joseph D; Tucker, Haley O; Sharpee, Tatyana O; Pfaff, Samuel L

2015-09-02

The coordination of multi-muscle movements originates in the circuitry that regulates the firing patterns of spinal motorneurons. Sensory neurons rely on the musculotopic organization of motorneurons to establish orderly connections, prompting us to examine whether the intraspinal circuitry that coordinates motor activity likewise uses cell position as an internal wiring reference. We generated a motorneuron-specific GCaMP6f mouse line and employed two-photon imaging to monitor the activity of lumbar motorneurons. We show that the central pattern generator neural network coordinately drives rhythmic columnar-specific motorneuron bursts at distinct phases of the locomotor cycle. Using multiple genetic strategies to perturb the subtype identity and orderly position of motorneurons, we found that neurons retained their rhythmic activity-but cell position was decoupled from the normal phasing pattern underlying flexion and extension. These findings suggest a hierarchical basis of motor circuit formation that relies on increasingly stringent matching of neuronal identity and position. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular Mechanisms at the Basis of Plasticity in the Developing Visual Cortex: Epigenetic Processes and Gene Programs

PubMed Central

Maya-Vetencourt, José Fernando; Pizzorusso, Tommaso

2013-01-01

Neuronal circuitries in the mammalian visual system change as a function of experience. Sensory experience modifies neuronal networks connectivity via the activation of different physiological processes such as excitatory/inhibitory synaptic transmission, neurotrophins, and signaling of extracellular matrix molecules. Long-lasting phenomena of plasticity occur when intracellular signal transduction pathways promote epigenetic alterations of chromatin structure that regulate the induction of transcription factors that in turn drive the expression of downstream targets, the products of which then work via the activation of structural and functional mechanisms that modify synaptic connectivity. Here, we review recent findings in the field of visual cortical plasticity while focusing on how physiological mechanisms associated with experience promote structural changes that determine functional modifications of neural circuitries in V1. We revise the role of microRNAs as molecular transducers of environmental stimuli and the role of immediate early genes that control gene expression programs underlying plasticity in the developing visual cortex. PMID:25157210

Moving towards causality in attention-deficit hyperactivity disorder: overview of neural and genetic mechanisms

PubMed Central

Gallo, Eduardo F; Posner, Jonathan

2016-01-01

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by developmentally inappropriate levels of inattention and hyperactivity or impulsivity. The heterogeneity of its clinical manifestations and the differential responses to treatment and varied prognoses have long suggested myriad underlying causes. Over the past decade, clinical and basic research efforts have uncovered many behavioural and neurobiological alterations associated with ADHD, from genes to higher order neural networks. Here, we review the neurobiology of ADHD by focusing on neural circuits implicated in the disorder and discuss how abnormalities in circuitry relate to symptom presentation and treatment. We summarise the literature on genetic variants that are potentially related to the development of ADHD, and how these, in turn, might affect circuit function and relevant behaviours. Whether these underlying neurobiological factors are causally related to symptom presentation remains unresolved. Therefore, we assess efforts aimed at disentangling issues of causality, and showcase the shifting research landscape towards endophenotype refinement in clinical and preclinical settings. Furthermore, we review approaches being developed to understand the neurobiological underpinnings of this complex disorder including the use of animal models, neuromodulation, and pharmaco-imaging studies. PMID:27183902

Searching for Cross-diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders

PubMed Central

Foss-Feig, Jennifer H.; Adkinson, Brendan D.; Ji, Jie Lisa; Yang, Genevieve; Srihari, Vinod H.; McPartland, James C.; Krystal, John H.; Murray, John D.; Anticevic, Alan

2017-01-01

Recent theoretical accounts have proposed excitation (E) and inhibition (I) imbalance as a possible mechanistic, network-level hypothesis underlying neural and behavioral dysfunction across neurodevelopmental disorders, particularly autism spectrum disorder (ASD) and schizophrenia (SCZ). These two disorders share some overlap in their clinical presentation as well as convergence in their underlying genes and neurobiology. However, there are also clear points of dissociation in terms of phenotypes and putatively affected neural circuitry. Here we highlight emerging work from the clinical neuroscience literature examining neural correlates of E/I imbalance across children and adults with ASD and adults with both chronic and early-course SCZ. We discuss findings from diverse neuroimaging studies across distinct modalities, conducted with EEG, MEG, 1H-MRS, and fMRI, including effects observed both during task and at rest. Throughout this review we discuss points of convergence and divergence in the ASD and SCZ literature, with a focus on disruptions in neural E/I balance. We also consider these findings in relation to predictions generated by theoretical neuroscience, particularly computational models predicting E/I imbalance across disorders. Finally, we discuss how human non-invasive neuroimaging can benefit from pharmacological challenge studies to reveal mechanisms in ASD and SCZ. Collectively, we attempt to shed light on shared and divergent neuroimaging effects across disorders with the goal of informing future research examining the mechanisms underlying the E/I imbalance hypothesis across neurodevelopmental disorders. We posit that such translational efforts are vital to facilitate development of neurobiologically informed treatment strategies across neuropsychiatric conditions. PMID:28434615

Lactate release from astrocytes to neurons contributes to cocaine memory formation.

PubMed

Boury-Jamot, Benjamin; Halfon, Olivier; Magistretti, Pierre J; Boutrel, Benjamin

2016-12-01

The identification of neural substrates underlying the long lasting debilitating impact of drug cues is critical for developing novel therapeutic tools. Metabolic coupling has long been considered a key mechanism through which astrocytes and neurons actively interact in response of neuronal activity, but recent findings suggested that disrupting metabolic coupling may represent an innovative approach to prevent memory formation, in particular drug-related memories. Here, we review converging evidence illustrating how memory and addiction share neural circuitry and molecular mechanisms implicating lactate-mediated metabolic coupling between astrocytes and neurons. With several aspects of addiction depending on mnemonic processes elicited by drug experience, disrupting lactate transport involved in the formation of a pathological learning, linking the incentive, and motivational effects of drugs with drug-conditioned stimuli represent a promising approach to encourage abstinence. © 2016 WILEY Periodicals, Inc.

Central control of body temperature

PubMed Central

Morrison, Shaun F.

2016-01-01

Central neural circuits orchestrate the behavioral and autonomic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response and behavioral states and in response to declining energy homeostasis. This review summarizes the central nervous system circuit mechanisms controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for thermogenesis. The activation of these thermoeffectors is regulated by parallel but distinct efferent pathways within the central nervous system that share a common peripheral thermal sensory input. The model for the neural circuit mechanism underlying central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation, for elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation, and for the discovery of novel therapeutic approaches to modulating body temperature and energy homeostasis. PMID:27239289

Central control of body temperature.

PubMed

Morrison, Shaun F

2016-01-01

Central neural circuits orchestrate the behavioral and autonomic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response and behavioral states and in response to declining energy homeostasis. This review summarizes the central nervous system circuit mechanisms controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for thermogenesis. The activation of these thermoeffectors is regulated by parallel but distinct efferent pathways within the central nervous system that share a common peripheral thermal sensory input. The model for the neural circuit mechanism underlying central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation, for elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation, and for the discovery of novel therapeutic approaches to modulating body temperature and energy homeostasis.

Sex differences in the development of emotion circuitry in adolescents at risk for substance abuse: a longitudinal fMRI study.

PubMed

Hardee, Jillian E; Cope, Lora M; Munier, Emily C; Welsh, Robert C; Zucker, Robert A; Heitzeg, Mary M

2017-06-01

There is substantial evidence for behavioral sex differences in risk trajectories for alcohol and substance use, with internalizing factors such as negative affectivity contributing more to female risk. Because the neural development of emotion circuitry varies between males and females across adolescence, it represents a potential mechanism by which underlying neurobiology contributes to risk for substance use. Longitudinal functional magnetic resonance imaging was conducted in males and females (n = 18 each) with a family history of alcohol use disorders starting at ages 8-13 years. Participants performed an affective word task during functional magnetic resonance imaging at 1- to 2-year intervals, covering the age range of 8.5-17.6 years (3-4 scans per participant). Significant age-related sex differences were found in the right amygdala and right precentral gyrus for the negative vs neutral word condition. Males showed a significant decrease in both amygdala and precentral gyrus activation with age, whereas the response in females persisted. The subjective experience of internalizing symptomatology significantly increased with age for females but not for males. Taken together, these results reveal sex differences in negative affect processing in at-risk adolescents, and offer longitudinal neural evidence for female substance use risk through internalizing pathways. © The Author (2017). Published by Oxford University Press.

The influence of emotion regulation on decision-making under risk.

PubMed

Martin, Laura N; Delgado, Mauricio R

2011-09-01

Cognitive strategies typically involved in regulating negative emotions have recently been shown to also be effective with positive emotions associated with monetary rewards. However, it is less clear how these strategies influence behavior, such as preferences expressed during decision-making under risk, and the underlying neural circuitry. That is, can the effective use of emotion regulation strategies during presentation of a reward-conditioned stimulus influence decision-making under risk and neural structures involved in reward processing such as the striatum? To investigate this question, we asked participants to engage in imagery-focused regulation strategies during the presentation of a cue that preceded a financial decision-making phase. During the decision phase, participants then made a choice between a risky and a safe monetary lottery. Participants who successfully used cognitive regulation, as assessed by subjective ratings about perceived success and facility in implementation of strategies, made fewer risky choices in comparison with trials where decisions were made in the absence of cognitive regulation. Additionally, BOLD responses in the striatum were attenuated during decision-making as a function of successful emotion regulation. These findings suggest that exerting cognitive control over emotional responses can modulate neural responses associated with reward processing (e.g., striatum) and promote more goal-directed decision-making (e.g., less risky choices), illustrating the potential importance of cognitive strategies in curbing risk-seeking behaviors before they become maladaptive (e.g., substance abuse).

Feed Your Head: Neurodevelopmental Control of Feeding and Metabolism

PubMed Central

Lee, Daniel A.; Blackshaw, Seth

2014-01-01

During critical periods of development early in life, excessive or scarce nutritional environments can disrupt the development of central feeding and metabolic neural circuitry, leading to obesity and metabolic disorders in adulthood. A better understanding of the genetic networks that control the development of feeding and metabolic neural circuits, along with knowledge of how and where dietary signals disrupt this process, can serve as the basis for future therapies aimed at reversing the public health crisis that is now building as a result of the global obesity epidemic. This review of animal and human studies highlights recent insights into the molecular mechanisms that regulate the development of central feeding circuitries, the mechanisms by which gestational and early postnatal nutritional status affects this process, and approaches aimed at counteracting the deleterious effects of early over- and underfeeding. PMID:24274739

Genetic control of postnatal human brain growth

PubMed Central

van Dyck, Laura I.; Morrow, Eric M.

2017-01-01

Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

Nonvolatile Array Of Synapses For Neural Network

NASA Technical Reports Server (NTRS)

Tawel, Raoul

1993-01-01

Elements of array programmed with help of ultraviolet light. A 32 x 32 very-large-scale integrated-circuit array of electronic synapses serves as building-block chip for analog neural-network computer. Synaptic weights stored in nonvolatile manner. Makes information content of array invulnerable to loss of power, and, by eliminating need for circuitry to refresh volatile synaptic memory, makes architecture simpler and more compact.

Positive clinical effects of gamma knife capsulotomy in a patient with deep brain stimulation-refractory Tourette Syndrome and Obsessive Compulsive Disorder.

PubMed

Richieri, Raphaëlle; Blackman, Graham; Musil, Richard; Spatola, Giorgio; Cavanna, Andrea E; Lançon, Christophe; Régis, Jean

2018-04-26

We report the first case of a patient with severe, intractable Tourette Syndrome with comorbid Obsessive Compulsive disorder, who recovered from both disorders with gamma-knife (GK) stereotactic radiosurgery following deep brain stimulation (DBS). This case highlights the possible role of the internal capsule within the neural circuitries underlying both TS and OCD, and suggests that in cases of treatment-refractory TS and comorbid OCD, bilateral anterior capsulotomy using stereotactic radiosurgery may be a viable treatment option. Copyright © 2018 Elsevier B.V. All rights reserved.

The storytelling brain. Commentary on "On social attribution: implications of recent cognitive neuroscience research for race, law, and politics".

PubMed

Nigam, Sanjay K

2012-09-01

The well-established techniques of the professional storyteller not only have the potential to model complex "truth" but also to dig deeply into that complexity, thereby perhaps getting closer to that truth. This applies not only to fiction, but also to medicine and even science. Compelling storytelling ability may have conferred an evolutionary survival advantage and, if so, is likely represented in the neural circuitry of the human brain. Functional imaging will likely point to a neuroanatomical basis for compelling storytelling ability; this will presumably reflect underlying cellular and molecular mechanisms.

Computational Models and Emergent Properties of Respiratory Neural Networks

PubMed Central

Lindsey, Bruce G.; Rybak, Ilya A.; Smith, Jeffrey C.

2012-01-01

Computational models of the neural control system for breathing in mammals provide a theoretical and computational framework bringing together experimental data obtained from different animal preparations under various experimental conditions. Many of these models were developed in parallel and iteratively with experimental studies and provided predictions guiding new experiments. This data-driven modeling approach has advanced our understanding of respiratory network architecture and neural mechanisms underlying generation of the respiratory rhythm and pattern, including their functional reorganization under different physiological conditions. Models reviewed here vary in neurobiological details and computational complexity and span multiple spatiotemporal scales of respiratory control mechanisms. Recent models describe interacting populations of respiratory neurons spatially distributed within the Bötzinger and pre-Bötzinger complexes and rostral ventrolateral medulla that contain core circuits of the respiratory central pattern generator (CPG). Network interactions within these circuits along with intrinsic rhythmogenic properties of neurons form a hierarchy of multiple rhythm generation mechanisms. The functional expression of these mechanisms is controlled by input drives from other brainstem components, including the retrotrapezoid nucleus and pons, which regulate the dynamic behavior of the core circuitry. The emerging view is that the brainstem respiratory network has rhythmogenic capabilities at multiple levels of circuit organization. This allows flexible, state-dependent expression of different neural pattern-generation mechanisms under various physiological conditions, enabling a wide repertoire of respiratory behaviors. Some models consider control of the respiratory CPG by pulmonary feedback and network reconfiguration during defensive behaviors such as cough. Future directions in modeling of the respiratory CPG are considered. PMID:23687564

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours.

PubMed

Voon, Valerie; Mole, Thomas B; Banca, Paula; Porter, Laura; Morris, Laurel; Mitchell, Simon; Lapa, Tatyana R; Karr, Judy; Harrison, Neil A; Potenza, Marc N; Irvine, Michael

2014-01-01

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions.

Neural Correlates of Sexual Cue Reactivity in Individuals with and without Compulsive Sexual Behaviours

PubMed Central

Voon, Valerie; Mole, Thomas B.; Banca, Paula; Porter, Laura; Morris, Laurel; Mitchell, Simon; Lapa, Tatyana R.; Karr, Judy; Harrison, Neil A.; Potenza, Marc N.; Irvine, Michael

2014-01-01

Although compulsive sexual behaviour (CSB) has been conceptualized as a “behavioural” addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions. PMID:25013940

Neural Substrates of Inhibitory Control Deficits in 22q11.2 Deletion Syndrome†

PubMed Central

Montojo, C.A.; Jalbrzikowski, M.; Congdon, E.; Domicoli, S.; Chow, C.; Dawson, C.; Karlsgodt, K.H.; Bilder, R.M.; Bearden, C.E.

2015-01-01

22q11.2 deletion syndrome (22q11DS) is associated with elevated levels of impulsivity, inattention, and distractibility, which may be related to underlying neurobiological dysfunction due to haploinsufficiency for genes involved in dopaminergic neurotransmission (i.e. catechol-O-methyltransferase). The Stop-signal task has been employed to probe the neural circuitry involved in response inhibition (RI); findings in healthy individuals indicate that a fronto-basal ganglia network underlies successful inhibition of a prepotent motor response. However, little is known about the neurobiological substrates of RI difficulties in 22q11DS. Here, we investigated this using functional magnetic resonance imaging while 45 adult participants (15 22q11DS patients, 30 matched controls) performed the Stop-signal task. Healthy controls showed significantly greater activation than 22q11DS patients within frontal cortical and basal ganglia regions during successful RI, whereas 22q11DS patients did not show increased neural activity relative to controls in any regions. Using the Barratt Impulsivity Scale, we also investigated whether neural dysfunction during RI was associated with cognitive impulsivity in 22q11DS patients. RI-related activity within left middle frontal gyrus and basal ganglia was associated with severity of self-reported cognitive impulsivity. These results suggest reduced engagement of RI-related brain regions in 22q11DS patients, which may be relevant to characteristic behavioral manifestations of the disorder. PMID:24177988

Mental training enhances attentional stability: Neural and behavioral evidence

PubMed Central

Lutz, Antoine; Slagter, Heleen A.; Rawlings, Nancy B.; Francis, Andrew D.; Greischar, Lawrence L.; Davidson, Richard J.

2009-01-01

The capacity to stabilize the content of attention over time varies among individuals and its impairment is a hallmark of several mental illnesses. Impairments in sustained attention in patients with attention disorders have been associated with increased trial-to-trial variability in reaction time and event-related potential (ERP) deficits during attention tasks. At present, it is unclear whether the ability to sustain attention and its underlying brain circuitry are transformable through training. Here, we show, with dichotic listening task performance and electroencephalography (EEG), that training attention, as cultivated by meditation, can improve the ability to sustain attention. Three months of intensive meditation training reduced variability in attentional processing of target tones, as indicated by both enhanced theta-band phase consistency of oscillatory neural responses over anterior brain areas and reduced reaction time variability. Furthermore, those individuals who showed the greatest increase in neural response consistency showed the largest decrease in behavioral response variability. Notably, we also observed reduced variability in neural processing, in particular in low-frequency bands, regardless of whether the deviant tone was attended or unattended. Focused attention meditation may thus affect both distracter and target processing, perhaps by enhancing entrainment of neuronal oscillations to sensory input rhythms; a mechanism important for controlling the content of attention. These novel findings highlight the mechanisms underlying focused attention meditation, and support the notion that mental training can significantly affect attention and brain function. PMID:19846729

Deconstructing Memory in Drosophila

PubMed Central

Margulies, Carla; Tully, Tim; Dubnau, Josh

2011-01-01

Unlike most organ systems, which have evolved to maintain homeostasis, the brain has been selected to sense and adapt to environmental stimuli by constantly altering interactions in a gene network that functions within a larger neural network. This unique feature of the central nervous system provides a remarkable plasticity of behavior, but also makes experimental investigations challenging. Each experimental intervention ramifies through both gene and neural networks, resulting in unpredicted and sometimes confusing phenotypic adaptations. Experimental dissection of mechanisms underlying behavioral plasticity ultimately must accomplish an integration across many levels of biological organization, including genetic pathways acting within individual neurons, neural network interactions which feed back to gene function, and phenotypic observations at the behavioral level. This dissection will be more easily accomplished for model systems such as Drosophila, which, compared with mammals, have relatively simple and manipulable nervous systems and genomes. The evolutionary conservation of behavioral phenotype and the underlying gene function ensures that much of what we learn in such model systems will be relevant to human cognition. In this essay, we have not attempted to review the entire Drosophila memory field. Instead, we have tried to discuss particular findings that provide some level of intellectual synthesis across three levels of biological organization: behavior, neural circuitry and biochemical pathways. We have attempted to use this integrative approach to evaluate distinct mechanistic hypotheses, and to propose critical experiments that will advance this field. PMID:16139203

Electrical and Optical Activation of Mesoscale Neural Circuits with Implications for Coding.

PubMed

Millard, Daniel C; Whitmire, Clarissa J; Gollnick, Clare A; Rozell, Christopher J; Stanley, Garrett B

2015-11-25

Artificial activation of neural circuitry through electrical microstimulation and optogenetic techniques is important for both scientific discovery of circuit function and for engineered approaches to alleviate various disorders of the nervous system. However, evidence suggests that neural activity generated by artificial stimuli differs dramatically from normal circuit function, in terms of both the local neuronal population activity at the site of activation and the propagation to downstream brain structures. The precise nature of these differences and the implications for information processing remain unknown. Here, we used voltage-sensitive dye imaging of primary somatosensory cortex in the anesthetized rat in response to deflections of the facial vibrissae and electrical or optogenetic stimulation of thalamic neurons that project directly to the somatosensory cortex. Although the different inputs produced responses that were similar in terms of the average cortical activation, the variability of the cortical response was strikingly different for artificial versus sensory inputs. Furthermore, electrical microstimulation resulted in highly unnatural spatial activation of cortex, whereas optical input resulted in spatial cortical activation that was similar to that induced by sensory inputs. A thalamocortical network model suggested that observed differences could be explained by differences in the way in which artificial and natural inputs modulate the magnitude and synchrony of population activity. Finally, the variability structure in the response for each case strongly influenced the optimal inputs for driving the pathway from the perspective of an ideal observer of cortical activation when considered in the context of information transmission. Artificial activation of neural circuitry through electrical microstimulation and optogenetic techniques is important for both scientific discovery and clinical translation. However, neural activity generated by these artificial means differs dramatically from normal circuit function, both locally and in the propagation to downstream brain structures. The precise nature of these differences and the implications for information processing remain unknown. The significance of this work is in quantifying the differences, elucidating likely mechanisms underlying the differences, and determining the implications for information processing. Copyright © 2015 the authors 0270-6474/15/3515702-14$15.00/0.

Fear Conditioning, Synaptic Plasticity, and the Amygdala: Implications for Posttraumatic Stress Disorder

PubMed Central

Mahan, Amy L.; Ressler, Kerry J.

2011-01-01

Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after a traumatic experience such as domestic violence, natural disasters or combat-related trauma. The cost of such disorders on society and the individual can be tremendous. In this article we will review how the neural circuitry implicated in PTSD in humans is related to the neural circuitry of fear. We then discuss how fear conditioning is a suitable model for studying the molecular mechanisms of the fear components which underlie PTSD, and the biology of fear conditioning with a particular focus on the brain derived neurotropic factor (BDNF)-TrkB, GABAergic and glutamatergic ligand-receptor systems. We then summarize how such approaches may help to inform our understanding of PTSD and other stress-related disorders and provide insight to new pharmacological avenues of treatment of PTSD. PMID:21798604

Understanding Overbidding: Using the Neural Circuitry of Reward to Design Economic Auctions

PubMed Central

Delgado, Mauricio R.; Schotter, Andrew; Ozbay, Erkut Y.; Phelps, Elizabeth A.

2011-01-01

We take advantage of our knowledge of the neural circuitry of reward to investigate a puzzling economic phenomenon: Why do people overbid in auctions? Using functional magnetic resonance imaging (fMRI), we observed that the social competition inherent in an auction results in a more pronounced blood oxygen level–dependent (BOLD) response to loss in the striatum, with greater overbidding correlated with the magnitude of this response. Leveraging these neuroimaging results, we design a behavioral experiment that demonstrates that framing an experimental auction to emphasize loss increases overbidding. These results highlight a role for the contemplation of loss in understanding the tendency to bid “too high.” Current economic theories suggest overbidding may result from either “joy of winning” or risk aversion. By combining neuroeconomic and behavioral economic techniques, we find that another factor, namely loss contemplation in a social context, may mediate overbidding in auctions. PMID:18818362

Understanding overbidding: using the neural circuitry of reward to design economic auctions.

PubMed

Delgado, Mauricio R; Schotter, Andrew; Ozbay, Erkut Y; Phelps, Elizabeth A

2008-09-26

We take advantage of our knowledge of the neural circuitry of reward to investigate a puzzling economic phenomenon: Why do people overbid in auctions? Using functional magnetic resonance imaging (fMRI), we observed that the social competition inherent in an auction results in a more pronounced blood oxygen level-dependent (BOLD) response to loss in the striatum, with greater overbidding correlated with the magnitude of this response. Leveraging these neuroimaging results, we design a behavioral experiment that demonstrates that framing an experimental auction to emphasize loss increases overbidding. These results highlight a role for the contemplation of loss in understanding the tendency to bid "too high." Current economic theories suggest overbidding may result from either "joy of winning" or risk aversion. By combining neuroeconomic and behavioral economic techniques, we find that another factor, namely loss contemplation in a social context, may mediate overbidding in auctions.

Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries.

PubMed

Fricchione, Gregory; Stefano, George B

2005-05-01

Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a role in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be an important signal molecule working at mu receptors on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects on these dopamine systems as well as on periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions.

Evolving a Neural Olfactorimotor System in Virtual and Real Olfactory Environments

PubMed Central

Rhodes, Paul A.; Anderson, Todd O.

2012-01-01

To provide a platform to enable the study of simulated olfactory circuitry in context, we have integrated a simulated neural olfactorimotor system with a virtual world which simulates both computational fluid dynamics as well as a robotic agent capable of exploring the simulated plumes. A number of the elements which we developed for this purpose have not, to our knowledge, been previously assembled into an integrated system, including: control of a simulated agent by a neural olfactorimotor system; continuous interaction between the simulated robot and the virtual plume; the inclusion of multiple distinct odorant plumes and background odor; the systematic use of artificial evolution driven by olfactorimotor performance (e.g., time to locate a plume source) to specify parameter values; the incorporation of the realities of an imperfect physical robot using a hybrid model where a physical robot encounters a simulated plume. We close by describing ongoing work toward engineering a high dimensional, reversible, low power electronic olfactory sensor which will allow olfactorimotor neural circuitry evolved in the virtual world to control an autonomous olfactory robot in the physical world. The platform described here is intended to better test theories of olfactory circuit function, as well as provide robust odor source localization in realistic environments. PMID:23112772

A case for spiking neural network simulation based on configurable multiple-FPGA systems.

PubMed

Yang, Shufan; Wu, Qiang; Li, Renfa

2011-09-01

Recent neuropsychological research has begun to reveal that neurons encode information in the timing of spikes. Spiking neural network simulations are a flexible and powerful method for investigating the behaviour of neuronal systems. Simulation of the spiking neural networks in software is unable to rapidly generate output spikes in large-scale of neural network. An alternative approach, hardware implementation of such system, provides the possibility to generate independent spikes precisely and simultaneously output spike waves in real time, under the premise that spiking neural network can take full advantage of hardware inherent parallelism. We introduce a configurable FPGA-oriented hardware platform for spiking neural network simulation in this work. We aim to use this platform to combine the speed of dedicated hardware with the programmability of software so that it might allow neuroscientists to put together sophisticated computation experiments of their own model. A feed-forward hierarchy network is developed as a case study to describe the operation of biological neural systems (such as orientation selectivity of visual cortex) and computational models of such systems. This model demonstrates how a feed-forward neural network constructs the circuitry required for orientation selectivity and provides platform for reaching a deeper understanding of the primate visual system. In the future, larger scale models based on this framework can be used to replicate the actual architecture in visual cortex, leading to more detailed predictions and insights into visual perception phenomenon.

Genetic Moderation of Stress Effects on Corticolimbic Circuitry.

PubMed

Bogdan, Ryan; Pagliaccio, David; Baranger, David Aa; Hariri, Ahmad R

2016-01-01

Stress exposure is associated with individual differences in corticolimbic structure and function that often mirror patterns observed in psychopathology. Gene x environment interaction research suggests that genetic variation moderates the impact of stress on risk for psychopathology. On the basis of these findings, imaging genetics, which attempts to link variability in DNA sequence and structure to neural phenotypes, has begun to incorporate measures of the environment. This research paradigm, known as imaging gene x environment interaction (iGxE), is beginning to contribute to our understanding of the neural mechanisms through which genetic variation and stress increase psychopathology risk. Although awaiting replication, evidence suggests that genetic variation within the canonical neuroendocrine stress hormone system, the hypothalamic-pituitary-adrenal axis, contributes to variability in stress-related corticolimbic structure and function, which, in turn, confers risk for psychopathology. For iGxE research to reach its full potential it will have to address many challenges, of which we discuss: (i) small effects, (ii) measuring the environment and neural phenotypes, (iii) the absence of detailed mechanisms, and (iv) incorporating development. By actively addressing these challenges, iGxE research is poised to help identify the neural mechanisms underlying genetic and environmental associations with psychopathology.

Alterations in the neural circuitry for emotion and attention associated with posttraumatic stress symptomatology

PubMed Central

Hayes, Jasmeet Pannu; LaBar, Kevin S.; Petty, Christopher M.; McCarthy, Gregory; Morey, Rajendra A.

2009-01-01

Information processing models of posttraumatic stress disorder (PTSD) suggest that PTSD is characterized by preferential allocation of attentional resources to potentially threatening stimuli. However, few studies have examined the neural pattern underlying attention and emotion in association with PTSD symptomatology. In the present study, combat veterans with PTSD symptomatology engaged in an emotional oddball task while undergoing functional magnetic resonance imaging (fMRI). Veterans were classified into a high or low symptomatology group based on their scores on the Davidson Trauma Scale (DTS). Participants discriminated infrequent target stimuli (circles) from frequent standards (squares) while emotional and neutral distractors were presented infrequently and irregularly. Results revealed that participants with greater PTSD symptomatology showed enhanced neural activity in ventral-limbic and dorsal regions for emotional stimuli and attenuated activity in dorsolateral prefrontal and parietal regions for attention targets. In the anterior cingulate gyrus, participants with fewer PTSD symptoms showed equivalent responses to attentional and emotional stimuli while the high symptom group showed greater activation for negative emotional stimuli. Taken together, the results suggest that hyperresponsive ventral-limbic activity coupled with altered dorsal-attention and anterior cingulate function may be a neural marker of attention bias in PTSD. PMID:19237269

Neural signatures of co-occurring reading and mathematical difficulties.

PubMed

Skeide, Michael A; Evans, Tanya M; Mei, Edward Z; Abrams, Daniel A; Menon, Vinod

2018-06-19

Impaired abilities in multiple domains is common in children with learning difficulties. Co-occurrence of low reading and mathematical abilities (LRLM) appears in almost every second child with learning difficulties. However, little is known regarding the neural bases of this combination. Leveraging a unique and tightly controlled sample including children with LRLM, isolated low reading ability (LR), and isolated low mathematical ability (LM), we uncover a distinct neural signature in children with co-occurring low reading and mathematical abilities differentiable from LR and LM. Specifically, we show that LRLM is neuroanatomically distinct from both LR and LM based on reduced cortical folding of the right parahippocampal gyrus, a medial temporal lobe region implicated in visual associative learning. LRLM children were further distinguished from LR and LM by patterns of intrinsic functional connectivity between parahippocampal gyrus and brain circuitry underlying reading and numerical quantity processing. Our results critically inform cognitive and neural models of LRLM by implicating aberrations in both domain-specific and domain-general brain regions involved in reading and mathematics. More generally, our results provide the first evidence for distinct multimodal neural signatures associated with LRLM, and suggest that this population displays an independent phenotype of learning difficulty that cannot be explained simply as a combination of isolated low reading and mathematical abilities. © 2018 John Wiley & Sons Ltd.

Renormalization of Collective Modes in Large-Scale Neural Dynamics

NASA Astrophysics Data System (ADS)

Moirogiannis, Dimitrios; Piro, Oreste; Magnasco, Marcelo O.

2017-05-01

The bulk of studies of coupled oscillators use, as is appropriate in Physics, a global coupling constant controlling all individual interactions. However, because as the coupling is increased, the number of relevant degrees of freedom also increases, this setting conflates the strength of the coupling with the effective dimensionality of the resulting dynamics. We propose a coupling more appropriate to neural circuitry, where synaptic strengths are under biological, activity-dependent control and where the coupling strength and the dimensionality can be controlled separately. Here we study a set of N→ ∞ strongly- and nonsymmetrically-coupled, dissipative, powered, rotational dynamical systems, and derive the equations of motion of the reduced system for dimensions 2 and 4. Our setting highlights the statistical structure of the eigenvectors of the connectivity matrix as the fundamental determinant of collective behavior, inheriting from this structure symmetries and singularities absent from the original microscopic dynamics.

Group Membership Modulates the Neural Circuitry Underlying Third Party Punishment

PubMed Central

Sambataro, Fabio; Perussia, Felice; Valentini, Maria Consuelo; Bara, Bruno G.; Bosco, Francesca M.

2016-01-01

This research aims to explore the neural correlates involved in altruistic punishment, parochial altruism and anti-social punishment, using the Third-Party Punishment (TPP) game. In particular, this study considered these punishment behaviors in in-group vs. out-group game settings, to compare how people behave with members of their own national group and with members of another national group. The results showed that participants act altruistically to protect in-group members. This study indicates that norm violation in in-group (but not in out-group) settings results in increased activity in the medial prefrontal cortex and temporo-parietal junction, brain regions involved in the mentalizing network, as the third-party attempts to understand or justify in-group members’ behavior. Finally, exploratory analysis during anti-social punishment behavior showed brain activation recruitment of the ventromedial prefrontal cortex, an area associated with altered regulation of emotions. PMID:27835675

Group Membership Modulates the Neural Circuitry Underlying Third Party Punishment.

PubMed

Morese, Rosalba; Rabellino, Daniela; Sambataro, Fabio; Perussia, Felice; Valentini, Maria Consuelo; Bara, Bruno G; Bosco, Francesca M

2016-01-01

This research aims to explore the neural correlates involved in altruistic punishment, parochial altruism and anti-social punishment, using the Third-Party Punishment (TPP) game. In particular, this study considered these punishment behaviors in in-group vs. out-group game settings, to compare how people behave with members of their own national group and with members of another national group. The results showed that participants act altruistically to protect in-group members. This study indicates that norm violation in in-group (but not in out-group) settings results in increased activity in the medial prefrontal cortex and temporo-parietal junction, brain regions involved in the mentalizing network, as the third-party attempts to understand or justify in-group members' behavior. Finally, exploratory analysis during anti-social punishment behavior showed brain activation recruitment of the ventromedial prefrontal cortex, an area associated with altered regulation of emotions.

Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders.

PubMed

Foss-Feig, Jennifer H; Adkinson, Brendan D; Ji, Jie Lisa; Yang, Genevieve; Srihari, Vinod H; McPartland, James C; Krystal, John H; Murray, John D; Anticevic, Alan

2017-05-15

Recent theoretical accounts have proposed excitation and inhibition (E/I) imbalance as a possible mechanistic, network-level hypothesis underlying neural and behavioral dysfunction across neurodevelopmental disorders, particularly autism spectrum disorder (ASD) and schizophrenia (SCZ). These two disorders share some overlap in their clinical presentation as well as convergence in their underlying genes and neurobiology. However, there are also clear points of dissociation in terms of phenotypes and putatively affected neural circuitry. We highlight emerging work from the clinical neuroscience literature examining neural correlates of E/I imbalance across children and adults with ASD and adults with both chronic and early-course SCZ. We discuss findings from diverse neuroimaging studies across distinct modalities, conducted with electroencephalography, magnetoencephalography, proton magnetic resonance spectroscopy, and functional magnetic resonance imaging, including effects observed both during task and at rest. Throughout this review, we discuss points of convergence and divergence in the ASD and SCZ literature, with a focus on disruptions in neural E/I balance. We also consider these findings in relation to predictions generated by theoretical neuroscience, particularly computational models predicting E/I imbalance across disorders. Finally, we discuss how human noninvasive neuroimaging can benefit from pharmacological challenge studies to reveal mechanisms in ASD and SCZ. Collectively, we attempt to shed light on shared and divergent neuroimaging effects across disorders with the goal of informing future research examining the mechanisms underlying the E/I imbalance hypothesis across neurodevelopmental disorders. We posit that such translational efforts are vital to facilitate development of neurobiologically informed treatment strategies across neuropsychiatric conditions. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Neural Circuitry of Impaired Emotion Regulation in Substance Use Disorders.

PubMed

Wilcox, Claire E; Pommy, Jessica M; Adinoff, Bryon

2016-04-01

Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders than treatments that dampen reactivity.

Neural Circuitry of Impaired Emotion Regulation in Substance Use Disorders

PubMed Central

Wilcox, Claire E.; Pommy, Jessica M.; Adinoff, Bryon

2016-01-01

Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders than treatments that dampen reactivity. PMID:26771738

Dissociable patterns of medial prefrontal and amygdala activity to face identity versus emotion in bipolar disorder.

PubMed

Keener, M T; Fournier, J C; Mullin, B C; Kronhaus, D; Perlman, S B; LaBarbara, E; Almeida, J C; Phillips, M L

2012-09-01

Individuals with bipolar disorder demonstrate abnormal social function. Neuroimaging studies in bipolar disorder have shown functional abnormalities in neural circuitry supporting face emotion processing, but have not examined face identity processing, a key component of social function. We aimed to elucidate functional abnormalities in neural circuitry supporting face emotion and face identity processing in bipolar disorder. Twenty-seven individuals with bipolar disorder I currently euthymic and 27 healthy controls participated in an implicit face processing, block-design paradigm. Participants labeled color flashes that were superimposed on dynamically changing background faces comprising morphs either from neutral to prototypical emotion (happy, sad, angry and fearful) or from one identity to another identity depicting a neutral face. Whole-brain and amygdala region-of-interest (ROI) activities were compared between groups. There was no significant between-group difference looking across both emerging face emotion and identity. During processing of all emerging emotions, euthymic individuals with bipolar disorder showed significantly greater amygdala activity. During facial identity and also happy face processing, euthymic individuals with bipolar disorder showed significantly greater amygdala and medial prefrontal cortical activity compared with controls. This is the first study to examine neural circuitry supporting face identity and face emotion processing in bipolar disorder. Our findings of abnormally elevated activity in amygdala and medial prefrontal cortex (mPFC) during face identity and happy face emotion processing suggest functional abnormalities in key regions previously implicated in social processing. This may be of future importance toward examining the abnormal self-related processing, grandiosity and social dysfunction seen in bipolar disorder.

The Influence of Emotion Regulation on Decision-making under Risk

PubMed Central

Martin, Laura N.; Delgado, Mauricio R.

2011-01-01

Cognitive strategies typically involved in regulating negative emotions have recently been shown to also be effective with positive emotions associated with monetary rewards. However, it is less clear how these strategies influence behavior, such as preferences expressed during decision-making under risk, and the underlying neural circuitry. That is, can the effective use of emotion regulation strategies during presentation of a reward-conditioned stimulus influence decision-making under risk and neural structures involved in reward processing such as the striatum? To investigate this question, we asked participants to engage in imagery-focused regulation strategies during the presentation of a cue that preceded a financial decision-making phase. During the decision phase, participants then made a choice between a risky and a safe monetary lottery. Participants who successfully used cognitive regulation, as assessed by subjective ratings about perceived success and facility in implementation of strategies, made fewer risky choices in comparison to trials where decisions were made in the absence of cognitive regulation. Additionally, blood-oxygen-level-dependent (BOLD) responses in the striatum were attenuated during decision-making as a function of successful emotion regulation. These findings suggest that exerting cognitive control over emotional responses can modulate neural responses associated with reward processing (e.g., striatum), and promote more goal-directed decision-making (e.g., less risky choices), illustrating the potential importance of cognitive strategies in curbing risk-seeking behaviors before they become maladaptive (e.g., substance abuse). PMID:21254801

Social pain and social gain in the adolescent brain: A common neural circuitry underlying both positive and negative social evaluation

PubMed Central

Dalgleish, Tim; Walsh, Nicholas D.; Mobbs, Dean; Schweizer, Susanne; van Harmelen, Anne-Laura; Dunn, Barnaby; Dunn, Valerie; Goodyer, Ian; Stretton, Jason

2017-01-01

Social interaction inherently involves the subjective evaluation of cues salient to social inclusion and exclusion. Testifying to the importance of such social cues, parts of the neural system dedicated to the detection of physical pain, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been shown to be equally sensitive to the detection of social pain experienced after social exclusion. However, recent work suggests that this dACC-AI matrix may index any socially pertinent information. We directly tested the hypothesis that the dACC-AI would respond to cues of both inclusion and exclusion, using a novel social feedback fMRI paradigm in a population-derived sample of adolescents. We show that the dACC and left AI are commonly activated by feedback cues of inclusion and exclusion. Our findings suggest that theoretical accounts of the dACC-AI network as a neural alarm system restricted within the social domain to the processing of signals of exclusion require significant revision. PMID:28169323

Self-esteem modulates amygdala-ventrolateral prefrontal cortex connectivity in response to mortality threats.

PubMed

Yanagisawa, Kuniaki; Abe, Nobuhito; Kashima, Emiko S; Nomura, Michio

2016-03-01

Reminders of death often elicit defensive responses in individuals, especially among those with low self-esteem. Although empirical evidence indicates that self-esteem serves as a buffer against mortality threats, the precise neural mechanism underlying this effect remains unknown. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that self-esteem modulates neural responses to death-related stimuli, especially functional connectivity within the limbic-frontal circuitry, thereby affecting subsequent defensive reactions. As predicted, individuals with high self-esteem subjected to a mortality threat exhibited increased amygdala-ventrolateral prefrontal cortex (VLPFC) connectivity during the processing of death-related stimuli compared with individuals who have low self-esteem. Further analysis revealed that stronger functional connectivity between the amygdala and the VLPFC predicted a subsequent decline in responding defensively to those who threaten one's beliefs. These results suggest that the amygdala-VLPFC interaction, which is modulated by self-esteem, can reduce the defensiveness caused by death-related stimuli, thereby providing a neural explanation for why individuals with high self-esteem exhibit less defensive reactions to mortality threats. (c) 2016 APA, all rights reserved).

Peril and Pleasure: An RDoC-inspired examination of threat responses and reward processing in anxiety and depression

PubMed Central

Dillon, Daniel G.; Rosso, Isabelle M.; Pechtel, Pia; Killgore, William D. S.; Rauch, Scott L.; Pizzagalli, Diego A.

2014-01-01

As a step toward addressing limitations in the current psychiatric diagnostic system, the NIMH recently developed the Research Domain Criteria (RDoC) to stimulate integrative research—spanning self-report, behavior, neural circuitry, and molecular/genetic mechanisms—on core psychological processes implicated in mental illness. Here, we use the RDoC conceptualization to review research on threat responses, reward processing, and their interaction. The first section of the manuscript highlights the pivotal role of exaggerated threat responses—mediated by circuits connecting the frontal cortex, amygdala, and midbrain—in anxiety, and reviews data indicating that genotypic variation in the serotonin system is associated with hyperactivity in this circuitry, which elevates the risk for anxiety and mood disorders. In the second section, we describe mounting evidence linking anhedonic behavior to deficits in psychological functions that rely heavily on dopamine signaling, especially cost/benefit decision-making and reward learning. The third section covers recent studies that document negative effects of acute threats and chronic stress on reward responses in humans. The mechanisms underlying such effects are unclear, but new optogenetic data in rodents indicate that GABAergic inhibition of midbrain dopamine neurons, driven by activation of the habenula, may play a fundamental role in stress-induced anhedonia. In addition to its basic scientific value, a better understanding of interactions between the neural systems that mediate threat and reward responses may offer relief from the burdensome condition of anxious depression. PMID:24151118

Analog Delta-Back-Propagation Neural-Network Circuitry

NASA Technical Reports Server (NTRS)

Eberhart, Silvio

1990-01-01

Changes in synapse weights due to circuit drifts suppressed. Proposed fully parallel analog version of electronic neural-network processor based on delta-back-propagation algorithm. Processor able to "learn" when provided with suitable combinations of inputs and enforced outputs. Includes programmable resistive memory elements (corresponding to synapses), conductances (synapse weights) adjusted during learning. Buffer amplifiers, summing circuits, and sample-and-hold circuits arranged in layers of electronic neurons in accordance with delta-back-propagation algorithm.

Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP.

PubMed

Cravo, Sergio L; Campos, Ruy R; Colombari, Eduardo; Sato, Mônica A; Bergamaschi, Cássia M; Pedrino, Gustavo R; Ferreira-Neto, Marcos L; Lopes, Oswaldo U

2009-09-01

Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.

Neural constraints on learning.

PubMed

Sadtler, Patrick T; Quick, Kristin M; Golub, Matthew D; Chase, Steven M; Ryu, Stephen I; Tyler-Kabara, Elizabeth C; Yu, Byron M; Batista, Aaron P

2014-08-28

Learning, whether motor, sensory or cognitive, requires networks of neurons to generate new activity patterns. As some behaviours are easier to learn than others, we asked if some neural activity patterns are easier to generate than others. Here we investigate whether an existing network constrains the patterns that a subset of its neurons is capable of exhibiting, and if so, what principles define this constraint. We employed a closed-loop intracortical brain-computer interface learning paradigm in which Rhesus macaques (Macaca mulatta) controlled a computer cursor by modulating neural activity patterns in the primary motor cortex. Using the brain-computer interface paradigm, we could specify and alter how neural activity mapped to cursor velocity. At the start of each session, we observed the characteristic activity patterns of the recorded neural population. The activity of a neural population can be represented in a high-dimensional space (termed the neural space), wherein each dimension corresponds to the activity of one neuron. These characteristic activity patterns comprise a low-dimensional subspace (termed the intrinsic manifold) within the neural space. The intrinsic manifold presumably reflects constraints imposed by the underlying neural circuitry. Here we show that the animals could readily learn to proficiently control the cursor using neural activity patterns that were within the intrinsic manifold. However, animals were less able to learn to proficiently control the cursor using activity patterns that were outside of the intrinsic manifold. These results suggest that the existing structure of a network can shape learning. On a timescale of hours, it seems to be difficult to learn to generate neural activity patterns that are not consistent with the existing network structure. These findings offer a network-level explanation for the observation that we are more readily able to learn new skills when they are related to the skills that we already possess.

Neural processes underlying cultural differences in cognitive persistence.

PubMed

Telzer, Eva H; Qu, Yang; Lin, Lynda C

2017-08-01

Self-improvement motivation, which occurs when individuals seek to improve upon their competence by gaining new knowledge and improving upon their skills, is critical for cognitive, social, and educational adjustment. While many studies have delineated the neural mechanisms supporting extrinsic motivation induced by monetary rewards, less work has examined the neural processes that support intrinsically motivated behaviors, such as self-improvement motivation. Because cultural groups traditionally vary in terms of their self-improvement motivation, we examined cultural differences in the behavioral and neural processes underlying motivated behaviors during cognitive persistence in the absence of extrinsic rewards. In Study 1, 71 American (47 females, M=19.68 years) and 68 Chinese (38 females, M=19.37 years) students completed a behavioral cognitive control task that required cognitive persistence across time. In Study 2, 14 American and 15 Chinese students completed the same cognitive persistence task during an fMRI scan. Across both studies, American students showed significant declines in cognitive performance across time, whereas Chinese participants demonstrated effective cognitive persistence. These behavioral effects were explained by cultural differences in self-improvement motivation and paralleled by increasing activation and functional coupling between the inferior frontal gyrus (IFG) and ventral striatum (VS) across the task among Chinese participants, neural activation and coupling that remained low in American participants. These findings suggest a potential neural mechanism by which the VS and IFG work in concert to promote cognitive persistence in the absence of extrinsic rewards. Thus, frontostriatal circuitry may be a neurobiological signal representing intrinsic motivation for self-improvement that serves an adaptive function, increasing Chinese students' motivation to engage in cognitive persistence. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural circuit activity in freely behaving zebrafish (Danio rerio).

PubMed

Issa, Fadi A; O'Brien, Georgeann; Kettunen, Petronella; Sagasti, Alvaro; Glanzman, David L; Papazian, Diane M

2011-03-15

Examining neuronal network activity in freely behaving animals is advantageous for probing the function of the vertebrate central nervous system. Here, we describe a simple, robust technique for monitoring the activity of neural circuits in unfettered, freely behaving zebrafish (Danio rerio). Zebrafish respond to unexpected tactile stimuli with short- or long-latency escape behaviors, which are mediated by distinct neural circuits. Using dipole electrodes immersed in the aquarium, we measured electric field potentials generated in muscle during short- and long-latency escapes. We found that activation of the underlying neural circuits produced unique field potential signatures that are easily recognized and can be repeatedly monitored. In conjunction with behavioral analysis, we used this technique to track changes in the pattern of circuit activation during the first week of development in animals whose trigeminal sensory neurons were unilaterally ablated. One day post-ablation, the frequency of short- and long-latency responses was significantly lower on the ablated side than on the intact side. Three days post-ablation, a significant fraction of escapes evoked by stimuli on the ablated side was improperly executed, with the animal turning towards rather than away from the stimulus. However, the overall response rate remained low. Seven days post-ablation, the frequency of escapes increased dramatically and the percentage of improperly executed escapes declined. Our results demonstrate that trigeminal ablation results in rapid reconfiguration of the escape circuitry, with reinnervation by new sensory neurons and adaptive changes in behavior. This technique is valuable for probing the activity, development, plasticity and regeneration of neural circuits under natural conditions.

Neural circuit activity in freely behaving zebrafish (Danio rerio)

PubMed Central

Issa, Fadi A.; O'Brien, Georgeann; Kettunen, Petronella; Sagasti, Alvaro; Glanzman, David L.; Papazian, Diane M.

2011-01-01

Examining neuronal network activity in freely behaving animals is advantageous for probing the function of the vertebrate central nervous system. Here, we describe a simple, robust technique for monitoring the activity of neural circuits in unfettered, freely behaving zebrafish (Danio rerio). Zebrafish respond to unexpected tactile stimuli with short- or long-latency escape behaviors, which are mediated by distinct neural circuits. Using dipole electrodes immersed in the aquarium, we measured electric field potentials generated in muscle during short- and long-latency escapes. We found that activation of the underlying neural circuits produced unique field potential signatures that are easily recognized and can be repeatedly monitored. In conjunction with behavioral analysis, we used this technique to track changes in the pattern of circuit activation during the first week of development in animals whose trigeminal sensory neurons were unilaterally ablated. One day post-ablation, the frequency of short- and long-latency responses was significantly lower on the ablated side than on the intact side. Three days post-ablation, a significant fraction of escapes evoked by stimuli on the ablated side was improperly executed, with the animal turning towards rather than away from the stimulus. However, the overall response rate remained low. Seven days post-ablation, the frequency of escapes increased dramatically and the percentage of improperly executed escapes declined. Our results demonstrate that trigeminal ablation results in rapid reconfiguration of the escape circuitry, with reinnervation by new sensory neurons and adaptive changes in behavior. This technique is valuable for probing the activity, development, plasticity and regeneration of neural circuits under natural conditions. PMID:21346131

Disruption of Boundary Encoding During Sensorimotor Sequence Learning: An MEG Study.

PubMed

Michail, Georgios; Nikulin, Vadim V; Curio, Gabriel; Maess, Burkhard; Herrojo Ruiz, María

2018-01-01

Music performance relies on the ability to learn and execute actions and their associated sounds. The process of learning these auditory-motor contingencies depends on the proper encoding of the serial order of the actions and sounds. Among the different serial positions of a behavioral sequence, the first and last (boundary) elements are particularly relevant. Animal and patient studies have demonstrated a specific neural representation for boundary elements in prefrontal cortical regions and in the basal ganglia, highlighting the relevance of their proper encoding. The neural mechanisms underlying the encoding of sequence boundaries in the general human population remain, however, largely unknown. In this study, we examined how alterations of auditory feedback, introduced at different ordinal positions (boundary or within-sequence element), affect the neural and behavioral responses during sensorimotor sequence learning. Analysing the neuromagnetic signals from 20 participants while they performed short piano sequences under the occasional effect of altered feedback (AF), we found that at around 150-200 ms post-keystroke, the neural activities in the dorsolateral prefrontal cortex (DLPFC) and supplementary motor area (SMA) were dissociated for boundary and within-sequence elements. Furthermore, the behavioral data demonstrated that feedback alterations on boundaries led to greater performance costs, such as more errors in the subsequent keystrokes. These findings jointly support the idea that the proper encoding of boundaries is critical in acquiring sensorimotor sequences. They also provide evidence for the involvement of a distinct neural circuitry in humans including prefrontal and higher-order motor areas during the encoding of the different classes of serial order.

Psychological and Neural Mechanisms of Experimental Extinction: A Selective Review

PubMed Central

Delamater, Andrew R.; Westbrook, R. Frederick

2013-01-01

The present review examines key psychological concepts in the study of experimental extinction and implications these have for an understanding of the underlying neurobiology of extinction learning. We suggest that many of the signature characteristics of extinction learning (spontaneous recovery, renewal, reinstatement, rapid reacquisition) can be accommodated by the standard associative learning theory assumption that extinction results in partial erasure of the original learning together with new inhibitory learning. Moreover, we consider recent behavioral and neural evidence that supports the partial erasure view of extinction, but also note shortcomings in our understanding of extinction circuits as these relate to the negative prediction error concept. Recent work suggests that common prediction error and stimulus-specific prediction error terms both may be required to explain neural plasticity both in acquisition and extinction learning. In addition, we suggest that many issues in the content of extinction learning have not been fully addressed in current research, but that neurobiological approaches should be especially helpful in addressing such issues. These include questions about the nature of extinction learning (excitatory CS-No US, inhibitory CS-US learning, occasion setting processes), especially as this relates to studies of the micro-circuitry of extinction, as well as its representational content (sensory, motivational, response). An additional understudied problem in extinction research is the role played by attention processes and their underlying neural networks, although some research and theory converge on the idea that extinction is accompanied by attention decrements (i.e., habituation-like processes). PMID:24104049

Psychological and neural mechanisms of experimental extinction: a selective review.

PubMed

Delamater, Andrew R; Westbrook, R Frederick

2014-02-01

The present review examines key psychological concepts in the study of experimental extinction and implications these have for an understanding of the underlying neurobiology of extinction learning. We suggest that many of the signature characteristics of extinction learning (spontaneous recovery, renewal, reinstatement, rapid reacquisition) can be accommodated by the standard associative learning theory assumption that extinction results in partial erasure of the original learning together with new inhibitory learning. Moreover, we consider recent behavioral and neural evidence that supports the partial erasure view of extinction, but also note shortcomings in our understanding of extinction circuits as these relate to the negative prediction error concept. Recent work suggests that common prediction error and stimulus-specific prediction error terms both may be required to explain neural plasticity both in acquisition and extinction learning. In addition, we suggest that many issues in the content of extinction learning have not been fully addressed in current research, but that neurobiological approaches should be especially helpful in addressing such issues. These include questions about the nature of extinction learning (excitatory CS-No US, inhibitory CS-US learning, occasion setting processes), especially as this relates to studies of the micro-circuitry of extinction, as well as its representational content (sensory, motivational, response). An additional understudied problem in extinction research is the role played by attention processes and their underlying neural networks, although some research and theory converge on the idea that extinction is accompanied by attention decrements (i.e., habituation-like processes). Copyright © 2013 Elsevier Inc. All rights reserved.

Behavioral characteristics and neural mechanisms mediating performance in a rodent version of the Balloon Analog Risk Task.

PubMed

Jentsch, James David; Woods, Jason A; Groman, Stephanie M; Seu, Emanuele

2010-07-01

The tendency for some individuals to partake in high-risk behaviors (eg, substance abuse, gambling, risky sexual activities) is a matter of great public health concern, yet the characteristics and neural bases of this vulnerability are largely unknown. Recent work shows that this susceptibility can be partially predicted by laboratory measures of reward seeking under risk, including the Balloon Analog Risk Task. Rats were trained to respond on two levers: one of which (the 'add lever') increased the size of a potential food reward and a second (the 'cash-out lever') that led to delivery of accrued reward. Crucially, each add-lever response was also associated with a risk that the trial would fail and no reward would be delivered. The relative probabilities that each add-lever press would lead to an addition food pellet or to trial failure (risk) were orthogonally varied. Rats exhibited a pattern of responding characteristic of incentive motivation and risk aversion, with a subset of rats showing traits of high-risk taking and/or suboptimal responding. Neural inactivation studies suggest that the orbitofrontal cortex supports greater reward seeking in the presence or absence of risk, whereas the medial prefrontal cortex is required for optimization of patterns of responding. These findings provide new information about the neural circuitry of decision making under risk and reveal new insights into the biological determinants of risk-taking behaviors that may be useful in developing biomarkers of vulnerability.

Dynamic neural network models of the premotoneuronal circuitry controlling wrist movements in primates.

PubMed

Maier, M A; Shupe, L E; Fetz, E E

2005-10-01

Dynamic recurrent neural networks were derived to simulate neuronal populations generating bidirectional wrist movements in the monkey. The models incorporate anatomical connections of cortical and rubral neurons, muscle afferents, segmental interneurons and motoneurons; they also incorporate the response profiles of four populations of neurons observed in behaving monkeys. The networks were derived by gradient descent algorithms to generate the eight characteristic patterns of motor unit activations observed during alternating flexion-extension wrist movements. The resulting model generated the appropriate input-output transforms and developed connection strengths resembling those in physiological pathways. We found that this network could be further trained to simulate additional tasks, such as experimentally observed reflex responses to limb perturbations that stretched or shortened the active muscles, and scaling of response amplitudes in proportion to inputs. In the final comprehensive network, motor units are driven by the combined activity of cortical, rubral, spinal and afferent units during step tracking and perturbations. The model displayed many emergent properties corresponding to physiological characteristics. The resulting neural network provides a working model of premotoneuronal circuitry and elucidates the neural mechanisms controlling motoneuron activity. It also predicts several features to be experimentally tested, for example the consequences of eliminating inhibitory connections in cortex and red nucleus. It also reveals that co-contraction can be achieved by simultaneous activation of the flexor and extensor circuits without invoking features specific to co-contraction.

Neurobiological Risk Factors for Suicide Insights from Brain Imaging

PubMed Central

Cox Lippard, Elizabeth T.; Johnston, Jennifer A.Y.; Blumberg, Hilary P.

2014-01-01

Context This article reviews neuroimaging studies on neural circuitry associated with suicide-related thoughts and behaviors to identify areas of convergence in findings. Gaps in the literature for which additional research is needed are identified. Evidence acquisition A PubMed search was conducted and articles published prior to March 2014 were reviewed that compared individuals who made suicide attempts to those with similar diagnoses who had not made attempts or to healthy comparison subjects. Articles on adults with suicidal ideation and adolescents who had made attempts, or with suicidal ideation, were also included. Reviewed imaging modalities included structural magnetic resonance imaging, diffusion tensor imaging, single photon emission computerized tomography, positron emission tomography, and functional magnetic resonance imaging. Evidence synthesis Although many studies include small samples, and subject characteristics and imaging methods vary across studies, there were convergent findings involving the structure and function of frontal neural systems and the serotonergic system. Conclusions These initial neuroimaging studies of suicide behavior have provided promising results. Future neuroimaging efforts could be strengthened by more strategic use of common data elements, and a focus on suicide risk trajectories. At-risk subgroups defined by biopsychosocial risk factors and multidimensional assessment of suicidal thoughts and behaviors may provide a clearer picture of the neural circuitry associated with risk status—both current and lifetime. Also needed are studies investigating neural changes associated with interventions that are effective in risk reduction. PMID:25145733

Circuit mechanisms of sensorimotor learning

PubMed Central

Makino, Hiroshi; Hwang, Eun Jung; Hedrick, Nathan G.; Komiyama, Takaki

2016-01-01

SUMMARY The relationship between the brain and the environment is flexible, forming the foundation for our ability to learn. Here we review the current state of our understanding of the modifications in the sensorimotor pathway related to sensorimotor learning. We divide the process in three hierarchical levels with distinct goals: 1) sensory perceptual learning, 2) sensorimotor associative learning, and 3) motor skill learning. Perceptual learning optimizes the representations of important sensory stimuli. Associative learning and the initial phase of motor skill learning are ensured by feedback-based mechanisms that permit trial-and-error learning. The later phase of motor skill learning may primarily involve feedback-independent mechanisms operating under the classic Hebbian rule. With these changes under distinct constraints and mechanisms, sensorimotor learning establishes dedicated circuitry for the reproduction of stereotyped neural activity patterns and behavior. PMID:27883902

Sleep and metabolism: role of hypothalamic neuronal circuitry.

PubMed

Rolls, Asya; Schaich Borg, Jana; de Lecea, Luis

2010-10-01

Sleep and metabolism are intertwined physiologically and behaviorally, but the neural systems underlying their coordination are still poorly understood. The hypothalamus is likely to play a major role in the regulation sleep, metabolism, and their interaction. And increasing evidence suggests that hypocretin cells in the lateral hypothalamus may provide particularly important contributions. Here we review: 1) direct interactions between biological arousal and metabolic systems in the hypothalamus, and 2) indirect interactions between these two systems mediated by stress or reward, emphasizing the role of hypocretins. An increased understanding of the mechanisms underlying these interactions may provide novel approaches for the treatment of patients with sleep disorders and obesity, as well as suggest new therapeutic strategies for symptoms of aging, stress, or addiction. Copyright © 2010. Published by Elsevier Ltd.

Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

PubMed

Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

2017-02-01

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Age and gender modulate the neural circuitry supporting facial emotion processing in adults with major depressive disorder.

PubMed

Briceño, Emily M; Rapport, Lisa J; Kassel, Michelle T; Bieliauskas, Linas A; Zubieta, Jon-Kar; Weisenbach, Sara L; Langenecker, Scott A

2015-03-01

Emotion processing, supported by frontolimbic circuitry known to be sensitive to the effects of aging, is a relatively understudied cognitive-emotional domain in geriatric depression. Some evidence suggests that the neurophysiological disruption observed in emotion processing among adults with major depressive disorder (MDD) may be modulated by both gender and age. Therefore, the present study investigated the effects of gender and age on the neural circuitry supporting emotion processing in MDD. Cross-sectional comparison of fMRI signal during performance of an emotion processing task. Outpatient university setting. One hundred adults recruited by MDD status, gender, and age. Participants underwent fMRI while completing the Facial Emotion Perception Test. They viewed photographs of faces and categorized the emotion perceived. Contrast for fMRI was of face perception minus animal identification blocks. Effects of depression were observed in precuneus and effects of age in a number of frontolimbic regions. Three-way interactions were present between MDD status, gender, and age in regions pertinent to emotion processing, including frontal, limbic, and basal ganglia. Young women with MDD and older men with MDD exhibited hyperactivation in these regions compared with their respective same-gender healthy comparison (HC) counterparts. In contrast, older women and younger men with MDD exhibited hypoactivation compared to their respective same-gender HC counterparts. This the first study to report gender- and age-specific differences in emotion processing circuitry in MDD. Gender-differential mechanisms may underlie cognitive-emotional disruption in older adults with MDD. The present findings have implications for improved probes into the heterogeneity of the MDD syndrome. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Neural Responses to Injury: Prevention, Protection, and Repair.

DTIC Science & Technology

1998-10-01

opioid-sensitive circuitry by electroacupuncture can suppress c-fos expression (21). Anesthetic agents and system- ically administered morphine can...ders Co., 1995, pp 397-460. 21. Lee JH, Beitz AJ: Electroacupuncture modifies the expression of c-fos in the spinal cord induced by noxious

The practical and fundamental limits of optical imaging in mammalian brains.

PubMed

Ji, Na

2014-09-17

Advances in chemistry and physics have profound effects on neuroimaging. Current and future progress in these disciplines will continue to aid in efforts to visualize neural circuitry, particularly in deeper layers of the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficient Computations and Representations of Visible Surfaces.

DTIC Science & Technology

1979-12-01

position as stated. The smooth contour generator may lie along a sharp ridge, for instance. Richards & Stevens -28- 6m lace contout s ?S ,.......... ceoonec...From understanding computation to understanding neural circuitry. Neurosci. Res. Prog. Bull. 13. 470-488. Metelli, F. 1970 An algebraic development of

Behavioral and neural stability of attention bias to threat in healthy adolescents

PubMed Central

Britton, Jennifer C.; Sequeira, Stefanie; Ronkin, Emily G.; Chen, Gang; Bar-Haim, Yair; Shechner, Tomer; Ernst, Monique; Fox, Nathan A.; Leibenluft, Ellen; Pine, Daniel S.

2016-01-01

Considerable translational research on anxiety examines attention bias to threat and the efficacy of attention training in reducing symptoms. Imaging research on the stability of brain functions engaged by attention bias tasks could inform such research. Perturbed fronto-amygdala function consistently arises in attention bias research on adolescent anxiety. The current report examines the stability of the activation and functional connectivity of these regions on the dot-probe task. Functional magnetic resonance imaging (fMRI) activation and connectivity data were acquired with the dot-probe task in 39 healthy youth (f =18, Mean Age = 13.71 years, SD = 2.31) at two time points, separated by approximately nine weeks. Intraclass-correlations demonstrate good reliability in both neural activation for the ventrolateral PFC and task-specific connectivity for fronto-amygdala circuitry. Behavioral measures showed generally poor test-retest reliability. These findings suggest potential avenues for future brain imaging work by highlighting brain circuitry manifesting stable functioning on the dot-probe attention bias task. PMID:27129757

Differences in brain circuitry for appetitive and reactive aggression as revealed by realistic auditory scripts

PubMed Central

Moran, James K.; Weierstall, Roland; Elbert, Thomas

2014-01-01

Aggressive behavior is thought to divide into two motivational elements: The first being a self-defensively motivated aggression against threat and a second, hedonically motivated “appetitive” aggression. Appetitive aggression is the less understood of the two, often only researched within abnormal psychology. Our approach is to understand it as a universal and adaptive response, and examine the functional neural activity of ordinary men (N = 50) presented with an imaginative listening task involving a murderer describing a kill. We manipulated motivational context in a between-subjects design to evoke appetitive or reactive aggression, against a neutral control, measuring activity with Magnetoencephalography (MEG). Results show differences in left frontal regions in delta (2–5 Hz) and alpha band (8–12 Hz) for aggressive conditions and right parietal delta activity differentiating appetitive and reactive aggression. These results validate the distinction of reward-driven appetitive aggression from reactive aggression in ordinary populations at the level of functional neural brain circuitry. PMID:25538590

GABAergic Inhibition in Visual Cortical Plasticity

PubMed Central

Sale, Alessandro; Berardi, Nicoletta; Spolidoro, Maria; Baroncelli, Laura; Maffei, Lamberto

2010-01-01

Experience is required for the shaping and refinement of developing neural circuits during well defined periods of early postnatal development called critical periods. Many studies in the visual cortex have shown that intracortical GABAergic circuitry plays a crucial role in defining the time course of the critical period for ocular dominance plasticity. With the end of the critical period, neural plasticity wanes and recovery from the effects of visual defects on visual acuity (amblyopia) or binocularity is much reduced or absent. Recent results pointed out that intracortical inhibition is a fundamental limiting factor for adult cortical plasticity and that its reduction by means of different pharmacological and environmental strategies makes it possible to greatly enhance plasticity in the adult visual cortex, promoting ocular dominance plasticity and recovery from amblyopia. Here we focus on the role of intracortical GABAergic circuitry in controlling both developmental and adult cortical plasticity. We shall also discuss the potential clinical application of these findings to neurological disorders in which synaptic plasticity is compromised because of excessive intracortical inhibition. PMID:20407586

The Iowa Gambling Task in fMRI Images

PubMed Central

Li, Xiangrui; Lu, Zhong-Lin; D'Argembeau, Arnaud; Ng, Marie; Bechara, Antoine

2009-01-01

The Iowa Gambling Task (IGT) is a sensitive test for the detection of decision-making impairments in several neurologic and psychiatric populations. Very few studies have employed the IGT in fMRI investigations, in part, because the task is cognitively complex. Here we report a method for exploring brain activity using fMRI during performance of the IGT. Decision-making during the IGT was associated with activity in several brain regions in a group of healthy individuals. The activated regions were consistent with the neural circuitry hypothesized to underlie somatic marker activation and decision-making. Specifically, a neural circuitry involving the dorsolateral prefrontal cortex (for working memory), the insula and posterior cingulate cortex (for representations of emotional states), the mesial orbitofrontal and ventromedial prefrontal cortex (for coupling the two previous processes), the ventral striatum and anterior cingulate/SMA (supplementary motor area) for implementing behavioral decisions was engaged. These results have implications for using the IGT to study abnormal mechanisms of decision making in a variety of clinical populations. PMID:19777556

A Conserved Developmental Mechanism Builds Complex Visual Systems in Insects and Vertebrates

PubMed Central

Joly, Jean-Stéphane; Recher, Gaelle; Brombin, Alessandro; Ngo, Kathy; Hartenstein, Volker

2016-01-01

The visual systems of vertebrates and many other bilaterian clades consist of complex neural structures guiding a wide spectrum of behaviors. Homologies at the level of cell types and even discrete neural circuits have been proposed, but many questions of how the architecture of visual neuropils evolved among different phyla remain open. In this review we argue that the profound conservation of genetic and developmental steps generating the eye and its target neuropils in fish and fruit flies supports a homology between some core elements of bilaterian visual circuitries. Fish retina and tectum, and fly optic lobe, develop from a partitioned, unidirectionally proliferating neurectodermal domain that combines slowly dividing neuroepithelial stem cells and rapidly amplifying progenitors with shared genetic signatures to generate large numbers and different types of neurons in a temporally ordered way. This peculiar ‘conveyor belt neurogenesis’ could play an essential role in generating the topographically ordered circuitry of the visual system. PMID:27780043

Pleasure systems in the brain

PubMed Central

Berridge, Kent C.; Kringelbach, Morten L.

2015-01-01

Pleasure is mediated by well-developed mesocorticolimbic circuitry, and serves adaptive functions. In affective disorders anhedonia (lack of pleasure) or dysphoria (negative affect) can result from breakdowns of that hedonic system. Human neuroimaging studies indicate that surprisingly similar circuitry is activated by quite diverse pleasures, suggesting a common neural currency shared by all. Wanting for rewards is generated by a large and distributed brain system. Liking, or pleasure itself, is generated by a smaller set of hedonic hotspots within limbic circuitry. Those hotspots also can be embedded in broader anatomical patterns of valence organization, such as in a keyboard pattern of nucleus accumbens generators for desire versus dread. In contrast, some of the best known textbook candidates for pleasure generators, including classic pleasure electrodes and the mesolimbic dopamine system, may not generate pleasure after all. These emerging insights into brain pleasure mechanisms may eventually facilitate better treatments for affective disorders. PMID:25950633

Optogenetic mapping of brain circuitry

NASA Astrophysics Data System (ADS)

Augustine, George J.; Berglund, Ken; Gill, Harin; Hoffmann, Carolin; Katarya, Malvika; Kim, Jinsook; Kudolo, John; Lee, Li M.; Lee, Molly; Lo, Daniel; Nakajima, Ryuichi; Park, Min Yoon; Tan, Gregory; Tang, Yanxia; Teo, Peggy; Tsuda, Sachiko; Wen, Lei; Yoon, Su-In

2012-10-01

Studies of the brain promise to be revolutionized by new experimental strategies that harness the combined power of optical techniques and genetics. We have mapped the circuitry of the mouse brain by using both optogenetic actuators that control neuronal activity and optogenetic sensors that detect neuronal activity. Using the light-activated cation channel, channelrhodopsin-2, to locally photostimulate neurons allows high-speed mapping of local and long-range circuitry. For example, with this approach we have mapped local circuits in the cerebral cortex, cerebellum and many other brain regions. Using the fluorescent sensor for chloride ions, Clomeleon, allows imaging of the spatial and temporal dimensions of inhibitory circuits in the brain. This approach allows imaging of both conventional "phasic" synaptic inhibition as well as unconventional "tonic" inhibition. The combined use of light to both control and monitor neural activity creates unprecedented opportunities to explore brain function, screen pharmaceutical agents, and potentially to use light to ameliorate psychiatric and neurological disorders.

Reversal learning as a measure of impulsive and compulsive behavior in addictions.

PubMed

Izquierdo, Alicia; Jentsch, J David

2012-01-01

Our ability to measure the cognitive components of complex decision-making across species has greatly facilitated our understanding of its neurobiological mechanisms. One task in particular, reversal learning, has proven valuable in assessing the inhibitory processes that are central to executive control. Reversal learning measures the ability to actively suppress reward-related responding and to disengage from ongoing behavior, phenomena that are biologically and descriptively related to impulsivity and compulsivity. Consequently, reversal learning could index vulnerability for disorders characterized by impulsivity such as proclivity for initial substance abuse as well as the compulsive aspects of dependence. Though we describe common variants and similar tasks, we pay particular attention to discrimination reversal learning, its supporting neural circuitry, neuropharmacology and genetic determinants. We also review the utility of this task in measuring impulsivity and compulsivity in addictions. We restrict our review to instrumental, reward-related reversal learning studies as they are most germane to addiction. The research reviewed here suggests that discrimination reversal learning may be used as a diagnostic tool for investigating the neural mechanisms that mediate impulsive and compulsive aspects of pathological reward-seeking and -taking behaviors. Two interrelated mechanisms are posited for the neuroadaptations in addiction that often translate to poor reversal learning: frontocorticostriatal circuitry dysregulation and poor dopamine (D2 receptor) modulation of this circuitry. These data suggest new approaches to targeting inhibitory control mechanisms in addictions.

Neural correlates of genetically abnormal social cognition in Williams syndrome.

PubMed

Meyer-Lindenberg, Andreas; Hariri, Ahmad R; Munoz, Karen E; Mervis, Carolyn B; Mattay, Venkata S; Morris, Colleen A; Berman, Karen Faith

2005-08-01

Williams-Beuren syndrome (WBS), caused by a microdeletion of approximately 21 genes on chromosome 7q11.23, is characterized by unique hypersociability combined with increased non-social anxiety. Using functional neuroimaging, we found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls. Activation and interactions of prefrontal regions linked to amygdala, especially orbitofrontal cortex, were abnormal, suggesting a genetically controlled neural circuitry for regulating human social behavior.

Neural Circuitry of Wakefulness and Sleep.

PubMed

Scammell, Thomas E; Arrigoni, Elda; Lipton, Jonathan O

2017-02-22

Sleep remains one of the most mysterious yet ubiquitous animal behaviors. We review current perspectives on the neural systems that regulate sleep/wake states in mammals and the circadian mechanisms that control their timing. We also outline key models for the regulation of rapid eye movement (REM) sleep and non-REM sleep, how mutual inhibition between specific pathways gives rise to these distinct states, and how dysfunction in these circuits can give rise to sleep disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Probing Compulsive and Impulsive Behaviors, from Animal Models to Endophenotypes: A Narrative Review

PubMed Central

Fineberg, Naomi A; Potenza, Marc N; Chamberlain, Samuel R; Berlin, Heather A; Menzies, Lara; Bechara, Antoine; Sahakian, Barbara J; Robbins, Trevor W; Bullmore, Edward T; Hollander, Eric

2010-01-01

Failures in cortical control of fronto-striatal neural circuits may underpin impulsive and compulsive acts. In this narrative review, we explore these behaviors from the perspective of neural processes and consider how these behaviors and neural processes contribute to mental disorders such as obsessive–compulsive disorder (OCD), obsessive–compulsive personality disorder, and impulse-control disorders such as trichotillomania and pathological gambling. We present findings from a broad range of data, comprising translational and human endophenotypes research and clinical treatment trials, focussing on the parallel, functionally segregated, cortico-striatal neural projections, from orbitofrontal cortex (OFC) to medial striatum (caudate nucleus), proposed to drive compulsive activity, and from the anterior cingulate/ventromedial prefrontal cortex to the ventral striatum (nucleus accumbens shell), proposed to drive impulsive activity, and the interaction between them. We suggest that impulsivity and compulsivity each seem to be multidimensional. Impulsive or compulsive behaviors are mediated by overlapping as well as distinct neural substrates. Trichotillomania may stand apart as a disorder of motor-impulse control, whereas pathological gambling involves abnormal ventral reward circuitry that identifies it more closely with substance addiction. OCD shows motor impulsivity and compulsivity, probably mediated through disruption of OFC-caudate circuitry, as well as other frontal, cingulate, and parietal connections. Serotonin and dopamine interact across these circuits to modulate aspects of both impulsive and compulsive responding and as yet unidentified brain-based systems may also have important functions. Targeted application of neurocognitive tasks, receptor-specific neurochemical probes, and brain systems neuroimaging techniques have potential for future research in this field. PMID:19940844

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder: Current Status and Working Hypotheses

ERIC Educational Resources Information Center

Vaidya, Chandan J.; Stollstorff, Melanie

2008-01-01

Cognitive neuroscience studies of Attention Deficit Hyperactivity Disorder (ADHD) suggest multiple loci of pathology with respect to both cognitive domains and neural circuitry. Cognitive deficits extend beyond executive functioning to include spatial, temporal, and lower-level "nonexecutive" functions. Atypical functional anatomy extends beyond…

Artificial neuron operations and spike-timing-dependent plasticity using memristive devices for brain-inspired computing

NASA Astrophysics Data System (ADS)

Marukame, Takao; Nishi, Yoshifumi; Yasuda, Shin-ichi; Tanamoto, Tetsufumi

2018-04-01

The use of memristive devices for creating artificial neurons is promising for brain-inspired computing from the viewpoints of computation architecture and learning protocol. We present an energy-efficient multiplier accumulator based on a memristive array architecture incorporating both analog and digital circuitries. The analog circuitry is used to full advantage for neural networks, as demonstrated by the spike-timing-dependent plasticity (STDP) in fabricated AlO x /TiO x -based metal-oxide memristive devices. STDP protocols for controlling periodic analog resistance with long-range stability were experimentally verified using a variety of voltage amplitudes and spike timings.

Introduction to the special issue from the 2014 meeting of the International Behavioral Neuroscience Society.

PubMed

Young, Jared W; Hall, F Scott; Pletnikov, Mikhail; Kent, Stephen

2015-11-01

In 2013, President Obama launched what has been optimistically described as the "decade of the brain". The launch of this effort comes on the back of widespread acknowledgement that more is required to aid those suffering from mental health disorders. Specifically, a greater understanding of the neural circuitry related to behaviors specific to mental health disorders is needed. The field of research that relates the circuitry of the brain to specific aspects of behavior is referred to as behavioral neuroscience. The International Behavioral Neuroscience Society (IBNS) was founded in 1992 specifically to meet on an annual basis and present the latest research findings in this field, and to gather together the international research community to discuss issues important for the development and progress of this scientific discipline. This special issue includes reviews of topics of emerging interest and advancing knowledge in behavioral neuroscience, based on symposia presented at the 2014 IBNS meeting. Topics discussed at the annual IBNS meeting ranged from investigations of the neural mechanisms underlying bipolar disorder, schizophrenia, depression, traumatic brain injury, and risk-taking behavior, to behavioral consequences of obesity and immune dysfunction. Novel treatment areas are covered such as the use of deep brain stimulation, as well as investigation of the behavioral impacts of nicotine withdrawal and how this research will influence the development of nicotine cessation treatments. Hence, this special issue covers a wide-range of topics in behavioral neuroscience offering an insight into the challenges faced by researchers in this decade of the brain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models

PubMed Central

Soontornniyomkij, Virawudh; Kesby, James P.; Morgan, Erin E.; Bischoff-Grethe, Amanda; Minassian, Arpi; Brown, Gregory G.; Grant, Igor

2016-01-01

Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research findings, as well as unpublished data, in humans and animal models with regard to neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro experimental systems, with an emphasis on findings emerging from the National Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120 transgenic mouse) models thus far suggest that combined HIV and Meth insults increase the likelihood of neural injury in the brain. The neurobehavioral effects include cognitive impairment and increased tendencies toward impaired behavioral inhibition and social cognition. These impairments are relevant to behaviors that affect personal and social risks, e.g. worse medication adherence, riskier behaviors, and greater likelihood of HIV transmission. The underlying mechanisms may include electrochemical changes in neuronal circuitries, injury to white matter microstructures, synaptodendritic damage, and selective neuronal loss. Utilization of research methodologies that are valid across species is instrumental in generating new knowledge with clinical translational value. PMID:27484318

Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models.

PubMed

Soontornniyomkij, Virawudh; Kesby, James P; Morgan, Erin E; Bischoff-Grethe, Amanda; Minassian, Arpi; Brown, Gregory G; Grant, Igor

2016-09-01

Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV and Meth insults may exacerbate neural injury in vulnerable neuroanatomic structures or circuitries in the brain, leading to increased behavioral disturbance and cognitive impairment. While acute and chronic effects of Meth in humans and animal models have been studied for decades, the neurobehavioral effects of Meth in the context of HIV infection are much less explored. In-depth understanding of the scope of neurobehavioral phenotypes and mechanisms in HIV/Meth intersection is needed. The present report summarizes published research findings, as well as unpublished data, in humans and animal models with regard to neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro experimental systems, with an emphasis on findings emerging from the National Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120 transgenic mouse) models thus far suggest that combined HIV and Meth insults increase the likelihood of neural injury in the brain. The neurobehavioral effects include cognitive impairment and increased tendencies toward impaired behavioral inhibition and social cognition. These impairments are relevant to behaviors that affect personal and social risks, e.g. worse medication adherence, riskier behaviors, and greater likelihood of HIV transmission. The underlying mechanisms may include electrochemical changes in neuronal circuitries, injury to white matter microstructures, synaptodendritic damage, and selective neuronal loss. Utilization of research methodologies that are valid across species is instrumental in generating new knowledge with clinical translational value.

Non-coding RNA networks underlying cognitive disorders across the lifespan

PubMed Central

Qureshi, Irfan A.; Mehler, Mark F.

2011-01-01

Non-coding RNAs (ncRNAs) and their associated regulatory networks are increasingly being implicated in mediating a complex repertoire of neurobiological functions. Cognitive and behavioral processes are proving to be no exception. Here, we discuss the emergence of many novel, diverse, and rapidly expanding classes and subclasses of short and long ncRNAs. We briefly review the life cycles and molecular functions of these ncRNAs. We also examine how ncRNA circuitry mediates brain development, plasticity, stress responses, and aging and highlight its potential roles in the pathophysiology of cognitive disorders, including neural developmental and age-associated neurodegenerative diseases as well as those that manifest throughout the lifespan. PMID:21411369

Differences in Behavior and Brain Activity during Hypothetical and Real Choices.

PubMed

Camerer, Colin; Mobbs, Dean

2017-01-01

Real behaviors are binding consequential commitments to a course of action, such as harming another person, buying an Apple watch, or fleeing from danger. Cognitive scientists are generally interested in the psychological and neural processes that cause such real behavior. However, for practical reasons, many scientific studies measure behavior using only hypothetical or imagined stimuli. Generalizing from such studies to real behavior implicitly assumes that the processes underlying the two types of behavior are similar. We review evidence of similarity and differences in hypothetical and real mental processes. In many cases, hypothetical choice tasks give an incomplete picture of brain circuitry that is active during real choice. Copyright © 2016. Published by Elsevier Ltd.

Dopaminergic Neurotransmission in the Human Brain: New Lessons from Perturbation and Imaging

PubMed Central

Ko, Ji Hyun; Strafella, Antonio P.

2012-01-01

Dopamine plays an important role in several brain functions and is involved in the pathogenesis of several psychiatric and neurological disorders. Neuroimaging techniques such as positron emission tomography allow us to quantify dopaminergic activity in the living human brain. Combining these with brain stimulation techniques offers us the unique opportunity to tackle questions regarding region-specific neurochemical activity. Such studies may aid clinicians and scientists to disentangle neural circuitries within the human brain and thereby help them to understand the underlying mechanisms of a given function in relation to brain diseases. Furthermore, it may also aid the development of alternative treatment approaches for various neurological and psychiatric conditions. PMID:21536838

Object Recognition using Feature- and Color-Based Methods

NASA Technical Reports Server (NTRS)

Duong, Tuan; Duong, Vu; Stubberud, Allen

2008-01-01

An improved adaptive method of processing image data in an artificial neural network has been developed to enable automated, real-time recognition of possibly moving objects under changing (including suddenly changing) conditions of illumination and perspective. The method involves a combination of two prior object-recognition methods one based on adaptive detection of shape features and one based on adaptive color segmentation to enable recognition in situations in which either prior method by itself may be inadequate. The chosen prior feature-based method is known as adaptive principal-component analysis (APCA); the chosen prior color-based method is known as adaptive color segmentation (ACOSE). These methods are made to interact with each other in a closed-loop system to obtain an optimal solution of the object-recognition problem in a dynamic environment. One of the results of the interaction is to increase, beyond what would otherwise be possible, the accuracy of the determination of a region of interest (containing an object that one seeks to recognize) within an image. Another result is to provide a minimized adaptive step that can be used to update the results obtained by the two component methods when changes of color and apparent shape occur. The net effect is to enable the neural network to update its recognition output and improve its recognition capability via an adaptive learning sequence. In principle, the improved method could readily be implemented in integrated circuitry to make a compact, low-power, real-time object-recognition system. It has been proposed to demonstrate the feasibility of such a system by integrating a 256-by-256 active-pixel sensor with APCA, ACOSE, and neural processing circuitry on a single chip. It has been estimated that such a system on a chip would have a volume no larger than a few cubic centimeters, could operate at a rate as high as 1,000 frames per second, and would consume in the order of milliwatts of power.

Neural mechanisms underlying sensitivity to reverse-phi motion in the fly

PubMed Central

Meier, Matthias; Serbe, Etienne; Eichner, Hubert; Borst, Alexander

2017-01-01

Optical illusions provide powerful tools for mapping the algorithms and circuits that underlie visual processing, revealing structure through atypical function. Of particular note in the study of motion detection has been the reverse-phi illusion. When contrast reversals accompany discrete movement, detected direction tends to invert. This occurs across a wide range of organisms, spanning humans and invertebrates. Here, we map an algorithmic account of the phenomenon onto neural circuitry in the fruit fly Drosophila melanogaster. Through targeted silencing experiments in tethered walking flies as well as electrophysiology and calcium imaging, we demonstrate that ON- or OFF-selective local motion detector cells T4 and T5 are sensitive to certain interactions between ON and OFF. A biologically plausible detector model accounts for subtle features of this particular form of illusory motion reversal, like the re-inversion of turning responses occurring at extreme stimulus velocities. In light of comparable circuit architecture in the mammalian retina, we suggest that similar mechanisms may apply even to human psychophysics. PMID:29261684

Neural mechanisms underlying sensitivity to reverse-phi motion in the fly.

PubMed

Leonhardt, Aljoscha; Meier, Matthias; Serbe, Etienne; Eichner, Hubert; Borst, Alexander

2017-01-01

Optical illusions provide powerful tools for mapping the algorithms and circuits that underlie visual processing, revealing structure through atypical function. Of particular note in the study of motion detection has been the reverse-phi illusion. When contrast reversals accompany discrete movement, detected direction tends to invert. This occurs across a wide range of organisms, spanning humans and invertebrates. Here, we map an algorithmic account of the phenomenon onto neural circuitry in the fruit fly Drosophila melanogaster. Through targeted silencing experiments in tethered walking flies as well as electrophysiology and calcium imaging, we demonstrate that ON- or OFF-selective local motion detector cells T4 and T5 are sensitive to certain interactions between ON and OFF. A biologically plausible detector model accounts for subtle features of this particular form of illusory motion reversal, like the re-inversion of turning responses occurring at extreme stimulus velocities. In light of comparable circuit architecture in the mammalian retina, we suggest that similar mechanisms may apply even to human psychophysics.

Neuropharmacology of brain-stimulation-evoked aggression.

PubMed

Siegel, A; Roeling, T A; Gregg, T R; Kruk, M R

1999-01-01

Evidence is reviewed concerning the brain areas and neurotransmitters involved in aggressive behavior in the cat and rodent. In the cat, two distinct neural circuits involving the hypothalamus and PAG subserve two different kinds of aggression: defensive rage and predatory (quiet-biting) attack. The roles played by the neurotransmitters serotonin, GABA, glutamate, opioids, cholecystokinin, substance P, norepinephrine, dopamine, and acetylcholine in the modulation and expression of aggression are discussed. For the rat, a single area, largely coincident with the intermediate hypothalamic area, is crucial for the expression of attack; variations in the rat attack response in natural settings are due largely to environmental variables. Experimental evidence emphasizing the roles of serotonin and GABA in modulating hypothalamically evoked attack in the rat is discussed. It is concluded that significant progress has been made concerning our knowledge of the circuitry underlying the neural basis of aggression. Although new and important insights have been made concerning neurotransmitter regulation of aggressive behavior, wide gaps in our knowledge remain.

Neurophysiological Influence of Musical Training on Speech Perception

PubMed Central

Shahin, Antoine J.

2011-01-01

Does musical training affect our perception of speech? For example, does learning to play a musical instrument modify the neural circuitry for auditory processing in a way that improves one's ability to perceive speech more clearly in noisy environments? If so, can speech perception in individuals with hearing loss (HL), who struggle in noisy situations, benefit from musical training? While music and speech exhibit some specialization in neural processing, there is evidence suggesting that skills acquired through musical training for specific acoustical processes may transfer to, and thereby improve, speech perception. The neurophysiological mechanisms underlying the influence of musical training on speech processing and the extent of this influence remains a rich area to be explored. A prerequisite for such transfer is the facilitation of greater neurophysiological overlap between speech and music processing following musical training. This review first establishes a neurophysiological link between musical training and speech perception, and subsequently provides further hypotheses on the neurophysiological implications of musical training on speech perception in adverse acoustical environments and in individuals with HL. PMID:21716639

Neurophysiological influence of musical training on speech perception.

PubMed

Shahin, Antoine J

2011-01-01

Does musical training affect our perception of speech? For example, does learning to play a musical instrument modify the neural circuitry for auditory processing in a way that improves one's ability to perceive speech more clearly in noisy environments? If so, can speech perception in individuals with hearing loss (HL), who struggle in noisy situations, benefit from musical training? While music and speech exhibit some specialization in neural processing, there is evidence suggesting that skills acquired through musical training for specific acoustical processes may transfer to, and thereby improve, speech perception. The neurophysiological mechanisms underlying the influence of musical training on speech processing and the extent of this influence remains a rich area to be explored. A prerequisite for such transfer is the facilitation of greater neurophysiological overlap between speech and music processing following musical training. This review first establishes a neurophysiological link between musical training and speech perception, and subsequently provides further hypotheses on the neurophysiological implications of musical training on speech perception in adverse acoustical environments and in individuals with HL.

Neural circuits and mechanisms involved in Pavlovian fear conditioning: A critical review

PubMed Central

Kim, Jeansok J.; Jung, Min Whan

2015-01-01

Pavlovian or classical fear conditioning is recognized as a model system to investigate the neurobiological mechanisms of learning and memory in the mammalian brain and to understand the root of fear-related disorders in humans. In recent decades, important progress has been made in delineating the essential neural circuitry and cellular–molecular mechanisms of fear conditioning. Converging lines of evidence indicate that the amygdala is necessarily involved in the acquisition, storage and expression of conditioned fear memory, and long-term potentiation (LTP) in the lateral nucleus of the amygdala is often proposed as the underlying synaptic mechanism of associative fear memory. Recent studies further implicate the prefrontal cortex–amygdala interaction in the extinction (or inhibition) of conditioned fear. Despite these advances, there are unresolved issues and findings that challenge the validity and sufficiency of the current amygdalar LTP hypothesis of fear conditioning. The purpose of this review is to critically evaluate the strengths and weaknesses of evidence indicating that fear conditioning depend crucially upon the amygdalar circuit and plasticity. PMID:16120461

Flexible theta sequence compression mediated via phase precessing interneurons

PubMed Central

Chadwick, Angus; van Rossum, Mark CW; Nolan, Matthew F

2016-01-01

Encoding of behavioral episodes as spike sequences during hippocampal theta oscillations provides a neural substrate for computations on events extended across time and space. However, the mechanisms underlying the numerous and diverse experimentally observed properties of theta sequences remain poorly understood. Here we account for theta sequences using a novel model constrained by the septo-hippocampal circuitry. We show that when spontaneously active interneurons integrate spatial signals and theta frequency pacemaker inputs, they generate phase precessing action potentials that can coordinate theta sequences in place cell populations. We reveal novel constraints on sequence generation, predict cellular properties and neural dynamics that characterize sequence compression, identify circuit organization principles for high capacity sequential representation, and show that theta sequences can be used as substrates for association of conditioned stimuli with recent and upcoming events. Our results suggest mechanisms for flexible sequence compression that are suited to associative learning across an animal’s lifespan. DOI: http://dx.doi.org/10.7554/eLife.20349.001 PMID:27929374

Opponent process theory of motivation: neurobiological evidence from studies of opiate dependence.

PubMed

Koob, G F; Stinus, L; Le Moal, M; Bloom, F E

1989-01-01

One hypothetical model for a mechanism of drug dependence involves the development of an adaptive process that is initiated to counter the acute effects of the drug. This adaptive process persists after the drug has been cleared from the brain, leaving an opposing reaction unopposed (abstinence signs). From a motivational perspective a particularly attractive hypothesis has been that of opponent process theory (32). Here many reinforcers elicit positive affective and hedonic processes that are opposed by negative affective and hedonic processes. Thus the intense pleasure of the opiate drug "rush" or "high" would be opposed by aversive withdrawal symptoms. The present paper presents neurobiological evidence to support the opponent process concept and suggests neural circuitry that may be involved. The region of the nucleus accumbens in the forebrain of the rat has been shown to be a particularly sensitive substrate not only for the acute reinforcing properties of opiate drugs, but also for the response disruptive effects of opiate antagonists in opiate dependent rats. This region also appears to be particularly sensitive to the aversive stimulus effects of opiate antagonists using a place aversion measure in dependent rats. These results suggest that the region of the nucleus accumbens and its neural circuitry may be an important neural substrate for both the positive and negative motivational aspects of drug dependence.

Neurophysiological correlates of anhedonia in feedback processing

PubMed Central

Mies, Gabry W.; Van den Berg, Ivo; Franken, Ingmar H. A.; Smits, Marion; Van der Molen, Maurits W.; Van der Veen, Frederik M.

2013-01-01

Disturbances in feedback processing and a dysregulation of the neural circuit in which the cingulate cortex plays a key role have been frequently observed in depression. Since depression is a heterogeneous disease, instead of focusing on the depressive state in general, this study investigated the relations between the two core symptoms of depression, i.e., depressed mood and anhedonia, and the neural correlates of feedback processing using fMRI. The focus was on the different subdivisions of the anterior cingulate cortex (ACC). Undergraduates with varying levels of depressed mood and anhedonia performed a time-estimation task in which they received positive and negative feedback that was either valid or invalid (i.e., related vs. unrelated to actual performance). The rostral cingulate zone (RCZ), corresponding to the dorsal part of the ACC, was less active in response to feedback in more anhedonic individuals, after correcting for the influence of depressed mood, whereas the subgenual ACC was more active in these individuals. Task performance was not affected by anhedonia, however. No statistically significant effects were found for depressed mood above and beyond the effects of anhedonia. This study therefore implies that increasing levels of anhedonia involve changes in the neural circuitry underlying feedback processing. PMID:23532800

The neurodevelopment of human sexual orientation.

PubMed

Rahman, Qazi

2005-01-01

One of the most enduring and controversial questions in the neuroscience of sexual behaviour surrounds the mechanisms which produce sexual attraction to either males or females. Here, evidence is reviewed which supports the proposal that sexual orientation in humans may be laid down in neural circuitry during early foetal development. Behaviour genetic investigations provide strong evidence for a heritable component to male and female sexual orientation. Linkage studies are partly suggestive of X-linked loci although candidate gene studies have produced null findings. Further evidence demonstrates a role for prenatal sex hormones which may influence the development of a putative network of sexual-orientation-related neural substrates. However, hormonal effects are often inconsistent and investigations rely heavily on 'proxy markers'. A consistent fraternal birth order effect in male sexual orientation also provides support for a model of maternal immunization processes affecting prenatal sexual differentiation. The notion that non-heterosexual preferences may reflect generalized neurodevelopmental perturbations is not supported by available data. These current theories have left little room for learning models of sexual orientation. Future investigations, across the neurosciences, should focus to elucidate the fundamental neural architecture underlying the target-specific direction of human sexual orientation, and their antecedents in developmental neurobiology.

Relaxed genetic control of cortical organization in human brains compared with chimpanzees

PubMed Central

Gómez-Robles, Aida; Hopkins, William D.; Schapiro, Steven J.; Sherwood, Chet C.

2015-01-01

The study of hominin brain evolution has focused largely on the neocortical expansion and reorganization undergone by humans as inferred from the endocranial fossil record. Comparisons of modern human brains with those of chimpanzees provide an additional line of evidence to define key neural traits that have emerged in human evolution and that underlie our unique behavioral specializations. In an attempt to identify fundamental developmental differences, we have estimated the genetic bases of brain size and cortical organization in chimpanzees and humans by studying phenotypic similarities between individuals with known kinship relationships. We show that, although heritability for brain size and cortical organization is high in chimpanzees, cerebral cortical anatomy is substantially less genetically heritable than brain size in humans, indicating greater plasticity and increased environmental influence on neurodevelopment in our species. This relaxed genetic control on cortical organization is especially marked in association areas and likely is related to underlying microstructural changes in neural circuitry. A major result of increased plasticity is that the development of neural circuits that underlie behavior is shaped by the environmental, social, and cultural context more intensively in humans than in other primate species, thus providing an anatomical basis for behavioral and cognitive evolution. PMID:26627234

The Neuropsychology of Ventral Prefrontal Cortex: Decision-Making and Reversal Learning

ERIC Educational Resources Information Center

Clark, L.; Cools, R.; Robbins, T. W.

2004-01-01

Converging evidence from human lesion, animal lesion, and human functional neuroimaging studies implicates overlapping neural circuitry in ventral prefrontal cortex in decision-making and reversal learning. The ascending 5-HT and dopamine neurotransmitter systems have a modulatory role in both processes. There is accumulating evidence that…

Neural Substrates of Cognitive Skill Learning in Parkinson's Disease

ERIC Educational Resources Information Center

Beauchamp, M. H.; Dagher, A.; Panisset, M.; Doyon, J.

2008-01-01

While cognitive skill learning is normally acquired implicitly through frontostrial circuitry in healthy individuals, neuroimaging studies suggest that patients with Parkinson's disease (PD) do so by activating alternate, intact brain areas associated with explicit memory processing. To further test this hypothesis, 10 patients with PD and 12…

Cognitive Inflexibility and Frontal-Cortical Activation in Pediatric Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Britton, Jennifer C.; Rauch, Scott L.; Rosso, Isabelle M.; Killgore, William D. S.; Price, Lauren M.; Ragan, Jennifer; Chosak, Anne; Hezel, Dianne M.; Pine, Daniel S.; Leibenluft, Ellen; Pauls, David L.; Jenike, Michael A.; Stewart, S. Evelyn

2010-01-01

Objective: Deficits in cognitive flexibility and response inhibition have been linked to perturbations in cortico-striatal-thalamic circuitry in adult obsessive-compulsive disorder (OCD). Although similar cognitive deficits have been identified in pediatric OCD, few neuroimaging studies have been conducted to examine its neural correlates in the…

System-Level Design of a 64-Channel Low Power Neural Spike Recording Sensor.

PubMed

Delgado-Restituto, Manuel; Rodriguez-Perez, Alberto; Darie, Angela; Soto-Sanchez, Cristina; Fernandez-Jover, Eduardo; Rodriguez-Vazquez, Angel

2017-04-01

This paper reports an integrated 64-channel neural spike recording sensor, together with all the circuitry to process and configure the channels, process the neural data, transmit via a wireless link the information and receive the required instructions. Neural signals are acquired, filtered, digitized and compressed in the channels. Additionally, each channel implements an auto-calibration algorithm which individually configures the transfer characteristics of the recording site. The system has two transmission modes; in one case the information captured by the channels is sent as uncompressed raw data; in the other, feature vectors extracted from the detected neural spikes are released. Data streams coming from the channels are serialized by the embedded digital processor. Experimental results, including in vivo measurements, show that the power consumption of the complete system is lower than 330 μW.

Neural substrates of inhibitory control deficits in 22q11.2 deletion syndrome.

PubMed

Montojo, C A; Jalbrzikowski, M; Congdon, E; Domicoli, S; Chow, C; Dawson, C; Karlsgodt, K H; Bilder, R M; Bearden, C E

2015-04-01

22q11.2 deletion syndrome (22q11DS) is associated with elevated levels of impulsivity, inattention, and distractibility, which may be related to underlying neurobiological dysfunction due to haploinsufficiency for genes involved in dopaminergic neurotransmission (i.e. catechol-O-methyltransferase). The Stop-signal task has been employed to probe the neural circuitry involved in response inhibition (RI); findings in healthy individuals indicate that a fronto-basal ganglia network underlies successful inhibition of a prepotent motor response. However, little is known about the neurobiological substrates of RI difficulties in 22q11DS. Here, we investigated this using functional magnetic resonance imaging while 45 adult participants (15 22q11DS patients, 30 matched controls) performed the Stop-signal task. Healthy controls showed significantly greater activation than 22q11DS patients within frontal cortical and basal ganglia regions during successful RI, whereas 22q11DS patients did not show increased neural activity relative to controls in any regions. Using the Barratt Impulsivity Scale, we also investigated whether neural dysfunction during RI was associated with cognitive impulsivity in 22q11DS patients. RI-related activity within left middle frontal gyrus and basal ganglia was associated with severity of self-reported cognitive impulsivity. These results suggest reduced engagement of RI-related brain regions in 22q11DS patients, which may be relevant to characteristic behavioral manifestations of the disorder. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Visual Place Learning in Drosophila melanogaster

PubMed Central

Ofstad, Tyler A.; Zuker, Charles S.; Reiser, Michael B.

2011-01-01

The ability of insects to learn and navigate to specific locations in the environment has fascinated naturalists for decades. While the impressive navigation abilities of ants, bees, wasps, and other insects clearly demonstrate that insects are capable of visual place learning1–4, little is known about the underlying neural circuits that mediate these behaviors. Drosophila melanogaster is a powerful model organism for dissecting the neural circuitry underlying complex behaviors, from sensory perception to learning and memory. Flies can identify and remember visual features such as size, color, and contour orientation5, 6. However, the extent to which they use vision to recall specific locations remains unclear. Here we describe a visual place-learning platform and demonstrate that Drosophila are capable of forming and retaining visual place memories to guide selective navigation. By targeted genetic silencing of small subsets of cells in the Drosophila brain we show that neurons in the ellipsoid body, but not in the mushroom bodies, are necessary for visual place learning. Together, these studies reveal distinct neuroanatomical substrates for spatial versus non-spatial learning, and substantiate Drosophila as a powerful model for the study of spatial memories. PMID:21654803

Abnormal Neural Activation to Faces in the Parents of Children with Autism

PubMed Central

Yucel, G. H.; Belger, A.; Bizzell, J.; Parlier, M.; Adolphs, R.; Piven, J.

2015-01-01

Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the “Broad Autism Phenotype ” (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality (“BAP+”). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. PMID:25056573

Optogenetic approaches to evaluate striatal function in animal models of Parkinson disease.

PubMed

Parker, Krystal L; Kim, Youngcho; Alberico, Stephanie L; Emmons, Eric B; Narayanan, Nandakumar S

2016-03-01

Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels. The introduction of optogenetic approaches has facilitated the dissection of neural circuits. Optogenetics allows for the precise stimulation and inhibition of specific sets of neurons and their projections with fine temporal specificity. These techniques are ideally suited to investigating neural circuitry underlying motor and cognitive dysfunction in animal models of human disease. Here, we focus on how optogenetics has been used over the last decade to probe striatal circuits that are involved in Parkinson disease, a neurodegenerative condition involving motor and cognitive abnormalities resulting from degeneration of midbrain dopaminergic neurons. The precise mechanisms underlying the striatal contribution to both cognitive and motor dysfunction in Parkinson disease are unknown. Although optogenetic approaches are somewhat removed from clinical use, insight from these studies can help identify novel therapeutic targets and may inspire new treatments for Parkinson disease. Elucidating how neuronal and behavioral functions are influenced and potentially rescued by optogenetic manipulation in animal models could prove to be translatable to humans. These insights can be used to guide future brain-stimulation approaches for motor and cognitive abnormalities in Parkinson disease and other neuropsychiatric diseases.

Feeding behavior of Aplysia: a model system for comparing cellular mechanisms of classical and operant conditioning.

PubMed

Baxter, Douglas A; Byrne, John H

2006-01-01

Feeding behavior of Aplysia provides an excellent model system for analyzing and comparing mechanisms underlying appetitive classical conditioning and reward operant conditioning. Behavioral protocols have been developed for both forms of associative learning, both of which increase the occurrence of biting following training. Because the neural circuitry that mediates the behavior is well characterized and amenable to detailed cellular analyses, substantial progress has been made toward a comparative analysis of the cellular mechanisms underlying these two forms of associative learning. Both forms of associative learning use the same reinforcement pathway (the esophageal nerve, En) and the same reinforcement transmitter (dopamine, DA). In addition, at least one cellular locus of plasticity (cell B51) is modified by both forms of associative learning. However, the two forms of associative learning have opposite effects on B51. Classical conditioning decreases the excitability of B51, whereas operant conditioning increases the excitability of B51. Thus, the approach of using two forms of associative learning to modify a single behavior, which is mediated by an analytically tractable neural circuit, is revealing similarities and differences in the mechanisms that underlie classical and operant conditioning.

The genetics of normal and defective color vision

PubMed Central

Neitz, Jay; Neitz, Maureen

2011-01-01

The contributions of genetics research to the science of normal and defective color vision over the previous few decades are reviewed emphasizing the developments in the 25 years since the last anniversary issue of Vision Research. Understanding of the biology underlying color vision has been vaulted forward through the application of the tools of molecular genetics. For all their complexity, the biological processes responsible for color vision are more accessible than for many other neural systems. This is partly because of the wealth of genetic variations that affect color perception, both within and across species, and because components of the color vision system lend themselves to genetic manipulation. Mutations and rearrangements in the genes encoding the long, middle, and short wavelength sensitive cone pigments are responsible for color vision deficiencies and mutations have been identified that affect the number of cone types, the absorption spectrum of the pigments, the functionality and viability of the cones, and the topography of the cone mosaic. The addition of an opsin gene, as occurred in the evolution of primate color vision, and has been done in experimental animals can produce expanded color vision capacities and this has provided insight into the underlying neural circuitry. PMID:21167193

Event-Related Oscillations in Alcoholism Research: A Review

PubMed Central

Pandey, Ashwini K; Kamarajan, Chella; Rangaswamy, Madhavi; Porjesz, Bernice

2013-01-01

Alcohol dependence is characterized as a multi-factorial disorder caused by a complex interaction between genetic and environmental liabilities across development. A variety of neurocognitive deficits/dysfunctions involving impairments in different brain regions and/or neural circuitries have been associated with chronic alcoholism, as well as with a predisposition to develop alcoholism. Several neurobiological and neurobehavioral approaches and methods of analyses have been used to understand the nature of these neurocognitive impairments/deficits in alcoholism. In the present review, we have examined relatively novel methods of analyses of the brain signals that are collectively referred to as event-related oscillations (EROs) and show promise to further our understanding of human brain dynamics while performing various tasks. These new measures of dynamic brain processes have exquisite temporal resolution and allow the study of neural networks underlying responses to sensory and cognitive events, thus providing a closer link to the physiology underlying them. Here, we have reviewed EROs in the study of alcoholism, their usefulness in understanding dynamical brain functions/dysfunctions associated with alcoholism as well as their utility as effective endophenotypes to identify and understand genes associated with both brain oscillations and alcoholism. PMID:24273686

Progress toward the maintenance and repair of degenerating retinal circuitry.

PubMed

Vugler, Anthony A

2010-01-01

Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

Brain and language: evidence for neural multifunctionality.

PubMed

Cahana-Amitay, Dalia; Albert, Martin L

2014-01-01

This review paper presents converging evidence from studies of brain damage and longitudinal studies of language in aging which supports the following thesis: the neural basis of language can best be understood by the concept of neural multifunctionality. In this paper the term "neural multifunctionality" refers to incorporation of nonlinguistic functions into language models of the intact brain, reflecting a multifunctional perspective whereby a constant and dynamic interaction exists among neural networks subserving cognitive, affective, and praxic functions with neural networks specialized for lexical retrieval, sentence comprehension, and discourse processing, giving rise to language as we know it. By way of example, we consider effects of executive system functions on aspects of semantic processing among persons with and without aphasia, as well as the interaction of executive and language functions among older adults. We conclude by indicating how this multifunctional view of brain-language relations extends to the realm of language recovery from aphasia, where evidence of the influence of nonlinguistic factors on the reshaping of neural circuitry for aphasia rehabilitation is clearly emerging.

Normative data on development of neural and behavioral mechanisms underlying attention orienting toward social-emotional stimuli: An exploratory study

PubMed Central

Lindstrom, Kara; Guyer, Amanda E.; Mogg, Karin; Bradley, Brendan P.; Fox, Nathan A.; Ernst, Monique; Nelson, Eric E.; Leibenluft, Ellen; Britton, Jennifer C.; Monk, Christopher S.; Pine, Daniel S.; Bar-Haim, Yair

2009-01-01

The ability of positive and negative facial signals to influence attention orienting is crucial to social functioning. Given the dramatic developmental change in neural architecture supporting social function, positive and negative facial cues may influence attention orienting differently in relatively young or old individuals. However, virtually no research examines such age-related differences in the neural circuitry supporting attention orienting to emotional faces. We examined age-related correlations in attention-orienting biases to positive and negative face emotions in a healthy sample (N=37; 9-40 years old) using functional magnetic resonance imaging and a dot-probe task. The dot-probe task in an fMRI setting yields both behavioral and neural indices of attention biases towards or away from an emotional cue (happy or angry face). In the full sample, angry-face attention bias scores did not correlate with age, and age did not correlate with brain activation to angry faces. However, age did positively correlate with attention bias towards happy faces; age also negatively correlated with left cuneus and left caudate activation to a happy-bias fMRI contrast. Secondary analyses suggested age-related changes in attention bias to happy faces. The tendency in younger children to direct attention away from happy faces (relative to neutral faces) was diminished in the older age groups, in tandem with increasing neural deactivation. Implications for future work on developmental changes in attention-emotion processing are discussed. PMID:19631626

Neural circuitry engaged by prostaglandins during the sickness syndrome.

PubMed

Saper, Clifford B; Romanovsky, Andrej A; Scammell, Thomas E

2012-07-26

During illnesses caused by infectious disease or other sources of inflammation, a suite of brain-mediated responses called the sickness syndrome occurs, which includes fever, anorexia, sleepiness, hyperalgesia and elevated corticosteroid secretion. Much of the sickness syndrome is mediated by prostaglandins acting on the brain and can be prevented by nonsteroidal anti-inflammatory drugs, such as aspirin or ibuprofen, that block prostaglandin synthesis. By examining which prostaglandins are produced at which sites and how they interact with the nervous system, researchers have identified specific neural circuits that underlie the sickness syndrome.

Neural Circuitry Engaged by Prostaglandins during the Sickness Syndrome

PubMed Central

Saper, Clifford B.; Romanovsky, Andrej A.; Scammell, Thomas E.

2013-01-01

During illnesses caused by infectious disease or other sources of inflammation, a suite of brain-mediated responses called the “sickness syndrome” occurs, including fever, anorexia, sleepiness, hyperalgesia, and elevated corticosteroid secretion. Much of the sickness syndrome is mediated by prostaglandins acting on the brain, and can be prevented by non-steroidal anti-inflammatory drugs, such as aspirin or ibuprofen, that block prostaglandin synthesis. By examining which prostaglandins are produced at which sites and how they interact with the nervous system, researchers have identified specific neural circuits that underlie the sickness syndrome. PMID:22837039

Low Temperature Performance of High-Speed Neural Network Circuits

NASA Technical Reports Server (NTRS)

Duong, T.; Tran, M.; Daud, T.; Thakoor, A.

1995-01-01

Artificial neural networks, derived from their biological counterparts, offer a new and enabling computing paradigm specially suitable for such tasks as image and signal processing with feature classification/object recognition, global optimization, and adaptive control. When implemented in fully parallel electronic hardware, it offers orders of magnitude speed advantage. Basic building blocks of the new architecture are the processing elements called neurons implemented as nonlinear operational amplifiers with sigmoidal transfer function, interconnected through weighted connections called synapses implemented using circuitry for weight storage and multiply functions either in an analog, digital, or hybrid scheme.

Multiplexing in the primate motion pathway.

PubMed

Huk, Alexander C

2012-06-01

This article begins by reviewing recent work on 3D motion processing in the primate visual system. Some of these results suggest that 3D motion signals may be processed in the same circuitry already known to compute 2D motion signals. Such "multiplexing" has implications for the study of visual cortical circuits and neural signals. A more explicit appreciation of multiplexing--and the computations required for demultiplexing--may enrich the study of the visual system by emphasizing the importance of a structured and balanced "encoding/decoding" framework. In addition to providing a fresh perspective on how successive stages of visual processing might be approached, multiplexing also raises caveats about the value of "neural correlates" for understanding neural computation.

Applying gene regulatory network logic to the evolution of social behavior.

PubMed

Baran, Nicole M; McGrath, Patrick T; Streelman, J Todd

2017-06-06

Animal behavior is ultimately the product of gene regulatory networks (GRNs) for brain development and neural networks for brain function. The GRN approach has advanced the fields of genomics and development, and we identify organizational similarities between networks of genes that build the brain and networks of neurons that encode brain function. In this perspective, we engage the analogy between developmental networks and neural networks, exploring the advantages of using GRN logic to study behavior. Applying the GRN approach to the brain and behavior provides a quantitative and manipulative framework for discovery. We illustrate features of this framework using the example of social behavior and the neural circuitry of aggression.

Brain Bases of Morphological Processing in Chinese-English Bilingual Children

ERIC Educational Resources Information Center

Ip, Ka I; Hsu, Lucy Shih-Ju; Arredondo, Maria M.; Tardif, Twila; Kovelman, Ioulia

2017-01-01

Can bilingual exposure impact children's neural circuitry for learning to read? To answer this question, we investigated the brain bases of morphological awareness, one of the key spoken language abilities for learning to read in English and Chinese. Bilingual Chinese-English and monolingual English children (N = 22, ages 7-12) completed…

[Effects of Bromazepam in qEEG by type writing].

PubMed

Machado, Dionis; Bastos, Victor Hugo; Cunha, Marlo; Furtado, Vernon; Cagy, Maurício; Piedade, Roberto; Ribeiro, Pedro

2005-06-01

The efficiency with which an information is processed by the brain's neural circuitry can be altered by neuromodulators. The use of Bromazepam in the pharmacological treatment of anxiety disorders is due to its anxiolytic property. However, the effects of this benzodiazepine in motor learning tasks are not entirely understood. In this context, the goal of this study was to assess the effects of Bromazepam (6 mg) on psychophysiological, behavioral, and electrophysiological variables, during the process of learning a motor task. The sample consisted of 26 healthy individuals, of both sexes, between 19 and 36 years of age. The control (placebo) and experimental (Bromazepam 6 mg) groups were submitted to a typewriting task, in a randomized, double-blind design. The results did not reveal differences for phychophysiological and behavioral variables between the groups. Statistical tests pointed out to an interaction between condition and moment, and a hemisphere main effect, i.e. a reduction of relative power in the right hemisphere. This reduction suggests a specialization of the neural circuitry in the hemisphere contralateral to the finger used in the task. Such reduction is independent from the drug administration.

Does the vestibular system contribute to head direction cell activity in the rat?

NASA Technical Reports Server (NTRS)

Brown, J. E.; Yates, B. J.; Taube, J. S.; Oman, C. M. (Principal Investigator)

2002-01-01

Head direction cells (HDC) located in several regions of the brain, including the anterior dorsal nucleus of the thalamus (ADN), postsubiculum (PoS), and lateral mammillary nuclei (LMN), provide the neural substrate for the determination of head direction. Although activity of HDC is influenced by various sensory signals and internally generated cues, lesion studies and some anatomical and physiological evidence suggest that vestibular inputs are critical for the maintenance of directional sensitivity of these cells. However, vestibular inputs must be transformed considerably in order to signal head direction, and the neuronal circuitry that accomplishes this signal processing has not been fully established. Furthermore, it is unclear why the removal of vestibular inputs abolishes the directional sensitivity of HDC, as visual and other sensory inputs and motor feedback signals strongly affect the firing of these neurons and would be expected to maintain their directional-related activity. Further physiological studies will be required to establish the role of vestibular system in producing HDC responses, and anatomical studies are needed to determine the neural circuitry that mediates vestibular influences on determination of head direction.

Energy efficient neural stimulation: coupling circuit design and membrane biophysics.

PubMed

Foutz, Thomas J; Ackermann, D Michael; Kilgore, Kevin L; McIntyre, Cameron C

2012-01-01

The delivery of therapeutic levels of electrical current to neural tissue is a well-established treatment for numerous indications such as Parkinson's disease and chronic pain. While the neuromodulation medical device industry has experienced steady clinical growth over the last two decades, much of the core technology underlying implanted pulse generators remain unchanged. In this study we propose some new methods for achieving increased energy-efficiency during neural stimulation. The first method exploits the biophysical features of excitable tissue through the use of a centered-triangular stimulation waveform. Neural activation with this waveform is achieved with a statistically significant reduction in energy compared to traditional rectangular waveforms. The second method demonstrates energy savings that could be achieved by advanced circuitry design. We show that the traditional practice of using a fixed compliance voltage for constant-current stimulation results in substantial energy loss. A portion of this energy can be recuperated by adjusting the compliance voltage to real-time requirements. Lastly, we demonstrate the potential impact of axon fiber diameter on defining the energy-optimal pulse-width for stimulation. When designing implantable pulse generators for energy efficiency, we propose that the future combination of a variable compliance system, a centered-triangular stimulus waveform, and an axon diameter specific stimulation pulse-width has great potential to reduce energy consumption and prolong battery life in neuromodulation devices.

The cholinergic anti-inflammatory pathway revisited.

PubMed

Murray, K; Reardon, C

2018-03-01

Inflammatory bowel disease negatively affects the quality of life of millions of patients around the world. Although the precise etiology of the disease remains elusive, aberrant immune system activation is an underlying cause. As such, therapies that selectively inhibit immune cell activation without broad immunosuppression are desired. Inhibition of immune cell activation preventing pro-inflammatory cytokine production through neural stimulation has emerged as one such treatment. These therapeutics are based on the discovery of the cholinergic anti-inflammatory pathway, a reflex arc that induces efferent vagal nerve signaling to reduce immune cell activation and consequently mortality during septic shock. Despite the success of preclinical and clinical trials, the neural circuitry and mechanisms of action of these immune-regulatory circuits are controversial. At the heart of this controversy is the protective effect of vagal nerve stimulation despite an apparent lack of neuroanatomical connections between the vagus and target organs. Additional studies have further emphasized the importance of sympathetic innervation of these organs, and that alternative neural circuits could be involved in neural regulation of the immune system. Such controversies also extend to the regulation of intestinal inflammation, with the importance of efferent vagus nerve signals in question. Experiments that better characterize these pathways have now been performed by Willemze et al. in this issue of Neurogastroenterology & Motility. These continued efforts will be critical to the development of better neurostimulator based therapeutics for inflammatory bowel disease. © 2018 John Wiley & Sons Ltd.

Insect Responses to Linearly Polarized Reflections: Orphan Behaviors Without Neural Circuits.

PubMed

Heinloth, Tanja; Uhlhorn, Juliane; Wernet, Mathias F

2018-01-01

The e-vector orientation of linearly polarized light represents an important visual stimulus for many insects. Especially the detection of polarized skylight by many navigating insect species is known to improve their orientation skills. While great progress has been made towards describing both the anatomy and function of neural circuit elements mediating behaviors related to navigation, relatively little is known about how insects perceive non-celestial polarized light stimuli, like reflections off water, leaves, or shiny body surfaces. Work on different species suggests that these behaviors are not mediated by the "Dorsal Rim Area" (DRA), a specialized region in the dorsal periphery of the adult compound eye, where ommatidia contain highly polarization-sensitive photoreceptor cells whose receptive fields point towards the sky. So far, only few cases of polarization-sensitive photoreceptors have been described in the ventral periphery of the insect retina. Furthermore, both the structure and function of those neural circuits connecting to these photoreceptor inputs remain largely uncharacterized. Here we review the known data on non-celestial polarization vision from different insect species (dragonflies, butterflies, beetles, bugs and flies) and present three well-characterized examples for functionally specialized non-DRA detectors from different insects that seem perfectly suited for mediating such behaviors. Finally, using recent advances from circuit dissection in Drosophila melanogaster , we discuss what types of potential candidate neurons could be involved in forming the underlying neural circuitry mediating non-celestial polarization vision.

Prefrontal consolidation supports the attainment of fear memory accuracy

PubMed Central

Vieira, Philip A.; Lovelace, Jonathan W.; Corches, Alex; Rashid, Asim J.; Josselyn, Sheena A.

2014-01-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive. PMID:25031365

Craving behavioral intervention for internet gaming disorder: remediation of functional connectivity of the ventral striatum.

PubMed

Zhang, Jin-Tao; Ma, Shan-Shan; Li, Chiang-Shan R; Liu, Lu; Xia, Cui-Cui; Lan, Jing; Wang, Ling-Jiao; Liu, Ben; Yao, Yuan-Wei; Fang, Xiao-Yi

2018-01-01

Psychobehavioral intervention is an effective treatment of Internet addiction, including Internet gaming disorder (IGD). However, the neural mechanisms underlying its efficacy remain unclear. Cortical-ventral striatum (VS) circuitry is a common target of psychobehavioral interventions in drug addiction, and cortical-VS dysfunction has been reported in IGD; hence, the primary aim of the study was to investigate how the VS circuitry responds to psychobehavioral interventions in IGD. In a cross-sectional study, we examined resting-state functional connectivity of the VS in 74 IGD subjects (IGDs) and 41 healthy controls (HCs). In a follow-up craving behavioral intervention (CBI) study, of the 74 IGD subjects, 20 IGD subjects received CBI (CBI+) and 16 IGD subjects did not (CBI-). All participants were scanned twice with similar time interval to assess the effects of CBI. IGD subjects showed greater resting-state functional connectivity of the VS to left inferior parietal lobule (lIPL), right inferior frontal gyrus and left middle frontal gyrus, in positive association with the severity of IGD. Moreover, compared with CBI-, CBI+ showed significantly greater decrease in VS-lIPL connectivity, along with amelioration in addiction severity following the intervention. These findings demonstrated that functional connectivity between VS and lIPL, each presumably mediating gaming craving and attentional bias, may be a potential biomarker of the efficacy of psychobehavioral intervention. These results also suggested that non-invasive techniques such as transcranial magnetic or direct current stimulation targeting the VS-IPL circuitry may be used in the treatment of Internet gaming disorders. © 2016 Society for the Study of Addiction.

Activation of Corticostriatal Circuitry Relieves Chronic Neuropathic Pain

PubMed Central

Lee, Michelle; Manders, Toby R.; Eberle, Sarah E.; Su, Chen; D'amour, James; Yang, Runtao; Lin, Hau Yueh; Deisseroth, Karl; Froemke, Robert C.

2015-01-01

Neural circuits that determine the perception and modulation of pain remain poorly understood. The prefrontal cortex (PFC) provides top-down control of sensory and affective processes. While animal and human imaging studies have shown that the PFC is involved in pain regulation, its exact role in pain states remains incompletely understood. A key output target for the PFC is the nucleus accumbens (NAc), an important component of the reward circuitry. Interestingly, recent human imaging studies suggest that the projection from the PFC to the NAc is altered in chronic pain. The function of this corticostriatal projection in pain states, however, is not known. Here we show that optogenetic activation of the PFC produces strong antinociceptive effects in a rat model (spared nerve injury model) of persistent neuropathic pain. PFC activation also reduces the affective symptoms of pain. Furthermore, we show that this pain-relieving function of the PFC is likely mediated by projections to the NAc. Thus, our results support a novel role for corticostriatal circuitry in pain regulation. PMID:25834050

Optimizing cholinergic tone through lynx modulators of nicotinic receptors: implications for plasticity and nicotine addiction.

PubMed

Miwa, Julie M; Lester, Henry A; Walz, Andreas

2012-08-01

The cholinergic system underlies both adaptive (learning and memory) and nonadaptive (addiction and dependency) behavioral changes through its ability to shape and regulate plasticity. Protein modulators such as lynx family members can fine tune the activity of the cholinergic system and contribute to the graded response of the cholinergic system, stabilizing neural circuitry through direct interaction with nicotinic receptors. Release of this molecular brake can unmask cholinergic-dependent mechanisms in the brain. Lynx proteins have the potential to provide top-down control over plasticity mechanisms, including addictive propensity. If this is indeed the case, then, what regulates the regulator? Transcriptional changes of lynx genes in response to pharmacological, physiological, and pathological alterations are explored in this review.

Neuropeptide Regulation of Fear and Anxiety: Implications of Cholecystokinin, Endogenous Opioids, and Neuropeptide Y

PubMed Central

Bowers, Mallory E.; Choi, Dennis C.; Ressler, Kerry J.

2012-01-01

The neural circuitry of fear likely underlies anxiety and fear-related disorders such as specific and social phobia, panic disorder, and posttraumatic stress disorder. The primary pharmacological treatments currently utilized for these disorders include benzodiazepines, which act on the GABAergic receptor system, and antidepressants, which modulate the monamine systems. However, recent work on the regulation of fear neural circuitry suggests that specific neuropeptide modulation of this system is of critical importance. Recent reviews have examined the roles of the hypothalamic-pituitary-adrenal axis neuropeptides as well as the roles of neurotrophic factors in regulating fear. The present review, instead, will focus on three neuropeptide systems which have received less attention in recent years but which are clearly involved in regulating fear and its extinction. The endogenous opioid system, particularly activating the μ opioid receptors, has been demonstrated to regulate fear expression and extinction, possibly through functioning as an error signal within the amygdala to mark unreinforced conditioned stimuli. The cholecystokinin (CCK) system initially led to much excitement through its potential role in panic disorder. More recent work in the CCK neuropeptide pathway suggests that it may act in concordance with the endogenous cannabinoid system in the modulation of fear inhibition and extinction. Finally, older as well as very recent data suggests that neuropeptide Y (NPY) may play a very interesting role in counteracting stress effects, enhancing extinction, and enhancing resilience in fear and stress preclinical models. Future work in understanding the mechanisms of neuropeptide functioning, particularly within well-known behavioral circuits, are likely to provide fascinating new clues into the understanding of fear behavior as well as suggesting novel therapeutics for treating disorders of anxiety and fear dysregulation. PMID:22429904

Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons.

PubMed

Li, Ai-Jun; Wang, Qing; Dinh, Thu T; Powers, Bethany R; Ritter, Sue

2014-02-15

Previous work has shown that hindbrain catecholamine neurons are required components of the brain's glucoregulatory circuitry. However, the mechanisms and circuitry underlying their glucoregulatory functions are poorly understood. Here we examined three drugs, glucosamine (GcA), phloridzin (Phl) and 5-thio-d-glucose (5TG), that stimulate food intake but interfere in different ways with cellular glucose utilization or transport. We examined feeding and blood glucose responses to each drug in male rats previously injected into the hypothalamic paraventricular nucleus with anti-dopamine-β-hydroxylase conjugated to saporin (DSAP), a retrogradely transported immunotoxin that selectively lesions noradrenergic and adrenergic neurons, or with unconjugated saporin (SAP) control. Our major findings were 1) that GcA, Phl, and 5TG all stimulated feeding in SAP controls whether injected into the lateral or fourth ventricle (LV or 4V), 2) that each drug's potency was similar for both LV and 4V injections, 3) that neither LV or 4V injection of these drugs evoked feeding in DSAP-lesioned rats, and 4) that only 5TG, which blocks glycolysis, stimulated a blood glucose response. The antagonist of the MEK/ERK signaling cascade, U0126, attenuated GcA-induced feeding, but not Phl- or 5TG-induced feeding. Thus GcA, Phl, and 5TG, although differing in mechanism and possibly activating different neural populations, stimulate feeding in a catecholamine-dependent manner. Although results do not exclude the possibility that catecholamine neurons possess glucose-sensing mechanisms responsive to all of these agents, currently available evidence favors the possibility that the feeding effects result from convergent neural circuits in which catecholamine neurons are a required component.

Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons

PubMed Central

Wang, Qing; Dinh, Thu T.; Powers, Bethany R.; Ritter, Sue

2013-01-01

Previous work has shown that hindbrain catecholamine neurons are required components of the brain's glucoregulatory circuitry. However, the mechanisms and circuitry underlying their glucoregulatory functions are poorly understood. Here we examined three drugs, glucosamine (GcA), phloridzin (Phl) and 5-thio-d-glucose (5TG), that stimulate food intake but interfere in different ways with cellular glucose utilization or transport. We examined feeding and blood glucose responses to each drug in male rats previously injected into the hypothalamic paraventricular nucleus with anti-dopamine-β-hydroxylase conjugated to saporin (DSAP), a retrogradely transported immunotoxin that selectively lesions noradrenergic and adrenergic neurons, or with unconjugated saporin (SAP) control. Our major findings were 1) that GcA, Phl, and 5TG all stimulated feeding in SAP controls whether injected into the lateral or fourth ventricle (LV or 4V), 2) that each drug's potency was similar for both LV and 4V injections, 3) that neither LV or 4V injection of these drugs evoked feeding in DSAP-lesioned rats, and 4) that only 5TG, which blocks glycolysis, stimulated a blood glucose response. The antagonist of the MEK/ERK signaling cascade, U0126, attenuated GcA-induced feeding, but not Phl- or 5TG-induced feeding. Thus GcA, Phl, and 5TG, although differing in mechanism and possibly activating different neural populations, stimulate feeding in a catecholamine-dependent manner. Although results do not exclude the possibility that catecholamine neurons possess glucose-sensing mechanisms responsive to all of these agents, currently available evidence favors the possibility that the feeding effects result from convergent neural circuits in which catecholamine neurons are a required component. PMID:24381177

Reduced neural activity of the prefrontal cognitive control circuitry during response inhibition to negative words in people with schizophrenia

PubMed Central

Vercammen, Ans; Morris, Richard; Green, Melissa J.; Lenroot, Rhoshel; Kulkarni, Jayashri; Carr, Vaughan J.; Weickert, Cynthia Shannon; Weickert, Thomas W.

2012-01-01

Background Schizophrenia is characterized by deficits in executive control and impairments in emotion processing. This study assessed the nature and extent of potential alterations in the neural substrates supporting the interaction between cognitive control mechanisms and emotion attribution processes in people with schizophrenia. Methods Functional magnetic resonance imaging was performed during a verbal emotional go/no-go task. People with schizophrenia and healthy controls responded to word stimuli of a prespecified emotional valence (positive, negative or neutral) while inhibiting responses to stimuli of a different valence. Results We enrolled 20 people with schizophrenia and 23 controls in the study. Healthy controls activated an extensive dorsal prefrontal–parietal network while inhibiting responses to negative words compared to neutral words, but showed deactivation of the midcingulate cortex while inhibiting responses to positive words compared to neutral words. People with schizophrenia failed to activate this network during response inhibition to negative words, whereas during response inhibition to positive words they did not deactivate the cingulate, but showed increased responsivity in the frontal cortex. Limitations Sample heterogeneity is characteristic of studies of schizophrenia and may have contributed to more variable neural responses in the patient sample despite the care taken to control for potentially confounding variables. Conclusion Our results showed that schizophrenia is associated with aberrant modulation of neural responses during the interaction between cognitive control and emotion processing. Failure of the frontal circuitry to regulate goal-directed behaviour based on emotion attributions may contribute to deficits in psychosocial functioning in daily life. PMID:22617625

Neural circuitry of abdominal pain-related fear learning and reinstatement in irritable bowel syndrome.

PubMed

Icenhour, A; Langhorst, J; Benson, S; Schlamann, M; Hampel, S; Engler, H; Forsting, M; Elsenbruch, S

2015-01-01

Altered pain anticipation likely contributes to disturbed central pain processing in chronic pain conditions like irritable bowel syndrome (IBS), but the learning processes shaping the expectation of pain remain poorly understood. We assessed the neural circuitry mediating the formation, extinction, and reactivation of abdominal pain-related memories in IBS patients compared to healthy controls (HC) in a differential fear conditioning paradigm. During fear acquisition, predictive visual cues (CS(+)) were paired with rectal distensions (US), while control cues (CS(-)) were presented unpaired. During extinction, only CSs were presented. Subsequently, memory reactivation was assessed with a reinstatement procedure involving unexpected USs. Using functional magnetic resonance imaging, group differences in neural activation to CS(+) vs CS(-) were analyzed, along with skin conductance responses (SCR), CS valence, CS-US contingency, state anxiety, salivary cortisol, and alpha-amylase activity. The contribution of anxiety symptoms was addressed in covariance analyses. Fear acquisition was altered in IBS, as indicated by more accurate contingency awareness, greater CS-related valence change, and enhanced CS(+)-induced differential activation of prefrontal cortex and amygdala. IBS patients further revealed enhanced differential cingulate activation during extinction and greater differential hippocampal activation during reinstatement. Anxiety affected neural responses during memory formation and reinstatement. Abdominal pain-related fear learning and memory processes are altered in IBS, mediated by amygdala, cingulate cortex, prefrontal areas, and hippocampus. Enhanced reinstatement may contribute to hypervigilance and central pain amplification, especially in anxious patients. Preventing a 'relapse' of learned fear utilizing extinction-based interventions may be a promising treatment goal in IBS. © 2014 John Wiley & Sons Ltd.

Synergistic Gating of Electro-Iono-Photoactive 2D Chalcogenide Neuristors: Coexistence of Hebbian and Homeostatic Synaptic Metaplasticity.

PubMed

John, Rohit Abraham; Liu, Fucai; Chien, Nguyen Anh; Kulkarni, Mohit R; Zhu, Chao; Fu, Qundong; Basu, Arindam; Liu, Zheng; Mathews, Nripan

2018-06-01

Emulation of brain-like signal processing with thin-film devices can lay the foundation for building artificially intelligent learning circuitry in future. Encompassing higher functionalities into single artificial neural elements will allow the development of robust neuromorphic circuitry emulating biological adaptation mechanisms with drastically lesser neural elements, mitigating strict process challenges and high circuit density requirements necessary to match the computational complexity of the human brain. Here, 2D transition metal di-chalcogenide (MoS 2 ) neuristors are designed to mimic intracellular ion endocytosis-exocytosis dynamics/neurotransmitter-release in chemical synapses using three approaches: (i) electronic-mode: a defect modulation approach where the traps at the semiconductor-dielectric interface are perturbed; (ii) ionotronic-mode: where electronic responses are modulated via ionic gating; and (iii) photoactive-mode: harnessing persistent photoconductivity or trap-assisted slow recombination mechanisms. Exploiting a novel multigated architecture incorporating electrical and optical biases, this incarnation not only addresses different charge-trapping probabilities to finely modulate the synaptic weights, but also amalgamates neuromodulation schemes to achieve "plasticity of plasticity-metaplasticity" via dynamic control of Hebbian spike-time dependent plasticity and homeostatic regulation. Coexistence of such multiple forms of synaptic plasticity increases the efficacy of memory storage and processing capacity of artificial neuristors, enabling design of highly efficient novel neural architectures. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neuromechanical simulation of the locust jump

PubMed Central

Cofer, D.; Cymbalyuk, G.; Heitler, W. J.; Edwards, D. H.

2010-01-01

The neural circuitry and biomechanics of kicking in locusts have been studied to understand their roles in the control of both kicking and jumping. It has been hypothesized that the same neural circuit and biomechanics governed both behaviors but this hypothesis was not testable with current technology. We built a neuromechanical model to test this and to gain a better understanding of the role of the semi-lunar process (SLP) in jump dynamics. The jumping and kicking behaviors of the model were tested by comparing them with a variety of published data, and were found to reproduce the results from live animals. This confirmed that the kick neural circuitry can produce the jump behavior. The SLP is a set of highly sclerotized bands of cuticle that can be bent to store energy for use during kicking and jumping. It has not been possible to directly test the effects of the SLP on jump performance because it is an integral part of the joint, and attempts to remove its influence prevent the locust from being able to jump. Simulations demonstrated that the SLP can significantly increase jump distance, power, total energy and duration of the jump impulse. In addition, the geometry of the joint enables the SLP force to assist leg flexion when the leg is flexed, and to assist extension once the leg has begun to extend. PMID:20228342

Evolution of the cerebellum as a neuronal machine for Bayesian state estimation

NASA Astrophysics Data System (ADS)

Paulin, M. G.

2005-09-01

The cerebellum evolved in association with the electric sense and vestibular sense of the earliest vertebrates. Accurate information provided by these sensory systems would have been essential for precise control of orienting behavior in predation. A simple model shows that individual spikes in electrosensory primary afferent neurons can be interpreted as measurements of prey location. Using this result, I construct a computational neural model in which the spatial distribution of spikes in a secondary electrosensory map forms a Monte Carlo approximation to the Bayesian posterior distribution of prey locations given the sense data. The neural circuit that emerges naturally to perform this task resembles the cerebellar-like hindbrain electrosensory filtering circuitry of sharks and other electrosensory vertebrates. The optimal filtering mechanism can be extended to handle dynamical targets observed from a dynamical platform; that is, to construct an optimal dynamical state estimator using spiking neurons. This may provide a generic model of cerebellar computation. Vertebrate motion-sensing neurons have specific fractional-order dynamical characteristics that allow Bayesian state estimators to be implemented elegantly and efficiently, using simple operations with asynchronous pulses, i.e. spikes. The computational neural models described in this paper represent a novel kind of particle filter, using spikes as particles. The models are specific and make testable predictions about computational mechanisms in cerebellar circuitry, while providing a plausible explanation of cerebellar contributions to aspects of motor control, perception and cognition.

Spatiotemporal dissociation of brain activity underlying threat and reward in social anxiety disorder

PubMed Central

Ghane, Merage; Valdespino, Andrew; Coffman, Marika C.; Strege, Marlene V.; White, Susan W.; Ollendick, Thomas H.

2017-01-01

Abstract Social anxiety disorder (SAD) involves abnormalities in social motivation, which may be independent of well-documented differences in fear and arousal systems. Yet, the neurobiology underlying motivational difficulties in SAD is not well understood. The aim of the current study was to spatiotemporally dissociate reward circuitry dysfunction from alterations in fear and arousal-related neural activity during anticipation and notification of social and non-social reward and punishment. During fMRI acquisition, non-depressed adults with social anxiety disorder (SAD; N = 21) and age-, sex- and IQ-matched control subjects (N = 22) completed eight runs of an incentive delay task, alternating between social and monetary outcomes and interleaved in alternating order between gain and loss outcomes. Adults with SAD demonstrated significantly reduced neural activity in ventral striatum during the anticipation of positive but not negative social outcomes. No differences between the SAD and control groups were observed during anticipation of monetary gain or loss outcomes or during anticipation of negative social images. However, consistent with previous work, the SAD group demonstrated amygdala hyper-activity upon notification of negative social outcomes. Degraded anticipatory processing in bilateral ventral striatum in SAD was constrained exclusively to anticipation of positive social information and dissociable from the effects of negative social outcomes previously observed in the amygdala. Alterations in anticipation-related neural signals may represent a promising target for treatment that is not addressed by available evidence-based interventions, which focus primarily on fear extinction and habituation processes. PMID:27798252

Neural circuitry of emotional and cognitive conflict revealed through facial expressions.

PubMed

Chiew, Kimberly S; Braver, Todd S

2011-03-09

Neural systems underlying conflict processing have been well studied in the cognitive realm, but the extent to which these overlap with those underlying emotional conflict processing remains unclear. A novel adaptation of the AX Continuous Performance Task (AX-CPT), a stimulus-response incompatibility paradigm, was examined that permits close comparison of emotional and cognitive conflict conditions, through the use of affectively-valenced facial expressions as the response modality. Brain activity was monitored with functional magnetic resonance imaging (fMRI) during performance of the emotional AX-CPT. Emotional conflict was manipulated on a trial-by-trial basis, by requiring contextually pre-cued facial expressions to emotional probe stimuli (IAPS images) that were either affectively compatible (low-conflict) or incompatible (high-conflict). The emotion condition was contrasted against a matched cognitive condition that was identical in all respects, except that probe stimuli were emotionally neutral. Components of the brain cognitive control network, including dorsal anterior cingulate cortex (ACC) and lateral prefrontal cortex (PFC), showed conflict-related activation increases in both conditions, but with higher activity during emotion conditions. In contrast, emotion conflict effects were not found in regions associated with affective processing, such as rostral ACC. These activation patterns provide evidence for a domain-general neural system that is active for both emotional and cognitive conflict processing. In line with previous behavioural evidence, greatest activity in these brain regions occurred when both emotional and cognitive influences additively combined to produce increased interference.

Neural Circuitry of Emotional and Cognitive Conflict Revealed through Facial Expressions

PubMed Central

Chiew, Kimberly S.; Braver, Todd S.

2011-01-01

Background Neural systems underlying conflict processing have been well studied in the cognitive realm, but the extent to which these overlap with those underlying emotional conflict processing remains unclear. A novel adaptation of the AX Continuous Performance Task (AX-CPT), a stimulus-response incompatibility paradigm, was examined that permits close comparison of emotional and cognitive conflict conditions, through the use of affectively-valenced facial expressions as the response modality. Methodology/Principal Findings Brain activity was monitored with functional magnetic resonance imaging (fMRI) during performance of the emotional AX-CPT. Emotional conflict was manipulated on a trial-by-trial basis, by requiring contextually pre-cued facial expressions to emotional probe stimuli (IAPS images) that were either affectively compatible (low-conflict) or incompatible (high-conflict). The emotion condition was contrasted against a matched cognitive condition that was identical in all respects, except that probe stimuli were emotionally neutral. Components of the brain cognitive control network, including dorsal anterior cingulate cortex (ACC) and lateral prefrontal cortex (PFC), showed conflict-related activation increases in both conditions, but with higher activity during emotion conditions. In contrast, emotion conflict effects were not found in regions associated with affective processing, such as rostral ACC. Conclusions/Significance These activation patterns provide evidence for a domain-general neural system that is active for both emotional and cognitive conflict processing. In line with previous behavioural evidence, greatest activity in these brain regions occurred when both emotional and cognitive influences additively combined to produce increased interference. PMID:21408006

Using Neural Networks in Decision Making for a Reconfigurable Electro Mechanical Actuator (EMA)

NASA Technical Reports Server (NTRS)

Latino, Carl D.

2001-01-01

The objectives of this project were to demonstrate applicability and advantages of a neural network approach for evaluating the performance of an electro-mechanical actuator (EMA). The EMA in question was intended for the X-37 Advanced Technology Vehicle. It will have redundant components for safety and reliability. The neural networks for this application are to monitor the operation of the redundant electronics that control the actuator in real time and decide on the operating configuration. The system we proposed consists of the actuator, sensors, control circuitry and dedicated (embedded) processors. The main purpose of the study was to develop suitable hardware and neural network capable of allowing real time reconfiguration decisions to be made. This approach was to be compared to other methods such as fuzzy logic and knowledge based systems considered for the same application. Over the course of the project a more general objective was the identification of the other neural network applications and the education of interested NASA personnel on the topic of Neural Networks.

The neurobiological drive for overeating implicated in Prader-Willi syndrome.

PubMed

Zhang, Yi; Wang, Jing; Zhang, Guansheng; Zhu, Qiang; Cai, Weiwei; Tian, Jie; Zhang, Yi Edi; Miller, Jennifer L; Wen, Xiaotong; Ding, Mingzhou; Gold, Mark S; Liu, Yijun

2015-09-16

Prader-Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous fMRI studies examined the activation of eating-related neural circuits in PWS patients with or without exposures to food cues and found an excessive eating motivation and a reduced inhibitory control of cognitive processing of food. However, the effective connectivity between various brain areas or neural circuitry critically implicated in both the biological and behavioral control of overeating in PWS is largely unexplored. The current study combined resting-state fMRI and Granger causality analysis (GCA) techniques to investigate interactive causal influences among key neural pathways underlying overeating in PWS. We first defined the regions of interest (ROIs) that demonstrated significant alterations of the baseline brain activity levels in children with PWS (n = 21) as compared to that of their normal siblings controls (n = 18), and then carried out GCA to characterize the region-to-region interactions among these ROIs. Our data revealed significantly enhanced causal influences from the amygdala to the hypothalamus and from both the medial prefrontal cortex and anterior cingulate cortex to the amygdala in patients with PWS (P < 0.001). These alterations offer new explanations for hypothalamic regulation of homeostatic energy intake and impairment in inhibitory control circuit. The deficits in these dual aspects may jointly contribute to the extreme hyperphagia in PWS. This study provides both a new methodological and a neurobiological perspective to aid in a better understanding of neural mechanisms underlying obesity in the general public. This article is part of a Special Issue entitled 1618. Copyright © 2015 Elsevier B.V. All rights reserved.

Integrating Early Childhood Education in a Health Program: An Example from El Salvador

ERIC Educational Resources Information Center

Borisova, Ivelina; Coddington, Cathy

2010-01-01

The early childhood years (conception to age 8) are not only the most critical time for human growth but also for development and learning. Neurological and behavioral scientists document how inadequate stimulation and interactions can disrupt basic neural circuitry and cause long-term challenges for child's cognitive development. Yet, despite the…

Face Engagement during Infancy Predicts Later Face Recognition Ability in Younger Siblings of Children with Autism

ERIC Educational Resources Information Center

de Klerk, Carina C. J. M.; Gliga, Teodora; Charman, Tony; Johnson, Mark H.

2014-01-01

Face recognition difficulties are frequently documented in children with autism spectrum disorders (ASD). It has been hypothesized that these difficulties result from a reduced interest in faces early in life, leading to decreased cortical specialization and atypical development of the neural circuitry for face processing. However, a recent study…

Spikes alone do not behavior make: Why neuroscience needs biomechanics

PubMed Central

Tytell, E.D.; Holmes, P.; Cohen, A.H.

2011-01-01

Neural circuits do not function in isolation; they interact with the physical world, accepting sensory inputs and producing outputs via muscles. Since both these pathways are constrained by physics, the activity of neural circuits can only be understood by considering biomechanics of muscles, bodies, and the exterior world. We discuss how animal bodies have natural stable motions that require relatively little activation or control from the nervous system. The nervous system can substantially alter these motions, by subtly changing mechanical properties such as leg sti ness. Mechanics can also provide robustness to perturbations without sensory reflexes. By considering a complete neuromechanical system, neuroscientists and biomechanicians together can provide a more integrated view of neural circuitry and behavior. PMID:21683575

Speed hysteresis and noise shaping of traveling fronts in neural fields: role of local circuitry and nonlocal connectivity

NASA Astrophysics Data System (ADS)

Capone, Cristiano; Mattia, Maurizio

2017-01-01

Neural field models are powerful tools to investigate the richness of spatiotemporal activity patterns like waves and bumps, emerging from the cerebral cortex. Understanding how spontaneous and evoked activity is related to the structure of underlying networks is of central interest to unfold how information is processed by these systems. Here we focus on the interplay between local properties like input-output gain function and recurrent synaptic self-excitation of cortical modules, and nonlocal intermodular synaptic couplings yielding to define a multiscale neural field. In this framework, we work out analytic expressions for the wave speed and the stochastic diffusion of propagating fronts uncovering the existence of an optimal balance between local and nonlocal connectivity which minimizes the fluctuations of the activation front propagation. Incorporating an activity-dependent adaptation of local excitability further highlights the independent role that local and nonlocal connectivity play in modulating the speed of propagation of the activation and silencing wavefronts, respectively. Inhomogeneities in space of local excitability give raise to a novel hysteresis phenomenon such that the speed of waves traveling in opposite directions display different velocities in the same location. Taken together these results provide insights on the multiscale organization of brain slow-waves measured during deep sleep and anesthesia.

Neural correlates of appetitive extinction in humans

PubMed Central

Tapia León, Isabell; Stark, Rudolf; Klucken, Tim

2017-01-01

Abstract Appetitive extinction receives attention as an important model for the treatment of psychiatric disorders. However, in humans, its underlying neural correlates remain unknown. To close this gap, we investigated appetitive acquisition and extinction with fMRI in a 2-day monetary incentive delay paradigm. During appetitive conditioning, one stimulus (CS+) was paired with monetary reward, while another stimulus (CS−) was never rewarded. Twenty-four hours later, subjects underwent extinction, in which neither CS was reinforced. Appetitive conditioning elicited stronger skin conductance responses to the CS+ as compared with the CS−. Regarding subjective ratings, the CS+ was rated more pleasant and arousing than the CS− after conditioning. Furthermore, fMRI-results (CS+ − CS−) showed activation of the reward circuitry including amygdala, midbrain and striatal areas. During extinction, conditioned responses were successfully extinguished. In the early phase of extinction, we found a significant activation of the caudate, the hippocampus, the dorsal and ventral anterior cingulate cortex (dACC and vACC). In the late phase, we found significant activation of the nucleus accumbens (NAcc) and the amygdala. Correlational analyses with subjective ratings linked extinction success to the vACC and the NAcc, while associating the dACC with reduced extinction. The results reveal neural correlates of appetitive extinction in humans and extend assumptions from models for human extinction learning. PMID:27803289

Evolution of motor innervation to vertebrate fins and limbs.

PubMed

Murakami, Yasunori; Tanaka, Mikiko

2011-07-01

The evolution and diversification of vertebrate behaviors associated with locomotion depend highly on the functional transformation of paired appendages. Although the evolution of fins into limbs has long been a focus of interest to scientists, the evolution of neural control during this transition has not received much attention. Recent studies have provided significant progress in the understanding of the genetic and developmental bases of the evolution of fin/limb motor circuitry in vertebrates. Here we compare the organization of the motor neurons in the spinal cord of various vertebrates. We also discuss recent advances in our understanding of these events and how they can provide a mechanistic explanation for the evolution of fin/limb motor circuitry in vertebrates. Copyright © 2011 Elsevier Inc. All rights reserved.

Multifunctional System for Observing, Measuring and Analyzing Stimulation-Evoked Neurochemical Signaling

PubMed Central

Kimble, Christopher J.; Boesche, Joshua B.; Eaker, Diane R.; Kressin, Kenneth R.; Trevathan, James K.; Paek, Seungleal; Asp, Anders J.; McIntosh, Malcolm B.; Lujan, J. Luis

2017-01-01

The ability to measure neurotransmitter activity using implanted electrochemical sensors offers researchers a potent technique for analyzing neural activity across specific neural circuitry. We have developed a wirelessly controlled device, WINCS Harmoni, to observe and measure neurotransmitter dynamics at up to four separate sensors, with high temporal and spatial resolution. WINCS Harmoni also incorporates a versatile neurostimulator that can be synchronized with electrochemical recording. The WINCS Harmoni platform is thus optimally suited for probing the neurochemical effects of neurostimulation, and may in turn enable the development of personalized therapies for multiple brain disorders. PMID:29202131

Fruitless, doublesex and the genetics of social behavior in Drosophila melanogaster.

PubMed

Siwicki, Kathleen K; Kravitz, Edward A

2009-04-01

Two genes coding for transcription factors, fruitless and doublesex, have been suggested to play important roles in the regulation of sexually dimorphic patterns of social behavior in Drosophila melanogaster. The generalization that fruitless specified the development of the nervous system and doublesex specified non-neural tissues culminated with claims that fruitless was both necessary and sufficient to establish sex-specific patterns of behavior. Several recent articles refute this notion, however, demonstrating that at a minimum, both fruitless and doublesex are involved in establishing sexually dimorphic features of neural circuitry and behavior in fruit flies.

The addictive dimensionality of obesity.

PubMed

Volkow, Nora D; Wang, Gene-Jack; Tomasi, Dardo; Baler, Ruben D

2013-05-01

Our brains are hardwired to respond and seek immediate rewards. Thus, it is not surprising that many people overeat, which in some can result in obesity, whereas others take drugs, which in some can result in addiction. Though food intake and body weight are under homeostatic regulation, when highly palatable food is available, the ability to resist the urge to eat hinges on self-control. There is no homeostatic regulator to check the intake of drugs (including alcohol); thus, regulation of drug consumption is mostly driven by self-control or unwanted effects (i.e., sedation for alcohol). Disruption in both the neurobiological processes that underlie sensitivity to reward and those that underlie inhibitory control can lead to compulsive food intake in some individuals and compulsive drug intake in others. There is increasing evidence that disruption of energy homeostasis can affect the reward circuitry and that overconsumption of rewarding food can lead to changes in the reward circuitry that result in compulsive food intake akin to the phenotype seen with addiction. Addiction research has produced new evidence that hints at significant commonalities between the neural substrates underlying the disease of addiction and at least some forms of obesity. This recognition has spurred a healthy debate to try and ascertain the extent to which these complex and dimensional disorders overlap and whether or not a deeper understanding of the crosstalk between the homeostatic and reward systems will usher in unique opportunities for prevention and treatment of both obesity and drug addiction. Published by Elsevier Inc.

Genetic approaches to understanding post-traumatic stress disorder

PubMed Central

Almli, Lynn M.; Fani, Negar; Smith, Alicia K.; Ressler, Kerry J.

2015-01-01

Post-traumatic stress disorder (PTSD) is increasingly recognized as both a disorder of enormous mental health and societal burden, but also as an anxiety disorder that may be particularly understandable from a scientific perspective. Specifically, PTSD can be conceptualized as a disorder of fear and stress dysregulation, and the neural circuitry underlying these pathways in both animals and humans are becoming increasingly well understood. Furthermore, PTSD is the only disorder in psychiatry in which the initiating factor, the trauma exposure, can be identified. Thus, the pathophysiology of the fear and stress response underlying PTSD can be examined and potentially interrupted. Twin studies have shown that the development of PTSD following a trauma is heritable, and that genetic risk factors may account for up to 30–40% of this heritability. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review will examine gene pathways that have recently been analysed, primarily through candidate gene studies (including neuroimaging studies of candidate genes), in addition to genome-wide associations and the epigenetic regulation of PTSD. Future and on-going studies are utilizing larger and collaborative cohorts to identify novel gene candidates through genome-wide association and other powerful genomic approaches. Identification of PTSD biological pathways strengthens the hope of progress in the mechanistic understanding of a model psychiatric disorder and allows for the development of targeted treatments and interventions. PMID:24103155

Diversity of bilateral synaptic assemblies for binaural computation in midbrain single neurons.

PubMed

He, Na; Kong, Lingzhi; Lin, Tao; Wang, Shaohui; Liu, Xiuping; Qi, Jiyao; Yan, Jun

2017-11-01

Binaural hearing confers many beneficial functions but our understanding of its underlying neural substrates is limited. This study examines the bilateral synaptic assemblies and binaural computation (or integration) in the central nucleus of the inferior colliculus (ICc) of the auditory midbrain, a key convergent center. Using in-vivo whole-cell patch-clamp, the excitatory and inhibitory postsynaptic potentials (EPSPs/IPSPs) of single ICc neurons to contralateral, ipsilateral and bilateral stimulation were recorded. According to the contralateral and ipsilateral EPSP/IPSP, 7 types of bilateral synaptic assemblies were identified. These include EPSP-EPSP (EE), E-IPSP (EI), E-no response (EO), II, IE, IO and complex-mode (CM) neurons. The CM neurons showed frequency- and/or amplitude-dependent EPSPs/IPSPs to contralateral or ipsilateral stimulation. Bilateral stimulation induced EPSPs/IPSPs that could be larger than (facilitation), similar to (ineffectiveness) or smaller than (suppression) those induced by contralateral stimulation. Our findings have allowed our group to characterize novel neural circuitry for binaural computation in the midbrain. Copyright © 2017 Elsevier B.V. All rights reserved.

Positive autobiographical memory retrieval reduces temporal discounting

PubMed Central

Lempert, Karolina M; Speer, Megan E; Delgado, Mauricio R

2017-01-01

Abstract People generally prefer rewards sooner rather than later. This phenomenon, temporal discounting, underlies many societal problems, including addiction and obesity. One way to reduce temporal discounting is to imagine positive future experiences. Since there is overlap in the neural circuitry associated with imagining future experiences and remembering past events, here we investigate whether recalling positive memories can also promote more patient choice. We found that participants were more patient after retrieving positive autobiographical memories, but not when they recalled negative memories. Moreover, individuals were more impulsive after imagining novel positive scenes that were not related to their memories, showing that positive imagery alone does not drive this effect. Activity in the striatum and temporo parietal junction during memory retrieval predicted more patient choice, suggesting that to the extent that memory recall is rewarding and involves perspective-taking, it influences decision-making. Furthermore, representational similarity in the ventromedial prefrontal cortex between memory recall and decision phases correlated with the behavioral effect across participants. Thus, we have identified a novel manipulation for reducing temporal discounting—remembering the positive past—and have begun to characterize the psychological and neural mechanisms behind it. PMID:28655195

Decoding the ubiquitous role of microRNAs in neurogenesis.

PubMed

Nampoothiri, Sreekala S; Rajanikant, G K

2017-04-01

Neurogenesis generates fledgling neurons that mature to form an intricate neuronal circuitry. The delusion on adult neurogenesis was far resolved in the past decade and became one of the largely explored domains to identify multifaceted mechanisms bridging neurodevelopment and neuropathology. Neurogenesis encompasses multiple processes including neural stem cell proliferation, neuronal differentiation, and cell fate determination. Each neurogenic process is specifically governed by manifold signaling pathways, several growth factors, coding, and non-coding RNAs. A class of small non-coding RNAs, microRNAs (miRNAs), is ubiquitously expressed in the brain and has emerged to be potent regulators of neurogenesis. It functions by fine-tuning the expression of specific neurogenic gene targets at the post-transcriptional level and modulates the development of mature neurons from neural progenitor cells. Besides the commonly discussed intrinsic factors, the neuronal morphogenesis is also under the control of several extrinsic temporal cues, which in turn are regulated by miRNAs. This review enlightens on dicer controlled switch from neurogenesis to gliogenesis, miRNA regulation of neuronal maturation and the differential expression of miRNAs in response to various extrinsic cues affecting neurogenesis.

Brain and Language: Evidence for Neural Multifunctionality

PubMed Central

Cahana-Amitay, Dalia; Albert, Martin L.

2014-01-01

This review paper presents converging evidence from studies of brain damage and longitudinal studies of language in aging which supports the following thesis: the neural basis of language can best be understood by the concept of neural multifunctionality. In this paper the term “neural multifunctionality” refers to incorporation of nonlinguistic functions into language models of the intact brain, reflecting a multifunctional perspective whereby a constant and dynamic interaction exists among neural networks subserving cognitive, affective, and praxic functions with neural networks specialized for lexical retrieval, sentence comprehension, and discourse processing, giving rise to language as we know it. By way of example, we consider effects of executive system functions on aspects of semantic processing among persons with and without aphasia, as well as the interaction of executive and language functions among older adults. We conclude by indicating how this multifunctional view of brain-language relations extends to the realm of language recovery from aphasia, where evidence of the influence of nonlinguistic factors on the reshaping of neural circuitry for aphasia rehabilitation is clearly emerging. PMID:25009368

The genetics of normal and defective color vision.

PubMed

Neitz, Jay; Neitz, Maureen

2011-04-13

The contributions of genetics research to the science of normal and defective color vision over the previous few decades are reviewed emphasizing the developments in the 25years since the last anniversary issue of Vision Research. Understanding of the biology underlying color vision has been vaulted forward through the application of the tools of molecular genetics. For all their complexity, the biological processes responsible for color vision are more accessible than for many other neural systems. This is partly because of the wealth of genetic variations that affect color perception, both within and across species, and because components of the color vision system lend themselves to genetic manipulation. Mutations and rearrangements in the genes encoding the long, middle, and short wavelength sensitive cone pigments are responsible for color vision deficiencies and mutations have been identified that affect the number of cone types, the absorption spectra of the pigments, the functionality and viability of the cones, and the topography of the cone mosaic. The addition of an opsin gene, as occurred in the evolution of primate color vision, and has been done in experimental animals can produce expanded color vision capacities and this has provided insight into the underlying neural circuitry. Copyright © 2010 Elsevier Ltd. All rights reserved.

Neural Mechanisms Underlying Lower Urinary Tract Dysfunction

PubMed Central

Ogawa, Teruyuki; Miyazato, Minoru; Kitta, Takeya; Furuta, Akira; Chancellor, Michael B.; Tyagi, Pradeep

2014-01-01

This article summarizes anatomical, neurophysiological, and pharmacological studies in humans and animals to provide insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract and alterations in these mechanisms in lower urinary tract dysfunction. The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These peripheral systems are integrated by excitatory and inhibitory regulation at the levels of the spinal cord and the brain. Therefore, injury or diseases of the nervous system, as well as disorders of the peripheral organs, can produce lower urinary tract dysfunction, leading to lower urinary tract symptoms, including both storage and voiding symptoms, and pelvic pain. Neuroplasticity underlying pathological changes in lower urinary tract function is discussed. PMID:24578802

Abnormal Neural Activation to Faces in the Parents of Children with Autism.

PubMed

Yucel, G H; Belger, A; Bizzell, J; Parlier, M; Adolphs, R; Piven, J

2015-12-01

Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the "Broad Autism Phenotype " (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality ("BAP+"). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Neuronal plasticity and seasonal reproduction in sheep

PubMed Central

Lehman, Michael N.; Ladha, Zamin; Coolen, Lique M.; Hileman, Stanley M.; Connors, John M.; Goodman, Robert L.

2010-01-01

Seasonal reproduction represents a naturally occurring example of functional plasticity in the adult brain since it reflects changes in neuroendocrine pathways controlling GnRH secretion and, in particular, the responsiveness of GnRH neurons to estradiol negative feedback. Structural plasticity within this neural circuitry may, in part, be responsible for seasonal switches in the negative feedback control of GnRH secretion that underlies annual reproductive transitions. In this paper, we review evidence for structural changes in the circuitry responsible for seasonal inhibition of GnRH secretion in sheep. These include changes in synaptic inputs onto GnRH neurons, as well as onto dopamine neurons in the A15 cell group, a nucleus that play a key role in estradiol negative feedback. We also present preliminary data suggesting a role for neurotrophins and neurotrophin receptors as an early mechanistic step in the plasticity that accompanies seasonal reproductive transitions in the sheep. Finally, we review recent evidence suggesting that kisspeptin cells of the arcuate nucleus constitute a critical intermediary in the control of seasonal reproduction. While a majority of the data for a role of neuronal plasticity in seasonal reproduction has come from the sheep model, the players and principles are likely to have relevance for reproduction in a wide variety of vertebrates, including humans, and in both health and disease. PMID:21143669

Reward loss and addiction: Opportunities for cross-pollination.

PubMed

Ortega, Leonardo A; Solano, José L; Torres, Carmen; Papini, Mauricio R

2017-03-01

Paradigms used to study the response to and consequences of exposure to reward loss have been underutilized in approaches to the psychobiology of substance use disorders. We propose here that bringing these two areas into contact will help expanding our understanding of both reward loss and addictive behavior, hence opening up opportunities for cross-pollination. This review focuses on two lines of research that point to parallels. First, several neurochemical systems involved in addiction are also involved in the modulation of the behavioral effects of reward loss, including opioid, GABA, and dopamine receptors. Second, there are extensive overlaps in the brain circuitry underlying both reward loss and addiction. Common components of this system include, at least, the amygdala, ventral and dorsal striatum, and various prefrontal cortex regions. Four emerging avenues of research that benefit from emphasis on the common ground between reward loss and addiction are reviewed, namely, the neural circuitry involved in reward devaluation, the influence of genetic and reward history on the behavioral vulnerability and resilience, the role of competing natural rewards, and emotional self-medication. An understanding of the role of reward loss in addiction will point to a deeper understanding of the initiation and maintenance of substance use disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Processing of social and monetary rewards in the human striatum.

PubMed

Izuma, Keise; Saito, Daisuke N; Sadato, Norihiro

2008-04-24

Despite an increasing focus on the neural basis of human decision making in neuroscience, relatively little attention has been paid to decision making in social settings. Moreover, although human social decision making has been explored in a social psychology context, few neural explanations for the observed findings have been considered. To bridge this gap and improve models of human social decision making, we investigated whether acquiring a good reputation, which is an important incentive in human social behaviors, activates the same reward circuitry as monetary rewards. In total, 19 subjects participated in functional magnetic resonance imaging (fMRI) experiments involving monetary and social rewards. The acquisition of one's good reputation robustly activated reward-related brain areas, notably the striatum, and these overlapped with the areas activated by monetary rewards. Our findings support the idea of a "common neural currency" for rewards and represent an important first step toward a neural explanation for complex human social behaviors.

Role of Autism Susceptibility Gene, CNTNAP2, in Neural Circuitry for Vocal Communication

DTIC Science & Technology

2012-10-01

experiments designed to test this hypothesis, we have now shown that FoxP2 protein in RA follows the mRNA pattern, with a striking change between...associated protein-like 2 (Cntnap2) is an exc iting molecule for the study of the genetic basis of language. In humans, Cntnap2 is a target of the FOXP2

Digital compression algorithms for HDTV transmission

NASA Technical Reports Server (NTRS)

Adkins, Kenneth C.; Shalkhauser, Mary JO; Bibyk, Steven B.

1990-01-01

Digital compression of video images is a possible avenue for high definition television (HDTV) transmission. Compression needs to be optimized while picture quality remains high. Two techniques for compression the digital images are explained and comparisons are drawn between the human vision system and artificial compression techniques. Suggestions for improving compression algorithms through the use of neural and analog circuitry are given.

Sleep: Helicon Cells Charge the Circuit.

PubMed

Yurgel, Maria E; Keene, Alex C

2018-04-02

A new study in the fruit fly, Drosophila melanogaster, has identified a neural circuitry that connects regions that control sleep with those that encode sleep pressure. These novel cells, termed helicon cells for their unique morphology, are modulated by sleep control centers and integrate sensory information, providing a novel mechanism for gating of sleep. Copyright © 2018 Elsevier Ltd. All rights reserved.

Converging on a core cognitive deficit: the impact of various neurodevelopmental insults on cognitive control

PubMed Central

O'Reilly, Kally C.; Kao, Hsin-Yi; Lee, Heekyung; Fenton, André A.

2014-01-01

Despite substantial effort and immense need, the treatment options for major neuropsychiatric illnesses like schizophrenia are limited and largely ineffective at improving the most debilitating cognitive symptoms that are central to mental illness. These symptoms include cognitive control deficits, the inability to selectively use information that is currently relevant and ignore what is currently irrelevant. Contemporary attempts to accelerate progress are in part founded on an effort to reconceptualize neuropsychiatric illness as a disorder of neural development. This neuro-developmental framework emphasizes abnormal neural circuits on the one hand, and on the other, it suggests there are therapeutic opportunities to exploit the developmental processes of excitatory neuron pruning, inhibitory neuron proliferation, elaboration of myelination, and other circuit refinements that extend through adolescence and into early adulthood. We have crafted a preclinical research program aimed at cognition failures that may be relevant to mental illness. By working with a variety of neurodevelopmental rodent models, we strive to identify a common pathophysiology that underlies cognitive control failure as well as a common strategy for improving cognition in the face of neural circuit abnormalities. Here we review our work to characterize cognitive control deficits in rats with a neonatal ventral hippocampus lesion and rats that were exposed to Methylazoxymethanol acetate (MAM) in utero. We review our findings as they pertain to early developmental processes, including neurogenesis, as well as the power of cognitive experience to refine neural circuit function within the mature and maturing brain's cognitive circuitry. PMID:24966811

Insect Responses to Linearly Polarized Reflections: Orphan Behaviors Without Neural Circuits

PubMed Central

Heinloth, Tanja; Uhlhorn, Juliane; Wernet, Mathias F.

2018-01-01

The e-vector orientation of linearly polarized light represents an important visual stimulus for many insects. Especially the detection of polarized skylight by many navigating insect species is known to improve their orientation skills. While great progress has been made towards describing both the anatomy and function of neural circuit elements mediating behaviors related to navigation, relatively little is known about how insects perceive non-celestial polarized light stimuli, like reflections off water, leaves, or shiny body surfaces. Work on different species suggests that these behaviors are not mediated by the “Dorsal Rim Area” (DRA), a specialized region in the dorsal periphery of the adult compound eye, where ommatidia contain highly polarization-sensitive photoreceptor cells whose receptive fields point towards the sky. So far, only few cases of polarization-sensitive photoreceptors have been described in the ventral periphery of the insect retina. Furthermore, both the structure and function of those neural circuits connecting to these photoreceptor inputs remain largely uncharacterized. Here we review the known data on non-celestial polarization vision from different insect species (dragonflies, butterflies, beetles, bugs and flies) and present three well-characterized examples for functionally specialized non-DRA detectors from different insects that seem perfectly suited for mediating such behaviors. Finally, using recent advances from circuit dissection in Drosophila melanogaster, we discuss what types of potential candidate neurons could be involved in forming the underlying neural circuitry mediating non-celestial polarization vision. PMID:29615868

Prefrontal consolidation supports the attainment of fear memory accuracy.

PubMed

Vieira, Philip A; Lovelace, Jonathan W; Corches, Alex; Rashid, Asim J; Josselyn, Sheena A; Korzus, Edward

2014-08-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive. © 2014 Vieira et al.; Published by Cold Spring Harbor Laboratory Press.

Sociability and synapse subtype-specific defects in mice lacking SRPX2, a language-associated gene

PubMed Central

Cong, Qifei; Palmer, Christian R.

2018-01-01

The FoxP2 transcription factor and its target genes have been implicated in developmental brain diseases with a prominent language component, such as developmental verbal dyspraxia and specific language impairment. How FoxP2 affects neural circuitry development remains poorly understood. The sushi domain protein SRPX2 is a target of FoxP2, and mutations in SRPX2 are associated with language defects in humans. We have previously shown that SRPX2 is a synaptogenic protein that increases excitatory synapse density. Here we provide the first characterization of mice lacking the SRPX2 gene, and show that these mice exhibit defects in both neural circuitry and communication and social behaviors. Specifically, we show that mice lacking SRPX2 show a specific reduction in excitatory VGlut2 synapses in the cerebral cortex, while VGlut1 and inhibitory synapses were largely unaffected. SRPX2 KO mice also exhibit an abnormal ultrasonic vocalization ontogenetic profile in neonatal pups, and reduced preference for social novelty. These data demonstrate a functional role for SRPX2 during brain development, and further implicate FoxP2 and its targets in regulating the development of vocalization and social circuits. PMID:29920554

Lateralization of the human mirror neuron system.

PubMed

Aziz-Zadeh, Lisa; Koski, Lisa; Zaidel, Eran; Mazziotta, John; Iacoboni, Marco

2006-03-15

A cortical network consisting of the inferior frontal, rostral inferior parietal, and posterior superior temporal cortices has been implicated in representing actions in the primate brain and is critical to imitation in humans. This neural circuitry may be an evolutionary precursor of neural systems associated with language. However, language is predominantly lateralized to the left hemisphere, whereas the degree of lateralization of the imitation circuitry in humans is unclear. We conducted a functional magnetic resonance imaging study of imitation of finger movements with lateralized stimuli and responses. During imitation, activity in the inferior frontal and rostral inferior parietal cortex, although fairly bilateral, was stronger in the hemisphere ipsilateral to the visual stimulus and response hand. This ipsilateral pattern is at variance with the typical contralateral activity of primary visual and motor areas. Reliably increased signal in the right superior temporal sulcus (STS) was observed for both left-sided and right-sided imitation tasks, although subthreshold activity was also observed in the left STS. Overall, the data indicate that visual and motor components of the human mirror system are not left-lateralized. The left hemisphere superiority for language, then, must be have been favored by other types of language precursors, perhaps auditory or multimodal action representations.

Context-driven Salt Seeking Test (Rats)

PubMed Central

Chang, Stephen E.; Smith, Kyle S.

2018-01-01

Changes in reward seeking behavior often occur through incremental learning based on the difference between what is expected and what actually happens. Behavioral flexibility of this sort requires experience with rewards as better or worse than expected. However, there are some instances in which behavior can change through non-incremental learning, which requires no further experience with an outcome. Such an example of non-incremental learning is the salt appetite phenomenon. In this case, animals such as rats will immediately seek out a highly-concentrated salt solution that was previously undesired when they are put in a novel state of sodium deprivation. Importantly, this adaptive salt-seeking behavior occurs despite the fact that the rats never tasted salt in the depleted state, and therefore never tasted it as a highly desirable reward. The following protocol is a method to investigate the neural circuitry mediating adaptive salt seeking using a conditioned place preference (CPP) procedure. The procedure is designed to provide an opportunity to discover possible dissociations between the neural circuitry mediating salt seeking and salt consumption to replenish the bodily deficit after sodium depletion. Additionally, this procedure is amenable to incorporating a number of neurobiological techniques for studying the brain basis of this behavior.

Structural and functional maturation of the developing primate brain.

PubMed

Levitt, Pat

2003-10-01

Descriptive studies have established that the developmental events responsible for the assembly of neural systems and circuitry are conserved across mammalian species. However, primates are unique regarding the time during which histogenesis occurs and the extended postnatal period during which myelination of pathways and circuitry formation occur and are then subsequently modified, particularly in the cerebral cortex. As in lower mammals, the framework for subcortical-cortical connectivity in primates is established before midgestation and already begins to remodel before birth. Association systems, responsible for modulating intracortical circuits that integrate information across functional domains, also form before birth, but their growth and reorganization extend into puberty. There are substantial differences across species in the patterns of development of specific neurochemical systems. The complexity is even greater when considering that the development of any particular cellular component may differ among cortical areas in the same primate species. Developmental and behavioral neurobiologists, psychologists, and pediatricians are challenged with understanding how functional maturation relates to the evolving anatomical organization of the human brain during childhood, and moreover, how genetic and environmental perturbations affect the adaptive changes exhibited by neural circuits in response to developmental disruption.

Cost-benefit decision circuitry: proposed modulatory role for acetylcholine.

PubMed

Fobbs, Wambura C; Mizumori, Sheri J Y

2014-01-01

In order to select which action should be taken, an animal must weigh the costs and benefits of possible outcomes associate with each action. Such decisions, called cost-benefit decisions, likely involve several cognitive processes (including memory) and a vast neural circuitry. Rodent models have allowed research to begin to probe the neural basis of three forms of cost-benefit decision making: effort-, delay-, and risk-based decision making. In this review, we detail the current understanding of the functional circuits that subserve each form of decision making. We highlight the extensive literature by detailing the ability of dopamine to influence decisions by modulating structures within these circuits. Since acetylcholine projects to all of the same important structures, we propose several ways in which the cholinergic system may play a local modulatory role that will allow it to shape these behaviors. A greater understanding of the contribution of the cholinergic system to cost-benefit decisions will permit us to better link the decision and memory processes, and this will help us to better understand and/or treat individuals with deficits in a number of higher cognitive functions including decision making, learning, memory, and language. © 2014 Elsevier Inc. All rights reserved.

Two organizing principles of vocal production: Implications for nonhuman and human primates.

PubMed

Owren, Michael J; Amoss, R Toby; Rendall, Drew

2011-06-01

Vocal communication in nonhuman primates receives considerable research attention, with many investigators arguing for similarities between this calling and speech in humans. Data from development and neural organization show a central role of affect in monkey and ape sounds, however, suggesting that their calls are homologous to spontaneous human emotional vocalizations while having little relation to spoken language. Based on this evidence, we propose two principles that can be useful in evaluating the many and disparate empirical findings that bear on the nature of vocal production in nonhuman and human primates. One principle distinguishes production-first from reception-first vocal development, referring to the markedly different role of auditory-motor experience in each case. The second highlights a phenomenon dubbed dual neural pathways, specifically that when a species with an existing vocal system evolves a new functionally distinct vocalization capability, it occurs through emergence of a second parallel neural pathway rather than through expansion of the extant circuitry. With these principles as a backdrop, we review evidence of acoustic modification of calling associated with background noise, conditioning effects, audience composition, and vocal convergence and divergence in nonhuman primates. Although each kind of evidence has been interpreted to show flexible cognitively mediated control over vocal production, we suggest that most are more consistent with affectively grounded mechanisms. The lone exception is production of simple, novel sounds in great apes, which is argued to reveal at least some degree of volitional vocal control. If also present in early hominins, the cortically based circuitry surmised to be associated with these rudimentary capabilities likely also provided the substrate for later emergence of the neural pathway allowing volitional production in modern humans. © 2010 Wiley-Liss, Inc.

Genetic subtype differences in neural circuitry of food motivation in Prader-Willi syndrome.

PubMed

Holsen, L M; Zarcone, J R; Chambers, R; Butler, M G; Bittel, D C; Brooks, W M; Thompson, T I; Savage, C R

2009-02-01

Differences in behavioral phenotypes between the two most common subtypes of Prader-Willi syndrome (PWS) (chromosome 15q deletions and maternal uniparental disomy 15 (UPD) indicate that distinct neural networks may be affected. Though both subtypes display hyperphagia, the deletion subgroup shows reduced behavioral inhibition around food, whereas those with UPD are generally more able to maintain cognitive control over food intake impulses. To examine the neural basis of phenotypic differences to better understand relationships between genetic subtypes and behavioral outcomes. We predicted greater food motivation circuitry activity in the deletion subtype and greater activity in higher order cognitive regions in the UPD group, especially after eating. Nine individuals with PWS due to UPD and nine individuals with PWS due to (type 2) deletion, matched for age, gender and body mass index, underwent functional magnetic resonance imaging (fMRI) while viewing food images during two food motivation states: one before (pre-meal) and one after (post-meal) eating a standardized 500 kcal meal. Both PWS subgroups showed greater activity in response to food pre- and post-meal compared with the healthy-weight group. Compared with UPD, the deletion subtype showed increased food motivation network activation both pre- and post-meal, especially in the medial prefrontal cortex (mPFC) and amygdala. In contrast, the UPD group showed greater activation than the deletion subtype post-meal in the dorsolateral prefrontal cortex (DLPFC) and parahippocampal gyrus (PHG). These preliminary findings are the first functional neuroimaging findings to support divergent neural mechanisms associated with behavioral phenotypes in genetic subtypes of PWS. Results are discussed within the framework of genetic mechanisms such as haploinsufficiency and gene dosage effects and their differential influence on deletion and UPD subtypes, respectively.

Self-Affirmation Activates the Ventral Striatum: A Possible Reward-Related Mechanism for Self-Affirmation.

PubMed

Dutcher, Janine M; Creswell, J David; Pacilio, Laura E; Harris, Peter R; Klein, William M P; Levine, John M; Bower, Julienne E; Muscatell, Keely A; Eisenberger, Naomi I

2016-04-01

Self-affirmation (reflecting on important personal values) has been shown to have a range of positive effects; however, the neural basis of self-affirmation is not known. Building on studies showing that thinking about self-preferences activates neural reward pathways, we hypothesized that self-affirmation would activate brain reward circuitry during functional MRI (fMRI) studies. In Study 1, with college students, making judgments about important personal values during self-affirmation activated neural reward regions (i.e., ventral striatum), whereas making preference judgments that were not self-relevant did not. Study 2 replicated these results in a community sample, again showing that self-affirmation activated the ventral striatum. These are among the first fMRI studies to identify neural processes during self-affirmation. The findings extend theory by showing that self-affirmation may be rewarding and may provide a first step toward identifying a neural mechanism by which self-affirmation may produce a wide range of beneficial effects. © The Author(s) 2016.

Neuroimaging in attention-deficit hyperactivity disorder: beyond the frontostriatal circuitry.

PubMed

Cherkasova, Mariya V; Hechtman, Lily

2009-10-01

To review the findings of structural and functional neuroimaging studies in attention-deficit hyperactivity disorder (ADHD), with a focus on abnormalities reported in brain regions that lie outside the frontostriatal circuitry, which is currently believed to play a central role in the pathophysiology of ADHD. Relevant publications were found primarily by searching the MEDLINE and PubMed databases using the keywords ADHD and the abbreviations of magnetic resonance imaging (MRI), functional MRI, positron emission tomography, and single photon emission computed tomography. The reference lists of the articles found through the databases were then reviewed for the purpose of finding additional articles. There is now substantial evidence of structural and functional alterations in regions outside the frontostriatal circuitry in ADHD, most notably in the cerebellum and the parietal lobes. Although there is compelling evidence suggesting that frontostriatal dysfunction may be central to the pathophysiology of ADHD, the neuroimaging findings point to distributed neural substrates rather than a single one. More research is needed to elucidate the nature of contributions of nonfrontostriatal regions to the pathophysiology of ADHD.

Reward Circuitry Plasticity in Pain Perception and Modulation

PubMed Central

DosSantos, Marcos F.; Moura, Brenda de Souza; DaSilva, Alexandre F.

2017-01-01

Although pain is a widely known phenomenon and an important clinical symptom that occurs in numerous diseases, its mechanisms are still barely understood. Owing to the scarce information concerning its pathophysiology, particularly what is involved in the transition from an acute state to a chronic condition, pain treatment is frequently unsatisfactory, therefore contributing to the amplification of the chronic pain burden. In fact, pain is an extremely complex experience that demands the recruitment of an intricate set of central nervous system components. This includes cortical and subcortical areas involved in interpretation of the general characteristics of noxious stimuli. It also comprises neural circuits that process the motivational-affective dimension of pain. Hence, the reward circuitry represents a vital element for pain experience and modulation. This review article focuses on the interpretation of the extensive data available connecting the major components of the reward circuitry to pain suffering, including the nucleus accumbens, ventral tegmental area, and the medial prefrontal cortex; with especial attention dedicated to the evaluation of neuroplastic changes affecting these structures found in chronic pain syndromes, such as migraine, trigeminal neuropathic pain, chronic back pain, and fibromyalgia. PMID:29209204

Evolution of central pattern generators and rhythmic behaviours

PubMed Central

Katz, Paul S.

2016-01-01

Comparisons of rhythmic movements and the central pattern generators (CPGs) that control them uncover principles about the evolution of behaviour and neural circuits. Over the course of evolutionary history, gradual evolution of behaviours and their neural circuitry within any lineage of animals has been a predominant occurrence. Small changes in gene regulation can lead to divergence of circuit organization and corresponding changes in behaviour. However, some behavioural divergence has resulted from large-scale rewiring of the neural network. Divergence of CPG circuits has also occurred without a corresponding change in behaviour. When analogous rhythmic behaviours have evolved independently, it has generally been with different neural mechanisms. Repeated evolution of particular rhythmic behaviours has occurred within some lineages due to parallel evolution or latent CPGs. Particular motor pattern generating mechanisms have also evolved independently in separate lineages. The evolution of CPGs and rhythmic behaviours shows that although most behaviours and neural circuits are highly conserved, the nature of the behaviour does not dictate the neural mechanism and that the presence of homologous neural components does not determine the behaviour. This suggests that although behaviour is generated by neural circuits, natural selection can act separately on these two levels of biological organization. PMID:26598733

Evolution of central pattern generators and rhythmic behaviours.

PubMed

Katz, Paul S

2016-01-05

Comparisons of rhythmic movements and the central pattern generators (CPGs) that control them uncover principles about the evolution of behaviour and neural circuits. Over the course of evolutionary history, gradual evolution of behaviours and their neural circuitry within any lineage of animals has been a predominant occurrence. Small changes in gene regulation can lead to divergence of circuit organization and corresponding changes in behaviour. However, some behavioural divergence has resulted from large-scale rewiring of the neural network. Divergence of CPG circuits has also occurred without a corresponding change in behaviour. When analogous rhythmic behaviours have evolved independently, it has generally been with different neural mechanisms. Repeated evolution of particular rhythmic behaviours has occurred within some lineages due to parallel evolution or latent CPGs. Particular motor pattern generating mechanisms have also evolved independently in separate lineages. The evolution of CPGs and rhythmic behaviours shows that although most behaviours and neural circuits are highly conserved, the nature of the behaviour does not dictate the neural mechanism and that the presence of homologous neural components does not determine the behaviour. This suggests that although behaviour is generated by neural circuits, natural selection can act separately on these two levels of biological organization. © 2015 The Author(s).

Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

PubMed Central

Phillips, Mary L.; Chase, Henry W.; Sheline, Yvette I.; Etkin, Amit; Almeida, Jorge R.C.; Deckersbach, Thilo; Trivedi, Madhukar H.

2015-01-01

Objective Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes. PMID:25640931

Neurophysiology and Neuroanatomy of Reflexive and Volitional Saccades: Evidence from Studies of Humans

PubMed Central

McDowell, Jennifer E.; Dyckman, Kara A.; Austin, Benjamin; Clementz, Brett A.

2008-01-01

This review provides a summary of the contributions made by human functional neuroimaging studies to the understanding of neural correlates of saccadic control. The generation of simple visually-guided saccades (redirections of gaze to a visual stimulus or prosaccades) and more complex volitional saccades require similar basic neural circuitry with additional neural regions supporting requisite higher level processes. The saccadic system has been studied extensively in non-human primates (e.g. single unit recordings) and humans (e.g. lesions and neuroimaging). Considerable knowledge of this system’s functional neuroanatomy makes it useful for investigating models of cognitive control. The network involved in prosaccade generation (by definition exogenously-driven) includes subcortical (striatum, thalamus, superior colliculus, and cerebellar vermis) and cortical structures (primary visual, extrastriate, and parietal cortices, and frontal and supplementary eye fields). Activation in these regions is also observed during endogenously-driven voluntary saccades (e.g. antisaccades, ocular motor delayed response or memory saccades, predictive tracking tasks and anticipatory saccades, and saccade sequencing), all of which require complex cognitive processes like inhibition and working memory. These additional requirements are supported by changes in neural activity in basic saccade circuitry and by recruitment of additional neural regions (such as prefrontal and anterior cingulate cortices). Activity in visual cortex is modulated as a function of task demands and may predict the type of saccade to be generated, perhaps via top-down control mechanisms. Neuroimaging studies suggest two foci of activation within FEF - medial and lateral - which may correspond to volitional and reflexive demands, respectively. Future research on saccade control could usefully (i) delineate important anatomical subdivisions that underlie functional differences, (ii) evaluate functional connectivity of anatomical regions supporting saccade generation using methods such as ICA and structural equation modeling, (iii) investigate how context affects behavior and brain activity, and (iv) use multi-modal neuroimaging to maximize spatial and temporal resolution. PMID:18835656

A sleep state in Drosophila larvae required for neural stem cell proliferation

PubMed Central

Szuperak, Milan; Churgin, Matthew A; Borja, Austin J; Raizen, David M; Fang-Yen, Christopher

2018-01-01

Sleep during development is involved in refining brain circuitry, but a role for sleep in the earliest periods of nervous system elaboration, when neurons are first being born, has not been explored. Here we identify a sleep state in Drosophila larvae that coincides with a major wave of neurogenesis. Mechanisms controlling larval sleep are partially distinct from adult sleep: octopamine, the Drosophila analog of mammalian norepinephrine, is the major arousal neuromodulator in larvae, but dopamine is not required. Using real-time behavioral monitoring in a closed-loop sleep deprivation system, we find that sleep loss in larvae impairs cell division of neural progenitors. This work establishes a system uniquely suited for studying sleep during nascent periods, and demonstrates that sleep in early life regulates neural stem cell proliferation. PMID:29424688

Closed-Loop and Activity-Guided Optogenetic Control

PubMed Central

Grosenick, Logan; Marshel, James H.; Deisseroth, Karl

2016-01-01

Advances in optical manipulation and observation of neural activity have set the stage for widespread implementation of closed-loop and activity-guided optical control of neural circuit dynamics. Closing the loop optogenetically (i.e., basing optogenetic stimulation on simultaneously observed dynamics in a principled way) is a powerful strategy for causal investigation of neural circuitry. In particular, observing and feeding back the effects of circuit interventions on physiologically relevant timescales is valuable for directly testing whether inferred models of dynamics, connectivity, and causation are accurate in vivo. Here we highlight technical and theoretical foundations as well as recent advances and opportunities in this area, and we review in detail the known caveats and limitations of optogenetic experimentation in the context of addressing these challenges with closed-loop optogenetic control in behaving animals. PMID:25856490

Real-Time Adaptive Color Segmentation by Neural Networks

NASA Technical Reports Server (NTRS)

Duong, Tuan A.

2004-01-01

Artificial neural networks that would utilize the cascade error projection (CEP) algorithm have been proposed as means of autonomous, real-time, adaptive color segmentation of images that change with time. In the original intended application, such a neural network would be used to analyze digitized color video images of terrain on a remote planet as viewed from an uninhabited spacecraft approaching the planet. During descent toward the surface of the planet, information on the segmentation of the images into differently colored areas would be updated adaptively in real time to capture changes in contrast, brightness, and resolution, all in an effort to identify a safe and scientifically productive landing site and provide control feedback to steer the spacecraft toward that site. Potential terrestrial applications include monitoring images of crops to detect insect invasions and monitoring of buildings and other facilities to detect intruders. The CEP algorithm is reliable and is well suited to implementation in very-large-scale integrated (VLSI) circuitry. It was chosen over other neural-network learning algorithms because it is better suited to realtime learning: It provides a self-evolving neural-network structure, requires fewer iterations to converge and is more tolerant to low resolution (that is, fewer bits) in the quantization of neural-network synaptic weights. Consequently, a CEP neural network learns relatively quickly, and the circuitry needed to implement it is relatively simple. Like other neural networks, a CEP neural network includes an input layer, hidden units, and output units (see figure). As in other neural networks, a CEP network is presented with a succession of input training patterns, giving rise to a set of outputs that are compared with the desired outputs. Also as in other neural networks, the synaptic weights are updated iteratively in an effort to bring the outputs closer to target values. A distinctive feature of the CEP neural network and algorithm is that each update of synaptic weights takes place in conjunction with the addition of another hidden unit, which then remains in place as still other hidden units are added on subsequent iterations. For a given training pattern, the synaptic weight between (1) the inputs and the previously added hidden units and (2) the newly added hidden unit is updated by an amount proportional to the partial derivative of a quadratic error function with respect to the synaptic weight. The synaptic weight between the newly added hidden unit and each output unit is given by a more complex function that involves the errors between the outputs and their target values, the transfer functions (hyperbolic tangents) of the neural units, and the derivatives of the transfer functions.

Dendritic Spine Pathology in Schizophrenia

PubMed Central

Glausier, Jill R.; Lewis, David A.

2012-01-01

Schizophrenia is a neurodevelopmental disorder whose clinical features include impairments in perception, cognition and motivation. These impairments reflect alterations in neuronal circuitry within and across multiple brain regions that are due, at least in part, to deficits in dendritic spines, the site of most excitatory synaptic connections. Dendritic spine alterations have been identified in multiple brain regions in schizophrenia, but are best characterized in layer 3 of the neocortex, where pyramidal cell spine density is lower. These spine deficits appear to arise during development, and thus are likely the result of disturbances in the molecular mechanisms that underlie spine formation, pruning, and/or maintenance. Each of these mechanisms may provide insight into novel therapeutic targets for preventing or repairing the alterations in neural circuitry that mediate the debilitating symptoms of schizophrenia. PMID:22546337

Spatiotemporal dissociation of brain activity underlying threat and reward in social anxiety disorder.

PubMed

A Richey, John; Ghane, Merage; Valdespino, Andrew; Coffman, Marika C; Strege, Marlene V; White, Susan W; Ollendick, Thomas H

2017-01-01

Social anxiety disorder (SAD) involves abnormalities in social motivation, which may be independent of well-documented differences in fear and arousal systems. Yet, the neurobiology underlying motivational difficulties in SAD is not well understood. The aim of the current study was to spatiotemporally dissociate reward circuitry dysfunction from alterations in fear and arousal-related neural activity during anticipation and notification of social and non-social reward and punishment. During fMRI acquisition, non-depressed adults with social anxiety disorder (SAD; N = 21) and age-, sex- and IQ-matched control subjects (N = 22) completed eight runs of an incentive delay task, alternating between social and monetary outcomes and interleaved in alternating order between gain and loss outcomes. Adults with SAD demonstrated significantly reduced neural activity in ventral striatum during the anticipation of positive but not negative social outcomes. No differences between the SAD and control groups were observed during anticipation of monetary gain or loss outcomes or during anticipation of negative social images. However, consistent with previous work, the SAD group demonstrated amygdala hyper-activity upon notification of negative social outcomes. Degraded anticipatory processing in bilateral ventral striatum in SAD was constrained exclusively to anticipation of positive social information and dissociable from the effects of negative social outcomes previously observed in the amygdala. Alterations in anticipation-related neural signals may represent a promising target for treatment that is not addressed by available evidence-based interventions, which focus primarily on fear extinction and habituation processes. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Evolutionary Origins for Social Vocalization in a Vertebrate Hindbrain–Spinal Compartment

PubMed Central

Bass, Andrew H.; Gilland, Edwin H.; Baker, Robert

2008-01-01

The macroevolutionary events leading to neural innovations for social communication, such as vocalization, are essentially unexplored. Many fish vocalize during female courtship and territorial defense, as do amphibians, birds, and mammals. Here, we map the neural circuitry for vocalization in larval fish and show that the vocal network develops in a segment-like region across the most caudal hindbrain and rostral spinal cord. Taxonomic analysis demonstrates a highly conserved pattern between fish and all major lineages of vocal tetrapods. We propose that the vocal basis for acoustic communication among vertebrates evolved from an ancestrally shared developmental compartment already present in the early fishes. PMID:18635807

Exposure to an obesogenic diet during adolescence leads to abnormal maturation of neural and behavioral substrates underpinning fear and anxiety.

PubMed

Vega-Torres, Julio David; Haddad, Elizabeth; Lee, Jeong Bin; Kalyan-Masih, Priya; Maldonado George, Wanda I; López Pérez, Leonardo; Piñero Vázquez, Darla M; Arroyo Torres, Yaría; Santiago Santana, José M; Obenaus, Andre; Figueroa, Johnny D

2018-05-01

Post-traumatic stress disorder (PTSD) and obesity are highly prevalent in adolescents. Emerging findings from our laboratory and others are consistent with the novel hypothesis that obese individuals may be predisposed to developing PTSD. Given that aberrant fear responses are pivotal in the pathogenesis of PTSD, the objective of this study was to determine the impact of an obesogenic Western-like high-fat diet (WD) on neural substrates associated with fear. Adolescent Lewis rats (n = 72) were fed with either the experimental WD (41.4% kcal from fat) or the control diet. The fear-potentiated startle paradigm was used to determine sustained and phasic fear responses. Diffusion tensor imaging metrics and T2 relaxation times were used to determine the structural integrity of the fear circuitry including the medial prefrontal cortex (mPFC) and the basolateral complex of the amygdala (BLA). The rats that consumed the WD exhibited attenuated fear learning and fear extinction. These behavioral impairments were associated with oversaturation of the fear circuitry and astrogliosis. The BLA T2 relaxation times were significantly decreased in the WD rats relative to the controls. We found elevated fractional anisotropy in the mPFC of the rats that consumed the WD. We show that consumption of a WD may lead to long-lasting damage to components of the fear circuitry. Our findings demonstrate that consumption of an obesogenic diet during adolescence has a profound impact in the maturation of the fear neurocircuitry. The implications of this research are significant as they identify potential biomarkers of risk for psychopathology in the growing obese population. Copyright © 2018 Elsevier Inc. All rights reserved.

Differential Patterns of Abnormal Activity and Connectivity in the Amygdala-Prefrontal Circuitry in Bipolar-I and Bipolar-NOS Youth

ERIC Educational Resources Information Center

Ladouceur, Cecile D.; Farchione, Tiffany; Diwadkar, Vaibhav; Pruitt, Patrick; Radwan, Jacqueline; Axelson, David A.; Birmaher, Boris; Phillips, Mary L.

2011-01-01

Objective: The functioning of neural systems supporting emotion processing and regulation in youth with bipolar disorder not otherwise specified (BP-NOS) remains poorly understood. We sought to examine patterns of activity and connectivity in youth with BP-NOS relative to youth with bipolar disorder type I (BP-I) and healthy controls (HC). Method:…

Achievements for Developing a Technology to Manage Post-Traumatic Pain With Ultrasound Neuromodulation

DTIC Science & Technology

2012-01-03

REPORT Phase 1 achievements for developing a technology to manage post-traumatic pain with ultrasound neuromodulation . 14. ABSTRACT 16. SECURITY...CLASSIFICATION OF: The objective of this effort is to demonstrate the feasibility of using ultrasound induced neuromodulation to manage pain. SynSonix, LLC...has been developing ultrasound neuromodulation (UNMOD) to noninvasively stimulate neural circuitry. Pain management for acute traumas is generally

The GABA system in schizophrenia: cells, molecules and microcircuitry.

PubMed

Benes, Francine M

2015-09-01

This is an overview of several papers that have been published in the Special Issue of Schizophrenia Research entitled The GABA System in Schizophrenia: Cells, Molecules and Microcircuitry. This issue presents a broad range of original reports and scholarly reviews regarding recent progress in studies of neural circuitry in corticolimbic brain regions in patients with schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

Age-dependent long-term structural and functional effects of early life seizures: evidence for a hippocampal critical period influencing plasticity in adulthood

PubMed Central

Meyerand, M.E.; Sutula, T.

2015-01-01

Neural activity promotes circuit formation in developing systems and during critical periods permanently modifies circuit organization and functional properties. These observations suggest that excessive neural activity, as occurs during seizures, might influence developing neural circuitry with long-term outcomes that depend on age at the time of seizures. We systematically examined long-term structural and functional consequences of seizures induced in rats by kainic acid, pentylenetetrazol, and hyperthermia across postnatal ages from birth through postnatal day 90 in adulthood (P90). Magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and electrophysiological methods at ≥P95 following seizures induced from P1 to P90 demonstrated consistent patterns of gross atrophy, microstructural abnormalities in the corpus callosum and hippocampus, and functional alterations in hippocampal circuitry at ≥P95 that were independent of the method of seizure induction and varied systematically as a function of age at the time of seizures. Three distinct epochs were observed in which seizures resulted in distinct long-term structural and functional outcomes at ≥P95. Seizures prior to P20 resulted in DTI abnormalities in corpus callosum and hippocampus in the absence of gross cerebral atrophy, and increased paired pulse inhibition (PPI) in the dentate gyrus at ≥P95. Seizures after P30 induced a different pattern of DTI abnormalities in the fimbria and hippocampus accompanied by gross cerebral atrophy with increases in lateral ventricular volume, as well as increased PPI in the dentate gyrus at ≥P95. In contrast, seizures between P20-P30 did not result in cerebral atrophy or significant imaging abnormalities in the hippocampus or white matter, but irreversibly decreased PPI in the dentate gyrus compared to normal adult controls. These age-specific long-term structural and functional outcomes identify P20-P30 as a potential critical period in hippocampal development defined by distinctive long-term structural and functional properties in adult hippocampal circuitry, including loss of capacity for seizure-induced plasticity in adulthood that could influence epileptogenesis and other hippocampal – dependent behaviors and functional properties. PMID:25555928

A Subconscious Interaction between Fixation and Anticipatory Pursuit

PubMed Central

Bal, Japjot; Heinen, Stephen J.

2017-01-01

Ocular smooth pursuit and fixation are typically viewed as separate systems, yet there is evidence that the brainstem fixation system inhibits pursuit. Here we present behavioral evidence that the fixation system modulates pursuit behavior outside of conscious awareness. Human observers (male and female) either pursued a small spot that translated across a screen, or fixated it as it remained stationary. As shown previously, pursuit trials potentiated the oculomotor system, producing anticipatory eye velocity on the next trial before the target moved that mimicked the stimulus-driven velocity. Randomly interleaving fixation trials reduced anticipatory pursuit, suggesting that a potentiated fixation system interacted with pursuit to suppress eye velocity in upcoming pursuit trials. The reduction was not due to passive decay of the potentiated pursuit signal because interleaving “blank” trials in which no target appeared did not reduce anticipatory pursuit. Interspersed short fixation trials reduced anticipation on long pursuit trials, suggesting that fixation potentiation was stronger than pursuit potentiation. Furthermore, adding more pursuit trials to a block did not restore anticipatory pursuit, suggesting that fixation potentiation was not overridden by certainty of an imminent pursuit trial but rather was immune to conscious intervention. To directly test whether cognition can override fixation suppression, we alternated pursuit and fixation trials to perfectly specify trial identity. Still, anticipatory pursuit did not rise above that observed with an equal number of random fixation trials. The results suggest that potentiated fixation circuitry interacts with pursuit circuitry at a subconscious level to inhibit pursuit. SIGNIFICANCE STATEMENT When an object moves, we view it with smooth pursuit eye movements. When an object is stationary, we view it with fixational eye movements. Pursuit and fixation are historically regarded as controlled by different neural circuitry, and alternating between invoking them is thought to be guided by a conscious decision. However, our results show that pursuit is actively suppressed by prior fixation of a stationary object. This suppression is involuntary, and cannot be avoided even if observers are certain that the object will move. The results suggest that the neural fixation circuitry is potentiated by engaging stationary objects, and interacts with pursuit outside of conscious awareness. PMID:29061701

A Subconscious Interaction between Fixation and Anticipatory Pursuit.

PubMed

Watamaniuk, Scott N J; Bal, Japjot; Heinen, Stephen J

2017-11-22

Ocular smooth pursuit and fixation are typically viewed as separate systems, yet there is evidence that the brainstem fixation system inhibits pursuit. Here we present behavioral evidence that the fixation system modulates pursuit behavior outside of conscious awareness. Human observers (male and female) either pursued a small spot that translated across a screen, or fixated it as it remained stationary. As shown previously, pursuit trials potentiated the oculomotor system, producing anticipatory eye velocity on the next trial before the target moved that mimicked the stimulus-driven velocity. Randomly interleaving fixation trials reduced anticipatory pursuit, suggesting that a potentiated fixation system interacted with pursuit to suppress eye velocity in upcoming pursuit trials. The reduction was not due to passive decay of the potentiated pursuit signal because interleaving "blank" trials in which no target appeared did not reduce anticipatory pursuit. Interspersed short fixation trials reduced anticipation on long pursuit trials, suggesting that fixation potentiation was stronger than pursuit potentiation. Furthermore, adding more pursuit trials to a block did not restore anticipatory pursuit, suggesting that fixation potentiation was not overridden by certainty of an imminent pursuit trial but rather was immune to conscious intervention. To directly test whether cognition can override fixation suppression, we alternated pursuit and fixation trials to perfectly specify trial identity. Still, anticipatory pursuit did not rise above that observed with an equal number of random fixation trials. The results suggest that potentiated fixation circuitry interacts with pursuit circuitry at a subconscious level to inhibit pursuit. SIGNIFICANCE STATEMENT When an object moves, we view it with smooth pursuit eye movements. When an object is stationary, we view it with fixational eye movements. Pursuit and fixation are historically regarded as controlled by different neural circuitry, and alternating between invoking them is thought to be guided by a conscious decision. However, our results show that pursuit is actively suppressed by prior fixation of a stationary object. This suppression is involuntary, and cannot be avoided even if observers are certain that the object will move. The results suggest that the neural fixation circuitry is potentiated by engaging stationary objects, and interacts with pursuit outside of conscious awareness. Copyright © 2017 the authors 0270-6474/17/3711424-07$15.00/0.

Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa.

PubMed

Holsen, Laura M; Lawson, Elizabeth A; Blum, Justine; Ko, Eunice; Makris, Nikos; Fazeli, Pouneh K; Klibanski, Anne; Goldstein, Jill M

2012-09-01

Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait. We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal. We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease. Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included. Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food's reward value and integration of these with interoceptive signalling of one's internal state of well-being, with important relations between brain activity and homeostatic and hedonic aspects of appetite. Our findings give novel evidence of disruption in neurobiological circuits and stress the importance of examining both state and trait characteristics in the investigation of brain phenotypes in individuals with anorexia nervosa.

Anything goes? Regulation of the neural processes underlying response inhibition in TBI patients.

PubMed

Moreno-López, Laura; Manktelow, Anne E; Sahakian, Barbara J; Menon, David K; Stamatakis, Emmanuel A

2017-02-01

Despite evidence for beneficial use of methylphenidate in response inhibition, no studies so far have investigated the effects of this drug in the neurobiology of inhibitory control in traumatic brain injury (TBI), even though impulsive behaviours are frequently reported in this patient group. We investigated the neural basis of response inhibition in a group of TBI patients using functional magnetic resonance imaging and a stop-signal paradigm. In a randomised double-blinded crossover study, the patients received either a single 30mg dose of methylphenidate or placebo and performed the stop-signal task. Activation in the right inferior frontal gyrus (RIFG), an area associated with response inhibition, was significantly lower in patients compared to healthy controls. Poor response inhibition in this group was associated with greater connectivity between the RIFG and a set of regions considered to be part of the default mode network (DMN), a finding that suggests the interplay between DMN and frontal executive networks maybe compromised. A single dose of methylphenidate rendered activity and connectivity profiles of the patients RIFG near normal. The results of this study indicate that the neural circuitry involved in response inhibition in TBI patients may be partially restored with methylphenidate. Given the known mechanisms of action of methylphenidate, the effect we observed may be due to increased dopamine and noradrenaline levels. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Toward a functional neuroanatomy of dysthymia: a functional magnetic resonance imaging study.

PubMed

Ravindran, Arun V; Smith, Andra; Cameron, Colin; Bhatla, Raj; Cameron, Ian; Georgescu, Tania M; Hogan, Matthew J

2009-12-01

Dysthymia is a common mood disorder. Recent studies have confirmed the neurobiological and treatment response overlap of dysthymia with major depression. There are no previous published studies of functional magnetic resonance imaging (fMRI) in dysthymia. fMRI was used to compare neural processing of 17 unmedicated dysthymic patients with 17 age, sex, and education-matched control subjects in a mood induction paradigm using the International Affective Pictures System (IAPS). Using a random effects analysis to compare the groups, the results revealed that the dysthymic patients had significantly reduced activation in the dorsolateral prefrontal cortex compared to controls. The dysthymic patients exhibited increased activation in the amygdala, anterior cingulate and insula compared to controls and these differences were more evident when processing negative than positive images. This study included both early and late subtypes of dysthymia, and participants were only imaged at one time point, which may limit the generalizability of the results. The findings suggest the involvement of the prefrontal cortex, anterior cingulate, amygdala, and insula in the neural circuitry underlying dysthymia. It is suggested that altered activation in some of these neural regions may be a common substrate for depressive disorders in general while others may relate specifically to symptom characteristics and the chronic course of dysthymia. These findings are particularly striking given the history of this deceptively mild disorder which is still confused by some with character pathology.

Separate Brain Circuits Support Integrative and Semantic Priming in the Human Language System.

PubMed

Feng, Gangyi; Chen, Qi; Zhu, Zude; Wang, Suiping

2016-07-01

Semantic priming is a crucial phenomenon to study the organization of semantic memory. A novel type of priming effect, integrative priming, has been identified behaviorally, whereby a prime word facilitates recognition of a target word when the 2 concepts can be combined to form a unitary representation. We used both functional and anatomical imaging approaches to investigate the neural substrates supporting such integrative priming, and compare them with those in semantic priming. Similar behavioral priming effects for both semantic (Bread-Cake) and integrative conditions (Cherry-Cake) were observed when compared with an unrelated condition. However, a clearly dissociated brain response was observed between these 2 types of priming. The semantic-priming effect was localized to the posterior superior temporal and middle temporal gyrus. In contrast, the integrative-priming effect localized to the left anterior inferior frontal gyrus and left anterior temporal cortices. Furthermore, fiber tractography showed that the integrative-priming regions were connected via uncinate fasciculus fiber bundle forming an integrative circuit, whereas the semantic-priming regions connected to the posterior frontal cortex via separated pathways. The results point to dissociable neural pathways underlying the 2 distinct types of priming, illuminating the neural circuitry organization of semantic representation and integration. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Targeting Neural Endophenotypes of Eating Disorders with Non-invasive Brain Stimulation

PubMed Central

Dunlop, Katharine A.; Woodside, Blake; Downar, Jonathan

2016-01-01

The term “eating disorders” (ED) encompasses a wide variety of disordered eating and compensatory behaviors, and so the term is associated with considerable clinical and phenotypic heterogeneity. This heterogeneity makes optimizing treatment techniques difficult. One class of treatments is non-invasive brain stimulation (NIBS). NIBS, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), are accessible forms of neuromodulation that alter the cortical excitability of a target brain region. It is crucial for NIBS to be successful that the target is well selected for the patient population in question. Targets may best be selected by stepping back from conventional DSM-5 diagnostic criteria to identify neural substrates of more basic phenotypes, including behavior related to rewards and punishment, cognitive control, and social processes. These phenotypic dimensions have been recently laid out by the Research Domain Criteria (RDoC) initiative. Consequently, this review is intended to identify potential dimensions as outlined by the RDoC and the underlying behavioral and neurobiological targets associated with ED. This review will also identify candidate targets for NIBS based on these dimensions and review the available literature on rTMS and tDCS in ED. This review systematically reviews abnormal neural circuitry in ED within the RDoC framework, and also systematically reviews the available literature investigating NIBS as a treatment for ED. PMID:26909013

Neural correlates of appetitive extinction in humans.

PubMed

Kruse, Onno; Tapia León, Isabell; Stark, Rudolf; Klucken, Tim

2017-01-01

Appetitive extinction receives attention as an important model for the treatment of psychiatric disorders. However, in humans, its underlying neural correlates remain unknown. To close this gap, we investigated appetitive acquisition and extinction with fMRI in a 2-day monetary incentive delay paradigm. During appetitive conditioning, one stimulus (CS+) was paired with monetary reward, while another stimulus (CS-) was never rewarded. Twenty-four hours later, subjects underwent extinction, in which neither CS was reinforced. Appetitive conditioning elicited stronger skin conductance responses to the CS+ as compared with the CS-. Regarding subjective ratings, the CS+ was rated more pleasant and arousing than the CS- after conditioning. Furthermore, fMRI-results (CS+ - CS-) showed activation of the reward circuitry including amygdala, midbrain and striatal areas. During extinction, conditioned responses were successfully extinguished. In the early phase of extinction, we found a significant activation of the caudate, the hippocampus, the dorsal and ventral anterior cingulate cortex (dACC and vACC). In the late phase, we found significant activation of the nucleus accumbens (NAcc) and the amygdala. Correlational analyses with subjective ratings linked extinction success to the vACC and the NAcc, while associating the dACC with reduced extinction. The results reveal neural correlates of appetitive extinction in humans and extend assumptions from models for human extinction learning. © The Author (2016). Published by Oxford University Press.

Increased neural responses to reward in adolescents and young adults with attention-deficit/hyperactivity disorder and their unaffected siblings.

PubMed

von Rhein, Daniel; Cools, Roshan; Zwiers, Marcel P; van der Schaaf, Marieke; Franke, Barbara; Luman, Marjolein; Oosterlaan, Jaap; Heslenfeld, Dirk J; Hoekstra, Pieter J; Hartman, Catharina A; Faraone, Stephen V; van Rooij, Daan; van Dongen, Eelco V; Lojowska, Maria; Mennes, Maarten; Buitelaar, Jan

2015-05-01

Attention-deficit/hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder associated with abnormal reward processing. Limited and inconsistent data exist about the neural mechanisms underlying this abnormality. Furthermore, it is not known whether reward processing is abnormal in unaffected siblings of participants with ADHD. We used event-related functional magnetic resonance imaging (fMRI) to investigate brain responses during reward anticipation and receipt with an adapted monetary incentive delay task in a large sample of adolescents and young adults with ADHD (n = 150), their unaffected siblings (n = 92), and control participants (n = 108), all of the same age. Participants with ADHD showed, relative to control participants, increased responses in the anterior cingulate, anterior frontal cortex, and cerebellum during reward anticipation, and in the orbitofrontal, occipital cortex and ventral striatum. Responses of unaffected siblings were increased in these regions as well, except for the cerebellum during anticipation and ventral striatum during receipt. ADHD in adolescents and young adults is associated with enhanced neural responses in frontostriatal circuitry to anticipation and receipt of reward. The findings support models emphasizing aberrant reward processing in ADHD, and suggest that processing of reward is subject to familial influences. Future studies using standard monetary incentive delay task parameters are needed to replicate our findings. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Avoidance-based human Pavlovian-to-instrumental transfer

PubMed Central

Lewis, Andrea H.; Niznikiewicz, Michael A.; Delamater, Andrew R.; Delgado, Mauricio R.

2013-01-01

The Pavlovian-to-instrumental transfer (PIT) paradigm probes the influence of Pavlovian cues over instrumentally learned behavior. The paradigm has been used extensively to probe basic cognitive and motivational processes in studies of animal learning but, more recently, PIT and its underlying neural basis have been extended to investigations in humans. These initial neuroimaging studies of PIT have focused on the influence of appetitively conditioned stimuli on instrumental responses maintained by positive reinforcement, and highlight the involvement of the striatum. In the current study, we sought to understand the neural correlates of PIT in an aversive Pavlovian learning situation when instrumental responding was maintained through negative reinforcement. Participants exhibited specific PIT, wherein selective increases in instrumental responding to conditioned stimuli occurred when the stimulus signaled a specific aversive outcome whose omission negatively reinforced the instrumental response. Additionally, a general PIT effect was observed such that when a stimulus was associated with a different aversive outcome than was used to negatively reinforce instrumental behavior, the presence of that stimulus caused a non-selective increase in overall instrumental responding. Both specific and general PIT behavioral effects correlated with increased activation in corticostriatal circuitry, particularly in the striatum, a region involved in cognitive and motivational processes. These results suggest that avoidance-based PIT utilizes a similar neural mechanism to that seen with PIT in an appetitive context, which has implications for understanding mechanisms of drug-seeking behavior during addiction and relapse. PMID:24118624

Emergence of transformation-tolerant representations of visual objects in rat lateral extrastriate cortex

PubMed Central

Tafazoli, Sina; Safaai, Houman; De Franceschi, Gioia; Rosselli, Federica Bianca; Vanzella, Walter; Riggi, Margherita; Buffolo, Federica; Panzeri, Stefano; Zoccolan, Davide

2017-01-01

Rodents are emerging as increasingly popular models of visual functions. Yet, evidence that rodent visual cortex is capable of advanced visual processing, such as object recognition, is limited. Here we investigate how neurons located along the progression of extrastriate areas that, in the rat brain, run laterally to primary visual cortex, encode object information. We found a progressive functional specialization of neural responses along these areas, with: (1) a sharp reduction of the amount of low-level, energy-related visual information encoded by neuronal firing; and (2) a substantial increase in the ability of both single neurons and neuronal populations to support discrimination of visual objects under identity-preserving transformations (e.g., position and size changes). These findings strongly argue for the existence of a rat object-processing pathway, and point to the rodents as promising models to dissect the neuronal circuitry underlying transformation-tolerant recognition of visual objects. DOI: http://dx.doi.org/10.7554/eLife.22794.001 PMID:28395730

What has fMRI told us about the Development of Cognitive Control through Adolescence?

PubMed Central

Luna, Beatriz; Padmanabhan, Aarthi; O’Hearn, Kirsten

2009-01-01

Cognitive control, the ability to voluntarily guide our behavior, continues to improve throughout adolescence. Below we review the literature on age-related changes in brain function related to response inhibition and working memory, which support cognitive control. Findings from studies using functional magnetic imaging (fMRI) indicate that processing errors, sustaining a cognitive control state, and reaching adult levels of precision, persist through adolescence. Developmental changes in patterns of brain function suggest that core regions of the circuitry underlying cognitive control are on-line early in development. However, age-related changes in localized processes across the brain and in establishing long range connections that support top-down modulation of behavior may support more effective neural processing for optimal mature executive function. While great progress has been made in understanding the age-related changes in brain processes underlying cognitive development, there are still important challenges in developmental neuroimaging methods and the interpretation of data that need to be addressed. PMID:19765880

Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism.

PubMed

Davis, Peter E; Peters, Jurriaan M; Krueger, Darcy A; Sahin, Mustafa

2015-07-01

Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of autism spectrum disorder (ASD). Tremendous progress in understanding the pathogenesis of TSC has been made in recent years, along with initial trials of medical treatment aimed specifically at the underlying mechanism of the disorder. At the cellular level, loss of TSC1 or TSC2 results in upregulation of the mechanistic target of rapamycin (mTOR) pathway. At the circuitry level, TSC and mTOR play crucial roles in axonal, dendritic, and synaptic development and function. In this review, we discuss the molecular mechanism underlying TSC, and how this disease results in aberrant neural connectivity at multiple levels in the central nervous system, leading to ASD symptoms. We then review recent advances in mechanism-based treatments of TSC, and the promise that these treatments provide for future mechanism-based treatment of ASD. Because of these recent advances, TSC represents an ideal model for how to make progress in understanding and treating the mechanisms that underlie ASD in general.

Selective updating of working memory content modulates meso-cortico-striatal activity.

PubMed

Murty, Vishnu P; Sambataro, Fabio; Radulescu, Eugenia; Altamura, Mario; Iudicello, Jennifer; Zoltick, Bradley; Weinberger, Daniel R; Goldberg, Terry E; Mattay, Venkata S

2011-08-01

Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating. Analyses revealed a functionally coupled network consisting of a midbrain region encompassing the substantia nigra/ventral tegmental area, caudate, and dorsolateral prefrontal cortex that was selectively engaged during working memory updating compared to the overwriting and maintenance of working memory content. Further analysis revealed differential midbrain-dorsolateral prefrontal interactions during selective updating between low-performing and high-performing individuals. These findings highlight the role of this meso-cortico-striatal circuitry during the selective updating of working memory in humans, which complements previous research in behavioral neuroscience and computational modeling. Published by Elsevier Inc.

Understanding alcohol use disorders with neuroelectrophysiology

PubMed Central

RANGASWAMY, MADHAVI; PORJESZ, BERNICE

2015-01-01

Neurocognitive deficits associated with impairments in various brain regions and neural circuitries, particularly involving frontal lobes, have been associated with chronic alcoholism, as well as with a predisposition to develop alcohol use and related disorders (AUDs). AUD is a multifactorial disorder caused by complex interactions between behavioral, genetic, and environmental liabilities. Neuroelectrophysiological techniques are instrumental in understanding brain and behavior relationships and have also proved very useful in evaluating the genetic diathesis of alcoholism. This chapter describes findings from neuroelectrophysiological measures (electroencephalogram, event-related potentials, and event-related oscillations) related to acute and chronic effects of alcohol on the brain and those that reflect underlying deficits related to a predisposition to develop AUDs and related disorders. The utility of these measures as effective endophenotypes to identify and understand genes associated with brain electrophysiology, cognitive networks, and AUDs has also been discussed. PMID:25307587

Predictability and hierarchy in Drosophila behavior.

PubMed

Berman, Gordon J; Bialek, William; Shaevitz, Joshua W

2016-10-18

Even the simplest of animals exhibit behavioral sequences with complex temporal dynamics. Prominent among the proposed organizing principles for these dynamics has been the idea of a hierarchy, wherein the movements an animal makes can be understood as a set of nested subclusters. Although this type of organization holds potential advantages in terms of motion control and neural circuitry, measurements demonstrating this for an animal's entire behavioral repertoire have been limited in scope and temporal complexity. Here, we use a recently developed unsupervised technique to discover and track the occurrence of all stereotyped behaviors performed by fruit flies moving in a shallow arena. Calculating the optimally predictive representation of the fly's future behaviors, we show that fly behavior exhibits multiple time scales and is organized into a hierarchical structure that is indicative of its underlying behavioral programs and its changing internal states.

Implicit aversive memory under anaesthesia in animal models: a narrative review.

PubMed

Samuel, N; Taub, A H; Paz, R; Raz, A

2018-07-01

Explicit memory after anaesthesia has gained considerable attention because of its negative implications, while implicit memory, which is more elusive and lacks patients' explicit recall, has received less attention and dedicated research. This is despite the likely impact of implicit memory on postoperative long-term well-being and behaviour. Given the scarcity of human data, fear conditioning in animals offers a reliable model of implicit learning, and importantly, one where we already have a good understanding of the underlying neural circuitry in awake conditions. Animal studies provide evidence that fear conditioning occurs under anaesthesia. The effects of different anaesthetics on memory are complex, with different drugs interacting at different stages of learning. Modulatory suppressive effects can be because of context, specific drugs, and dose dependency. In some cases, low doses of general anaesthetics can actually lead to a paradoxical opposite effect. The underlying mechanisms involve several neurotransmitter systems, acting mainly in the amygdala, hippocampus, and neocortex. Here, we review animal studies of aversive conditioning under anaesthesia, discuss the complex picture that arises, identify the gaps in knowledge that require further investigation, and highlight the potential translational relevance of the models. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Role of Basal Ganglia in Sleep–Wake Regulation: Neural Circuitry and Clinical Significance

PubMed Central

Vetrivelan, Ramalingam; Qiu, Mei-Hong; Chang, Celene; Lu, Jun

2010-01-01

Researchers over the last decade have made substantial progress toward understanding the roles of dopamine and the basal ganglia (BG) in the control of sleep–wake behavior. In this review, we outline recent advancements regarding dopaminergic modulation of sleep through the BG and extra-BG sites. Our main hypothesis is that dopamine promotes sleep by its action on the D2 receptors in the BG and promotes wakefulness by its action on D1 and D2 receptors in the extra-BG sites. This hypothesis implicates dopamine depletion in the BG (such as in Parkinson's disease) in causing frequent nighttime arousal and overall insomnia. Furthermore, the arousal effects of psychostimulants (methamphetamine, cocaine, and modafinil) may be linked to the ventral periaquductal gray (vPAG) dopaminergic circuitry targeting the extra-BG sleep–wake network. PMID:21151379

Development and Evaluation of Micro-Electrocorticography Arrays for Neural Interfacing Applications

NASA Astrophysics Data System (ADS)

Schendel, Amelia Ann

Neural interfaces have great promise for both electrophysiological research and therapeutic applications. Whether for the study of neural circuitry or for neural prosthetic or other therapeutic applications, micro-electrocorticography (micro-ECoG) arrays have proven extremely useful as neural interfacing devices. These devices strike a balance between invasiveness and signal resolution, an important step towards eventual human application. The objective of this research was to make design improvements to micro-ECoG devices to enhance both biocompatibility and device functionality. To best evaluate the effectiveness of these improvements, a cranial window imaging method for in vivo monitoring of the longitudinal tissue response post device implant was developed. Employment of this method provided valuable insight into the way tissue grows around micro-ECoG arrays after epidural implantation, spurring a study of the effects of substrate geometry on the meningeal tissue response. The results of the substrate footprint comparison suggest that a more open substrate geometry provides an easy path for the tissue to grow around to the top side of the device, whereas a solid device substrate encourages the tissue to thicken beneath the device, between the electrode sites and the brain. The formation of thick scar tissue between the recording electrode sites and the neural tissue is disadvantageous for long-term recorded signal quality, and thus future micro-ECoG device designs should incorporate open-architecture substrates for enhanced longitudinal in vivo function. In addition to investigating improvements for long-term device reliability, it was also desired to enhance the functionality of micro-ECoG devices for neural electrophysiology research applications. To achieve this goal, a completely transparent graphene-based device was fabricated for use with the cranial window imaging method and optogenetic techniques. The use of graphene as the conductive material provided the transparency necessary to image tissues directly below the micro-ECoG electrode sites, and to transmit light through the electrode sites to underlying neural tissue, for optical stimulation of neural cells. The flexibility and broad-spectrum transparency of graphene make it an ideal choice for thin-film, flexible electronic devices.

Neural division of labor in reading is constrained by culture: a training study of reading Chinese characters.

PubMed

Zhao, Jingjing; Wang, Xiaoyi; Frost, Stephen J; Sun, Wan; Fang, Shin-Yi; Mencl, W Einar; Pugh, Kenneth R; Shu, Hua; Rueckl, Jay G

2014-04-01

Word reading in alphabetic language involves a cortical system with multiple components whose division of labor depends on the transparency of the writing system. To gain insight about the neural division of labor between phonology and semantics subserving word reading in Chinese, a deep non-alphabetic writing system, functional magnetic resonance imaging (fMRI) was used to investigate the effects of phonological and semantic training on the cortical circuitry for oral naming of Chinese characters. In a training study, we examined whether a training task that differentially focused readers' attention on the phonological or semantic properties of a Chinese character changes the patterns of cortical activation that was evoked by that character in a subsequent naming task. Our imaging results corroborate that the cortical regions underlying reading in Chinese largely overlap the left-hemisphere reading system responsible for reading in alphabetic languages, with some cortical regions in the left-hemisphere uniquely recruited for reading in Chinese. However, in contrast to findings from studies of English word naming, we observed considerable overlap in the neural activation patterns associated with phonological and semantic training on naming Chinese characters, which we suggest may reflect a balanced neural division of labor between phonology and semantics in Chinese character reading. The equitable division of labor for Chinese reading might be driven by the special statistical structure of the writing system, which includes equally systematic mappings in the correspondences between written forms and their pronunciations and meanings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Noise-invariant Neurons in the Avian Auditory Cortex: Hearing the Song in Noise

PubMed Central

Moore, R. Channing; Lee, Tyler; Theunissen, Frédéric E.

2013-01-01

Given the extraordinary ability of humans and animals to recognize communication signals over a background of noise, describing noise invariant neural responses is critical not only to pinpoint the brain regions that are mediating our robust perceptions but also to understand the neural computations that are performing these tasks and the underlying circuitry. Although invariant neural responses, such as rotation-invariant face cells, are well described in the visual system, high-level auditory neurons that can represent the same behaviorally relevant signal in a range of listening conditions have yet to be discovered. Here we found neurons in a secondary area of the avian auditory cortex that exhibit noise-invariant responses in the sense that they responded with similar spike patterns to song stimuli presented in silence and over a background of naturalistic noise. By characterizing the neurons' tuning in terms of their responses to modulations in the temporal and spectral envelope of the sound, we then show that noise invariance is partly achieved by selectively responding to long sounds with sharp spectral structure. Finally, to demonstrate that such computations could explain noise invariance, we designed a biologically inspired noise-filtering algorithm that can be used to separate song or speech from noise. This novel noise-filtering method performs as well as other state-of-the-art de-noising algorithms and could be used in clinical or consumer oriented applications. Our biologically inspired model also shows how high-level noise-invariant responses could be created from neural responses typically found in primary auditory cortex. PMID:23505354

Pathophysiological Bases of Comorbidity: Traumatic Brain Injury and Post-Traumatic Stress Disorder.

PubMed

Kaplan, Gary B; Leite-Morris, Kimberly A; Wang, Lei; Rumbika, Kendra K; Heinrichs, Stephen C; Zeng, Xiang; Wu, Liquan; Arena, Danielle T; Teng, Yang D

2018-01-15

The high rates of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) diagnoses encountered in recent years by the United States Veterans Affairs Healthcare System have increased public awareness and research investigation into these conditions. In this review, we analyze the neural mechanisms underlying the TBI/PTSD comorbidity. TBI and PTSD present with common neuropsychiatric symptoms including anxiety, irritability, insomnia, personality changes, and memory problems, and this overlap complicates diagnostic differentiation. Interestingly, both TBI and PTSD can be produced by overlapping pathophysiological changes that disrupt neural connections termed the "connectome." The neural disruptions shared by PTSD and TBI and the comorbid condition include asymmetrical white matter tract abnormalities and gray matter changes in the basolateral amygdala, hippocampus, and prefrontal cortex. These neural circuitry dysfunctions result in behavioral changes that include executive function and memory impairments, fear retention, fear extinction deficiencies, and other disturbances. Pathophysiological etiologies can be identified using experimental models of TBI, such as fluid percussion or blast injuries, and for PTSD, using models of fear conditioning, retention, and extinction. In both TBI and PTSD, there are discernible signs of neuroinflammation, excitotoxicity, and oxidative damage. These disturbances produce neuronal death and degeneration, axonal injury, and dendritic spine dysregulation and changes in neuronal morphology. In laboratory studies, various forms of pharmacological or psychological treatments are capable of reversing these detrimental processes and promoting axonal repair, dendritic remodeling, and neurocircuitry reorganization, resulting in behavioral and cognitive functional enhancements. Based on these mechanisms, novel neurorestorative therapeutics using anti-inflammatory, antioxidant, and anticonvulsant agents may promote better outcomes for comorbid TBI and PTSD.

Neural Correlates of Antidepressant Treatment Response in Adolescents with Major Depressive Disorder

PubMed Central

Klimes-Dougan, Bonnie; Vu, Dung Pham; Westlund Schreiner, Melinda; Mueller, Bryon A.; Eberly, Lynn E.; Camchong, Jazmin; Westervelt, Ana; Lim, Kelvin O.

2016-01-01

Abstract Objective: The neural changes underlying response to antidepressant treatment in adolescents are unknown. Identification of neural change correlates of treatment response could (1) aid in understanding mechanisms of depression and its treatment and (2) serve as target biomarkers for future research. Method: Using functional magnetic resonance imaging, we examined changes in brain activation and functional connectivity in 13 unmedicated adolescents with major depressive disorder (MDD) before and after receiving treatment with a selective serotonin reuptake inhibitor medication for 8 weeks. Specifically, we examined brain activation during a negative emotion task and resting-state functional connectivity (RSFC), focusing on the amygdala to capture networks relevant to negative emotion. We conducted whole-brain analyses to identify how symptom improvement was related to change in brain activation during a negative emotion task or amygdala RSFC. Results: After treatment, clinical improvement was associated with decreased task activation in rostral and subgenual anterior cingulate cortex and increased activation in bilateral insula, bilateral middle frontal cortices, right parahippocampus, and left cerebellum. Analysis of change in amygdala RSFC showed that treatment response was associated with increased amygdala RSFC with right frontal cortex, but decreased amygdala RSFC with right precuneus and right posterior cingulate cortex. Conclusion: The findings represent a foothold for advancing understanding of pathophysiology of MDD in adolescents by revealing the critical neural circuitry changes that underlie a positive response to a standard treatment. Although preliminary, the present study provides a research platform for future work needed to confirm these biomarkers at a larger scale before using them in future target engagement studies of novel treatments. PMID:27159204

Noise-invariant neurons in the avian auditory cortex: hearing the song in noise.

PubMed

Moore, R Channing; Lee, Tyler; Theunissen, Frédéric E

2013-01-01

Given the extraordinary ability of humans and animals to recognize communication signals over a background of noise, describing noise invariant neural responses is critical not only to pinpoint the brain regions that are mediating our robust perceptions but also to understand the neural computations that are performing these tasks and the underlying circuitry. Although invariant neural responses, such as rotation-invariant face cells, are well described in the visual system, high-level auditory neurons that can represent the same behaviorally relevant signal in a range of listening conditions have yet to be discovered. Here we found neurons in a secondary area of the avian auditory cortex that exhibit noise-invariant responses in the sense that they responded with similar spike patterns to song stimuli presented in silence and over a background of naturalistic noise. By characterizing the neurons' tuning in terms of their responses to modulations in the temporal and spectral envelope of the sound, we then show that noise invariance is partly achieved by selectively responding to long sounds with sharp spectral structure. Finally, to demonstrate that such computations could explain noise invariance, we designed a biologically inspired noise-filtering algorithm that can be used to separate song or speech from noise. This novel noise-filtering method performs as well as other state-of-the-art de-noising algorithms and could be used in clinical or consumer oriented applications. Our biologically inspired model also shows how high-level noise-invariant responses could be created from neural responses typically found in primary auditory cortex.

Positive autobiographical memory retrieval reduces temporal discounting.

PubMed

Lempert, Karolina M; Speer, Megan E; Delgado, Mauricio R; Phelps, Elizabeth A

2017-10-01

People generally prefer rewards sooner rather than later. This phenomenon, temporal discounting, underlies many societal problems, including addiction and obesity. One way to reduce temporal discounting is to imagine positive future experiences. Since there is overlap in the neural circuitry associated with imagining future experiences and remembering past events, here we investigate whether recalling positive memories can also promote more patient choice. We found that participants were more patient after retrieving positive autobiographical memories, but not when they recalled negative memories. Moreover, individuals were more impulsive after imagining novel positive scenes that were not related to their memories, showing that positive imagery alone does not drive this effect. Activity in the striatum and temporo parietal junction during memory retrieval predicted more patient choice, suggesting that to the extent that memory recall is rewarding and involves perspective-taking, it influences decision-making. Furthermore, representational similarity in the ventromedial prefrontal cortex between memory recall and decision phases correlated with the behavioral effect across participants. Thus, we have identified a novel manipulation for reducing temporal discounting-remembering the positive past-and have begun to characterize the psychological and neural mechanisms behind it. © The Author (2017). Published by Oxford University Press.

Recent advances in understanding the role of the hypothalamic circuit during aggression

PubMed Central

Falkner, Annegret L.; Lin, Dayu

2014-01-01

The hypothalamus was first implicated in the classic “fight or flight” response nearly a century ago, and since then, many important strides have been made in understanding both the circuitry and the neural dynamics underlying the generation of these behaviors. In this review, we will focus on the role of the hypothalamus in aggression, paying particular attention to recent advances in the field that have allowed for functional identification of relevant hypothalamic subnuclei. Recent progress in this field has been aided by the development of new techniques for functional manipulation including optogenetics and pharmacogenetics, as well as advances in technology used for chronic in vivo recordings during complex social behaviors. We will examine the role of the hypothalamus through the complimentary lenses of (1) loss of function studies, including pharmacology and pharmacogenetics; (2) gain of function studies, including specific comparisons between results from classic electrical stimulation studies and more recent work using optogenetics; and (3) neural activity, including both immediate early gene and awake-behaving recordings. Lastly, we will outline current approaches to identifying the precise role of the hypothalamus in promoting aggressive motivation and aggressive action. PMID:25309351

Effects of Long-term Diving Training on Cortical Gyrification.

PubMed

Zhang, Yuanchao; Zhao, Lu; Bi, Wenwei; Wang, Yue; Wei, Gaoxia; Evans, Alan; Jiang, Tianzi

2016-06-20

During human brain development, cortical gyrification, which is believed to facilitate compact wiring of neural circuits, has been shown to follow an inverted U-shaped curve, coinciding with the two-stage neurodevelopmental process of initial synaptic overproduction with subsequent pruning. This trajectory allows postnatal experiences to refine the wiring, which may manifest as endophenotypic changes in cortical gyrification. Diving experts, typical elite athletes who commence intensive motor training at a very young age in their early childhood, serve ideal models for examining the gyrification changes related to long-term intensive diving training. Using local gyrification index (LGI), we compared the cortical gyrification between 12 diving experts and 12 controls. Compared with controls, diving experts showed widespread LGI reductions in regions relevant to diving performance. Negative correlations between LGIs and years of diving training were also observed in diving experts. Further exploratory network efficiency analysis of structural cortical networks, inferred from interregional correlation of LGIs, revealed comparable global and local efficiency in diving experts relative to controls. These findings suggest that gyrification reductions in diving experts may be the result of long-term diving training which could refine the neural circuitry (via synaptic pruning) and might be the anatomical substrate underlying their extraordinary diving performance.

Mechanisms for Adjusting Interaural Time Differences to Achieve Binaural Coincidence Detection

PubMed Central

Seidl, Armin H.; Rubel, Edwin W; Harris, David M.

2010-01-01

Understanding binaural perception requires detailed analyses of the neural circuitry responsible for the computation of interaural time differences (ITDs). In the avian brainstem, this circuit consists of internal axonal delay lines innervating an array of coincidence detector neurons that encode external ITDs. Nucleus magnocellularis (NM) neurons project to the dorsal dendritic field of the ipsilateral nucleus laminaris (NL) and to the ventral field of the contralateral NL. Contralateral-projecting axons form a delay line system along a band of NL neurons. Binaural acoustic signals in the form of phase-locked action potentials from NM cells arrive at NL and establish a topographic map of sound source location along the azimuth. These pathways are assumed to represent a circuit similar to the Jeffress model of sound localization, establishing a place code along an isofrequency contour of NL. Three-dimensional measurements of axon lengths reveal major discrepancies with the current model; the temporal offset based on conduction length alone makes encoding of physiological ITDs impossible. However, axon diameter and distances between Nodes of Ranvier also influence signal propagation times along an axon. Our measurements of these parameters reveal that diameter and internode distance can compensate for the temporal offset inferred from axon lengths alone. Together with other recent studies these unexpected results should inspire new thinking on the cellular biology, evolution and plasticity of the circuitry underlying low frequency sound localization in both birds and mammals. PMID:20053889

Functional connectivity of neural motor networks is disrupted in children with developmental coordination disorder and attention-deficit/hyperactivity disorder

PubMed Central

McLeod, Kevin R.; Langevin, Lisa Marie; Goodyear, Bradley G.; Dewey, Deborah

2014-01-01

Developmental coordination disorder (DCD) and attention deficit/hyperactivity disorder (ADHD) are prevalent childhood disorders that frequently co-occur. Evidence from neuroimaging research suggests that children with these disorders exhibit disruptions in motor circuitry, which could account for the high rate of co-occurrence. The primary objective of this study was to investigate the functional connections of the motor network in children with DCD and/or ADHD compared to typically developing controls, with the aim of identifying common neurophysiological substrates. Resting-state fMRI was performed on seven children with DCD, 21 with ADHD, 18 with DCD + ADHD and 23 controls. Resting-state connectivity of the primary motor cortex was compared between each group and controls, using age as a co-factor. Relative to controls, children with DCD and/or ADHD exhibited similar reductions in functional connectivity between the primary motor cortex and the bilateral inferior frontal gyri, right supramarginal gyrus, angular gyri, insular cortices, amygdala, putamen, and pallidum. In addition, children with DCD and/or ADHD exhibited different age-related patterns of connectivity, compared to controls. These findings suggest that children with DCD and/or ADHD exhibit disruptions in motor circuitry, which may contribute to problems with motor functioning and attention. Our results support the existence of common neurophysiological substrates underlying both motor and attention problems. PMID:24818082

Computing with Neural Synchrony

PubMed Central

Brette, Romain

2012-01-01

Neurons communicate primarily with spikes, but most theories of neural computation are based on firing rates. Yet, many experimental observations suggest that the temporal coordination of spikes plays a role in sensory processing. Among potential spike-based codes, synchrony appears as a good candidate because neural firing and plasticity are sensitive to fine input correlations. However, it is unclear what role synchrony may play in neural computation, and what functional advantage it may provide. With a theoretical approach, I show that the computational interest of neural synchrony appears when neurons have heterogeneous properties. In this context, the relationship between stimuli and neural synchrony is captured by the concept of synchrony receptive field, the set of stimuli which induce synchronous responses in a group of neurons. In a heterogeneous neural population, it appears that synchrony patterns represent structure or sensory invariants in stimuli, which can then be detected by postsynaptic neurons. The required neural circuitry can spontaneously emerge with spike-timing-dependent plasticity. Using examples in different sensory modalities, I show that this allows simple neural circuits to extract relevant information from realistic sensory stimuli, for example to identify a fluctuating odor in the presence of distractors. This theory of synchrony-based computation shows that relative spike timing may indeed have computational relevance, and suggests new types of neural network models for sensory processing with appealing computational properties. PMID:22719243

Neural Encoding and Integration of Learned Probabilistic Sequences in Avian Sensory-Motor Circuitry

PubMed Central

Brainard, Michael S.

2013-01-01

Many complex behaviors, such as human speech and birdsong, reflect a set of categorical actions that can be flexibly organized into variable sequences. However, little is known about how the brain encodes the probabilities of such sequences. Behavioral sequences are typically characterized by the probability of transitioning from a given action to any subsequent action (which we term “divergence probability”). In contrast, we hypothesized that neural circuits might encode the probability of transitioning to a given action from any preceding action (which we term “convergence probability”). The convergence probability of repeatedly experienced sequences could naturally become encoded by Hebbian plasticity operating on the patterns of neural activity associated with those sequences. To determine whether convergence probability is encoded in the nervous system, we investigated how auditory-motor neurons in vocal premotor nucleus HVC of songbirds encode different probabilistic characterizations of produced syllable sequences. We recorded responses to auditory playback of pseudorandomly sequenced syllables from the bird's repertoire, and found that variations in responses to a given syllable could be explained by a positive linear dependence on the convergence probability of preceding sequences. Furthermore, convergence probability accounted for more response variation than other probabilistic characterizations, including divergence probability. Finally, we found that responses integrated over >7–10 syllables (∼700–1000 ms) with the sign, gain, and temporal extent of integration depending on convergence probability. Our results demonstrate that convergence probability is encoded in sensory-motor circuitry of the song-system, and suggest that encoding of convergence probability is a general feature of sensory-motor circuits. PMID:24198363

Vortioxetine reduces BOLD signal during performance of the N-back working memory task: a randomised neuroimaging trial in remitted depressed patients and healthy controls.

PubMed

Smith, J; Browning, M; Conen, S; Smallman, R; Buchbjerg, J; Larsen, K G; Olsen, C K; Christensen, S R; Dawson, G R; Deakin, J F; Hawkins, P; Morris, R; Goodwin, G; Harmer, C J

2018-05-01

Cognitive dysfunction is common in depression during both acute episodes and remission. Vortioxetine is a novel multimodal antidepressant that has improved cognitive function including executive function in depressed patients in randomised placebo-controlled clinical trials. However, it is unclear whether vortioxetine is able to target directly the neural circuitry implicated in the cognitive deficits in depression. Remitted depressed (n=48) and healthy volunteers (n=48) were randomised to receive 14 days treatment with 20 mg vortioxetine or placebo in a double-blind design. The effects of treatment on functional magnetic resonance imaging responses during an N-back working memory task were assessed at baseline and at the end of treatment. Neuropsychological measures of executive function, speed and information processing, attention and learning and memory were examined with the Trail Making Test (TMT), Rey Auditory Learning Test and Digit Symbol Substitution Test before and after treatment; subjective cognitive function was assessed using the Perceived Deficits Questionnaire (PDQ). Compared with placebo, vortioxetine reduced activation in the right dorsolateral prefrontal cortex and left hippocampus during the N-back task compared with placebo. Vortioxetine also increased TMT-A performance and self-reported cognitive function on the PDQ. These effects were seen across both subject groups. Vortioxetine modulates neural responses across a circuit subserving working memory in a direction opposite to the changes described in depression, when performance is maintained. This study provides evidence that vortioxetine has direct effects on the neural circuitry supporting cognitive function that can be dissociated from its effects on the mood symptoms of depression.

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2013-09-01

implemented to significantly decrease the IIR system response time, especially when artifacts were highly reproducible in consecutive stimulation...cycles. The proposed system architecture was hardware- implemented on a field- programmable gate array (FPGA) and tested using two sets of prerecorded...its FPGA implementation and testing with prerecorded neural datasets are reported in a manuscript currently in press with the IEEE Transactions on

Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence

PubMed Central

Shaw, Daniel S.; Sitnick, Stephanie L.; Musselman, Samuel C.; Forbes, Erika E.

2015-01-01

Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function. PMID:24795442

Integrated biocircuits: engineering functional multicellular circuits and devices.

PubMed

Prox, Jordan; Smith, Tory; Holl, Chad; Chehade, Nick; Guo, Liang

2018-04-01

Implantable neurotechnologies have revolutionized neuromodulatory medicine for treating the dysfunction of diseased neural circuitry. However, challenges with biocompatibility and lack of full control over neural network communication and function limits the potential to create more stable and robust neuromodulation devices. Thus, we propose a platform technology of implantable and programmable cellular systems, namely Integrated Biocircuits, which use only cells as the functional components of the device. We envision the foundational principles for this concept begins with novel in vitro platforms used for the study and reconstruction of cellular circuitry. Additionally, recent advancements in organoid and 3D culture systems account for microenvironment factors of cytoarchitecture to construct multicellular circuits as they are normally formed in the brain. We explore the current state of the art of these platforms to provide knowledge of their advancements in circuit fabrication and identify the current biological principles that could be applied in designing integrated biocircuit devices. We have highlighted the exemplary methodologies and techniques of in vitro circuit fabrication and propose the integration of selected controllable parameters, which would be required in creating suitable biodevices. We provide our perspective and propose new insights into the future of neuromodulaion devices within the scope of living cellular systems that can be applied in designing more reliable and biocompatible stimulation-based neuroprosthetics.

Integrated biocircuits: engineering functional multicellular circuits and devices

NASA Astrophysics Data System (ADS)

Prox, Jordan; Smith, Tory; Holl, Chad; Chehade, Nick; Guo, Liang

2018-04-01

Objective. Implantable neurotechnologies have revolutionized neuromodulatory medicine for treating the dysfunction of diseased neural circuitry. However, challenges with biocompatibility and lack of full control over neural network communication and function limits the potential to create more stable and robust neuromodulation devices. Thus, we propose a platform technology of implantable and programmable cellular systems, namely Integrated Biocircuits, which use only cells as the functional components of the device. Approach. We envision the foundational principles for this concept begins with novel in vitro platforms used for the study and reconstruction of cellular circuitry. Additionally, recent advancements in organoid and 3D culture systems account for microenvironment factors of cytoarchitecture to construct multicellular circuits as they are normally formed in the brain. We explore the current state of the art of these platforms to provide knowledge of their advancements in circuit fabrication and identify the current biological principles that could be applied in designing integrated biocircuit devices. Main results. We have highlighted the exemplary methodologies and techniques of in vitro circuit fabrication and propose the integration of selected controllable parameters, which would be required in creating suitable biodevices. Significance. We provide our perspective and propose new insights into the future of neuromodulaion devices within the scope of living cellular systems that can be applied in designing more reliable and biocompatible stimulation-based neuroprosthetics.

Glucose-monitoring neurons in the mediodorsal prefrontal cortex.

PubMed

Nagy, Bernadett; Szabó, István; Papp, Szilárd; Takács, Gábor; Szalay, Csaba; Karádi, Zoltán

2012-03-20

The mediodorsal prefrontal cortex (mdPFC), a key structure of the limbic neural circuitry, plays important roles in the central regulation of feeding. As an integrant part of the forebrain dopamine (DA) system, it performs complex roles via interconnections with various brain areas where glucose-monitoring (GM) neurons have been identified. The main goal of the present experiments was to examine whether similar GM neurons exist in the mediodorsal prefrontal cortex. To search for such chemosensory cells here, and to estimate their involvement in the DA circuitry, extracellular single neuron activity of the mediodorsal prefrontal cortex of anesthetized Wistar and Sprague-Dawley rats was recorded by means of tungsten wire multibarreled glass microelectrodes during microelectrophoretic administration of d-glucose and DA. One fourth of the neurons tested changed in firing rate in response to glucose, thus, proved to be elements of the forebrain GM neural network. DA responsive neurons in the mdPFC were found to represent similar proportion of all cells; the glucose-excited units were shown to display excitatory whereas the glucose-inhibited neurons were demonstrated to exert mainly inhibitory responses to dopamine. The glucose-monitoring neurons of the mdPFC and their distinct DA sensitivity are suggested to be of particular significance in adaptive processes of the central feeding control. Copyright © 2012 Elsevier B.V. All rights reserved.

Lesions of the ventral premammillary nucleus disrupt the dynamic changes in Kiss1 and GnRH expression characteristic of the proestrus-estrus transition

PubMed Central

Donato, Jose; Lee, Charlotte; Ratra, Dhirender; Franci, Celso R.; Canteras, Newton S.; Elias, Carol F.

2013-01-01

We have recently demonstrated that the ventral premammillary nucleus (PMV) plays a key role in the metabolic control of the female reproductive axis. However, whether PMV neurons modulate the reproductive neural circuitry and/or the expression of sexual behaviors has not been determined. Here, we showed that the expression of estrogen and progesterone receptors in the PMV is modulated by changing levels of sex steroids across the estrous cycle. We also showed that sexual behavior, not the high physiologic levels of sex steroids, induces Fos in PMV neurons. Bilateral lesions of the PMV caused no significant changes in proceptive behavior but a high percentage of PMV-lesioned rats failed to exhibit lordosis behavior when exposed to a sexually-experienced male rat (50% vs. 18% in the control group). Notably, lesions of the PMV disrupted the physiologic fluctuations of Kiss1 and GnRH mRNA expression characteristic of the proestrus-to-estrus transition. This neurochemical imbalance may ultimately alter female reproductive behavior. Our findings suggest that the PMV is a component of the neural circuitry that modulates the physiologic fluctuations of key neuroendocrine players (i.e., Kiss1 and GnRH) in the control of the female reproductive physiology. PMID:23518222

Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.

PubMed

Goldstein, Jill M; Lancaster, Katie; Longenecker, Julia M; Abbs, Brandon; Holsen, Laura M; Cherkerzian, Sara; Whitfield-Gabrieli, Susan; Makris, Nicolas; Tsuang, Ming T; Buka, Stephen L; Seidman, Larry J; Klibanski, Anne

2015-06-30

Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Phototaxis and the origin of visual eyes

PubMed Central

Randel, Nadine

2016-01-01

Vision allows animals to detect spatial differences in environmental light levels. High-resolution image-forming eyes evolved from low-resolution eyes via increases in photoreceptor cell number, improvements in optics and changes in the neural circuits that process spatially resolved photoreceptor input. However, the evolutionary origins of the first low-resolution visual systems have been unclear. We propose that the lowest resolving (two-pixel) visual systems could initially have functioned in visual phototaxis. During visual phototaxis, such elementary visual systems compare light on either side of the body to regulate phototactic turns. Another, even simpler and non-visual strategy is characteristic of helical phototaxis, mediated by sensory–motor eyespots. The recent mapping of the complete neural circuitry (connectome) of an elementary visual system in the larva of the annelid Platynereis dumerilii sheds new light on the possible paths from non-visual to visual phototaxis and to image-forming vision. We outline an evolutionary scenario focusing on the neuronal circuitry to account for these transitions. We also present a comprehensive review of the structure of phototactic eyes in invertebrate larvae and assign them to the non-visual and visual categories. We propose that non-visual systems may have preceded visual phototactic systems in evolution that in turn may have repeatedly served as intermediates during the evolution of image-forming eyes. PMID:26598725

Exploring the relationship between cortical GABA concentrations, auditory gamma-band responses and development in ASD: Evidence for an altered maturational trajectory in ASD.

PubMed

Port, Russell G; Gaetz, William; Bloy, Luke; Wang, Dah-Jyuu; Blaskey, Lisa; Kuschner, Emily S; Levy, Susan E; Brodkin, Edward S; Roberts, Timothy P L

2017-04-01

Autism spectrum disorder (ASD) is hypothesized to arise from imbalances between excitatory and inhibitory neurotransmission (E/I imbalance). Studies have demonstrated E/I imbalance in individuals with ASD and also corresponding rodent models. One neural process thought to be reliant on E/I balance is gamma-band activity (Gamma), with support arising from observed correlations between motor, as well as visual, Gamma and underlying GABA concentrations in healthy adults. Additionally, decreased Gamma has been observed in ASD individuals and relevant animal models, though the direct relationship between Gamma and GABA concentrations in ASD remains unexplored. This study combined magnetoencephalography (MEG) and edited magnetic resonance spectroscopy (MRS) in 27 typically developing individuals (TD) and 30 individuals with ASD. Auditory cortex localized phase-locked Gamma was compared to resting Superior Temporal Gyrus relative cortical GABA concentrations for both children/adolescents and adults. Children/adolescents with ASD exhibited significantly decreased GABA+/Creatine (Cr) levels, though typical Gamma. Additionally, these children/adolescents lacked the typical maturation of GABA+/Cr concentrations and gamma-band coherence. Furthermore, children/adolescents with ASD additionally failed to exhibit the typical GABA+/Cr to gamma-band coherence association. This altered coupling during childhood/adolescence may result in Gamma decreases observed in the adults with ASD. Therefore, individuals with ASD exhibit improper local neuronal circuitry maturation during a childhood/adolescence critical period, when GABA is involved in configuring of such circuit functioning. Provocatively a novel line of treatment is suggested (with a critical time window); by increasing neural GABA levels in children/adolescents with ASD, proper local circuitry maturation may be restored resulting in typical Gamma in adulthood. Autism Res 2017, 10: 593-607. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

The neural circuit basis of learning

NASA Astrophysics Data System (ADS)

Patrick, Kaifosh William John

The astounding capacity for learning ranks among the nervous system's most impressive features. This thesis comprises studies employing varied approaches to improve understanding, at the level of neural circuits, of the brain's capacity for learning. The first part of the thesis contains investigations of hippocampal circuitry -- both theoretical work and experimental work in the mouse Mus musculus -- as a model system for declarative memory. To begin, Chapter 2 presents a theory of hippocampal memory storage and retrieval that reflects nonlinear dendritic processing within hippocampal pyramidal neurons. As a prelude to the experimental work that comprises the remainder of this part, Chapter 3 describes an open source software platform that we have developed for analysis of data acquired with in vivo Ca2+ imaging, the main experimental technique used throughout the remainder of this part of the thesis. As a first application of this technique, Chapter 4 characterizes the content of signaling at synapses between GABAergic neurons of the medial septum and interneurons in stratum oriens of hippocampal area CA1. Chapter 5 then combines these techniques with optogenetic, pharmacogenetic, and pharmacological manipulations to uncover inhibitory circuit mechanisms underlying fear learning. The second part of this thesis focuses on the cerebellum-like electrosensory lobe in the weakly electric mormyrid fish Gnathonemus petersii, as a model system for non-declarative memory. In Chapter 6, we study how short-duration EOD motor commands are recoded into a complex temporal basis in the granule cell layer, which can be used to cancel Purkinje-like cell firing to the longer duration and temporally varying EOD-driven sensory responses. In Chapter 7, we consider not only the temporal aspects of the granule cell code, but also the encoding of body position provided from proprioceptive and efference copy sources. Together these studies clarify how the cerebellum-like circuitry of the electrosensory lobe combines information of different forms and then uses this combined information to predict the complex dependence of sensory responses on body position and timing relative to electric organ discharge.

Vector Symbolic Spiking Neural Network Model of Hippocampal Subarea CA1 Novelty Detection Functionality.

PubMed

Agerskov, Claus

2016-04-01

A neural network model is presented of novelty detection in the CA1 subdomain of the hippocampal formation from the perspective of information flow. This computational model is restricted on several levels by both anatomical information about hippocampal circuitry and behavioral data from studies done in rats. Several studies report that the CA1 area broadcasts a generalized novelty signal in response to changes in the environment. Using the neural engineering framework developed by Eliasmith et al., a spiking neural network architecture is created that is able to compare high-dimensional vectors, symbolizing semantic information, according to the semantic pointer hypothesis. This model then computes the similarity between the vectors, as both direct inputs and a recalled memory from a long-term memory network by performing the dot-product operation in a novelty neural network architecture. The developed CA1 model agrees with available neuroanatomical data, as well as the presented behavioral data, and so it is a biologically realistic model of novelty detection in the hippocampus, which can provide a feasible explanation for experimentally observed dynamics.

Design, fabrication, and packaging of an integrated, wirelessly-powered optrode array for optogenetics application

PubMed Central

Kwon, Ki Yong; Lee, Hyung-Min; Ghovanloo, Maysam; Weber, Arthur; Li, Wen

2015-01-01

The recent development of optogenetics has created an increased demand for advancing engineering tools for optical modulation of neural circuitry. This paper details the design, fabrication, integration, and packaging procedures of a wirelessly-powered, light emitting diode (LED) coupled optrode neural interface for optogenetic studies. The LED-coupled optrode array employs microscale LED (μLED) chips and polymer-based microwaveguides to deliver light into multi-level cortical networks, coupled with microelectrodes to record spontaneous changes in neural activity. An integrated, implantable, switched-capacitor based stimulator (SCS) system provides high instantaneous power to the μLEDs through an inductive link to emit sufficient light and evoke neural activities. The presented system is mechanically flexible, biocompatible, miniaturized, and lightweight, suitable for chronic implantation in small freely behaving animals. The design of this system is scalable and its manufacturing is cost effective through batch fabrication using microelectromechanical systems (MEMS) technology. It can be adopted by other groups and customized for specific needs of individual experiments. PMID:25999823

Playing Music for a Smarter Ear: Cognitive, Perceptual and Neurobiological Evidence

PubMed Central

Strait, Dana; Kraus, Nina

2012-01-01

Human hearing depends on a combination of cognitive and sensory processes that function by means of an interactive circuitry of bottom-up and top-down neural pathways, extending from the cochlea to the cortex and back again. Given that similar neural pathways are recruited to process sounds related to both music and language, it is not surprising that the auditory expertise gained over years of consistent music practice fine-tunes the human auditory system in a comprehensive fashion, strengthening neurobiological and cognitive underpinnings of both music and speech processing. In this review we argue not only that common neural mechanisms for speech and music exist, but that experience in music leads to enhancements in sensory and cognitive contributors to speech processing. Of specific interest is the potential for music training to bolster neural mechanisms that undergird language-related skills, such as reading and hearing speech in background noise, which are critical to academic progress, emotional health, and vocational success. PMID:22993456

Online contributions of auditory feedback to neural activity in avian song control circuitry

PubMed Central

Sakata, Jon T.; Brainard, Michael S.

2008-01-01

Birdsong, like human speech, relies critically on auditory feedback to provide information about the quality of vocalizations. Although the importance of auditory feedback to vocal learning is well established, whether and how feedback signals influence vocal premotor circuitry has remained obscure. Previous studies in singing birds have not detected changes to vocal premotor activity following perturbations of auditory feedback, leading to the hypothesis that contributions of feedback to vocal plasticity might rely on ‘offline’ processing. Here, we recorded single and multi-unit activity in the premotor nucleus HVC of singing Bengalese finches in response to feedback perturbations that are known to drive plastic changes in song. We found that transient feedback perturbation caused reliable decreases in HVC activity at short latencies (20-80 ms). Similar changes to HVC activity occurred in awake, non-singing finches when the bird’s own song was played back with auditory perturbations that simulated those experienced by singing birds. These data indicate that neurons in avian vocal premotor circuitry are rapidly influenced by perturbations of auditory feedback and support the possibility that feedback information in HVC contributes online to the production and plasticity of vocalizations. PMID:18971480

Reward system dysfunction in autism spectrum disorders

PubMed Central

Schulte-Rüther, Martin; Nehrkorn, Barbara; Müller, Kristin; Fink, Gereon R.; Kamp-Becker, Inge; Herpertz-Dahlmann, Beate; Schultz, Robert T.; Konrad, Kerstin

2013-01-01

Although it has been suggested that social deficits of autism spectrum disorders (ASDs) are related to reward circuitry dysfunction, very little is known about the neural reward mechanisms in ASD. In the current functional magnetic resonance imaging study, we investigated brain activations in response to both social and monetary reward in a group of children with ASD, relative to matched controls. Participants with ASD showed the expected hypoactivation in the mesocorticolimbic circuitry in response to both reward types. In particular, diminished activation in the nucleus accumbens was observed when money, but not when social reward, was at stake, whereas the amygdala and anterior cingulate cortex were hypoactivated within the ASD group in response to both rewards. These data indicate that the reward circuitry is compromised in ASD in social as well as in non-social, i.e. monetary conditions, which likely contributes to atypical motivated behaviour. Taken together, with incentives used in this study sample, there is evidence for a general reward dysfunction in ASD. However, more ecologically valid social reward paradigms are needed to fully understand, whether there is any domain specificity to the reward deficit that appears evident in ASD, which would be most consistent with the ASD social phenotype. PMID:22419119

Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry

PubMed Central

Castro, Daniel C.; Cole, Shannon L.; Berridge, Kent C.

2015-01-01

The study of the neural bases of eating behavior, hunger, and reward has consistently implicated the lateral hypothalamus (LH) and its interactions with mesocorticolimbic circuitry, such as mesolimbic dopamine projections to nucleus accumbens (NAc) and ventral pallidum (VP), in controlling motivation to eat. The NAc and VP play special roles in mediating the hedonic impact (“liking”) and motivational incentive salience (“wanting”) of food rewards, and their interactions with LH help permit regulatory hunger/satiety modulation of food motivation and reward. Here, we review some progress that has been made regarding this circuitry and its functions: the identification of localized anatomical hedonic hotspots within NAc and VP for enhancing hedonic impact; interactions of NAc/VP hedonic hotspots with specific LH signals such as orexin; an anterior-posterior gradient of sites in NAc shell for producing intense appetitive eating vs. intense fearful reactions; and anatomically distributed appetitive functions of dopamine and mu opioid signals in NAc shell and related structures. Such findings help improve our understanding of NAc, VP, and LH interactions in mediating affective and motivation functions, including “liking” and “wanting” for food rewards. PMID:26124708

Autonomic responses to exercise: where is central command?

PubMed

Williamson, J W

2015-03-01

A central command is thought to involve a signal arising in a central area of the brain eliciting a parallel activation of the autonomic nervous system and skeletal muscle contraction during exercise. Although much of the neural circuitry involved in autonomic control has been identified, defining the specific higher brain region(s) serving in a central command capacity has proven more challenging. Investigators have been faced with redundancies in regulatory systems, feedback mechanisms and the complexities ofhuman neural connectivity. Several studies have attempted to address these issues and provide more definitive neuroanatomical information. However, none have clearly answered the question, "where is central command?" Copyright © 2014 Elsevier B.V. All rights reserved.

The physiology of boredom, depression and senile dementia.

PubMed

Saunders, M N

1996-05-01

Mental stimulation ensures the flow of blood, oxygen and nutrients to the brain. The stimulation can be either generated internally from thought and rumination or externally from our environment via the senses. Without this stimulation, neuron shrinkage and atrophy eventually may lead to depression and senile dementia. This paper explains why mental stimulation may be prevented from realizing its beneficial effects of increasing the blood flow to the brain. The hypothesis is based on feedback biological mechanisms that prevent overload of the neural circuitry due to excessive mental stimulation. However, if overstimulation is maintained over a long period and, with it, the overload protection process, it may eventually lead to permanent depletion of neuron connections and also neural communications.

Pathological choice: the neuroscience of gambling and gambling addiction.

PubMed

Clark, Luke; Averbeck, Bruno; Payer, Doris; Sescousse, Guillaume; Winstanley, Catharine A; Xue, Gui

2013-11-06

Gambling is pertinent to neuroscience research for at least two reasons. First, gambling is a naturalistic and pervasive example of risky decision making, and thus gambling games can provide a paradigm for the investigation of human choice behavior and "irrationality." Second, excessive gambling involvement (i.e., pathological gambling) is currently conceptualized as a behavioral addiction, and research on this condition may provide insights into addictive mechanisms in the absence of exogenous drug effects. This article is a summary of topics covered in a Society for Neuroscience minisymposium, focusing on recent advances in understanding the neural basis of gambling behavior, including translational findings in rodents and nonhuman primates, which have begun to delineate neural circuitry and neurochemistry involved.

Microstructural and functional connectivity in the developing preterm brain

PubMed Central

Lubsen, Julia; Vohr, Betty; Myers, Eliza; Hampson, Michelle; Lacadie, Cheryl; Schneider, Karen C.; Katz, Karol H.; Constable, R. Todd; Ment, Laura R.

2011-01-01

Prematurely born children are at increased risk for cognitive deficits, but the neurobiological basis of these findings remains poorly understood. Since variations in neural circuitry may influence performance on cognitive tasks, recent investigations have explored the impact of preterm birth on connectivity in the developing brain. Diffusion tensor imaging studies demonstrate widespread alterations in fractional anisotropy, a measure of axonal integrity and microstructural connectivity, throughout the developing preterm brain. Functional connectivity studies report that preterm neonates, children and adolescents exhibit alterations in both resting state and task-based connectivity when compared to term control subjects. Taken together, these data suggest that neurodevelopmental impairment following preterm birth may represent a disease of neural connectivity. PMID:21255705

Understanding the role of speech production in reading: Evidence for a print-to-speech neural network using graphical analysis.

PubMed

Cummine, Jacqueline; Cribben, Ivor; Luu, Connie; Kim, Esther; Bahktiari, Reyhaneh; Georgiou, George; Boliek, Carol A

2016-05-01

The neural circuitry associated with language processing is complex and dynamic. Graphical models are useful for studying complex neural networks as this method provides information about unique connectivity between regions within the context of the entire network of interest. Here, the authors explored the neural networks during covert reading to determine the role of feedforward and feedback loops in covert speech production. Brain activity of skilled adult readers was assessed in real word and pseudoword reading tasks with functional MRI (fMRI). The authors provide evidence for activity coherence in the feedforward system (inferior frontal gyrus-supplementary motor area) during real word reading and in the feedback system (supramarginal gyrus-precentral gyrus) during pseudoword reading. Graphical models provided evidence of an extensive, highly connected, neural network when individuals read real words that relied on coordination of the feedforward system. In contrast, when individuals read pseudowords the authors found a limited/restricted network that relied on coordination of the feedback system. Together, these results underscore the importance of considering multiple pathways and articulatory loops during language tasks and provide evidence for a print-to-speech neural network. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Alzheimer's disease Braak Stage progressions: reexamined and redefined as Borrelia infection transmission through neural circuits.

PubMed

MacDonald, Alan B

2007-01-01

Brain structure in health is a dynamic energized equation incorporating chemistry, neuronal structure, and circuitry components. The chemistry "piece" is represented by multiple neurotransmitters such as Acetylcholine, Serotonin, and Dopamine. The neuronal structure "piece" incorporates synapses and their connections. And finally circuits of neurons establish "architectural blueprints" of anatomic wiring diagrams of the higher order of brain neuron organizations. In Alzheimer's disease, there are progressive losses in all of these components. Brain structure crumbles. The deterioration in Alzheimer's is ordered, reproducible, and stepwise. Drs. Braak and Braak have described stages in the Alzheimer disease continuum. "Progressions" through Braak Stages benchmark "Regressions" in Cognitive function. Under the microscope, the Stages of Braak commence in brain regions near to the hippocampus, and over time, like a tsunami wave of destruction, overturn healthy brain regions, with neurofibrillary tangle damaged neurons "marching" through the temporal lobe, neocortex and occipital cortex. In effect the destruction ascends from the limbic regions to progressively destroy the higher brain centers. Rabies infection also "begins low and finishes high" in its wave of destruction of brain tissue. Herpes Zoster infections offer the paradigm of clinical latency of infection inside of nerves before the "marching commences". Varicella Zoster virus enters neurons in the pediatric years. Dormant virus remains inside the neurons for 50-80 years, tissue damage late in life (shingles) demonstrates the "march of the infection" down neural pathways (dermatomes) as linear areas of painful blisters loaded with virus from a childhood infection. Amalgamation of Zoster with Rabies models produces a hybrid model to explain all of the Braak Stages of Alzheimer's disease under a new paradigm, namely "Alzheimer's neuroborreliosis" in which latent Borrelia infections ascend neural circuits through the hippocampus to the higher brain centers, creating a trail of neurofibrillary tangle injured neurons in neural circuits of cholinergic neurons by transsynaptic transmission of infection from nerve to nerve.

Neuronal replacement therapy: previous achievements and challenges ahead

NASA Astrophysics Data System (ADS)

Grade, Sofia; Götz, Magdalena

2017-10-01

Lifelong neurogenesis and incorporation of newborn neurons into mature neuronal circuits operates in specialized niches of the mammalian brain and serves as role model for neuronal replacement strategies. However, to which extent can the remaining brain parenchyma, which never incorporates new neurons during the adulthood, be as plastic and readily accommodate neurons in networks that suffered neuronal loss due to injury or neurological disease? Which microenvironment is permissive for neuronal replacement and synaptic integration and which cells perform best? Can lost function be restored and how adequate is the participation in the pre-existing circuitry? Could aberrant connections cause malfunction especially in networks dominated by excitatory neurons, such as the cerebral cortex? These questions show how important connectivity and circuitry aspects are for regenerative medicine, which is the focus of this review. We will discuss the impressive advances in neuronal replacement strategies and success from exogenous as well as endogenous cell sources. Both have seen key novel technologies, like the groundbreaking discovery of induced pluripotent stem cells and direct neuronal reprogramming, offering alternatives to the transplantation of fetal neurons, and both herald great expectations. For these to become reality, neuronal circuitry analysis is key now. As our understanding of neuronal circuits increases, neuronal replacement therapy should fulfill those prerequisites in network structure and function, in brain-wide input and output. Now is the time to incorporate neural circuitry research into regenerative medicine if we ever want to truly repair brain injury.

Reorganization of Functional Networks in Verbal Working Memory Circuitry in Early Midlife: The Impact of Sex and Menopausal Status.

PubMed

Jacobs, Emily G; Weiss, Blair; Makris, Nikos; Whitfield-Gabrieli, Sue; Buka, Stephen L; Klibanski, Anne; Goldstein, Jill M

2017-05-01

Converging preclinical and human evidence indicates that the decline in ovarian estradiol production during the menopausal transition may play a mechanistic role in the neuronal changes that occur early in the aging process. Here, we present findings from a population-based fMRI study characterizing regional and network-level differences in working memory (WM) circuitry in midlife men and women (N = 142; age range 46-53), as a function of sex and reproductive stage. Reproductive histories and hormonal evaluations were used to determine menopausal status. Participants performed a verbal WM task during fMRI scanning. Results revealed robust differences in task-evoked responses in dorsolateral prefrontal cortex and hippocampus as a function of women's reproductive stage, despite minimal variance in chronological age. Sex differences in regional activity and functional connectivity that were pronounced between men and premenopausal women were diminished for postmenopausal women. Critically, analyzing data without regard to sex or reproductive status obscured group differences in the circuit-level neural strategies associated with successful working memory performance. These findings underscore the importance of reproductive age and hormonal status, over and above chronological age, for understanding sex differences in the aging of memory circuitry. Further, these findings suggest that early changes in working memory circuitry are evident decades before the age range typically targeted in cognitive aging studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The effect of exogenous cortisol during sleep on the behavioral and neural correlates of emotional memory consolidation in humans.

PubMed

van Marle, Hein J F; Hermans, Erno J; Qin, Shaozheng; Overeem, Sebastiaan; Fernández, Guillén

2013-09-01

A host of animal work demonstrates that the retention benefit for emotionally aversive over neutral memories is regulated by glucocorticoid action during memory consolidation. Particularly, glucocorticoids may affect systems-level processes that promote the gradual reorganization of emotional memory traces. These effects remain largely uninvestigated in humans. Therefore, in this functional magnetic resonance imaging study we administered hydrocortisone during a polysomnographically monitored night of sleep directly after healthy volunteers studied negative and neutral pictures in a double-blind, placebo-controlled, between-subjects design. The following evening memory consolidation was probed during a recognition memory test in the MR scanner by assessing the difference in brain activity associated with memory for the consolidated items studied before sleep and new, unconsolidated items studied shortly before test (remote vs. recent memory paradigm). Hydrocortisone administration resulted in elevated cortisol levels throughout the experimental night with no group difference at recent encoding or test. Behaviorally, we showed that cortisol enhanced the difference between emotional and neutral consolidated memory, effectively prioritizing emotional memory consolidation. On a neural level, we found that cortisol reduced amygdala reactivity related to the retrieval of these same consolidated, negative items. These findings show that cortisol administration during first post-encoding sleep had a twofold effect on the first 24h of emotional memory consolidation. While cortisol prioritized recognition memory for emotional items, it reduced reactivation of the neural circuitry underlying emotional responsiveness during retrieval. These findings fit recent theories on emotional depotentiation following consolidation during sleep, although future research should establish the sleep-dependence of this effect. Moreover, our data may shed light on mechanisms underlying potential therapeutic effects of cortisol administration following psychological trauma. Copyright © 2013 Elsevier Ltd. All rights reserved.

Motor control in a Drosophila taste circuit

PubMed Central

Gordon, Michael D.; Scott, Kristin

2009-01-01

Tastes elicit innate behaviors critical for directing animals to ingest nutritious substances and reject toxic compounds, but the neural basis of these behaviors is not understood. Here, we use a neural silencing screen to identify neurons required for a simple Drosophila taste behavior, and characterize a neural population that controls a specific subprogram of this behavior. By silencing and activating subsets of the defined cell population, we identify the neurons involved in the taste behavior as a pair of motor neurons located in the subesophageal ganglion (SOG). The motor neurons are activated by sugar stimulation of gustatory neurons and inhibited by bitter compounds; however, experiments utilizing split-GFP detect no direct connections between the motor neurons and primary sensory neurons, indicating that further study will be necessary to elucidate the circuitry bridging these populations. Combined, these results provide a general strategy and a valuable starting point for future taste circuit analysis. PMID:19217375

Six networks on a universal neuromorphic computing substrate.

PubMed

Pfeil, Thomas; Grübl, Andreas; Jeltsch, Sebastian; Müller, Eric; Müller, Paul; Petrovici, Mihai A; Schmuker, Michael; Brüderle, Daniel; Schemmel, Johannes; Meier, Karlheinz

2013-01-01

In this study, we present a highly configurable neuromorphic computing substrate and use it for emulating several types of neural networks. At the heart of this system lies a mixed-signal chip, with analog implementations of neurons and synapses and digital transmission of action potentials. Major advantages of this emulation device, which has been explicitly designed as a universal neural network emulator, are its inherent parallelism and high acceleration factor compared to conventional computers. Its configurability allows the realization of almost arbitrary network topologies and the use of widely varied neuronal and synaptic parameters. Fixed-pattern noise inherent to analog circuitry is reduced by calibration routines. An integrated development environment allows neuroscientists to operate the device without any prior knowledge of neuromorphic circuit design. As a showcase for the capabilities of the system, we describe the successful emulation of six different neural networks which cover a broad spectrum of both structure and functionality.

The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans

PubMed Central

Taylor, Sara B; Lewis, Candace R; Olive, M Foster

2013-01-01

Illicit psychostimulant addiction remains a significant problem worldwide, despite decades of research into the neural underpinnings and various treatment approaches. The purpose of this review is to provide a succinct overview of the neurocircuitry involved in drug addiction, as well as the acute and chronic effects of cocaine and amphetamines within this circuitry in humans. Investigational pharmacological treatments for illicit psychostimulant addiction are also reviewed. Our current knowledge base clearly demonstrates that illicit psychostimulants produce lasting adaptive neural and behavioral changes that contribute to the progression and maintenance of addiction. However, attempts at generating pharmacological treatments for psychostimulant addiction have historically focused on intervening at the level of the acute effects of these drugs. The lack of approved pharmacological treatments for psychostimulant addiction highlights the need for new treatment strategies, especially those that prevent or ameliorate the adaptive neural, cognitive, and behavioral changes caused by chronic use of this class of illicit drugs. PMID:24648786

Six Networks on a Universal Neuromorphic Computing Substrate

PubMed Central

Pfeil, Thomas; Grübl, Andreas; Jeltsch, Sebastian; Müller, Eric; Müller, Paul; Petrovici, Mihai A.; Schmuker, Michael; Brüderle, Daniel; Schemmel, Johannes; Meier, Karlheinz

2013-01-01

In this study, we present a highly configurable neuromorphic computing substrate and use it for emulating several types of neural networks. At the heart of this system lies a mixed-signal chip, with analog implementations of neurons and synapses and digital transmission of action potentials. Major advantages of this emulation device, which has been explicitly designed as a universal neural network emulator, are its inherent parallelism and high acceleration factor compared to conventional computers. Its configurability allows the realization of almost arbitrary network topologies and the use of widely varied neuronal and synaptic parameters. Fixed-pattern noise inherent to analog circuitry is reduced by calibration routines. An integrated development environment allows neuroscientists to operate the device without any prior knowledge of neuromorphic circuit design. As a showcase for the capabilities of the system, we describe the successful emulation of six different neural networks which cover a broad spectrum of both structure and functionality. PMID:23423583

Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens

PubMed Central

Woolfrey, Kevin M.; Penzes, Peter

2013-01-01

Converging evidence from cellular, electrophysiological, anatomic, and behavioral studies suggests that the remodeling of synapse structure and function is a critical component of cognition. This modulation of neuroplasticity can be achieved through the actions of numerous extracellular signals. Moreover, it is thought that it is the integration of different extracellular signals regulation of neuroplasticity that greatly influences cognitive function. One group of signals that exerts powerful effects on multiple neurologic processes is estrogens. Classically, estrogens have been described to exert their effects over a period of hours to days. However, there is now increasing evidence that estrogens can rapidly influence multiple behaviors, including those that require forebrain neural circuitry. Moreover, these effects are found in both sexes. Critically, it is now emerging that the modulation of cognition by rapid estrogenic signaling is achieved by activation of specific signaling cascades and regulation of synapse structure and function, cumulating in the rewiring of neural circuits. The importance of understanding the rapid effects of estrogens on forebrain function and circuitry is further emphasized as investigations continue to consider the potential of estrogenic-based therapies for neuropathologies. This review focuses on how estrogens can rapidly influence cognition and the emerging mechanisms that underlie these effects. We discuss the potential sources and the biosynthesis of estrogens within the brain and the consequences of rapid estrogenic-signaling on the remodeling of neural circuits. Furthermore, we argue that estrogens act via distinct signaling pathways to modulate synapse structure and function in a manner that may vary with cell type, developmental stage, and sex. Finally, we present a model in which the coordination of rapid estrogenic-signaling and activity-dependent stimuli can result in long-lasting changes in neural circuits, contributing to cognition, with potential relevance for the development of novel estrogenic-based therapies for neurodevelopmental or neurodegenerative disorders. PMID:24076546

Dual polarized, heat spreading rectenna

NASA Technical Reports Server (NTRS)

Epp, Larry W. (Inventor); Khan, Abdur R. (Inventor); Smith, R. Peter (Inventor); Smith, Hugh K. (Inventor)

1999-01-01

An aperture coupled patch splits energy from two different polarization components to different locations to spread heat. In addition, there is no physical electrical connection between the slot, patch and circuitry. The circuitry is located under a ground plane which shields against harmonic radiation back to the RF source.

Translating birdsong: songbirds as a model for basic and applied medical research.

PubMed

Brainard, Michael S; Doupe, Allison J

2013-07-08

Songbirds, long of interest to basic neuroscience, have great potential as a model system for translational neuroscience. Songbirds learn their complex vocal behavior in a manner that exemplifies general processes of perceptual and motor skill learning and, more specifically, resembles human speech learning. Song is subserved by circuitry that is specialized for vocal learning and production but that has strong similarities to mammalian brain pathways. The combination of highly quantifiable behavior and discrete neural substrates facilitates understanding links between brain and behavior, both in normal states and in disease. Here we highlight (a) behavioral and mechanistic parallels between birdsong and aspects of speech and social communication, including insights into mirror neurons, the function of auditory feedback, and genes underlying social communication disorders, and (b) contributions of songbirds to understanding cortical-basal ganglia circuit function and dysfunction, including the possibility of harnessing adult neurogenesis for brain repair.

Translating Birdsong: Songbirds as a model for basic and applied medical research

PubMed Central

2014-01-01

Songbirds, long of interest to basic neuroscientists, have great potential as a model system for translational neuroscience. Songbirds learn their complex vocal behavior in a manner that exemplifies general processes of perceptual and motor skill learning, and more specifically resembles human speech learning. Song is subserved by circuitry that is specialized for vocal learning and production, but that has strong similarities to mammalian brain pathways. The combination of a highly quantifiable behavior and discrete neural substrates facilitates understanding links between brain and behavior, both normally and in disease. Here we highlight 1) behavioral and mechanistic parallels between birdsong and aspects of speech and social communication, including insights into mirror neurons, the function of auditory feedback, and genes underlying social communication disorders, and 2) contributions of songbirds to understanding cortical-basal ganglia circuit function and dysfunction, including the possibility of harnessing adult neurogenesis for brain repair. PMID:23750515

Savoring the past: Positive memories evoke value representations in the striatum

PubMed Central

Speer, Megan E.; Bhanji, Jamil P.; Delgado, Mauricio R.

2014-01-01

Summary Reminders of happy memories can bring back pleasant feelings tied to the original experience, suggesting an intrinsic value in reminiscing about the positive past. However, the neural circuitry underlying the rewarding aspects of autobiographical memory is poorly understood. Using fMRI, we observed enhanced activity during the recall of positive relative to neutral autobiographical memories in corticostriatal circuits that also responded to monetary rewards. Enhanced activity in the striatum and medial prefrontal cortex was associated with increases in positive emotion during recall and striatal engagement further correlated with individual measures of resiliency. Striatal response to the recall of positive memories was greater in individuals whose mood improved after the task. Notably, participants were willing to sacrifice more tangible monetary rewards in order to reminisce about positive past experiences. Our findings suggest that recalling positive autobiographical memories is intrinsically valuable, which may be adaptive for regulating positive emotion and promoting better well-being. PMID:25451197

Translational Research on Habit and Alcohol.

PubMed

McKim, Theresa H; Shnitko, Tatiana A; Robinson, Donita L; Boettiger, Charlotte A

2016-03-01

Habitual actions enable efficient daily living, but they can also contribute to pathological behaviors that resistant change, such as alcoholism. Habitual behaviors are learned actions that appear goal-directed but are in fact no longer under the control of the action's outcome. Instead, these actions are triggered by stimuli, which may be exogenous or interoceptive, discrete or contextual. A major hallmark characteristic of alcoholism is continued alcohol use despite serious negative consequences. In essence, although the outcome of alcohol seeking and drinking is dramatically devalued, these actions persist, often triggered by environmental cues associated with alcohol use. Thus, alcoholism meets the definition of an initially goal-directed behavior that converts to a habit-based process. Habit and alcohol have been well investigated in rodent models, with comparatively less research in non-human primates and people. This review focuses on translational research on habit and alcohol with an emphasis on cross-species methodology and neural circuitry.

Neural circuits underlying visually evoked escapes in larval zebrafish

PubMed Central

Dunn, Timothy W.; Gebhardt, Christoph; Naumann, Eva A.; Riegler, Clemens; Ahrens, Misha B.; Engert, Florian; Del Bene, Filippo

2015-01-01

SUMMARY Escape behaviors deliver organisms away from imminent catastrophe. Here, we characterize behavioral responses of freely swimming larval zebrafish to looming visual stimuli simulating predators. We report that the visual system alone can recruit lateralized, rapid escape motor programs, similar to those elicited by mechanosensory modalities. Two-photon calcium imaging of retino-recipient midbrain regions isolated the optic tectum as an important center processing looming stimuli, with ensemble activity encoding the critical image size determining escape latency. Furthermore, we describe activity in retinal ganglion cell terminals and superficial inhibitory interneurons in the tectum during looming and propose a model for how temporal dynamics in tectal periventricular neurons might arise from computations between these two fundamental constituents. Finally, laser ablations of hindbrain circuitry confirmed that visual and mechanosensory modalities share the same premotor output network. Together, we establish a circuit for the processing of aversive stimuli in the context of an innate visual behavior. PMID:26804997

Genes, Circuits, and Precision Therapies for Autism and Related Neurodevelopmental Disorders

PubMed Central

2016-01-01

Research in genetics of neurodevelopmental disorders such as autism suggests that several hundred genes are likely risk factors for these disorders. This heterogeneity presents a challenge and an opportunity at the same time. While the exact identity of many of the genes remains to be discovered, genes identified to date encode for proteins that play roles in certain conserved pathways: protein synthesis, transcriptional/epigenetic regulation and synaptic signaling. Next generation of research in neurodevelopmental disorders needs to address the neural circuitry underlying the behavioral symptoms and co-morbidities, the cell types playing critical roles in these circuits and common intercellular signaling pathways that link diverse genes. Results from clinical trials have been mixed so far. Only when we are able to leverage the heterogeneity of neurodevelopmental disorders into precision medicine, will the mechanism-based therapeutics for these disorders start to unlock success. PMID:26472761

Growth cone travel in space and time: the cellular ensemble of cytoskeleton, adhesion, and membrane.

PubMed

Vitriol, Eric A; Zheng, James Q

2012-03-22

Growth cones, found at the tip of axonal projections, are the sensory and motile organelles of developing neurons that enable axon pathfinding and target recognition for precise wiring of the neural circuitry. To date, many families of conserved guidance molecules and their corresponding receptors have been identified that work in space and time to ensure billions of axons to reach their targets. Research in the past two decades has also gained significant insight into the ways in which growth cones translate extracellular signals into directional migration. This review aims to examine new progress toward understanding the cellular mechanisms underlying directional motility of the growth cone and to discuss questions that remain to be addressed. Specifically, we will focus on the cellular ensemble of cytoskeleton, adhesion, and membrane and examine how the intricate interplay between these processes orchestrates the directed movement of growth cones. Copyright © 2012 Elsevier Inc. All rights reserved.

In search of the motor engram: motor map plasticity as a mechanism for encoding motor experience.

PubMed

Monfils, Marie-H; Plautz, Erik J; Kleim, Jeffrey A

2005-10-01

Motor skill acquisition occurs through modification and organization of muscle synergies into effective movement sequences. The learning process is reflected neurophysiologically as a reorganization of movement representations within the primary motor cortex, suggesting that the motor map is a motor engram. However, the specific neural mechanisms underlying map plasticity are unknown. Here the authors review evidence that 1) motor map topography reflects the capacity for skilled movement, 2) motor skill learning induces reorganization of motor maps in a manner that reflects the kinematics of acquired skilled movement, 3) map plasticity is supported by a reorganization of cortical microcircuitry involving changes in synaptic efficacy, and 4) motor map integrity and topography are influenced by various neurochemical signals that coordinate changes in cortical circuitry to encode motor experience. Finally, the role of motor map plasticity in recovery of motor function after brain damage is discussed.

The Tell-Tale Tasks: A Review of Saccadic Research in Psychiatric Patient Populations

PubMed Central

Gooding, Diane C.; Basso, Michele A.

2008-01-01

This review focuses on saccade research with adult psychiatric patients. It begins with an introduction of the various types of saccades and the tasks used to evoke them. The functional significance of the different types of eye movements is briefly discussed. Research findings regarding the saccadic performance of different adult psychiatric patient populations are discussed in detail, with particular emphasis on findings regarding error rates, response latencies, and any specific task parameters that might affect those variables. Findings regarding the symptom, neurocognitive, and neural correlates of saccadic performance and the functional significance of patients’ saccadic deficits are also discussed. We also discuss the saccadic deficits displayed by various patient groups in terms of circuitry (e.g. cortical/basal ganglia circuits) that may be implicated in the underlying pathophysiology of several of these disorders. Future directions for research in this growing area are offered. PMID:18950927

Newborn Insula Gray Matter Volume is Prospectively Associated With Early Life Adiposity Gain

PubMed Central

Rasmussen, Jerod M.; Entringer, Sonja; Kruggel, Frithjof; Cooper, Dan M.; Styner, Martin; Gilmore, John H.; Potkin, Steven G.; Wadhwa, Pathik D.; Buss, Claudia

2017-01-01

Background The importance of energy homeostasis brain circuitry in the context of obesity is well established, however, the developmental ontogeny of this circuitry in humans is currently unknown. Here, we investigate the prospective association between newborn gray matter (GM) volume in the insula, a key brain region underlying energy homeostasis, and change in percent body fat accrual over the first six months of postnatal life, an outcome that represents among the most reliable infant predictors of childhood obesity risk. Methods 52 infants (29 male, 23 female, gestational age at birth=39[1.5] weeks) were assessed using structural MRI shortly after birth (postnatal age at MRI scan=25.9[12.2] days), and serial Dual X-Ray Absorptiometry shortly after birth (postnatal age at DXA scan 1=24.6[11.4] days) and at six months of age (postnatal age at DXA scan 2=26.7[3.3] weeks). Results Insula GM volume was inversely associated with change in percent body fat from birth to six-months postnatal age and accounted for 19% of its variance (β=-3.6%/S.D., p=0.001). This association was driven by the central-posterior portion of the insula, a region of particular importance for gustation and interoception. The direction of this effect is in concordance with observations in adults, and the results remained statistically significant after adjusting for relevant covariates and potential confounding variables. Conclusions Together, these findings suggest an underlying neural basis of childhood obesity that precedes the influence of the postnatal environment. The identification of plausible brain-related biomarkers of childhood obesity risk that predate the influence of the postnatal obesogenic environment may contribute to an improved understanding of propensity for obesity, early identification of at-risk individuals, and intervention targets for primary prevention. PMID:28487552

Age-related changes in the functional neuroanatomy of overt speech production.

PubMed

Sörös, Peter; Bose, Arpita; Sokoloff, Lisa Guttman; Graham, Simon J; Stuss, Donald T

2011-08-01

Alterations of existing neural networks during healthy aging, resulting in behavioral deficits and changes in brain activity, have been described for cognitive, motor, and sensory functions. To investigate age-related changes in the neural circuitry underlying overt non-lexical speech production, functional MRI was performed in 14 healthy younger (21-32 years) and 14 healthy older individuals (62-84 years). The experimental task involved the acoustically cued overt production of the vowel /a/ and the polysyllabic utterance /pataka/. In younger and older individuals, overt speech production was associated with the activation of a widespread articulo-phonological network, including the primary motor cortex, the supplementary motor area, the cingulate motor areas, and the posterior superior temporal cortex, similar in the /a/ and /pataka/ condition. An analysis of variance with the factors age and condition revealed a significant main effect of age. Irrespective of the experimental condition, significantly greater activation was found in the bilateral posterior superior temporal cortex, the posterior temporal plane, and the transverse temporal gyri in younger compared to older individuals. Significantly greater activation was found in the bilateral middle temporal gyri, medial frontal gyri, middle frontal gyri, and inferior frontal gyri in older vs. younger individuals. The analysis of variance did not reveal a significant main effect of condition and no significant interaction of age and condition. These results suggest a complex reorganization of neural networks dedicated to the production of speech during healthy aging. Copyright © 2009 Elsevier Inc. All rights reserved.

Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa

PubMed Central

Holsen, Laura M.; Lawson, Elizabeth A.; Christensen, Kara; Klibanski, Anne; Goldstein, Jill M.

2014-01-01

Evidence contributing to the understanding of neurobiological mechanisms underlying appetite dysregulation in anorexia nervosa draws heavily on separate lines of research into neuroendocrine and neural circuitry functioning. In particular, studies consistently cite elevated ghrelin and abnormal activation patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula) regions governing appetite. The current preliminary study examined the interaction of these systems, based on research demonstrating associations between circulating ghrelin levels and activity in these regions in healthy individuals. In a cross-sectional design, we studied 13 women with active anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy-weight control women using a food cue functional magnetic resonance imaging paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight control women exhibited significant positive associations between fasting acylated ghrelin and activity in the right amygdala, hippocampus, insula, and orbitofrontal cortex in response to high-calorie foods, associations which were absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative relationship between ghrelin and activity in the left hippocampus in response to high-calorie foods, while women with AN showed a positive association between ghrelin and activity in the right orbitofrontal cortex in response to low-calorie foods. Findings suggest a breakdown in the interaction between ghrelin signaling and neural activity in relation to reward responsivity in AN, a phenomenon that may be further characterized using pharmacogenetic studies. PMID:24862390

Neural division of labor in reading is constrained by culture: A training study of reading Chinese characters

PubMed Central

Zhao, Jingjing; Wang, Xiaoyi; Frost, Stephen J.; Sun, Wan; Fang, Shin-Yi; Mencl, W. Einar; Pugh, Kenneth R.; Shu, Hua; Rueckl, Jay G.

2014-01-01

Word reading in alphabetic language involves a cortical system with multiple components whose division of labor depends on the transparency of the writing system. To gain insight about the division of labor between phonology and semantics subserving word reading in Chinese, a deep non-alphabetic writing system, fMRI was used to investigate the effects of phonological and semantic training on the cortical circuitry for oral naming of Chinese characters. In a training study, we examined whether a training task that differentially focused readers' attention on the phonological or semantic properties of a Chinese character changes the patterns of cortical activation that was evoked by that character in a subsequent naming task. Our imaging results corroborate that the cortical regions underlying reading in Chinese largely overlaps the left-hemisphere reading system responsible for reading in alphabetic languages, with some cortical regions in the left-hemisphere uniquely recruited for reading in Chinese. However, in contrast to findings from studies of English word naming, we observed considerable overlap in the neural activation patterns associated with phonological and semantic training on naming Chinese characters, which we suggest may reflect a balanced neural division of labor between phonology and semantics in Chinese character reading. The equitable division of labor for Chinese reading might be driven by the special statistical structure of the writing system, which includes equally systematic mappings in the correspondences between written forms and their pronunciations and meanings. PMID:24607883

Genetic determinants of aggression and impulsivity in humans.

PubMed

Pavlov, Konstantin A; Chistiakov, Dimitry A; Chekhonin, Vladimir P

2012-02-01

Human aggression/impulsivity-related traits have a complex background that is greatly influenced by genetic and non-genetic factors. The relationship between aggression and anxiety is regulated by highly conserved brain regions including amygdala, which controls neural circuits triggering defensive, aggressive, or avoidant behavioral models. The dysfunction of neural circuits responsible for emotional control was shown to represent an etiological factor of violent behavior. In addition to the amygdala, these circuits also involve the anterior cingulated cortex and regions of the prefrontal cortex. Excessive reactivity in the amygdala coupled with inadequate prefrontal regulation serves to increase the likelihood of aggressive behavior. Developmental alterations in prefrontal-subcortical circuitry as well as neuromodulatory and hormonal abnormality appear to play a role. Imbalance in testosterone/serotonin and testosterone/cortisol ratios (e.g., increased testosterone levels and reduced cortisol levels) increases the propensity toward aggression because of reduced activation of the neural circuitry of impulse control and self-regulation. Serotonin facilitates prefrontal inhibition, and thus insufficient serotonergic activity can enhance aggression. Genetic predisposition to aggression appears to be deeply affected by the polymorphic genetic variants of the serotoninergic system that influences serotonin levels in the central and peripheral nervous system, biological effects of this hormone, and rate of serotonin production, synaptic release and degradation. Among these variants, functional polymorphisms in the monoamine oxidase A (MAOA) and serotonin transporter (5-HTT) may be of particular importance due to the relationship between these polymorphic variants and anatomical changes in the limbic system of aggressive people. Furthermore, functional variants of MAOA and 5-HTT are capable of mediating the influence of environmental factors on aggression-related traits. In this review, we consider genetic determinants of human aggression, with special emphasis on genes involved in serotonin and dopamine metabolism and function.

Vortioxetine reduces BOLD signal during performance of the N-back working memory task: a randomised neuroimaging trial in remitted depressed patients and healthy controls

PubMed Central

Smith, J; Browning, M; Conen, S; Smallman, R; Buchbjerg, J; Larsen, K G; Olsen, C K; Christensen, S R; Dawson, G R; Deakin, J F; Hawkins, P; Morris, R; Goodwin, G; Harmer, C J

2018-01-01

Cognitive dysfunction is common in depression during both acute episodes and remission. Vortioxetine is a novel multimodal antidepressant that has improved cognitive function including executive function in depressed patients in randomised placebo-controlled clinical trials. However, it is unclear whether vortioxetine is able to target directly the neural circuitry implicated in the cognitive deficits in depression. Remitted depressed (n=48) and healthy volunteers (n=48) were randomised to receive 14 days treatment with 20 mg vortioxetine or placebo in a double-blind design. The effects of treatment on functional magnetic resonance imaging responses during an N-back working memory task were assessed at baseline and at the end of treatment. Neuropsychological measures of executive function, speed and information processing, attention and learning and memory were examined with the Trail Making Test (TMT), Rey Auditory Learning Test and Digit Symbol Substitution Test before and after treatment; subjective cognitive function was assessed using the Perceived Deficits Questionnaire (PDQ). Compared with placebo, vortioxetine reduced activation in the right dorsolateral prefrontal cortex and left hippocampus during the N-back task compared with placebo. Vortioxetine also increased TMT-A performance and self-reported cognitive function on the PDQ. These effects were seen across both subject groups. Vortioxetine modulates neural responses across a circuit subserving working memory in a direction opposite to the changes described in depression, when performance is maintained. This study provides evidence that vortioxetine has direct effects on the neural circuitry supporting cognitive function that can be dissociated from its effects on the mood symptoms of depression. PMID:28533517

Amygdala activity and prefrontal cortex-amygdala effective connectivity to emerging emotional faces distinguish remitted and depressed mood states in bipolar disorder.

PubMed

Perlman, Susan B; Almeida, Jorge R C; Kronhaus, Dina M; Versace, Amelia; Labarbara, Edmund J; Klein, Crystal R; Phillips, Mary L

2012-03-01

Few studies have employed effective connectivity (EC) to examine the functional integrity of neural circuitry supporting abnormal emotion processing in bipolar disorder (BD), a key feature of the illness. We used Granger Causality Mapping (GCM) to map EC between the prefrontal cortex (PFC) and bilateral amygdala and a novel paradigm to assess emotion processing in adults with BD. Thirty-one remitted adults with BD [(remitted BD), mean age = 32 years], 21 adults with BD in a depressed episode [(depressed BD), mean age = 33 years], and 25 healthy control participants [(HC), mean age = 31 years] performed a block-design emotion processing task requiring color-labeling of a color flash superimposed on a task-irrelevant face morphing from neutral to emotional (happy, sad, angry, or fearful). GCM measured EC preceding (top-down) and following (bottom-up) activity between the PFC and the left and right amygdalae. Our findings indicated patterns of abnormally elevated bilateral amygdala activity in response to emerging fearful, sad, and angry facial expressions in remitted-BD subjects versus HC, and abnormally elevated right amygdala activity to emerging fearful faces in depressed-BD subjects versus HC. We also showed distinguishable patterns of abnormal EC between the amygdala and dorsomedial and ventrolateral PFC, especially to emerging happy and sad facial expressions in remitted-BD and depressed-BD subjects. EC measures of neural system level functioning can further understanding of neural mechanisms associated with abnormal emotion processing and regulation in BD. Our findings suggest major differences in recruitment of amygdala-PFC circuitry, supporting implicit emotion processing between remitted-BD and depressed-BD subjects, which may underlie changes from remission to depression in BD. © 2012 John Wiley and Sons A/S.

Regulation of endogenous neural stem/progenitor cells for neural repair—factors that promote neurogenesis and gliogenesis in the normal and damaged brain

PubMed Central

Christie, Kimberly J.; Turnley, Ann M.

2012-01-01

Neural stem/precursor cells in the adult brain reside in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. These cells primarily generate neuroblasts that normally migrate to the olfactory bulb (OB) and the dentate granule cell layer respectively. Following brain damage, such as traumatic brain injury, ischemic stroke or in degenerative disease models, neural precursor cells from the SVZ in particular, can migrate from their normal route along the rostral migratory stream (RMS) to the site of neural damage. This neural precursor cell response to neural damage is mediated by release of endogenous factors, including cytokines and chemokines produced by the inflammatory response at the injury site, and by the production of growth and neurotrophic factors. Endogenous hippocampal neurogenesis is frequently also directly or indirectly affected by neural damage. Administration of a variety of factors that regulate different aspects of neural stem/precursor biology often leads to improved functional motor and/or behavioral outcomes. Such factors can target neural stem/precursor proliferation, survival, migration and differentiation into appropriate neuronal or glial lineages. Newborn cells also need to subsequently survive and functionally integrate into extant neural circuitry, which may be the major bottleneck to the current therapeutic potential of neural stem/precursor cells. This review will cover the effects of a range of intrinsic and extrinsic factors that regulate neural stem/precursor cell functions. In particular it focuses on factors that may be harnessed to enhance the endogenous neural stem/precursor cell response to neural damage, highlighting those that have already shown evidence of preclinical effectiveness and discussing others that warrant further preclinical investigation. PMID:23346046

Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa

PubMed Central

Holsen, Laura M.; Lawson, Elizabeth A.; Blum, Justine; Ko, Eunice; Makris, Nikos; Fazeli, Pouneh K.; Klibanski, Anne; Goldstein, Jill M.

2012-01-01

Background Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait. Methods We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal. Results We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease. Limitations Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included. Conclusion Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food’s reward value and integration of these with interoceptive signalling of one’s internal state of well-being, with important relations between brain activity and homeostatic and hedonic aspects of appetite. Our findings give novel evidence of disruption in neurobiological circuits and stress the importance of examining both state and trait characteristics in the investigation of brain phenotypes in individuals with anorexia nervosa. PMID:22498079

Spatiochromatic Interactions between Individual Cone Photoreceptors in the Human Retina

PubMed Central

Sabesan, Ramkumar; Sincich, Lawrence C.

2017-01-01

A remarkable feature of human vision is that the retina and brain have evolved circuitry to extract useful spatial and spectral information from signals originating in a photoreceptor mosaic with trichromatic constituents that vary widely in their relative numbers and local spatial configurations. A critical early transformation applied to cone signals is horizontal-cell-mediated lateral inhibition, which imparts a spatially antagonistic surround to individual cone receptive fields, a signature inherited by downstream neurons and implicated in color signaling. In the peripheral retina, the functional connectivity of cone inputs to the circuitry that mediates lateral inhibition is not cone-type specific, but whether these wiring schemes are maintained closer to the fovea remains unsettled, in part because central retinal anatomy is not easily amenable to direct physiological assessment. Here, we demonstrate how the precise topography of the long (L)-, middle (M)-, and short (S)-wavelength-sensitive cones in the human parafovea (1.5° eccentricity) shapes perceptual sensitivity. We used adaptive optics microstimulation to measure psychophysical detection thresholds from individual cones with spectral types that had been classified independently by absorptance imaging. Measured against chromatic adapting backgrounds, the sensitivities of L and M cones were, on average, receptor-type specific, but individual cone thresholds varied systematically with the number of preferentially activated cones in the immediate neighborhood. The spatial and spectral patterns of these interactions suggest that interneurons mediating lateral inhibition in the central retina, likely horizontal cells, establish functional connections with L and M cones indiscriminately, implying that the cone-selective circuitry supporting red–green color vision emerges after the first retinal synapse. SIGNIFICANCE STATEMENT We present evidence for spatially antagonistic interactions between individual, spectrally typed cones in the central retina of human observers using adaptive optics. Using chromatic adapting fields to modulate the relative steady-state activity of long (L)- and middle (M)-wavelength-sensitive cones, we found that single-cone detection thresholds varied predictably with the spectral demographics of the surrounding cones. The spatial scale and spectral pattern of these photoreceptor interactions were consistent with lateral inhibition mediated by retinal horizontal cells that receive nonselective input from L and M cones. These results demonstrate a clear link between the neural architecture of the visual system inputs—cone photoreceptors—and visual perception and have implications for the neural locus of the cone-specific circuitry supporting color vision. PMID:28871030

Gustatory processing and taste memory in Drosophila

PubMed Central

Masek, Pavel; Keene, Alex C.

2018-01-01

Taste allows animals to discriminate the value and potential toxicity of food prior to ingestion. Many tastants elicit an innate attractive or avoidance response that is modifiable with nutritional state and prior experience. A powerful genetic tool kit, well-characterized gustatory system, and standardized behavioral assays make the fruit fly, Drosophila melanogaster, an excellent system for investigating taste processing and memory. Recent studies have used this system to identify the neural basis for acquired taste preference. These studies have revealed a role for dopamine-mediated plasticity of the mushroom bodies that modulate the threshold of response to appetitive tastants. The identification of neural circuitry regulating taste memory provides a system to study the genetic and physiological processes that govern plasticity within a defined memory circuit. PMID:27328844

Multistability and metastability: understanding dynamic coordination in the brain

PubMed Central

Kelso, J. A. Scott

2012-01-01

Multistable coordination dynamics exists at many levels, from multifunctional neural circuits in vertebrates and invertebrates to large-scale neural circuitry in humans. Moreover, multistability spans (at least) the domains of action and perception, and has been found to place constraints upon, even dictating the nature of, intentional change and the skill-learning process. This paper reviews some of the key evidence for multistability in the aforementioned areas, and illustrates how it has been measured, modelled and theoretically understood. It then suggests how multistability—when combined with essential aspects of coordination dynamics such as instability, transitions and (especially) metastability—provides a platform for understanding coupling and the creative dynamics of complex goal-directed systems, including the brain and the brain–behaviour relation. PMID:22371613

Chronic pain. Decreased motivation during chronic pain requires long-term depression in the nucleus accumbens.

PubMed

Schwartz, Neil; Temkin, Paul; Jurado, Sandra; Lim, Byung Kook; Heifets, Boris D; Polepalli, Jai S; Malenka, Robert C

2014-08-01

Several symptoms associated with chronic pain, including fatigue and depression, are characterized by reduced motivation to initiate or complete goal-directed tasks. However, it is unknown whether maladaptive modifications in neural circuits that regulate motivation occur during chronic pain. Here, we demonstrate that the decreased motivation elicited in mice by two different models of chronic pain requires a galanin receptor 1-triggered depression of excitatory synaptic transmission in indirect pathway nucleus accumbens medium spiny neurons. These results demonstrate a previously unknown pathological adaption in a key node of motivational neural circuitry that is required for one of the major sequela of chronic pain states and syndromes. Copyright © 2014, American Association for the Advancement of Science.

Neural signatures of cognitive and emotional biases in depression

PubMed Central

Fossati, Philippe

2008-01-01

Functional brain imaging studies suggest that depression is a system-level disorder affecting discrete but functionally linked cortical and limbic structures, with abnormalities in the anterior cingulate, lateral, ami medial prefrontal cortex, amygdala, ami hippocampus. Within this circuitry, abnormal corticolimbic interactions underlie cognitive deficits ami emotional impairment in depression. Depression involves biases toward processing negative emotional information and abnormal self-focus in response to emotional stimuli. These biases in depression could reflect excessive analytical self-focus in depression, as well as impaired cognitive control of emotional response to negative stimuli. By combining structural and functional investigations, brain imaging studies mav help to generate novel antidepressant treatments that regulate structural and factional plasticity within the neural network regulating mood and affective behavior.

Neural Correlates of Psychotherapeutic Treatment of Post-traumatic Stress Disorder: A Systematic Literature Review.

PubMed

Malejko, Kathrin; Abler, Birgit; Plener, Paul L; Straub, Joana

2017-01-01

Post-traumatic stress disorder (PTSD) is a common psychiatric disease with changes in neural circuitries. Neurobiological models conceptualize the symptoms of PTSD as correlates of a dysfunctional stress reaction to traumatic events. Functional imaging studies showed an increased amygdala and a decreased prefrontal cortex response in PTSD patients. As psychotherapeutic approaches represent the gold standard for PTSD treatment, it is important to examine its underlying neurobiological correlates. Studies published until August 2016 were selected through systematic literature research in the databases PubMed, PsychInfo, and Cochrane Library's Central Register of Controlled Trials or were identified manually by searching reference lists of selected articles. Search terms were "neural correlates" OR "fMRI" OR "SPECT," AND "therapy" AND "PTSD." A total of 19 articles were included in the present review whereof 15 studies compared pre-to-post-therapy signal changes, six studies related pre-treatment activity to pre-to-post-symptom improvement, and four studies compared neural correlates of responders versus non-responders. The disposed therapy forms were cognitive behavioral therapy (CBT), eye movement desensitization and reprocessing, cognitive therapy, exposure therapy, mindfulness-based intervention, brief eclectic psychotherapy, and unspecified therapy. Successful psychotherapy of PTSD was repeatedly shown to be accompanied by decreased activity in the amygdala and the insula as well as increased activity in the dorsal anterior cingulate cortex (dACC) and hippocampus. Elevated dACC activity prior to treatment was related to subsequent treatment success and a positive predictor for treatment response. Elevated amygdala and insula pre-treatment activities were related to treatment failure. Decreased activity in limbic brain regions and increased activity in frontal brain areas in PTSD patients after successful psychotherapeutic treatment might reflect regained top-down control over previously impaired bottom-up processes.

Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes.

PubMed

Olivo, Gaia; Wiemerslage, Lyle; Nilsson, Emil K; Solstrand Dahlberg, Linda; Larsen, Anna L; Olaya Búcaro, Marcela; Gustafsson, Veronica P; Titova, Olga E; Bandstein, Marcus; Larsson, Elna-Marie; Benedict, Christian; Brooks, Samantha J; Schiöth, Helgi B

2016-01-01

Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.

Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes

PubMed Central

Olivo, Gaia; Wiemerslage, Lyle; Nilsson, Emil K.; Solstrand Dahlberg, Linda; Larsen, Anna L.; Olaya Búcaro, Marcela; Gustafsson, Veronica P.; Titova, Olga E.; Bandstein, Marcus; Larsson, Elna-Marie; Benedict, Christian; Brooks, Samantha J.; Schiöth, Helgi B.

2016-01-01

Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention. PMID:26924971

Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards.

PubMed

Damiano, Cara R; Aloi, Joseph; Dunlap, Kaitlyn; Burrus, Caley J; Mosner, Maya G; Kozink, Rachel V; McLaurin, Ralph Edward; Mullette-Gillman, O'Dhaniel A; Carter, Ronald McKell; Huettel, Scott A; McClernon, Francis Joseph; Ashley-Koch, Allison; Dichter, Gabriel S

2014-01-31

There has been significant progress in identifying genes that confer risk for autism spectrum disorders (ASDs). However, the heterogeneity of symptom presentation in ASDs impedes the detection of ASD risk genes. One approach to understanding genetic influences on ASD symptom expression is to evaluate relations between variants of ASD candidate genes and neural endophenotypes in unaffected samples. Allelic variations in the oxytocin receptor (OXTR) gene confer small but significant risk for ASDs for which the underlying mechanisms may involve associations between variability in oxytocin signaling pathways and neural response to rewards. The purpose of this preliminary study was to investigate the influence of allelic variability in the OXTR gene on neural responses to monetary rewards in healthy adults using functional magnetic resonance imaging (fMRI). The moderating effects of three single nucleotide polymorphisms (SNPs) (rs1042778, rs2268493 and rs237887) of the OXTR gene on mesolimbic responses to rewards were evaluated using a monetary incentive delay fMRI task. T homozygotes of the rs2268493 SNP demonstrated relatively decreased activation in mesolimbic reward circuitry (including the nucleus accumbens, amygdala, insula, thalamus and prefrontal cortical regions) during the anticipation of rewards but not during the outcome phase of the task. Allelic variation of the rs1042778 and rs237887 SNPs did not moderate mesolimbic activation during either reward anticipation or outcomes. This preliminary study suggests that the OXTR SNP rs2268493, which has been previously identified as an ASD risk gene, moderates mesolimbic responses during reward anticipation. Given previous findings of decreased mesolimbic activation during reward anticipation in ASD, the present results suggest that OXTR may confer ASD risk via influences on the neural systems that support reward anticipation.

Differential Expression of Phosphorylated Mitogen-Activated Protein Kinase (pMAPK) in the Lateral Amygdala of Mice Selectively Bred for High and Low Fear

DTIC Science & Technology

2013-07-02

amygdala induced by hippocampal formation stimulation in vivo. The Journal of neuroscience: the official journal of the Society for Neuroscience 15...6 Figure 1.3. Schematic model of the neural circuitry of Pavlovian auditory fear conditioning. Model shows how an auditory conditioned...stimulus and a nociceptive unconditioned foot shock stimulus converge in the lateral amygdala (LA) via auditory thalamus and cortex and somatosensory

TQUID Magnetometer and Artificial Neural Circuitry Based on a Topological Kondo Insulator

DTIC Science & Technology

2016-05-01

phenomena in this surface-bulk system. Sufficient Joule heating , induced by an external DC current, can heat the bulk into a less insulating state, and...are the surface and bulk resistances with insulating gap Δ; H = H0(/0)3 and are the heat capacity dominated by phonons and...0, while Δ is the energy gap in the insulating bulk; is the temperature independent heat transfer rate trough external leads, which plays the

The Cerebellum, Sensitive Periods, and Autism

PubMed Central

Wang, Samuel S.-H.; Kloth, Alexander D.; Badura, Aleksandra

2014-01-01

Cerebellar research has focused principally on adult motor function. However, the cerebellum also maintains abundant connections with nonmotor brain regions throughout postnatal life. Here we review evidence that the cerebellum may guide the maturation of remote nonmotor neural circuitry and influence cognitive development, with a focus on its relationship with autism. Specific cerebellar zones influence neocortical substrates for social interaction, and we propose that sensitive-period disruption of such internal brain communication can account for autism's key features. PMID:25102558

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2014-09-01

2004. He served as Guest Coeditor of a special issue on applied neurodynamics for the Journal of Neural Engineering with Dr. Peter Thomas in December...for the millions of individuals who are left with permanent motor and cognitive impairments after acquired brain injury, as occurs in stroke and...Other investigators have proposed a closed-loop approach for a cognitive prosthesis that has shown promise in animal models (40). Other potential

Differences in Brain Activity during a Verbal Associative Memory Encoding Task in High- and Low-fit Adolescents

PubMed Central

Herting, Megan M.; Nagel, Bonnie J.

2013-01-01

Aerobic fitness is associated with better memory performance as well as larger volumes in memory-related brain regions in children, adolescents, and elderly. It is unclear if aerobic exercise also influences learning and memory functional neural circuitry. Here, we examine brain activity in 17 high-fit (HF) and 17 low-fit (LF) adolescents during a subsequent memory encoding paradigm using fMRI. Despite similar memory performance, HF and LF youth displayed a number of differences in memory-related and default mode (DMN) brain regions during encoding later remembered versus forgotten word pairs. Specifically, HF youth displayed robust deactivation in DMN areas, including the ventral medial PFC and posterior cingulate cortex, whereas LF youth did not show this pattern. Furthermore, LF youth showed greater bilateral hippocampal and right superior frontal gyrus activation during encoding of later remembered versus forgotten word pairs. Follow-up task-dependent functional correlational analyses showed differences in hippocampus and DMN activity coupling during successful encoding between the groups, suggesting aerobic fitness during adolescents may impact functional connectivity of the hippocampus and DMN during memory encoding. To our knowledge, this study is the first to examine the influence of aerobic fitness on hippocampal function and memory-related neural circuitry using fMRI. Taken together with previous research, these findings suggest aerobic fitness can influence not only memory-related brain structure, but also brain function. PMID:23249350

Mapping Compulsivity in the DSM-5 Obsessive Compulsive and Related Disorders: Cognitive Domains, Neural Circuitry, and Treatment

PubMed Central

Apergis-Schoute, Annemieke M; Vaghi, Matilde M; Banca, Paula; Gillan, Claire M; Voon, Valerie; Chamberlain, Samuel R; Cinosi, Eduardo; Reid, Jemma; Shahper, Sonia; Bullmore, Edward T; Sahakian, Barbara J; Robbins, Trevor W

2018-01-01

Abstract Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce harm. Growing evidence suggests that the neurocognitive mechanisms mediating behavioral inhibition (motor inhibition, cognitive inflexibility) reversal learning and habit formation (shift from goal-directed to habitual responding) contribute toward compulsive activity in a broad range of disorders. In obsessive compulsive disorder, distributed network perturbation appears focused around the prefrontal cortex, caudate, putamen, and associated neuro-circuitry. Obsessive compulsive disorder-related attentional set-shifting deficits correlated with reduced resting state functional connectivity between the dorsal caudate and the ventrolateral prefrontal cortex on neuroimaging. In contrast, experimental provocation of obsessive compulsive disorder symptoms reduced neural activation in brain regions implicated in goal-directed behavioral control (ventromedial prefrontal cortex, caudate) with concordant increased activation in regions implicated in habit learning (presupplementary motor area, putamen). The ventromedial prefrontal cortex plays a multifaceted role, integrating affective evaluative processes, flexible behavior, and fear learning. Findings from a neuroimaging study of Pavlovian fear reversal, in which obsessive compulsive disorder patients failed to flexibly update fear responses despite normal initial fear conditioning, suggest there is an absence of ventromedial prefrontal cortex safety signaling in obsessive compulsive disorder, which potentially undermines explicit contingency knowledge and may help to explain the link between cognitive inflexibility, fear, and anxiety processing in compulsive disorders such as obsessive compulsive disorder. PMID:29036632

Translational studies of goal-directed action as a framework for classifying deficits across psychiatric disorders

PubMed Central

Griffiths, Kristi R.; Morris, Richard W.; Balleine, Bernard W.

2014-01-01

The ability to learn contingencies between actions and outcomes in a dynamic environment is critical for flexible, adaptive behavior. Goal-directed actions adapt to changes in action-outcome contingencies as well as to changes in the reward-value of the outcome. When networks involved in reward processing and contingency learning are maladaptive, this fundamental ability can be lost, with detrimental consequences for decision-making. Impaired decision-making is a core feature in a number of psychiatric disorders, ranging from depression to schizophrenia. The argument can be developed, therefore, that seemingly disparate symptoms across psychiatric disorders can be explained by dysfunction within common decision-making circuitry. From this perspective, gaining a better understanding of the neural processes involved in goal-directed action, will allow a comparison of deficits observed across traditional diagnostic boundaries within a unified theoretical framework. This review describes the key processes and neural circuits involved in goal-directed decision-making using evidence from animal studies and human neuroimaging. Select studies are discussed to outline what we currently know about causal judgments regarding actions and their consequences, action-related reward evaluation, and, most importantly, how these processes are integrated in goal-directed learning and performance. Finally, we look at how adaptive decision-making is impaired across a range of psychiatric disorders and how deepening our understanding of this circuitry may offer insights into phenotypes and more targeted interventions. PMID:24904322

OPTOGENETICS, SEX AND VIOLENCE IN THE BRAIN: IMPLICATIONS FOR PSYCHIATRY

PubMed Central

Anderson, David J.

2012-01-01

Pathological aggression, and the inability to control aggressive impulses, takes a tremendous toll on society. Yet aggression is a normal component of the innate behavior repertoire of most vertebrate animal species, as well as of many invertebrates. Progress in understanding the etiology of disorders of aggressive behavior, whether genetic or environmental in nature, therefore requires an understanding of the brain circuitry that controls normal aggression. Efforts to understand this circuitry at the level of specific neuronal populations have been constrained by the limited resolution of classical methodologies, such as electrical stimulation and electrolytic lesion. The availability of new, genetically based tools for mapping and manipulating neural circuits at the level of specific, genetically defined neuronal subtypes provides an opportunity to investigate the functional organization of aggression circuitry with cellular resolution. However these technologies are optimally applied in the mouse, where there has been surprisingly little traditional work on the functional neuroanatomy of aggression. Here we discuss recent, initial efforts to apply optogenetics and other state-of-the-art methods to the dissection of aggression circuitry in the mouse. We find, surprisingly, that neurons necessary and sufficient for inter-male aggression are located within the ventrolateral subdivision of the ventromedial hypothalamic nucleus (VMHvl), a structure traditionally associated with reproductive behavior. These neurons are intermingled with neurons activated during male-female mating, with ~20% overlap between the populations. We discuss the significance of these findings with respect to neuroethological and neuroanatomical perspectives on the functional organization of innate behaviors, and their potential implications for psychiatry. PMID:22209636

Catecholaminergic connectivity to the inner ear, central auditory and vocal motor circuitry in the plainfin midshipman fish, Porichthys notatus

PubMed Central

Forlano, Paul M.; Kim, Spencer D.; Krzyminska, Zuzanna M.; Sisneros, Joseph A.

2014-01-01

Although the neuroanatomical distribution of catecholaminergic (CA) neurons has been well documented across all vertebrate classes, few studies have examined CA connectivity to physiologically and anatomically identified neural circuitry that controls behavior. The goal of this study was to characterize CA distribution in the brain and inner ear of the plainfin midshipman fish (Porichthys notatus) with particular emphasis on their relationship with anatomically labeled circuitry that both produces and encodes social acoustic signals in this species. Neurobiotin labeling of the main auditory endorgan, the saccule, combined with tyrosine hydroxylase immunofluorescence (TH-ir) revealed a strong CA innervation of both the peripheral and central auditory system. Diencephalic TH-ir neurons in the periventricular posterior tuberculum, known to be dopaminergic, send ascending projections to the ventral telencephalon and prominent descending projections to vocal-acoustic integration sites, notably the hindbrain octavolateralis efferent nucleus, as well as onto the base of hair cells in the saccule via nerve VIII. Neurobiotin backfills of the vocal nerve in combination with TH-ir revealed CA terminals on all components of the vocal pattern generator which appears to largely originate from local TH-ir neurons but may include diencephalic projections as well. This study provides strong evidence for catecholamines as important neuromodulators of both auditory and vocal circuitry and acoustic-driven social behavior in midshipman fish. This first demonstration of TH-ir terminals in the main endorgan of hearing in a non-mammalian vertebrate suggests a conserved and important anatomical and functional role for dopamine in normal audition. PMID:24715479

Aging of human short-wave cone pathways

PubMed Central

Shinomori, Keizo; Werner, John S.

2012-01-01

The retinal image is sampled concurrently, and largely independently, by three physiologically and anatomically distinct pathways, each with separate ON and OFF subdivisions. The retinal circuitry giving rise to an ON pathway receiving input from the short-wave-sensitive (S) cones is well understood, but the S-cone OFF circuitry is more controversial. Here, we characterize the temporal properties of putative S-cone ON and OFF pathways in younger and older observers by measuring thresholds for stimuli that produce increases or decreases in S-cone stimulation, while the middle- and long-wave-sensitive cones are unmodulated. We characterize the data in terms of an impulse response function, the theoretical response to a flash of infinitely short duration, from which the response to any temporally varying stimulus may be predicted. Results show that the S-cone response to increments is faster than to decrements, but this difference is significantly greater for older individuals. The impulse response function amplitudes for increment and decrement responses are highly correlated across individuals, whereas the timing is not. This strongly suggests that the amplitude is controlled by neural circuitry that is common to S-cone ON and OFF responses (photoreceptors), whereas the timing is controlled by separate postreceptoral pathways. The slower response of the putative OFF pathway is ascribed to different retinal circuitry, possibly attributable to a sign-inverting amacrine cell not present in the ON pathway. It is significant that this pathway is affected selectively in the elderly by becoming slower, whereas the temporal properties of the S-cone ON response are stable across the life span of an individual. PMID:22847416

An Implantable Neural Sensing Microsystem with Fiber-Optic Data Transmission and Power Delivery

PubMed Central

Park, Sunmee; Borton, David A.; Kang, Mingyu; Nurmikko, Arto V.; Song, Yoon-Kyu

2013-01-01

We have developed a prototype cortical neural sensing microsystem for brain implantable neuroengineering applications. Its key feature is that both the transmission of broadband, multichannel neural data and power required for the embedded microelectronics are provided by optical fiber access. The fiber-optic system is aimed at enabling neural recording from rodents and primates by converting cortical signals to a digital stream of infrared light pulses. In the full microsystem whose performance is summarized in this paper, an analog-to-digital converter and a low power digital controller IC have been integrated with a low threshold, semiconductor laser to extract the digitized neural signals optically from the implantable unit. The microsystem also acquires electrical power and synchronization clocks via optical fibers from an external laser by using a highly efficient photovoltaic cell on board. The implantable unit employs a flexible polymer substrate to integrate analog and digital microelectronics and on-chip optoelectronic components, while adapting to the anatomical and physiological constraints of the environment. A low power analog CMOS chip, which includes preamplifier and multiplexing circuitry, is directly flip-chip bonded to the microelectrode array to form the cortical neurosensor device. PMID:23666130

Evolutionarily conserved mechanisms for the selection and maintenance of behavioural activity.

PubMed

Fiore, Vincenzo G; Dolan, Raymond J; Strausfeld, Nicholas J; Hirth, Frank

2015-12-19

Survival and reproduction entail the selection of adaptive behavioural repertoires. This selection manifests as phylogenetically acquired activities that depend on evolved nervous system circuitries. Lorenz and Tinbergen already postulated that heritable behaviours and their reliable performance are specified by genetically determined programs. Here we compare the functional anatomy of the insect central complex and vertebrate basal ganglia to illustrate their role in mediating selection and maintenance of adaptive behaviours. Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons. These clusters are specified by genetic mechanisms that link birth time and order to their neuronal identities and functions. Their subsequent connections and associated functions are characterized by similar mechanisms that implement dimensionality reduction and transition through attractor states, whereby spatially organized parallel-projecting loops integrate and convey sensorimotor representations that select and maintain behavioural activity. In both taxa, these neural systems are modulated by dopamine signalling that also mediates memory-like processes. The multiplicity of similarities between central complex and basal ganglia suggests evolutionarily conserved computational mechanisms for action selection. We speculate that these may have originated from ancestral ground pattern circuitries present in the brain of the last common ancestor of insects and vertebrates. © 2015 The Authors.

Pathological anxiety and function/dysfunction in the brain's fear/defense circuitry.

PubMed

Lang, Peter J; McTeague, Lisa M; Bradley, Margaret M

2014-01-01

Research from the University of Florida Center for the Study of Emotion and Attention aims to develop neurobiological measures that objectively discriminate among symptom patterns in patients with anxiety disorders. From this perspective, anxiety and mood pathologies are considered to be brain disorders, resulting from dysfunction and maladaptive plasticity in the neural circuits that determine fearful/defensive and appetitive/reward behavior (Insel et al., 2010). We review recent studies indicating that an enhanced probe startle reflex during the processing of fear memory cues (mediated by cortico-limbic circuitry and thus indicative of plastic brain changes), varies systematically in strength over a spectrum-wide dimension of anxiety pathology-across and within diagnoses-extending from strong focal fear reactions to a consistently blunted reaction in patients with more generalized anxiety and comorbid mood disorders. Preliminary studies with functional magnetic resonance imaging (fMRI) encourage the hypothesis that fear/defense circuit dysfunction covaries with this same dimension of psychopathology. Plans are described for an extended study of the brain's motivation circuitry in anxiety spectrum patients, with the aim of defining the specifics of circuit dysfunction in severe disorders. A sub-project explores the use of real-time fMRI feedback in circuit analysis and as a modality to up-regulate circuit function in the context of blunted affect.

Evolutionarily conserved mechanisms for the selection and maintenance of behavioural activity

PubMed Central

Fiore, Vincenzo G.; Dolan, Raymond J.; Strausfeld, Nicholas J.; Hirth, Frank

2015-01-01

Survival and reproduction entail the selection of adaptive behavioural repertoires. This selection manifests as phylogenetically acquired activities that depend on evolved nervous system circuitries. Lorenz and Tinbergen already postulated that heritable behaviours and their reliable performance are specified by genetically determined programs. Here we compare the functional anatomy of the insect central complex and vertebrate basal ganglia to illustrate their role in mediating selection and maintenance of adaptive behaviours. Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons. These clusters are specified by genetic mechanisms that link birth time and order to their neuronal identities and functions. Their subsequent connections and associated functions are characterized by similar mechanisms that implement dimensionality reduction and transition through attractor states, whereby spatially organized parallel-projecting loops integrate and convey sensorimotor representations that select and maintain behavioural activity. In both taxa, these neural systems are modulated by dopamine signalling that also mediates memory-like processes. The multiplicity of similarities between central complex and basal ganglia suggests evolutionarily conserved computational mechanisms for action selection. We speculate that these may have originated from ancestral ground pattern circuitries present in the brain of the last common ancestor of insects and vertebrates. PMID:26554043

Convergent pharmacological mechanisms in impulsivity and addiction: insights from rodent models

PubMed Central

Jupp, B; Dalley, J W

2014-01-01

Research over the last two decades has widely demonstrated that impulsivity, in its various forms, is antecedent to the development of drug addiction and an important behavioural trait underlying the inability of addicts to refrain from continued drug use. Impulsivity describes a variety of rapidly and prematurely expressed behaviours that span several domains from impaired response inhibition to an intolerance of delayed rewards, and is a core symptom of attention deficit hyperactivity disorder (ADHD) and other brain disorders. Various theories have been advanced to explain how impulsivity interacts with addiction both causally and as a consequence of chronic drug abuse; these acknowledge the strong overlaps in neural circuitry and mechanisms between impulsivity and addiction and the seemingly paradoxical treatment of ADHD with stimulant drugs with high abuse potential. Recent years have witnessed unprecedented progress in the elucidation of pharmacological mechanisms underpinning impulsivity. Collectively, this work has significantly improved the prospect for new therapies in ADHD as well as our understanding of the neural mechanisms underlying the shift from recreational drug use to addiction. In this review, we consider the extent to which pharmacological interventions that target impulsive behaviour are also effective in animal models of addiction. We highlight several promising examples of convergence based on empirical findings in rodent-based studies. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24866553

Abnormal brain activation during directed forgetting of negative memory in depressed patients.

PubMed

Yang, Wenjing; Chen, Qunlin; Liu, Peiduo; Cheng, Hongsheng; Cui, Qian; Wei, Dongtao; Zhang, Qinglin; Qiu, Jiang

2016-01-15

The frequent occurrence of uncontrollable negative thoughts and memories is a troubling aspect of depression. Thus, knowledge on the mechanism underlying intentional forgetting of these thoughts and memories is crucial to develop an effective emotion regulation strategy for depressed individuals. Behavioral studies have demonstrated that depressed participants cannot intentionally forget negative memories. However, the neural mechanism underlying this process remains unclear. In this study, participants completed the directed forgetting task in which they were instructed to remember or forget neutral or negative words. Standard univariate analysis based on the General Linear Model showed that the depressed participants have higher activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), superior parietal gyrus (SPG), and inferior temporal gyrus (ITG) than the healthy individuals. The results indicated that depressed participants recruited more frontal and parietal inhibitory control resources to inhibit the TBF items, but the attempt still failed because of negative bias. We also used the Support Vector Machine to perform multivariate pattern classification based on the brain activation during directed forgetting. The pattern of brain activity in directed forgetting of negative words allowed correct group classification with an overall accuracy of 75% (P=0.012). The brain regions which are critical for this discrimination showed abnormal activation when depressed participants were attempting to forget negative words. These results indicated that the abnormal neural circuitry when depressed individuals tried to forget the negative words might provide neurobiological markers for depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

PubMed

Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

2014-09-09

Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Impaired fear extinction in adolescent rodents: Behavioural and neural analyses.

PubMed

Baker, Kathryn D; Bisby, Madelyne A; Richardson, Rick

2016-11-01

Despite adolescence being a developmental window of vulnerability, up until very recently there were surprisingly few studies on fear extinction during this period. Here we summarise the recent work in this area, focusing on the unique behavioural and neural characteristics of fear extinction in adolescent rodents, and humans where relevant. A prominent hypothesis posits that anxiety disorders peak during late childhood/adolescence due to the non-linear maturation of the fear inhibition neural circuitry. We discuss evidence that impaired extinction retention in adolescence is due to subregions of the medial prefrontal cortex and amygdala mediating fear inhibition being underactive while other subregions that mediate fear expression are overactive. We also review work on various interventions and surprising circumstances which enhance fear extinction in adolescence. This latter work revealed that the neural correlates of extinction in adolescence are different to that in younger and older animals even when extinction retention is not impaired. This growing body of work highlights that adolescence is a unique period of development for fear inhibition. Copyright © 2016 Elsevier Ltd. All rights reserved.

The precuneus may encode irrationality in human gambling.

PubMed

Sacre, P; Kerr, M S D; Subramanian, S; Kahn, K; Gonzalez-Martinez, J; Johnson, M A; Sarma, S V; Gale, J T

2016-08-01

Humans often make irrational decisions, especially psychiatric patients who have dysfunctional cognitive and emotional circuitry. Understanding the neural basis of decision-making is therefore essential towards patient management, yet current studies suffer from several limitations. Functional magnetic resonance imaging (fMRI) studies in humans have dominated decision-making neuroscience, but have poor temporal resolution and the blood oxygenation level-dependent signal is only a proxy for neural activity. On the other hand, lesion studies in humans used to infer functionality in decision-making lack characterization of neural activity altogether. Using a combination of local field potential recordings in human subjects performing a financial decision-making task, spectral analyses, and non-parametric cluster statistics, we analyzed the activity in the precuneus. In nine subjects, the neural activity modulated significantly between rational and irrational trials in the precuneus (p <; 0.001). In particular, high-frequency activity (70-100 Hz) increased when irrational decisions were made. Although preliminary, these results suggest suppression of gamma rhythms via electrical stimulation in the precuneus as a therapeutic intervention for pathological decision-making.

Neural correlates of nesting behavior in zebra finches (Taeniopygia guttata).

PubMed

Hall, Zachary J; Bertin, Marion; Bailey, Ida E; Meddle, Simone L; Healy, Susan D

2014-05-01

Nest building in birds involves a behavioral sequence (nest material collection and deposition in the nest) that offers a unique model for addressing how the brain sequences motor actions. In this study, we identified brain regions involved in nesting behavior in male and female zebra finches (Taeniopygia guttata). We used Fos immunohistochemistry to quantify production of the immediate early gene protein product Fos (a molecular indicator of neuronal activity) in the brain correlated this expression with the variation in nesting behavior. Using this technique, we found that neural circuitry involved in motor sequencing, social behavior, reward and motivation were active during nesting. Within pairs of nesting birds, the number of times a male picked up or deposited nesting material and the amount of time a female spent in the nest explained the variation in Fos expression in the anterior motor pathway, social behavior network, and reward neural circuits. Identification of the brain regions that are involved in nesting enables us to begin studying the roles of motor sequencing, context, and reward in construction behavior at the neural level. Copyright © 2014 Elsevier B.V. All rights reserved.

Neural correlates of nesting behavior in zebra finches (Taeniopygia guttata)

PubMed Central

Hall, Zachary J.; Bertin, Marion; Bailey, Ida E.; Meddle, Simone L.; Healy, Susan D.

2014-01-01

Nest building in birds involves a behavioral sequence (nest material collection and deposition in the nest) that offers a unique model for addressing how the brain sequences motor actions. In this study, we identified brain regions involved in nesting behavior in male and female zebra finches (Taeniopygia guttata). We used Fos immunohistochemistry to quantify production of the immediate early gene protein product Fos (a molecular indicator of neuronal activity) in the brain correlated this expression with the variation in nesting behavior. Using this technique, we found that neural circuitry involved in motor sequencing, social behavior, reward and motivation were active during nesting. Within pairs of nesting birds, the number of times a male picked up or deposited nesting material and the amount of time a female spent in the nest explained the variation in Fos expression in the anterior motor pathway, social behavior network, and reward neural circuits. Identification of the brain regions that are involved in nesting enables us to begin studying the roles of motor sequencing, context, and reward in construction behavior at the neural level. PMID:24508238

Neural Correlation Is Stimulus Modulated by Feedforward Inhibitory Circuitry

PubMed Central

Middleton, Jason W.; Omar, Cyrus; Doiron, Brent; Simons, Daniel J.

2012-01-01

Correlated variability of neural spiking activity has important consequences for signal processing. How incoming sensory signals shape correlations of population responses remains unclear. Cross-correlations between spiking of different neurons may be particularly consequential in sparsely firing neural populations such as those found in layer 2/3 of sensory cortex. In rat whisker barrel cortex, we found that pairs of excitatory layer 2/3 neurons exhibit similarly low levels of spike count correlation during both spontaneous and sensory-evoked states. The spontaneous activity of excitatory–inhibitory neuron pairs is positively correlated, while sensory stimuli actively decorrelate joint responses. Computational modeling shows how threshold nonlinearities and local inhibition form the basis of a general decorrelating mechanism. We show that inhibitory population activity maintains low correlations in excitatory populations, especially during periods of sensory-evoked coactivation. The role of feedforward inhibition has been previously described in the context of trial-averaged phenomena. Our findings reveal a novel role for inhibition to shape correlations of neural variability and thereby prevent excessive correlations in the face of feedforward sensory-evoked activation. PMID:22238086

Loss of Neurofilament Labeling in the Primary Visual Cortex of Monocularly Deprived Monkeys

PubMed Central

Duffy, Kevin R.; Livingstone, Margaret S.

2009-01-01

Visual experience during early life is important for the development of neural organizations that support visual function. Closing one eye (monocular deprivation) during this sensitive period can cause a reorganization of neural connections within the visual system that leaves the deprived eye functionally disconnected. We have assessed the pattern of neurofilament labeling in monocularly deprived macaque monkeys to examine the possibility that a cytoskeleton change contributes to deprivation-induced reorganization of neural connections within the primary visual cortex (V-1). Monocular deprivation for three months starting around the time of birth caused a significant loss of neurofilament labeling within deprived-eye ocular dominance columns. Three months of monocular deprivation initiated in adulthood did not produce a loss of neurofilament labeling. The evidence that neurofilament loss was found only when deprivation occurred during the sensitive period supports the notion that the loss permits restructuring of deprived-eye neural connections within the visual system. These results provide evidence that, in addition to reorganization of LGN inputs, the intrinsic circuitry of V-1 neurons is altered when monocular deprivation occurs early in development. PMID:15563721

The Basolateral Amygdala and Nucleus Accumbens Core Mediate Dissociable Aspects of Drug Memory Reconsolidation

ERIC Educational Resources Information Center

Theberge, Florence R. M.; Milton, Amy L.; Belin, David; Lee, Jonathan L. C.; Everitt, Barry J.

2010-01-01

A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug craving and relapse. Exposure to drug-paired cues not only precipitates relapse, but also triggers the reactivation and reconsolidation of the cue-drug memory. However, the limbic cortical-striatal circuitry underlying drug memory reconsolidation is unclear. The aim…

An update on contextual fear memory mechanisms: Transition between Amygdala and Hippocampus.

PubMed

Chaaya, Nicholas; Battle, Andrew R; Johnson, Luke R

2018-05-09

Context is an ever-present combination of discrete environmental elements capable of influencing many psychological processes. When context is associated with an aversive stimulus, a permanent contextual fear memory is formed. Context is hypothesized to greatly influence the treatability of various fear-based pathologies, in particular, post-traumatic stress disorder (PTSD). In order to understand how contextual fear memories are encoded and impact underlying fear pathology, delineation of the underlying neural circuitry of contextual fear memory consolidation and maintenance is essential. Past understandings of contextual fear suggest that the hippocampus only creates a unitary, or single, representation of context. This representation is sent to the amygdala, which creates the associative contextual fear memory. In contrast, here we review new evidence from the literature showing contextual fear memories to be consolidated and maintained by both amygdala and hippocampus. Based on this evidence, we revise the current model of contextual fear memory consolidation, highlighting a larger role for hippocampus. This new model may better explain the role of the hippocampus in PTSD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Structural and synaptic plasticity in stress-related disorders

PubMed Central

Christoffel, Daniel J.; Golden, Sam A.; Russo, Scott J.

2011-01-01

Stress can have a lasting impact on the structure and function of brain circuitry that results in long-lasting changes in the behavior of an organism. Synaptic plasticity is the mechanism by which information is stored and maintained within individual synapses, neurons, and neuronal circuits to guide the behavior of an organism. Although these mechanisms allow the organism to adapt to its constantly evolving environment, not all of these adaptations are beneficial. Under prolonged bouts of physical or psychological stress, these mechanisms become dysregulated, and the connectivity between brain regions becomes unbalanced, resulting in pathological behaviors. In this review, we highlight the effects of stress on the structure and function of neurons within the mesocorticolimbic brain systems known to regulate mood and motivation. We then discuss the implications of these spine adaptations on neuronal activity and pathological behaviors implicated in mood disorders. Finally, we end by discussing recent brain imaging studies in human depression within the context of these basic findings to provide insight into the underlying mechanisms leading to neural dysfunction in depression. PMID:21967517

Importance of reward and prefrontal circuitry in hunger and satiety: Prader-Willi syndrome vs simple obesity.

PubMed

Holsen, L M; Savage, C R; Martin, L E; Bruce, A S; Lepping, R J; Ko, E; Brooks, W M; Butler, M G; Zarcone, J R; Goldstein, J M

2012-05-01

The majority of research on obesity (OB) has focused primarily on clinical features (eating behavior, adiposity measures) or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions that are associated with appetite-regulatory hormones are also involved in the development and maintenance of OB. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic OB. Simple (non-PWS) OB represents an OB-control state. This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (that is, hypothalamus, amygdala) and prefrontal regions associated with cognitive control (that is, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC) after eating. A total of 14 individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC and DLPFC. Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in the hypothalamus and hippocampus in response to food (vs non-food) images pre-meal. Post meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared with OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. In PWS, compared with OB per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple OB.

Importance of Reward and Prefrontal Circuitry in Hunger and Satiety: Prader-Willi Syndrome vs. Simple Obesity

PubMed Central

Holsen, Laura M.; Savage, Cary R.; Martin, Laura E.; Bruce, Amanda S.; Lepping, Rebecca J.; Ko, Eunice; Brooks, William M.; Butler, Merlin G.; Zarcone, Jennifer R.; Goldstein, Jill M.

2011-01-01

Background The majority of research on obesity has focused primarily on clinical features (eating behavior, adiposity measures), or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions which are associated with appetite-regulatory hormones are also involved in the development and maintenance of obesity. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic obesity. Simple (non-PWS) obesity (OB) represents an obesity control state. Objective This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (i.e., hypothalamus, amygdala) and prefrontal regions associated with cognitive control [i.e., dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC)] after eating. Design and Participants Fourteen individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls (HWC) viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC, and DLPFC. Results Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in hypothalamus and hippocampus, in response to food (vs. non-food) images pre-meal. Post-meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared to OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. Conclusion In PWS compared with obesity per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple obesity. PMID:22024642

Aberrant functioning of the theory-of-mind network in children and adolescents with autism.

PubMed

Kana, Rajesh K; Maximo, Jose O; Williams, Diane L; Keller, Timothy A; Schipul, Sarah E; Cherkassky, Vladimir L; Minshew, Nancy J; Just, Marcel Adam

2015-01-01

Theory-of-mind (ToM), the ability to infer people's thoughts and feelings, is a pivotal skill in effective social interactions. Individuals with autism spectrum disorders (ASD) have been found to have altered ToM skills, which significantly impacts the quality of their social interactions. Neuroimaging studies have reported altered activation of the ToM cortical network, especially in adults with autism, yet little is known about the brain responses underlying ToM in younger individuals with ASD. This functional magnetic resonance imaging (fMRI) study investigated the neural mechanisms underlying ToM in high-functioning children and adolescents with ASD and matched typically developing (TD) peers. fMRI data were acquired from 13 participants with ASD and 13 TD control participants while they watched animations involving two "interacting" geometrical shapes. Participants with ASD showed significantly reduced activation, relative to TD controls, in regions considered part of the ToM network, the mirror network, and the cerebellum. Functional connectivity analyses revealed underconnectivity between frontal and posterior regions during task performance in the ASD participants. Overall, the findings of this study reveal disruptions in the brain circuitry underlying ToM in ASD at multiple levels, including decreased activation and decreased functional connectivity.

Improved expression of halorhodopsin for light-induced silencing of neuronal activity

PubMed Central

Zhao, Shengli; Cunha, Catarina; Zhang, Feng; Liu, Qun; Gloss, Bernd; Deisseroth, Karl; Augustine, George J.; Feng, Guoping

2011-01-01

The ability to control and manipulate neuronal activity within an intact mammalian brain is of key importance for mapping functional connectivity and for dissecting the neural circuitry underlying behaviors. We have previously generated transgenic mice that express channelrhodopsin-2 for light-induced activation of neurons and mapping of neural circuits. Here we describe transgenic mice that express halorhodopsin (NpHR), a light-driven chloride pump, that can be used to silence neuronal activity via light. Using the Thy-1 promoter to target NpHR expression to neurons, we found that neurons in these mice expressed high levels of NpHR-YFP and that illumination of cortical pyramidal neurons expressing NpHR-YFP led to rapid, reversible photoinhibition of action potential firing in these cells. However, NpHR-YFP expression led to the formation of numerous intracellular blebs, which may disrupt neuronal function. Labeling of various subcellular markers indicated that the blebs arise from retention of NpHR-YFP in the endoplasmic reticulum. By improving the signal peptide sequence and adding an ER export signal to NpHR-YFP, we eliminated the formation of blebs and dramatically increased the membrane expression of NpHR-YFP. Thus, the improved version of NpHR should serve as an excellent tool for neuronal silencing in vitro and in vivo. PMID:18931914

Cortical Plasticity in Depression

PubMed Central

Cantone, Mariagiovanna; Bramanti, Alessia; Pennisi, Manuela; Bramanti, Placido; Pennisi, Giovanni; Bella, Rita

2017-01-01

Neural plasticity is considered the neurophysiological correlate of learning and memory, although several studies have also noted that it plays crucial roles in a number of neurological and psychiatric diseases. Indeed, impaired brain plasticity may be one of the pathophysiological mechanisms that underlies both cognitive decline and major depression. Moreover, a degree of cognitive impairment is frequently observed throughout the clinical spectrum of mood disorders, and the relationship between depression and cognition is often bidirectional. However, most evidence for dysfunctional neural plasticity in depression has been indirect. Transcranial magnetic stimulation has emerged as a noninvasive tool for investigating several parameters of cortical excitability with the aim of exploring the functions of different neurotransmission pathways and for probing in vivo plasticity in both healthy humans and those with pathological conditions. In particular, depressed patients exhibit a significant interhemispheric difference in motor cortex excitability, an imbalanced inhibitory or excitatory intracortical neurochemical circuitry, reduced postexercise facilitation, and an impaired long-term potentiation-like response to paired-associative transcranial magnetic stimulation, and these symptoms may indicate disrupted plasticity. Research aimed at disentangling the mechanism by which neuroplasticity plays a role in the pathological processes that lead to depression and evaluating the effects of modulating neuroplasticity are needed for the field to facilitate more powerful translational research studies and identify novel therapeutic targets. PMID:28629225

Pharmacogenetic and optical dissection for mechanistic understanding of Parkinson's disease: potential utilities revealed through behavioural assessment.

PubMed

Sharma, Puneet; Pienaar, Ilse S

2014-11-01

The technology toolbox by which neural elements can be selectively manipulated in vertebrate and invertebrate brains has expanded greatly in recent years, to now include sophisticated optogenetics and novel designer receptors. Application of such tools allow for ascertaining whether a particular behavioural phenotype associates with interrogation of a specific neural circuit. Optogenetics has already found application in the study of Parkinson's disease (PD) circuitry and therapies, whereas novel designer receptors hold promise for enlightening on current understanding of the mechanisms underlying parkinsonian motor and non-motor symptoms. In particular, this new generation of research tools provide a method by which significant insights can be gained on brain networks implicated in brain diseases such as PD. These tools also promise to assist in the development of novel therapies for targeting degenerated dopaminergic and non-dopaminergic neurons in the diseased basal ganglia system of PD patients, for providing symptomatic relief or even reverse neurodegenerative processes. The present review discusses how such technologies, in conjunction with application of sensitive behavioural assays, continue to significantly advance our knowledge of circuit and signalling properties inherent to PD pathology. The discussion also highlights how such experimental approaches provide additional explorative avenues which may result in dramatically improved therapeutic options for PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Striatal activation and frontostriatal connectivity during non-drug reward anticipation in alcohol dependence.

PubMed

Becker, Alena; Kirsch, Martina; Gerchen, Martin Fungisai; Kiefer, Falk; Kirsch, Peter

2017-05-01

According to prevailing neurobiological theories of addiction, altered function in neural reward circuitry is a central mechanism of alcohol dependence. Growing evidence postulates that the ventral striatum (VS), as well as areas of the prefrontal cortex, contribute to the increased incentive salience of alcohol-associated cues, diminished motivation to pursue non-drug rewards and weakened strength of inhibitory cognitive control, which are central to addiction. The present study aims to investigate the neural response and functional connectivity underlying monetary, non-drug reward processing in alcohol dependence. We utilized a reward paradigm to investigate the anticipation of monetary reward in 32 alcohol-dependent inpatients and 35 healthy controls. Functional magnetic resonance imaging was used to measure task-related brain activation and connectivity. Alcohol-dependent patients showed increased activation of the VS during anticipation of monetary gain compared with healthy controls. Generalized psychophysiological interaction analyses revealed decreased functional connectivity between the VS and the dorsolateral prefrontal cortex in alcohol dependent patients relative to controls. Increased activation of the VS and reduced frontostriatal connectivity were associated with increased craving. These findings provide evidence that alcohol dependence is rather associated with disrupted integration of striatal and prefrontal processes than with a global reward anticipation deficit. © 2016 Society for the Study of Addiction.

Neural signals of vicarious extinction learning

PubMed Central

Haaker, Jan; Selbing, Ida; Olsson, Andreas

2016-01-01

Social transmission of both threat and safety is ubiquitous, but little is known about the neural circuitry underlying vicarious safety learning. This is surprising given that these processes are critical to flexibly adapt to a changeable environment. To address how the expression of previously learned fears can be modified by the transmission of social information, two conditioned stimuli (CS + s) were paired with shock and the third was not. During extinction, we held constant the amount of direct, non-reinforced, exposure to the CSs (i.e. direct extinction), and critically varied whether another individual—acting as a demonstrator—experienced safety (CS + vic safety) or aversive reinforcement (CS + vic reinf). During extinction, ventromedial prefrontal cortex (vmPFC) responses to the CS + vic reinf increased but decreased to the CS + vic safety. This pattern of vmPFC activity was reversed during a subsequent fear reinstatement test, suggesting a temporal shift in the involvement of the vmPFC. Moreover, only the CS + vic reinf association recovered. Our data suggest that vicarious extinction prevents the return of conditioned fear responses, and that this efficacy is reflected by diminished vmPFC involvement during extinction learning. The present findings may have important implications for understanding how social information influences the persistence of fear memories in individuals suffering from emotional disorders. PMID:27278792

Role of Autism Susceptibility Gene, CNTNAP2, in Neural Circuitry for Vocal Communication

DTIC Science & Technology

2013-10-01

Grimbert et al., 2003), and ATP2C2 is part of a pathway responsible for shuttling divalent ions to the Golgi apparatus (Faddy et al., 2008...L., & Wuytack, F. (2007). Calcium in the Golgi apparatus . Cell Calcium, 41(5), 405–416. doi:10.1016/j. ceca.2006.11.001 Mizutani, A., Matsuzaki, A...determination. Nature Structural & Molecular Biology, 16(4), 365–371. doi:10.1038/nsmb.1576 This is a contribution from New Perspectives on the Origins

Brain Plasticity and Disease: A Matter of Inhibition

PubMed Central

Baroncelli, Laura; Braschi, Chiara; Spolidoro, Maria; Begenisic, Tatjana; Maffei, Lamberto; Sale, Alessandro

2011-01-01

One major goal in Neuroscience is the development of strategies promoting neural plasticity in the adult central nervous system, when functional recovery from brain disease and injury is limited. New evidence has underscored a pivotal role for cortical inhibitory circuitries in regulating plasticity both during development and in adulthood. This paper summarizes recent findings showing that the inhibition-excitation balance controls adult brain plasticity and is at the core of the pathogenesis of neurodevelopmental disorders like autism, Down syndrome, and Rett syndrome. PMID:21766040

Child neurology: autism as a model: considerations for advanced training in behavioral child neurology.

PubMed

Jeste, Shafali S; Friedman, Sandra L; Urion, David K

2009-09-01

In this article, we advocate for advanced training for child neurologists in behavior and development in order to facilitate the investigation of childhood behavioral and neurodevelopmental disabilities, with autism serving as a model disorder. We explore the current training options and then propose alternative subspecialty training options that focus on behavior and development, with appreciation that most developmental disabilities are not static encephalopathies but, rather, dynamic processes representing the influence of genetics and environment on neural circuitry.

Adaptive Proactive Inhibitory Control for Embedded Real-Time Applications

PubMed Central

Yang, Shufan; McGinnity, T. Martin; Wong-Lin, KongFatt

2012-01-01

Psychologists have studied the inhibitory control of voluntary movement for many years. In particular, the countermanding of an impending action has been extensively studied. In this work, we propose a neural mechanism for adaptive inhibitory control in a firing-rate type model based on current findings in animal electrophysiological and human psychophysical experiments. We then implement this model on a field-programmable gate array (FPGA) prototyping system, using dedicated real-time hardware circuitry. Our results show that the FPGA-based implementation can run in real-time while achieving behavioral performance qualitatively suggestive of the animal experiments. Implementing such biological inhibitory control in an embedded device can lead to the development of control systems that may be used in more realistic cognitive robotics or in neural prosthetic systems aiding human movement control. PMID:22701420

High-Density Liquid-State Machine Circuitry for Time-Series Forecasting.

PubMed

Rosselló, Josep L; Alomar, Miquel L; Morro, Antoni; Oliver, Antoni; Canals, Vincent

2016-08-01

Spiking neural networks (SNN) are the last neural network generation that try to mimic the real behavior of biological neurons. Although most research in this area is done through software applications, it is in hardware implementations in which the intrinsic parallelism of these computing systems are more efficiently exploited. Liquid state machines (LSM) have arisen as a strategic technique to implement recurrent designs of SNN with a simple learning methodology. In this work, we show a new low-cost methodology to implement high-density LSM by using Boolean gates. The proposed method is based on the use of probabilistic computing concepts to reduce hardware requirements, thus considerably increasing the neuron count per chip. The result is a highly functional system that is applied to high-speed time series forecasting.

Old Dogs Learning New Tricks: Neuroplasticity Beyond the Juvenile Period

PubMed Central

Lillard, Angeline S.; Erisir, Alev

2014-01-01

Twenty years ago, the prevalent view in psychology was that although learning and the formation of new memories are lifelong occurrences, the neural changes associated with these events were all in the existing receptors. No new neural hardware, from synapses to neurons, was thought to appear after a protracted period early in life. In the past 20 years, another view has supplanted this one, showing that although the juvenile period is especially suited to neuroplastic adaptation, there is hard neuroplastic change later in life as well. We review a selection of evidence for this view from both animal and human models, showing how it reflects three principles of neuroplasticity: 1) earlier and later experience-induced changes to neuroarchitecture differ in degree more so than in type; 2) the types of experiences that lead to neuroplastic change narrow with age; and 3) differences in the amenability of neural circuitry to change result from basic differences in neuroarchitecture and neuroenvironment in different phases of development. PMID:24648605

Nonlinear decoding of a complex movie from the mammalian retina

PubMed Central

Deny, Stéphane; Martius, Georg

2018-01-01

Retina is a paradigmatic system for studying sensory encoding: the transformation of light into spiking activity of ganglion cells. The inverse problem, where stimulus is reconstructed from spikes, has received less attention, especially for complex stimuli that should be reconstructed “pixel-by-pixel”. We recorded around a hundred neurons from a dense patch in a rat retina and decoded movies of multiple small randomly-moving discs. We constructed nonlinear (kernelized and neural network) decoders that improved significantly over linear results. An important contribution to this was the ability of nonlinear decoders to reliably separate between neural responses driven by locally fluctuating light signals, and responses at locally constant light driven by spontaneous-like activity. This improvement crucially depended on the precise, non-Poisson temporal structure of individual spike trains, which originated in the spike-history dependence of neural responses. We propose a general principle by which downstream circuitry could discriminate between spontaneous and stimulus-driven activity based solely on higher-order statistical structure in the incoming spike trains. PMID:29746463

Neural representation of expected value in the adolescent brain.

PubMed

Barkley-Levenson, Emily; Galván, Adriana

2014-01-28

Previous work shows that the adolescent reward system is hyperactive, but this finding may be confounded by differences in how teens value money. To address this, we examined the neural ontogeny of objective value representation. Adolescent and adult participants performed a monetary gambling task in which they chose to accept or reject gambles of varying expected value. Increasing expected value had a stronger influence over gambling choices in adolescents relative to adults, an effect that was paralleled by greater activation in the ventral striatum in adolescents. This unique adolescent ventral striatum response remained even after matching groups on acceptance behavior. These behavioral and neural data suggest that the value of available options has a greater influence in adolescent versus adult choices, even when objective value and subjective choice are held constant. This research provides further evidence that hyperactivation of reward circuitry in adolescence may be a normative ontogenetic shift that is due to greater valuation in the adolescent brain.

Neural representation of expected value in the adolescent brain

PubMed Central

Barkley-Levenson, Emily; Galván, Adriana

2014-01-01

Previous work shows that the adolescent reward system is hyperactive, but this finding may be confounded by differences in how teens value money. To address this, we examined the neural ontogeny of objective value representation. Adolescent and adult participants performed a monetary gambling task in which they chose to accept or reject gambles of varying expected value. Increasing expected value had a stronger influence over gambling choices in adolescents relative to adults, an effect that was paralleled by greater activation in the ventral striatum in adolescents. This unique adolescent ventral striatum response remained even after matching groups on acceptance behavior. These behavioral and neural data suggest that the value of available options has a greater influence in adolescent versus adult choices, even when objective value and subjective choice are held constant. This research provides further evidence that hyperactivation of reward circuitry in adolescence may be a normative ontogenetic shift that is due to greater valuation in the adolescent brain. PMID:24474790

Towards cortex sized artificial neural systems.

PubMed

Johansson, Christopher; Lansner, Anders

2007-01-01

We propose, implement, and discuss an abstract model of the mammalian neocortex. This model is instantiated with a sparse recurrently connected neural network that has spiking leaky integrator units and continuous Hebbian learning. First we study the structure, modularization, and size of neocortex, and then we describe a generic computational model of the cortical circuitry. A characterizing feature of the model is that it is based on the modularization of neocortex into hypercolumns and minicolumns. Both a floating- and fixed-point arithmetic implementation of the model are presented along with simulation results. We conclude that an implementation on a cluster computer is not communication but computation bounded. A mouse and rat cortex sized version of our model executes in 44% and 23% of real-time respectively. Further, an instance of the model with 1.6 x 10(6) units and 2 x 10(11) connections performed noise reduction and pattern completion. These implementations represent the current frontier of large-scale abstract neural network simulations in terms of network size and running speed.

A post-transcriptional mechanism pacing expression of neural genes with precursor cell differentiation status.

PubMed

Dai, Weijun; Li, Wencheng; Hoque, Mainul; Li, Zhuyun; Tian, Bin; Makeyev, Eugene V

2015-07-06

Nervous system (NS) development relies on coherent upregulation of extensive sets of genes in a precise spatiotemporal manner. How such transcriptome-wide effects are orchestrated at the molecular level remains an open question. Here we show that 3'-untranslated regions (3' UTRs) of multiple neural transcripts contain AU-rich cis-elements (AREs) recognized by tristetraprolin (TTP/Zfp36), an RNA-binding protein previously implicated in regulation of mRNA stability. We further demonstrate that the efficiency of ARE-dependent mRNA degradation declines in the neural lineage because of a decrease in the TTP protein expression mediated by the NS-enriched microRNA miR-9. Importantly, TTP downregulation in this context is essential for proper neuronal differentiation. On the other hand, inactivation of TTP in non-neuronal cells leads to dramatic upregulation of multiple NS-specific genes. We conclude that the newly identified miR-9/TTP circuitry limits unscheduled accumulation of neuronal mRNAs in non-neuronal cells and ensures coordinated upregulation of these transcripts in neurons.

Epigenetic and Neural Circuitry Landscape of Psychotherapeutic Interventions

PubMed Central

2017-01-01

The science behind psychotherapy has garnered considerable interest, as objective measures are being developed to map the patient's subjective change over the course of treatment. Prenatal and early life influences have a lasting impact on how genes are expressed and the manner in which neural circuits are consolidated. Transgenerationally transmitted epigenetic markers as well as templates of enhanced thought flexibility versus evasion can be passed down from parent to child. This influences gene expression/repression (impacting neuroplasticity) and kindling of neurocircuitry which can perpetuate maladaptive cognitive processing seen in a number of psychiatric conditions. Importantly, genetic factors and the compounding effects of early life adversity do not inexorably lead to certain fated outcomes. The concepts of vulnerability and resilience are becoming more integrated into the framework of “differential susceptibility,” speaking to how corrective environmental factors may promote epigenetic change and reconfigure neural templates, allowing for symptomatic improvement. Psychotherapy is one such factor, and this review will focus on our current knowledge of its epigenetic and neurocircuitry impact. PMID:29226124

The Future of Contextual Fear Learning for PTSD Research: A Methodological Review of Neuroimaging Studies.

PubMed

Glenn, Daniel E; Risbrough, Victoria B; Simmons, Alan N; Acheson, Dean T; Stout, Daniel M

2017-10-21

There has been a great deal of recent interest in human models of contextual fear learning, particularly due to the use of such paradigms for investigating neural mechanisms related to the etiology of posttraumatic stress disorder. However, the construct of "context" in fear conditioning research is broad, and the operational definitions and methods used to investigate contextual fear learning in humans are wide ranging and lack specificity, making it difficult to interpret findings about neural activity. Here we will review neuroimaging studies of contextual fear acquisition in humans. We will discuss the methodology associated with four broad categories of how contextual fear learning is manipulated in imaging studies (colored backgrounds, static picture backgrounds, virtual reality, and configural stimuli) and highlight findings for the primary neural circuitry involved in each paradigm. Additionally, we will offer methodological recommendations for human studies of contextual fear acquisition, including using stimuli that distinguish configural learning from discrete cue associations and clarifying how context is experimentally operationalized.

Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsu, Jer-Yuan; Crawley, Suzanne; Chen, Michael

Under homeostatic conditions, animals use well-defined hypothalamic neural circuits to help maintain stable body weight, by integrating metabolic and hormonal signals from the periphery to balance food consumption and energy expenditure1,2. In stressed or disease conditions, however, animals use alternative neuronal pathways to adapt to the metabolic challenges of altered energy demand3. Recent studies have identified brain areas outside the hypothalamus that are activated under these ‘non-homeostatic’ conditions4,5,6, but the molecular nature of the peripheral signals and brain-localized receptors that activate these circuits remains elusive. Here we identify glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as a brainstem-restricted receptormore » for growth and differentiation factor 15 (GDF15). GDF15 regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses; we show that Gfral knockout mice are hyperphagic under stressed conditions and are resistant to chemotherapy-induced anorexia and body weight loss. GDF15 activates GFRAL-expressing neurons localized exclusively in the area postrema and nucleus tractus solitarius of the mouse brainstem. It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitute part of the ‘emergency circuit’ that shapes feeding responses to stressful conditions7. GDF15 levels increase in response to tissue stress and injury, and elevated levels are associated with body weight loss in numerous chronic human diseases8,9. By isolating GFRAL as the receptor for GDF15-induced anorexia and weight loss, we identify a mechanistic basis for the non-homeostatic regulation of neural circuitry by a peripheral signal associated with tissue damage and stress. These findings provide opportunities to develop therapeutic agents for the treatment of disorders with altered energy demand.« less

Dysfunctional overnight memory consolidation in ecstasy users.

PubMed

Smithies, Vanessa; Broadbear, Jillian; Verdejo-Garcia, Antonio; Conduit, Russell

2014-08-01

Sleep plays an important role in the consolidation and integration of memory in a process called overnight memory consolidation. Previous studies indicate that ecstasy users have marked and persistent neurocognitive and sleep-related impairments. We extend past research by examining overnight memory consolidation among regular ecstasy users (n=12) and drug naïve healthy controls (n=26). Memory recall of word pairs was evaluated before and after a period of sleep, with and without interference prior to testing. In addition, we assessed neurocognitive performances across tasks of learning, memory and executive functioning. Ecstasy users demonstrated impaired overnight memory consolidation, a finding that was more pronounced following associative interference. Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long-term memory, encoding, working memory and complex planning. We suggest that ecstasy-associated dysfunction in fronto-temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users. © The Author(s) 2014.

Skilled movements require non-apoptotic Bax/Bak pathway-mediated corticospinal circuit reorganization

PubMed Central

Gu, Zirong; Serradj, Najet; Ueno, Masaki; Liang, Mishi; Li, Jie; Baccei, Mark L.; Martin, John H.; Yoshida, Yutaka

2017-01-01

Early postnatal mammals, including human babies, can perform only basic motor tasks. The acquisition of skilled behaviors occurs later, requiring anatomical changes in neural circuitry to support the development of coordinated activation or suppression of functionally related muscle groups. How this circuit reorganization occurs during postnatal development remains poorly understood. Here we explore the connectivity between corticospinal (CS) neurons in the motor cortex and muscles in mice. Using trans-synaptic viral and electrophysiological assays, we identify the early postnatal reorganization of CS circuitry for antagonistic muscle pairs. We further show that this synaptic rearrangement requires the activity-dependent, non-apoptotic Bax/Bak-caspase signaling cascade. Adult Bax/Bak mutant mice exhibit aberrant co-activation of antagonistic muscle pairs and skilled grasping deficits but normal reaching and retrieval behaviors. Our findings reveal key cellular and molecular mechanisms driving postnatal motor circuit reorganization and the resulting impacts on muscle activation patterns and the execution of skilled movements. PMID:28472660

Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

PubMed

Boeva, Valentina; Louis-Brennetot, Caroline; Peltier, Agathe; Durand, Simon; Pierre-Eugène, Cécile; Raynal, Virginie; Etchevers, Heather C; Thomas, Sophie; Lermine, Alban; Daudigeos-Dubus, Estelle; Geoerger, Birgit; Orth, Martin F; Grünewald, Thomas G P; Diaz, Elise; Ducos, Bertrand; Surdez, Didier; Carcaboso, Angel M; Medvedeva, Irina; Deller, Thomas; Combaret, Valérie; Lapouble, Eve; Pierron, Gaelle; Grossetête-Lalami, Sandrine; Baulande, Sylvain; Schleiermacher, Gudrun; Barillot, Emmanuel; Rohrer, Hermann; Delattre, Olivier; Janoueix-Lerosey, Isabelle

2017-09-01

Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

Process Versus Product in Social Learning: Comparative Diffusion Tensor Imaging of Neural Systems for Action Execution–Observation Matching in Macaques, Chimpanzees, and Humans

PubMed Central

Hecht, Erin E.; Gutman, David A.; Preuss, Todd M.; Sanchez, Mar M.; Parr, Lisa A.; Rilling, James K.

2013-01-01

Social learning varies among primate species. Macaques only copy the product of observed actions, or emulate, while humans and chimpanzees also copy the process, or imitate. In humans, imitation is linked to the mirror system. Here we compare mirror system connectivity across these species using diffusion tensor imaging. In macaques and chimpanzees, the preponderance of this circuitry consists of frontal–temporal connections via the extreme/external capsules. In contrast, humans have more substantial temporal–parietal and frontal–parietal connections via the middle/inferior longitudinal fasciculi and the third branch of the superior longitudinal fasciculus. In chimpanzees and humans, but not in macaques, this circuitry includes connections with inferior temporal cortex. In humans alone, connections with superior parietal cortex were also detected. We suggest a model linking species differences in mirror system connectivity and responsivity with species differences in behavior, including adaptations for imitation and social learning of tool use. PMID:22539611

Control of stress-induced persistent anxiety by an extra-amygdala septohypothalamic circuit

PubMed Central

Anthony, Todd E.; Dee, Nick; Bernard, Amy; Lerchner, Walter; Heintz, Nathaniel; Anderson, David J.

2014-01-01

The extended amygdala has dominated research on the neural circuitry of fear and anxiety, but the septo-hippocampal axis plays an important role as well. The lateral septum (LS) is thought to suppress fear and anxiety, through its outputs to the hypothalamus. However, this structure has not yet been dissected using modern tools. The type 2 CRF receptor (Crfr2) marks a subset of LS neurons, whose functional connectivity we have investigated using optogenetics. Crfr2+ cells include GABAergic projection neurons that connect with the anterior hypothalamus. Surprisingly, we find that these LS outputs enhance stress-induced behavioral measures of anxiety. Furthermore, transient activation of Crfr2+ neurons promotes, while inhibition suppresses, persistent anxious behaviors. LS Crfr2+ outputs also positively regulate circulating corticosteroid levels. These data identify a subset of LS projection neurons that promote, rather than suppress, stress-induced behavioral and endocrinological dimensions of persistent anxiety states, and provide a cellular point-of-entry to LS circuitry. PMID:24485458

Easy to remember, difficult to forget: the development of fear regulation

PubMed Central

Johnson, D.C.; Casey, B.J.

2014-01-01

Fear extinction learning is a highly adaptive process that involves the integrity of frontolimbic circuitry. Its disruption has been associated with emotional dysregulation in stress and anxiety disorders. In this article we consider how age, genetics and experiences shape our capacity to regulate fear in cross-species studies. Evidence for adolescent-specific diminished fear extinction learning is presented in the context of immature frontolimbic circuitry. We also present evidence for less neural plasticity in fear regulation as a function of early life stress and by genotype, focusing on the common brain derived neurotrophin factor (BDNF) Val66Met polymorphism. Finally, we discuss this work in the context of exposure-based behavioral therapies for the treatment of anxiety and stress disorders that are based on principles of fear extinction. We conclude by speculating on how such therapies may be optimized for the individual based on the patient’s age, genetic profile and personal history to move from standard treatment of care to personalized and precision medicine. PMID:25238998

MEMS technologies for epiretinal stimulation of the retina

NASA Astrophysics Data System (ADS)

Mokwa, W.

2004-09-01

It has been shown that electrical stimulation of retinal ganglion cells yields visual sensations. Therefore, a retina implant for blind humans suffering from retinitis pigmentosa based on this concept seems to be feasible. In Germany, there are two projects funded by the government working on different approaches namely the subretinal and the epiretinal approaches. This paper describes the epiretinal approach for such a system. The extraocular part of this system records visual images. The images are transformed by a neural net into corresponding signals for stimulation of the retinal ganglion cells. These signals are transmitted to a receiver unit of an intraocular implant, the retina stimulator. Integrated circuitry of this unit decodes the signals and transfers the data to a stimulation circuitry that selects stimulation electrodes placed onto the retina and generates current pulses to the electrodes. By this, action potentials in retinal ganglion cells are evoked, causing a visual sensation. This paper concentrates on the MEMS part of this implant.

Influence of neurobehavioral incentive valence and magnitude on alcohol drinking behavior

PubMed Central

Joseph, Jane E.; Zhu, Xun; Corbly, Christine R.; DeSantis, Stacia; Lee, Dustin C.; Baik, Grace; Kiser, Seth; Jiang, Yang; Lynam, Donald R.; Kelly, Thomas H.

2014-01-01

The monetary incentive delay (MID) task is a widely used probe for isolating neural circuitry in the human brain associated with incentive motivation. In the present functional magnetic resonance imaging (fMRI) study, 82 young adults, characterized along dimensions of impulsive sensation seeking, completed a MID task. fMRI and behavioral incentive functions were decomposed into incentive valence and magnitude parameters, which were used as predictors in linear regression to determine whether mesolimbic response is associated with problem drinking and recent alcohol use. Alcohol use was best explained by higher fMRI response to anticipation of losses and feedback on high gains in the thalamus. In contrast, problem drinking was best explained by reduced sensitivity to large incentive values in meso-limbic regions in the anticipation phase and increased sensitivity to small incentive values in the dorsal caudate nucleus in the feedback phase. Altered fMRI responses to monetary incentives in mesolimbic circuitry, particularly those alterations associated with problem drinking, may serve as potential early indicators of substance abuse trajectories. PMID:25261001

Low-Cutoff, High-Pass Digital Filtering of Neural Signals

NASA Technical Reports Server (NTRS)

Mojarradi,Mohammad; Johnson, Travis; Ortiz, Monico; Cunningham, Thomas; Andersen, Richard

2004-01-01

The figure depicts the major functional blocks of a system, now undergoing development, for conditioning neural signals acquired by electrodes implanted in a brain. The overall functions to be performed by this system can be summarized as preamplification, multiplexing, digitization, and high-pass filtering. Other systems under development for recording neural signals typically contain resistor-capacitor analog low-pass filters characterized by cutoff frequencies in the vicinity of 100 Hz. In the application for which this system is being developed, there is a requirement for a cutoff frequency of 5 Hz. Because the resistors needed to obtain such a low cutoff frequency would be impractically large, it was decided to perform low-pass filtering by use of digital rather than analog circuitry. In addition, it was decided to timemultiplex the digitized signals from the multiple input channels into a single stream of data in a single output channel. The signal in each input channel is first processed by a preamplifier having a voltage gain of approximately 50. Embedded in each preamplifier is a low-pass anti-aliasing filter having a cutoff frequency of approximately 10 kHz. The anti-aliasing filters make it possible to couple the outputs of the preamplifiers to the input ports of a multiplexer. The output of the multiplexer is a single stream of time-multiplexed samples of analog signals. This stream is processed by a main differential amplifier, the output of which is sent to an analog-to-digital converter (ADC). The output of the ADC is sent to a digital signal processor (DSP).

Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa.

PubMed

Holsen, Laura M; Lawson, Elizabeth A; Christensen, Kara; Klibanski, Anne; Goldstein, Jill M

2014-08-30

Evidence contributing to the understanding of neurobiological mechanisms underlying appetite dysregulation in anorexia nervosa draws heavily on separate lines of research into neuroendocrine and neural circuitry functioning. In particular, studies consistently cite elevated ghrelin and abnormal activation patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula) regions governing appetite. The current preliminary study examined the interaction of these systems, based on research demonstrating associations between circulating ghrelin levels and activity in these regions in healthy individuals. In a cross-sectional design, we studied 13 women with active anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy-weight control women using a food cue functional magnetic resonance imaging paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight control women exhibited significant positive associations between fasting acylated ghrelin and activity in the right amygdala, hippocampus, insula, and orbitofrontal cortex in response to high-calorie foods, associations which were absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative relationship between ghrelin and activity in the left hippocampus in response to high-calorie foods, while women with AN showed a positive association between ghrelin and activity in the right orbitofrontal cortex in response to low-calorie foods. Findings suggest a breakdown in the interaction between ghrelin signaling and neural activity in relation to reward responsivity in AN, a phenomenon that may be further characterized using pharmacogenetic studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Overexpressing corticotropin-releasing hormone (CRH) in the primate amygdala increases anxious temperament and alters its neural circuit

PubMed Central

Kalin, Ned H; Fox, Andrew S; Kovner, Rothem; Riedel, Marissa K; Fekete, Eva M; Roseboom, Patrick H; Tromp, Do P M; Grabow, Benjamin P; Olsen, Miles E; Brodsky, Ethan K; McFarlin, Daniel R.; Alexander, Andrew L; Emborg, Marina E; Block, Walter F; Fudge, Julie L; Oler, Jonathan A

2016-01-01

Background Nonhuman primate models are critical for understanding mechanisms underlying human psychopathology. We established a non-human primate model of anxious temperament (AT) for studying the early-life risk to develop anxiety and depression. Studies have identified the central nucleus of the amygdala (Ce) as an essential component of AT’s neural substrates. Corticotropin-releasing hormone (CRH) is expressed in the Ce, has a role in stress, and is linked to psychopathology. Here, in young rhesus monkeys, we combined viral vector technology with assessments of anxiety and multimodal neuroimaging to understand the consequences of chronically increased CRH in the Ce-region. Methods Using real-time intraoperative MRI-guided convection-enhanced delivery, 5 monkeys received bilateral dorsal amygdala Ce-region infusions of adeno-associated virus serotype 2 (AAV2) containing the CRH construct. Their cage-mates served as unoperated controls. AT, regional brain metabolism, “resting” fMRI, and diffusion tensor imaging (DTI) were assessed before and two months after viral infusions. Results Dorsal amygdala CRH overexpression significantly increased AT and metabolism within the dorsal amygdala. Additionally, we observed changes in metabolism in other AT-related regions, as well as in measures of functional and structural connectivity. Conclusion This study provides a translational roadmap that is important for understanding human psychopathology by combining molecular manipulations used in rodents with behavioral phenotyping and multimodal neuroimaging measures used in humans. The results indicate that chronic CRH overexpression in primates not only increases AT, but also affects metabolism and connectivity within components of AT’s neural circuitry. PMID:27016385

Real-time cerebellar neuroprosthetic system based on a spiking neural network model of motor learning.

PubMed

Xu, Tao; Xiao, Na; Zhai, Xiaolong; Kwan Chan, Pak; Tin, Chung

2018-02-01

Damage to the brain, as a result of various medical conditions, impacts the everyday life of patients and there is still no complete cure to neurological disorders. Neuroprostheses that can functionally replace the damaged neural circuit have recently emerged as a possible solution to these problems. Here we describe the development of a real-time cerebellar neuroprosthetic system to substitute neural function in cerebellar circuitry for learning delay eyeblink conditioning (DEC). The system was empowered by a biologically realistic spiking neural network (SNN) model of the cerebellar neural circuit, which considers the neuronal population and anatomical connectivity of the network. The model simulated synaptic plasticity critical for learning DEC. This SNN model was carefully implemented on a field programmable gate array (FPGA) platform for real-time simulation. This hardware system was interfaced in in vivo experiments with anesthetized rats and it used neural spikes recorded online from the animal to learn and trigger conditioned eyeblink in the animal during training. This rat-FPGA hybrid system was able to process neuronal spikes in real-time with an embedded cerebellum model of ~10 000 neurons and reproduce learning of DEC with different inter-stimulus intervals. Our results validated that the system performance is physiologically relevant at both the neural (firing pattern) and behavioral (eyeblink pattern) levels. This integrated system provides the sufficient computation power for mimicking the cerebellar circuit in real-time. The system interacts with the biological system naturally at the spike level and can be generalized for including other neural components (neuron types and plasticity) and neural functions for potential neuroprosthetic applications.

Complex computation in the retina

NASA Astrophysics Data System (ADS)

Deshmukh, Nikhil Rajiv

Elucidating the general principles of computation in neural circuits is a difficult problem requiring both a tractable model circuit as well as sophisticated measurement tools. This thesis advances our understanding of complex computation in the salamander retina and its underlying circuitry and furthers the development of advanced tools to enable detailed study of neural circuits. The retina provides an ideal model system for neural circuits in general because it is capable of producing complex representations of the visual scene, and both its inputs and outputs are accessible to the experimenter. Chapter 2 describes the biophysical mechanisms that give rise to the omitted stimulus response in retinal ganglion cells described in Schwartz et al., (2007) and Schwartz and Berry, (2008). The extra response to omitted flashes is generated at the input to bipolar cells, and is separable from the characteristic latency shift of the OSR apparent in ganglion cells, which must occur downstream in the circuit. Chapter 3 characterizes the nonlinearities at the first synapse of the ON pathway in response to high contrast flashes and develops a phenomenological model that captures the effect of synaptic activation and intracellular signaling dynamics on flash responses. This work is the first attempt to model the dynamics of the poorly characterized mGluR6 transduction cascade unique to ON bipolar cells, and explains the second lobe of the biphasic flash response. Complementary to the study of neural circuits, recent advances in wafer-scale photolithography have made possible new devices to measure the electrical and mechanical properties of neurons. Chapter 4 reports a novel piezoelectric sensor that facilitates the simultaneous measurement of electrical and mechanical signals in neural tissue. This technology could reveal the relationship between the electrical activity of neurons and their local mechanical environment, which is critical to the study of mechanoreceptors, neural development, and traumatic brain injury. Chapter 5 describes advances in the development, fabrication, and testing of a prototype silicon micropipette for patch clamp physiology. Nanoscale photolithography addresses some of the limitations of traditional glass patch electrodes, such as the rapid dialysis of the cell with internal solution, and provides a platform for integration of microfluidics and electronics into the device, which can enable novel experimental methodology.

Distinguishing between Unipolar Depression and Bipolar Depression: Current and Future Clinical and Neuroimaging Perspectives

PubMed Central

de Almeida, Jorge Renner Cardoso; Phillips, Mary Louise

2012-01-01

Differentiating bipolar disorder (BD) from recurrent unipolar depression (UD) is a major clinical challenge. Main reasons for this include the higher prevalence of depressive relative to hypo/manic symptoms during the course of BD illness and the high prevalence of subthreshold manic symptoms in both BD and UD depression. Identifying objective markers of BD might help improve accuracy in differentiating between BD and UD depression, to ultimately optimize clinical and functional outcome for all depressed individuals. Yet, only eight neuroimaging studies to date directly compared UD and BD depressed individuals. Findings from these studies suggest more widespread abnormalities in white matter connectivity and white matter hyperintensities in BD than UD depression, habenula volume reductions in BD but not UD depression, and differential patterns of functional abnormalities in emotion regulation and attentional control neural circuitry in the two depression types. These findings suggest different pathophysiologic processes, especially in emotion regulation, reward and attentional control neural circuitry in BD versus UD depression. This review thereby serves as a “call to action” to highlight the pressing need for more neuroimaging studies, using larger samples sizes, comparing BD and UD depressed individuals. These future studies should also include dimensional approaches, studies of at risk individuals, and more novel neuroimaging approaches, such as, connectivity analysis and machine learning. Ultimately, these approaches might provide biomarkers to identify individuals at future risk for BD versus UD, and biological targets for more personalized treatment and new treatment developments for BD and UD depression. PMID:22784485

Rhythmic arm movements are less affected than discrete ones after a stroke.

PubMed

Leconte, Patricia; Orban de Xivry, Jean-Jacques; Stoquart, Gaëtan; Lejeune, Thierry; Ronsse, Renaud

2016-06-01

Recent reports indicate that rhythmic and discrete upper-limb movements are two different motor primitives which recruit, at least partially, distinct neural circuitries. In particular, rhythmic movements recruit a smaller cortical network than discrete movements. The goal of this paper is to compare the levels of disability in performing rhythmic and discrete movements after a stroke. More precisely, we tested the hypothesis that rhythmic movements should be less affected than discrete ones, because they recruit neural circuitries that are less likely to be damaged by the stroke. Eleven stroke patients and eleven age-matched control subjects performed discrete and rhythmic movements using an end-effector robot (REAplan). The rhythmic movement condition was performed with and without visual targets to further decrease cortical recruitment. Movement kinematics was analyzed through specific metrics, capturing the degree of smoothness and harmonicity. We reported three main observations: (1) the movement smoothness of the paretic arm was more severely degraded for discrete movements than rhythmic movements; (2) most of the patients performed rhythmic movements with a lower harmonicity than controls; and (3) visually guided rhythmic movements were more altered than non-visually guided rhythmic movements. These results suggest a hierarchy in the levels of impairment: Discrete movements are more affected than rhythmic ones, which are more affected if they are visually guided. These results are a new illustration that discrete and rhythmic movements are two fundamental primitives in upper-limb movements. Moreover, this hierarchy of impairment opens new post-stroke rehabilitation perspectives.

Altered prefrontal cortical function during processing of fear-relevant stimuli in pregnancy.

PubMed

Roos, Annerine; Robertson, Frances; Lochner, Christine; Vythilingum, Bavanisha; Stein, Dan J

2011-09-12

In non-pregnant individuals, the prefrontal cortex (PFC) is involved in the regulation of emotion, and appears to play a role in anxiety. Near-infrared spectroscopy (NIRS) detects cortical neural activation without harmful radiation making it safe for use in pregnancy. The aims of this study were to assess neural circuitry involved in processing fear-relevant stimuli during pregnancy using NIRS, and to determine associations between activation of this circuitry, distress and anxiety symptoms, attention to threat, cortisol, estrogen, progesterone and testosterone levels. There was significant activation of the PFC in response to fearful faces compared to rest in both pregnant and control groups. Within pregnancy, the activation was most pronounced at trimester 2, compared to the other trimesters. In pregnant women only (all trimesters), PFC activation was significantly associated with increased distress and anxiety, but with decreased selective attention to masked fear. PFC activation was also significantly associated with increased levels of cortisol and testosterone in pregnancy. PFC function appears to be altered during processing of fear-relevant stimuli in pregnancy. Changes in hormone levels may lead to changes in PFC function, and in turn to changes in cognitive-affective processing and anxiety. Further work is needed, however, to explore precisely how PFC function is altered in pregnancy; it is possible that certain changes reflect altered processing of threat stimuli, while others reflect attempts to compensate for distressing and anxious symptoms that emerge during pregnancy. Copyright © 2011 Elsevier B.V. All rights reserved.

Closing the Loop for Memory Prostheses: Detecting the Role of Hippocampal Neural Ensembles Using Nonlinear Models

PubMed Central

Hampson, Robert E.; Song, Dong; Chan, Rosa H.M.; Sweatt, Andrew J.; Riley, Mitchell R.; Goonawardena, Anushka V.; Marmarelis, Vasilis Z.; Gerhardt, Greg A.; Berger, Theodore W.; Deadwyler, Sam A.

2012-01-01

A major factor involved in providing closed loop feedback for control of neural function is to understand how neural ensembles encode online information critical to the final behavioral endpoint. This issue was directly assessed in rats performing a short-term delay memory task in which successful encoding of task information is dependent upon specific spatiotemporal firing patterns recorded from ensembles of CA3 and CA1 hippocampal neurons. Such patterns, extracted by a specially designed nonlinear multi-input multi-output (MIMO) nonlinear mathematical model, were used to predict successful performance online via a closed loop paradigm which regulated trial difficulty (time of retention) as a function of the “strength” of stimulus encoding. The significance of the MIMO model as a neural prosthesis has been demonstrated by substituting trains of electrical stimulation pulses to mimic these same ensemble firing patterns. This feature was used repeatedly to vary “normal” encoding as a means of understanding how neural ensembles can be “tuned” to mimic the inherent process of selecting codes of different strength and functional specificity. The capacity to enhance and tune hippocampal encoding via MIMO model detection and insertion of critical ensemble firing patterns shown here provides the basis for possible extension to other disrupted brain circuitry. PMID:22498704

Trait-level temporal lobe hypoactivation to social exclusion in unaffected siblings of children and adolescents with autism spectrum disorders

PubMed Central

Bolling, Danielle Z.; Pelphrey, Kevin A.; Vander Wyk, Brent C.

2015-01-01

Social exclusion elicits powerful feelings of negative affect associated with rejection. Additionally, experiencing social exclusion reliably recruits neural circuitry associated with emotion processing. Recent work has demonstrated abnormal neural responses to social exclusion in children and adolescents with autism spectrum disorders (ASD). However, it remains unknown to what extent these abnormalities are due to atypical social experiences versus genetic predispositions to atypical neural processing. To address this question, the current study investigated brain responses to social exclusion compared to a baseline condition of fair play in unaffected siblings of youth with ASD using functional magnetic resonance imaging. We identified common deviations between unaffected siblings and ASD probands that might represent trait-level abnormalities in processing social exclusion versus fair play, specifically in the right anterior temporoparietal junction extending into posterior superior temporal sulcus. Thus, hypoactivation to social exclusion versus fair play in this region may represent a shared genetic vulnerability to developing autism. In addition, we present evidence supporting the idea that one’s status as an unaffected sibling moderates the relationship between IQ and neural activation to social exclusion versus fair play in anterior cingulate cortex. These results are discussed in the context of previous literature on neural endophenotypes of autism. PMID:26011751

Sex differences in the neural correlates of affective experience

PubMed Central

Moriguchi, Yoshiya; Touroutoglou, Alexandra; Dickerson, Bradford C.

2014-01-01

People believe that women are more emotionally intense than men, but the scientific evidence is equivocal. In this study, we tested the novel hypothesis that men and women differ in the neural correlates of affective experience, rather than in the intensity of neural activity, with women being more internally (interoceptively) focused and men being more externally (visually) focused. Adult men (n = 17) and women (n = 17) completed a functional magnetic resonance imaging study while viewing affectively potent images and rating their moment-to-moment feelings of subjective arousal. We found that men and women do not differ overall in their intensity of moment-to-moment affective experiences when viewing evocative images, but instead, as predicted, women showed a greater association between the momentary arousal ratings and neural responses in the anterior insula cortex, which represents bodily sensations, whereas men showed stronger correlations between their momentary arousal ratings and neural responses in the visual cortex. Men also showed enhanced functional connectivity between the dorsal anterior insula cortex and the dorsal anterior cingulate cortex, which constitutes the circuitry involved with regulating shifts of attention to the world. These results demonstrate that the same affective experience is realized differently in different people, such that women’s feelings are relatively more self-focused, whereas men’s feelings are relatively more world-focused. PMID:23596188

Category-Specific Neural Oscillations Predict Recall Organization During Memory Search

PubMed Central

Morton, Neal W.; Kahana, Michael J.; Rosenberg, Emily A.; Baltuch, Gordon H.; Litt, Brian; Sharan, Ashwini D.; Sperling, Michael R.; Polyn, Sean M.

2013-01-01

Retrieved-context models of human memory propose that as material is studied, retrieval cues are constructed that allow one to target particular aspects of past experience. We examined the neural predictions of these models by using electrocorticographic/depth recordings and scalp electroencephalography (EEG) to characterize category-specific oscillatory activity, while participants studied and recalled items from distinct, neurally discriminable categories. During study, these category-specific patterns predict whether a studied item will be recalled. In the scalp EEG experiment, category-specific activity during study also predicts whether a given item will be recalled adjacent to other same-category items, consistent with the proposal that a category-specific retrieval cue is used to guide memory search. Retrieved-context models suggest that integrative neural circuitry is involved in the construction and maintenance of the retrieval cue. Consistent with this hypothesis, we observe category-specific patterns that rise in strength as multiple same-category items are studied sequentially, and find that individual differences in this category-specific neural integration during study predict the degree to which a participant will use category information to organize memory search. Finally, we track the deployment of this retrieval cue during memory search: Category-specific patterns are stronger when participants organize their responses according to the category of the studied material. PMID:22875859