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.

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

Intergenerational Neuroimaging of Human Brain Circuitry

PubMed Central

Ho, Tiffany C.; Sanders, Stephan J.; Gotlib, Ian H.; Hoeft, Fumiko

2016-01-01

Neuroscientists are increasingly using advanced neuroimaging methods to elucidate the intergenerational transmission of human brain circuitry. This new line of work promises to shed insight into the ontogeny of complex behavioral traits, including psychiatric disorders, and possible mechanisms of transmission. Here, we highlight recent intergenerational neuroimaging studies and provide recommendations for future work. PMID:27623194

Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence

PubMed Central

Herringa, Ryan J.; Birn, Rasmus M.; Ruttle, Paula L.; Burghy, Cory A.; Stodola, Diane E.; Davidson, Richard J.; Essex, Marilyn J.

2013-01-01

Maltreatment during childhood is a major risk factor for anxiety and depression, which are major public health problems. However, the underlying brain mechanism linking maltreatment and internalizing disorders remains poorly understood. Maltreatment may alter the activation of fear circuitry, but little is known about its impact on the connectivity of this circuitry in adolescence and whether such brain changes actually lead to internalizing symptoms. We examined the associations between experiences of maltreatment during childhood, resting-state functional brain connectivity (rs-FC) of the amygdala and hippocampus, and internalizing symptoms in 64 adolescents participating in a longitudinal community study. Childhood experiences of maltreatment were associated with lower hippocampus–subgenual cingulate rs-FC in both adolescent females and males and lower amygdala–subgenual cingulate rs-FC in females only. Furthermore, rs-FC mediated the association of maltreatment during childhood with adolescent internalizing symptoms. Thus, maltreatment in childhood, even at the lower severity levels found in a community sample, may alter the regulatory capacity of the brain’s fear circuit, leading to increased internalizing symptoms by late adolescence. These findings highlight the importance of fronto–hippocampal connectivity for both sexes in internalizing symptoms following maltreatment in childhood. Furthermore, the impact of maltreatment during childhood on both fronto–amygdala and –hippocampal connectivity in females may help explain their higher risk for internalizing disorders such as anxiety and depression. PMID:24191026

Brain serotonergic circuitries

PubMed Central

Charnay, Yves; Leger, Lucienne

2010-01-01

Brain serotonergic circuitries interact with other neurotransmitter systems on a multitude of different molecular levels. In humans, as in other mammalian species, serotonin (5-HT) plays a modulatory role in almost every physiological function. Furthermore, serotonergic dysfunction is thought to be implicated in several psychiatric and neurodegenerative disorders. We describe the neuroanatomy and neurochemistry of brain serotonergic circuitries. The contribution of emergent in vivo imaging methods to the regional localization of binding site receptors and certain aspects of their functional connectivity in correlation to behavior is also discussed. 5-HT cell bodies, mainly localized in the raphe nuclei, send axons to almost every brain region. It is argued that the specificity of the local chemocommunication between 5-HT and other neuronal elements mainly depends on mechanisms regulating the extracellular concentration of 5-HT, the diversity of high-affinity membrane receptors, and their specific transduction modalities. PMID:21319493

Genomics analysis of potassium channel genes in songbirds reveals molecular specializations of brain circuits for the maintenance and production of learned vocalizations

PubMed Central

2013-01-01

Background A fundamental question in molecular neurobiology is how genes that determine basic neuronal properties shape the functional organization of brain circuits underlying complex learned behaviors. Given the growing availability of complete vertebrate genomes, comparative genomics represents a promising approach to address this question. Here we used genomics and molecular approaches to study how ion channel genes influence the properties of the brain circuitry that regulates birdsong, a learned vocal behavior with important similarities to human speech acquisition. We focused on potassium (K-)Channels, which are major determinants of neuronal cell excitability. Starting with the human gene set of K-Channels, we used cross-species mRNA/protein alignments, and syntenic analysis to define the full complement of orthologs, paralogs, allelic variants, as well as novel loci not previously predicted in the genome of zebra finch (Taeniopygia guttata). We also compared protein coding domains in chicken and zebra finch orthologs to identify genes under positive selective pressure, and those that contained lineage-specific insertions/deletions in functional domains. Finally, we conducted comprehensive in situ hybridizations to determine the extent of brain expression, and identify K-Channel gene enrichments in nuclei of the avian song system. Results We identified 107 K-Channel finch genes, including 6 novel genes common to non-mammalian vertebrate lineages. Twenty human genes are absent in songbirds, birds, or sauropsids, or unique to mammals, suggesting K-Channel properties may be lineage-specific. We also identified specific family members with insertions/deletions and/or high dN/dS ratios compared to chicken, a non-vocal learner. In situ hybridization revealed that while most K-Channel genes are broadly expressed in the brain, a subset is selectively expressed in song nuclei, representing molecular specializations of the vocal circuitry. Conclusions Together, these findings shed new light on genes that may regulate biophysical and excitable properties of the song circuitry, identify potential targets for the manipulation of the song system, and reveal genomic specializations that may relate to the emergence of vocal learning and associated brain areas in birds. PMID:23845108

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

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.

Tonic and Rhythmic Spinal Activity Underlying Locomotion.

PubMed

Ivanenko, Yury P; Gurfinkel, Victor S; Selionov, Victor A; Solopova, Irina A; Sylos-Labini, Francesca; Guertin, Pierre A; Lacquaniti, Francesco

2017-05-12

In recent years, many researches put significant efforts into understanding and assessing the functional state of the spinal locomotor circuits in humans. Various techniques have been developed to stimulate the spinal cord circuitries, which may include both diffuse and quite specific tuning effects. Overall, the findings indicate that tonic and rhythmic spinal activity control are not separate phenomena but are closely integrated to properly initiate and sustain stepping. The spinal cord does not simply transmit information to and from the brain. Its physiologic state determines reflex, postural and locomotor control and, therefore, may affect the recovery of the locomotor function in individuals with spinal cord and brain injuries. This review summarizes studies that examine the rhythmogenesis capacity of cervical and lumbosacral neuronal circuitries in humans and its importance in developing central pattern generator-modulating therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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),…

Barrels XXX meeting report: Barrels in Baltimore.

PubMed

Shin, Hyeyoung; Bitzidou, Malamati; Palaguachi, Fernando; Brumberg, Joshua C

2018-03-01

The Barrels meeting annually brings together researchers focused on the rodent whisker to cortical barrel system prior to the Society for Neuroscience meeting. The 2017 meeting focused on the classification of cortical interneurons, the role interneurons have in shaping brain dynamics, and finally on the circuitry underlying oral sensations. The meeting highlighted the latest advancements in this rapidly advancing field.

Central Brain Circuitry for Color-Vision-Modulated Behaviors.

PubMed

Longden, Kit D

2016-10-24

Color is famous for not existing in the external world: our brains create the perception of color from the spatial and temporal patterns of the wavelength and intensity of light. For an intangible quality, we have detailed knowledge of its origins and consequences. Much is known about the organization and evolution of the first phases of color processing, the filtering of light in the eye and processing in the retina, and about the final phases, the roles of color in behavior and natural selection. To understand how color processing in the central brain has evolved, we need well-defined pathways or circuitry where we can gauge how color contributes to the computations involved in specific behaviors. Examples of such pathways or circuitry that are dedicated to processing color cues are rare, despite the separation of color and luminance pathways early in the visual system of many species, and despite the traditional definition of color as being independent of luminance. This minireview presents examples in which color vision contributes to behaviors dominated by other visual modalities, examples that are not part of the canon of color vision circuitry. The pathways and circuitry process a range of chromatic properties of objects and their illumination, and are taken from a variety of species. By considering how color processing complements luminance processing, rather than being independent of it, we gain an additional way to account for the diversity of color coding in the central brain, its consequences for specific behaviors and ultimately the evolution of color vision. Copyright © 2016 Elsevier Ltd. All rights reserved.

Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation.

PubMed

Da Cunha, Claudio; Boschen, Suelen L; Gómez-A, Alexander; Ross, Erika K; Gibson, William S J; Min, Hoon-Ki; Lee, Kendall H; Blaha, Charles D

2015-11-01

This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toward sophisiticated basal ganglia neuromodulation: review on basal gaglia deep brain stimulation

PubMed Central

Da Cunha, Claudio; Boschen, Suelen L.; Gómez-A, Alexander; Ross, Erika K.; Gibson, William S. J.; Min, Hoon-Ki; Lee, Kendall H.; Blaha, Charles D.

2015-01-01

This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson’s disease, Huntington’s disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. PMID:25684727

Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain.

PubMed

Hulbert, Samuel W; Jiang, Yong-Hui

2017-04-01

Transgenic mice carrying mutations that cause Autism Spectrum Disorders (ASDs) continue to be valuable for determining the molecular underpinnings of the disorders. Recently, researchers have taken advantage of such models combined with Cre-loxP and similar systems to manipulate gene expression over space and time. Thus, a clearer picture is starting to emerge of the cell types, circuits, brain regions, and developmental time periods underlying ASDs. ASD-causing mutations have been restricted to or rescued specifically in excitatory or inhibitory neurons, different neurotransmitter systems, and cells specific to the forebrain or cerebellum. In addition, mutations have been induced or corrected in adult mice, providing some evidence for the plasticity and reversibility of core ASD symptoms. The limited availability of Cre lines that are highly specific to certain cell types or time periods provides a challenge to determining the cellular and circuitry bases of autism, but other technological advances may eventually overcome this obstacle.

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

A Multiscale Parallel Computing Architecture for Automated Segmentation of the Brain Connectome

PubMed Central

Knobe, Kathleen; Newton, Ryan R.; Schlimbach, Frank; Blower, Melanie; Reid, R. Clay

2015-01-01

Several groups in neurobiology have embarked into deciphering the brain circuitry using large-scale imaging of a mouse brain and manual tracing of the connections between neurons. Creating a graph of the brain circuitry, also called a connectome, could have a huge impact on the understanding of neurodegenerative diseases such as Alzheimer’s disease. Although considerably smaller than a human brain, a mouse brain already exhibits one billion connections and manually tracing the connectome of a mouse brain can only be achieved partially. This paper proposes to scale up the tracing by using automated image segmentation and a parallel computing approach designed for domain experts. We explain the design decisions behind our parallel approach and we present our results for the segmentation of the vasculature and the cell nuclei, which have been obtained without any manual intervention. PMID:21926011

Time-dependent reorganization of the brain components underlying memory retention in trace eyeblink conditioning.

PubMed

Takehara, Kaori; Kawahara, Shigenori; Kirino, Yutaka

2003-10-29

Many studies have confirmed the time-limited involvement of the hippocampus in mnemonic processes and suggested that there is reorganization of the responsible brain circuitry during memory consolidation. To clarify such reorganization, we chose trace classical eyeblink conditioning, in which hippocampal ablation produces temporally graded retrograde amnesia. Here, we extended the temporal characterization of retrograde amnesia to other regions that are involved in acquisition during this task: the medial prefrontal cortex (mPFC) and the cerebellum. At a various time interval after establishing the trace conditioned response (CR), rats received an aspiration of one of the three regions. After recovery, the animals were tested for their CR retention. When ablated 1 d after the learning, both the hippocampal lesion and the cerebellar lesion group of rats exhibited a severe impairment in retention of the CR, whereas the mPFC lesion group showed only a slight decline. With an increase in interval between the lesion and the learning, the effect of the hippocampal lesion diminished and that of the mPFC lesion increased. When ablated 4 weeks after the learning, the hippocampal lesion group exhibited as robust CRs as its corresponding control group. In contrast, the mPFC lesion and the cerebellar lesion groups failed to retain the CRs. These results indicate that the hippocampus and the cerebellum, but only marginally the mPFC, constitute a brain circuitry that mediates recently acquired memory. As time elapses, the circuitry is reorganized to use mainly the mPFC and the cerebellum, but not the hippocampus, for remotely acquired memory.

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.

Brain Correlates of Phasic Autonomic Response to Acupuncture Stimulation: An Event-Related fMRI Study

PubMed Central

Napadow, Vitaly; Lee, Jeungchan; Kim, Jieun; Cina, Stephen; Maeda, Yumi; Barbieri, Riccardo; Harris, Richard E.; Kettner, Norman; Park, Kyungmo

2013-01-01

Autonomic nervous system (ANS) response to acupuncture has been investigated by multiple studies; however, the brain circuitry underlying this response is not well understood. We applied event-related fMRI (er-fMRI) in conjunction with ANS recording (heart rate, HR; skin conductance response, SCR). Brief manual acupuncture stimuli were delivered at acupoints ST36 and SP9, while sham stimuli were delivered at control location, SH1. Acupuncture produced activation in S2, insula, and mid-cingulate cortex, and deactivation in default mode network (DMN) areas. On average, HR deceleration (HR–) and SCR were noted following both real and sham acupuncture, though magnitude of response was greater following real acupuncture and inter-subject magnitude of response correlated with evoked sensation intensity. Acupuncture events with strong SCR also produced greater anterior insula activation than without SCR. Moreover, acupuncture at SP9, which produced greater SCR, also produced stronger sharp pain sensation, and greater anterior insula activation. Conversely, acupuncture-induced HR– was associated with greater DMN deactivation. Between-event correlation demonstrated that this association was strongest for ST36, which also produced more robust HR–. In fact, DMN deactivation was significantly more pronounced across acupuncture stimuli producing HR–, versus those events characterized by acceleration (HR+). Thus, differential brain response underlying acupuncture stimuli may be related to differential autonomic outflows and may result from heterogeneity in evoked sensations. Our er-fMRI approach suggests that ANS response to acupuncture, consistent with previously characterized orienting and startle/defense responses, arises from activity within distinct subregions of the more general brain circuitry responding to acupuncture stimuli. PMID:22504841

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.

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.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

MedlinePlus

... addition to depression. SNRIs ease depression by impacting chemical messengers (neurotransmitters) used to communicate between brain cells. Like most antidepressants, SNRIs work by ultimately effecting changes in brain chemistry and communication in brain nerve cell circuitry known ...

Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits.

PubMed

Hashmi, Javeria A; Baliki, Marwan N; Huang, Lejian; Baria, Alex T; Torbey, Souraya; Hermann, Kristina M; Schnitzer, Thomas J; Apkarian, A Vania

2013-09-01

Chronic pain conditions are associated with abnormalities in brain structure and function. Moreover, some studies indicate that brain activity related to the subjective perception of chronic pain may be distinct from activity for acute pain. However, the latter are based on observations from cross-sectional studies. How brain activity reorganizes with transition from acute to chronic pain has remained unexplored. Here we study this transition by examining brain activity for rating fluctuations of back pain magnitude. First we compared back pain-related brain activity between subjects who have had the condition for ∼2 months with no prior history of back pain for 1 year (early, acute/subacute back pain group, n = 94), to subjects who have lived with back pain for >10 years (chronic back pain group, n = 59). In a subset of subacute back pain patients, we followed brain activity for back pain longitudinally over a 1-year period, and compared brain activity between those who recover (recovered acute/sub-acute back pain group, n = 19) and those in which the back pain persists (persistent acute/sub-acute back pain group, n = 20; based on a 20% decrease in intensity of back pain in 1 year). We report results in relation to meta-analytic probabilistic maps related to the terms pain, emotion, and reward (each map is based on >200 brain imaging studies, derived from neurosynth.org). We observed that brain activity for back pain in the early, acute/subacute back pain group is limited to regions involved in acute pain, whereas in the chronic back pain group, activity is confined to emotion-related circuitry. Reward circuitry was equally represented in both groups. In the recovered acute/subacute back pain group, brain activity diminished in time, whereas in the persistent acute/subacute back pain group, activity diminished in acute pain regions, increased in emotion-related circuitry, and remained unchanged in reward circuitry. The results demonstrate that brain representation for a constant percept, back pain, can undergo large-scale shifts in brain activity with the transition to chronic pain. These observations challenge long-standing theoretical concepts regarding brain and mind relationships, as well as provide important novel insights regarding definitions and mechanisms of chronic pain.

Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits

PubMed Central

Hashmi, Javeria A.; Baliki, Marwan N.; Huang, Lejian; Baria, Alex T.; Torbey, Souraya; Hermann, Kristina M.; Schnitzer, Thomas J.; Apkarian, A. Vania

2013-01-01

Chronic pain conditions are associated with abnormalities in brain structure and function. Moreover, some studies indicate that brain activity related to the subjective perception of chronic pain may be distinct from activity for acute pain. However, the latter are based on observations from cross-sectional studies. How brain activity reorganizes with transition from acute to chronic pain has remained unexplored. Here we study this transition by examining brain activity for rating fluctuations of back pain magnitude. First we compared back pain-related brain activity between subjects who have had the condition for ∼2 months with no prior history of back pain for 1 year (early, acute/subacute back pain group, n = 94), to subjects who have lived with back pain for >10 years (chronic back pain group, n = 59). In a subset of subacute back pain patients, we followed brain activity for back pain longitudinally over a 1-year period, and compared brain activity between those who recover (recovered acute/sub-acute back pain group, n = 19) and those in which the back pain persists (persistent acute/sub-acute back pain group, n = 20; based on a 20% decrease in intensity of back pain in 1 year). We report results in relation to meta-analytic probabilistic maps related to the terms pain, emotion, and reward (each map is based on >200 brain imaging studies, derived from neurosynth.org). We observed that brain activity for back pain in the early, acute/subacute back pain group is limited to regions involved in acute pain, whereas in the chronic back pain group, activity is confined to emotion-related circuitry. Reward circuitry was equally represented in both groups. In the recovered acute/subacute back pain group, brain activity diminished in time, whereas in the persistent acute/subacute back pain group, activity diminished in acute pain regions, increased in emotion-related circuitry, and remained unchanged in reward circuitry. The results demonstrate that brain representation for a constant percept, back pain, can undergo large-scale shifts in brain activity with the transition to chronic pain. These observations challenge long-standing theoretical concepts regarding brain and mind relationships, as well as provide important novel insights regarding definitions and mechanisms of chronic pain. PMID:23983029

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.

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.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nord, Alex S.; Pattabiraman, Kartik; Visel, Axel

The forebrain is the seat of higher-order brain functions, and many human neuropsychiatric disorders are due to genetic defects affecting forebrain development, making it imperative to understand the underlying genetic circuitry. We report that recent progress now makes it possible to begin fully elucidating the genomic regulatory mechanisms that control forebrain gene expression. Here, we discuss the current knowledge of how transcription factors drive gene expression programs through their interactions with cis-acting genomic elements, such as enhancers; how analyses of chromatin and DNA modifications provide insights into gene expression states; and how these approaches yield insights into the evolution ofmore » the human brain.« less

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.

Optogenetic manipulation of neural circuits in awake marmosets

PubMed Central

MacDougall, Matthew; Nummela, Samuel U.; Coop, Shanna; Disney, Anita; Mitchell, Jude F.

2016-01-01

Optogenetics has revolutionized the study of functional neuronal circuitry (Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. Nat Neurosci 8: 1263–1268, 2005; Deisseroth K. Nat Methods 8: 26–29, 2011). Although these techniques have been most successfully implemented in rodent models, they have the potential to be similarly impactful in studies of nonhuman primate brains. Common marmosets (Callithrix jacchus) have recently emerged as a candidate primate model for gene editing, providing a potentially powerful model for studies of neural circuitry and disease in primates. The application of viral transduction methods in marmosets for identifying and manipulating neuronal circuitry is a crucial step in developing this species for neuroscience research. In the present study we developed a novel, chronic method to successfully induce rapid photostimulation in individual cortical neurons transduced by adeno-associated virus to express channelrhodopsin (ChR2) in awake marmosets. We found that large proportions of neurons could be effectively photoactivated following viral transduction and that this procedure could be repeated for several months. These data suggest that techniques for viral transduction and optical manipulation of neuronal populations are suitable for marmosets and can be combined with existing behavioral preparations in the species to elucidate the functional neural circuitry underlying perceptual and cognitive processes. PMID:27334951

Sex Differences in Stress Response Circuitry Activation Dependent on Female Hormonal Cycle

PubMed Central

Goldstein, Jill M.; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos

2010-01-01

Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this fMRI study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right-handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry (amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal and medial prefrontal cortices (OFC and mPFC), and anterior cingulate gyrus (ACG). Women were scanned twice based on normal variation in menstrual cycle hormones (i.e., early follicular (EF) compared with late follicular-midcycle menstrual phases (LF/MC)). Using SPM8b, there were few significant differences in BOLD signal changes in men compared to EF women, except ventromedial (VMN) and lateral (LHA) hypothalamus, left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males. PMID:20071507

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

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

Inferring distinct mechanisms in the absence of subjective differences: Placebo and centrally acting analgesic underlie unique brain adaptations.

PubMed

Tétreault, Pascal; Baliki, Marwan N; Baria, Alexis T; Bauer, William R; Schnitzer, Thomas J; Apkarian, A Vania

2018-05-01

Development and maintenance of chronic pain is associated with structural and functional brain reorganization. However, few studies have explored the impact of drug treatments on such changes. The extent to which long-term analgesia is related to brain adaptations and its effects on the reversibility of brain reorganization remain unclear. In a randomized placebo-controlled clinical trial, we contrasted pain relief (3-month treatment period), and anatomical (gray matter density [GMD], assessed by voxel-based morphometry) and functional connectivity (resting state fMRI nodal degree count [DC]) adaptations, in 39 knee osteoarthritis (OA) patients (22 females), randomized to duloxetine (DLX, 60 mg once daily) or placebo. Pain relief was equivalent between treatment types. However, distinct circuitry (GMD and DC) could explain pain relief in each group: up to 85% of variance for placebo analgesia and 49% of variance for DLX analgesia. No behavioral measures (collected at entry into the study) could independently explain observed analgesia. Identified circuitry were outside of nociceptive circuitry and minimally overlapped with OA-abnormal or placebo response predictive brain regions. Mediation analysis revealed that changes in GMD and DC can influence each other across remote brain regions to explain observed analgesia. Therefore, we can conclude that distinct brain mechanisms underlie DLX and placebo analgesia in OA. The results demonstrate that even in the absence of differences in subjective pain relief, pharmacological treatments can be differentiated from placebo based on objective brain biomarkers. This is a crucial step to untangling mechanisms and advancing personalized therapy approaches for chronic pain. © 2018 Wiley Periodicals, Inc.

Breaking symmetry: the zebrafish as a model for understanding left-right asymmetry in the developing brain.

PubMed

Roussigne, Myriam; Blader, Patrick; Wilson, Stephen W

2012-03-01

How does left-right asymmetry develop in the brain and how does the resultant asymmetric circuitry impact on brain function and lateralized behaviors? By enabling scientists to address these questions at the levels of genes, neurons, circuitry and behavior,the zebrafish model system provides a route to resolve the complexity of brain lateralization. In this review, we present the progress made towards characterizing the nature of the gene networks and the sequence of morphogenetic events involved in the asymmetric development of zebrafish epithalamus. In an attempt to integrate the recent extensive knowledge into a working model and to identify the future challenges,we discuss how insights gained at a cellular/developmental level can be linked to the data obtained at a molecular/genetic level. Finally, we present some evolutionary thoughts and discuss how significant discoveries made in zebrafish should provide entry points to better understand the evolutionary origins of brain lateralization.

Unique neurobiology during the sensitive period for attachment produces distinctive infant trauma processing

PubMed Central

Opendak, Maya; Sullivan, Regina M.

2016-01-01

Background Trauma has neurobehavioral effects when experienced at any stage of development, but trauma experienced in early life has unique neurobehavioral outcomes related to later life psychiatric sequelae. Recent evidence has further highlighted the context of infant trauma as a critical variable in determining its immediate and enduring consequences. Trauma experienced from an attachment figure, such as occurs in cases of caregiver child maltreatment, is particularly detrimental. Methods Using data primarily from rodent models, we review the literature on the interaction between trauma and attachment in early life, which highlights the role of the caregiver’s presence in engagement of attachment brain circuitry and suppressing threat processing by the amygdala. We then consider how trauma with and without the caregiver produces long-term changes in emotionality and behavior, and suggest that these experiences initiate distinct pathways to pathology. Results Together these data suggest that infant trauma processing and its enduring effects are impacted by both the immaturity of brain areas for processing trauma and the unique functioning of the early-life brain, which is biased toward processing information within the attachment circuitry. Conclusion An understanding of developmental differences in trauma processing as well as the critical role of the caregiver in further altering early life brain processing of trauma is important for developing age-relevant treatment and interventions. Highlights of this article Trauma experienced in early life has been linked with life-long outcomes for mental health through a mechanism that remains unclear. Trauma experienced in the presence of a caregiver has unique consequences. The infant brain is predisposed toward processing information using attachment circuitry rather than threat circuitry. Data from rodent models suggest that repeated trauma in the presence of a caregiver prematurely engages brain areas important for threat, which may play a role in deleterious outcome. PMID:27837581

Genomic Perspectives of Transcriptional Regulation in Forebrain Development

DOE PAGES

Nord, Alex S.; Pattabiraman, Kartik; Visel, Axel; ...

2015-01-07

The forebrain is the seat of higher-order brain functions, and many human neuropsychiatric disorders are due to genetic defects affecting forebrain development, making it imperative to understand the underlying genetic circuitry. We report that recent progress now makes it possible to begin fully elucidating the genomic regulatory mechanisms that control forebrain gene expression. Here, we discuss the current knowledge of how transcription factors drive gene expression programs through their interactions with cis-acting genomic elements, such as enhancers; how analyses of chromatin and DNA modifications provide insights into gene expression states; and how these approaches yield insights into the evolution ofmore » the human brain.« less

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

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

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.

Sex differences in stress response circuitry activation dependent on female hormonal cycle.

PubMed

Goldstein, Jill M; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos

2010-01-13

Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this functional magnetic resonance imaging study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry [amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and anterior cingulate gyrus (ACG)]. Women were scanned twice based on normal variation in menstrual cycle hormones [i.e., early follicular (EF) compared with late follicular-midcycle (LF/MC) menstrual phases]. Using SPM8b, there were few significant differences in blood oxygenation level-dependent (BOLD) signal changes in men compared to EF women, except ventromedial nucleus (VMN), lateral hypothalamic area (LHA), left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males.

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.

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2012-09-01

Oral presentations (Dr. Nudo):  Invited Speaker, Neuroprosthetic tools for repair of the injured brain, American Society for Neurorehabilitation... Neuroprosthetic tools for repair of the injured brain, Neurobiology of Disease Course, University of Texas Health Science Center, Houston, Texas...Congress of NeuroRehabilitation, Melbourne, Australia, May 17, 2012.  Invited Speaker, Novel neuroprosthetic tools for repair of the injured brain

Emotions and motivated behavior converge on an amygdala-like structure in the zebrafish

PubMed Central

von Trotha, Jakob William; Vernier, Philippe; Bally-Cuif, Laure

2014-01-01

The brain reward circuitry plays a key role in emotional and motivational behaviors, and its dysfunction underlies neuropsychiatric disorders such as schizophrenia, depression and drug addiction. Here, we characterized the neuronal activity pattern induced by acute amphetamine administration and during drug-seeking behavior in the zebrafish, and demonstrate the existence of conserved underlying brain circuitry. Combining quantitative analyses of cfos expression with neuronal subtype-specific markers at single-cell resolution, we show that acute d-amphetamine administration leads to both increased neuronal activation and the recruitment of neurons in the medial (Dm) and the lateral (Dl) domains of the adult zebrafish pallium, which contain homologous structures to the mammalian amygdala and hippocampus, respectively. Calbindin-positive and glutamatergic neurons are recruited in Dm, and glutamatergic and γ-aminobutyric acid (GABAergic) neurons in Dl. The drug-activated neurons in Dm and Dl are born at juvenile stage rather than in the embryo or during adulthood. Furthermore, the same territory in Dm is activated during both drug-seeking approach and light avoidance behavior, while these behaviors do not elicit activation in Dl. These data identify the pallial territories involved in acute psychostimulant response and reward formation in the adult zebrafish. They further suggest an evolutionarily conserved function of amygdala-like structures in positive emotions and motivated behavior in zebrafish and mammals. PMID:25145867

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

Visual cortical areas of the mouse: comparison of parcellation and network structure with primates

PubMed Central

Laramée, Marie-Eve; Boire, Denis

2015-01-01

Brains have evolved to optimize sensory processing. In primates, complex cognitive tasks must be executed and evolution led to the development of large brains with many cortical areas. Rodents do not accomplish cognitive tasks of the same level of complexity as primates and remain with small brains both in relative and absolute terms. But is a small brain necessarily a simple brain? In this review, several aspects of the visual cortical networks have been compared between rodents and primates. The visual system has been used as a model to evaluate the level of complexity of the cortical circuits at the anatomical and functional levels. The evolutionary constraints are first presented in order to appreciate the rules for the development of the brain and its underlying circuits. The organization of sensory pathways, with their parallel and cross-modal circuits, is also examined. Other features of brain networks, often considered as imposing constraints on the development of underlying circuitry, are also discussed and their effect on the complexity of the mouse and primate brain are inspected. In this review, we discuss the common features of cortical circuits in mice and primates and see how these can be useful in understanding visual processing in these animals. PMID:25620914

Visual cortical areas of the mouse: comparison of parcellation and network structure with primates.

PubMed

Laramée, Marie-Eve; Boire, Denis

2014-01-01

Brains have evolved to optimize sensory processing. In primates, complex cognitive tasks must be executed and evolution led to the development of large brains with many cortical areas. Rodents do not accomplish cognitive tasks of the same level of complexity as primates and remain with small brains both in relative and absolute terms. But is a small brain necessarily a simple brain? In this review, several aspects of the visual cortical networks have been compared between rodents and primates. The visual system has been used as a model to evaluate the level of complexity of the cortical circuits at the anatomical and functional levels. The evolutionary constraints are first presented in order to appreciate the rules for the development of the brain and its underlying circuits. The organization of sensory pathways, with their parallel and cross-modal circuits, is also examined. Other features of brain networks, often considered as imposing constraints on the development of underlying circuitry, are also discussed and their effect on the complexity of the mouse and primate brain are inspected. In this review, we discuss the common features of cortical circuits in mice and primates and see how these can be useful in understanding visual processing in these animals.

Values: Understanding Written Language and the Mind through Brain Biology.

ERIC Educational Resources Information Center

Brand, Alice G.

Suggesting that neuroscience and the actualities of brain circuitry can provide guidance for what is misunderstood in writing education, namely, the role of subjectivity and values in the composing process, this paper argues that neuroscience provides corporeal evidence for the salience of particular brain structures and processes responsible for…

Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry.

PubMed

Pratelli, Marta; Migliarini, Sara; Pelosi, Barbara; Napolitano, Francesco; Usiello, Alessandro; Pasqualetti, Massimo

2017-01-01

Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron development and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2 fl ° x conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organization. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring.

Synaptic plasticity in drug reward circuitry.

PubMed

Winder, Danny G; Egli, Regula E; Schramm, Nicole L; Matthews, Robert T

2002-11-01

Drug addiction is a major public health issue worldwide. The persistence of drug craving coupled with the known recruitment of learning and memory centers in the brain has led investigators to hypothesize that the alterations in glutamatergic synaptic efficacy brought on by synaptic plasticity may play key roles in the addiction process. Here we review the present literature, examining the properties of synaptic plasticity within drug reward circuitry, and the effects that drugs of abuse have on these forms of plasticity. Interestingly, multiple forms of synaptic plasticity can be induced at glutamatergic synapses within the dorsal striatum, its ventral extension the nucleus accumbens, and the ventral tegmental area, and at least some of these forms of plasticity are regulated by behaviorally meaningful administration of cocaine and/or amphetamine. Thus, the present data suggest that regulation of synaptic plasticity in reward circuits is a tractable candidate mechanism underlying aspects of addiction.

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.

Hemispheric specialization for visual words is shaped by attention to sublexical units during initial learning.

PubMed

Yoncheva, Yuliya N; Wise, Jessica; McCandliss, Bruce

2015-01-01

Selective attention to grapheme-phoneme mappings during learning can impact the circuitry subsequently recruited during reading. Here we trained literate adults to read two novel scripts of glyph words containing embedded letters under different instructions. For one script, learners linked each embedded letter to its corresponding sound within the word (grapheme-phoneme focus); for the other, decoding was prevented so entire words had to be memorized. Post-training, ERPs were recorded during a reading task on the trained words within each condition and on untrained but decodable (transfer) words. Within this condition, reaction-time patterns suggested both trained and transfer words were accessed via sublexical units, yet a left-lateralized, late ERP response showed an enhanced left lateralization for transfer words relative to trained words, potentially reflecting effortful decoding. Collectively, these findings show that selective attention to grapheme-phoneme mappings during learning drives the lateralization of circuitry that supports later word recognition. This study thus provides a model example of how different instructional approaches to the same material may impact changes in brain circuitry. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The Neurobiology of Attachment to Nurturing and Abusive Caregivers

PubMed Central

Sullivan, Regina M.

2013-01-01

Decades of research have shown that childhood experiences interact with our genetics to change the structure and function of the brain. Within the range of normal experiences, this system enables the brain to be modified during development to adapt to various environments and cultures. Experiences with and attachment to the caregiver appear particularly important, and recent research suggests this may be due, in part, to the attachment circuitry within the brain. Children have brain circuitry to ensure attachment to their caregivers. Attachment depends on the offspring learning about the caregiver in a process that begins prenatally and continues through most of early life. This attachment serves two basic functions. First, attachment ensures the infant remain in the proximity of the caregiver to procure resources for survival and protection. Second, attachment “quality programs” the brain. This programming impacts immediate behaviors, as well as behaviors that emerge later in development. Animal research has uncovered segments of the attachment circuitry within the brain and has highlighted rapid, robust learning to support this attachment. A child attaches to the caregiver regardless of the quality of care received, even if the caregiver is abusive and neglectful. While a neural system that ensures attachment regardless of the quality of care has immediate benefits, this attachment comes with a high cost. Traumatic experiences interact with genetics to change the structure and function of the brain, compromising emotional and cognitive development and initiating a pathway to pathology. Neurobiological research on animals suggests that trauma during attachment is processed differently by the brain, with maternal presence dramatically attenuating the fear center of the brain (amygdala). Thus, the immaturity of the brain combined with the unique processing of trauma may underlie the enduring effects of abuse, which remain largely hidden in early life but emerge as mental health issues in periadolescence. PMID:24049190

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.

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

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.

Emerging therapeutics in sleep.

PubMed

Saper, Clifford B; Scammell, Thomas E

2013-09-01

The development of new therapeutics for sleep disorders is increasingly dependent upon understanding the basic brain circuitry that underlies sleep-wake regulation, and how it may be pharmacologically manipulated. In this review, we consider the pathophysiological basis of major sleep disorders that often are seen by neurologists, including excessive daytime sleepiness, insomnia, narcolepsy, rapid eye movement sleep behavior disorder, and restless legs syndrome, as well as circadian disorders, and we review the current and potential future therapeutic approaches. Copyright © 2013 American Neurological Association.

Brain basis of early parent–infant interactions: psychology, physiology, and in vivo functional neuroimaging studies

PubMed Central

Swain, James E.; Lorberbaum, Jeffrey P.; Kose, Samet; Strathearn, Lane

2015-01-01

Parenting behavior critically shapes human infants’ current and future behavior. The parent–infant relationship provides infants with their first social experiences, forming templates of what they can expect from others and how to best meet others’ expectations. In this review, we focus on the neurobiology of parenting behavior, including our own functional magnetic resonance imaging (fMRI) brain imaging experiments of parents. We begin with a discussion of background, perspectives and caveats for considering the neurobiology of parent–infant relationships. Then, we discuss aspects of the psychology of parenting that are significantly motivating some of the more basic neuroscience research. Following that, we discuss some of the neurohormones that are important for the regulation of social bonding, and the dysregulation of parenting with cocaine abuse. Then, we review the brain circuitry underlying parenting, proceeding from relevant rodent and nonhuman primate research to human work. Finally, we focus on a study-by-study review of functional neuroimaging studies in humans. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support aspects of parent response to infants, including the emotion, attention, motivation, empathy, decision-making and other thinking that are required to navigate the complexities of parenting. Specifically, infant stimuli activate basal forebrain regions, which regulate brain circuits that handle specific nurturing and caregiving responses and activate the brain’s more general circuitry for handling emotions, motivation, attention, and empathy – all of which are crucial for effective parenting. We argue that an integrated understanding of the brain basis of parenting has profound implications for mental health. PMID:17355399

Effects of Cognitive-Behavioral Therapy (CBT) on Brain Connectivity Supporting Catastrophizing in Fibromyalgia.

PubMed

Lazaridou, Asimina; Kim, Jieun; Cahalan, Christine M; Loggia, Marco L; Franceschelli, Olivia; Berna, Chantal; Schur, Peter; Napadow, Vitaly; Edwards, Robert R

2017-03-01

Fibromyalgia (FM) is a chronic, common pain disorder characterized by hyperalgesia. A key mechanism by which cognitive-behavioral therapy (CBT) fosters improvement in pain outcomes is via reductions in hyperalgesia and pain-related catastrophizing, a dysfunctional set of cognitive-emotional processes. However, the neural underpinnings of these CBT effects are unclear. Our aim was to assess CBT's effects on the brain circuitry underlying hyperalgesia in FM patients, and to explore the role of treatment-associated reduction in catastrophizing as a contributor to normalization of pain-relevant brain circuitry and clinical improvement. In total, 16 high-catastrophizing FM patients were enrolled in the study and randomized to 4 weeks of individual treatment with either CBT or a Fibromyalgia Education (control) condition. Resting state functional magnetic resonance imaging scans evaluated functional connectivity between key pain-processing brain regions at baseline and posttreatment. Clinical outcomes were assessed at baseline, posttreatment, and 6-month follow-up. Catastrophizing correlated with increased resting state functional connectivity between S1 and anterior insula. The CBT group showed larger reductions (compared with the education group) in catastrophizing at posttreatment (P<0.05), and CBT produced significant reductions in both pain and catastrophizing at the 6-month follow-up (P<0.05). Patients in the CBT group also showed reduced resting state connectivity between S1 and anterior/medial insula at posttreatment; these reductions in resting state connectivity were associated with concurrent treatment-related reductions in catastrophizing. The results add to the growing support for the clinically important associations between S1-insula connectivity, clinical pain, and catastrophizing, and suggest that CBT may, in part via reductions in catastrophizing, help to normalize pain-related brain responses in FM.

Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders.

PubMed

Arnsten, Amy F T; Rubia, Katya

2012-04-01

This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Studies of animals, normally developing children, and patients with neurodevelopmental disorders were reviewed, with focus on neuroimaging studies. The PFC provides "top-down" regulation of attention, inhibition/cognitive control, motivation, and emotion through connections with posterior cortical and subcortical structures. Dorsolateral and inferior PFC regulate attention and cognitive/inhibitory control, whereas orbital and ventromedial structures regulate motivation and affect. PFC circuitries are very sensitive to their neurochemical environment, and small changes in the underlying neurotransmitter systems, e.g. by medications, can produce large effects on mediated function. Neuroimaging studies of children with neurodevelopmental disorders show altered brain structure and function in distinctive circuits respecting this organization. Children with attention-deficit/hyperactivity disorder show prominent abnormalities in the inferior PFC and its connections to striatal, cerebellar, and parietal regions, whereas children with conduct disorder show alterations in the paralimbic system, comprising ventromedial, lateral orbitofrontal, and superior temporal cortices together with specific underlying limbic regions, regulating motivation and emotion control. Children with major depressive disorder show alterations in ventral orbital and limbic activity, particularly in the left hemisphere, mediating emotions. Finally, children with obsessive-compulsive disorder appear to have a dysregulation in orbito-fronto-striatal inhibitory control pathways, but also deficits in dorsolateral fronto-parietal systems of attention. Altogether, there is a good correspondence between anatomical circuitry mediating compromised functions and patterns of brain structure and function changes in children with neuropsychiatric disorders. Medications may optimize the neurochemical environment in PFC and associated circuitries, and improve structure and function. Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Implantable Microsystems for Anatomical Rewiring of Cortical Circuitry: A New Approach for Brain Repair

DTIC Science & Technology

2009-03-01

dopamine or serotonin, provide outputs to large regions of the brain that affect mood, learning, and cognition [4]. Hence, understanding brain function on a...Sutton, B. T. Higashikubo, C. A. Chestek, H. J. Chiel, and H. B. Martin, “Diamond electrodes for neurodynamic studies in Aplysia californica,” Diam

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

Testicular atrophy and reproductive quiescence in photorefractory and scotosensitive quail: Involvement of hypothalamic deep brain photoreceptors and GnRH-GnIH system.

PubMed

Banerjee, Somanshu; Chaturvedi, Chandra Mohini

2017-10-01

Birds time their daily and seasonal activities in synchronization with circadian and annual periodicities in the environment, which is mainly provided by changes in photoperiod/day length conditions. Photoperiod appears to act at the level of eye, pineal and encephalic/deep brain photoperception and thus entrain the hypothalamic clock as well as reproductive circuitry in different avian species. In this article our focus of study is to elucidate out the underlying molecular mechanism of modulation of the hypothalamic reproductive circuitry following the photoperception through the hypothalamic photoreceptor cells and the subsequent alteration in the reproductive responses in quail, kept under different simulated photoperiodic conditions. Present study investigated the different simulated photoperiodic conditions induced hypothalamic DBP-GnRH-GnIH system mediated translation of photoperiodic information and subsequent exhibition of differential photosexual responses (scoto-/photo-sensitivity and refractoriness) in Japanese quail, Coturnix coturnix japonica. Paired testes weight and paired testicular volume increased 15.9 and 22.6-fold respectively in scotorefractory quail compare to that of scotosensitive phase and 12.8 and 24.3-fold in photosensitive quail compare to that of photorefractory phase. The pineal/eye melatonin (through melatonin receptor subtype Mel 1c R) and hypothalamic deep brain photoreceptor (DBPs) cells directly modulate the hypothalamic GnRH-I/II and GnIH system and thus exhibit testicular stimulation or regression in response to different photoperiodic conditions (PS, PR, SS and SR). The hypothalamic alteration of DBP(s) and GnRH-GnIH system thus may induce the testicular stimulation in PS and SR quail and testicular regression in SS and PR quail. Copyright © 2017 Elsevier B.V. All rights reserved.

Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia.

PubMed

Bossong, Matthijs G; Niesink, Raymond J M

2010-11-01

Cannabis use during adolescence increases the risk of developing psychotic disorders later in life. However, the neurobiological processes underlying this relationship are unknown. This review reports the results of a literature search comprising various neurobiological disciplines, ultimately converging into a model that might explain the neurobiology of cannabis-induced schizophrenia. The article briefly reviews current insights into brain development during adolescence. In particular, the role of the excitatory neurotransmitter glutamate in experience-dependent maturation of specific cortical circuitries is examined. The review also covers recent hypotheses regarding disturbances in strengthening and pruning of synaptic connections in the prefrontal cortex, and the link with latent psychotic disorders. In the present model, cannabis-induced schizophrenia is considered to be a distortion of normal late postnatal brain maturation. Distortion of glutamatergic transmission during critical periods may disturb prefrontal neurocircuitry in specific brain areas. Our model postulates that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the primary psychoactive substance in cannabis, transiently disturbs physiological control of the endogenous cannabinoid system over glutamate and GABA release. As a result, THC may adversely affect adolescent experience-dependent maturation of neural circuitries within prefrontal cortical areas. Depending on dose, exact time window and duration of exposure, this may ultimately lead to the development of psychosis or schizophrenia. The proposed model provides testable hypotheses which can be addressed in future studies, including animal experiments, reanalysis of existing epidemiological data, and prospective epidemiological studies in which the role of the dose-time-effect relationship should be central. Copyright © 2010 Elsevier Ltd. All rights reserved.

Current Status of Research on Providing Sight to the Blind by Electrical Stimulation of the Brain

ERIC Educational Resources Information Center

Dobelle, William H.

1977-01-01

Described is a prosthesis that connects a television camera and associated circuitry to the visual centers of the brain to restore a limited amount of visual sensation to totally blind persons. (Author/MH)

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

The Interface between Neuroscience and Neuro-Psychoanalysis: Focus on Brain Connectivity

PubMed Central

Salone, Anatolia; Di Giacinto, Alessandra; Lai, Carlo; De Berardis, Domenico; Iasevoli, Felice; Fornaro, Michele; De Risio, Luisa; Santacroce, Rita; Martinotti, Giovanni; Giannantonio, Massimo Di

2016-01-01

Over the past 20 years, the advent of advanced techniques has significantly enhanced our knowledge on the brain. Yet, our understanding of the physiological and pathological functioning of the mind is still far from being exhaustive. Both the localizationist and the reductionist neuroscientific approaches to psychiatric disorders have proven to be largely unsatisfactory and are outdated. Accruing evidence suggests that psychoanalysis can engage the neurosciences in a productive and mutually enriching dialogue that may further our understanding of psychiatric disorders. In particular, advances in brain connectivity research have provided evidence supporting the convergence of neuroscientific findings and psychoanalysis and helped characterize the circuitry and mechanisms that underlie higher brain functions. In the present paper we discuss how knowledge on brain connectivity can impact neuropsychoanalysis, with a particular focus on schizophrenia. Brain connectivity studies in schizophrenic patients indicate complex alterations in brain functioning and circuitry, with particular emphasis on the role of cortical midline structures (CMS) and the default mode network (DMN). These networks seem to represent neural correlates of psychodynamic concepts central to the understanding of schizophrenia and of core psychopathological alterations of this disorder (i.e., ego disturbances and impaired primary process thinking). PMID:26869904

Hunger does not motivate reward in women remitted from anorexia nervosa

PubMed Central

Wierenga, Christina E.; Bischoff-Grethe, Amanda; Melrose, A. James; Irvine, Zoe; Torres, Laura; Bailer, Ursula F.; Simmons, Alan; Fudge, Julie L.; McClure, Samuel M.; Ely, Alice; Kaye, Walter H.

2014-01-01

Background Hunger enhances sensitivity to reward, yet individuals with anorexia nervosa (AN) are not motivated to eat when starved. This study examined whether diminished response to reward could underlie food restriction in AN by investigating brain response to rewards during hunger and satiated states. Methods Using a delay discounting monetary decision task known to discriminate brain regions contributing to processing of immediate rewards and cognitive control important for decision making regarding future rewards, we compared 23 adults remitted from AN (to reduce the confounding effects of starvation [RAN]) to 17 healthy women (CW). Monetary rewards were used because the rewarding value of food may be confounded by anxiety in AN. Results Interactions of group (RAN, CW) × visit (hunger, satiety) revealed that, for CW, hunger significantly increased activation in reward salience circuitry (ventral striatum, dorsal caudate, anterior cingulate cortex) during processing of immediate reward, whereas satiety increased activation in cognitive control circuitry (ventrolateral prefrontal cortex, insula) during decision-making. In contrast, brain response in reward and cognitive neurocircuitry did not differ during hunger and satiety in RAN. A main effect of group revealed elevated response in the middle frontal gyrus for RAN. Conclusions RAN failed to increase activation of reward valuation circuitry when hungry and showed elevated response in cognitive control circuitry independent of metabolic state. Decreased sensitivity to hunger’s motivational drive may explain AN individuals’ ability to restrict food when emaciated. Moreover, difficulties in valuating emotional salience may contribute to inabilities to appreciate the risks inherent in this deadly disorder. PMID:25481622

Networks of phobic fear: Functional connectivity shifts in two subtypes of specific phobia.

PubMed

Stefanescu, Maria R; Endres, Ralph J; Hilbert, Kevin; Wittchen, Hans-Ulrich; Lueken, Ulrike

2018-01-01

Anxiety disorders can be conceptualized by an abnormal interplay of emotion-processing brain circuits; however, knowledge of brain connectivity measures in specific phobia is still limited. To explore functional interactions within selected fear-circuitry structures (anterior cingulate cortex (ACC), amygdala, insula), we re-examined three task-based fMRI studies using a symptom provocation approach (n=94 subjects in total) on two different phobia subtypes (animal subtype as represented by snake phobia (SP) and blood-injection-injury subtype as represented by dental phobia (DP)), and a non-phobic healthy control group (HC). Functional connectivity (FC) analyses detected a negative coupling between the amygdala and the ACC in HC for both classes of phobic stimuli, while SP and DP lacked this inhibitory relationship during visual stimulus presentation. However, a negative FC between the insula and the amygdala was observed in DP during visual symptom provocation, which reversed to a positive FC under auditory symptom provocation pointing to effects depending on stimulus modality in DP. SP showed significantly higher FC towards snake-anxiety eliciting stimuli than HC on an average measure of FC, while DP showed a similar pattern under auditory stimulation only. These findings altogether indicate FC shifts during symptom provocation in specific phobia possibly reflecting impaired emotion regulation processes within fear-circuitry networks. FC hence could represent a prime target for neuroscience-informed augmentation strategies when treating pathological forms of fear. Copyright © 2017 Elsevier B.V. All rights reserved.

Motor and Nonmotor Circuitry Activation Induced by Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease: Intraoperative Functional Magnetic Resonance Imaging for Deep Brain Stimulation.

PubMed

Knight, Emily J; Testini, Paola; Min, Hoon-Ki; Gibson, William S; Gorny, Krzysztof R; Favazza, Christopher P; Felmlee, Joel P; Kim, Inyong; Welker, Kirk M; Clayton, Daniel A; Klassen, Bryan T; Chang, Su-youne; Lee, Kendall H

2015-06-01

To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease would affect the activity of motor and nonmotor networks, we applied intraoperative functional magnetic resonance imaging (fMRI) to patients receiving DBS. Ten patients receiving STN DBS for Parkinson disease underwent intraoperative 1.5-T fMRI during high-frequency stimulation delivered via an external pulse generator. The study was conducted between January 1, 2013, and September 30, 2014. We observed blood oxygen level-dependent (BOLD) signal changes (false discovery rate <0.001) in the motor circuitry (including the primary motor, premotor, and supplementary motor cortices; thalamus; pedunculopontine nucleus; and cerebellum) and in the limbic circuitry (including the cingulate and insular cortices). Activation of the motor network was observed also after applying a Bonferroni correction (P<.001) to the data set, suggesting that across patients, BOLD changes in the motor circuitry are more consistent compared with those occurring in the nonmotor network. These findings support the modulatory role of STN DBS on the activity of motor and nonmotor networks and suggest complex mechanisms as the basis of the efficacy of this treatment modality. Furthermore, these results suggest that across patients, BOLD changes in the motor circuitry are more consistent than those in the nonmotor network. With further studies combining the use of real-time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. clinicaltrials.gov Identifier: NCT01809613. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Peers Increase Adolescent Risk Taking by Enhancing Activity in the Brain's Reward Circuitry

ERIC Educational Resources Information Center

Chein, Jason; Albert, Dustin; O'Brien, Lia; Uckert, Kaitlyn; Steinberg, Laurence

2011-01-01

The presence of peers increases risk taking among adolescents but not adults. We posited that the presence of peers may promote adolescent risk taking by sensitizing brain regions associated with the anticipation of potential rewards. Using fMRI, we measured brain activity in adolescents, young adults, and adults as they made decisions in a…

Reward circuitry in resilience to severe trauma: An fMRI investigation of resilient special forces soldiers

PubMed Central

Vythilingam, Meena; Nelson, Eric E.; Scaramozza, Matthew; Waldeck, Tracy; Hazlett, Gary; Southwick, Steven M.; Pine, Daniel S.; Drevets, Wayne; Charney, Dennis S.; Ernst, Monique

2008-01-01

Enhanced brain reward function could contribute to resilience to trauma. Reward circuitry in active duty, resilient special forces (SF) soldiers was evaluated using fMRI during a monetary incentive delay task. Findings in this group of resilient individuals revealed unique patterns of activation during expectation of reward in the subgenual prefrontal cortex and nucleus accumbens area; regions pivotal to reward processes. PMID:19243926

Synaptic mechanisms underlying persistent cocaine craving

PubMed Central

Wolf, Marina E.

2017-01-01

Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction. PMID:27150400

Neuroimaging and Drug Taking in Primates Abbreviated title: Neuroimaging and Drug taking

PubMed Central

Murnane, Kevin S.; Howell, Leonard L.

2011-01-01

Rationale Neuroimaging techniques have led to significant advances in our understanding of the neurobiology of drug-taking and the treatment of drug addiction in humans. Neuroimaging approaches provide a powerful translational approach that can link findings from humans and laboratory animals. Objective This review describes the utility of neuroimaging toward understanding the neurobiological basis of drug taking, and documents the close concordance that can be achieved among neuroimaging, neurochemical and behavioral endpoints. Results The study of drug interactions with dopamine and serotonin transporters in vivo has identified pharmacological mechanisms of action associated with the abuse liability of stimulants. Neuroimaging has identified the extended limbic system, including the prefrontal cortex and anterior cingulate, as important neuronal circuitry that underlies drug taking. The ability to conduct within-subject, longitudinal assessments of brain chemistry and neuronal function has enhanced our efforts to document long-term changes in dopamine D2 receptors, monoamine transporters, and prefrontal metabolism due to chronic drug exposure. Dysregulation of dopamine function and brain metabolic changes in areas involved in reward circuitry have been linked to drug-taking behavior, cognitive impairment and treatment response. Conclusions Experimental designs employing neuroimaging should consider well-documented determinants of drug taking, including pharmacokinetic considerations, subject history and environmental variables. Methodological issues to consider include limited molecular probes, lack of neurochemical specificity in brain activation studies, and the potential influence of anesthetics in animal studies. Nevertheless, these integrative approaches should have important implications for understanding drug-taking behavior and the treatment of drug addiction. PMID:21360099

Generation of dense statistical connectomes from sparse morphological data

PubMed Central

Egger, Robert; Dercksen, Vincent J.; Udvary, Daniel; Hege, Hans-Christian; Oberlaender, Marcel

2014-01-01

Sensory-evoked signal flow, at cellular and network levels, is primarily determined by the synaptic wiring of the underlying neuronal circuitry. Measurements of synaptic innervation, connection probabilities and subcellular organization of synaptic inputs are thus among the most active fields of research in contemporary neuroscience. Methods to measure these quantities range from electrophysiological recordings over reconstructions of dendrite-axon overlap at light-microscopic levels to dense circuit reconstructions of small volumes at electron-microscopic resolution. However, quantitative and complete measurements at subcellular resolution and mesoscopic scales to obtain all local and long-range synaptic in/outputs for any neuron within an entire brain region are beyond present methodological limits. Here, we present a novel concept, implemented within an interactive software environment called NeuroNet, which allows (i) integration of sparsely sampled (sub)cellular morphological data into an accurate anatomical reference frame of the brain region(s) of interest, (ii) up-scaling to generate an average dense model of the neuronal circuitry within the respective brain region(s) and (iii) statistical measurements of synaptic innervation between all neurons within the model. We illustrate our approach by generating a dense average model of the entire rat vibrissal cortex, providing the required anatomical data, and illustrate how to measure synaptic innervation statistically. Comparing our results with data from paired recordings in vitro and in vivo, as well as with reconstructions of synaptic contact sites at light- and electron-microscopic levels, we find that our in silico measurements are in line with previous results. PMID:25426033

Structural and Functional Plasticity in the Maternal Brain Circuitry

ERIC Educational Resources Information Center

Pereira, Mariana

2016-01-01

Parenting recruits a distributed network of brain structures (and neuromodulators) that coordinates caregiving responses attuned to the young's affect, needs, and developmental stage. Many of these structures and connections undergo significant structural and functional plasticity, mediated by the interplay between maternal hormones and social…

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.

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.

Function and Dysfunction of Prefrontal Brain Circuitry in Alcoholic Korsakoff’s Syndrome

PubMed Central

Oscar-Berman, Marlene

2013-01-01

The signature symptom of alcohol-induced persisting amnestic disorder, more commonly referred to as alcoholic Korsakoff’s syndrome (KS), is anterograde amnesia, or memory loss for recent events, and until the mid 20th Century, the putative brain damage was considered to be in diencephalic and medial temporal lobe structures. Overall intelligence, as measured by standardized IQ tests, usually remains intact. Preservation of IQ occurs because memories formed before the onset of prolonged heavy drinking — the types of information and abilities tapped by intelligence tests — remain relatively well preserved compared with memories recently acquired. However, clinical and experimental evidence has shown that neurobehavioral dysfunction in alcoholic patients with KS does include nonmnemonic abilities, and further brain damage involves extensive frontal and limbic circuitries. Among the abnormalities are confabulation, disruption of elements of executive functioning and cognitive control, and emotional impairments. Here, we discuss the relationship between neurobehavioral impairments in KS and alcoholism-related brain damage. More specifically, we examine the role of damage to prefrontal brain systems in the neuropsychological profile of alcoholic KS. PMID:22538385

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

Adult neurogenesis is necessary to refine and maintain circuit specificity.

PubMed

Cummings, Diana M; Snyder, Jason S; Brewer, Michelle; Cameron, Heather A; Belluscio, Leonardo

2014-10-08

The circuitry of the olfactory bulb contains a precise anatomical map that links isofunctional regions within each olfactory bulb. This intrabulbar map forms perinatally and undergoes activity-dependent refinement during the first postnatal weeks. Although this map retains its plasticity throughout adulthood, its organization is remarkably stable despite the addition of millions of new neurons to this circuit. Here we show that the continuous supply of new neuroblasts from the subventricular zone is necessary for both the restoration and maintenance of this precise central circuit. Using pharmacogenetic methods to conditionally ablate adult neurogenesis in transgenic mice, we find that the influx of neuroblasts is required for recovery of intrabulbar map precision after disruption due to sensory block. We further demonstrate that eliminating adult-born interneurons in naive animals leads to an expansion of tufted cell axons that is identical to the changes caused by sensory block, thus revealing an essential role for new neurons in circuit maintenance under baseline conditions. These findings show, for the first time, that inhibiting adult neurogenesis alters the circuitry of projection neurons in brain regions that receive new interneurons and points to a critical role for adult-born neurons in stabilizing a brain circuit that exhibits high levels of plasticity. Copyright © 2014 the authors 0270-6474/14/3413801-10$15.00/0.

Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women.

PubMed

Kullmann, Stephanie; Frank, Sabine; Heni, Martin; Ketterer, Caroline; Veit, Ralf; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

2013-01-01

There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. We performed 'resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy. Copyright © 2012 S. Karger AG, Basel.

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.

Pharmacological Modulation of Noradrenergic Arousal Circuitry Disrupts Functional Connectivity of the Locus Ceruleus in Humans

PubMed Central

Song, Andrew H.

2017-01-01

State-dependent activity of locus ceruleus (LC) neurons has long suggested a role for noradrenergic modulation of arousal. However, in vivo insights into noradrenergic arousal circuitry have been constrained by the fundamental inaccessibility of the human brain for invasive studies. Functional magnetic resonance imaging (fMRI) studies performed during site-specific pharmacological manipulations of arousal levels may be used to study brain arousal circuitry. Dexmedetomidine is an anesthetic that alters the level of arousal by selectively targeting α2 adrenergic receptors on LC neurons, resulting in reduced firing rate and norepinephrine release. Thus, we hypothesized that dexmedetomidine-induced altered arousal would manifest with reduced functional connectivity between the LC and key brain regions involved in the regulation of arousal. To test this hypothesis, we acquired resting-state fMRI data in right-handed healthy volunteers 18–36 years of age (n = 15, 6 males) at baseline, during dexmedetomidine-induced altered arousal, and recovery states. As previously reported, seed-based resting-state fMRI analyses revealed that the LC was functionally connected to a broad network of regions including the reticular formation, basal ganglia, thalamus, posterior cingulate cortex (PCC), precuneus, and cerebellum. Functional connectivity of the LC to only a subset of these regions (PCC, thalamus, and caudate nucleus) covaried with the level of arousal. Functional connectivity of the PCC to the ventral tegmental area/pontine reticular formation and thalamus, in addition to the LC, also covaried with the level of arousal. We propose a framework in which the LC, PCC, thalamus, and basal ganglia comprise a functional arousal circuitry. SIGNIFICANCE STATEMENT Electrophysiological studies of locus ceruleus (LC) neurons have long suggested a role for noradrenergic mechanisms in mediating arousal. However, the fundamental inaccessibility of the human brain for invasive studies has limited a precise understanding of putative brain regions that integrate with the LC to regulate arousal. Our results suggest that the PCC, thalamus, and basal ganglia are key components of a LC-noradrenergic arousal circuit. PMID:28626012

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.

Altered small-world topology of structural brain networks in infants with intrauterine growth restriction and its association with later neurodevelopmental outcome.

PubMed

Batalle, Dafnis; Eixarch, Elisenda; Figueras, Francesc; Muñoz-Moreno, Emma; Bargallo, Nuria; Illa, Miriam; Acosta-Rojas, Ruthy; Amat-Roldan, Ivan; Gratacos, Eduard

2012-04-02

Intrauterine growth restriction (IUGR) due to placental insufficiency affects 5-10% of all pregnancies and it is associated with a wide range of short- and long-term neurodevelopmental disorders. Prediction of neurodevelopmental outcomes in IUGR is among the clinical challenges of modern fetal medicine and pediatrics. In recent years several studies have used magnetic resonance imaging (MRI) to demonstrate differences in brain structure in IUGR subjects, but the ability to use MRI for individual predictive purposes in IUGR is limited. Recent research suggests that MRI in vivo access to brain connectivity might have the potential to help understanding cognitive and neurodevelopment processes. Specifically, MRI based connectomics is an emerging approach to extract information from MRI data that exhaustively maps inter-regional connectivity within the brain to build a graph model of its neural circuitry known as brain network. In the present study we used diffusion MRI based connectomics to obtain structural brain networks of a prospective cohort of one year old infants (32 controls and 24 IUGR) and analyze the existence of quantifiable brain reorganization of white matter circuitry in IUGR group by means of global and regional graph theory features of brain networks. Based on global and regional analyses of the brain network topology we demonstrated brain reorganization in IUGR infants at one year of age. Specifically, IUGR infants presented decreased global and local weighted efficiency, and a pattern of altered regional graph theory features. By means of binomial logistic regression, we also demonstrated that connectivity measures were associated with abnormal performance in later neurodevelopmental outcome as measured by Bayley Scale for Infant and Toddler Development, Third edition (BSID-III) at two years of age. These findings show the potential of diffusion MRI based connectomics and graph theory based network characteristics for estimating differences in the architecture of neural circuitry and developing imaging biomarkers of poor neurodevelopment outcome in infants with prenatal diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

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

Introduction to the special section: Myelin and oligodendrocyte abnormalities in schizophrenia.

PubMed

Haroutunian, Vahram; Davis, Kenneth L

2007-08-01

A central tenet of modern views of the neurobiology of schizophrenia is that the symptoms of schizophrenia arise from a failure of adequate communication between different brain regions and disruption of the circuitry that underlies behaviour and perception. Historically this disconnectivity syndrome has been approached from a neurotransmitter-based perspective. However, efficient communication between brain circuits is also contingent on saltatory signal propagation and salubrious myelination of axons. The papers in this Special Section examine the neuroanatomical and molecular biological evidence for abnormal myelination and oligodendroglial function in schizophrenia through studies of post-mortem brain tissue and animal model systems. The picture that emerges from the studies described suggests that although schizophrenia is not characterized by gross abnormalities of white matter such as those evident in multiple sclerosis, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths.

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.

Network analysis reveals disrupted functional brain circuitry in drug-naive social anxiety disorder.

PubMed

Yang, Xun; Liu, Jin; Meng, Yajing; Xia, Mingrui; Cui, Zaixu; Wu, Xi; Hu, Xinyu; Zhang, Wei; Gong, Gaolang; Gong, Qiyong; Sweeney, John A; He, Yong

2017-12-07

Social anxiety disorder (SAD) is a common and disabling condition characterized by excessive fear and avoidance of public scrutiny. Psychoradiology studies have suggested that the emotional and behavior deficits in SAD are associated with abnormalities in regional brain function and functional connectivity. However, little is known about whether intrinsic functional brain networks in patients with SAD are topologically disrupted. Here, we collected resting-state fMRI data from 33 drug-naive patients with SAD and 32 healthy controls (HC), constructed functional networks with 34 predefined regions based on previous meta-analytic research with task-based fMRI in SAD, and performed network-based statistic and graph-theory analyses. The network-based statistic analysis revealed a single connected abnormal circuitry including the frontolimbic circuit (termed the "fear circuit", including the dorsolateral prefrontal cortex, ventral medial prefrontal cortex and insula) and posterior cingulate/occipital areas supporting perceptual processing. In this single altered network, patients with SAD had higher functional connectivity than HC. At the global level, graph-theory analysis revealed that the patients exhibited a lower normalized characteristic path length than HC, which suggests a disorder-related shift of network topology toward randomized configurations. SAD-related deficits in nodal degree, efficiency and participation coefficient were detected in the parahippocampal gyrus, posterior cingulate cortex, dorsolateral prefrontal cortex, insula and the calcarine sulcus. Aspects of abnormal connectivity were associated with anxiety symptoms. These findings highlight the aberrant topological organization of functional brain network organization in SAD, which provides insights into the neural mechanisms underlying excessive fear and avoidance of social interactions in patients with debilitating social anxiety. Copyright © 2017. Published by Elsevier Inc.

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

Female-Specific Intergenerational Transmission Patterns of the Human Corticolimbic Circuitry

PubMed Central

Yamagata, Bun; Murayama, Kou; Black, Jessica M.; Hancock, Roeland; Mimura, Masaru; Yang, Tony T.; Reiss, Allan L.

2016-01-01

Parents have large genetic and environmental influences on offspring's cognition, behavior, and brain. These intergenerational effects are observed in mood disorders, with particularly robust association in depression between mothers and daughters. No studies have thus far examined the neural bases of these intergenerational effects in humans. Corticolimbic circuitry is known to be highly relevant in a wide range of processes, including mood regulation and depression. These findings suggest that corticolimbic circuitry may also show matrilineal transmission patterns. Therefore, we examined human parent–offspring association in this neurocircuitry and investigated the degree of association in gray matter volume between parent and offspring. We used voxelwise correlation analysis in a total of 35 healthy families, consisting of parents and their biological offspring. We found positive associations of regional gray matter volume in the corticolimbic circuit, including the amygdala, hippocampus, anterior cingulate cortex, and ventromedial prefrontal cortex between biological mothers and daughters. This association was significantly greater than mother–son, father–daughter, and father–son associations. The current study suggests that the corticolimbic circuitry, which has been implicated in mood regulation, shows a matrilineal-specific transmission patterns. Our preliminary findings are consistent with what has been found behaviorally in depression and may have clinical implications for disorders known to have dysfunction in mood regulation such as depression. Studies such as ours will likely bridge animal work examining gene expression in the brains and clinical symptom-based observations and provide promising ways to investigate intergenerational transmission patterns in the human brain. SIGNIFICANCE STATEMENT Parents have large genetic and environmental influences on the offspring, known as intergenerational effects. Specifically, depression has been shown to exhibit strong matrilineal transmission patterns. Although intergenerational transmission patterns in the human brain are virtually unknown, this would suggest that the corticolimbic circuitry relevant to a wide range of processes including mood regulation may also show matrilineal transmission patterns. Therefore, we examined the degree of association in corticolimbic gray matter volume (GMV) between parent and offspring in 35 healthy families. We found that positive correlations in maternal corticolimbic GMV with daughters were significantly greater than other parent–offspring dyads. Our findings provide new insight into the potential neuroanatomical basis of circuit-based female-specific intergenerational transmission patterns in depression. PMID:26818513

Hunger does not motivate reward in women remitted from anorexia nervosa.

PubMed

Wierenga, Christina E; Bischoff-Grethe, Amanda; Melrose, A James; Irvine, Zoe; Torres, Laura; Bailer, Ursula F; Simmons, Alan; Fudge, Julie L; McClure, Samuel M; Ely, Alice; Kaye, Walter H

2015-04-01

Hunger enhances sensitivity to reward, yet individuals with anorexia nervosa (AN) are not motivated to eat when starved. This study investigated brain response to rewards during hunger and satiated states to examine whether diminished response to reward could underlie food restriction in AN. Using a delay discounting monetary decision task known to discriminate brain regions contributing to processing of immediate rewards and cognitive control important for decision making regarding future rewards, we compared 23 women remitted from AN (RAN group; to reduce the confounding effects of starvation) with 17 healthy comparison women (CW group). Monetary rewards were used because the rewarding value of food may be confounded by anxiety in AN. Interactions of Group (RAN, CW) × Visit (hunger, satiety) revealed that, for the CW group, hunger significantly increased activation in reward salience circuitry (ventral striatum, dorsal caudate, anterior cingulate cortex) during processing of immediate reward, whereas satiety increased activation in cognitive control circuitry (ventrolateral prefrontal cortex, insula) during decision making. In contrast, brain response in reward and cognitive neurocircuitry did not differ during hunger and satiety in the RAN group. A main effect of group revealed elevated response in the middle frontal gyrus for the RAN group compared with the CW group. Women remitted from AN failed to increase activation of reward valuation circuitry when hungry and showed elevated response in cognitive control circuitry independent of metabolic state. Decreased sensitivity to the motivational drive of hunger may explain the ability of individuals with AN to restrict food when emaciated. Difficulties in valuating emotional salience may contribute to inabilities to appreciate the risks inherent in this disorder. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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.

Differential neural circuitry and self-interest in real vs hypothetical moral decisions

PubMed Central

Dalgleish, Tim; Thompson, Russell; Evans, Davy; Schweizer, Susanne; Mobbs, Dean

2012-01-01

Classic social psychology studies demonstrate that people can behave in ways that contradict their intentions—especially within the moral domain. We measured brain activity while subjects decided between financial self-benefit (earning money) and preventing physical harm (applying an electric shock) to a confederate under both real and hypothetical conditions. We found a shared neural network associated with empathic concern for both types of decisions. However, hypothetical and real moral decisions also recruited distinct neural circuitry: hypothetical moral decisions mapped closely onto the imagination network, while real moral decisions elicited activity in the bilateral amygdala and anterior cingulate—areas essential for social and affective processes. Moreover, during real moral decision-making, distinct regions of the prefrontal cortex (PFC) determined whether subjects make selfish or pro-social moral choices. Together, these results reveal not only differential neural mechanisms for real and hypothetical moral decisions but also that the nature of real moral decisions can be predicted by dissociable networks within the PFC. PMID:22711879

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2014-09-01

810. 22. Plow EB, Carey JR, Nudo RJ, Pascual-Leone A (2009) Invasive cortical stimulation to promote recovery of function after stroke: A critical...stimulation of the motor cortex enhances pro- genitor cell migration in the adult rat brain. Exp Brain Res 231(2):165–177. 28. Edwardson MA, Lucas TH, Carey ...The screws and rod were further secured with dental acrylic (all animals). In both the ADS and OLS groups, a hybrid, 16-channel, single-shank, chronic

Neurocognitive and electrophysiological evidence of altered face processing in parents of children with autism: implications for a model of abnormal development of social brain circuitry in autism.

PubMed

Dawson, Geraldine; Webb, Sara Jane; Wijsman, Ellen; Schellenberg, Gerard; Estes, Annette; Munson, Jeffrey; Faja, Susan

2005-01-01

Neuroimaging and behavioral studies have shown that children and adults with autism have impaired face recognition. Individuals with autism also exhibit atypical event-related brain potentials to faces, characterized by a failure to show a negative component (N170) latency advantage to face compared to nonface stimuli and a bilateral, rather than right lateralized, pattern of N170 distribution. In this report, performance by 143 parents of children with autism on standardized verbal, visual-spatial, and face recognition tasks was examined. It was found that parents of children with autism exhibited a significant decrement in face recognition ability relative to their verbal and visual spatial abilities. Event-related brain potentials to face and nonface stimuli were examined in 21 parents of children with autism and 21 control adults. Parents of children with autism showed an atypical event-related potential response to faces, which mirrored the pattern shown by children and adults with autism. These results raise the possibility that face processing might be a functional trait marker of genetic susceptibility to autism. Discussion focuses on hypotheses regarding the neurodevelopmental and genetic basis of altered face processing in autism. A general model of the normal emergence of social brain circuitry in the first year of life is proposed, followed by a discussion of how the trajectory of normal development of social brain circuitry, including cortical specialization for face processing, is altered in individuals with autism. The hypothesis that genetic-mediated dysfunction of the dopamine reward system, especially its functioning in social contexts, might account for altered face processing in individuals with autism and their relatives is discussed.

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

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…

Motor and non-motor circuitry activation induced by subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson’s disease patients: Intraoperative fMRI for DBS

PubMed Central

Knight, Emily J.; Testini, Paola; Min, Hoon-Ki; Gibson, William S.; Gorny, Krzysztof R.; Favazza, Christopher P.; Felmlee, Joel P.; Kim, Inyong; Welker, Kirk M.; Clayton, Daniel A.; Klassen, Bryan T.; Chang, Su-youne; Lee, Kendall H.

2015-01-01

Objective To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with PD would affect the activity of both motor and non-motor networks, we applied intraoperative fMRI to patients receiving DBS. Patients and Methods Ten patients receiving STN DBS for PD underwent intraoperative 1.5T fMRI during high frequency stimulation delivered via an external pulse generator. The study was conducted between the dates of January 1, 2013 and September 30, 2014. Results We observed blood oxygen level dependent (BOLD) signal changes (FDR<.001) in the motor circuitry, including primary motor, premotor, and supplementary motor cortices, thalamus, pedunculopontine nucleus (PPN), and cerebellum, as well as in the limbic circuitry, including cingulate and insular cortices. Activation of the motor network was observed also after applying a Bonferroni correction (p<.001) to our dataset, suggesting that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. Conclusions These findings support the modulatory role of STN DBS on the activity of motor and non-motor networks, and suggest complex mechanisms at the basis of the efficacy of this treatment modality. Furthermore, these results suggest that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. With further studies combining the use of real time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning, but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. PMID:26046412

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.

Lessons from sleeping flies: insights from Drosophila melanogaster on the neuronal circuitry and importance of sleep.

PubMed

Potdar, Sheetal; Sheeba, Vasu

2013-06-01

Sleep is a highly conserved behavior whose role is as yet unknown, although it is widely acknowledged as being important. Here we provide an overview of many vital questions regarding this behavior, that have been addressed in recent years using the genetically tractable model organism Drosophila melanogaster in several laboratories around the world. Rest in D. melanogaster has been compared to mammalian sleep and its homeostatic and circadian regulation have been shown to be controlled by intricate neuronal circuitry involving circadian clock neurons, mushroom bodies, and pars intercerebralis, although their exact roles are not entirely clear. We draw attention to the yet unanswered questions and contradictions regarding the nature of the interactions between the brain regions implicated in the control of sleep. Dopamine, octopamine, γ-aminobutyric acid (GABA), and serotonin are the chief neurotransmitters identified as functioning in different limbs of this circuit, either promoting arousal or sleep by modulating membrane excitability of underlying neurons. Some studies have suggested that certain brain areas may contribute towards both sleep and arousal depending on activation of specific subsets of neurons. Signaling pathways implicated in the sleep circuit include cyclic adenosine monophosphate (cAMP) and epidermal growth factor receptor-extracellular signal-regulated kinase (EGFR-ERK) signaling pathways that operate on different neural substrates. Thus, this field of research appears to be on the cusp of many new and exciting findings that may eventually help in understanding how this complex physiological phenomenon is modulated by various neuronal circuits in the brain. Finally, some efforts to approach the "Holy Grail" of why we sleep have been summarized.

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

Neurocircuitry of drug reward

PubMed Central

Ikemoto, Satoshi; Bonci, Antonello

2013-01-01

In recent years, neuroscientists have produced profound conceptual and mechanistic advances on the neurocircuitry of reward and substance use disorders. Here, we will provide a brief review of intracranial drug self-administration and optogenetic self-stimulation studies that identified brain regions and neurotransmitter systems involved in drug- and reward-related behaviors. Also discussed is a theoretical framework that helps to understand the functional properties of the circuitry involved in these behaviors. The circuitry appears to be homeostatically regulated and mediate anticipatory processes that regulate behavioral interaction with the environment in response to salient stimuli. That is, abused drugs or, at least, some may act on basic motivation and mood processes, regulating behavior-environment interaction. Optogenetics and related technologies have begun to uncover detailed circuit mechanisms linking key brain regions in which abused drugs act for rewarding effects. PMID:23664810

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

Pathophysiology and Management of Parkinsonian Tremor.

PubMed

Helmich, Rick C; Dirkx, Michiel F

2017-04-01

Parkinson's tremor is one of the cardinal motor symptoms of Parkinson's disease. The pathophysiology of Parkinson's tremor is different from that of other motor symptoms such as bradykinesia and rigidity. In this review, the authors discuss evidence suggesting that tremor is a network disorder that arises from distinct pathophysiological changes in the basal ganglia and in the cerebellothalamocortical circuit. They also discuss how interventions in this circuitry, for example, deep brain surgery and noninvasive brain stimulation, can modulate or even treat tremor. Future research may focus on understanding sources for the large variability between patients in terms of treatment response, on understanding the contextual factors that modulate tremor (stress, voluntary movements), and on focused interventions in the tremor circuitry. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

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.

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2011-09-01

cerebral cortex of a rat’s brain. The flow chart for spike discrimination algorithm is also shown. Negative threshold level (not shown in bottom left...portion of the transistor drain current can flow into its bulk due to impact ionization effect [40], greatly degrading the output impedance of the...current source. This can be solved by connecting the bulk and source of together, as also seen in Fig. 4, allowing its drain-bulk current to also flow

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

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

Heterogeneous integration of adult-generated granule cells into the epileptic brain

PubMed Central

Murphy, Brian L.; Pun, Raymund Y.K.; Yin, Hulian; Faulkner, Christian R.; Loepke, Andreas W.; Danzer, Steve C.

2011-01-01

The functional impact of adult-generated granule cells in the epileptic brain is unclear, with data supporting both protective and maladaptive roles. These conflicting findings could be explained if new granule cells integrate heterogeneously, with some cells taking neutral or adaptive roles, while others contribute to recurrent circuitry supporting seizures. Here, we tested this hypothesis by completing detailed morphological characterizations of age- and experience-defined cohorts of adult-generated granule cells from transgenic mice. The majority of newborn cells exposed to an epileptogenic insult exhibited reductions in dendritic spine number, suggesting reduced excitatory input to these cells. A significant subset, however, exhibited higher spine numbers. These latter cells tended to have enlarged cell bodies, long basal dendrites or both. Moreover, cells with basal dendrites received significantly more recurrent mossy fiber input through their apical dendrites, indicating that these cells are robustly integrated into the pathological circuitry of the epileptic brain. These data imply that newborn cells play complex – and potentially conflicting – roles in epilepsy. PMID:21209195

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.

Sleep state switching.

PubMed

Saper, Clifford B; Fuller, Patrick M; Pedersen, Nigel P; Lu, Jun; Scammell, Thomas E

2010-12-22

We take for granted the ability to fall asleep or to snap out of sleep into wakefulness, but these changes in behavioral state require specific switching mechanisms in the brain that allow well-defined state transitions. In this review, we examine the basic circuitry underlying the regulation of sleep and wakefulness and discuss a theoretical framework wherein the interactions between reciprocal neuronal circuits enable relatively rapid and complete state transitions. We also review how homeostatic, circadian, and allostatic drives help regulate sleep state switching and discuss how breakdown of the switching mechanism may contribute to sleep disorders such as narcolepsy. Copyright © 2010 Elsevier Inc. All rights reserved.

Sleep State Switching

PubMed Central

Saper, Clifford B.; Fuller, Patrick M.; Pedersen, Nigel P.; Lu, Jun; Scammell, Thomas E.

2010-01-01

We take for granted the ability to fall asleep or to snap out of sleep into wakefulness, but these changes in behavioral state require specific switching mechanisms in the brain that allow well-defined state transitions. In this review, we examine the basic circuitry underlying the regulation of sleep and wakefulness, and discuss a theoretical framework wherein the interactions between reciprocal neuronal circuits enable relatively rapid and complete state transitions. We also review how homeostatic, circadian, and allostatic drives help regulate sleep state switching, and discuss how breakdown of the switching mechanism may contribute to sleep disorders such as narcolepsy. PMID:21172606

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.

Associative Learning and Sensory Neuroplasticity: How Does It Happen and What Is It Good For?

ERIC Educational Resources Information Center

McGann, John P.

2015-01-01

Historically, the body's sensory systems have been presumed to provide the brain with raw information about the external environment, which the brain must interpret to select a behavioral response. Consequently, studies of the neurobiology of learning and memory have focused on circuitry that interfaces between sensory inputs and behavioral…

A systematic review of the neural bases of psychotherapy for anxiety and related disorders

PubMed Central

Brooks, Samantha J.; Stein, Dan J.

2015-01-01

Brain imaging studies over two decades have delineated the neural circuitry of anxiety and related disorders, particularly regions involved in fear processing and in obsessive-compulsive symptoms. The neural circuitry of fear processing involves the amygdala, anterior cingulate, and insular cortex, while cortico-striatal-thalamic circuitry plays a key role in obsessive-compulsive disorder. More recently, neuroimaging studies have examined how psychotherapy for anxiety and related disorders impacts on these neural circuits. Here we conduct a systematic review of the findings of such work, which yielded 19 functional magnetic resonance imaging studies examining the neural bases of cognitive-behavioral therapy (CBT) in 509 patients with anxiety and related disorders. We conclude that, although each of these related disorders is mediated by somewhat different neural circuitry, CBT may act in a similar way to increase prefrontal control of subcortical structures. These findings are consistent with an emphasis in cognitive-affective neuroscience on the potential therapeutic value of enhancing emotional regulation in various psychiatric conditions. PMID:26487807

A systematic review of the neural bases of psychotherapy for anxiety and related disorders.

PubMed

Brooks, Samantha J; Stein, Dan J

2015-09-01

Brain imaging studies over two decades have delineated the neural circuitry of anxiety and related disorders, particularly regions involved in fear processing and in obsessive-compulsive symptoms. The neural circuitry of fear processing involves the amygdala, anterior cingulate, and insular cortex, while cortico-striatal-thalamic circuitry plays a key role in obsessive-compulsive disorder. More recently, neuroimaging studies have examined how psychotherapy for anxiety and related disorders impacts on these neural circuits. Here we conduct a systematic review of the findings of such work, which yielded 19 functional magnetic resonance imaging studies examining the neural bases of cognitive-behavioral therapy (CBT) in 509 patients with anxiety and related disorders. We conclude that, although each of these related disorders is mediated by somewhat different neural circuitry, CBT may act in a similar way to increase prefrontal control of subcortical structures. These findings are consistent with an emphasis in cognitive-affective neuroscience on the potential therapeutic value of enhancing emotional regulation in various psychiatric conditions.

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2013-09-01

were requested to provide further evidence, either neurophysiological or neuroanatomical, of enhanced connectivity (no additional studies in new...report. The algorithms developed during the course of the manuscript revision have proved to be very enlightening . During Year 3, we revisited our Year...to our local IACUC and subsequently, to ACURO during Year 4. As a result of the Nature reviews, we focused on a more neurophysiological approach to

Focusing on symptoms rather than diagnoses in brain dysfunction: conscious and nonconscious expression in impulsiveness and decision-making.

PubMed

Palomo, T; Beninger, R J; Kostrzewa, R M; Archer, T

2008-08-01

Symptoms and syndromes in neuropathology, whether expressed in conscious or nonconscious behaviour, remain imbedded in often complex diagnostic categories. Symptom-based strategies for studying brain disease states are driven by assessments of presenting symptoms, signs, assay results, neuroimages and biomarkers. In the present account, symptom-based strategies are contrasted with existing diagnostic classifications. Topics include brain areas and regional circuitry underlying decision-making and impulsiveness, and motor and learned expressions of explicit and implicit processes. In three self-report studies on young adult and adolescent healthy individuals, it was observed that linear regression analyses between positive and negative affect, self-esteem, four different types of situational motivation: intrinsic, identified regulation, extrinsic regulation and amotivation, and impulsiveness predicted significant associations between impulsiveness with negative affect and lack of motivation (i.e., amotivation) and internal locus of control, on the one hand, and non-impulsiveness with positive affect, self-esteem, and high motivation (i.e., intrinsic motivation and identified regulation), on the other. Although presymptomatic, these cognitive-affective characterizations illustrate individuals' choice behaviour in appraisals of situations, events and proclivities essentially of distal perspective. Neuropathological expressions provide the proximal realities of symptoms and syndromes with underlying dysfunctionality of brain regions, circuits and molecular mechanisms.

Common and distinct networks underlying reward valence and processing stages: A meta-analysis of functional neuroimaging studies

PubMed Central

Liu, Xun; Hairston, Jacqueline; Schrier, Madeleine; Fan, Jin

2011-01-01

To better understand the reward circuitry in human brain, we conducted activation likelihood estimation (ALE) and parametric voxel-based meta-analyses (PVM) on 142 neuroimaging studies that examined brain activation in reward-related tasks in healthy adults. We observed several core brain areas that participated in reward-related decision making, including the nucleus accumbens (NAcc), caudate, putamen, thalamus, orbitofrontal cortex (OFC), bilateral anterior insula, anterior (ACC) and posterior (PCC) cingulate cortex, as well as cognitive control regions in the inferior parietal lobule and prefrontal cortex (PFC). The NAcc was commonly activated by both positive and negative rewards across various stages of reward processing (e.g., anticipation, outcome, and evaluation). In addition, the medial OFC and PCC preferentially responded to positive rewards, whereas the ACC, bilateral anterior insula, and lateral PFC selectively responded to negative rewards. Reward anticipation activated the ACC, bilateral anterior insula, and brain stem, whereas reward outcome more significantly activated the NAcc, medial OFC, and amygdala. Neurobiological theories of reward-related decision making should therefore distributed and interrelated representations of reward valuation and valence assessment into account. PMID:21185861

Negative functional coupling between the right fronto-parietal and limbic resting state networks predicts increased self-control and later substance use onset in adolescence.

PubMed

Lee, Tae-Ho; Telzer, Eva H

2016-08-01

Recent developmental brain imaging studies have demonstrated that negatively coupled prefrontal-limbic circuitry implicates the maturation of brain development in adolescents. Using resting-state functional magnetic resonance imaging (rs-fMRI) and independent component analysis (ICA), the present study examined functional network coupling between prefrontal and limbic systems and links to self-control and substance use onset in adolescents. Results suggest that negative network coupling (anti-correlated temporal dynamics) between the right fronto-parietal and limbic resting state networks is associated with greater self-control and later substance use onset in adolescents. These findings increase our understanding of the developmental importance of prefrontal-limbic circuitry for adolescent substance use at the resting-state network level. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling

PubMed Central

Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich; Kim, Woo-Yang

2014-01-01

Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. PMID:25224226

MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling.

PubMed

Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich; Kim, Woo-Yang

2014-11-01

Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

Synaptic Mechanisms of Blast-Induced Brain Injury

PubMed Central

Przekwas, Andrzej; Somayaji, Mahadevabharath R.; Gupta, Raj K.

2016-01-01

Blast wave-induced traumatic brain injury (TBI) is one of the most common injuries to military personnel. Brain tissue compression/tension due to blast-induced cranial deformations and shear waves due to head rotation may generate diffuse micro-damage to neuro-axonal structures and trigger a cascade of neurobiological events culminating in cognitive and neurodegenerative disorders. Although diffuse axonal injury is regarded as a signature wound of mild TBI (mTBI), blast loads may also cause synaptic injury wherein neuronal synapses are stretched and sheared. This synaptic injury may result in temporary disconnect of the neural circuitry and transient loss in neuronal communication. We hypothesize that mTBI symptoms such as loss of consciousness or dizziness, which start immediately after the insult, could be attributed to synaptic injury. Although empirical evidence is beginning to emerge; the detailed mechanisms underlying synaptic injury are still elusive. Coordinated in vitro–in vivo experiments and mathematical modeling studies can shed light into the synaptic injury mechanisms and their role in the potentiation of mTBI symptoms. PMID:26834697

Tentative Evidence for Striatal Hyperactivity in Adolescent Cannabis Using Boys: A Cross-Sectional Multicenter fMRI Study

PubMed Central

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

2013-01-01

Adolescents' risk-taking behavior has been linked to a maturational imbalance between reward (“go”) and inhibitory-control (“stop”) related brain circuitry. This may drive adolescent drug-taking, such as cannabis use. In this study we assessed the non-acute effects of adolescent cannabis use on reward-related brain function. We performed a two-site (United States and Netherlands; pooled data) functional magnetic resonance imaging (fMRI) study with a cross-sectional design. Twenty-one abstinent but frequent cannabis-using boys were compared with 24 non-using peers on reward-related brain function, using a monetary incentive delay task with fMRI. Focus was on anticipatory and response stages of reward and brain areas critically involved in reward processing like the striatum. Performance in users was normal. Region-of-interest analysis indicated striatal hyperactivity during anticipatory stages of reward in users. Intriguingly, this effect was most pronounced during non-rewarding events. Striatal hyperactivity in adolescent cannabis users may signify an overly sensitive motivational brain circuitry. Frequent cannabis use during adolescence may induce diminished ability to disengage the motivational circuit when no reward can be obtained. This could strengthen the search for reinforcements like drugs of abuse, even when facing the negative (non-rewarding) consequences. PMID:23909003

Tentative evidence for striatal hyperactivity in adolescent cannabis-using boys: a cross-sectional multicenter fMRI study.

PubMed

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

2013-01-01

Adolescents' risk-taking behavior has been linked to a maturational imbalance between reward ("go") and inhibitory-control ("stop")-related brain circuitry. This may drive adolescent drug-taking, such as cannabis use. In this study, we assessed the non-acute effects of adolescent cannabis use on reward-related brain function. We performed a two-site (United States and Netherlands; pooled data) functional magnetic resonance imaging (fMRI) study with a cross-sectional design. Twenty-one abstinent but frequent cannabis-using boys were compared with 24 non-using peers on reward-related brain function, using a monetary incentive delay task with fMRI. Focus was on anticipatory and response stages of reward and brain areas critically involved in reward processing like the striatum. Performance in users was normal. Region-of-interest analysis indicated striatal hyperactivity during anticipatory stages of reward in users. Intriguingly, this effect was most pronounced during non-rewarding events. Striatal hyperactivity in adolescent cannabis users may signify an overly sensitive motivational brain circuitry. Frequent cannabis use during adolescence may induce diminished ability to disengage the motivational circuit when no reward can be obtained. This could strengthen the search for reinforcements like drugs of abuse, even when facing the negative (non-rewarding) consequences.

An analysis of the circuitry of the visual pathway of the lateral eye of limullus

NASA Technical Reports Server (NTRS)

Sjoestrand, F. S.

1970-01-01

The methodology is discussed for three-dimensional analysis of the nervous system on the basis of electron micrographs of serial sections. An analysis is presented of a part of the circuitry of the rabbit retina. In addition, some exploratory work is reported with respect to the visual cortex of the cat brain. A proper technique for preservation of the visual cortex was worked out and a technique to localize microelectrode tips in the tissue in connection with electron microscopy was partially worked out.

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

Are You Smarter Than a Teenager? Maybe Not When It Comes to Reinforcement Learning.

PubMed

DiMenichi, Brynne C; Tricomi, Elizabeth

2016-10-05

Adolescence is a time of tumultuous behavior that may result, in part, from brain circuitry that enhances reward seeking. In this issue of Neuron, Davidow et al. (2016) present a convincing argument that adolescent brain functionality can be adaptive in certain contexts, particularly probabilistic learning environments. Copyright © 2016. Published by Elsevier Inc.

Neurophysiological effects of modafinil on cue-exposure in cocaine dependence: a randomized placebo-controlled cross-over study using pharmacological fMRI.

PubMed

Goudriaan, Anna E; Veltman, Dick J; van den Brink, Wim; Dom, Geert; Schmaal, Lianne

2013-02-01

Enhanced reactivity to substance related cues is a central characteristic of addiction and has been associated with increased activity in motivation, attention, and memory related brain circuits and with a higher probability of relapse. Modafinil was promising in the first clinical trials in cocaine dependence, and was able to reduce craving in addictive disorders. However, its mechanism of action remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study therefore, cue reactivity in cocaine dependent patients was compared to cue reactivity in healthy controls (HCs) under modafinil and placebo conditions. An fMRI cue reactivity study, with a double-blind, placebo-controlled cross-over challenge with a single dose of modafinil (200mg) was employed in 13 treatment seeking cocaine dependent patients and 16 HCs. In the placebo condition, watching cocaine-related pictures (versus neutral pictures) resulted in higher brain activation in the medial frontal cortex, anterior cingulate cortex, angular gyrus, left orbitofrontal cortex, and ventral tegmental area (VTA) in the cocaine dependent group compared to HCs. However, in the modafinil condition, no differences in brain activation patterns were found between cocaine dependent patients and HCs. Group interactions revealed decreased activity in the VTA and increased activity in the right ACC and putamen in the modafinil condition relative to the placebo condition in cocaine dependent patients, whereas such changes were not present in healthy controls. Decreases in self-reported craving when watching cocaine-related cues after modafinil administration compared to the placebo condition were associated with modafinil-induced increases in ACC and putamen activation. Enhanced cue reactivity in the cocaine dependent group compared to healthy controls was found in brain circuitries related to reward, motivation, and autobiographical memory processes. In cocaine dependent patients, these enhanced brain responses were attenuated by modafinil, mainly due to decreases in cue- reactivity in reward-related brain areas (VTA) and increases in cue reactivity in cognitive control areas (ACC). These modafinil-induced changes in brain activation in response to cocaine-related visual stimuli were associated with diminished self-reported craving. These findings imply that in cocaine dependent patients, modafinil, although mainly known as a cognitive enhancer, acts on both the motivational and the cognitive brain circuitry. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2015-11-01

or asymmetric biphasic current pulses up to ~100 A with passive discharge , and W-level digital signal processing 6 (DSP) unit for real-time SAR...voltage compliance of 4.68 V with a 5 V supply, when configured for monophasic stimulation with passive discharge . The programmable microstimulator...superficial aspects of the corona radiate was evident. In the full study, impact parameters will be altered slightly (somewhat larger impact tip, slightly

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

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization

PubMed Central

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P.; Johnson, G. Allan

2015-01-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved 3D reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate accurate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. PMID:26043869

Which Classes of Prescription Drugs Are Commonly Misused?

MedlinePlus

... a part of addiction, but they are not equivalent. Addiction involves other changes to brain circuitry and ... physicians should assess pain and functioning, consider if non-opioid treatment options are appropriate, discuss a treatment ...

Marijuana and cannabinoid regulation of brain reward circuits.

PubMed

Lupica, Carl R; Riegel, Arthur C; Hoffman, Alexander F

2004-09-01

The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Delta(9)-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self-administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Delta(9)-THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Delta(9)-THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA.

Brain-to-brain synchrony in parent-child dyads and the relationship with emotion regulation revealed by fNIRS-based hyperscanning.

PubMed

Reindl, Vanessa; Gerloff, Christian; Scharke, Wolfgang; Konrad, Kerstin

2018-05-26

Parent-child synchrony, the coupling of behavioral and biological signals during social contact, may fine-tune the child's brain circuitries associated with emotional bond formation and the child's development of emotion regulation. Here, we examined the neurobiological underpinnings of these processes by measuring parent's and child's prefrontal neural activity concurrently with functional near-infrared spectroscopy hyperscanning. Each child played both a cooperative and a competitive game with the parent, mostly the mother, as well as an adult stranger. During cooperation, parent's and child's brain activities synchronized in the dorsolateral prefrontal and frontopolar cortex (FPC), which was predictive for their cooperative performance in subsequent trials. No significant brain-to-brain synchrony was observed in the conditions parent-child competition, stranger-child cooperation and stranger-child competition. Furthermore, parent-child compared to stranger-child brain-to-brain synchrony during cooperation in the FPC mediated the association between the parent's and the child's emotion regulation, as assessed by questionnaires. Thus, we conclude that brain-to-brain synchrony may represent an underlying neural mechanism of the emotional connection between parent and child, which is linked to the child's development of adaptive emotion regulation. Future studies may uncover whether brain-to-brain synchrony can serve as a neurobiological marker of the dyad's socio-emotional interaction, which is sensitive to risk conditions, and can be modified by interventions. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Hermetic electronic packaging of an implantable brain-machine-interface with transcutaneous optical data communication.

PubMed

Schuettler, Martin; Kohler, Fabian; Ordonez, Juan S; Stieglitz, Thomas

2012-01-01

Future brain-computer-interfaces (BCIs) for severely impaired patients are implanted to electrically contact the brain tissue. Avoiding percutaneous cables requires amplifier and telemetry electronics to be implanted too. We developed a hermetic package that protects the electronic circuitry of a BCI from body moisture while permitting infrared communication through the package wall made from alumina ceramic. The ceramic package is casted in medical grade silicone adhesive, for which we identified MED2-4013 as a promising candidate.

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2011-09-01

parietal bones, and a threaded rod was implanted into the interparietal bone. These were affixed to the skull with dental acrylic. A hybrid, 16...then sealed with a silicone polymer (Kwik-Cast, WPI). The base of the probe connector was lowered onto the dental acrylic and fixed into place. An...the skull using a dental drill with a trephine bit over the cortex contralateral to the dominant forelimb. A total of 14 animals received CCI in the

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

PPL2ab neurons restore sexual responses in aged Drosophila males through dopamine.

PubMed

Kuo, Shu-Yun; Wu, Chia-Lin; Hsieh, Min-Yen; Lin, Chen-Ta; Wen, Rong-Kun; Chen, Lien-Cheng; Chen, Yu-Hui; Yu, Yhu-Wei; Wang, Horng-Dar; Su, Yi-Ju; Lin, Chun-Ju; Yang, Cian-Yi; Guan, Hsien-Yu; Wang, Pei-Yu; Lan, Tsuo-Hung; Fu, Tsai-Feng

2015-06-30

Male sexual desire typically declines with ageing. However, our understanding of the neurobiological basis for this phenomenon is limited by our knowledge of the brain circuitry and neuronal pathways controlling male sexual desire. A number of studies across species suggest that dopamine (DA) affects sexual desire. Here we use genetic tools and behavioural assays to identify a novel subset of DA neurons that regulate age-associated male courtship activity in Drosophila. We find that increasing DA levels in a subset of cells in the PPL2ab neuronal cluster is necessary and sufficient for increased sustained courtship in both young and aged male flies. Our results indicate that preventing the age-related decline in DA levels in PPL2ab neurons alleviates diminished courtship behaviours in male Drosophila. These results may provide the foundation for deciphering the circuitry involved in sexual motivation in the male Drosophila brain.

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

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

Mechanism of Chronic Pain in Rodent Brain Imaging

NASA Astrophysics Data System (ADS)

Chang, Pei-Ching

Chronic pain is a significant health problem that greatly impacts the quality of life of individuals and imparts high costs to society. Despite intense research effort in understanding of the mechanism of pain, chronic pain remains a clinical problem that has few effective therapies. The advent of human brain imaging research in recent years has changed the way that chronic pain is viewed. To further extend the use of human brain imaging techniques for better therapies, the adoption of imaging technique onto the animal pain models is essential, in which underlying brain mechanisms can be systematically studied using various combination of imaging and invasive techniques. The general goal of this thesis is to addresses how brain develops and maintains chronic pain in an animal model using fMRI. We demonstrate that nucleus accumbens, the central component of mesolimbic circuitry, is essential in development of chronic pain. To advance our imaging technique, we develop an innovative methodology to carry out fMRI in awake, conscious rat. Using this cutting-edge technique, we show that allodynia is assoicated with shift brain response toward neural circuits associated nucleus accumbens and prefrontal cortex that regulate affective and cognitive component of pain. Taken together, this thesis provides a deeper understanding of how brain mediates pain. It builds on the existing body of knowledge through maximizing the depth of insight into brain imaging of chronic pain.

Optogenetic dissection of medial prefrontal cortex circuitry

PubMed Central

Riga, Danai; Matos, Mariana R.; Glas, Annet; Smit, August B.; Spijker, Sabine; Van den Oever, Michel C.

2014-01-01

The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders. PMID:25538574

Optogenetic dissection of medial prefrontal cortex circuitry.

PubMed

Riga, Danai; Matos, Mariana R; Glas, Annet; Smit, August B; Spijker, Sabine; Van den Oever, Michel C

2014-01-01

The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.

Supernatural believers attribute more intentions to random movement than skeptics: an fMRI study.

PubMed

Riekki, Tapani; Lindeman, Marjaana; Raij, Tuukka T

2014-01-01

A host of research has attempted to explain why some believe in the supernatural and some do not. One suggested explanation for commonly held supernatural beliefs is that they are a by-product of theory of mind (ToM) processing. However, this does not explain why skeptics with intact ToM processes do not believe. We employed fMRI to investigate activation differences in ToM-related brain circuitries between supernatural believers (N = 12) and skeptics (N = 11) while they watched 2D animations of geometric objects moving intentionally or randomly and rated the intentionality of the animations. The ToM-related circuitries in the medial prefrontal cortex (mPFC) were localized by contrasting intention-rating-related and control-rating-related brain activation. Compared with the skeptics, the supernatural believers rated the random movements as more intentional and had stronger activation of the ToM-related circuitries during the animation with random movement. The strength of the ToM-related activation covaried with the intentionality ratings. These findings provide evidence that differences in ToM-related activations are associated with supernatural believers' tendency to interpret random phenomena in mental terms. Thus, differences in ToM processing may contribute to differences between believing and unbelieving.

Epigenetic dysregulation of the dopamine system in diet-induced obesity.

PubMed

Vucetic, Zivjena; Carlin, Jesse Lea; Totoki, Kathy; Reyes, Teresa M

2012-03-01

Chronic intake of high-fat (HF) diet is known to alter brain neurotransmitter systems that participate in the central regulation of food intake. Dopamine (DA) system changes in response to HF diet have been observed in the hypothalamus, important in the homeostatic control of food intake, as well as within the central reward circuitry [ventral tegmental area (VTA), nucleus accumbens (NAc), and pre-frontal cortex (PFC)], critical for coding the rewarding properties of palatable food and important in hedonically driven feeding behavior. Using a mouse model of diet-induced obesity (DIO), significant alterations in the expression of DA-related genes were documented in adult animals, and the general pattern of gene expression changes was opposite within the hypothalamus versus the reward circuitry (increased vs. decreased, respectively). Differential DNA methylation was identified within the promoter regions of tyrosine hydroxylase (TH) and dopamine transporter (DAT), and the pattern of this response was consistent with the pattern of gene expression. Behaviors consistent with increased hypothalamic DA and decreased reward circuitry DA were observed. These data identify differential DNA methylation as an epigenetic mechanism linking the chronic intake of HF diet with altered DA-related gene expression, and this response varies by brain region and DNA sequence. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

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

A review of brain circuitries involved in stuttering

PubMed Central

Craig-McQuaide, Anna; Akram, Harith; Zrinzo, Ludvic; Tripoliti, Elina

2014-01-01

Stuttering has been the subject of much research, nevertheless its etiology remains incompletely understood. This article presents a critical review of the literature on stuttering, with particular reference to the role of the basal ganglia (BG). Neuroimaging and lesion studies of developmental and acquired stuttering, as well as pharmacological and genetic studies are discussed. Evidence of structural and functional changes in the BG in those who stutter indicates that this motor speech disorder is due, at least in part, to abnormal BG cues for the initiation and termination of articulatory movements. Studies discussed provide evidence of a dysfunctional hyperdopaminergic state of the thalamocortical pathways underlying speech motor control in stuttering. Evidence that stuttering can improve, worsen or recur following deep brain stimulation for other indications is presented in order to emphasize the role of BG in stuttering. Further research is needed to fully elucidate the pathophysiology of this speech disorder, which is associated with significant social isolation. PMID:25452719

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.

Reward-related brain response and craving correlates of marijuana cue exposure: a preliminary study in treatment-seeking marijuana-dependent subjects.

PubMed

Goldman, Marina; Szucs-Reed, Regina P; Jagannathan, Kanchana; Ehrman, Ronald N; Wang, Ze; Li, Yin; Suh, Jesse J; Kampman, Kyle; O'Brien, Charles P; Childress, Anna Rose; Franklin, Teresa R

2013-01-01

: Determining the brain substrates underlying the motivation to abuse addictive drugs is critical for understanding and treating addictive disorders. Laboratory neuroimaging studies have demonstrated differential activation of limbic and motivational circuitry (eg, amygdala, hippocampus, ventral striatum, insula, and orbitofrontal cortex) triggered by cocaine, heroin, nicotine, and alcohol cues. The literature on neural responses to marijuana cues is sparse. Thus, the goals of this study were to characterize the brain's response to marijuana cues, a major motivator underlying drug use and relapse, and determine whether these responses are linked to self-reported craving in a clinically relevant population of treatment-seeking marijuana-dependent subjects. : Marijuana craving was assessed in 12 marijuana-dependent subjects using the Marijuana Craving Questionnaire-Short Form. Subsequently, blood oxygen level dependent functional magnetic resonance imaging data were acquired during exposure to alternating 20-second blocks of marijuana-related versus matched nondrug visual cues. : Brain activation during marijuana cue exposure was significantly greater in the bilateral amygdala and the hippocampus. Significant positive correlations between craving scores and brain activation were found in the ventral striatum and the medial and lateral orbitofrontal cortex (P < 0.0001). : This study presents direct evidence for a link between reward-relevant brain responses to marijuana cues and craving and extends the current literature on marijuana cue reactivity. Furthermore, the correlative relationship between craving and brain activity in reward-related regions was observed in a clinically relevant sample (treatment-seeking marijuana-dependent subjects). Results are consistent with prior findings in cocaine, heroin, nicotine, and alcohol cue studies, indicating that the brain substrates of cue-triggered drug motivation are shared across abused substances.

"Liking" and "wanting" linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry.

PubMed

Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

2012-01-01

In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: "liking,"learning," and "wanting" [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or "wanting" hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily selfadministered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens (NAC), and they stimulate the functioning of brain reward circuitry (producing the "high" that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions.

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

Bridging the Gap: Towards a Cell-Type Specific Understanding of Neural Circuits Underlying Fear Behaviors

PubMed Central

McCullough, KM; Morrison, FG; Ressler, KJ

2016-01-01

Fear and anxiety-related disorders are remarkably common and debilitating, and are often characterized by dysregulated fear responses. Rodent models of fear learning and memory have taken great strides towards elucidating the specific neuronal circuitries underlying the learning of fear responses. The present review addresses recent research utilizing optogenetic approaches to parse circuitries underlying fear behaviors. It also highlights the powerful advances made when optogenetic techniques are utilized in a genetically defined, cell-type specific, manner. The application of next-generation genetic and sequencing approaches in a cell-type specific context will be essential for a mechanistic understanding of the neural circuitry underlying fear behavior and for the rational design of targeted, circuit specific, pharmacologic interventions for the treatment and prevention of fear-related disorders. PMID:27470092

Taste Reward Circuitry Related Brain Structures Characterize Ill and Recovered Anorexia Nervosa and Bulimia Nervosa

PubMed Central

Frank, Guido K.; Shott, Megan E.; Hagman, Jennifer O.; Mittal, Vijay A.

2013-01-01

Objective The pathophysiology of the eating disorder anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. Here we assessed taste pleasantness and reward sensitivity in relation to brain structure, which might be related to food avoidance commonly seen in eating disorders. Method We used structural magnetic resonance brain imaging to study gray and white matter volumes in individuals with restricting type currently ill (n = 19) or recovered-anorexia nervosa (n = 24), bulimia nervosa (n= 19) and healthy control women (n=24). Results All eating disorder groups showed increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manually tracing confirmed larger gyrus rectus volume, and predicted taste pleasantness across all groups. The analyses also indicated other morphological differences between diagnostic categories: Ill and recovered-anorexia nervosa had increased right, while bulimia nervosa had increased left antero-ventral insula gray matter volumes compared to controls. Furthermore, dorsal striatum volumes were reduced in recovered-anorexia and bulimia nervosa, and predicted sensitivity to reward in the eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas when compared to healthy controls. Notably, the results held when controlling for a range of covariates (e.g., age, depression, anxiety, medications). Conclusion Brain structure in medial orbitofrontal cortex, insula and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value. PMID:23680873

Dorsomedial prefontal cortex supports spontaneous thinking per se.

PubMed

Raij, T T; Riekki, T J J

2017-06-01

Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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.

Pharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm.

PubMed

Castilla-Ortega, Estela; Blanco, Eduardo; Serrano, Antonia; Ladrón de Guevara-Miranda, David; Pedraz, María; Estivill-Torrús, Guillermo; Pavón, Francisco Javier; Rodríguez de Fonseca, Fernando; Santín, Luis J

2016-05-01

We investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesis-reduced mice showed normal CPP acquisition but engaged an alternate brain circuit where the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus) were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model. © 2015 Society for the Study of Addiction.

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

Separate Circuitries Encode the Hedonic and Nutritional Values of Sugar

PubMed Central

Tellez, Luis A.; Han, Wenfei; Zhang, Xiaobing; Ferreira, Tatiana L.; Perez, Isaac O.; Shammah-Lagnado, Sara J.; van den Pol, Anthony N.; de Araujo, Ivan E.

2016-01-01

Sugar exerts its potent reinforcing effects via both gustatory and post-ingestive pathways. It is however unknown if sweetness and nutritional signals engage segregated brain networks to motivate ingestion. We show in mice that separate basal ganglia circuitries mediate the hedonic and nutritional actions of sugar. We found that, during sugar intake, suppressing hedonic value inhibited dopamine release in ventral but not dorsal striatum, whereas suppressing nutritional value inhibited dopamine release in dorsal but not ventral striatum. Consistently, cell-specific ablation of dopamine-excitable cells in dorsal, but not ventral, striatum inhibited sugar’s ability to drive the ingestion of unpalatable solutions. Conversely, optogenetic stimulation of dopamine-excitable cells in dorsal, but not ventral, striatum substituted for sugar in its ability to drive the ingestion of unpalatable solutions. Our data demonstrate that sugar recruits a distributed dopamine-excitable striatal circuitry that acts to prioritize energy seeking over taste quality. PMID:26807950

Separate circuitries encode the hedonic and nutritional values of sugar.

PubMed

Tellez, Luis A; Han, Wenfei; Zhang, Xiaobing; Ferreira, Tatiana L; Perez, Isaac O; Shammah-Lagnado, Sara J; van den Pol, Anthony N; de Araujo, Ivan E

2016-03-01

Sugar exerts its potent reinforcing effects via both gustatory and post-ingestive pathways. It is, however, unknown whether sweetness and nutritional signals engage segregated brain networks to motivate ingestion. We found in mice that separate basal ganglia circuitries mediated the hedonic and nutritional actions of sugar. During sugar intake, suppressing hedonic value inhibited dopamine release in ventral, but not dorsal, striatum, whereas suppressing nutritional value inhibited dopamine release in dorsal, but not ventral, striatum. Consistently, cell-specific ablation of dopamine-excitable cells in dorsal, but not ventral, striatum inhibited sugar's ability to drive the ingestion of unpalatable solutions. Conversely, optogenetic stimulation of dopamine-excitable cells in dorsal, but not ventral, striatum substituted for sugar in its ability to drive the ingestion of unpalatable solutions. Our data indicate that sugar recruits a distributed dopamine-excitable striatal circuitry that acts to prioritize energy-seeking over taste quality.

Neurogenetics and Nutrigenomics of Neuro-Nutrient Therapy for Reward Deficiency Syndrome (RDS): Clinical Ramifications as a Function of Molecular Neurobiological Mechanisms

PubMed Central

Blum, Kenneth; Oscar-Berman, Marlene; Stuller, Elizabeth; Miller, David; Giordano, John; Morse, Siobhan; McCormick, Lee; Downs, William B; Waite, Roger L; Barh, Debmalya; Neal, Dennis; Braverman, Eric R; Lohmann, Raquel; Borsten, Joan; Hauser, Mary; Han, David; Liu, Yijun; Helman, Manya; Simpatico, Thomas

2013-01-01

In accord with the new definition of addiction published by American Society of Addiction Medicine (ASAM) it is well-known that individuals who present to a treatment center involved in chemical dependency or other documented reward dependence behaviors have impaired brain reward circuitry. They have hypodopaminergic function due to genetic and/or environmental negative pressures upon the reward neuro-circuitry. This impairment leads to aberrant craving behavior and other behaviors such as Substance Use Disorder (SUD). Neurogenetic research in both animal and humans revealed that there is a well-defined cascade in the reward site of the brain that leads to normal dopamine release. This cascade has been termed the “Brain Reward Cascade” (BRC). Any impairment due to either genetics or environmental influences on this cascade will result in a reduced amount of dopamine release in the brain reward site. Manipulation of the BRC has been successfully achieved with neuro-nutrient therapy utilizing nutrigenomic principles. After over four decades of development, neuro-nutrient therapy has provided important clinical benefits when appropriately utilized. This is a review, with some illustrative case histories from a number of addiction professionals, of certain molecular neurobiological mechanisms which if ignored may lead to clinical complications. PMID:23926462

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.

Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

PubMed

Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

2017-03-01

Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization.

PubMed

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P; Johnson, G Allan

2015-08-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. © 2015 Wiley Periodicals, Inc.

Sharing self-related information is associated with intrinsic functional connectivity of cortical midline brain regions

PubMed Central

Meshi, Dar; Mamerow, Loreen; Kirilina, Evgeniya; Morawetz, Carmen; Margulies, Daniel S.; Heekeren, Hauke R.

2016-01-01

Human beings are social animals and they vary in the degree to which they share information about themselves with others. Although brain networks involved in self-related cognition have been identified, especially via the use of resting-state experiments, the neural circuitry underlying individual differences in the sharing of self-related information is currently unknown. Therefore, we investigated the intrinsic functional organization of the brain with respect to participants’ degree of self-related information sharing using resting state functional magnetic resonance imaging and self-reported social media use. We conducted seed-based correlation analyses in cortical midline regions previously shown in meta-analyses to be involved in self-referential cognition: the medial prefrontal cortex (MPFC), central precuneus (CP), and caudal anterior cingulate cortex (CACC). We examined whether and how functional connectivity between these regions and the rest of the brain was associated with participants’ degree of self-related information sharing. Analyses revealed associations between the MPFC and right dorsolateral prefrontal cortex (DLPFC), as well as the CP with the right DLPFC, the left lateral orbitofrontal cortex and left anterior temporal pole. These findings extend our present knowledge of functional brain connectivity, specifically demonstrating how the brain’s intrinsic functional organization relates to individual differences in the sharing of self-related information. PMID:26948055

Activity-Dependent NPAS4 Expression and the Regulation of Gene Programs Underlying Plasticity in the Central Nervous System

PubMed Central

2013-01-01

The capability of the brain to change functionally in response to sensory experience is most active during early stages of development but it decreases later in life when major alterations of neuronal network structures no longer take place in response to experience. This view has been recently challenged by experimental strategies based on the enhancement of environmental stimulation levels, genetic manipulations, and pharmacological treatments, which all have demonstrated that the adult brain retains a degree of plasticity that allows for a rewiring of neuronal circuitries over the entire life course. A hot spot in the field of neuronal plasticity centres on gene programs that underlie plastic phenomena in adulthood. Here, I discuss the role of the recently discovered neuronal-specific and activity-dependent transcription factor NPAS4 as a critical mediator of plasticity in the nervous system. A better understanding of how modifications in the connectivity of neuronal networks occur may shed light on the treatment of pathological conditions such as brain damage or disease in adult life, some of which were once considered untreatable. PMID:24024041

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

Mechanisms of human cerebellar dysmetria: experimental evidence and current conceptual bases

PubMed Central

Manto, Mario

2009-01-01

The human cerebellum contains more neurons than any other region in the brain and is a major actor in motor control. Cerebellar circuitry is unique by its stereotyped architecture and its modular organization. Understanding the motor codes underlying the organization of limb movement and the rules of signal processing applied by the cerebellar circuits remains a major challenge for the forthcoming decades. One of the cardinal deficits observed in cerebellar patients is dysmetria, designating the inability to perform accurate movements. Patients overshoot (hypermetria) or undershoot (hypometria) the aimed target during voluntary goal-directed tasks. The mechanisms of cerebellar dysmetria are reviewed, with an emphasis on the roles of cerebellar pathways in controlling fundamental aspects of movement control such as anticipation, timing of motor commands, sensorimotor synchronization, maintenance of sensorimotor associations and tuning of the magnitudes of muscle activities. An overview of recent advances in our understanding of the contribution of cerebellar circuitry in the elaboration and shaping of motor commands is provided, with a discussion on the relevant anatomy, the results of the neurophysiological studies, and the computational models which have been proposed to approach cerebellar function. PMID:19364396

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

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

The human cerebellum: a review of physiologic neuroanatomy.

PubMed

Roostaei, Tina; Nazeri, Arash; Sahraian, Mohammad Ali; Minagar, Alireza

2014-11-01

The cerebellum resides in the posterior cranial fossa dorsal to the brainstem and has diverse connections to the cerebrum, brain stem, and spinal cord. It is anatomically and physiologically divided into distinct functional compartments and is composed of highly regular arrays of neuronal units, each sharing the same basic cerebellar microcircuitry. Its circuitry is critically involved in motor control and motor learning, and its role in nonmotor cognitive and affective functions is becoming increasingly recognized. This article describes the cerebellar gross and histologic neuroanatomy in relation to its function, and the relevance of cerebellar circuitry and firing patterns to motor learning. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

“Liking” and “Wanting” Linked to Reward Deficiency Syndrome (RDS): Hypothesizing Differential Responsivity in Brain Reward Circuitry

PubMed Central

Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

2013-01-01

In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: “liking,” “learning,” and “wanting” [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or “wanting” hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily self-administered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens, and they stimulate the functioning of brain reward circuitry (producing the “high” that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions. PMID:22236117

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

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.

Glutamatergic drive facilitates synaptic inhibition of dorsal vagal motor neurons after experimentally induced diabetes in mice

PubMed Central

Boychuk, Carie R.

2016-01-01

The role of central regulatory circuits in modulating diabetes-associated glucose dysregulation has only recently been under rigorous investigation. One brain region of interest is the dorsal motor nucleus of the vagus (DMV), which contains preganglionic parasympathetic motor neurons that regulate subdiaphragmatic visceral function. Previous research has demonstrated that glutamatergic and GABAergic neurotransmission are independently remodeled after chronic hyperglycemia/hypoinsulinemia. However, glutamatergic circuitry within the dorsal brain stem impinges on GABAergic regulation of the DMV. The present study investigated the role of glutamatergic neurotransmission in synaptic GABAergic control of DMV neurons after streptozotocin (STZ)-induced hyperglycemia/hypoinsulinemia by using electrophysiological recordings in vitro. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was elevated in DMV neurons from STZ-treated mice. The effect was abolished in the presence of the ionotropic glutamate receptor blocker kynurenic acid or the sodium channel blocker tetrodotoxin, suggesting that after STZ-induced hyperglycemia/hypoinsulinemia, increased glutamatergic receptor activity occurs at a soma-dendritic location on local GABA neurons projecting to the DMV. Although sIPSCs in DMV neurons normally demonstrated considerable amplitude variability, this variability was significantly increased after STZ-induced hyperglycemia/hypoinsulinemia. The elevated amplitude variability was not related to changes in quantal release, but rather correlated with significantly elevated frequency of sIPSCs in these mice. Taken together, these findings suggest that GABAergic regulation of central vagal circuitry responsible for the regulation of energy homeostasis undergoes complex functional reorganization after several days of hyperglycemia/hypoinsulinemia, including both glutamate-dependent and -independent forms of plasticity. PMID:27385796

Individual Differences in Sleep Timing Relate to Melanopsin-Based Phototransduction in Healthy Adolescents and Young Adults.

PubMed

van der Meijden, Wisse P; Van Someren, Jamie L; Te Lindert, Bart H W; Bruijel, Jessica; van Oosterhout, Floor; Coppens, Joris E; Kalsbeek, Andries; Cajochen, Christian; Bourgin, Patrice; Van Someren, Eus J W

2016-06-01

Individual differences in sleep timing have been widely recognized and are of particular relevance in adolescents and young adults who often show mild to severely delayed sleep. The biological mechanisms underlying the between-subject variance remain to be determined. Recent human genetics studies showed an association between sleep timing and melanopsin gene variation, but support for functional effects on downstream pathways and behavior was not demonstrated before. We therefore investigated the association between the autonomic (i.e., pupil diameter) and behavioral (i.e., sleep timing) readouts of two different downstream brain areas, both affected by the same melanopsin-dependent retinal phototransduction: the olivary pretectal nucleus (OPN) and the suprachiasmatic nucleus (SCN). Our study population included 71 healthy individuals within an age range with known vulnerability to a delayed sleep phase (16.8-35.7 y, 37 males, 34 females). Pupillometry was performed to estimate functionality of the intrinsic melanopsin-signaling circuitry based on the OPN-mediated post-illumination pupil response (PIPR) to blue light. Sleep timing was quantified by estimating the SCN-mediated mid-sleep timing in three different ways in parallel: using a chronotype questionnaire, a sleep diary, and actigraphy. All three measures consistently showed that those individuals with a later mid-sleep timing had a more pronounced PIPR (0.03 < P < 0.05), indicating a stronger blue-light responsiveness of the intrinsic melanopsin-based phototransduction circuitry. Trait-like individual differences in the melanopsin phototransduction circuitry contribute to individual differences in sleep timing. Blue light-sensitive young individuals are more prone to delayed sleep. © 2016 Associated Professional Sleep Societies, LLC.

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.

Emotional speech synchronizes brains across listeners and engages large-scale dynamic brain networks

PubMed Central

Nummenmaa, Lauri; Saarimäki, Heini; Glerean, Enrico; Gotsopoulos, Athanasios; Jääskeläinen, Iiro P.; Hari, Riitta; Sams, Mikko

2014-01-01

Speech provides a powerful means for sharing emotions. Here we implement novel intersubject phase synchronization and whole-brain dynamic connectivity measures to show that networks of brain areas become synchronized across participants who are listening to emotional episodes in spoken narratives. Twenty participants' hemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI) while they listened to 45-s narratives describing unpleasant, neutral, and pleasant events spoken in neutral voice. After scanning, participants listened to the narratives again and rated continuously their feelings of pleasantness–unpleasantness (valence) and of arousal–calmness. Instantaneous intersubject phase synchronization (ISPS) measures were computed to derive both multi-subject voxel-wise similarity measures of hemodynamic activity and inter-area functional dynamic connectivity (seed-based phase synchronization, SBPS). Valence and arousal time series were subsequently used to predict the ISPS and SBPS time series. High arousal was associated with increased ISPS in the auditory cortices and in Broca's area, and negative valence was associated with enhanced ISPS in the thalamus, anterior cingulate, lateral prefrontal, and orbitofrontal cortices. Negative valence affected functional connectivity of fronto-parietal, limbic (insula, cingulum) and fronto-opercular circuitries, and positive arousal affected the connectivity of the striatum, amygdala, thalamus, cerebellum, and dorsal frontal cortex. Positive valence and negative arousal had markedly smaller effects. We propose that high arousal synchronizes the listeners' sound-processing and speech-comprehension networks, whereas negative valence synchronizes circuitries supporting emotional and self-referential processing. PMID:25128711

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

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

Dopamine homeostasis: brain functional connectivity in reward deficiency syndrome.

PubMed

Febo, Marcelo; Blum, Kenneth; Badgaiyan, Rajendra D; Baron, David; Thanos, Panayotis K; Colon-Perez, Luis M; Demortrovics, Zsolt; Gold, Mark S

2017-01-01

Reward deficiency syndrome (RDS) was first proposed by Kenneth Blum in 1995 to provide a clinically relevant and predictive term for conditions involving deficits in mesocorticolimbic dopamine function. Genetic, molecular, and neuronal alterations in key components of this circuitry contribute to a reward deficit state that can drive drug-seeking, consumption, and relapse. Among the dysfunctions observed in RDS are dysregulated resting state networks, which recently have been assessed in detail in chronic drug users by, positron emission tomography, functional magnetic resonance imaging, and functional connectivity analysis. A growing number of studies are helping to determine the putative roles of dopamine and glutamatergic neurotransmission in the regulation of activity in resting state networks, particularly in brain reward circuitry affected in drug use disorders. Indeed, we hypothesize in the present review that loss of homeostasis of these systems may lead to 'unbalanced' functional networks that might be both cause and outcome of disrupted synaptic communication between cortical and subcortical systems essential for controlling reward, emotional control, sensation seeking, and chronic drug use.

Local cerebral glucose metabolism in patients with long-term behavioral and cognitive deficits following mild traumatic brain injury.

PubMed

Gross, H; Kling, A; Henry, G; Herndon, C; Lavretsky, H

1996-01-01

A retrospective study of 20 patients with mild traumatic brain injury (MTBI) examined brain regions of interest by comparing [18F]-2-deoxyglucose PET, neuropsychological test results, and continuing behavioral dysfunction. Abnormal local cerebral metabolic rates (rLCMs) were most prominent in midtemporal, anterior cingulate, precuneus, anterior temporal, frontal white, and corpus callosum brain regions. Abnormal rLCMs were significantly correlated statistically with 1) overall clinical complaints, most specifically with inconsistent attention/concentration and 2) overall neuropsychological test results. The authors conclude that 1) even mild TBI may result in continuing brain behavioral deficits; 2) PET can help elucidate dysfunctional brain circuitry in neurobehavioral disorders; and 3) specific brain areas may correlate with deficits in daily neurobehavioral functioning and neuropsychological test findings.

The coevolution of innovation and technical intelligence in primates

PubMed Central

Street, Sally E.; Whalen, Andrew; Laland, Kevin N.

2016-01-01

In birds and primates, the frequency of behavioural innovation has been shown to covary with absolute and relative brain size, leading to the suggestion that large brains allow animals to innovate, and/or that selection for innovativeness, together with social learning, may have driven brain enlargement. We examined the relationship between primate brain size and both technical (i.e. tool using) and non-technical innovation, deploying a combination of phylogenetically informed regression and exploratory causal graph analyses. Regression analyses revealed that absolute and relative brain size correlated positively with technical innovation, and exhibited consistently weaker, but still positive, relationships with non-technical innovation. These findings mirror similar results in birds. Our exploratory causal graph analyses suggested that technical innovation shares strong direct relationships with brain size, body size, social learning rate and social group size, whereas non-technical innovation did not exhibit a direct relationship with brain size. Nonetheless, non-technical innovation was linked to brain size indirectly via diet and life-history variables. Our findings support ‘technical intelligence’ hypotheses in linking technical innovation to encephalization in the restricted set of primate lineages where technical innovation has been reported. Our findings also provide support for a broad co-evolving complex of brain, behaviour, life-history, social and dietary variables, providing secondary support for social and ecological intelligence hypotheses. The ability to gain access to difficult-to-extract, but potentially nutrient-rich, resources through tool use may have conferred on some primates adaptive advantages, leading to selection for brain circuitry that underlies technical proficiency. PMID:26926276

The coevolution of innovation and technical intelligence in primates.

PubMed

Navarrete, Ana F; Reader, Simon M; Street, Sally E; Whalen, Andrew; Laland, Kevin N

2016-03-19

In birds and primates, the frequency of behavioural innovation has been shown to covary with absolute and relative brain size, leading to the suggestion that large brains allow animals to innovate, and/or that selection for innovativeness, together with social learning, may have driven brain enlargement. We examined the relationship between primate brain size and both technical (i.e. tool using) and non-technical innovation, deploying a combination of phylogenetically informed regression and exploratory causal graph analyses. Regression analyses revealed that absolute and relative brain size correlated positively with technical innovation, and exhibited consistently weaker, but still positive, relationships with non-technical innovation. These findings mirror similar results in birds. Our exploratory causal graph analyses suggested that technical innovation shares strong direct relationships with brain size, body size, social learning rate and social group size, whereas non-technical innovation did not exhibit a direct relationship with brain size. Nonetheless, non-technical innovation was linked to brain size indirectly via diet and life-history variables. Our findings support 'technical intelligence' hypotheses in linking technical innovation to encephalization in the restricted set of primate lineages where technical innovation has been reported. Our findings also provide support for a broad co-evolving complex of brain, behaviour, life-history, social and dietary variables, providing secondary support for social and ecological intelligence hypotheses. The ability to gain access to difficult-to-extract, but potentially nutrient-rich, resources through tool use may have conferred on some primates adaptive advantages, leading to selection for brain circuitry that underlies technical proficiency. © 2016 The Author(s).

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.

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

Endogenous Opioid Peptides and Epilepsy: Quieting the Seizing Brain?

DTIC Science & Technology

1988-08-01

circuitry and highly sen- upon EEG findings could be tor, acid systems, remains sitive to epileptogenesis (see Refs misleading. to be l iated. The...Langwinski, R. (1986) Drug Alchoho! Depend. 18. 361-367: " Meldrum . B. S. et a. (1979) Brain Res. 170, 333-348; ’Sajorek, J. G. and Lomax, P. (1982... Acids . Peptides and Trophic Factors Engel, J., Jr, eds), pp. 263-274, Raven the outcome of which depends (Ferrendelli. J., Collins, R. and Johnson

Thalamocortical Dysfunction and Thalamic Injury after Asphyxial Cardiac Arrest in Developing Rats

PubMed Central

Shoykhet, Michael; Simons, Daniel J.; Alexander, Henry; Hosler, Christina; Kochanek, Patrick M.; Clark, Robert S. B.

2012-01-01

Global hypoxia-ischemia interrupts oxygen delivery and blood flow to the entire brain. Previous studies of global brain hypoxia ischemia have primarily focused on injury to the cerebral cortex and to the hippocampus. Susceptible neuronal populations also include inhibitory neurons in the thalamic Reticular Nucleus. We therefore investigated the impact of global brain hypoxia-ischemia on the thalamic circuit function in the somatosensory system of young rats. We used single neuron recordings and controlled whisker deflections to examine responses of thalamocortical neurons to sensory stimulation in rat survivors of 9 min of asphyxial cardiac arrest incurred on post-natal day 17. We found that 48–72 hours after cardiac arrest, thalamocortical neurons demonstrate significantly elevated firing rates both during spontaneous activity and in response to whisker deflections. The elevated evoked firing rates persist for at least 6–8 weeks after injury. Despite the overall increase in firing, by 6 weeks, thalamocortical neurons display degraded receptive fields, with decreased responses to adjacent whiskers. Nine min of asphyxial cardiac arrest was associated with extensive degeneration of neurites in the somatosensory nucleus as well as activation of microglia in the Reticular Nucleus. Global brain hypoxia-ischemia during cardiac arrest has a long-term impact on processing and transfer of sensory information by thalamic circuitry. Thalamic circuitry and normalization of its function may represent a distinct therapeutic target after cardiac arrest. PMID:22492052

Addiction and brain reward and antireward pathways.

PubMed

Gardner, Eliot L

2011-01-01

Addictive drugs have in common that they are voluntarily self-administered by laboratory animals (usually avidly), and that they enhance the functioning of the reward circuitry of the brain (producing the 'high' that the drug user seeks). The core reward circuitry consists of an 'in-series' circuit linking the ventral tegmental area, nucleus accumbens and ventral pallidum via the medial forebrain bundle. Although originally believed to simply encode the set point of hedonic tone, these circuits are now believed to be functionally far more complex, also encoding attention, expectancy of reward, disconfirmation of reward expectancy, and incentive motivation. 'Hedonic dysregulation' within these circuits may lead to addiction. The 'second-stage' dopaminergic component in this reward circuitry is the crucial addictive-drug-sensitive component. All addictive drugs have in common that they enhance (directly or indirectly or even transsynaptically) dop-aminergic reward synaptic function in the nucleus accumbens. Drug self-administration is regulated by nucleus accumbens dopamine levels, and is done to keep nucleus accumbens dopamine within a specific elevated range (to maintain a desired hedonic level). For some classes of addictive drugs (e.g. opiates), tolerance to the euphoric effects develops with chronic use. Postuse dysphoria then comes to dominate reward circuit hedonic tone, and addicts no longer use drugs to get high, but simply to get back to normal ('get straight'). The brain circuits mediating the pleasurable effects of addictive drugs are anatomically, neurophysiologically and neurochemically different from those mediating physical dependence, and from those mediating craving and relapse. There are important genetic variations in vulnerability to drug addiction, yet environmental factors such as stress and social defeat also alter brain-reward mechanisms in such a manner as to impart vulnerability to addiction. In short, the 'bio-psycho-social' model of etiology holds very well for addiction. Addiction appears to correlate with a hypodopaminergic dysfunctional state within the reward circuitry of the brain. Neuroimaging studies in humans add credence to this hypothesis. Credible evidence also implicates serotonergic, opioid, endocannabinoid, GABAergic and glutamatergic mechanisms in addiction. Critically, drug addiction progresses from occasional recreational use to impulsive use to habitual compulsive use. This correlates with a progression from reward-driven to habit-driven drug-seeking behavior. This behavioral progression correlates with a neuroanatomical progression from ventral striatal (nucleus accumbens) to dorsal striatal control over drug-seeking behavior. The three classical sets of craving and relapse triggers are (a) reexposure to addictive drugs, (b) stress, and (c) reexposure to environmental cues (people, places, things) previously associated with drug-taking behavior. Drug-triggered relapse involves the nucleus accumbens and the neurotransmitter dopamine. Stress-triggered relapse involves (a) the central nucleus of the amygdala, the bed nucleus of the stria terminalis, and the neurotransmitter corticotrophin-releasing factor, and (b) the lateral tegmental noradrenergic nuclei of the brain stem and the neurotransmitter norepinephrine. Cue-triggered relapse involves the basolateral nucleus of the amygdala, the hippocampus and the neurotransmitter glutamate. Knowledge of the neuroanatomy, neurophysiology, neurochemistry and neuropharmacology of addictive drug action in the brain is currently producing a variety of strategies for pharmacotherapeutic treatment of drug addiction, some of which appear promising. Copyright © 2011 S. Karger AG, Basel.

Special issue on the teenage brain: Sensitivity to social evaluation

PubMed Central

Somerville, Leah H.

2013-01-01

Relative to childhood, peer relationships take on a heightened importance during adolescence. Might adolescents be highly attuned to information that concerns when and how they are being evaluated, and what their peers think of them? This review evaluates how continuing brain development - which influences brain function - partially explains or reflects adolescents’ attunement to social evaluation. Though preliminary, evidence is mounting to suggest that while processing information relevant to social evaluation and the internal states of other people, adolescents respond with greater emotional intensity and corresponding nonlinear recruitment of socioaffective brain circuitry. This review highlights research findings that relate trajectories of brain development and social behavior, and discusses promising avenues of future research that will inform how brain development might lead adolescents sensitized to social evaluation. PMID:24761055

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

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.

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.

The Brain Reward Circuitry in Mood Disorders

PubMed Central

Russo, Scott J.; Nestler, Eric J.

2013-01-01

Mood disorders are common and debilitating conditions characterized in part by profound deficits in reward-related behavioral domains. A recent literature has identified important structural and functional alterations within the brain’s reward circuitry —particularly in the ventral tegmental area to nucleus accumbens pathway — that are associated with symptoms such as anhedonia and aberrant reward-associated perception and memory. This review synthesizes recent data from human and rodent studies from which emerges a circuit-level framework for understanding reward deficits in depression. We also discuss some of the molecular and cellular underpinnings of this framework, ranging from adaptations in glutamatergic synapses and neurotrophic factors to transcriptional and epigenetic mechanisms. PMID:23942470

Focusing on optic tectum circuitry through the lens of genetics.

PubMed

Nevin, Linda M; Robles, Estuardo; Baier, Herwig; Scott, Ethan K

2010-09-28

The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation by the vertebrate brain.

Effects of Early Serotonin Programming on Fear Response, Memory and Aggression

USDA-ARS?s Scientific Manuscript database

The neurotransmitter serotonin (5-HT) also acts as a neurogenic compound in the developing brain. Early administration of a 5-HT agonist could alter development of serotonergic circuitry, altering behaviors mediated by 5-HT signaling, including memory, fear and aggression. The present study was desi...

Effects of Postnatal Serotonin Agonism on Fear Response and Memory

USDA-ARS?s Scientific Manuscript database

The neurotransmitter serotonin (5-HT) also acts as a neurogenic compound in the developing brain. Early administration of a 5-HT agonist could alter the development of the serotonergic circuitry, altering behaviors mediated by 5-HT signaling, such as memory, fear and aggression. White leghorn chicks...

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…

The Relationship of Neurogenesis and Growth of Brain Regions to Song Learning

ERIC Educational Resources Information Center

Kirn, John R.

2010-01-01

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…

Effects of early serotonin programming on behavior and central monoamine concentrations in an avian model

USDA-ARS?s Scientific Manuscript database

Serotonin (5-HT) acts as a neurogenic compound in the developing brain; however serotonin altering drugs such as SSRIs are often prescribed to pregnant and lactating mothers. Early agonism of 5-HT receptors could alter the development of serotonergic circuitry, altering neurotransmission and behavio...

Examination of corticothalamic fiber projections in United States service members with mild traumatic brain injury

NASA Astrophysics Data System (ADS)

Rashid, Faisal M.; Dennis, Emily L.; Villalon-Reina, Julio E.; Jin, Yan; Lewis, Jeffrey D.; York, Gerald E.; Thompson, Paul M.; Tate, David F.

2017-11-01

Mild traumatic brain injury (mTBI) is characterized clinically by a closed head injury involving differential or rotational movement of the brain inside the skull. Over 3 million mTBIs occur annually in the United States alone. Many of the individuals who sustain an mTBI go on to recover fully, but around 20% experience persistent symptoms. These symptoms often last for many weeks to several months. The thalamus, a structure known to serve as a global networking or relay system for the rest of the brain, may play a critical role in neurorehabiliation and its integrity and connectivity after injury may also affect cognitive outcomes. To examine the thalamus, conventional tractography methods to map corticothalamic pathways with diffusion-weighted MRI (DWI) lead to sparse reconstructions that may contain false positive fibers that are anatomically inaccurate. Using a specialized method to zero in on corticothalamic pathways with greater robustness, we noninvasively examined corticothalamic fiber projections using DWI, in 68 service members. We found significantly lower fractional anisotropy (FA), a measure of white matter microstructural integrity, in pathways projecting to the left pre- and postcentral gyri - consistent with sensorimotor deficits often found post-mTBI. Mapping of neural circuitry in mTBI may help to further our understanding of mechanisms underlying recovery post-TBI.

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

A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

DTIC Science & Technology

2015-10-01

This project is focused on conducting the first randomized-controlled trial of Cognitive Enhancement Therapy (CET) in 54 verbal adults with autism ...of the neuroplastic effects of CET on brain function in support of cognitive enhancement in adult autism . Analyses of treatment effects to date...the need and potential for CET to be a significant treatment advance for verbal adults with autism . Importantly, improvements were found in daily life function and in brain circuitry supporting core abilities.

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.

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.

Fear learning and memory across adolescent development Hormones and Behavior Special Issue: Puberty and Adolescence

PubMed Central

Pattwell, Siobhan S.; Lee, Francis S.; Casey, B.J.

2013-01-01

Throughout the past several decades, studies have uncovered a wealth of information about the neural circuitry underlying fear learning and extinction that has helped to inform treatments for fear-related disorders such as post-traumatic stress and anxiety. Yet, up to 40 percent of people do not respond to such treatments. Adolescence, in particular, is a developmental stage during which anxiety disorders peak, yet little is known about the development of fear-related neural circuitry during this period. Moreover, pharmacological and behavioral therapies that have been developed are based on mature circuitry and function. Here, we review neural circuitry implicated in fear learning and data from adolescent mouse and human fear learning studies. In addition, we propose a developmental model of fear neural circuitry that may optimize current treatments and inform when, during development, specific treatments for anxiety may be most effective. PMID:23998679

Fear learning and memory across adolescent development: Hormones and Behavior Special Issue: Puberty and Adolescence.

PubMed

Pattwell, Siobhan S; Lee, Francis S; Casey, B J

2013-07-01

Throughout the past several decades, studies have uncovered a wealth of information about the neural circuitry underlying fear learning and extinction that has helped to inform treatments for fear-related disorders such as post-traumatic stress and anxiety. Yet, up to 40% of people do not respond to such treatments. Adolescence, in particular, is a developmental stage during which anxiety disorders peak, yet little is known about the development of fear-related neural circuitry during this period. Moreover, pharmacological and behavioral therapies that have been developed are based on mature circuitry and function. Here, we review neural circuitry implicated in fear learning and data from adolescent mouse and human fear learning studies. In addition, we propose a developmental model of fear neural circuitry that may optimize current treatments and inform when, during development, specific treatments for anxiety may be most effective. Copyright © 2013 Elsevier Inc. All rights reserved.

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 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.

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.

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.

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.

Altered metabolic activity in the developing brain of rats predisposed to high versus low depression-like behavior

PubMed Central

Melendez-Ferro, Miguel; Perez-Costas, Emma; Glover, Matthew E.; Jackson, Nateka L.; Stringfellow, Sara A.; Pugh, Phyllis C.; Fant, Andrew D.; Clinton, Sarah M.

2016-01-01

Individual differences in human temperament can increase risk for psychiatric disorders like depression and anxiety. Our laboratory utilized a rat model of temperamental differences to assess neurodevelopmental factors underlying emotional behavior differences. Rats selectively bred for low novelty exploration (Low Responders, LR) display high levels of anxiety- and depression-like behavior compared to High Novelty Responder (HR) rats. Using transcriptome profiling, the present study uncovered vast gene expression differences in the early postnatal HR versus LR limbic brain, including changes in genes involved in cellular metabolism. These data led us to hypothesize that rats prone to high (versus low) anxiety/depression-like behavior exhibit distinct patterns of brain metabolism during the first weeks of life, which may reflect disparate patterns of synaptogenesis and brain circuit development. Thus, in a second experiment we examined activity of Cytochrome C Oxidase (COX), an enzyme responsible for ATP production and a correlate of metabolic activity, to explore functional energetic differences in HR/LR early postnatal brain. We found that HR rats display higher COX activity in the amygdala and specific hippocampal subregions compared to LRs during the first 2 weeks of life. Correlational analysis examining COX levels across several brain regions and multiple early postnatal time points suggested desynchronization in the developmental timeline of the limbic HR versus LR brain during the first two postnatal weeks. These early divergent COX activity levels may reflect altered circuitry or synaptic activity in the early postnatal HR/LR brain, which could contribute to the emergence of their distinct behavioral phenotypes. PMID:26979051

A Role for Brain Stress Systems in Addiction

PubMed Central

Koob, George F.

2009-01-01

Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take drugs and has been linked to dysregulation of brain regions that mediate reward and stress. Activation of brain stress systems is hypothesized to be key to the negative emotional state produced by dependence that drives drug seeking through negative reinforcement mechanisms. This review explores the role of brain stress systems (corticotropin-releasing factor, norepinephrine, orexin [hypocretin], vasopressin, dynorphin) and brain antistress systems (neuropeptide Y, nociceptin [orphanin FQ]) in drug dependence, with emphasis on the neuropharmacological function of extrahypothalamic systems in the extended amygdala. The brain stress and antistress systems may play a key role in the transition to and maintenance of drug dependence once initiated. Understanding the role of brain stress and antistress systems in addiction provides novel targets for treatment and prevention of addiction and insights into the organization and function of basic brain emotional circuitry. PMID:18614026

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.

Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase in hippocampal circuitry is required for consolidation and reconsolidation of recognition memory.

PubMed

Kelly, Aine; Laroche, Serge; Davis, Sabrina

2003-06-15

Consolidation and reconsolidation of long-term memory have been shown to be dependent on the synthesis of new proteins, but the specific molecular mechanisms underlying these events remain to be elucidated. The mitogen-activated protein kinase (MAPK) pathway can trigger genomic responses in neurons, leading to changes in protein synthesis, and several studies have identified its pivotal role in synaptic plasticity and long-term memory formation. In this study, we analyze the involvement of this pathway in the consolidation and reconsolidation of long-term recognition memory, using an object recognition task. We show that inhibition of the MAPK pathway by intracerebroventricular injection of the MEK [MAPK/extracellular signal-regulated kinase (ERK)] inhibitor UO126 blocks consolidation of object recognition memory but does not affect short-term memory. Brain regions of the entorhinal cortex-hippocampal circuitry were analyzed for ERK activation, and it was shown that consolidation of recognition memory was associated with increased phosphorylation of ERK in the dentate gyrus and entorhinal cortex, although total expression of ERK was unchanged. We also report that inhibition of the MAPK pathway blocks reconsolidation of recognition memory, and this was shown to be dependent on reactivation of the memory trace by brief reexposure to the objects. In addition, reconsolidation of memory was associated with an increase in the phosphorylation of ERK in entorhinal cortex and CA1. In summary, our data show that the MAPK kinase pathway is required for both consolidation and reconsolidation of long-term recognition memory, and that this is associated with hyperphosphorylation of ERK in different subregions of the entorhinal cortex-hippocampal circuitry.

Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress.

PubMed

Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Cooper, Sarah; Gajewski, Paula; Eagle, Andrew; Mazei-Robison, Michelle; Nestler, Eric J; Robison, A J

2015-12-01

Major depressive disorder is thought to arise in part from dysfunction of the brain's "reward circuitry", consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression--the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus--in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 h following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of early communicative behavior in mouse models of Neurofibromatosis type 1

PubMed Central

Maloney, Susan E.; Chandler, Krystal C.; Anastasaki, Corina; Rieger, Michael A.; Gutmann, David H.; Dougherty, Joseph D.

2017-01-01

Scientific Abstract Neurofibromatosis type 1 (NF1) is a monogenic neurodevelopmental disease caused by germline loss-of-function mutations in the NF1 tumor suppressor gene. Cognitive impairments are observed in approximately 80% of children with this disease, with 45–60% exhibiting autism spectrum disorder (ASD) symptomatology. In light of the high comorbidity rate between ASD and NF1, we assessed early communicative behavior by maternal-separation induced pup ultrasonic vocalizations (USV) and developmental milestones in two distinct Nf1 genetically-engineered models, one modeling clinical germline heterozygous loss of Nf1 function (Nf1+/− mice), and a second with somatic biallelic Nf1 inactivation in neuroglial progenitor cells (Nf1GFAPCKO mice). We observed altered USV production in both models: Nf1+/− mice exhibited both increased USVs across development and alterations in aspects of pitch, while Nf1GFAPCKO mice demonstrated a decrease in USVs. Developmental milestones, such as weight, pinnae detachment and eye opening, were not disrupted in either model, indicating the USV deficits were not due to gross developmental delay, and likely reflected more specific alterations in USV circuitry. In this respect, increased whole-brain serotonin was observed in Nf1+/− mice, but whole-brain levels of dopamine and its metabolites were unchanged at the age of peak USV disruption, and USV alterations did not correlate with overall level of neurofibromin loss. The early communicative phenotypes reported herein should motivate further studies into the risks mediated by haploinsufficiency and biallelic deletion of Nf1 across a full battery of ASD-relevant behavioral phenotypes, and a targeted analysis of underlying circuitry disruptions. PMID:28842941

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

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.

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.

Centromedian-parafascicular deep brain stimulation induces differential functional inhibition of the motor, associative, and limbic circuits in large animals.

PubMed

Kim, Joo Pyung; Min, Hoon-Ki; Knight, Emily J; Duffy, Penelope S; Abulseoud, Osama A; Marsh, Michael P; Kelsey, Katherine; Blaha, Charles D; Bennet, Kevin E; Frye, Mark A; Lee, Kendall H

2013-12-15

Deep brain stimulation (DBS) of the centromedian-parafascicular (CM-Pf) thalamic nuclei has been considered an option for treating Tourette syndrome. Using a large animal DBS model, this study was designed to explore the network effects of CM-Pf DBS. The combination of DBS and functional magnetic resonance imaging is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. With a within-subjects design, we tested the proportional effects of CM and Pf DBS by manipulating current spread and varying stimulation contacts in healthy pigs (n = 5). Our results suggests that CM-Pf DBS has an inhibitory modulating effect in areas that have been suggested as contributing to impaired sensory-motor and emotional processing. The results also help to define the differential neural circuitry effects of the CM and Pf with evidence of prominent sensorimotor/associative effects for CM DBS and prominent limbic/associative effects for Pf DBS. Our results support the notion that stimulation of deep brain structures, such as the CM-Pf, modulates multiple networks with cortical effects. The networks affected by CM-Pf stimulation in this study reinforce the conceptualization of Tourette syndrome as a condition with psychiatric and motor symptoms and of CM-Pf DBS as a potentially effective tool for treating both types of symptoms. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Chronic wheel running affects cocaine-induced c-Fos expression in brain reward areas in rats.

PubMed

Zlebnik, Natalie E; Hedges, Valerie L; Carroll, Marilyn E; Meisel, Robert L

2014-03-15

Emerging evidence from human and animal studies suggests that exercise is a highly effective treatment for drug addiction. However, most work has been done in behavioral models, and the effects of exercise on the neurobiological substrates of addiction have not been identified. Specifically, it is unknown whether prior exercise exposure alters neuronal activation of brain reward circuitry in response to drugs of abuse. To investigate this hypothesis, rats were given 21 days of daily access to voluntary wheel running in a locked or unlocked running wheel. Subsequently, they were challenged with a saline or cocaine (15 mg/kg, i.p.) injection and sacrificed for c-Fos immunohistochemistry. The c-Fos transcription factor is a measure of cellular activity and was used to quantify cocaine-induced activation of reward-processing areas of the brain: nucleus accumbens (NAc), caudate putamen (CPu), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). The mean fold change in cocaine-induced c-Fos cell counts relative to saline-induced c-Fos cell counts was significantly higher in exercising compared to control rats in the NAc core, dorsomedial and dorsolateral CPu, the prelimbic area, and the OFC, indicating differential cocaine-specific cellular activation of brain reward circuitry between exercising and control animals. These results suggest neurobiological mechanisms by which voluntary wheel running attenuates cocaine-motivated behaviors and provide support for exercise as a novel treatment for drug addiction. Copyright © 2013 Elsevier B.V. All rights reserved.

Research Review: A Neuroscience Framework for Pediatric Anxiety Disorders

ERIC Educational Resources Information Center

Pine, Daniel S.

2007-01-01

Across a range of mammalian species, early developmental variations in fear-related behaviors constrain patterns of anxious behavior throughout life. Individual differences in anxiety among rodents and non-human primates have been shown to reflect early-life influences of genes and the environment on brain circuitry. However, in humans, the manner…

The Effects of Seizures on the Connectivity and Circuitry of the Developing Brain

ERIC Educational Resources Information Center

Swann, John W.

2004-01-01

Recurring seizures in infants and children are often associated with cognitive deficits, but the reason for the learning difficulties is unclear. Recent studies in several animal models suggest that seizures themselves may contribute in important ways to these deficits. Other studies in animals have shown that recurring seizures result in…

Introduction: Addiction and Brain Reward and Anti-Reward Pathways

PubMed Central

Gardner, Eliot L.

2013-01-01

Addictive drugs have in common that they are voluntarily self-administered by laboratory animals (usually avidly) and that they enhance the functioning of the reward circuitry of the brain (producing the “high” that the drug-user seeks). The core reward circuitry consists of an “in series” circuit linking the ventral tegmental area, nucleus accumbens, and ventral pallidum - via the medial forebrain bundle. Although originally believed to encode simply the set-point of hedonic tone, these circuits are now believed to be functionally far more complex - also encoding attention, expectancy of reward, disconfirmation of reward expectancy, and incentive motivation. “Hedonic dysregulation” within these circuits may lead to addiction. The “second-stage” dopaminergic component in this reward circuitry is the crucial addictive-drug-sensitive component. All addictive drugs have in common that they enhance (directly or indirectly or even transsynaptically) dopaminergic reward synaptic function in the nucleus accumbens. Drug self-administration is regulated by nucleus accumbens dopamine levels, and is done to keep nucleus accumbens dopamine within a specific elevated range (to maintain a desired hedonic level). For some classes of addictive drugs (e.g., opiates), tolerance to the euphoric effects develops with chronic use. Post-use dysphoria then comes to dominate reward circuit hedonic tone, and addicts no longer use drugs to get “high,” but simply to get back to normal (“get straight”). The brain circuits mediating the pleasurable effects of addictive drugs are anatomically, neurophysiologically, and neurochemically different from those mediating physical dependence, and from those mediating craving and relapse. There are important genetic variations in vulnerability to drug addiction, yet environmental factors such as stress and social defeat also alter brain-reward mechanisms in such a manner as to impart vulnerability to addiction. In short, the “bio-psycho-social” model of etiology holds very well for addiction. Addiction appears to correlate with a hypo-dopaminergic dysfunctional state within the reward circuitry of the brain. Neuroimaging studies in humans add credence to this hypothesis. Credible evidence also implicates serotonergic, opioid, endocannabinoid, GABAergic, and glutamatergic mechanisms in addiction. Critically, drug addiction progresses from occasional recreational use to impulsive use to habitual compulsive use. This correlates with a progression from reward-driven to habit-driven drug-seeking behavior. This behavioral progression correlates with a neuroanatomical progression from ventral striatal (nucleus accumbens) to dorsal striatal control over drug-seeking behavior. The three classical sets of craving and relapse triggers are a) re-exposure to addictive drugs, b) stress, and c) re-exposure to environmental cues (“people, places, things”) previously associated with drug-taking behavior. Drug-triggered relapse involves the nucleus accumbens and the neurotransmitter dopamine. Stress-triggered relapse involves a) the central nucleus of the amygdala, the bed nucleus of the stria terminalis, and the neurotransmitter CRF; and b) the lateral tegmental noradrenergic nuclei of the brain stem and the neurotransmitter norepinephrine. Cue-triggered relapse involves the basolateral nucleus of the amygdala, the hippocampus, and the neurotransmitter glutamate. Knowledge of the neuroanatomy, neurophysiology, neurochemistry, and neuropharmacology of addictive drug action in the brain is currently producing a variety of strategies for pharmacotherapeutic treatment of drug addiction, some of which appear promising. PMID:21508625

Social Support Modulates Stress-Related Gene Expression in Various Brain Regions of Piglets.

PubMed

Kanitz, Ellen; Hameister, Theresa; Tuchscherer, Armin; Tuchscherer, Margret; Puppe, Birger

2016-01-01

The presence of an affiliative conspecific may alleviate an individual's stress response in threatening conditions. However, the mechanisms and neural circuitry underlying the process of social buffering have not yet been elucidated. Using the domestic pig as an animal model, we examined the effect of a 4-h maternal and littermate deprivation on stress hormones and on mRNA expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11ß-hydroxysteroid dehydrogenase (11ß-HSD) types 1 and 2 and the immediate early gene c-fos in various brain regions of 7-, 21- and 35-day old piglets. The deprivation occurred either alone or with a familiar or unfamiliar age-matched piglet. Compared to piglets deprived alone, the presence of a conspecific animal significantly reduced free plasma cortisol concentrations and altered the MR/GR balance and 11ß-HSD2 and c-fos mRNA expression in the prefrontal cortex (PFC), amygdala and hypothalamus, but not in the hippocampus. The alterations in brain mRNA expression were particularly found in 21- or 35-day old piglets, which may reflect the species-specific postnatal ontogeny of the investigated brain regions. The buffering effects of social support were most pronounced in the amygdala, indicating its significance both for the assessment of social conspecifics as biologically relevant stimuli and for the processing of emotional states. In conclusion, the present findings provide further evidence for the importance of the cortico-limbic network underlying the abilities of individuals to cope with social stress and strongly emphasize the benefits of social partners in livestock with respect to positive welfare and health.

The Impact of Reading Intervention on Brain Responses Underlying Language in Children With Autism.

PubMed

Murdaugh, Donna L; Deshpande, Hrishikesh D; Kana, Rajesh K

2016-01-01

Deficits in language comprehension have been widely reported in children with autism spectrum disorders (ASD), with behavioral and neuroimaging studies finding increased reliance on visuospatial processing to aid in language comprehension. However, no study to date, has taken advantage of this strength in visuospatial processing to improve language comprehension difficulties in ASD. This study used a translational neuroimaging approach to test the role of a visual imagery-based reading intervention in improving the brain circuitry underlying language processing in children with ASD. Functional magnetic resonance imaging (MRI), in a longitudinal study design, was used to investigate intervention-related change in sentence comprehension, brain activation, and functional connectivity in three groups of participants (age 8-13 years): an experimental group of ASD children (ASD-EXP), a wait-list control group of ASD children (ASD-WLC), and a group of typically developing control children. After intervention, the ASD-EXP group showed significant increase in activity in visual and language areas and right-hemisphere language area homologues, putamen, and thalamus, suggestive of compensatory routes to increase proficiency in reading comprehension. Additionally, ASD children who had the most improvement in reading comprehension after intervention showed greater functional connectivity between left-hemisphere language areas, the middle temporal gyrus and inferior frontal gyrus while reading high imagery sentences. Thus, the findings of this study, which support the principles of dual coding theory [Paivio 2007], suggest the potential of a strength-based reading intervention in changing brain responses and facilitating better reading comprehension in ASD children. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Changes in intrinsic local connectivity after reading intervention in children with autism.

PubMed

Maximo, Jose O; Murdaugh, Donna L; O'Kelley, Sarah; Kana, Rajesh K

2017-12-01

Most of the existing behavioral and cognitive intervention programs in autism spectrum disorders (ASD) have not been tested at the neurobiological level, thus falling short of finding quantifiable neurobiological changes underlying behavioral improvement. The current study takes a translational neuroimaging approach to test the impact of a structured visual imagery-based reading intervention on improving reading comprehension and assessing its underlying local neural circuitry. Behavioral and resting state functional MRI (rs-fMRI) data were collected from children with ASD who were randomly assigned to an Experimental group (ASD-EXP; n=14) and a Wait-list control group (ASD-WLC; n=14). Participants went through an established reading intervention training program (Visualizing and Verbalizing for language comprehension and thinking or V/V; 4-h per day, 10-weeks, 200h of face-to-face instruction). Local functional connectivity was examined using a connection density approach from graph theory focusing on brain areas considered part of the Reading Network. The main results are as follows: (I) the ASD-EXP group showed significant improvement, compared to the ASD-WLC group, in their reading comprehension ability evidenced from change in comprehension scores; (II) the ASD-EXP group showed increased local brain connectivity in Reading Network regions compared to the ASD-WLC group post-intervention; (III) intervention-related changes in local brain connectivity were observed in the ASD-EXP from pre to post-intervention; and (IV) improvement in language comprehension significantly predicted changes in local connectivity. The findings of this study provide novel insights into brain plasticity in children with developmental disorders using targeted intervention programs. Published by Elsevier Inc.

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…

Listening to humans walking together activates the social brain circuitry.

PubMed

Saarela, Miiamaaria V; Hari, Riitta

2008-01-01

Human footsteps carry a vast amount of social information, which is often unconsciously noted. Using functional magnetic resonance imaging, we analyzed brain networks activated by footstep sounds of one or two persons walking. Listening to two persons walking together activated brain areas previously associated with affective states and social interaction, such as the subcallosal gyrus bilaterally, the right temporal pole, and the right amygdala. These areas seem to be involved in the analysis of persons' identity and complex social stimuli on the basis of auditory cues. Single footsteps activated only the biological motion area in the posterior STS region. Thus, hearing two persons walking together involved a more widespread brain network than did hearing footsteps from a single person.

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.

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

Fully Passive Wireless Acquisition of Neuropotentials

NASA Astrophysics Data System (ADS)

Schwerdt, Helen N.

The ability to monitor electrophysiological signals from the sentient brain is requisite to decipher its enormously complex workings and initiate remedial solutions for the vast amount of neurologically-based disorders. Despite immense advancements in creating a variety of instruments to record signals from the brain, the translation of such neurorecording instrumentation to real clinical domains places heavy demands on their safety and reliability, both of which are not entirely portrayed by presently existing implantable recording solutions. In an attempt to lower these barriers, alternative wireless radar backscattering techniques are proposed to render the technical burdens of the implant chip to entirely passive neurorecording processes that transpire in the absence of formal integrated power sources or powering schemes along with any active circuitry. These radar-like wireless backscattering mechanisms are used to conceive of fully passive neurorecording operations of an implantable microsystem. The fully passive device potentially manifests inherent advantages over current wireless implantable and wired recording systems: negligible heat dissipation to reduce risks of brain tissue damage and minimal circuitry for long term reliability as a chronic implant. Fully passive neurorecording operations are realized via intrinsic nonlinear mixing properties of the varactor diode. These mixing and recording operations are directly activated by wirelessly interrogating the fully passive device with a microwave carrier signal. This fundamental carrier signal, acquired by the implant antenna, mixes through the varactor diode along with the internal targeted neuropotential brain signals to produce higher frequency harmonics containing the targeted neuropotential signals. These harmonics are backscattered wirelessly to the external interrogator that retrieves and recovers the original neuropotential brain signal. The passive approach removes the need for internal power sources and may alleviate heat trauma and reliability issues that limit practical implementation of existing implantable neurorecorders.

Stress, trauma and PTSD: translational insights into the core synaptic circuitry and its modulation.

PubMed

Bennett, Maxwell R; Hatton, Sean N; Lagopoulos, Jim

2016-06-01

Evidence is considered as to whether behavioral criteria for diagnosis of post-traumatic stress disorder (PTSD) are applicable to that of traumatized animals and whether the phenomena of acquisition, extinction and reactivation of fear behavior in animals are also successfully applicable to humans. This evidence suggests an affirmative answer in both cases. Furthermore, the deficits in gray matter found in PTSD, determined with magnetic resonance imaging, are also observed in traumatized animals, lending neuropsychological support to the use of animals to probe what has gone awry in PTSD. Such animal experiments indicate that the core synaptic circuitry mediating behavior following trauma consists of the amygdala, ventral-medial prefrontal cortex and hippocampus, all of which are modulated by the basal ganglia. It is not clear if this is the case in PTSD as the observations using fMRI are equivocal and open to technical objections. Nevertheless, the effects of the basal ganglia in controlling glutamatergic synaptic transmission through dopaminergic and serotonergic synaptic mechanisms in the core synaptic circuitry provides a ready explanation for why modifying these mechanisms delays extinction in animal models and predisposes towards PTSD. In addition, changes of brain-derived neurotrophic factor (BDNF) in the core synaptic circuitry have significant effects on acquisition and extinction in animal experiments with single nucleotide polymorphisms in the BDNF gene predisposing to PTSD.

Perceptual alternation in obsessive compulsive disorder--implications for a role of the cortico-striatal circuitry in mediating awareness.

PubMed

Li, C S; Chen, M C; Yang, Y Y; Chang, H L; Liu, C Y; Shen, S; Chen, C Y

2000-06-15

Mounting evidence suggests that obsessive compulsive disorder (OCD) results from functional aberrations of the fronto-striatal circuitry. However, empirical studies of the behavioral manifestations of OCD have been relatively lacking. The present study employs a behavioral task that allows a quantitative measure of how alternative percepts are formed from one moment to another, a process mimicking the brain state in which different thoughts and imageries compete for access to awareness. Eighteen patients with OCD, 12 with generalized anxiety disorder, and 18 normal subjects participated in the experiment, in which they viewed one of the three Schröder staircases and responded by pressing a key to each perceptual reversal. The results demonstrate that the patients with OCD have a higher perceptual alternation rate than the normal controls. Moreover, the frequency of perceptual alternation is significantly correlated with the Yale-Brown obsessive compulsive and the Hamilton anxiety scores. The increase in the frequency of perceptual reversals cannot easily be accounted for by learning or by different patterns of eye fixations on the task. These results provide further evidence that an impairment of the inhibitory function of the cortico-striatal circuitry might underlie the etiology of OCD. The implications of the results for a general role of the cortico-striatal circuitry in mediating awareness are discussed.

Rewiring the connectome: Evidence and effects.

PubMed

Bennett, Sophie H; Kirby, Alastair J; Finnerty, Gerald T

2018-05-01

Neuronal connections form the physical basis for communication in the brain. Recently, there has been much interest in mapping the "connectome" to understand how brain structure gives rise to brain function, and ultimately, to behaviour. These attempts to map the connectome have largely assumed that connections are stable once formed. Recent studies, however, indicate that connections in mammalian brains may undergo rewiring during learning and experience-dependent plasticity. This suggests that the connectome is more dynamic than previously thought. To what extent can neural circuitry be rewired in the healthy adult brain? The connectome has been subdivided into multiple levels of scale, from synapses and microcircuits through to long-range tracts. Here, we examine the evidence for rewiring at each level. We then consider the role played by rewiring during learning. We conclude that harnessing rewiring offers new avenues to treat brain diseases. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Anxiety and nicotine dependence: Emerging role of the habenulo-interpeduncular axis

PubMed Central

Molas, Susanna; DeGroot, Steven; Zhao-Shea, Rubing; Tapper, Andrew R.

2016-01-01

While innovative modern neuroscience approaches have aided in discerning brain circuitry underlying negative emotional behaviors including fear and anxiety responses, how these circuits are recruited in normal and pathological conditions remains poorly understood. Recently, genetic tools that selectively manipulate single neuronal populations have uncovered an understudied circuit, the medial habenula (mHb)-interpeduncular (IPN) axis, that modulates basal negative emotional responses. Interestingly, the mHb-IPN pathway also represents an essential circuit that signals heightened anxiety induced by nicotine withdrawal. Insights into how this circuit inter-connects with regions more classically associated with anxiety and how chronic nicotine exposure induces neuroadaptations resulting in an anxiogenic state, may thereby provide novel strategies and molecular targets for therapies that facilitate smoking cessation, as well as, anxiety relief. PMID:27890353

Targeting circuits of sexual desire as a treatment strategy for hypoactive sexual desire disorder.

PubMed

Stahl, Stephen M

2010-07-01

Hypoactive sexual desire disorder (HSDD) is hypothesized to be a disorder of the brain's reward circuitry. Neurotransmitters in reward circuits are thus therapeutic targets for improving sexual desire. Novel treatment strategies are to enhance dopamine (DA) actions, reduce serotonin (5-HT) actions, or both. (c) Copyright 2010 Physicians Postgraduate Press, Inc.

Dopaminergic and Cholinergic Modulations of Visual-Spatial Attention and Working Memory: Insights from Molecular Genetic Research and Implications for Adult Cognitive Development

ERIC Educational Resources Information Center

Stormer, Viola S.; Passow, Susanne; Biesenack, Julia; Li, Shu-Chen

2012-01-01

Attention and working memory are fundamental for selecting and maintaining behaviorally relevant information. Not only do both processes closely intertwine at the cognitive level, but they implicate similar functional brain circuitries, namely the frontoparietal and the frontostriatal networks, which are innervated by cholinergic and dopaminergic…

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…

Knowledge Representation and Data Mining of Neuronal Morphologies Using Neuroinformatics Tools and Formal Ontologies

ERIC Educational Resources Information Center

Polavaram, Sridevi

2016-01-01

Neuroscience can greatly benefit from using novel methods in computer science and informatics, which enable knowledge discovery in unexpected ways. Currently one of the biggest challenges in Neuroscience is to map the functional circuitry of the brain. The applications of this goal range from understanding structural reorganization of neurons to…

Neurogenesis in the aging brain.

PubMed

Apple, Deana M; Solano-Fonseca, Rene; Kokovay, Erzsebet

2017-10-01

Adult neurogenesis is the process of producing new neurons from neural stem cells (NSCs) for integration into the brain circuitry. Neurogenesis occurs throughout life in the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. However, during aging, NSCs and their progenitors exhibit reduced proliferation and neuron production, which is thought to contribute to age-related cognitive impairment and reduced plasticity that is necessary for some types of brain repair. In this review, we describe NSCs and their niches during tissue homeostasis and how they undergo age-associated remodeling and dysfunction. We also discuss some of the functional ramifications in the brain from NSC aging. Finally, we discuss some recent insights from interventions in NSC aging that could eventually translate into therapies for healthy brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Food-induced brain responses and eating behaviour.

PubMed

Smeets, Paul A M; Charbonnier, Lisette; van Meer, Floor; van der Laan, Laura N; Spetter, Maartje S

2012-11-01

The brain governs food intake behaviour by integrating many different internal and external state and trait-related signals. Understanding how the decisions to start and to stop eating are made is crucial to our understanding of (maladaptive patterns of) eating behaviour. Here, we aim to (1) review the current state of the field of 'nutritional neuroscience' with a focus on the interplay between food-induced brain responses and eating behaviour and (2) highlight research needs and techniques that could be used to address these. The brain responses associated with sensory stimulation (sight, olfaction and taste), gastric distension, gut hormone administration and food consumption are the subject of increasing investigation. Nevertheless, only few studies have examined relations between brain responses and eating behaviour. However, the neural circuits underlying eating behaviour are to a large extent generic, including reward, self-control, learning and decision-making circuitry. These limbic and prefrontal circuits interact with the hypothalamus, a key homeostatic area. Target areas for further elucidating the regulation of food intake are: (eating) habit and food preference formation and modification, the neural correlates of self-control, nutrient sensing and dietary learning, and the regulation of body adiposity. Moreover, to foster significant progress, data from multiple studies need to be integrated. This requires standardisation of (neuroimaging) measures, data sharing and the application and development of existing advanced analysis and modelling techniques to nutritional neuroscience data. In the next 20 years, nutritional neuroscience will have to prove its potential for providing insights that can be used to tackle detrimental eating behaviour.

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

Dual roles of dopamine in food- and drug-seeking: the drive-reward paradox

PubMed Central

Wise, Roy A.

2012-01-01

The question of whether (or to what degree) obesity reflects addiction to high energy foods often narrows to the question of whether the overeating of these foods causes the same long-term neuroadaptations as are identified with the late stages of addiction. Of equal or perhaps greater interest is the question of whether common brain mechanisms mediate the acquisition and development of eating and drug-taking habits. The earliest evidence on this question is rooted in early studies of brain stimulation reward. Lateral hypothalamic electrical stimulation can be reinforcing in some conditions and can motivate feeding in others. That stimulation of the same brain region should be both reinforcing and drive-inducing is paradoxical; why should an animal work to induce a drive-like state such as hunger? This is known as the “drive-reward paradox.” Insights into the substrates of the drive-reward paradox suggest an answer to the controversial question of whether the dopamine system—a system “downstream” from the stimulated fibers of the lateral hypothalamus—is more critically involved in “wanting” or in “liking” of various rewards including food and addictive drugs. That the same brain circuitry is implicated in the motivation for and the reinforcement by both food and addictive drugs extends the argument for a common mechanism underlying compulsive overeating and compulsive drug-taking. PMID:23044182

Oligodendrocytes as Regulators of Neuronal Networks during Early Postnatal Development

PubMed Central

Ramos, Maria; Ikrar, Taruna; Kinoshita, Chisato; De Mei, Claudia; Tirotta, Emanuele; Xu, Xiangmin; Borrelli, Emiliana

2011-01-01

Oligodendrocytes are the glial cells responsible for myelin formation. Myelination occurs during the first postnatal weeks and, in rodents, is completed during the third week after birth. Myelin ensures the fast conduction of the nerve impulse; in the adult, myelin proteins have an inhibitory role on axon growth and regeneration after injury. During brain development, oligodendrocytes precursors originating in multiple locations along the antero-posterior axis actively proliferate and migrate to colonize the whole brain. Whether the initial interactions between oligodendrocytes and neurons might play a functional role before the onset of myelination is still not completely elucidated. In this article, we addressed this question by transgenically targeted ablation of proliferating oligodendrocytes during cerebellum development. Interestingly, we show that depletion of oligodendrocytes at postnatal day 1 (P1) profoundly affects the establishment of cerebellar circuitries. We observed an impressive deregulation in the expression of molecules involved in axon growth, guidance and synaptic plasticity. These effects were accompanied by an outstanding increase of neurofilament staining observed 4 hours after the beginning of the ablation protocol, likely dependent from sprouting of cerebellar fibers. Oligodendrocyte ablation modifies localization and function of ionotropic glutamate receptors in Purkinje neurons. These results show a novel oligodendrocyte function expressed during early postnatal brain development, where these cells participate in the formation of cerebellar circuitries, and influence its development. PMID:21589880

The neural circuitry of visual artistic production and appreciation: A proposition.

PubMed

Chakravarty, Ambar

2012-04-01

The nondominant inferior parietal lobule is probably a major "store house" of artistic creativity. The ventromedial prefrontal lobe (VMPFL) is supposed to be involved in creative cognition and the dorsolateral prefrontal lobe (DLPFL) in creative output. The conceptual ventral and dorsal visual system pathways likely represent the inferior and superior longitudinal fasciculi. During artistic production, conceptualization is conceived in the VMPFL and the executive part is operated through the DLFPL. The latter transfers the concept to the visual brain through the superior longitudinal fasciculus (SLF), relaying on its path to the parietal cortex. The conceptualization at VMPFL is influenced by activity from the anterior temporal lobe through the uncinate fasciculus and limbic system pathways. The final visual image formed in the visual brain is subsequently transferred back to the DLPFL through the SLF and then handed over to the motor cortex for execution. During art appreciation, the image at the visual brain is transferred to the frontal lobe through the SLF and there it is matched with emotional and memory inputs from the anterior temporal lobe transmitted through the uncinate fasiculus. Beauty is perceived at the VMPFL and transferred through the uncinate fasciculus to the hippocampo-amygdaloid complex in the anterior temporal lobe. The limbic system (Papez circuit) is activated and emotion of appreciation is evoked. It is postulated that in practice the entire circuitry is activated simultaneously.

Have we been ignoring the elephant in the room? Seven arguments for considering the cerebellum as part of addiction circuitry.

PubMed

Miquel, Marta; Vazquez-Sanroman, Dolores; Carbo-Gas, María; Gil-Miravet, Isis; Sanchis-Segura, Carla; Carulli, Daniela; Manzo, Jorge; Coria-Avila, Genaro A

2016-01-01

Addiction involves alterations in multiple brain regions that are associated with functions such as memory, motivation and executive control. Indeed, it is now well accepted that addictive drugs produce long-lasting molecular and structural plasticity changes in corticostriatal-limbic loops. However, there are brain regions that might be relevant to addiction other than the prefrontal cortex, amygdala, hippocampus and basal ganglia. In addition to these circuits, a growing amount of data suggests the involvement of the cerebellum in many of the brain functions affected in addicts, though this region has been overlooked, traditionally, in the addiction field. Therefore, in the present review we provide seven arguments as to why we should consider the cerebellum in drug addiction. We present and discuss compelling evidence about the effects of drugs of abuse on cerebellar plasticity, the involvement of the cerebellum in drug-induced cue-related memories, and several findings showing that the instrumental memory and executive functions also recruit the cerebellar circuitry. In addition, a hypothetical model of the cerebellum's role relative to other areas within corticostriatal-limbic networks is also provided. Our goal is not to review animal and human studies exhaustively but to support the inclusion of cerebellar alterations as a part of the physiopathology of addiction disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

The neural circuitry of visual artistic production and appreciation: A proposition

PubMed Central

Chakravarty, Ambar

2012-01-01

The nondominant inferior parietal lobule is probably a major “store house” of artistic creativity. The ventromedial prefrontal lobe (VMPFL) is supposed to be involved in creative cognition and the dorsolateral prefrontal lobe (DLPFL) in creative output. The conceptual ventral and dorsal visual system pathways likely represent the inferior and superior longitudinal fasciculi. During artistic production, conceptualization is conceived in the VMPFL and the executive part is operated through the DLFPL. The latter transfers the concept to the visual brain through the superior longitudinal fasciculus (SLF), relaying on its path to the parietal cortex. The conceptualization at VMPFL is influenced by activity from the anterior temporal lobe through the uncinate fasciculus and limbic system pathways. The final visual image formed in the visual brain is subsequently transferred back to the DLPFL through the SLF and then handed over to the motor cortex for execution. During art appreciation, the image at the visual brain is transferred to the frontal lobe through the SLF and there it is matched with emotional and memory inputs from the anterior temporal lobe transmitted through the uncinate fasiculus. Beauty is perceived at the VMPFL and transferred through the uncinate fasciculus to the hippocampo–amygdaloid complex in the anterior temporal lobe. The limbic system (Papez circuit) is activated and emotion of appreciation is evoked. It is postulated that in practice the entire circuitry is activated simultaneously. PMID:22566716

Central control of visceral pain and urinary tract function.

PubMed

Lovick, Thelma A

2016-10-01

Afferent input from Aδ and C-fibres innervating the urinary bladder are processed differently by the brain, and have different roles in signaling bladder sensation. Aδ fibres that signal bladder filling activate a spino-bulbo-spinal loop, which relays in the midbrain periaqueductal grey (PAG) and pontine micturition centre (PMC). The excitability of this circuitry is regulated by tonic GABAergic inhibitory processes. In humans and socialised animals micturition is normally under volitional control and influenced by a host of psychosocial factors. Higher nervous decision-making in a social context to 'go now' or 'do not go' probably resides in frontal cortical areas, which act as a central control switch for micturition. Exposure to psychosocial stress can have profoundly disruptive influence on the process and lead to maladaptive changes in the bladder. During sleeping the voiding reflex threshold appears to be reset to a higher level to promote urinary continence. Under physiological conditions C-fibre bladder afferents are normally silent but are activated in inflammatory bladder states and by intense distending pressure. Following prolonged stimulation visceral nociceptors sensitise, leading to a lowered threshold and heightened sensitivity. In addition, sensitization may occur within the central pain processing circuitry, which outlasts the original nociceptive insult. Visceral nociception may also be influenced by genetic and environmental influences. A period of chronic stress can produce increased sensitivity to visceral pain that lasts for months. Adverse early life events can produce even longer lasting epigenetic changes, which increase the individual's susceptibility to developing visceral pain states in adulthood. Copyright © 2016 Elsevier B.V. All rights reserved.

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

The contribution of brain reward circuits to the obesity epidemic

PubMed Central

Stice, Eric; Figlewicz, Dianne P.; Gosnell, Blake A.; Levine, Allen S.; Pratt, Wayne E.

2012-01-01

One of the defining characteristics of the research of Ann E. Kelley was her recognition that the neuroscience underlying basic learning and motivation processes also shed significant light upon mechanisms underlying drug addiction and maladaptive eating patterns. In this review, we examine the parallels that exist in the neural pathways that process both food and drug reward, as determined by recent studies in animal models and human neuroimaging experiments. We discuss contemporary research that suggests that hyperphagia leading to obesity is associated with substantial neurochemical changes in the brain. These findings verify the relevance of reward pathways for promoting consumption of palatable, calorically dense foods, and lead to the important question of whether changes in reward circuitry in response to intake of such foods serve a causal role in the development and maintenance of some cases of obesity. Finally, we discuss the potential value for future studies at the intersection of the obesity epidemic and the neuroscience of motivation, as well as the potential concerns that arise from viewing excessive food intake as an “addiction”. We suggest that it might be more useful to focus on overeating that results in frank obesity, and multiple health, interpersonal, and occupational negative consequences as a form of food “abuse”. PMID:23237885

Autonomous Circuitry for Substrate Exploration in Freely Moving Drosophila Larvae

PubMed Central

Berni, Jimena; Pulver, Stefan R.; Griffith, Leslie C.; Bate, Michael

2014-01-01

Summary Background Many organisms, from bacteria to human hunter-gatherers, use specialized random walk strategies to explore their environment. Such behaviors are an efficient stratagem for sampling the environment and usually consist of an alternation between straight runs and turns that redirect these runs. Drosophila larvae execute an exploratory routine of this kind that consists of sequences of straight crawls, pauses, turns, and redirected crawls. Central pattern generating networks underlying rhythmic movements are distributed along the anteroposterior axis of the nervous system. The way in which the operation of these networks is incorporated into extended behavioral routines such as substrate exploration has not yet been explored. In particular, the part played by the brain in dictating the sequence of movements required is unknown. Results We report the use of a genetic method to block synaptic activity acutely in the brain and subesophageal ganglia (SOG) of larvae during active exploratory behavior. We show that the brain and SOG are not required for the normal performance of an exploratory routine. Alternation between crawls and turns is an intrinsic property of the abdominal and/or thoracic networks. The brain modifies this autonomous routine during goal-directed movements such as those of chemotaxis. Nonetheless, light avoidance behavior can be mediated in the absence of brain activity solely by the sensorimotor system of the abdomen and thorax. Conclusions The sequence of movements for substrate exploration is an autonomous capacity of the thoracic and abdominal nervous system. The brain modulates this exploratory routine in response to environmental cues. PMID:22940472

Temperature Induced Syllable Breaking Unveils Nonlinearly Interacting Timescales in Birdsong Motor Pathway

PubMed Central

Goldin, Matías A.; Alonso, Leandro M.; Alliende, Jorge A.; Goller, Franz; Mindlin, Gabriel B.

2013-01-01

The nature of telencephalic control over premotor and motor circuits is debated. Hypotheses range from complete usurping of downstream circuitry to highly interactive mechanisms of control. We show theoretically and experimentally, that telencephalic song motor control in canaries is consistent with a highly interactive strategy. As predicted from a theoretical model of respiratory control, mild cooling of a forebrain nucleus (HVC) led to song stretching, but further cooling caused progressive restructuring of song, consistent with the hypothesis that respiratory gestures are subharmonic responses to a timescale present in the output of HVC. This interaction between a life-sustaining motor function (respiration) and telencephalic song motor control suggests a more general mechanism of how nonlinear integration of evolutionarily new brain structures into existing circuitry gives rise to diverse, new behavior. PMID:23818988

Temperature induced syllable breaking unveils nonlinearly interacting timescales in birdsong motor pathway.

PubMed

Goldin, Matías A; Alonso, Leandro M; Alliende, Jorge A; Goller, Franz; Mindlin, Gabriel B

2013-01-01

The nature of telencephalic control over premotor and motor circuits is debated. Hypotheses range from complete usurping of downstream circuitry to highly interactive mechanisms of control. We show theoretically and experimentally, that telencephalic song motor control in canaries is consistent with a highly interactive strategy. As predicted from a theoretical model of respiratory control, mild cooling of a forebrain nucleus (HVC) led to song stretching, but further cooling caused progressive restructuring of song, consistent with the hypothesis that respiratory gestures are subharmonic responses to a timescale present in the output of HVC. This interaction between a life-sustaining motor function (respiration) and telencephalic song motor control suggests a more general mechanism of how nonlinear integration of evolutionarily new brain structures into existing circuitry gives rise to diverse, new behavior.

Additive effects of oxytocin receptor gene polymorphisms on reward circuitry in youth with autism.

PubMed

Hernandez, L M; Krasileva, K; Green, S A; Sherman, L E; Ponting, C; McCarron, R; Lowe, J K; Geschwind, D H; Bookheimer, S Y; Dapretto, M

2017-08-01

Several common alleles in the oxytocin receptor gene (OXTR) are associated with altered brain function in reward circuitry in neurotypical adults and may increase risk for autism spectrum disorders (ASD). Yet, it is currently unknown how variation in the OXTR relates to brain functioning in individuals with ASD, and, critically, whether neural endophenotypes vary as a function of aggregate genetic risk. Here, for we believe the first time, we use a multi-locus approach to examine how genetic variation across several OXTR single-nucleotide polymorphisms (SNPs) affect functional connectivity of the brain's reward network. Using data from 41 children with ASD and 41 neurotypical children, we examined functional connectivity of the nucleus accumbens (NAcc) - a hub of the reward network - focusing on how connectivity varies with OXTR risk-allele dosage. Youth with ASD showed reduced NAcc connectivity with other areas in the reward circuit as a function of increased OXTR risk-allele dosage, as well as a positive association between risk-allele dosage and symptom severity, whereas neurotypical youth showed increased NAcc connectivity with frontal brain regions involved in mentalizing. In addition, we found that increased NAcc-frontal cortex connectivity in typically developing youth was related to better scores on a standardized measure of social functioning. Our results indicate that cumulative genetic variation on the OXTR impacts reward system connectivity in both youth with ASD and neurotypical controls. By showing differential genetic effects on neuroendophenotypes, these pathways elucidate mechanisms of vulnerability versus resilience in carriers of disease-associated risk alleles.

Dynamic circuitry for updating spatial representations. II. Physiological evidence for interhemispheric transfer in area LIP of the split-brain macaque.

PubMed

Heiser, Laura M; Berman, Rebecca A; Saunders, Richard C; Colby, Carol L

2005-11-01

With each eye movement, a new image impinges on the retina, yet we do not notice any shift in visual perception. This perceptual stability indicates that the brain must be able to update visual representations to take our eye movements into account. Neurons in the lateral intraparietal area (LIP) update visual representations when the eyes move. The circuitry that supports these updated representations remains unknown, however. In this experiment, we asked whether the forebrain commissures are necessary for updating in area LIP when stimulus representations must be updated from one visual hemifield to the other. We addressed this question by recording from LIP neurons in split-brain monkeys during two conditions: stimulus traces were updated either across or within hemifields. Our expectation was that across-hemifield updating activity in LIP would be reduced or abolished after transection of the forebrain commissures. Our principal finding is that LIP neurons can update stimulus traces from one hemifield to the other even in the absence of the forebrain commissures. This finding provides the first evidence that representations in parietal cortex can be updated without the use of direct cortico-cortical links. The second main finding is that updating activity in LIP is modified in the split-brain monkey: across-hemifield signals are reduced in magnitude and delayed in onset compared with within-hemifield signals, which indicates that the pathways for across-hemifield updating are less effective in the absence of the forebrain commissures. Together these findings reveal a dynamic circuit that contributes to updating spatial representations.

But is helping you worth the risk? Defining Prosocial Risk Taking in adolescence

PubMed Central

Do, Kathy T.; Guassi Moreira, João F.; Telzer, Eva H.

2017-01-01

Recent work has shown that the same neural circuitry that typically underlies risky behaviors also contributes to prosocial behaviors. Despite the striking overlap between two seemingly distinct behavioral patterns, little is known about how risk taking and prosociality interact and inform adolescent decision making. We review literature on adolescent brain development as it pertains to risk taking and prosociality and propose a new area of study, Prosocial Risk Taking, which suggests that adolescents can make risky decisions with the intention of helping other individuals. Given key socialization processes and ongoing neurodevelopmental changes during this time, adolescence may represent a sensitive period for the emergence of Prosocial Risk Taking, especially within a wide variety of social contexts when youth’s increased sensitivity to social evaluation and belonging impacts their behaviors. Prosocial Risk Taking in adolescence is an area of study that has been overlooked in the literature, but could help explain how ontogenetic changes in the adolescent brain may create not only vulnerabilities, but also opportunities for healthy prosocial development. PMID:28063823

Understanding the mechanisms of cognitive impairments in developmental coordination disorder.

PubMed

Deng, Shining; Li, Wei-Guang; Ding, Jing; Wu, Jinlin; Zhang, Yuanyuan; Li, Fei; Shen, Xiaoming

2014-01-01

Developmental coordination disorder (DCD), a neurodevelopmental disability in which a child's motor coordination difficulties significantly interfere with activities of daily life or academic achievement, together with additional symptoms of diseases with childhood sensorimotor impairments, increases the risk of many cognitive problems. This exhibits the dynamic interplay between sensorimotor and cognition systems. However, the brain structures and pathways involved have remained unknown over the past decades. Here, we review developments in recent years that elucidate the neural mechanisms involved in the sensorimotor-cognitive difficulties. First, we briefly address the clinical and epidemiological discoveries in DCD as well as its comorbidities. Subsequently, we group the growing evidence including our findings that support the notion that sensorimotor manipulation indeed affects the cognition development at systematic, circuitry, cellular, and molecular levels. This corresponds to changes in diverse brain regions, synaptic plasticity, and neurotransmitter and receptor activity during development under these effects. Finally, we address the treatment potentials of task-oriented sensorimotor enhancement, as a new therapeutic strategy for cognitive rehabilitation, based on our current understanding of the neurobiology of cognitive-sensorimotor interaction.

Sleep and its disorders in translational medicine.

PubMed

Paterson, Louise M; Nutt, David J; Wilson, Sue J

2011-09-01

The study of sleep is a useful approach to studying the brain in psychiatric disorders and in investigating the effects of psychotropic drugs. Sleep physiology lends itself well to pharmacological and physiological manipulation, as it has the advantage of a functional output, the electroencephalograph, which is common to all mammals, and can be measured in freely moving (or naturally sleeping) animals under controlled laboratory conditions or in a naturalistic home environment. The complexity of sleep architecture varies between species but all share features which are comparable. In addition, sleep architecture is sensitive to changes in brain neurotransmitters such as serotonin, so cross-species sleep measurement can be combined with pharmacological manipulation to investigate the receptor mechanisms controlling sleep-wake regulation and sleep architecture in response to known and novel agents. Translational approaches such as these have improved our understanding of sleep circuitry and facilitated the development of new treatments for sleep disorders, particularly insomnia. This review provides examples of how research findings within the sleep field have been translated between animal models, healthy volunteers and patient populations with particular focus on the serotonergic system.

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.

Commonalities in the central nervous system's involvement with complementary medical therapies: limbic morphinergic processes.

PubMed

Esch, Tobias; Guarna, Massimo; Bianchi, Enrica; Zhu, Wei; Stefano, George B

2004-06-01

Currently, complementary and alternative medicine (CAM) are experiencing growing popularity, especially in former industrialized countries. However, most of the underlying physiological and molecular mechanisms as well as participating biological structures are still speculative. Specific and non-specific effects may play a role in CAM. Moreover, trust, belief, and expectation may be of importance, pointing towards common central nervous system (CNS) pathways involved in CAM. Four CAM approaches (acupuncture, meditation, music therapy, and massage therapy) were examined with regard to the CNS activity pattern involved. CNS commonalities between different approaches were investigated. Frontal/prefrontal and limbic brain structures play a role in CAM. Particularly, left-anterior regions of the brain and reward or motivation circuitry constituents are involved, indicating positive affect and emotion-related memory processing--accompanied by endocrinologic and autonomic functions--as crucial components of CAM effects. Thus, trust and belief in a therapist or positive therapy expectations seem to be important. However, besides common non-specific or subjective effects, specific (objective) physiological components also exist. Non-specific CNS commonalities are involved in various CAM therapies. Different therapeutic approaches physiologically overlap in the brain. However, molecular correspondents of the detected CNS analogies still have to be specified. In particular, fast acting autoregulatory signaling molecules presumably play a role. These may also be involved in the placebo response.

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

PubMed Central

McArthur, Simon

2010-01-01

The classic view of estrogen actions in the brain was confined to regulation of ovulation and reproductive behavior in the female of all mamamalian species studied, including humans. Burgeoning evidence now documents profound effects of estrogens on learning, memory, and mood as well as neurodevelopmental and neurodegenerative processes. Most data derive from studies in females, but there is mounting recognition that estrogens play important roles in the male brain, where they can be generated from circulating testosterone by local aromatase enzymes or synthesized de novo by neurons and glia. Estrogen-based therapy therefore holds considerable promise for brain disorders that affect both men and women. However, as investigations are beginning to consider the role of estrogens in the male brain more carefully, it emerges that they have different, even opposite, effects as well as similar effects in male and female brains. This review focuses on these differences, including sex dimorphisms in the ability of estradiol to influence synaptic plasticity, neurotransmission, neurodegeneration, and cognition, which, we argue, are due in a large part to sex differences in the organization of the underlying circuitry. There are notable sex differences in the incidence and manifestations of virtually all central nervous system disorders, including neurodegenerative disease (Parkinson's and Alzheimer's), drug abuse, anxiety, and depression. Understanding the cellular and molecular basis of sex differences in brain physiology and responses to estrogen and estrogen mimics is, therefore, vitally important for understanding the nature and origins of sex-specific pathological conditions and for designing novel hormone-based therapeutic agents that will have optimal effectiveness in men or women. PMID:20392807

Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs.

PubMed

Ochoa, Melissa; Malbert, Charles-Henri; Meurice, Paul; Val-Laillet, David

2016-01-01

Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; P<0.0001), regardless of the diet. All groups presented similar insulin sensitivity index (ISI = 1.39±0.10 mL·min-1·μUI·kg). Compared to starch, chronic exposure to fructose and glucose induced bilateral brain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these brain functional characteristics.

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

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.

A Psycho-Genetic Study of Hedonic Responsiveness in Relation to “Food Addiction”

PubMed Central

Davis, Caroline; Loxton, Natalie J.

2014-01-01

While food addiction has no formally-recognized definition, it is typically operationalized according to the diagnostic principles established by the Yale Food Addiction Scale—an inventory based on the symptom criteria for substance dependence in the DSM-IV. Currently, there is little biologically-based research investigating the risk factors for food addiction. What does exist has focused almost exclusively on dopaminergic reward pathways in the brain. While brain opioid signaling has also been strongly implicated in the control of food intake, there is no research examining this neural circuitry in the association with food addiction. The purpose of the study was therefore to test a model predicting that a stronger activation potential of opioid circuitry-as indicated by the functional A118G marker of the mu-opioid receptor gene-would serve as an indirect risk factor for food addiction via a heightened hedonic responsiveness to palatable food. Results confirmed these relationships. In addition, our findings that the food-addiction group had significantly higher levels of hedonic responsiveness to food suggests that this bio-behavioral trait may foster a proneness to overeating, to episodes of binge eating, and ultimately to a compulsive and addictive pattern of food intake. PMID:25325253

A psycho-genetic study of hedonic responsiveness in relation to "food addiction".

PubMed

Davis, Caroline; Loxton, Natalie J

2014-10-16

While food addiction has no formally-recognized definition, it is typically operationalized according to the diagnostic principles established by the Yale Food Addiction Scale-an inventory based on the symptom criteria for substance dependence in the DSM-IV. Currently, there is little biologically-based research investigating the risk factors for food addiction. What does exist has focused almost exclusively on dopaminergic reward pathways in the brain. While brain opioid signaling has also been strongly implicated in the control of food intake, there is no research examining this neural circuitry in the association with food addiction. The purpose of the study was therefore to test a model predicting that a stronger activation potential of opioid circuitry-as indicated by the functional A118G marker of the mu-opioid receptor gene-would serve as an indirect risk factor for food addiction via a heightened hedonic responsiveness to palatable food. Results confirmed these relationships. In addition, our findings that the food-addiction group had significantly higher levels of hedonic responsiveness to food suggests that this bio-behavioral trait may foster a proneness to overeating, to episodes of binge eating, and ultimately to a compulsive and addictive pattern of food intake.

Neural correlates of RDoC reward constructs in adolescents with diverse psychiatric symptoms: A Reward Flanker Task pilot study.

PubMed

Bradley, Kailyn A L; Case, Julia A C; Freed, Rachel D; Stern, Emily R; Gabbay, Vilma

2017-07-01

There has been growing interest under the Research Domain Criteria initiative to investigate behavioral constructs and their underlying neural circuitry. Abnormalities in reward processes are salient across psychiatric conditions and may precede future psychopathology in youth. However, the neural circuitry underlying such deficits has not been well defined. Therefore, in this pilot, we studied youth with diverse psychiatric symptoms and examined the neural underpinnings of reward anticipation, attainment, and positive prediction error (PPE, unexpected reward gain). Clinically, we focused on anhedonia, known to reflect deficits in reward function. Twenty-two psychotropic medication-free youth, 16 with psychiatric symptoms, exhibiting a full range of anhedonia, were scanned during the Reward Flanker Task. Anhedonia severity was quantified using the Snaith-Hamilton Pleasure Scale. Functional magnetic resonance imaging analyses were false discovery rate corrected for multiple comparisons. Anticipation activated a broad network, including the medial frontal cortex and ventral striatum, while attainment activated memory and emotion-related regions such as the hippocampus and parahippocampal gyrus, but not the ventral striatum. PPE activated a right-dominant fronto-temporo-parietal network. Anhedonia was only correlated with activation of the right angular gyrus during anticipation and the left precuneus during PPE at an uncorrected threshold. Findings are preliminary due to the small sample size. This pilot characterized the neural circuitry underlying different aspects of reward processing in youth with diverse psychiatric symptoms. These results highlight the complexity of the neural circuitry underlying reward anticipation, attainment, and PPE. Furthermore, this study underscores the importance of RDoC research in youth. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Testing the Paleolithic-human-warfare hypothesis of blood-injection phobia in the Baltimore ECA Follow-up Study--towards a more etiologically-based conceptualization for DSM-V.

PubMed

Bracha, H Stefan; Bienvenu, O Joseph; Eaton, William W

2007-01-01

The research agenda for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) has emphasized the need for a more etiologically-based classification system, especially for stress-induced and fear-circuitry disorders. Testable hypotheses based on threats to survival during particular segments of the human era of evolutionary adaptedness (EEA) may be useful in developing a brain-evolution-based classification for the wide spectrum of disorders ranging from disorders which are mostly overconsolidationally such as PTSD, to fear-circuitry disorders which are mostly innate such as specific phobias. The recently presented Paleolithic-human-warfare hypothesis posits that blood-injection phobia can be traced to a "survival (fitness) enhancing" trait, which evolved in some females of reproductive-age during the millennia of intergroup warfare in the Paleolithic EEA. The study presented here tests the key a priori prediction of this hypothesis-that current blood-injection phobia will have higher prevalence in reproductive-age women than in post-menopausal women. The Diagnostic Interview Schedule (version III-R), which included a section on blood and injection phobia, was administered to 1920 subjects in the Baltimore ECA Follow-up Study. Data on BII phobia was available on 1724 subjects (1078 women and 646 males). The prevalence of current blood-injection phobia was 3.3% in women aged 27-49 and 1.1% in women over age 50 (OR 3.05, 95% CI 1.20-7.73). [The corresponding figures for males were 0.8% and 0.7% (OR 1.19, 95% CI 0.20-7.14)]. This epidemiological study provides one source of support for the Paleolithic-human-warfare (Paleolithic-threat) hypothesis regarding the evolutionary (distal) etiology of bloodletting-related phobia, and may contribute to a more brain-evolution-based re-conceptualization and classification of this fear circuitry-related trait for the DSM-V. In addition, the finding reported here may also stimulate new research directions on more proximal mechanisms which can lead to the development of evidence-based psychopharmacological preventive interventions for this common and sometimes disabling fear-circuitry disorder.

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

Trace Eyeblink Conditioning in Mice Is Dependent upon the Dorsal Medial Prefrontal Cortex, Cerebellum, and Amygdala: Behavioral Characterization and Functional Circuitry1,2,3

PubMed Central

Taylor, William; Kalmbach, Brian; Desai, Niraj S.

2015-01-01

Abstract Trace eyeblink conditioning is useful for studying the interaction of multiple brain areas in learning and memory. The goal of the current work was to determine whether trace eyeblink conditioning could be established in a mouse model in the absence of elicited startle responses and the brain circuitry that supports this learning. We show here that mice can acquire trace conditioned responses (tCRs) devoid of startle while head-restrained and permitted to freely run on a wheel. Most mice (75%) could learn with a trace interval of 250 ms. Because tCRs were not contaminated with startle-associated components, we were able to document the development and timing of tCRs in mice, as well as their long-term retention (at 7 and 14 d) and flexible expression (extinction and reacquisition). To identify the circuitry involved, we made restricted lesions of the medial prefrontal cortex (mPFC) and found that learning was prevented. Furthermore, inactivation of the cerebellum with muscimol completely abolished tCRs, demonstrating that learned responses were driven by the cerebellum. Finally, inactivation of the mPFC and amygdala in trained animals nearly abolished tCRs. Anatomical data from these critical regions showed that mPFC and amygdala both project to the rostral basilar pons and overlap with eyelid-associated pontocerebellar neurons. The data provide the first report of trace eyeblink conditioning in mice in which tCRs were driven by the cerebellum and required a localized region of mPFC for acquisition. The data further reveal a specific role for the amygdala as providing a conditioned stimulus-associated input to the cerebellum. PMID:26464998

Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression

PubMed Central

Fales, Christina L.; Barch, Deanna M.; Rundle, Melissa M.; Mintun, Mark A.; Snyder, Abraham Z.; Cohen, Jonathan D.; Mathews, Jose; Sheline, Yvette I.

2008-01-01

Background Major depression is characterized by a negativity bias: an enhanced responsiveness to, and memory for, affectively negative stimuli. However it is not yet clear whether this bias represents (1) impaired top-down cognitive control over affective responses, potentially linked to deficits in dorsolateral prefrontal cortex function; or (2) enhanced bottom-up responses to affectively-laden stimuli that dysregulate cognitive control mechanisms, potentially linked to deficits in amygdala and anterior cingulate function. Methods We used an attentional interference task using emotional distracters to test for top-down versus bottom-up dysfunction in the interaction of cognitive-control circuitry and emotion-processing circuitry. A total of 27 patients with major depression and 24 controls were tested. Event-related functional magnetic resonance imaging was carried out as participants directly attended to, or attempted to ignore, fear-related stimuli. Results Compared to controls, patients with depression showed an enhanced amygdala response to unattended fear-related stimuli (relative to unattended neutral). By contrast, control participants showed increased activity in right dorsolateral prefrontal cortex (Brodmann areas 46/9) when ignoring fear stimuli (relative to neutral), which the patients with depression did not. In addition, the depressed participants failed to show evidence of error-related cognitive adjustments (increased activity in bilateral dorsolateral prefrontal cortex on post-error trials), but the control group did show them. Conclusions These results suggest multiple sources of dysregulation in emotional and cognitive control circuitry in depression, implicating both top-down and bottom-up dysfunction. PMID:17719567

Impact of Sex and Menopausal Status on Episodic Memory Circuitry in Early Midlife.

PubMed

Jacobs, Emily G; Weiss, Blair K; Makris, Nikos; Whitfield-Gabrieli, Sue; Buka, Stephen L; Klibanski, Anne; Goldstein, Jill M

2016-09-28

Cognitive neuroscience of aging studies traditionally target participants age 65 and older. However, epidemiological surveys show that many women report increased forgetfulness earlier in the aging process, as they transition to menopause. In this population-based fMRI study, we stepped back by over a decade to characterize the changes in memory circuitry that occur in early midlife, as a function of sex and women's reproductive stage. Participants (N = 200; age range, 45-55) performed a verbal encoding task during fMRI scanning. Reproductive histories and serologic evaluations were used to determine menopausal status. Results revealed a pronounced impact of reproductive stage on task-evoked hippocampal responses, despite minimal difference in chronological age. Next, we examined the impact of sex and reproductive stage on functional connectivity across task-related brain regions. Postmenopausal women showed enhanced bilateral hippocampal connectivity relative to premenopausal and perimenopausal women. Across women, lower 17β-estradiol concentrations were related to more pronounced alterations in hippocampal connectivity and poorer performance on a subsequent memory retrieval task, strongly implicating sex steroids in the regulation of this circuitry. Finally, subgroup analyses revealed that high-performing postmenopausal women (relative to low and middle performers) exhibited a pattern of brain activity akin to premenopausal women. Together, these findings underscore the importance of considering reproductive stage, not simply chronological age, to identify neuronal and cognitive changes that unfold in the middle decades of life. In keeping with preclinical studies, these human findings suggest that the decline in ovarian estradiol production during menopause plays a significant role in shaping memory circuitry. Maintaining intact memory function with age is one of the greatest public health challenges of our time, and women have an increased risk for memory disorders relative to men later in life. We studied adults early in the aging process, as women transition into menopause, to identify neuronal and cognitive changes that unfold in the middle decades of life. Results demonstrate regional and network-level differences in memory encoding-related activity as a function of women's reproductive stage, independent of chronological age. Analyzing data without regard to sex or menopausal status obscured group differences in circuit-level neural strategies associated with successful memory retrieval. These findings suggest that early changes in memory circuitry are evident decades before the age range traditionally targeted by cognitive neuroscience of aging studies. Copyright © 2016 the authors 0270-6474/16/3610163-11$15.00/0.

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

The national DBS brain tissue network pilot study: need for more tissue and more standardization.

PubMed

Vedam-Mai, V; Krock, N; Ullman, M; Foote, K D; Shain, W; Smith, K; Yachnis, A T; Steindler, D; Reynolds, B; Merritt, S; Pagan, F; Marjama-Lyons, J; Hogarth, P; Resnick, A S; Zeilman, P; Okun, M S

2011-08-01

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

UCP2 regulates mitochondrial fission and ventromedial nucleus control of glucose responsiveness

PubMed Central

Toda, Chitoku; Kim, Jung Dae; Impellizzeri, Daniela; Cuzzocrea, Salvatore; Liu, Zhong-Wu; Diano, Sabrina

2016-01-01

Summary The ventromedial nucleus of the hypothalamus (VMH) plays a critical role in regulating systemic glucose homeostasis. How neurons in this brain area adapt to the changing metabolic environment to regulate circulating glucose levels is ill-defined. Here we show that glucose load results in mitochondrial fission and reduced reactive oxygen species in VMH neurons mediated by dynamin-related peptide 1 (DRP1) under the control of uncoupling protein 2 (UCP2). Probed by genetic manipulations and chemical-genetic control of VMH neuronal circuitry, we unmasked that this mitochondrial adaptation determines the size of the pool of glucose-excited neurons in the VMH, and, that this process regulates systemic glucose homoeostasis. Thus, our data unmasked a critical cellular biological process controlled by mitochondrial dynamics in VMH regulation of systemic glucose homeostasis. PMID:26919426

Anxiety and Nicotine Dependence: Emerging Role of the Habenulo-Interpeduncular Axis.

PubMed

Molas, Susanna; DeGroot, Steven R; Zhao-Shea, Rubing; Tapper, Andrew R

2017-02-01

While innovative modern neuroscience approaches have aided in discerning brain circuitry underlying negative emotional behaviors including fear and anxiety responses, how these circuits are recruited in normal and pathological conditions remains poorly understood. Recently, genetic tools that selectively manipulate single neuronal populations have uncovered an understudied circuit, the medial habenula (mHb)-interpeduncular (IPN) axis, that modulates basal negative emotional responses. Interestingly, the mHb-IPN pathway also represents an essential circuit that signals heightened anxiety induced by nicotine withdrawal. Insights into how this circuit interconnects with regions more classically associated with anxiety, and how chronic nicotine exposure induces neuroadaptations resulting in an anxiogenic state, may thereby provide novel strategies and molecular targets for therapies that facilitate smoking cessation, as well as for anxiety relief. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic neuroscience of mammalian learning and memory.

PubMed Central

Tonegawa, Susumu; Nakazawa, Kazu; Wilson, Matthew A

2003-01-01

Our primary research interest is to understand the molecular and cellular mechanisms on neuronal circuitry underlying the acquisition, consolidation and retrieval of hippocampus-dependent memory in rodents. We study these problems by producing genetically engineered (i.e. spatially targeted and/or temporally restricted) mice and analysing these mice by multifaceted methods including molecular and cellular biology, in vitro and in vivo physiology and behavioural studies. We attempt to identify deficits at each of the multiple levels of complexity in specific brain areas or cell types and deduce those deficits that underlie specific learning or memory. We will review our recent studies on the acquisition, consolidation and recall of memories that have been conducted with mouse strains in which genetic manipulations were targeted to specific types of cells in the hippocampus or forebrain of young adult mice. PMID:12740125

UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness.

PubMed

Toda, Chitoku; Kim, Jung Dae; Impellizzeri, Daniela; Cuzzocrea, Salvatore; Liu, Zhong-Wu; Diano, Sabrina

2016-02-25

The ventromedial nucleus of the hypothalamus (VMH) plays a critical role in regulating systemic glucose homeostasis. How neurons in this brain area adapt to the changing metabolic environment to regulate circulating glucose levels is ill defined. Here, we show that glucose load results in mitochondrial fission and reduced reactive oxygen species in VMH neurons mediated by dynamin-related peptide 1 (DRP1) under the control of uncoupling protein 2 (UCP2). Probed by genetic manipulations and chemical-genetic control of VMH neuronal circuitry, we unmasked that this mitochondrial adaptation determines the size of the pool of glucose-excited neurons in the VMH and that this process regulates systemic glucose homeostasis. Thus, our data unmasked a critical cellular biological process controlled by mitochondrial dynamics in VMH regulation of systemic glucose homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Deep Brain Stimulation

PubMed Central

Lyketsos, Constantine G.; Pendergrass, Jo Cara; Lozano, Andres M.

2012-01-01

Recent studies have identified an association between memory deficits and defects of the integrated neuronal cortical areas known collectively as the default mode network. It is conceivable that the amyloid deposition or other molecular abnormalities seen in patients with Alzheimer’s disease may interfere with this network and disrupt neuronal circuits beyond the localized brain areas. Therefore, Alzheimer’s disease may be both a degenerative disease and a broader system-level disorder affecting integrated neuronal pathways involved in memory. In this paper, we describe the rationale and provide some evidence to support the study of deep brain stimulation of the hippocampal fornix as a novel treatment to improve neuronal circuitry within these integrated networks and thereby sustain memory function in early Alzheimer’s disease. PMID:23346514

Molecular mechanisms of synaptic remodeling in alcoholism

PubMed Central

Kyzar, Evan J.; Pandey, Subhash C.

2015-01-01

Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the “dark side” of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. PMID:25623036

Molecular mechanisms of synaptic remodeling in alcoholism.

PubMed

Kyzar, Evan J; Pandey, Subhash C

2015-08-05

Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. Published by Elsevier Ireland Ltd.

Mechanisms of Long Non-Coding RNAs in the Assembly and Plasticity of Neural Circuitry.

PubMed

Wang, Andi; Wang, Junbao; Liu, Ying; Zhou, Yan

2017-01-01

The mechanisms underlying development processes and functional dynamics of neural circuits are far from understood. Long non-coding RNAs (lncRNAs) have emerged as essential players in defining identities of neural cells, and in modulating neural activities. In this review, we summarized latest advances concerning roles and mechanisms of lncRNAs in assembly, maintenance and plasticity of neural circuitry, as well as lncRNAs' implications in neurological disorders. We also discussed technical advances and challenges in studying functions and mechanisms of lncRNAs in neural circuitry. Finally, we proposed that lncRNA studies would advance our understanding on how neural circuits develop and function in physiology and disease conditions.

The neurobiology of addiction: the perspective from magnetic resonance imaging present and future

PubMed Central

Nestor, Liam J.

2016-01-01

Abstract Background and Aims Addiction is associated with severe economic and social consequences and personal tragedies, the scientific exploration of which draws upon investigations at the molecular, cellular and systems levels with a wide variety of technologies. Magnetic resonance imaging (MRI) has been key to mapping effects observed at the microscopic and mesoscopic scales. The range of measurements from this apparatus has opened new avenues linking neurobiology to behaviour. This review considers the role of MRI in addiction research, and what future technological improvements might offer. Methods A hermeneutic strategy supplemented by an expansive, systematic search of PubMed, Scopus and Web of Science databases, covering from database inception to October 2015, with a conjunction of search terms relevant to addiction and MRI. Formal meta‐analyses were prioritized. Results Results from methods that probe brain structure and function suggest frontostriatal circuitry disturbances within specific cognitive domains, some of which predict drug relapse and treatment response. New methods of processing imaging data are opening opportunities for understanding the role of cerebral vasculature, a global view of brain communication and the complex topology of the cortical surface and drug action. Future technological advances include increases in MRI field strength, with concomitant improvements in image quality. Conclusions The magnetic resonance imaging literature provides a limited but convergent picture of the neurobiology of addiction as global changes to brain structure and functional disturbances to frontostriatal circuitry, accompanied by changes in anterior white matter. PMID:27452960

How placebos change the patient's brain.

PubMed

Benedetti, Fabrizio; Carlino, Elisa; Pollo, Antonella

2011-01-01

Although placebos have long been considered a nuisance in clinical research, today they represent an active and productive field of research and, because of the involvement of many mechanisms, the study of the placebo effect can actually be viewed as a melting pot of concepts and ideas for neuroscience. Indeed, there exists not a single but many placebo effects, with different mechanisms and in different systems, medical conditions, and therapeutic interventions. For example, brain mechanisms of expectation, anxiety, and reward are all involved, as well as a variety of learning phenomena, such as Pavlovian conditioning, cognitive, and social learning. There is also some experimental evidence of different genetic variants in placebo responsiveness. The most productive models to better understand the neurobiology of the placebo effect are pain and Parkinson's disease. In these medical conditions, the neural networks that are involved have been identified: that is, the opioidergic-cholecystokinergic-dopaminergic modulatory network in pain and part of the basal ganglia circuitry in Parkinson's disease. Important clinical implications emerge from these recent advances in placebo research. First, as the placebo effect is basically a psychosocial context effect, these data indicate that different social stimuli, such as words and rituals of the therapeutic act, may change the chemistry and circuitry of the patient's brain. Second, the mechanisms that are activated by placebos are the same as those activated by drugs, which suggests a cognitive/affective interference with drug action. Third, if prefrontal functioning is impaired, placebo responses are reduced or totally lacking, as occurs in dementia of the Alzheimer's type.

Ontogenetic ritualization of primate gesture as a case study in dyadic brain modeling.

PubMed

Gasser, Brad; Cartmill, Erica A; Arbib, Michael A

2014-01-01

This paper introduces dyadic brain modeling - the simultaneous, computational modeling of the brains of two interacting agents - to explore ways in which our understanding of macaque brain circuitry can ground new models of brain mechanisms involved in ape interaction. Specifically, we assess a range of data on gestural communication of great apes as the basis for developing an account of the interactions of two primates engaged in ontogenetic ritualization, a proposed learning mechanism through which a functional action may become a communicative gesture over repeated interactions between two individuals (the 'dyad'). The integration of behavioral, neural, and computational data in dyadic (or, more generally, social) brain modeling has broad application to comparative and evolutionary questions, particularly for the evolutionary origins of cognition and language in the human lineage. We relate this work to the neuroinformatics challenges of integrating and sharing data to support collaboration between primatologists, neuroscientists and modelers that will help speed the emergence of what may be called comparative neuro-primatology.

Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry.

PubMed

Wang, Gene-Jack; Yang, Julia; Volkow, Nora D; Telang, Frank; Ma, Yeming; Zhu, Wei; Wong, Christopher T; Tomasi, Dardo; Thanos, Panayotis K; Fowler, Joanna S

2006-10-17

The neurobiological mechanisms underlying overeating in obesity are not understood. Here, we assessed the neurobiological responses to an Implantable Gastric Stimulator (IGS), which induces stomach expansion via electrical stimulation of the vagus nerve to identify the brain circuits responsible for its effects in decreasing food intake. Brain metabolism was measured with positron emission tomography and 2-deoxy-2[18F]fluoro-D-glucose in seven obese subjects who had the IGS implanted for 1-2 years. Brain metabolism was evaluated twice during activation (on) and during deactivation (off) of the IGS. The Three-Factor Eating Questionnaire was obtained to measure the behavioral components of eating (cognitive restraint, uncontrolled eating, and emotional eating). The largest difference was in the right hippocampus, where metabolism was 18% higher (P < 0.01) during the "on" than "off" condition, and these changes were associated with scores on "emotional eating," which was lower during the on than off condition and with "uncontrolled eating," which did not differ between conditions. Metabolism also was significantly higher in right anterior cerebellum, orbitofrontal cortex, and striatum during the on condition. These findings corroborate the role of the vagus nerve in regulating hippocampal activity and the importance of the hippocampus in modulating eating behaviors linked to emotional eating and lack of control. IGS-induced activation of regions previously shown to be involved in drug craving in addicted subjects (orbitofrontal cortex, hippocampus, cerebellum, and striatum) suggests that similar brain circuits underlie the enhanced motivational drive for food and drugs seen in obese and drug-addicted subjects, respectively.

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.

Probabilistic diffusion tractography and graph theory analysis reveal abnormal white matter structural connectivity networks in drug-naive boys with attention deficit/hyperactivity disorder.

PubMed

Cao, Qingjiu; Shu, Ni; An, Li; Wang, Peng; Sun, Li; Xia, Ming-Rui; Wang, Jin-Hui; Gong, Gao-Lang; Zang, Yu-Feng; Wang, Yu-Feng; He, Yong

2013-06-26

Attention-deficit/hyperactivity disorder (ADHD), which is characterized by core symptoms of inattention and hyperactivity/impulsivity, is one of the most common neurodevelopmental disorders of childhood. Neuroimaging studies have suggested that these behavioral disturbances are associated with abnormal functional connectivity among brain regions. However, the alterations in the structural connections that underlie these behavioral and functional deficits remain poorly understood. Here, we used diffusion magnetic resonance imaging and probabilistic tractography method to examine whole-brain white matter (WM) structural connectivity in 30 drug-naive boys with ADHD and 30 healthy controls. The WM networks of the human brain were constructed by estimating inter-regional connectivity probability. The topological properties of the resultant networks (e.g., small-world and network efficiency) were then analyzed using graph theoretical approaches. Nonparametric permutation tests were applied for between-group comparisons of these graphic metrics. We found that both the ADHD and control groups showed an efficient small-world organization in the whole-brain WM networks, suggesting a balance between structurally segregated and integrated connectivity patterns. However, relative to controls, patients with ADHD exhibited decreased global efficiency and increased shortest path length, with the most pronounced efficiency decreases in the left parietal, frontal, and occipital cortices. Intriguingly, the ADHD group showed decreased structural connectivity in the prefrontal-dominant circuitry and increased connectivity in the orbitofrontal-striatal circuitry, and these changes significantly correlated with the inattention and hyperactivity/impulsivity symptoms, respectively. The present study shows disrupted topological organization of large-scale WM networks in ADHD, extending our understanding of how structural disruptions of neuronal circuits underlie behavioral disturbances in patients with ADHD.

Individual Differences in Sleep Timing Relate to Melanopsin-Based Phototransduction in Healthy Adolescents and Young Adults

PubMed Central

van der Meijden, Wisse P.; Van Someren, Jamie L.; te Lindert, Bart H.W.; Bruijel, Jessica; van Oosterhout, Floor; Coppens, Joris E.; Kalsbeek, Andries; Cajochen, Christian; Bourgin, Patrice; Van Someren, Eus J.W.

2016-01-01

Study Objectives: Individual differences in sleep timing have been widely recognized and are of particular relevance in adolescents and young adults who often show mild to severely delayed sleep. The biological mechanisms underlying the between-subject variance remain to be determined. Recent human genetics studies showed an association between sleep timing and melanopsin gene variation, but support for functional effects on downstream pathways and behavior was not demonstrated before. We therefore investigated the association between the autonomic (i.e., pupil diameter) and behavioral (i.e., sleep timing) readouts of two different downstream brain areas, both affected by the same melanopsin-dependent retinal phototransduction: the olivary pretectal nucleus (OPN) and the suprachiasmatic nucleus (SCN). Methods: Our study population included 71 healthy individuals within an age range with known vulnerability to a delayed sleep phase (16.8–35.7 y, 37 males, 34 females). Pupillometry was performed to estimate functionality of the intrinsic melanopsin-signaling circuitry based on the OPN-mediated post-illumination pupil response (PIPR) to blue light. Sleep timing was quantified by estimating the SCN-mediated mid-sleep timing in three different ways in parallel: using a chronotype questionnaire, a sleep diary, and actigraphy. Results: All three measures consistently showed that those individuals with a later mid-sleep timing had a more pronounced PIPR (0.03 < P < 0.05), indicating a stronger blue-light responsiveness of the intrinsic melanopsin-based phototransduction circuitry. Conclusions: Trait-like individual differences in the melanopsin phototransduction circuitry contribute to individual differences in sleep timing. Blue light-sensitive young individuals are more prone to delayed sleep. Citation: van der Meijden WP, Van Someren JL; te Lindert BH, Bruijel J, van Oosterhout F, Coppens JE, Kalsbeek A, Cajochen C, Bourgin P, Van Someren EJ. Individual differences in sleep timing relate to melanopsin-based phototransduction in healthy adolescents and young adults. SLEEP 2016;39(6):1305–1310. PMID:27091519

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.

Cannabis use and memory brain function in adolescent boys: a cross-sectional multicenter functional magnetic resonance imaging study.

PubMed

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

2010-06-01

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 executive control. Prefrontal and temporal regions are critically involved in these functions. Maturational processes leave these brain areas prone to the potentially harmful effects of cannabis use. We performed a two-site (United States and The Netherlands; pooled data) functional magnetic resonance imaging (MRI) study with a cross-sectional design, investigating the effects of adolescent cannabis use on working memory (WM) and associative memory (AM) brain function in 21 abstinent but frequent cannabis-using boys (13-19) years of age and compared them with 24 nonusing peers. Brain activity during WM was assessed before and after rule-based learning (automatization). AM was assessed using a pictorial hippocampal-dependent memory task. Cannabis users performed normally on both memory tasks. During WM assessment, cannabis users showed excessive activity in prefrontal regions when a task was novel, whereas automatization of the task reduced activity to the same level in users and controls. No effect of cannabis use on AM-related brain function was found. In adolescent cannabis users, the WM system was overactive during a novel task, suggesting functional compensation. Inefficient WM recruitment was not related to a failure in automatization but became evident when processing continuously changing information. The results seem to confirm the vulnerability of still developing frontal lobe functioning for early-onset cannabis use. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Pathophysiology of premenstrual syndrome and premenstrual dysphoric disorder.

PubMed

Rapkin, Andrea J; Akopians, Alin L

2012-06-01

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder are triggered by hormonal events ensuing after ovulation. The symptoms can begin in the early, mid or late luteal phase and are not associated with defined concentrations of any specific gonadal or non-gonadal hormone. Although evidence for a hormonal abnormality has not been established, the symptoms of the premenstrual disorders are related to the production of progesterone by the ovary. The two best-studied and relevant neurotransmitter systems implicated in the genesis of the symptoms are the GABArgic and the serotonergic systems. Metabolites of progesterone formed by the corpus luteum of the ovary and in the brain bind to a neurosteroid-binding site on the membrane of the gamma-aminobutyric acid (GABA) receptor, changing its configuration, rendering it resistant to further activation and finally decreasing central GABA-mediated inhibition. By a similar mechanism, the progestogens in some hormonal contraceptives are also thought to adversely affect the GABAergic system. The lowering of serotonin can give rise to PMS-like symptoms and serotonergic functioning seems to be deficient by some methods of estimating serotonergic activity in the brain; agents that augment serotonin are efficacious and are as effective even if administered only in the luteal phase. However, similar to the affective disorders, PMS is ultimately not likely to be related to the dysregulation of individual neurotransmitters. Brain imaging studies have begun to shed light on the complex brain circuitry underlying affect and behaviour and may help to explicate the intricate neurophysiological foundation of the syndrome.

Multi-objective optimization of piezoelectric circuitry network for mode delocalization and suppression of bladed disk

NASA Astrophysics Data System (ADS)

Yoo, David; Tang, J.

2017-04-01

Since weakly-coupled bladed disks are highly sensitive to the presence of uncertainties, they can easily undergo vibration localization. When vibration localization occurs, vibration modes of bladed disk become dramatically different from those under the perfectly periodic condition, and the dynamic response under engine-order excitation is drastically amplified. In previous studies, it is investigated that amplified vibration response can be suppressed by connecting piezoelectric circuitry into individual blades to induce the damped absorber effect, and localized vibration modes can be alleviated by integrating piezoelectric circuitry network. Delocalization of vibration modes and vibration suppression of bladed disk, however, require different optimal set of circuit parameters. In this research, multi-objective optimization approach is developed to enable finding the best circuit parameters, simultaneously achieving both objectives. In this way, the robustness and reliability in bladed disk can be ensured. Gradient-based optimizations are individually developed for mode delocalization and vibration suppression, which are then integrated into multi-objective optimization framework.

Building a neuroscience of pleasure and well-being

PubMed Central

Berridge, Kent C; Kringelbach, Morten L

2012-01-01

Background How is happiness generated via brain function in lucky individuals who have the good fortune to be happy? Conceptually, well-being or happiness has long been viewed as requiring at least two crucial ingredients: positive affect or pleasure (hedonia) and a sense of meaningfulness or engagement in life (eudaimonia). Science has recently made progress in relating hedonic pleasure to brain function, and so here we survey new insights into how brains generate the hedonic ingredient of sustained or frequent pleasure. We also briefly discuss how brains might connect hedonia states of pleasure to eudaimonia assessments of meaningfulness, and so create balanced states of positive well-being. Results Notable progress has been made in understanding brain bases of hedonic processing, producing insights into that brain systems that cause and/or code sensory pleasures. Progress has been facilitated by the recognition that hedonic brain mechanisms are largely shared between humans and other mammals, allowing application of conclusions from animal studies to a better understanding of human pleasures. In the past few years, evidence has also grown to indicate that for humans, brain mechanisms of higher abstract pleasures strongly overlap with more basic sensory pleasures. This overlap may provide a window into underlying brain circuitry that generates all pleasures, including even the hedonic quality of pervasive well-being that detaches from any particular sensation to apply to daily life in a more sustained or frequent fashion. Conclusions Hedonic insights are applied to understanding human well-being here. Our strategy combines new findings on brain mediators that generate the pleasure of sensations with evidence that human brains use many of the same hedonic circuits from sensory pleasures to create the higher pleasures. This in turn may be linked to how hedonic systems interact with other brain systems relevant to self-understanding and the meaning components of eudaimonic happiness. Finally, we speculate a bit about how brains that generate hedonia states might link to eudaimonia assessments to create properly balanced states of positive well-being that approach true happiness. PMID:22328976

Anatomy and computational modeling of networks underlying cognitive-emotional interaction.

PubMed

John, Yohan J; Bullock, Daniel; Zikopoulos, Basilis; Barbas, Helen

2013-01-01

The classical dichotomy between cognition and emotion equated the first with rationality or logic and the second with irrational behaviors. The idea that cognition and emotion are separable, antagonistic forces competing for dominance of mind has been hard to displace despite abundant evidence to the contrary. For instance, it is now known that a pathological absence of emotion leads to profound impairment of decision making. Behavioral observations of this kind are corroborated at the mechanistic level: neuroanatomical studies reveal that brain areas typically described as underlying either cognitive or emotional processes are linked in ways that imply complex interactions that do not resemble a simple mutual antagonism. Instead, physiological studies and network simulations suggest that top-down signals from prefrontal cortex realize "cognitive control" in part by either suppressing or promoting emotional responses controlled by the amygdala, in a way that facilitates adaptation to changing task demands. Behavioral, anatomical, and physiological data suggest that emotion and cognition are equal partners in enabling a continuum or matrix of flexible behaviors that are subserved by multiple brain regions acting in concert. Here we focus on neuroanatomical data that highlight circuitry that structures cognitive-emotional interactions by directly or indirectly linking prefrontal areas with the amygdala. We also present an initial computational circuit model, based on anatomical, physiological, and behavioral data to explicitly frame the learning and performance mechanisms by which cognition and emotion interact to achieve flexible behavior.

MicroRNA's impact on neurotransmitter and neuropeptide systems: small but mighty mediators of anxiety.

PubMed

Martinetz, Stefanie

2016-06-01

Psychiatric disorders rank among the most common severe diseases worldwide, with millions of people affected worldwide every year. The symptoms are manifold, and the outcome for the patients is often unclear. As a high and yearly rising cost burden for society, anxiety disorders, depression and their related mental disorders are currently a well-researched topic in order to develop new functional pharmacological therapies as alternatives to those that are in use and bear many unpleasant side effects. Brain circuitries, such as those underlying anxiety formations, are mainly driven by the interplay of various neurotransmitter systems and the interaction of different brain loci, as well as the modulating impact of neuropeptides. Targeting those networks is a complex but promising way to regulate mood. Alterations on molecular level of the neuronal cell in response to respective receptor activation, especially at post-transcriptional level via the highly regulatory function of non-coding RNAs such as microRNAs (miRNAs) seem to hold a promising future in the development of novel therapeutic strategies and are therefore under intensified investigation. This review focusses on the impact of miRNAs on the neurotransmitter and neuropeptide systems of the central nervous system relevant for the formation of anxiety disorders and discusses the potential of miRNAs for the development of new therapeutic strategies for anxiety and mood disorders.

Motor Sequence Learning-Induced Neural Efficiency in Functional Brain Connectivity

PubMed Central

Karim, Helmet T; Huppert, Theodore J; Erickson, Kirk I; Wollam, Mariegold E; Sparto, Patrick J; Sejdić, Ervin; VanSwearingen, Jessie M

2016-01-01

Previous studies have shown the functional neural circuitry differences before and after an explicitly learned motor sequence task, but have not assessed these changes during the process of motor skill learning. Functional magnetic resonance imaging activity was measured while participants (n=13) were asked to tap their fingers to visually presented sequences in blocks that were either the same sequence repeated (learning block) or random sequences (control block). Motor learning was associated with a decrease in brain activity during learning compared to control. Lower brain activation was noted in the posterior parietal association area and bilateral thalamus during the later periods of learning (not during the control). Compared to the control condition, we found the task-related motor learning was associated with decreased connectivity between the putamen and left inferior frontal gyrus and left middle cingulate brain regions. Motor learning was associated with changes in network activity, spatial extent, and connectivity. PMID:27845228

Prediction complements explanation in understanding the developing brain.

PubMed

Rosenberg, Monica D; Casey, B J; Holmes, Avram J

2018-02-21

A central aim of human neuroscience is understanding the neurobiology of cognition and behavior. Although we have made significant progress towards this goal, reliance on group-level studies of the developed adult brain has limited our ability to explain population variability and developmental changes in neural circuitry and behavior. In this review, we suggest that predictive modeling, a method for predicting individual differences in behavior from brain features, can complement descriptive approaches and provide new ways to account for this variability. Highlighting the outsized scientific and clinical benefits of prediction in developmental populations including adolescence, we show that predictive brain-based models are already providing new insights on adolescent-specific risk-related behaviors. Together with large-scale developmental neuroimaging datasets and complementary analytic approaches, predictive modeling affords us the opportunity and obligation to identify novel treatment targets and individually tailor the course of interventions for developmental psychopathologies that impact so many young people today.

Data warehousing methods and processing infrastructure for brain recovery research.

PubMed

Gee, T; Kenny, S; Price, C J; Seghier, M L; Small, S L; Leff, A P; Pacurar, A; Strother, S C

2010-09-01

In order to accelerate translational neuroscience with the goal of improving clinical care it has become important to support rapid accumulation and analysis of large, heterogeneous neuroimaging samples and their metadata from both normal control and patient groups. We propose a multi-centre, multinational approach to accelerate the data mining of large samples and facilitate data-led clinical translation of neuroimaging results in stroke. Such data-driven approaches are likely to have an early impact on clinically relevant brain recovery while we simultaneously pursue the much more challenging model-based approaches that depend on a deep understanding of the complex neural circuitry and physiological processes that support brain function and recovery. We present a brief overview of three (potentially converging) approaches to neuroimaging data warehousing and processing that aim to support these diverse methods for facilitating prediction of cognitive and behavioral recovery after stroke, or other types of brain injury or disease.

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

Large-Scale Brain Systems in ADHD: Beyond the Prefrontal-Striatal Model

PubMed Central

Castellanos, F. Xavier; Proal, Erika

2012-01-01

Attention-deficit/hyperactivity disorder (ADHD) has long been thought to reflect dysfunction of prefrontal-striatal circuitry, with involvement of other circuits largely ignored. Recent advances in systems neuroscience-based approaches to brain dysfunction enable the development of models of ADHD pathophysiology that encompass a number of different large-scale “resting state” networks. Here we review progress in delineating large-scale neural systems and illustrate their relevance to ADHD. We relate frontoparietal, dorsal attentional, motor, visual, and default networks to the ADHD functional and structural literature. Insights emerging from mapping intrinsic brain connectivity networks provide a potentially mechanistic framework for understanding aspects of ADHD, such as neuropsychological and behavioral inconsistency, and the possible role of primary visual cortex in attentional dysfunction in the disorder. PMID:22169776

Nonimpact brain injury: neuropsychological and behavioral correlates with consideration of physiological findings.

PubMed

Henry, G K; Gross, H S; Herndon, C A; Furst, C J

2000-01-01

This retrospective clinical study investigated the neuropsychological, physiological, and behavioral functioning of 32 adult outpatients up to 65 months following nonimpact brain injury (i.e., whiplash). All participants were administered a flexible battery of cognitive tests, and some underwent neurodiagnostic procedures and sleep studies. Compared with published norms, neuropsychological data revealed significant and persistent age-adjusted cognitive deficits, primarily in the area of executive functioning. Participants frequently complained of problems with behavioral control, sleep, and sexuality. Although structural neuroimaging was not sensitive in detecting brain pathology, quantitative electroencephalography was abnormal in all the participants evaluated, showing frontocentral slowing and increased spike wave activity. We propose that whiplash injury can produce wide-ranging circuitry dysfunction and that test selection is critical in identifying cognitive deficits.

Developmental origins of brain disorders: roles for dopamine

PubMed Central

Money, Kelli M.; Stanwood, Gregg D.

2013-01-01

Neurotransmitters and neuromodulators, such as dopamine, participate in a wide range of behavioral and cognitive functions in the adult brain, including movement, cognition, and reward. Dopamine-mediated signaling plays a fundamental neurodevelopmental role in forebrain differentiation and circuit formation. These developmental effects, such as modulation of neuronal migration and dendritic growth, occur before synaptogenesis and demonstrate novel roles for dopaminergic signaling beyond neuromodulation at the synapse. Pharmacologic and genetic disruptions demonstrate that these effects are brain region- and receptor subtype-specific. For example, the striatum and frontal cortex exhibit abnormal neuronal structure and function following prenatal disruption of dopamine receptor signaling. Alterations in these processes are implicated in the pathophysiology of neuropsychiatric disorders, and emerging studies of neurodevelopmental disruptions may shed light on the pathophysiology of abnormal neuronal circuitry in neuropsychiatric disorders. PMID:24391541

Longitudinal variations of brain functional connectivity: A case report study based on a mouse model of epilepsy.

PubMed

Erramuzpe, A; Encinas, J M; Sierra, A; Maletic-Savatic, M; Brewster, A L; Anderson, Anne E; Stramaglia, S; Cortes, Jesus M

2015-01-01

Brain Functional Connectivity (FC) quantifies statistical dependencies between areas of the brain. FC has been widely used to address altered function of brain circuits in control conditions compared to different pathological states, including epilepsy, a major neurological disorder. However, FC also has the as yet unexplored potential to help us understand the pathological transformation of the brain circuitry. Our hypothesis is that FC can differentiate global brain interactions across a time-scale of days. To this end, we present a case report study based on a mouse model for epilepsy and analyze longitudinal intracranial electroencephalography data of epilepsy to calculate FC changes from the initial insult (status epilepticus) and over the latent period, when epileptogenic networks emerge, and at chronic epilepsy, when unprovoked seizures occur as spontaneous events. We found that the overall network FC at low frequency bands decreased immediately after status epilepticus was provoked, and increased monotonously later on during the latent period. Overall, our results demonstrate the capacity of FC to address longitudinal variations of brain connectivity across the establishment of pathological states.

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

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.

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

The Neuropathology of Autism

PubMed Central

Blatt, Gene J.

2012-01-01

Autism is a behaviorally defined neurodevelopmental disorder that affects over 1% of new births in the United States and about 2% of boys. The etiologies are unknown and they are genetically complex. There may be epigenetic effects, environmental influences, and other factors that contribute to the mechanisms and affected neural pathway(s). The underlying neuropathology of the disorder has been evolving in the literature to include specific brain areas in the cerebellum, limbic system, and cortex. Part(s) of structures appear to be affected most rather than the entire structure, for example, select nuclei of the amygdala, the fusiform face area, and so forth. Altered cortical organization characterized by more frequent and narrower minicolumns and early overgrowth of the frontal portion of the brain, affects connectivity. Abnormalities include cytoarchitectonic laminar differences, excess white matter neurons, decreased numbers of GABAergic cerebellar Purkinje cells, and other events that can be traced developmentally and cause anomalies in circuitry. Problems with neurotransmission are evident by recent receptor and binding site studies especially in the inhibitory GABA system likely contributing to an imbalance of excitatory/inhibitory transmission. As postmortem findings are related to core behavior symptoms, and technology improves, researchers are gaining a much better perspective of contributing factors to the disorder. PMID:24278731

The neurobiological and behavioral overlaps of nicotine and food addiction.

PubMed

Criscitelli, Kristen; Avena, Nicole M

2016-11-01

Both cigarette smoking and obesity are significant public health concerns and are associated with increased risk of early mortality. It is well established that the mesolimbic dopamine pathway is an important component of the reward system within the brain and is implicated in the development of addiction. Indeed, nicotine and highly palatable foods are capable of altering dopamine release within this system, engendering addictive like responses in susceptible individuals. Although additional research is warranted, findings from animal and human literature have elucidated many of neuroadaptions that occur from exposure to nicotine and highly palatable foods, leading to a greater understanding of the underlying mechanisms contributing to these aberrant behaviors. In this review we present the findings taken from preclinical and clinical literature of the known effects of exposure to nicotine and highly palatable foods on the reward related circuitry within the brain. Further, we compare the neurobiological and behavioral overlaps between nicotine, highly palatable foods and obesity. Lastly, we examine the stigma associated with smoking, obesity and food addiction, and the consequences stigma has on the overall health and wellbeing of an individual. Copyright © 2016. Published by Elsevier Inc.

Alterations in Striatal Circuits Underlying Addiction-Like Behaviors.

PubMed

Kim, Hyun Jin; Lee, Joo Han; Yun, Kyunghwa; Kim, Joung-Hun

2017-06-30

Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.

Research progress on Drosophila visual cognition in China.

PubMed

Guo, AiKe; Zhang, Ke; Peng, YueQin; Xi, Wang

2010-03-01

Visual cognition, as one of the fundamental aspects of cognitive neuroscience, is generally associated with high-order brain functions in animals and human. Drosophila, as a model organism, shares certain features of visual cognition in common with mammals at the genetic, molecular, cellular, and even higher behavioral levels. From learning and memory to decision making, Drosophila covers a broad spectrum of higher cognitive behaviors beyond what we had expected. Armed with powerful tools of genetic manipulation in Drosophila, an increasing number of studies have been conducted in order to elucidate the neural circuit mechanisms underlying these cognitive behaviors from a genes-brain-behavior perspective. The goal of this review is to integrate the most important studies on visual cognition in Drosophila carried out in mainland China during the last decade into a body of knowledge encompassing both the basic neural operations and circuitry of higher brain function in Drosophila. Here, we consider a series of the higher cognitive behaviors beyond learning and memory, such as visual pattern recognition, feature and context generalization, different feature memory traces, salience-based decision, attention-like behavior, and cross-modal leaning and memory. We discuss the possible general gain-gating mechanism implementing by dopamine - mushroom body circuit in fly's visual cognition. We hope that our brief review on this aspect will inspire further study on visual cognition in flies, or even beyond.

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

Brain Circuitry Supporting Multi-Organ Autonomic Outflow in Response to Nausea.

PubMed

Sclocco, Roberta; Kim, Jieun; Garcia, Ronald G; Sheehan, James D; Beissner, Florian; Bianchi, Anna M; Cerutti, Sergio; Kuo, Braden; Barbieri, Riccardo; Napadow, Vitaly

2016-02-01

While autonomic outflow is an important co-factor of nausea physiology, central control of this outflow is poorly understood. We evaluated sympathetic (skin conductance level) and cardiovagal (high-frequency heart rate variability) modulation, collected synchronously with functional MRI (fMRI) data during nauseogenic visual stimulation aimed to induce vection in susceptible individuals. Autonomic data guided analysis of neuroimaging data, using a stimulus-based (analysis windows set by visual stimulation protocol) and percept-based (windows set by subjects' ratings) approach. Increased sympathetic and decreased parasympathetic modulation was associated with robust and anti-correlated brain activity in response to nausea. Specifically, greater autonomic response was associated with reduced fMRI signal in brain regions such as the insula, suggesting an inhibitory relationship with premotor brainstem nuclei. Interestingly, some sympathetic/parasympathetic specificity was noted. Activity in default mode network and visual motion areas was anti-correlated with parasympathetic outflow at peak nausea. In contrast, lateral prefrontal cortical activity was anti-correlated with sympathetic outflow during recovery, soon after cessation of nauseogenic stimulation. These results suggest divergent central autonomic control for sympathetic and parasympathetic response to nausea. Autonomic outflow and the central autonomic network underlying ANS response to nausea may be an important determinant of overall nausea intensity and, ultimately, a potential therapeutic target. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cognitive interventions for addiction medicine: Understanding the underlying neurobiological mechanisms

PubMed Central

Zilverstand, Anna; Parvaz, Muhammad A.; Moeller, Scott J.; Goldstein, Rita Z.

2016-01-01

Neuroimaging provides a tool for investigating the neurobiological mechanisms of cognitive interventions in addiction. The aim of this review was to describe the brain circuits that are recruited during cognitive interventions, examining differences between various treatment modalities while highlighting core mechanisms, in drug addicted individuals. Based on a systematic Medline search we reviewed neuroimaging studies on cognitive behavioral therapy, cognitive inhibition of craving, motivational interventions, emotion regulation, mindfulness, and neurofeedback training in addiction. Across intervention modalities, common results included the normalization of aberrant activity in the brain’s reward circuitry, and the recruitment and strengthening of the brain’s inhibitory control network. Results suggest that different cognitive interventions act, at least partly, through recruitment of a common inhibitory control network as a core mechanism. This implies potential transfer effects between training modalities. Overall, results confirm that chronically hypoactive prefrontal regions implicated in cognitive control in addiction can be normalized through cognitive means. PMID:26822363

Reality of auditory verbal hallucinations.

PubMed

Raij, Tuukka T; Valkonen-Korhonen, Minna; Holi, Matti; Therman, Sebastian; Lehtonen, Johannes; Hari, Riitta

2009-11-01

Distortion of the sense of reality, actualized in delusions and hallucinations, is the key feature of psychosis but the underlying neuronal correlates remain largely unknown. We studied 11 highly functioning subjects with schizophrenia or schizoaffective disorder while they rated the reality of auditory verbal hallucinations (AVH) during functional magnetic resonance imaging (fMRI). The subjective reality of AVH correlated strongly and specifically with the hallucination-related activation strength of the inferior frontal gyri (IFG), including the Broca's language region. Furthermore, how real the hallucination that subjects experienced was depended on the hallucination-related coupling between the IFG, the ventral striatum, the auditory cortex, the right posterior temporal lobe, and the cingulate cortex. Our findings suggest that the subjective reality of AVH is related to motor mechanisms of speech comprehension, with contributions from sensory and salience-detection-related brain regions as well as circuitries related to self-monitoring and the experience of agency.

Reality of auditory verbal hallucinations

PubMed Central

Valkonen-Korhonen, Minna; Holi, Matti; Therman, Sebastian; Lehtonen, Johannes; Hari, Riitta

2009-01-01

Distortion of the sense of reality, actualized in delusions and hallucinations, is the key feature of psychosis but the underlying neuronal correlates remain largely unknown. We studied 11 highly functioning subjects with schizophrenia or schizoaffective disorder while they rated the reality of auditory verbal hallucinations (AVH) during functional magnetic resonance imaging (fMRI). The subjective reality of AVH correlated strongly and specifically with the hallucination-related activation strength of the inferior frontal gyri (IFG), including the Broca's language region. Furthermore, how real the hallucination that subjects experienced was depended on the hallucination-related coupling between the IFG, the ventral striatum, the auditory cortex, the right posterior temporal lobe, and the cingulate cortex. Our findings suggest that the subjective reality of AVH is related to motor mechanisms of speech comprehension, with contributions from sensory and salience-detection-related brain regions as well as circuitries related to self-monitoring and the experience of agency. PMID:19620178

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.

A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and roadmap for future research

PubMed Central

Phillips, Mary L; Swartz, Holly A.

2014-01-01

Objective This critical review appraises neuroimaging findings in bipolar disorder in emotion processing, emotion regulation, and reward processing neural circuitry, to synthesize current knowledge of the neural underpinnings of bipolar disorder, and provide a neuroimaging research “roadmap” for future studies. Method We examined findings from all major studies in bipolar disorder that used fMRI, volumetric analyses, diffusion imaging, and resting state techniques, to inform current conceptual models of larger-scale neural circuitry abnormalities in bipolar disorder Results Bipolar disorder can be conceptualized in neural circuitry terms as parallel dysfunction in bilateral prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward processing circuitry, that result in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation and heightened reward sensitivity. A potential structural basis for these functional abnormalities are gray matter decreases in prefrontal and temporal cortices, amygdala and hippocampus, and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Conclusion Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuitries supporting emotion processing, emotion regulation and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in bipolar disorder and at-risk youth; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful, individual-level data. Such studies will help identify clinically-relevant biomarkers to guide diagnosis and treatment decision-making for individuals with bipolar disorder. PMID:24626773

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.

Her versus his migraine: multiple sex differences in brain function and structure

PubMed Central

Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

2012-01-01

Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a ‘sex phenotype’ in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs. PMID:22843414

Her versus his migraine: multiple sex differences in brain function and structure.

PubMed

Maleki, Nasim; Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

2012-08-01

Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a 'sex phenotype' in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs.

Virtual reality adaptive stimulation of limbic networks in the mental readiness training.

PubMed

Cosić, Kresimir; Popović, Sinisa; Kostović, Ivica; Judas, Milos

2010-01-01

A significant proportion of severe psychological problems in recent large-scale peacekeeping operations underscores the importance of effective methods for strengthening the stress resilience. Virtual reality (VR) adaptive stimulation, based on the estimation of the participant's emotional state from physiological signals, may enhance the mental readiness training (MRT). Understanding neurobiological mechanisms by which the MRT based on VR adaptive stimulation can affect the resilience to stress is important for practical application in the stress resilience management. After the delivery of a traumatic audio-visual stimulus in the VR, the cascade of events occurs in the brain, which evokes various physiological manifestations. In addition to the "limbic" emotional and visceral brain circuitry, other large-scale sensory, cognitive, and memory brain networks participate with less known impact in this physiological response. The MRT based on VR adaptive stimulation may strengthen the stress resilience through targeted brain-body interactions. Integrated interdisciplinary efforts, which would integrate the brain imaging and the proposed approach, may contribute to clarifying the neurobiological foundation of the resilience to stress.

Bilinguals Use Language-Control Brain Areas More Than Monolinguals to Perform Non-Linguistic Switching Tasks

PubMed Central

Rodríguez-Pujadas, Aina; Sanjuán, Ana; Ventura-Campos, Noelia; Román, Patricia; Martin, Clara; Barceló, Francisco; Costa, Albert; Ávila, César

2013-01-01

We tested the hypothesis that early bilinguals use language-control brain areas more than monolinguals when performing non-linguistic executive control tasks. We do so by exploring the brain activity of early bilinguals and monolinguals in a task-switching paradigm using an embedded critical trial design. Crucially, the task was designed such that the behavioural performance of the two groups was comparable, allowing then to have a safer comparison between the corresponding brain activity in the two groups. Despite the lack of behavioural differences between both groups, early bilinguals used language-control areas – such as left caudate, and left inferior and middle frontal gyri – more than monolinguals, when performing the switching task. Results offer direct support for the notion that, early bilingualism exerts an effect in the neural circuitry responsible for executive control. This effect partially involves the recruitment of brain areas involved in language control when performing domain-general executive control tasks, highlighting the cross-talk between these two domains. PMID:24058456

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.

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

Coping styles and behavioural flexibility: towards underlying mechanisms

PubMed Central

Coppens, Caroline M.; de Boer, Sietse F.; Koolhaas, Jaap M.

2010-01-01

A coping style (also termed behavioural syndrome or personality) is defined as a correlated set of individual behavioural and physiological characteristics that is consistent over time and across situations. This relatively stable trait is a fundamental and adaptively significant phenomenon in the biology of a broad range of species, i.e. it confers differential fitness consequences under divergent environmental conditions. Behavioural flexibility appears to be an important underlying attribute or feature of the coping style that might explain consistency across situations. Proactive coping is characterized by low flexibility expressed as rather rigid, routine-like behavioural tendencies and reduced impulse control (behavioural inhibition) in operant conditioning paradigms. This article summarizes some of the evidence that individual differentiation in behavioural flexibility emerges as a function of underlying variability in the activation of a brain circuitry that includes the prefrontal cortex and its key neurochemical signalling pathways (e.g. dopaminergic and serotonergic input). We argue that the multidimensional nature of animal personality and the terminology used for the various dimensions should reflect the differential pattern of activation of the underlying neuronal network and the behavioural control function of its components. Accordingly, unravelling the molecular mechanisms that give rise to individual differences in the coping style will be an important topic in biobehavioural neurosciences, ecology and evolutionary biology. PMID:21078654

Synaptic reorganization of inhibitory hilar interneuron circuitry after traumatic brain injury in mice

PubMed Central

Hunt, Robert F.; Scheff, Stephen W.; Smith, Bret N.

2011-01-01

Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found in granule cells after paired electrical stimulation of the hilus. Despite reduced inhibitory input to granule cells, action potential and EPSC frequencies were increased in hilar GABA neurons from slices ipsilateral to the injury, versus those from control or contralateral slices. Further, increased excitatory synaptic activity was detected in hilar GABA neurons ipsilateral to the injury after glutamate photostimulation of either the granule cell or CA3 pyramidal cell layers. Together, these findings suggest that excitatory drive to surviving hilar GABA neurons is enhanced by convergent input from both pyramidal and granule cells, but synaptic inhibition of granule cells is not fully restored after injury. This rewiring of circuitry regulating hilar inhibitory neurons may reflect an important compensatory mechanism, but it may also contribute to network destabilization by increasing the relative impact of surviving individual interneurons in controlling granule cell excitability in the posttraumatic dentate gyrus. PMID:21543618

Pro-Dopamine Regulator – (KB220) to Balance Brain Reward Circuitry in Reward Deficiency Syndrome (RDS)

PubMed Central

Blum, Kenneth; Febo, Marcelo; Fried, Lyle; Baron, David; Braverman, Eric R.; Dushaj, Kristina; Li, Mona; Demetrovics, Zsolt; Badgaiyan, Rajendra D.

2017-01-01

We are faced with a worldwide opiate/opioid epidemic that is devastating. According to the Centers for Disease Control and Prevention (CDC), at least 127 people, young and old, are dying every day in America due to narcotic overdose. The Food and Drug Administration (FDA) has approved Medication-Assisted Treatments (MATs) for opiate/opioids as well as alcohol and nicotine. The mechanism of action of most MATS favors either blocking of dopaminergic function or a form of Opiate Substitution Therapy (OST). These treatment options are adequate for short-term treatment of the symptoms of addiction and harm reduction but fail long-term to deal with the cause or lead to recovery. There is a need to continue to seek better treatment options. This mini-review is the history of the development of one such treatment; a glutaminergic-dopaminergic optimization complex called KB220. Growing evidence indicates that brain reward circuitry controls drug addiction, in conjunction with “anti-reward systems” as the “anti-reward systems” can be affected by both glutaminergic and dopaminergic transmission. KB220 may likely alter the function of these regions and provide for the possible eventual balancing the brain reward system and the induction of “dopamine homeostasis.” Many of these concepts have been reported elsewhere and have become an integral part of the addiction science literature. However, the concise review may encourage readership to reconsider these facts and stimulate further research focused on the impact that the induction of “dopamine homeostasis” may have on recovery and relapse prevention. PMID:28804788

The neurobiology of addiction: the perspective from magnetic resonance imaging present and future.

PubMed

Suckling, John; Nestor, Liam J

2017-02-01

Addiction is associated with severe economic and social consequences and personal tragedies, the scientific exploration of which draws upon investigations at the molecular, cellular and systems levels with a wide variety of technologies. Magnetic resonance imaging (MRI) has been key to mapping effects observed at the microscopic and mesoscopic scales. The range of measurements from this apparatus has opened new avenues linking neurobiology to behaviour. This review considers the role of MRI in addiction research, and what future technological improvements might offer. A hermeneutic strategy supplemented by an expansive, systematic search of PubMed, Scopus and Web of Science databases, covering from database inception to October 2015, with a conjunction of search terms relevant to addiction and MRI. Formal meta-analyses were prioritized. Results from methods that probe brain structure and function suggest frontostriatal circuitry disturbances within specific cognitive domains, some of which predict drug relapse and treatment response. New methods of processing imaging data are opening opportunities for understanding the role of cerebral vasculature, a global view of brain communication and the complex topology of the cortical surface and drug action. Future technological advances include increases in MRI field strength, with concomitant improvements in image quality. The magnetic resonance imaging literature provides a limited but convergent picture of the neurobiology of addiction as global changes to brain structure and functional disturbances to frontostriatal circuitry, accompanied by changes in anterior white matter. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits.

PubMed

Salamone, J D; Correa, M; Farrar, A; Mingote, S M

2007-04-01

Over the last several years, it has become apparent that there are critical problems with the hypothesis that brain dopamine (DA) systems, particularly in the nucleus accumbens, directly mediate the rewarding or primary motivational characteristics of natural stimuli such as food. Hypotheses related to DA function are undergoing a substantial restructuring, such that the classic emphasis on hedonia and primary reward is giving way to diverse lines of research that focus on aspects of instrumental learning, reward prediction, incentive motivation, and behavioral activation. The present review discusses dopaminergic involvement in behavioral activation and, in particular, emphasizes the effort-related functions of nucleus accumbens DA and associated forebrain circuitry. The effects of accumbens DA depletions on food-seeking behavior are critically dependent upon the work requirements of the task. Lever pressing schedules that have minimal work requirements are largely unaffected by accumbens DA depletions, whereas reinforcement schedules that have high work (e.g., ratio) requirements are substantially impaired by accumbens DA depletions. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related decision making. Rats with accumbens DA depletions reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead, these rats select a less-effortful type of food-seeking behavior. Along with prefrontal cortex and the amygdala, nucleus accumbens is a component of the brain circuitry regulating effort-related functions. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as energy-related disorders such as psychomotor slowing, fatigue, or anergia in depression.

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

Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z

PubMed Central

Badgaiyan, Rajendra D.; Thanos, Panayotis K.; Kulkarni, Praveen; Giordano, John; Baron, David; Gold, Mark S.

2017-01-01

Dopaminergic reward dysfunction in addictive behaviors is well supported in the literature. There is evidence that alterations in synchronous neural activity between brain regions subserving reward and various cognitive functions may significantly contribute to substance-related disorders. This study presents the first evidence showing that a pro-dopaminergic nutraceutical (KB220Z) significantly enhances, above placebo, functional connectivity between reward and cognitive brain areas in the rat. These include the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic loci. Significant functional connectivity, increased brain connectivity volume recruitment (potentially neuroplasticity), and dopaminergic functionality were found across the brain reward circuitry. Increases in functional connectivity were specific to these regions and were not broadly distributed across the brain. While these initial findings have been observed in drug naïve rodents, this robust, yet selective response implies clinical relevance for addicted individuals at risk for relapse, who show reductions in functional connectivity after protracted withdrawal. Future studies will evaluate KB220Z in animal models of addiction. PMID:28445527

Fluorescence laminar optical tomography for brain imaging: system implementation and performance evaluation.

PubMed

Azimipour, Mehdi; Sheikhzadeh, Mahya; Baumgartner, Ryan; Cullen, Patrick K; Helmstetter, Fred J; Chang, Woo-Jin; Pashaie, Ramin

2017-01-01

We present our effort in implementing a fluorescence laminar optical tomography scanner which is specifically designed for noninvasive three-dimensional imaging of fluorescence proteins in the brains of small rodents. A laser beam, after passing through a cylindrical lens, scans the brain tissue from the surface while the emission signal is captured by the epi-fluorescence optics and is recorded using an electron multiplication CCD sensor. Image reconstruction algorithms are developed based on Monte Carlo simulation to model light–tissue interaction and generate the sensitivity matrices. To solve the inverse problem, we used the iterative simultaneous algebraic reconstruction technique. The performance of the developed system was evaluated by imaging microfabricated silicon microchannels embedded inside a substrate with optical properties close to the brain as a tissue phantom and ultimately by scanning brain tissue in vivo. Details of the hardware design and reconstruction algorithms are discussed and several experimental results are presented. The developed system can specifically facilitate neuroscience experiments where fluorescence imaging and molecular genetic methods are used to study the dynamics of the brain circuitries.

Stress response in postpartum women with and without obsessive–compulsive symptoms: an fMRI study

PubMed Central

Lord, Catherine; Steiner, Meir; Soares, Claudio N.; Carew, Caitlin L.; Hall, Geoffrey B.

2012-01-01

Background During the postpartum period, some women might be under a considerable amount of stress and at increased risk for onset or exacerbation of obsessive–compulsive disorder (OCD). Little is known about the stress response correlates during the postpartum period and in patients with OCD. This study aimed to examine the cerebral, psychologic and endocrine correlates of the stress response in patients with OCD and during the postpartum period. Methods Women with postpartum OCD, healthy postpartum women and healthy mothers past the postpartum period underwent functional magnetic resonance imaging while facing a reliable psychosocial stressor (the Montreal Imaging Stress Task). Stress-related psychologic and endocrine responses (i.e., cortisol) were obtained. Results We enrolled 12 women with postpartum OCD, 16 healthy postpartum women and 11 healthy mothers past the postpartum period in our study. Compared with healthy postpartum counterparts, postpartum women with OCD had a heightened self-reported and endocrine stress response associated with a distinct brain activation pattern in response to psychosocial stress involving the orbitofrontal and temporal cortices. Moreover, compared with mothers assessed in a period of time beyond the postpartum period, healthy postpartum women did not differ in psychologic and cortisol response to stress, but recruited different brain regions, such as the dorsolateral pre-frontal cortex and the anterior cingulate cortex, during exposure to stress. Limitations Potential confounding factors, such as medication use, breastfeeding, parity and personality factors, may have modulated the stress-related endocrine response and could not be assessed in this study. Conclusion Obsessive–compulsive disorder and the postpartum period differentially influence the brain circuitry underlying psychosocial stress as well as the psychologic and endocrine responses. PMID:22122779

Divergent neuronal circuitries underlying acute orexigenic effects of peripheral or central ghrelin: critical role of brain accessibility

PubMed Central

Cabral, Agustina; Valdivia, Spring; Fernandez, Gimena; Reynaldo, Mirta; Perello, Mario

2014-01-01

Ghrelin is an octanoylated peptide hormone that potently and rapidly increases food intake. The orexigenic action of ghrelin involves the hypothalamic arcuate nucleus (ARC), which is accessible to plasma ghrelin and expresses high levels of the ghrelin receptor. Local administration of ghrelin in a variety of other brain nuclei also increases food intake. It is currently unclear, however, if these non-ARC ghrelin brain targets are impacted by physiological increases of plasma ghrelin. Thus, the current study was designed to clarify which ghrelin brain targets participate in the short-term orexigenic actions of ghrelin. First, c-Fos induction into mouse brains centrally or peripherally treated with ghrelin was analyzed. It was confirmed that peripherally administered ghrelin dose dependently increases food intake and mainly activates c-Fos in ARC neurons. In contrast, centrally administered ghrelin activates c-Fos in a larger number of brain nuclei. To determine which nuclei are directly accessible to ghrelin, mice were centrally or peripherally injected with a fluorescent ghrelin tracer. It was found that peripherally injected tracer mainly accesses the ARC while centrally injected tracer reaches most brain areas known to express ghrelin receptors. Following that, ghrelin effects in ARC-ablated mice were tested and it was found that these mice failed to increase food intake in response to peripherally administered ghrelin but fully responded to centrally administered ghrelin. ARC-ablated mice showed similar patterns of ghrelin-induced c-Fos expression as seen in control mice with the exception of the ARC, where no c-Fos was found. Thus, peripheral ghrelin mainly accesses the ARC, which is required for the orexigenic effects of the hormone. Central ghrelin accesses a variety of nuclei, which can mediate the orexigenic effects of the hormone even in the absence of an intact ARC. PMID:24888783

Differences in brain morphology and working memory capacity across childhood.

PubMed

Bathelt, Joe; Gathercole, Susan E; Johnson, Amy; Astle, Duncan E

2018-05-01

Working memory (WM) skills are closely associated with learning progress in key areas such as reading and mathematics across childhood. As yet, however, little is known about how the brain systems underpinning WM develop over this critical developmental period. The current study investigated whether and how structural brain correlates of components of the working memory system change over development. Verbal and visuospatial short-term and working memory were assessed in 153 children between 5.58 and 15.92 years, and latent components of the working memory system were derived. Fractional anisotropy and cortical thickness maps were derived from T1-weighted and diffusion-weighted MRI and processed using eigenanatomy decomposition. There was a greater involvement of the corpus callosum and posterior temporal white matter in younger children for performance associated with the executive part of the working memory system. For older children, this was more closely linked with the thickness of the occipitotemporal cortex. These findings suggest that increasing specialization leads to shifts in the contribution of neural substrates over childhood, moving from an early dependence on a distributed system supported by long-range connections to later reliance on specialized local circuitry. Our findings demonstrate that despite the component factor structure being stable across childhood, the underlying brain systems supporting working memory change. Taking the age of the child into account, and not just their overall score, is likely to be critical for understanding the nature of the limitations on their working memory capacity. © 2017 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

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

Deep-Brain Stimulation for Basal Ganglia Disorders.

PubMed

Wichmann, Thomas; Delong, Mahlon R

2011-07-01

The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of 'motor' portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the 'limbic' basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders.

How Prediction Errors Shape Perception, Attention, and Motivation

PubMed Central

den Ouden, Hanneke E. M.; Kok, Peter; de Lange, Floris P.

2012-01-01

Prediction errors (PE) are a central notion in theoretical models of reinforcement learning, perceptual inference, decision-making and cognition, and prediction error signals have been reported across a wide range of brain regions and experimental paradigms. Here, we will make an attempt to see the forest for the trees and consider the commonalities and differences of reported PE signals in light of recent suggestions that the computation of PE forms a fundamental mode of brain function. We discuss where different types of PE are encoded, how they are generated, and the different functional roles they fulfill. We suggest that while encoding of PE is a common computation across brain regions, the content and function of these error signals can be very different and are determined by the afferent and efferent connections within the neural circuitry in which they arise. PMID:23248610

Reward, salience, and attentional networks are activated by religious experience in devout Mormons

PubMed Central

Ferguson, Michael A.; Nielsen, Jared A.; King, Jace B.; Dai, Li; Giangrasso, Danielle M.; Holman, Rachel; Korenberg, Julie R.; Anderson, Jeffrey S.

2017-01-01

High-level cognitive and emotional experience arises from brain activity, but the specific brain substrates for religious and spiritual euphoria remain unclear. We demonstrate using functional magnetic resonance imaging scans in 19 devout Mormons that a recognizable feeling central to their devotional practice was reproducibly associated with activation in nucleus accumbens, ventromedial prefrontal cortex, and frontal attentional regions. Nucleus accumbens activation preceded peak spiritual feelings by 1–3 s and was replicated in four separate tasks. Attentional activation in the anterior cingulate and frontal eye fields was greater in the right hemisphere. The association of abstract ideas and brain reward circuitry may interact with frontal attentional and emotive salience processing, suggesting a mechanism whereby doctrinal concepts may come to be intrinsically rewarding and motivate behavior in religious individuals. PMID:27834117

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.

Advances in the neurobiological bases for food ‘liking’ versus ‘wanting’

PubMed Central

Castro, D.C.; Berridge, K.C.

2014-01-01

The neural basis of food sensory pleasure has become an increasingly studied topic in neuroscience and psychology. Progress has been aided by the discovery of localized brain subregions called hedonic hotspots in the early 2000’s, which are able to causally amplify positive affective reactions to palatable tastes (‘liking’) in response to particular neurochemical or neurobiological stimulations. Those hedonic mechanisms are at least partly distinct from larger mesocorticolimbic circuitry that generates the incentive motivation to eat (‘wanting’). In this review, we aim to describe findings on these brain hedonic hotspots, especially in the nucleus accumbens and ventral pallidum, and discuss their role in generating food pleasure and appetite. PMID:24874776

Brain imaging in the context of food perception and eating.

PubMed

Hollmann, Maurice; Pleger, Burkhard; Villringer, Arno; Horstmann, Annette

2013-02-01

Eating behavior depends heavily on brain function. In recent years, brain imaging has proved to be a powerful tool to elucidate brain function and brain structure in the context of eating. In this review, we summarize recent findings in the fast growing body of literature in the field and provide an overview of technical aspects as well as the basic brain mechanisms identified with imaging. Furthermore, we highlight findings linking neural processing of eating-related stimuli with obesity. The consumption of food is based on a complex interplay between homeostatic and hedonic mechanisms. Several hormones influence brain activity to regulate food intake and interact with the brain's reward circuitry, which is partly mediated by dopamine signaling. Additionally, it was shown that food stimuli trigger cognitive control mechanisms that incorporate internal goals into food choice. The brain mechanisms observed in this context are strongly influenced by genetic factors, sex and personality traits. Overall, a complex picture arises from brain-imaging findings, because a multitude of factors influence human food choice. Although several key mechanisms have been identified, there is no comprehensive model that is able to explain the behavioral observations to date. Especially a careful characterization of patients according to genotypes and phenotypes could help to better understand the current and future findings in neuroimaging studies.

Zebrafish transgenic constructs label specific neurons in Xenopus laevis spinal cord and identify frog V0v spinal neurons.

PubMed

Juárez-Morales, José L; Martinez-De Luna, Reyna I; Zuber, Michael E; Roberts, Alan; Lewis, Katharine E

2017-09-01

A correctly functioning spinal cord is crucial for locomotion and communication between body and brain but there are fundamental gaps in our knowledge of how spinal neuronal circuitry is established and functions. To understand the genetic program that regulates specification and functions of this circuitry, we need to connect neuronal molecular phenotypes with physiological analyses. Studies using Xenopus laevis tadpoles have increased our understanding of spinal cord neuronal physiology and function, particularly in locomotor circuitry. However, the X. laevis tetraploid genome and long generation time make it difficult to investigate how neurons are specified. The opacity of X. laevis embryos also makes it hard to connect functional classes of neurons and the genes that they express. We demonstrate here that Tol2 transgenic constructs using zebrafish enhancers that drive expression in specific zebrafish spinal neurons label equivalent neurons in X. laevis and that the incorporation of a Gal4:UAS amplification cassette enables cells to be observed in live X. laevis tadpoles. This technique should enable the molecular phenotypes, morphologies and physiologies of distinct X. laevis spinal neurons to be examined together in vivo. We have used an islet1 enhancer to label Rohon-Beard sensory neurons and evx enhancers to identify V0v neurons, for the first time, in X. laevis spinal cord. Our work demonstrates the homology of spinal cord circuitry in zebrafish and X. laevis, suggesting that future work could combine their relative strengths to elucidate a more complete picture of how vertebrate spinal cord neurons are specified, and function to generate behavior. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1007-1020, 2017. © 2017 Wiley Periodicals, Inc.

Functional dysconnectivity of corticostriatal circuitry as a risk phenotype for psychosis.

PubMed

Fornito, Alex; Harrison, Ben J; Goodby, Emmeline; Dean, Anna; Ooi, Cinly; Nathan, Pradeep J; Lennox, Belinda R; Jones, Peter B; Suckling, John; Bullmore, Edward T

2013-11-01

Dysregulation of corticostriatal circuitry has long been thought to be critical in the etiology of psychotic disorders, although the differential roles played by dorsal and ventral systems in mediating risk for psychosis have been contentious. To use resting-state functional magnetic resonance imaging to characterize disease-related, risk-related, and symptom-related changes of corticostriatal functional circuitry in patients with first-episode psychosis and their unaffected first-degree relatives. This case-control cross-sectional study was conducted at a specialist early psychosis clinic, GlaxoSmithKline Clinical Unit, and magnetic resonance imaging facility. Nineteen patients with first-episode psychosis, 25 of their unaffected first-degree relatives, and 26 healthy control subjects were included in this study. Voxelwise statistical parametric maps testing differences in the strength of functional connectivity between 6 striatal seed regions of interest (3 caudate and 3 putamen) per hemisphere and all other brain regions. Disease-related changes, reflecting differences between patients and control subjects, involved widespread dysregulation of corticostriatal systems characterized most prominently by a dorsal-to-ventral gradient of hypoconnectivity to hyperconnectivity between striatal and prefrontal regions. A similar gradient was evident in comparisons between relatives and control subjects, identifying it as a genetically inherited risk phenotype. In patients, functional connectivity in risk-affected and disease-affected dorsal frontostriatal circuitry correlated with the severity of both positive and negative symptoms. First-episode psychosis is associated with pronounced dysregulation of corticostriatal systems, characterized most prominently by hypoconnectivity of dorsal and hyperconnectivity of ventral frontostriatal circuits. These changes correlate with symptom severity and are also apparent in unaffected first-degree relatives, suggesting that they represent a putative risk phenotype for psychotic illness.

Effects of Anterior Capsulotomy on Decision Making in Patients with Refractory Obsessive–Compulsive Disorder

PubMed Central

Zhang, Chencheng; Chen, Yilin; Tian, Shuaiwei; Wang, Tao; Xie, Yile; Jin, Haiyan; Lin, Guozhen; Gong, Hengfen; Zeljic, Kristina; Sun, Bomin; Yang, Tianming; Zhan, Shikun

2017-01-01

Despite various lines of evidence implicating impaired decision-making ability in individuals with obsessive–compulsive disorder (OCD), neuropsychological investigation has generated inconsistent findings. Although the cortico-striato-thalamo-cortical (CSTC) circuitry has been suggested, the involvement of the cortex has not yet been fully demonstrated. Moreover, it is unknown whether surgical intervention on the CSTC circuitry results in a predicted improvement of decision-making ability of OCD. Here we present a study of decision making based on the Iowa Gambling Task (IGT) to investigate decision making in a large sample of individuals with treatment-resistant OCD with and without anterior capsulotomy (AC). Task performance was evaluated in healthy subjects, individuals with OCD that had not undergone surgery, and postsurgical OCD patients with AC. The latter group was further divided into a short-term postsurgical group and a long-term postsurgical group. We found that the OCD patients without surgery performed significantly worse than the healthy controls on the IGT. There were no significant differences in decision-making between the presurgical OCD patients and those at the short-term postsurgical follow-up. Decision-making ability of the long-term postsurgical OCD patients was improved to the level comparable to that of healthy controls. All clinical symptoms (OCD, depression, and anxiety) assessed by psychiatric rating scales were significantly alleviated post-surgically, but exhibited no correlation with their IGT task performance. Our findings provide strong evidence that OCD is linked to impairments in decision-making ability; that impaired CSTC circuitry function is directly involved in the manifestation of OCD; and that AC related improvements in cognitive functions are caused by long-term plasticity in the brain circuitry. PMID:29089909

Effects of Anterior Capsulotomy on Decision Making in Patients with Refractory Obsessive-Compulsive Disorder.

PubMed

Zhang, Chencheng; Chen, Yilin; Tian, Shuaiwei; Wang, Tao; Xie, Yile; Jin, Haiyan; Lin, Guozhen; Gong, Hengfen; Zeljic, Kristina; Sun, Bomin; Yang, Tianming; Zhan, Shikun

2017-01-01

Despite various lines of evidence implicating impaired decision-making ability in individuals with obsessive-compulsive disorder (OCD), neuropsychological investigation has generated inconsistent findings. Although the cortico-striato-thalamo-cortical (CSTC) circuitry has been suggested, the involvement of the cortex has not yet been fully demonstrated. Moreover, it is unknown whether surgical intervention on the CSTC circuitry results in a predicted improvement of decision-making ability of OCD. Here we present a study of decision making based on the Iowa Gambling Task (IGT) to investigate decision making in a large sample of individuals with treatment-resistant OCD with and without anterior capsulotomy (AC). Task performance was evaluated in healthy subjects, individuals with OCD that had not undergone surgery, and postsurgical OCD patients with AC. The latter group was further divided into a short-term postsurgical group and a long-term postsurgical group. We found that the OCD patients without surgery performed significantly worse than the healthy controls on the IGT. There were no significant differences in decision-making between the presurgical OCD patients and those at the short-term postsurgical follow-up. Decision-making ability of the long-term postsurgical OCD patients was improved to the level comparable to that of healthy controls. All clinical symptoms (OCD, depression, and anxiety) assessed by psychiatric rating scales were significantly alleviated post-surgically, but exhibited no correlation with their IGT task performance. Our findings provide strong evidence that OCD is linked to impairments in decision-making ability; that impaired CSTC circuitry function is directly involved in the manifestation of OCD; and that AC related improvements in cognitive functions are caused by long-term plasticity in the brain circuitry.

Brain Hypoactivation, Autonomic Nervous System Dysregulation, and Gonadal Hormones in Depression: A Preliminary Study

PubMed Central

Holsen, Laura M.; Lee, Jong-Hwan; Spaeth, Sarah B.; Ogden, Lauren A.; Klibanski, Anne; Whitfield-Gabrieli, Susan; Sloan, Richard P.; Goldstein, Jill M.

2012-01-01

The comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) is among the 10th leading cause of morbidity and mortality worldwide. Thus, understanding the co-occurrence of these disorders will have major public health significance. MDD is associated with an abnormal stress response, manifested in brain circuitry deficits, gonadal dysfunction, and autonomic nervous system (ANS) dysregulation. Contribution of the relationships between these systems to the pathophysiology of MDD is not well understood. The objective of this preliminary study was to investigate, in parallel, relationships between HPG-axis functioning, stress response circuitry activation, and parasympathetic reactivity in healthy controls and women with MDD. Using fMRI with pulse oximetry [from which we calculated the high frequency (HF) component of R-R interval variability (HF-RRV), a measure of parasympathetic modulation] and hormone data, we studied eight women with recurrent MDD in remission and six controls during a stress response paradigm. We demonstrated that hypoactivations of hypothalamus, amygdala, hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and subgenual ACC were associated with lower parasympathetic cardiac modulation in MDD women. Estradiol and progesterone attenuated group differences in the effect of HF-RRV on hypoactivation in the amygdala, hippocampus, ACC, and OFC in MDD women. Findings have implications for understanding the relationship between mood, arousal, heart regulation, and gonadal hormones, and may provide insights into MDD and CVD risk comorbidity. PMID:22395084

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.

Neurocognitive Development of Risk Aversion from Early Childhood to Adulthood

PubMed Central

Paulsen, David J.; Carter, R. McKell; Platt, Michael L.; Huettel, Scott A.; Brannon, Elizabeth M.

2012-01-01

Human adults tend to avoid risk. In behavioral economic studies, risk aversion is manifest as a preference for sure gains over uncertain gains. However, children tend to be less averse to risk than adults. Given that many of the brain regions supporting decision-making under risk do not reach maturity until late adolescence or beyond it is possible that mature risk-averse behavior may emerge from the development of decision-making circuitry. To explore this hypothesis, we tested 5- to 8-year-old children, 14- to 16-year-old adolescents, and young adults in a risky-decision task during functional magnetic resonance imaging (fMRI) data acquisition. To our knowledge, this is the youngest sample of children in an fMRI decision-making task. We found a number of decision-related brain regions to increase in activation with age during decision-making, including areas associated with contextual memory retrieval and the incorporation of prior outcomes into the current decision-making strategy, e.g., insula, hippocampus, and amygdala. Further, children who were more risk-averse showed increased activation during decision-making in ventromedial prefrontal cortex and ventral striatum. Our findings indicate that the emergence of adult levels of risk aversion co-occurs with the recruitment of regions supporting decision-making under risk, including the integration of prior outcomes into current decision-making behavior. This pattern of results suggests that individual differences in the development of risk aversion may reflect differences in the maturation of these neural processes. PMID:22291627

Anatomy and computational modeling of networks underlying cognitive-emotional interaction

PubMed Central

John, Yohan J.; Bullock, Daniel; Zikopoulos, Basilis; Barbas, Helen

2013-01-01

The classical dichotomy between cognition and emotion equated the first with rationality or logic and the second with irrational behaviors. The idea that cognition and emotion are separable, antagonistic forces competing for dominance of mind has been hard to displace despite abundant evidence to the contrary. For instance, it is now known that a pathological absence of emotion leads to profound impairment of decision making. Behavioral observations of this kind are corroborated at the mechanistic level: neuroanatomical studies reveal that brain areas typically described as underlying either cognitive or emotional processes are linked in ways that imply complex interactions that do not resemble a simple mutual antagonism. Instead, physiological studies and network simulations suggest that top–down signals from prefrontal cortex realize “cognitive control” in part by either suppressing or promoting emotional responses controlled by the amygdala, in a way that facilitates adaptation to changing task demands. Behavioral, anatomical, and physiological data suggest that emotion and cognition are equal partners in enabling a continuum or matrix of flexible behaviors that are subserved by multiple brain regions acting in concert. Here we focus on neuroanatomical data that highlight circuitry that structures cognitive-emotional interactions by directly or indirectly linking prefrontal areas with the amygdala. We also present an initial computational circuit model, based on anatomical, physiological, and behavioral data to explicitly frame the learning and performance mechanisms by which cognition and emotion interact to achieve flexible behavior. PMID:23565082

Neurocognitive development of risk aversion from early childhood to adulthood.

PubMed

Paulsen, David J; Carter, R McKell; Platt, Michael L; Huettel, Scott A; Brannon, Elizabeth M

2011-01-01

Human adults tend to avoid risk. In behavioral economic studies, risk aversion is manifest as a preference for sure gains over uncertain gains. However, children tend to be less averse to risk than adults. Given that many of the brain regions supporting decision-making under risk do not reach maturity until late adolescence or beyond it is possible that mature risk-averse behavior may emerge from the development of decision-making circuitry. To explore this hypothesis, we tested 5- to 8-year-old children, 14- to 16-year-old adolescents, and young adults in a risky-decision task during functional magnetic resonance imaging (fMRI) data acquisition. To our knowledge, this is the youngest sample of children in an fMRI decision-making task. We found a number of decision-related brain regions to increase in activation with age during decision-making, including areas associated with contextual memory retrieval and the incorporation of prior outcomes into the current decision-making strategy, e.g., insula, hippocampus, and amygdala. Further, children who were more risk-averse showed increased activation during decision-making in ventromedial prefrontal cortex and ventral striatum. Our findings indicate that the emergence of adult levels of risk aversion co-occurs with the recruitment of regions supporting decision-making under risk, including the integration of prior outcomes into current decision-making behavior. This pattern of results suggests that individual differences in the development of risk aversion may reflect differences in the maturation of these neural processes.

Motivational deficits after brain injury: effects of bromocriptine in 11 patients.

PubMed Central

Powell, J H; al-Adawi, S; Morgan, J; Greenwood, R J

1996-01-01

OBJECTIVE: To test the hypothesis that treatment with bromocriptine would ameliorate deficits in clinical motivation, responsiveness to reward, and frontal cognitive function after brain injury. METHOD: An open trial in six men and five women who had had either traumatic brain injury or subarachnoid haemorrhage between two months and five years previously. After repeated baseline assessments, bromocriptine was given in gradually increasing doses. Assessments were repeated at increasing doses, during maintenance, and after withdrawal. Novel structured instruments for quantifying motivation were developed; measures of anxiety and depression, and cognitive tests sensitive to motivation or frontal lobe involvement were also given. RESULTS: Bromocriptine treatment was followed by improved scores on all measures other than mood. Improvement was maintained after bromocriptine withdrawal in eight of the patients. CONCLUSION: Poor motivation in patients with brain injury may result from dysfunction in the mesolimbic/mesocortical dopaminergic circuitry, giving rise to associated deficiencies in reward responsiveness and frontal cognitive function. PMID:8774407

Canonical Genetic Signatures of the Adult Human Brain

PubMed Central

Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

2015-01-01

The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

Mapping remodeling of thalamocortical projections in the living reeler mouse brain by diffusion tractography

PubMed Central

Harsan, Laura-Adela; Dávid, Csaba; Reisert, Marco; Schnell, Susanne; Hennig, Jürgen; von Elverfeldt, Dominik; Staiger, Jochen F.

2013-01-01

A major challenge in neuroscience is to accurately decipher in vivo the entire brain circuitry (connectome) at a microscopic level. Currently, the only methodology providing a global noninvasive window into structural brain connectivity is diffusion tractography. The extent to which the reconstructed pathways reflect realistic neuronal networks depends, however, on data acquisition and postprocessing factors. Through a unique combination of approaches, we designed and evaluated herein a framework for reliable fiber tracking and mapping of the living mouse brain connectome. One important wiring scheme, connecting gray matter regions and passing fiber-crossing areas, was closely examined: the lemniscal thalamocortical (TC) pathway. We quantitatively validated the TC projections inferred from in vivo tractography with correlative histological axonal tracing in the same wild-type and reeler mutant mice. We demonstrated noninvasively that changes in patterning of the cortical sheet, such as highly disorganized cortical lamination in reeler, led to spectacular compensatory remodeling of the TC pathway. PMID:23610438

Oscillatory brain activity in spontaneous and induced sleep stages in flies.

PubMed

Yap, Melvyn H W; Grabowska, Martyna J; Rohrscheib, Chelsie; Jeans, Rhiannon; Troup, Michael; Paulk, Angelique C; van Alphen, Bart; Shaw, Paul J; van Swinderen, Bruno

2017-11-28

Sleep is a dynamic process comprising multiple stages, each associated with distinct electrophysiological properties and potentially serving different functions. While these phenomena are well described in vertebrates, it is unclear if invertebrates have distinct sleep stages. We perform local field potential (LFP) recordings on flies spontaneously sleeping, and compare their brain activity to flies induced to sleep using either genetic activation of sleep-promoting circuitry or the GABA A agonist Gaboxadol. We find a transitional sleep stage associated with a 7-10 Hz oscillation in the central brain during spontaneous sleep. Oscillatory activity is also evident when we acutely activate sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila. In contrast, sleep following Gaboxadol exposure is characterized by low-amplitude LFPs, during which dFB-induced effects are suppressed. Sleep in flies thus appears to involve at least two distinct stages: increased oscillatory activity, particularly during sleep induction, followed by desynchronized or decreased brain activity.

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.

Motor sequence learning-induced neural efficiency in functional brain connectivity.

PubMed

Karim, Helmet T; Huppert, Theodore J; Erickson, Kirk I; Wollam, Mariegold E; Sparto, Patrick J; Sejdić, Ervin; VanSwearingen, Jessie M

2017-02-15

Previous studies have shown the functional neural circuitry differences before and after an explicitly learned motor sequence task, but have not assessed these changes during the process of motor skill learning. Functional magnetic resonance imaging activity was measured while participants (n=13) were asked to tap their fingers to visually presented sequences in blocks that were either the same sequence repeated (learning block) or random sequences (control block). Motor learning was associated with a decrease in brain activity during learning compared to control. Lower brain activation was noted in the posterior parietal association area and bilateral thalamus during the later periods of learning (not during the control). Compared to the control condition, we found the task-related motor learning was associated with decreased connectivity between the putamen and left inferior frontal gyrus and left middle cingulate brain regions. Motor learning was associated with changes in network activity, spatial extent, and connectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

Altered fronto-cerebellar connectivity in alcohol-naïve youth with a family history of alcoholism

PubMed Central

Herting, Megan M.; Fair, Damien; Nagel, Bonnie J.

2011-01-01

Fronto-cerebellar connections are thought to be involved in higher-order cognitive functioning. It is suspected that damage to this network may contribute to cognitive deficits in chronic alcoholics. However, it remains to be elucidated if fronto-cerebellar circuitry is altered in high-risk individuals even prior to alcohol use onset. The current study used functional connectivity MRI (fcMRI) to examine fronto-cerebellar circuitry in 13 alcohol-naïve, at-risk youth with a family history of alcoholism (FH+) and 14 age-matched controls. In addition, we examined how white matter microstructure, as evidenced by fractional anisotropy (FA) related to fcMRI. FH+ youth showed significantly reduced functional connectivity between bilateral anterior prefrontal cortices and contralateral cerebellar seed regions compared to controls. We found that this reduction in connectivity significantly correlated with reduced FA in the anterior limb of the internal capsule and the superior longitudinal fasciculus. Taken together, our findings reflect associated aberrant functional and structural connectivity in substance-naïve FH+ adolescents, perhaps suggesting an identifiable neurophenotypic precursor to substance use. Given the role of frontal and cerebellar brain regions in subserving executive functioning, the presence of premorbid abnormalities in fronto-cerebellar circuitry may heighten the risk for developing an alcohol use disorder in FH+ youth through atypical control processing. PMID:20970506

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.

Stress integration after acute and chronic predator stress: differential activation of central stress circuitry and sensitization of the hypothalamo-pituitary-adrenocortical axis.

PubMed

Figueiredo, Helmer F; Bodie, Bryan L; Tauchi, Miyuki; Dolgas, C Mark; Herman, James P

2003-12-01

Predator exposure is a naturalistic stressor of high ethological relevance. In the current study, our group examined central and peripheral integration of stress responses in rats after acute or repeated exposure to a natural predator (cat). Acute cat exposure rapidly induced hypothalamo-pituitary-adrenocortical (HPA) axis activation and paraventricular nucleus (PVN) CRH mRNA production. Repeated daily cat exposure (7 and 14 d) also up-regulated PVN mRNA CRH expression, but did not result in frank adrenocortical hyperactivity. Unlike other chronic homotypic stress regimens, repeated cat exposure facilitated corticosterone secretion after the 6th or 13th day of exposure. Notably, ACTH secretion and central amygdaloid nucleus CRH mRNA expression were enhanced in animals that were preexposed to the holding chamber relative to chamber-naive rats, suggesting that contextual cues can sensitize subsequent responses to a fearful stimulus. Analysis of c-fos activation was then used to identify brain circuits activated by acute predator stress. Cat exposure elicited a pattern of central c-fos activation that differed substantially from that after either restraint or hypoxia. Predator-specific c-fos mRNA induction was observed in several brain regions comprising the hypothetical brain defense circuit (bed nucleus of the stria terminalis, medial region of the ventromedial nucleus, and dorsal premammillary nucleus). Surprisingly, acute cat exposure did not induce c-fos expression in the PVN. In summary, the data indicate that 1) predation stress invokes a unique stress circuitry that promotes homotypic sensitization of the HPA axis, and 2) familiarization of animals to testing environments can prime central stress pathways to respond robustly to novel threats.

Structural connectivity patterns associated with the putative visual word form area and children's reading ability.

PubMed

Fan, Qiuyun; Anderson, Adam W; Davis, Nicole; Cutting, Laurie E

2014-10-24

With the advent of neuroimaging techniques, especially functional MRI (fMRI), studies have mapped brain regions that are associated with good and poor reading, most centrally a region within the left occipito-temporal/fusiform region (L-OT/F) often referred to as the visual word form area (VWFA). Despite an abundance of fMRI studies of the putative VWFA, research about its structural connectivity has just started. Provided that the putative VWFA may be connected to distributed regions in the brain, it remains unclear how this network is engaged in constituting a well-tuned reading circuitry in the brain. Here we used diffusion MRI to study the structural connectivity patterns of the putative VWFA and surrounding areas within the L-OT/F in children with typically developing (TD) reading ability and with word recognition deficits (WRD; sometimes referred to as dyslexia). We found that L-OT/F connectivity varied along a posterior-anterior gradient, with specific structural connectivity patterns related to reading ability in the ROIs centered upon the putative VWFA. Findings suggest that the architecture of the putative VWFA connectivity is fundamentally different between TD and WRD, with TD showing greater connectivity to linguistic regions than WRD, and WRD showing greater connectivity to visual and parahippocampal regions than TD. Findings thus reveal clear structural abnormalities underlying the functional abnormalities in the putative VWFA in WRD. Copyright © 2014 Elsevier B.V. All rights reserved.

A circuitry and biochemical basis for tuberous sclerosis symptoms: from epilepsy to neurocognitive deficits.

PubMed

Feliciano, David M; Lin, Tiffany V; Hartman, Nathaniel W; Bartley, Christopher M; Kubera, Cathryn; Hsieh, Lawrence; Lafourcade, Carlos; O'Keefe, Rachel A; Bordey, Angelique

2013-11-01

Tuberous sclerosis complex (TSC) is an autosomal dominant monogenetic disorder that is characterized by the formation of benign tumors in several organs as well as brain malformations and neuronal defects. TSC is caused by inactivating mutations in one of two genes, TSC1 and TSC2, resulting in increased activity of the mammalian Target of Rapamycin (mTOR). Here, we explore the cytoarchitectural and functional CNS aberrations that may account for the neurological presentations of TSC, notably seizures, hydrocephalus, and cognitive and psychological impairments. In particular, recent mouse models of brain lesions are presented with an emphasis on using electroporation to allow the generation of discrete lesions resulting from loss of heterozygosity during perinatal development. Cortical lesions are thought to contribute to epileptogenesis and worsening of cognitive defects. However, it has recently been suggested that being born with a mutant allele without loss of heterozygosity and associated cortical lesions is sufficient to generate cognitive and neuropsychiatric problems. We will thus discuss the function of mTOR hyperactivity on neuronal circuit formation and the potential consequences of being born heterozygous on neuronal function and the biochemistry of synaptic plasticity, the cellular substrate of learning and memory. Ultimately, a major goal of TSC research is to identify the cellular and molecular mechanisms downstream of mTOR underlying the neurological manifestations observed in TSC patients and identify novel therapeutic targets to prevent the formation of brain lesions and restore neuronal function. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

What is special about the adolescent (JME) brain?

PubMed

Craiu, Dana

2013-07-01

Juvenile myoclonic epilepsy (JME) involves cortico-thalamo-cortical networks. Thalamic, frontal gray matter, connectivity, and neurotransmitter disturbances have been demonstrated by structural/functional imaging studies. Few patients with JME show mutations in genes coding ion channels or GABAA (gamma-aminobutyric acid) receptor subunits. Recent research points to EFHC1 gene mutations leading to microdysgenesis and possible aberrant circuitry. Imaging studies have shown massive structural/functional changes of normally developing adolescent brain structures maturing at strikingly different rates and times. Gray matter (GM) volume diminishes in cortical areas (frontal and parietal) and deep structures (anterior thalamus, putamen, and caudate). Diffusion tensor imaging (DTI) findings support continued microstructural change in WM (white matter) during late adolescence with robust developmental changes in thalamocortical connectivity. The GABAA receptor distribution and specific receptor subunits' expression patterns change with age from neonate to adolescent/adult, contributing to age-related changes in brain excitability. Hormonal influence on brain structure development during adolescence is presented. Possible implications of brain changes during adolescence on the course of JME are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Transient-Switch-Signal Suppressor

NASA Technical Reports Server (NTRS)

Bozeman, Richard J., Jr.

1995-01-01

Circuit delays transmission of switch-opening or switch-closing signal until after preset suppression time. Used to prevent transmission of undesired momentary switch signal. Basic mode of operation simple. Beginning of switch signal initiates timing sequence. If switch signal persists after preset suppression time, circuit transmits switch signal to external circuitry. If switch signal no longer present after suppression time, switch signal deemed transient, and circuit does not pass signal on to external circuitry, as though no transient switch signal. Suppression time preset at value large enough to allow for damping of underlying pressure wave or other mechanical transient.

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.

Enhanced inhibitory control by neuropeptide Y Y5 receptor blockade in rats.

PubMed

Bari, A; Dec, A; Lee, A W; Lee, J; Song, D; Dale, E; Peterson, J; Zorn, S; Huang, X; Campbell, B; Robbins, T W; West, A R

2015-03-01

The neuropeptide Y (NPY) system acts in synergy with the classic neurotransmitters to regulate a large variety of functions including autonomic, affective, and cognitive processes. Research on the effects of NPY in the central nervous system has focused on food intake control and affective processes, but growing evidence of NPY involvement in attention-deficit/hyperactivity disorder (ADHD) and other psychiatric conditions motivated the present study. We tested the effects of the novel and highly selective NPY Y5 receptor antagonist Lu AE00654 on impulsivity and the underlying cortico-striatal circuitry in rats to further explore the possible involvement of the NPY system in pathologies characterized by inattention and impulsive behavior. A low dose of Lu AE00654 (0.03 mg/kg) selectively facilitated response inhibition as measured by the stop-signal task, whereas no effects were found at higher doses (0.3 and 3 mg/kg). Systemic administration of Lu AE00654 also enhanced the inhibitory influence of the dorsal frontal cortex on neurons in the caudate-putamen, this fronto-striatal circuitry being implicated in the executive control of behavior. Finally, by locally injecting a Y5 agonist, we observed reciprocal activation between dorsal frontal cortex and caudate-putamen neurons. Importantly, the effects of the Y5 agonist were attenuated by pretreatment with Lu AE00654, confirming the presence of Y5 binding sites modulating functional interactions within frontal-subcortical circuits. These results suggest that the NPY system modulates inhibitory neurotransmission in brain areas important for impulse control, and may be relevant for the treatment of pathologies such as ADHD and drug abuse.

Sensory-driven and spontaneous gamma oscillations engage distinct cortical circuitry

PubMed Central

2015-01-01

Gamma oscillations are a robust component of sensory responses but are also part of the background spontaneous activity of the brain. To determine whether the properties of gamma oscillations in cortex are specific to their mechanism of generation, we compared in mouse visual cortex in vivo the laminar geometry and single-neuron rhythmicity of oscillations produced during sensory representation with those occurring spontaneously in the absence of stimulation. In mouse visual cortex under anesthesia (isoflurane and xylazine), visual stimulation triggered oscillations mainly between 20 and 50 Hz, which, because of their similar functional significance to gamma oscillations in higher mammals, we define here as gamma range. Sensory representation in visual cortex specifically increased gamma oscillation amplitude in the supragranular (L2/3) and granular (L4) layers and strongly entrained putative excitatory and inhibitory neurons in infragranular layers, while spontaneous gamma oscillations were distributed evenly through the cortical depth and primarily entrained putative inhibitory neurons in the infragranular (L5/6) cortical layers. The difference in laminar distribution of gamma oscillations during the two different conditions may result from differences in the source of excitatory input to the cortex. In addition, modulation of superficial gamma oscillation amplitude did not result in a corresponding change in deep-layer oscillations, suggesting that superficial and deep layers of cortex may utilize independent but related networks for gamma generation. These results demonstrate that stimulus-driven gamma oscillations engage cortical circuitry in a manner distinct from spontaneous oscillations and suggest multiple networks for the generation of gamma oscillations in cortex. PMID:26719085

Molecular mechanism: ERK signaling, drug addiction and behavioral effects

PubMed Central

Sun, Wei-Lun; Quizon, Pamela M.; Zhu, Jun

2017-01-01

Addiction to psychostimulants has been considered as a chronic psychiatric disorder, characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that results in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction. PMID:26809997

Local corticotropin releasing hormone (CRH) signals to its receptor CRHR1 during postnatal development of the mouse olfactory bulb.

PubMed

Garcia, Isabella; Bhullar, Paramjit K; Tepe, Burak; Ortiz-Guzman, Joshua; Huang, Longwen; Herman, Alexander M; Chaboub, Lesley; Deneen, Benjamin; Justice, Nicholas J; Arenkiel, Benjamin R

2016-01-01

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related behaviors. Further, we provide electrophysiological evidence that CRHR1-expressing granule cells functionally respond to CRH ligand, and that the physiological circuitry of CRHR1 knockout mice is abnormal, leading to impaired olfactory behaviors. Together, these data suggest a physiologically relevant role for local CRH signaling towards shaping the neuronal circuitry within the mouse OB.

Dysregulation of prefrontal cortex-mediated slow evolving limbic dynamics drives stress-induced emotional pathology

PubMed Central

Hultman, Rainbo; Mague, Stephen D.; Li, Qiang; Katz, Brittany M.; Michel, Nadine; Lin, Lizhen; Wang, Joyce; David, Lisa K.; Blount, Cameron; Chandy, Rithi; Carlson, David; Ulrich, Kyle; Carin, Lawrence; Dunson, David; Kumar, Sunil; Deisseroth, Karl; Moore, Scott D.; Dzirasa, Kafui

2016-01-01

Summary Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social-defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. PMID:27346529

Active medulloblastoma enhancers reveal subgroup-specific cellular origins

PubMed Central

Lin, Charles Y.; Erkek, Serap; Tong, Yiai; Yin, Linlin; Federation, Alexander J.; Zapatka, Marc; Haldipur, Parthiv; Kawauchi, Daisuke; Risch, Thomas; Warnatz, Hans-Jörg; Worst, Barbara C.; Ju, Bensheng; Orr, Brent A.; Zeid, Rhamy; Polaski, Donald R.; Segura-Wang, Maia; Waszak, Sebastian M.; Jones, David T.W.; Kool, Marcel; Hovestadt, Volker; Buchhalter, Ivo; Sieber, Laura; Johann, Pascal; Chavez, Lukas; Gröschel, Stefan; Ryzhova, Marina; Korshunov, Andrey; Chen, Wenbiao; Chizhikov, Victor V.; Millen, Kathleen J.; Amstislavskiy, Vyacheslav; Lehrach, Hans; Yaspo, Marie-Laure; Eils, Roland; Lichter, Peter; Korbel, Jan O.; Pfister, Stefan M.; Bradner, James E.; Northcott, Paul A.

2016-01-01

Summary Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Using H3K27ac and BRD4 ChIP-Seq, coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-Seq, that are responsible for subgroup divergence and implicate candidate cells-of-origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins. PMID:26814967

Common variation in the autism risk gene CNTNAP2, brain structural connectivity and multisensory speech integration.

PubMed

Ross, Lars A; Del Bene, Victor A; Molholm, Sophie; Jae Woo, Young; Andrade, Gizely N; Abrahams, Brett S; Foxe, John J

2017-11-01

Three lines of evidence motivated this study. 1) CNTNAP2 variation is associated with autism risk and speech-language development. 2) CNTNAP2 variations are associated with differences in white matter (WM) tracts comprising the speech-language circuitry. 3) Children with autism show impairment in multisensory speech perception. Here, we asked whether an autism risk-associated CNTNAP2 single nucleotide polymorphism in neurotypical adults was associated with multisensory speech perception performance, and whether such a genotype-phenotype association was mediated through white matter tract integrity in speech-language circuitry. Risk genotype at rs7794745 was associated with decreased benefit from visual speech and lower fractional anisotropy (FA) in several WM tracts (right precentral gyrus, left anterior corona radiata, right retrolenticular internal capsule). These structural connectivity differences were found to mediate the effect of genotype on audiovisual speech perception, shedding light on possible pathogenic pathways in autism and biological sources of inter-individual variation in audiovisual speech processing in neurotypicals. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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).

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

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

Deep-Brain Stimulation for Basal Ganglia Disorders

PubMed Central

Wichmann, Thomas; DeLong, Mahlon R.

2011-01-01

The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of ‘motor’ portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the ‘limbic’ basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders. PMID:21804953

Corticolimbic anatomical characteristics predetermine risk for chronic pain

PubMed Central

Vachon-Presseau, Etienne; Tétreault, Pascal; Petre, Bogdan; Huang, Lejian; Berger, Sara E.; Torbey, Souraya; Baria, Alexis T.; Mansour, Ali R.; Hashmi, Javeria A.; Griffith, James W.; Comasco, Erika; Schnitzer, Thomas J.

2016-01-01

See Tracey (doi:10.1093/brain/aww147) for a scientific commentary on this article. Mechanisms of chronic pain remain poorly understood. We tracked brain properties in subacute back pain patients longitudinally for 3 years as they either recovered from or transitioned to chronic pain. Whole-brain comparisons indicated corticolimbic, but not pain-related circuitry, white matter connections predisposed patients to chronic pain. Intra-corticolimbic white matter connectivity analysis identified three segregated communities: dorsal medial prefrontal cortex–amygdala–accumbens, ventral medial prefrontal cortex–amygdala, and orbitofrontal cortex–amygdala–hippocampus. Higher incidence of white matter and functional connections within the dorsal medial prefrontal cortex–amygdala–accumbens circuit, as well as smaller amygdala volume, represented independent risk factors, together accounting for 60% of the variance for pain persistence. Opioid gene polymorphisms and negative mood contributed indirectly through corticolimbic anatomical factors, to risk for chronic pain. Our results imply that persistence of chronic pain is predetermined by corticolimbic neuroanatomical factors. PMID:27190016

Brain-wide neuronal dynamics during motor adaptation in zebrafish.

PubMed

Ahrens, Misha B; Li, Jennifer M; Orger, Michael B; Robson, Drew N; Schier, Alexander F; Engert, Florian; Portugues, Ruben

2012-05-09

A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioural adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behaviour.

Brain-wide neuronal dynamics during motor adaptation in zebrafish

PubMed Central

Ahrens, Misha B; Li, Jennifer M; Orger, Michael B; Robson, Drew N; Schier, Alexander F; Engert, Florian; Portugues, Ruben

2013-01-01

A fundamental question in neuroscience is how entire neural circuits generate behavior and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record activity of large populations of neurons at the cellular level throughout the brain of larval zebrafish expressing a genetically-encoded calcium sensor, while the paralyzed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neural response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioral adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behavior. PMID:22622571

Peer Influence Via Instagram: Effects on Brain and Behavior in Adolescence and Young Adulthood.

PubMed

Sherman, Lauren E; Greenfield, Patricia M; Hernandez, Leanna M; Dapretto, Mirella

2018-01-01

Mobile social media often feature the ability to "Like" content posted by others. This study examined the effect of Likes on youths' neural and behavioral responses to photographs. High school and college students (N = 61, ages 13-21) viewed theirs and others' Instagram photographs while undergoing functional Magnetic Resonance Imaging (fMRI). Participants more often Liked photographs that appeared to have received many (vs. few) Likes. Popular photographs elicited greater activity in multiple brain regions, including the nucleus accumbens (NAcc), a hub of the brain's reward circuitry. NAcc responsivity increased with age for high school but not college students. When viewing images depicting risk-taking (vs. nonrisky photographs), high school students, but not college students, showed decreased activation of neural regions implicated in cognitive control. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Integrative biological analysis for neuropsychopharmacology.

PubMed

Emmett, Mark R; Kroes, Roger A; Moskal, Joseph R; Conrad, Charles A; Priebe, Waldemar; Laezza, Fernanda; Meyer-Baese, Anke; Nilsson, Carol L

2014-01-01

Although advances in psychotherapy have been made in recent years, drug discovery for brain diseases such as schizophrenia and mood disorders has stagnated. The need for new biomarkers and validated therapeutic targets in the field of neuropsychopharmacology is widely unmet. The brain is the most complex part of human anatomy from the standpoint of number and types of cells, their interconnections, and circuitry. To better meet patient needs, improved methods to approach brain studies by understanding functional networks that interact with the genome are being developed. The integrated biological approaches--proteomics, transcriptomics, metabolomics, and glycomics--have a strong record in several areas of biomedicine, including neurochemistry and neuro-oncology. Published applications of an integrated approach to projects of neurological, psychiatric, and pharmacological natures are still few but show promise to provide deep biological knowledge derived from cells, animal models, and clinical materials. Future studies that yield insights based on integrated analyses promise to deliver new therapeutic targets and biomarkers for personalized medicine.

Brain circuits mediating baroreflex bradycardia inhibition in rats: an anatomical and functional link between the cuneiform nucleus and the periaqueductal grey

PubMed Central

Netzer, Florence; Bernard, Jean-François; Verberne, Anthony J M; Hamon, Michel; Camus, Françoise; Benoliel, Jean-Jacques; Sévoz-Couche, Caroline

2011-01-01

Abstract Defence responses triggered experimentally in rats by stimulation of the dorsomedial nucleus of the hypothalamus (DMH) and the dorsolateral periaqueductal grey matter (PAG) inhibit the cardiac baroreflex response (i.e. bradycardia). It has also been proposed that the midbrain cuneiform nucleus (CnF) is involved in active responses. Our aim was to identify the neurocircuitry involved in defence-induced baroreflex inhibition, with a particular focus on the link between DMH, CnF and dorsolateral PAG. Microinjection of the anterograde tracer Phaseolus vulgaris leucoaggutinin into the CnF revealed a dense projection to the dorsolateral PAG. Moreover, activation of neurons in the CnF induced increased expression of Fos protein in the dorsolateral PAG. Inhibition of neurons of the CnF or dorsolateral PAG prevented the inhibition of baroreflex bradycardia induced by DMH or CnF stimulation, respectively. These results provide a detailed description of the brain circuitry underlying acute baroreflex modulation by neurons of the DMH. Our data have shown for the first time that the CnF plays a key role in defence reaction-associated cardiovascular changes; its stimulation, from the DMH, activates the dorsolateral PAG, which, in turn, inhibits baroreflex bradycardia. PMID:21486808

Prefrontal connections express individual differences in intrinsic resistance to trading off honesty values against economic benefits

PubMed Central

Dogan, Azade; Morishima, Yosuke; Heise, Felix; Tanner, Carmen; Gibson, Rajna; Wagner, Alexander F.; Tobler, Philippe N.

2016-01-01

Individuals differ profoundly when they decide whether to tell the truth or to be dishonest, particularly in situations where moral motives clash with economic motives, i.e., when truthfulness comes at a monetary cost. These differences should be expressed in the decision network, particularly in prefrontal cortex. However, the interactions between the core players of the decision network during honesty-related decisions involving trade-offs with economic costs remain poorly understood. To investigate brain connectivity patterns associated with individual differences in responding to economic costs of truthfulness, we used functional magnetic resonance imaging and measured brain activations, while participants made decisions concerning honesty. We found that in participants who valued honesty highly, dorsolateral and dorsomedial parts of prefrontal cortex were more tightly coupled with the inferior frontal cortex when economic costs were high compared to when they were low. Finer-grained analysis revealed that information flow from the inferior frontal cortex to the dorsolateral prefrontal cortex and bidirectional information flow between the inferior frontal cortex and dorsomedial prefrontal cortex was associated with a reduced tendency to trade off honesty for economic benefits. Our findings provide a novel account of the neural circuitry that underlies honest decisions in the face of economic temptations. PMID:27646044

fMRI responses to Jung's Word Association Test: implications for theory, treatment and research.

PubMed

Petchkovsky, Leon; Petchkovsky, Michael; Morris, Philip; Dickson, Paul; Montgomery, Danielle; Dwyer, Jonathan; Burnett, Patrick

2013-06-01

Jung's Word Association Test was performed under fMRI conditions by 12 normal subjects. Pooled complexed responses were contrasted against pooled neutral ones. The fMRI activation pattern of this generic 'complexed response' was very strong (corrected Z scores ranging from 4.90 to 5.69). The activation pattern in each hemisphere includes mirror neurone areas that track 'otherness' (perspectival empathy), anterior insula (both self-awareness and emotional empathy), and cingulated gyrus (self-awareness and conflict-monitoring). These are the sites described by Siegel and colleagues as the 'resonance circuitry' in the brain which is central to mindfulness (awareness of self) and empathy (sense of the other), negotiations between self awareness and the 'internal other'. But there is also an interhemispheric dialogue. Within 3 seconds, the left hemisphere over-rides the right (at least in our normal subjects). Mindfulness and empathy are central to good psychotherapy, and complexes can be windows of opportunity if left-brain hegemony is resisted. This study sets foundations for further research: (i) QEEG studies (with their finer temporal resolution) of complexed responses in normal subjects (ii) QEEG and fMRI studies of complexed responses in other conditions, like schizophrenia, PTSD, disorders of self organization. © 2013, The Society of Analytical Psychology.

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.

Brain Circulation during Panic Attack: A Transcranial Doppler Study with Clomipramine Challenge.

PubMed

Rotella, Francesco; Marinoni, Marinella; Lejeune, Francesca; Alari, Fabiana; Depinesi, Daniela; Cosci, Fiammetta; Faravelli, Carlo

2014-01-01

Introduction. Cerebral blood flow has been well studied in patients with panic disorder, but only few studies analyzed the mechanisms underlying the onset of a panic attack. The aim of the present study was to monitor the cerebral hemodynamics modifications during a panic attack. Materials and Methods. 10 panic disorder patients with recent onset, fully drug naïve, were compared to 13 patients with panic disorder with a previous history of treatment and to 14 controls. A continuous bilateral monitoring of mean flow velocities in right and left middle cerebral arteries was performed by transcranial Doppler. Clomipramine was chosen as challenge. Results. Eight out of 10 patients drug naïve and 6 control subjects out of 13 had a full blown panic attack during the test, whereas none of the patients with a history of treatment panicked. The occurrence of a panic attack was accompanied by a rapid decrease of flow velocities in both right and left middle cerebral arteries. Discussion. The bilateral acute decrease of mean flow velocity during a panic attack suggests the vasoconstriction of the microcirculation of deep brain structures perfused by middle cerebral arteries and involved in the so-called "fear circuitry," thus suggesting that cerebral homeostatic dysfunctions seem to have a key role in the onset of a panic attack.

Splenium of Corpus Callosum: Patterns of Interhemispheric Interaction in Children and Adults

PubMed Central

Knyazeva, Maria G.

2013-01-01

The splenium of the corpus callosum connects the posterior cortices with fibers varying in size from thin late-myelinating axons in the anterior part, predominantly connecting parietal and temporal areas, to thick early-myelinating fibers in the posterior part, linking primary and secondary visual areas. In the adult human brain, the function of the splenium in a given area is defined by the specialization of the area and implemented via excitation and/or suppression of the contralateral homotopic and heterotopic areas at the same or different level of visual hierarchy. These mechanisms are facilitated by interhemispheric synchronization of oscillatory activity, also supported by the splenium. In postnatal ontogenesis, structural MRI reveals a protracted formation of the splenium during the first two decades of human life. In doing so, the slow myelination of the splenium correlates with the formation of interhemispheric excitatory influences in the extrastriate areas and the EEG synchronization, while the gradual increase of inhibitory effects in the striate cortex is linked to the local inhibitory circuitry. Reshaping interactions between interhemispherically distributed networks under various perceptual contexts allows sparsification of responses to superfluous information from the visual environment, leading to a reduction of metabolic and structural redundancy in a child's brain. PMID:23577273

Cross-entropy optimization for neuromodulation.

PubMed

Brar, Harleen K; Yunpeng Pan; Mahmoudi, Babak; Theodorou, Evangelos A

2016-08-01

This study presents a reinforcement learning approach for the optimization of the proportional-integral gains of the feedback controller represented in a computational model of epilepsy. The chaotic oscillator model provides a feedback control systems view of the dynamics of an epileptic brain with an internal feedback controller representative of the natural seizure suppression mechanism within the brain circuitry. Normal and pathological brain activity is simulated in this model by adjusting the feedback gain values of the internal controller. With insufficient gains, the internal controller cannot provide enough feedback to the brain dynamics causing an increase in correlation between different brain sites. This increase in synchronization results in the destabilization of the brain dynamics, which is representative of an epileptic seizure. To provide compensation for an insufficient internal controller an external controller is designed using proportional-integral feedback control strategy. A cross-entropy optimization algorithm is applied to the chaotic oscillator network model to learn the optimal feedback gains for the external controller instead of hand-tuning the gains to provide sufficient control to the pathological brain and prevent seizure generation. The correlation between the dynamics of neural activity within different brain sites is calculated for experimental data to show similar dynamics of epileptic neural activity as simulated by the network of chaotic oscillators.

Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer.

PubMed

Ngô, Huân M; Zhou, Ying; Lorenzi, Hernan; Wang, Kai; Kim, Taek-Kyun; Zhou, Yong; El Bissati, Kamal; Mui, Ernest; Fraczek, Laura; Rajagopala, Seesandra V; Roberts, Craig W; Henriquez, Fiona L; Montpetit, Alexandre; Blackwell, Jenefer M; Jamieson, Sarra E; Wheeler, Kelsey; Begeman, Ian J; Naranjo-Galvis, Carlos; Alliey-Rodriguez, Ney; Davis, Roderick G; Soroceanu, Liliana; Cobbs, Charles; Steindler, Dennis A; Boyer, Kenneth; Noble, A Gwendolyn; Swisher, Charles N; Heydemann, Peter T; Rabiah, Peter; Withers, Shawn; Soteropoulos, Patricia; Hood, Leroy; McLeod, Rima

2017-09-13

One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: "Orbital-deconvolution" elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. "Cluster-deconvolution" revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, "disease-deconvolution" identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer's disease, and cancer. This "reconstruction-deconvolution" logic provides templates of progenitor cells' potentiating effects, and components affecting human brain parasitism and diseases.

Multimodal neuroimaging of male and female brain structure in health and disease across the life span

PubMed Central

Thompson, Paul M.

2016-01-01

Sex differences in brain development and aging are important to identify, as they may help to understand risk factors and outcomes in brain disorders that are more prevalent in one sex compared with the other. Brain imaging techniques have advanced rapidly in recent years, yielding detailed structural and functional maps of the living brain. Even so, studies are often limited in sample size, and inconsistent findings emerge, one example being varying findings regarding sex differences in the size of the corpus callosum. More recently, large‐scale neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium have formed, pooling together expertise, data, and resources from hundreds of institutions around the world to ensure adequate power and reproducibility. These initiatives are helping us to better understand how brain structure is affected by development, disease, and potential modulators of these effects, including sex. This review highlights some established and disputed sex differences in brain structure across the life span, as well as pitfalls related to interpreting sex differences in health and disease. We also describe sex‐related findings from the ENIGMA consortium, and ongoing efforts to better understand sex differences in brain circuitry. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. PMID:27870421

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

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.

Neurobiology of dysregulated motivational systems in drug addiction

PubMed Central

Edwards, Scott; Koob, George F

2010-01-01

The progression from recreational drug use to drug addiction impacts multiple neurobiological processes and can be conceptualized as a transition from positive to negative reinforcement mechanisms driving both drug-taking and drug-seeking behaviors. Neurobiological mechanisms for negative reinforcement, defined as drug taking that alleviates a negative emotional state, involve changes in the brain reward system and recruitment of brain stress (or antireward) systems within forebrain structures, including the extended amygdala. These systems are hypothesized to be dysregulated by excessive drug intake and to contribute to allostatic changes in reinforcement mechanisms associated with addiction. Points of intersection between positive and negative motivational circuitry may further drive the compulsivity of drug addiction but also provide a rich neurobiological substrate for therapeutic intervention. PMID:20563312

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

Minimizing the effect of process mismatch in a neuromorphic system using spike-timing-dependent adaptation.

PubMed

Cameron, Katherine; Murray, Alan

2008-05-01

This paper investigates whether spike-timing-dependent plasticity (STDP) can minimize the effect of mismatch within the context of a depth-from-motion algorithm. To improve noise rejection, this algorithm contains a spike prediction element, whose performance is degraded by analog very large scale integration (VLSI) mismatch. The error between the actual spike arrival time and the prediction is used as the input to an STDP circuit, to improve future predictions. Before STDP adaptation, the error reflects the degree of mismatch within the prediction circuitry. After STDP adaptation, the error indicates to what extent the adaptive circuitry can minimize the effect of transistor mismatch. The circuitry is tested with static and varying prediction times and chip results are presented. The effect of noisy spikes is also investigated. Under all conditions the STDP adaptation is shown to improve performance.

GABA regulates synaptic integration of newly generated neurons in the adult brain

NASA Astrophysics Data System (ADS)

Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

2006-02-01

Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

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.

Ultrasonic pulser-receiver

DOEpatents

Taylor, Steven C.

2006-09-12

Ultrasonic pulser-receiver circuitry, for use with an ultrasonic transducer, the circuitry comprising a circuit board; ultrasonic pulser circuitry supported by the circuit board and configured to be coupled to an ultrasonic transducer and to cause the ultrasonic transducer to emit an ultrasonic output pulse; receiver circuitry supported by the circuit board, coupled to the pulser circuitry, including protection circuitry configured to protect against the ultrasonic pulse and including amplifier circuitry configured to amplify an echo, received back by the transducer, of the output pulse; and a connector configured to couple the ultrasonic transducer directly to the circuit board, to the pulser circuitry and receiver circuitry, wherein impedance mismatches that would result if the transducer was coupled to the circuit board via a cable can be avoided.

Basal ganglia, movement disorders and deep brain stimulation: advances made through non-human primate research.

PubMed

Wichmann, Thomas; Bergman, Hagai; DeLong, Mahlon R

2018-03-01

Studies in non-human primates (NHPs) have led to major advances in our understanding of the function of the basal ganglia and of the pathophysiologic mechanisms of hypokinetic movement disorders such as Parkinson's disease and hyperkinetic disorders such as chorea and dystonia. Since the brains of NHPs are anatomically very close to those of humans, disease states and the effects of medical and surgical approaches, such as deep brain stimulation (DBS), can be more faithfully modeled in NHPs than in other species. According to the current model of the basal ganglia circuitry, which was strongly influenced by studies in NHPs, the basal ganglia are viewed as components of segregated networks that emanate from specific cortical areas, traverse the basal ganglia, and ventral thalamus, and return to the frontal cortex. Based on the presumed functional domains of the different cortical areas involved, these networks are designated as 'motor', 'oculomotor', 'associative' and 'limbic' circuits. The functions of these networks are strongly modulated by the release of dopamine in the striatum. Striatal dopamine release alters the activity of striatal projection neurons which, in turn, influences the (inhibitory) basal ganglia output. In parkinsonism, the loss of striatal dopamine results in the emergence of oscillatory burst patterns of firing of basal ganglia output neurons, increased synchrony of the discharge of neighboring basal ganglia neurons, and an overall increase in basal ganglia output. The relevance of these findings is supported by the demonstration, in NHP models of parkinsonism, of the antiparkinsonian effects of inactivation of the motor circuit at the level of the subthalamic nucleus, one of the major components of the basal ganglia. This finding also contributed strongly to the revival of the use of surgical interventions to treat patients with Parkinson's disease. While ablative procedures were first used for this purpose, they have now been largely replaced by DBS of the subthalamic nucleus or internal pallidal segment. These procedures are not only effective in the treatment of parkinsonism, but also in the treatment of hyperkinetic conditions (such as chorea or dystonia) which result from pathophysiologic changes different from those underlying Parkinson's disease. Thus, these interventions probably do not counteract specific aspects of the pathophysiology of movement disorders, but non-specifically remove the influence of the different types of disruptive basal ganglia output from the relatively intact portions of the motor circuitry downstream from the basal ganglia. Knowledge gained from studies in NHPs remains critical for our understanding of the pathophysiology of movement disorders, of the effects of DBS on brain network activity, and the development of better treatments for patients with movement disorders and other neurologic or psychiatric conditions.

System level latchup mitigation for single event and transient radiation effects on electronics

DOEpatents

Kimbrough, J.R.; Colella, N.J.

1997-09-30

A ``blink`` technique, analogous to a person blinking at a flash of bright light, is provided for mitigating the effects of single event current latchup and prompt pulse destructive radiation on a micro-electronic circuit. The system includes event detection circuitry, power dump logic circuitry, and energy limiting measures with autonomous recovery. The event detection circuitry includes ionizing radiation pulse detection means for detecting a pulse of ionizing radiation and for providing at an output terminal thereof a detection signal indicative of the detection of a pulse of ionizing radiation. The current sensing circuitry is coupled to the power bus for determining an occurrence of excess current through the power bus caused by ionizing radiation or by ion-induced destructive latchup of a semiconductor device. The power dump circuitry includes power dump logic circuitry having a first input terminal connected to the output terminal of the ionizing radiation pulse detection circuitry and having a second input terminal connected to the output terminal of the current sensing circuitry. The power dump logic circuitry provides an output signal to the input terminal of the circuitry for opening the power bus and the circuitry for shorting the power bus to a ground potential to remove power from the power bus. The energy limiting circuitry with autonomous recovery includes circuitry for opening the power bus and circuitry for shorting the power bus to a ground potential. The circuitry for opening the power bus and circuitry for shorting the power bus to a ground potential includes a series FET and a shunt FET. The invention provides for self-contained sensing for latchup, first removal of power to protect latched components, and autonomous recovery to enable transparent operation of other system elements. 18 figs.

System level latchup mitigation for single event and transient radiation effects on electronics

DOEpatents

Kimbrough, Joseph Robert; Colella, Nicholas John

1997-01-01

A "blink" technique, analogous to a person blinking at a flash of bright light, is provided for mitigating the effects of single event current latchup and prompt pulse destructive radiation on a micro-electronic circuit. The system includes event detection circuitry, power dump logic circuitry, and energy limiting measures with autonomous recovery. The event detection circuitry includes ionizing radiation pulse detection means for detecting a pulse of ionizing radiation and for providing at an output terminal thereof a detection signal indicative of the detection of a pulse of ionizing radiation. The current sensing circuitry is coupled to the power bus for determining an occurrence of excess current through the power bus caused by ionizing radiation or by ion-induced destructive latchup of a semiconductor device. The power dump circuitry includes power dump logic circuitry having a first input terminal connected to the output terminal of the ionizing radiation pulse detection circuitry and having a second input terminal connected to the output terminal of the current sensing circuitry. The power dump logic circuitry provides an output signal to the input terminal of the circuitry for opening the power bus and the circuitry for shorting the power bus to a ground potential to remove power from the power bus. The energy limiting circuitry with autonomous recovery includes circuitry for opening the power bus and circuitry for shorting the power bus to a ground potential. The circuitry for opening the power bus and circuitry for shorting the power bus to a ground potential includes a series FET and a shunt FET. The invention provides for self-contained sensing for latchup, first removal of power to protect latched components, and autonomous recovery to enable transparent operation of other system elements.

Repeated transcranial direct current stimulation reduces food craving in Wistar rats.

PubMed

Macedo, I C; de Oliveira, C; Vercelino, R; Souza, A; Laste, G; Medeiros, L F; Scarabelot, V L; Nunes, E A; Kuo, J; Fregni, F; Caumo, W; Torres, I L S

2016-08-01

It has been suggested that food craving-an intense desire to consume a specific food (particularly foods high in sugar and fat)-can lead to obesity. This behavior has also been associated with abuse of other substances, such as drugs. Both drugs and food cause dependence by acting on brain circuitry involved in reward, motivation, and decision-making processes. The dorsolateral prefrontal cortex (DLPFC) can be activated following evocation and is implicated in alterations in food behavior and craving. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique capable of modulates brain activity significantly, has emerged as a promising treatment to inhibit craving. This technique is considered safe and inexpensive; however, there is scant research using animal models. Such studies could help elucidate the behavioral and molecular mechanisms of eating disorders, including food craving. The aim of our study was to evaluate palatable food consumption in rats receiving tDCS treatment (anode right/cathode left). Eighteen adult male Wistar rats were randomized by weight and divided into three groups (n = 6/group): control, with no stimulation; sham, receiving daily 30 s tDCS (500 μA) sessions for 8 consecutive days; and tDCS, receiving daily 20 min tDCS (500 μA) sessions for 8 consecutive days. All rats were evaluated for locomotor activity and anxiety-like behavior. A palatable food consumption test was performed at baseline and on treatment completion (24 h after the last tDCS session) under fasting and feeding conditions and showed that tDCS decreased food craving, thus corroborating human studies. This result confirms the important role of the prefrontal cortex in food behavior, which can be modulated by noninvasive brain stimulation. Copyright © 2016. Published by Elsevier Ltd.

Hypothalamic Dysfunction of the Thrombospondin Receptor α2δ-1 Underlies the Overeating and Obesity Triggered by Brain-Derived Neurotrophic Factor Deficiency

PubMed Central

Cordeira, Joshua W.; Felsted, Jennifer A.; Teillon, Sarah; Daftary, Shabrine; Panessiti, Micaella; Wirth, Jena; Sena-Esteves, Miguel

2014-01-01

Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are critical components of the neural circuitry controlling appetite and body weight. Diminished BDNF signaling in mice results in severe hyperphagia and obesity. In humans, BDNF haploinsufficiency and the functional Bdnf Val66Met polymorphism have been linked to elevated food intake and body weight. The mechanisms underlying this dysfunction are poorly defined. We demonstrate a chief role of α2δ-1, a calcium channel subunit and thrombospondin receptor, in triggering overeating in mice with central BDNF depletion. We show reduced α2δ-1 cell-surface expression in the BDNF mutant ventromedial hypothalamus (VMH), an energy balance-regulating center. This deficit contributes to the hyperphagia exhibited by BDNF mutant mice because selective inhibition of α2δ-1 by gabapentin infusion into wild-type VMH significantly increases feeding and body weight gain. Importantly, viral-mediated α2δ-1 rescue in BDNF mutant VMH significantly mitigates their hyperphagia, obesity, and liver steatosis and normalizes deficits in glucose homeostasis. Whole-cell recordings in BDNF mutant VMH neurons revealed normal calcium currents but reduced frequency of EPSCs. These results suggest calcium channel-independent effects of α2δ-1 on feeding and implicate α2δ-1–thrombospondin interactions known to facilitate excitatory synapse assembly. Our findings identify a central mechanism mediating the inhibitory effects of BDNF on feeding. They also demonstrate a novel and critical role for α2δ-1 in appetite control and suggest a mechanism underlying weight gain in humans treated with gabapentinoid drugs. PMID:24403154

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

Selective early-acquired fear memories undergo temporary suppression during adolescence

PubMed Central

Pattwell, Siobhan S.; Bath, Kevin G.; Casey, B. J.; Ninan, Ipe; Lee, Francis S.

2011-01-01

Highly conserved neural circuitry between rodents and humans has allowed for in-depth characterization of behavioral and molecular processes associated with emotional learning and memory. Despite increased prevalence of affective disorders in adolescent humans, few studies have characterized how associative-emotional learning changes during the transition through adolescence or identified mechanisms underlying such changes. By examining fear conditioning in mice, as they transitioned into and out of adolescence, we found that a suppression of contextual fear occurs during adolescence. Although contextual fear memories were not expressed during early adolescence, they could be retrieved and expressed as the mice transitioned out of adolescence. This temporary suppression of contextual fear was associated with blunted synaptic activity in the basal amygdala and decreased PI3K and MAPK signaling in the hippocampus. These findings reveal a unique form of brain plasticity in fear learning during early adolescence and may prove informative for understanding endogenous mechanisms to suppress unwanted fear memories. PMID:21220344

Context Processing and the Neurobiology of Post-Traumatic Stress Disorder

PubMed Central

Liberzon, Israel; Abelson, James L.

2016-01-01

Summary Progress in clinical and affective neuroscience is redefining psychiatric illness as symptomatic expression of cellular/molecular dysfunctions in specific brain circuits. Post-traumatic stress disorder (PTSD) has been an exemplar of this progress, with improved understanding of neurobiological systems subserving fear learning, salience detection, and emotion regulation explaining much of its phenomenology and neurobiology. However, many features remain unexplained and a parsimonious model that more fully accounts for symptoms and the core neurobiology remains elusive. Contextual processing is a key modulatory function of hippocampal-prefrontal-thalamic circuitry, allowing organisms to disambiguate cues and derive situation-specific meaning from the world. We propose that dysregulation within this context-processing circuit is at the core of PTSD pathophysiology, accounting for much of its phenomenology and most of its biological findings. Understanding core mechanisms like this, and their underlying neural circuits, will sharpen diagnostic precision and understanding of risk factors, enhancing our ability to develop preventive and “personalized” interventions. PMID:27710783

Long term potentiation, but not depression, in interlamellar hippocampus CA1.

PubMed

Sun, Duk-Gyu; Kang, Hyeri; Tetteh, Hannah; Su, Junfeng; Lee, Jihwan; Park, Sung-Won; He, Jufang; Jo, Jihoon; Yang, Sungchil; Yang, Sunggu

2018-03-26

Synaptic plasticity in the lamellar CA3 to CA1 circuitry has been extensively studied while interlamellar CA1 to CA1 connections have not yet received much attention. One of our earlier studies demonstrated that axons of CA1 pyramidal neurons project to neighboring CA1 neurons, implicating information transfer along a longitudinal interlamellar network. Still, it remains unclear whether long-term synaptic plasticity is present within this longitudinal CA1 network. Here, we investigate long-term synaptic plasticity between CA1 pyramidal cells, using in vitro and in vivo extracellular recordings and 3D holography glutamate uncaging. We found that the CA1-CA1 network exhibits NMDA receptor-dependent long-term potentiation (LTP) without direction or layer selectivity. By contrast, we find no significant long-term depression (LTD) under various LTD induction protocols. These results implicate unique synaptic properties in the longitudinal projection suggesting that the interlamellar CA1 network could be a promising structure for hippocampus-related information processing and brain diseases.

Impulsivity and emotion dysregulation as predictors of food addiction.

PubMed

Pivarunas, Bernadette; Conner, Bradley T

2015-12-01

Food addiction is the clinical occurrence in which individuals develop physical and psychological dependencies on high fat, high sugar, and highly palatable foods. Past research has demonstrated a number of similarities between food addiction and drug use disorders including the activation of specific brain regions and neurotransmitters, disrupted neuronal circuitry, and behavioral indicators of addiction such as continued use despite negative consequences. The present study examined the role of impulsivity and emotion dysregulation in food addiction as both play salient roles in drug use disorders. Poisson regression analyses using data from 878 undergraduate students revealed negative urgency, the tendency to act impulsively when under distress, and emotion dysregulation positively predicted symptom count on the Yale Food Addiction Scale (Gearhardt, Corbin, & Brownell, 2009) whereas a lack of premeditation negatively predicted symptom count (all ps<0.05). Future research is needed to confirm precursors to eating episodes in food addiction, elucidate causal mechanisms, and support an explanatory model of food addiction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spatial band-pass filtering aids decoding musical genres from auditory cortex 7T fMRI.

PubMed

Sengupta, Ayan; Pollmann, Stefan; Hanke, Michael

2018-01-01

Spatial filtering strategies, combined with multivariate decoding analysis of BOLD images, have been used to investigate the nature of the neural signal underlying the discriminability of brain activity patterns evoked by sensory stimulation -- primarily in the visual cortex. Reported evidence indicates that such signals are spatially broadband in nature, and are not primarily comprised of fine-grained activation patterns. However, it is unclear whether this is a general property of the BOLD signal, or whether it is specific to the details of employed analyses and stimuli. Here we performed an analysis of publicly available, high-resolution 7T fMRI on the response BOLD response to musical genres in primary auditory cortex that matches a previously conducted study on decoding visual orientation from V1.  The results show that the pattern of decoding accuracies with respect to different types and levels of spatial filtering is comparable to that obtained from V1, despite considerable differences in the respective cortical circuitry.

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

The State of the NIH BRAIN Initiative.

PubMed

Koroshetz, Walter; Gordon, Joshua; Adams, Amy; Beckel-Mitchener, Andrea; Churchill, James; Farber, Gregory; Freund, Michelle; Gnadt, Jim; Hsu, Nina; Langhals, Nicholas; Lisanby, Sarah; Liu, Guoying; Peng, Grace; Ramos, Khara; Steinmetz, Michael; Talley, Edmund; White, Samantha

2018-06-19

The BRAIN Initiative® arose from a grand challenge to "accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought." The BRAIN Initiative is a public-private effort focused on the development and use of powerful tools for acquiring fundamental insights about how information processing occurs in the central nervous system. As the Initiative enters its fifth year, NIH has supported over 500 principal investigators, who have answered the Initiative's challenge via hundreds of publications describing novel tools, methods, and discoveries that address the Initiative's seven scientific priorities. We describe scientific advances produced by individual labs, multi-investigator teams, and entire consortia that, over the coming decades, will produce more comprehensive and dynamic maps of the brain, deepen our understanding of how circuit activity can produce a rich tapestry of behaviors, and lay the foundation for understanding how its circuitry is disrupted in brain disorders. Much more work remains to bring this vision to fruition, and NIH continues to look to the diverse scientific community, from mathematics, to physics, chemistry, engineering, neuroethics, and neuroscience, to ensure that the greatest scientific benefit arises from this unique research Initiative. Copyright © 2018 the authors.

Is it useful to view the brain as a secondary sexual characteristic?

PubMed

Ball, Gregory F; Balthazart, Jacques; McCarthy, Margaret M

2014-10-01

Many sex differences in brain and behavior related to reproduction are thought to have evolved based on sexual selection involving direct competition for mates during male-male competition and female choice. Therefore, certain aspects of brain circuitry can be viewed as secondary sexual characteristics. The study of proximate causes reveals that sex differences in the brain of mammals and birds reflect organizational and activational effects of sex steroids as articulated by Young and collaborators. However, sex differences in brain and behavior have been identified in the cognitive domain with no obvious link to reproduction. Recent views of sexual selection advocate for a broader view of how intra-sexual selection might occur including such examples as competition within female populations for resources that facilitate access to mates rather than mating competition per se. Sex differences can also come about for other reasons than sexual selection and recent work on neuroendocrine mechanisms has identified a plethora of ways that the brain can develop in a sex specific manner. Identifying the brain as sexually selected requires careful hypothesis testing so that one can link a sex-biased aspect of a neural trait to a behavior that provides an advantage in a competitive mating situation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Loss of T cells influences sex differences in behavior and brain structure.

PubMed

Rilett, Kelly C; Friedel, Miriam; Ellegood, Jacob; MacKenzie, Robyn N; Lerch, Jason P; Foster, Jane A

2015-05-01

Clinical and animal studies demonstrate that immune-brain communication influences behavior and brain function. Mice lacking T cell receptor β and δ chains were tested in the elevated plus maze, open field, and light-dark test and showed reduced anxiety-like behavior compared to wild type. Interestingly sex differences were observed in the behavioural phenotype of TCRβ-/-δ- mice. Specifically, female TCRβ-/-δ- mice spent more time in the light chamber compared to wild type females, whereas male TCRβ-/-δ- spent more time in the center of the open field compared to wild type males. In addition, TCRβ-/-δ- mice did not show sex differences in activity-related behaviors observed in WT mice. Ex vivo brain imaging (7 Tesla MRI) revealed volume changes in hippocampus, hypothalamus, amygdala, periaqueductal gray, and dorsal raphe and other brain regions between wild type and T cell receptor knockout mice. There was also a loss of sexual dimorphism in brain volume in the bed nucleus of the stria terminalis, normally the most sexually dimorphic region in the brain, in immune compromised mice. These data demonstrate the presence of T cells is important in the development of sex differences in CNS circuitry and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Device for detecting imminent failure of high-dielectric stress capacitors. [Patent application

DOEpatents

McDuff, G.G.

1980-11-05

A device is described for detecting imminent failure of a high-dielectric stress capacitor utilizing circuitry for detecting pulse width variations and pulse magnitude variations. Inexpensive microprocessor circuitry is utilized to make numerical calculations of digital data supplied by detection circuitry for comparison of pulse width data and magnitude data to determine if preselected ranges have been exceeded, thereby indicating imminent failure of a capacitor. Detection circuitry may be incorporated in transmission lines, pulse power circuitry, including laser pulse circuitry or any circuitry where capacitors or capacitor banks are utilized.

Device for detecting imminent failure of high-dielectric stress capacitors

DOEpatents

McDuff, George G.

1982-01-01

A device for detecting imminent failure of a high-dielectric stress capacitor utilizing circuitry for detecting pulse width variations and pulse magnitude variations. Inexpensive microprocessor circuitry is utilized to make numerical calculations of digital data supplied by detection circuitry for comparison of pulse width data and magnitude data to determine if preselected ranges have been exceeded, thereby indicating imminent failure of a capacitor. Detection circuitry may be incorporated in transmission lines, pulse power circuitry, including laser pulse circuitry or any circuitry where capacitors or capactior banks are utilized.

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

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.

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.

Neuroscience of Internet Pornography Addiction: A Review and Update.

PubMed

Love, Todd; Laier, Christian; Brand, Matthias; Hatch, Linda; Hajela, Raju

2015-09-18

Many recognize that several behaviors potentially affecting the reward circuitry in human brains lead to a loss of control and other symptoms of addiction in at least some individuals. Regarding Internet addiction, neuroscientific research supports the assumption that underlying neural processes are similar to substance addiction. The American Psychiatric Association (APA) has recognized one such Internet related behavior, Internet gaming, as a potential addictive disorder warranting further study, in the 2013 revision of their Diagnostic and Statistical Manual. Other Internet related behaviors, e.g., Internet pornography use, were not covered. Within this review, we give a summary of the concepts proposed underlying addiction and give an overview about neuroscientific studies on Internet addiction and Internet gaming disorder. Moreover, we reviewed available neuroscientific literature on Internet pornography addiction and connect the results to the addiction model. The review leads to the conclusion that Internet pornography addiction fits into the addiction framework and shares similar basic mechanisms with substance addiction. Together with studies on Internet addiction and Internet Gaming Disorder we see strong evidence for considering addictive Internet behaviors as behavioral addiction. Future research needs to address whether or not there are specific differences between substance and behavioral addiction.

Neuroscience of Internet Pornography Addiction: A Review and Update

PubMed Central

Love, Todd; Laier, Christian; Brand, Matthias; Hatch, Linda; Hajela, Raju

2015-01-01

Many recognize that several behaviors potentially affecting the reward circuitry in human brains lead to a loss of control and other symptoms of addiction in at least some individuals. Regarding Internet addiction, neuroscientific research supports the assumption that underlying neural processes are similar to substance addiction. The American Psychiatric Association (APA) has recognized one such Internet related behavior, Internet gaming, as a potential addictive disorder warranting further study, in the 2013 revision of their Diagnostic and Statistical Manual. Other Internet related behaviors, e.g., Internet pornography use, were not covered. Within this review, we give a summary of the concepts proposed underlying addiction and give an overview about neuroscientific studies on Internet addiction and Internet gaming disorder. Moreover, we reviewed available neuroscientific literature on Internet pornography addiction and connect the results to the addiction model. The review leads to the conclusion that Internet pornography addiction fits into the addiction framework and shares similar basic mechanisms with substance addiction. Together with studies on Internet addiction and Internet Gaming Disorder we see strong evidence for considering addictive Internet behaviors as behavioral addiction. Future research needs to address whether or not there are specific differences between substance and behavioral addiction. PMID:26393658

A mechanism underlying position-specific regulation of alternative splicing

PubMed Central

Hamid, Fursham M.

2017-01-01

Abstract Many RNA-binding proteins including a master regulator of splicing in developing brain and muscle, polypyrimidine tract-binding protein 1 (PTBP1), can either activate or repress alternative exons depending on the pre-mRNA recruitment position. When bound upstream or within regulated exons PTBP1 tends to promote their skipping, whereas binding to downstream sites often stimulates inclusion. How this switch is orchestrated at the molecular level is poorly understood. Using bioinformatics and biochemical approaches we show that interaction of PTBP1 with downstream intronic sequences can activate natural cassette exons by promoting productive docking of the spliceosomal U1 snRNP to a suboptimal 5′ splice site. Strikingly, introducing upstream PTBP1 sites to this circuitry leads to a potent splicing repression accompanied by the assembly of an exonic ribonucleoprotein complex with a tightly bound U1 but not U2 snRNP. Our data suggest a molecular mechanism underlying the transition between a better-known repressive function of PTBP1 and its role as a bona fide splicing activator. More generally, we argue that the functional outcome of individual RNA contacts made by an RNA-binding protein is subject to extensive context-specific modulation.

Aberrant Cerebral Blood Flow in Response to Hunger and Satiety in Women Remitted from Anorexia Nervosa

PubMed Central

Wierenga, Christina E.; Bischoff-Grethe, Amanda; Rasmusson, Grace; Bailer, Ursula F.; Berner, Laura A.; Liu, Thomas T.; Kaye, Walter H.

2017-01-01

The etiology of pathological eating in anorexia nervosa (AN) remains poorly understood. Cerebral blood flow (CBF) is an indirect marker of neuronal function. In healthy adults, fasting increases CBF, reflecting increased delivery of oxygen and glucose to support brain metabolism. This study investigated whether women remitted from restricting-type AN (RAN) have altered CBF in response to hunger that may indicate homeostatic dysregulation contributing to their ability to restrict food. We compared resting CBF measured with pulsed arterial spin labeling in 21 RAN and 16 healthy comparison women (CW) when hungry (after a 16-h fast) and after a meal. Only remitted subjects were examined to avoid the confounding effects of malnutrition on brain function. Compared to CW, RAN demonstrated a reduced difference in the Hungry − Fed CBF contrast in the right ventral striatum, right subgenual anterior cingulate cortex (pcorr < 0.05) and left posterior insula (punc < 0.05); RAN had decreased CBF when hungry versus fed, whereas CW had increased CBF when hungry versus fed. Moreover, decreased CBF when hungry in the left insula was associated with greater hunger ratings on the fasted day for RAN. This represents the first study to show that women remitted from AN have aberrant resting neurovascular function in homeostatic neural circuitry in response to hunger. Regions involved in homeostatic regulation showed group differences in the Hungry − Fed contrast, suggesting altered cellular energy metabolism in this circuitry that may reduce motivation to eat. PMID:28770207

Aberrant Cerebral Blood Flow in Response to Hunger and Satiety in Women Remitted from Anorexia Nervosa.

PubMed

Wierenga, Christina E; Bischoff-Grethe, Amanda; Rasmusson, Grace; Bailer, Ursula F; Berner, Laura A; Liu, Thomas T; Kaye, Walter H

2017-01-01

The etiology of pathological eating in anorexia nervosa (AN) remains poorly understood. Cerebral blood flow (CBF) is an indirect marker of neuronal function. In healthy adults, fasting increases CBF, reflecting increased delivery of oxygen and glucose to support brain metabolism. This study investigated whether women remitted from restricting-type AN (RAN) have altered CBF in response to hunger that may indicate homeostatic dysregulation contributing to their ability to restrict food. We compared resting CBF measured with pulsed arterial spin labeling in 21 RAN and 16 healthy comparison women (CW) when hungry (after a 16-h fast) and after a meal. Only remitted subjects were examined to avoid the confounding effects of malnutrition on brain function. Compared to CW, RAN demonstrated a reduced difference in the Hungry - Fed CBF contrast in the right ventral striatum, right subgenual anterior cingulate cortex ( p corr  < 0.05) and left posterior insula ( p unc  < 0.05); RAN had decreased CBF when hungry versus fed, whereas CW had increased CBF when hungry versus fed. Moreover, decreased CBF when hungry in the left insula was associated with greater hunger ratings on the fasted day for RAN. This represents the first study to show that women remitted from AN have aberrant resting neurovascular function in homeostatic neural circuitry in response to hunger. Regions involved in homeostatic regulation showed group differences in the Hungry - Fed contrast, suggesting altered cellular energy metabolism in this circuitry that may reduce motivation to eat.

Quest for the basic plan of nervous system circuitry

PubMed Central

Swanson, Larry W.

2007-01-01

The basic plan of nervous system organization has been investigated since classical antiquity. The first model centered on pneumas pumped from sensory nerves through the ventricular system and out motor nerves to muscles. It was popular well into the seventeenth century and diverted attention from the organization of brain parenchyma itself. Willis focused on gray matter production and white matter conduction of pneumas in 1664, and by the late nineteenth century a clear cellular model of nervous system organization based on sensory, motor, and association neuron classes transmitting nerve impulses was elaborated by Cajal and his contemporaries. Today, revolutionary advances in experimental pathway tracing methods, molecular genetics, and computer science inspire systems neuroscience. Seven minimal requirements are outlined for knowledge management systems capable of describing, analyzing, and modeling the basic plan of nervous system circuitry in general, and the plan evolved for vertebrates, for mammals, and ultimately for humans in particular. The goal remains a relatively simple, easy to understand model analogous to the one Harvey elaborated in 1628 for circulation in the cardiovascular system. As Cajal wrote in 1909, “To extend our understanding of neural function to the most complex human physiological and psychological activities, it is essential that we first generate a clear and accurate view of the structure of the relevant centers, and of the human brain itself, so that the basic plan—the overview—can be grasped in the blink of an eye.” PMID:17267046

Comparison of brain connectivity between Internet gambling disorder and Internet gaming disorder: A preliminary study.

PubMed

Bae, Sujin; Han, Doug Hyun; Jung, Jaebum; Nam, Ki Chun; Renshaw, Perry F

2017-12-01

Background and aims Given the similarities in clinical symptoms, Internet gaming disorder (IGD) is thought to be diagnostically similar to Internet-based gambling disorder (ibGD). However, cognitive enhancement and educational use of Internet gaming suggest that the two disorders derive from different neurobiological mechanisms. The goal of this study was to compare subjects with ibGD to those with IGD. Methods Fifteen patients with IGD, 14 patients with ibGD, and 15 healthy control subjects were included in this study. Resting-state functional magnetic resonance imaging data for all participants were acquired using a 3.0 Tesla MRI scanner (Philips, Eindhoven, The Netherlands). Seed-based analyses, the three brain networks of default mode, cognitive control, and reward circuitry, were performed. Results Both IGD and ibGD groups demonstrated decreased functional connectivity (FC) within the default-mode network (DMN) (family-wise error p < .001) compared with healthy control subjects. However, the IGD group demonstrated increased FC within the cognitive network compared with both the ibGD (p < .01) and healthy control groups (p < .01). In contrast, the ibGD group demonstrated increased FC within the reward circuitry compared with both IGD (p < .01) and healthy control subjects (p < .01). Discussion and conclusions The IGD and ibGD groups shared the characteristic of decreased FC in the DMN. However, the IGD group demonstrated increased FC within the cognitive network compared with both ibGD and healthy comparison groups.

Evolution of the circuitry for conscious color vision in primates

PubMed Central

Neitz, J; Neitz, M

2017-01-01

There are many ganglion cell types and subtypes in our retina that carry color information. These have appeared at different times over the history of the evolution of the vertebrate visual system. They project to several different places in the brain and serve a variety of purposes allowing wavelength information to contribute to diverse visual functions. These include circadian photoentrainment, regulation of sleep and mood, guidance of orienting movements, detection and segmentation of objects. Predecessors to some of the circuits serving these purposes presumably arose before mammals evolved and different functions are represented by distinct ganglion cell types. However, while other animals use color information to elicit motor movements and regulate activity rhythms, as do humans, using phylogenetically ancient circuitry, the ability to appreciate color appearance may have been refined in ancestors to primates, mediated by a special set of ganglion cells that serve only that purpose. Understanding the circuitry for color vision has implications for the possibility of treating color blindness using gene therapy by recapitulating evolution. In addition, understanding how color is encoded, including how chromatic and achromatic percepts are separated is a step toward developing a complete picture of the diversity of ganglion cell types and their functions. Such knowledge could be useful in developing therapeutic strategies for blinding eye disorders that rely on stimulating elements in the retina, where more than 50 different neuron types are organized into circuits that transform signals from photoreceptors into specialized detectors many of which are not directly involved in conscious vision. PMID:27935605

Evolution of the circuitry for conscious color vision in primates.

PubMed

Neitz, J; Neitz, M

2017-02-01

There are many ganglion cell types and subtypes in our retina that carry color information. These have appeared at different times over the history of the evolution of the vertebrate visual system. They project to several different places in the brain and serve a variety of purposes allowing wavelength information to contribute to diverse visual functions. These include circadian photoentrainment, regulation of sleep and mood, guidance of orienting movements, detection and segmentation of objects. Predecessors to some of the circuits serving these purposes presumably arose before mammals evolved and different functions are represented by distinct ganglion cell types. However, while other animals use color information to elicit motor movements and regulate activity rhythms, as do humans, using phylogenetically ancient circuitry, the ability to appreciate color appearance may have been refined in ancestors to primates, mediated by a special set of ganglion cells that serve only that purpose. Understanding the circuitry for color vision has implications for the possibility of treating color blindness using gene therapy by recapitulating evolution. In addition, understanding how color is encoded, including how chromatic and achromatic percepts are separated is a step toward developing a complete picture of the diversity of ganglion cell types and their functions. Such knowledge could be useful in developing therapeutic strategies for blinding eye disorders that rely on stimulating elements in the retina, where more than 50 different neuron types are organized into circuits that transform signals from photoreceptors into specialized detectors many of which are not directly involved in conscious vision.

Relationship between Duration of Untreated Psychosis and Intrinsic Corticostriatal Connectivity in Patients with Early Phase Schizophrenia.

PubMed

Sarpal, Deepak K; Robinson, Delbert G; Fales, Christina; Lencz, Todd; Argyelan, Miklos; Karlsgodt, Katherine H; Gallego, Juan A; John, Majnu; Kane, John M; Szeszko, Philip R; Malhotra, Anil K

2017-10-01

Patients with first-episode psychosis experience psychotic symptoms for a mean of up to 2 years prior to initiation of treatment, and long duration of untreated psychosis (DUP) is associated with poor clinical outcomes. Meanwhile, evidence compiled from numerous studies suggests that longer DUP is not associated with structural brain abnormalities. To date, few studies have examined the relationship between DUP and functional neuroimaging measures. In the present study, we used seed-based resting-state functional connectivity to examine the impact of DUP on corticostriatal circuitry. We included 83 patients with early phase schizophrenia and minimal exposure to antipsychotic drugs (<2 years), who underwent resting state scanning while entering 12 weeks of prospective treatment with second-generation antipsychotic drugs. Functional connectivity maps of the striatum were generated and examined in relation to DUP as a covariate. Mediation analyses were performed on a composite measure of corticostriatal connectivity derived from the significant results of our DUP analysis. We found that longer DUP correlated with worse response to treatment as well as overall decreased functional connectivity between striatal nodes and specific regions within frontal and parietal cortices. Moreover, the relationship between DUP and treatment response was significantly mediated by corticostriatal connectivity. Our results indicate that variation in corticostriatal circuitry may play a role in the relationship between longer DUP and worsened response to treatment. Future prospective studies are necessary to further characterize potential causal links between DUP, striatal circuitry and clinical outcomes.

Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

ERIC Educational Resources Information Center

Freeman, John H.; Steinmetz, Adam B.

2011-01-01

Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

Brain profiling and clinical-neuroscience.

PubMed

Peled, Avi

2006-01-01

The current psychiatric diagnostic system, the diagnostic statistic manual, has recently come under increasing criticism. The major reason for the shortcomings of the current psychiatric diagnosis is the lack of a scientific brain-related etiological knowledge about mental disorders. The advancement toward such knowledge is further hampered by the lack of a theoretical framework or "language" that translates clinical findings of mental disorders to brain disturbances and insufficiencies. Here such a theoretical construct is proposed based on insights from neuroscience and neural-computation models. Correlates between clinical manifestations and presumed neuronal network disturbances are proposed in the form of a practical diagnostic system titled "Brain Profiling". Three dimensions make-up brain profiling, "neural complexity disorders", "neuronal resilience insufficiency", and "context-sensitive processing decline". The first dimension relates to disturbances occurring to fast neuronal activations in the millisecond range, it incorporates connectivity and hierarchical imbalances appertaining typically to psychotic and schizophrenic clinical manifestations. The second dimension relates to disturbances that alter slower changes namely long-term synaptic modulations, and incorporates disturbances to optimization and constraint satisfactions within relevant neuronal circuitry. Finally, the level of internal representations related to personality disorders is presented by a "context-sensitive process decline" as the third dimension. For practical use of brain profiling diagnosis a consensual list of psychiatric clinical manifestations provides a "diagnostic input vector", clinical findings are coded 1 for "detection" and 0 for "non-detection", 0.5 is coded for "questionable". The entries are clustered according to their presumed neuronal dynamic relationships and coefficients determine their relevance to the specific related brain disturbance. Relevant equations calculate and normalize the different values attributed to relevant brain disturbances culminating in a three-digit estimation representing the three diagnostic dimensions. brain profiling has the promise for a future brain-related diagnosis. It offers testable predictions about the etiology of mental disorders because being brain-related it lends readily to brain imaging investigations. Being presented also as a one-point representation in a three-dimensional space, multiple follow-up diagnoses trace a trajectory representing an easy-to-see clinical history of the patient. Additional, more immediate, advantages involve reduced stigma because it relaters the disorder to the brain not the person, in addition the three-digit diagnostic code is clinically informative unlike the DSM codes that have no clinical relevance. To conclude, brain profiling diagnosis of mental disorders could be a bold new step toward a "clinical-neuroscience" substituting "psychiatry".

Attention and Motivated Response to Simulated Male Advertisement Call Activates Forebrain Dopaminergic and Social Decision-Making Network Nuclei in Female Midshipman Fish.

PubMed

Forlano, Paul M; Licorish, Roshney R; Ghahramani, Zachary N; Timothy, Miky; Ferrari, Melissa; Palmer, William C; Sisneros, Joseph A

2017-10-01

Little is known regarding the coordination of audition with decision-making and subsequent motor responses that initiate social behavior including mate localization during courtship. Using the midshipman fish model, we tested the hypothesis that the time spent by females attending and responding to the advertisement call is correlated with the activation of a specific subset of catecholaminergic (CA) and social decision-making network (SDM) nuclei underlying auditory- driven sexual motivation. In addition, we quantified the relationship of neural activation between CA and SDM nuclei in all responders with the goal of providing a map of functional connectivity of the circuitry underlying a motivated state responsive to acoustic cues during mate localization. In order to make a baseline qualitative comparison of this functional brain map to unmotivated females, we made a similar correlative comparison of brain activation in females who were unresponsive to the advertisement call playback. Our results support an important role for dopaminergic neurons in the periventricular posterior tuberculum and ventral thalamus, putative A11 and A13 tetrapod homologues, respectively, as well as the posterior parvocellular preoptic area and dorsomedial telencephalon, (laterobasal amygdala homologue) in auditory attention and appetitive sexual behavior in fishes. These findings may also offer insights into the function of these highly conserved nuclei in the context of auditory-driven reproductive social behavior across vertebrates. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

The missing link: evolution of the primate cerebellum.

PubMed

MacLeod, Carol

2012-01-01

The cerebellum has too often been seen as the "little brain," subservient to the "big brain," the cerebrum. That is changing, as neuroimaging uncovers the cerebellum as the "missing link" in the neurological underpinnings of many cognitive domains. Connections between the neocortex and the cerebellum are now more precisely defined, with functionally localized areas of cerebellar cortex understood for cognitive tasks in humans. Comparative volumetric studies of the primate cerebellum have isolated some elements of circuitry, and our field is moving toward a better integration with the neurosciences in a systematic comparative framework. The next decade may show great advances, as relatively noninvasive techniques of neuroimaging have the potential to build a comparative model of the evolution of primate neurocircuitry. Copyright © 2012 Elsevier B.V. All rights reserved.

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 motivation for very early intervention for infants at high risk for autism spectrum disorders.

PubMed

Webb, Sara Jane; Jones, Emily J H; Kelly, Jean; Dawson, Geraldine

2014-02-01

The first Autism Research Matrix (IACC, 2003) listed the identification of behavioural and biological markers of risk for autism as a top priority. This emphasis was based on the hypothesis that intervention with infants at-risk, at an early age when the brain is developing and before core autism symptoms have emerged, could significantly alter the developmental trajectory of children at risk for the disorder and impact long-range outcome. Research has provided support for specific models of early autism intervention (e.g., Early Start Denver Model) for improving outcomes in young children with autism, based on both behavioural and brain activity measures. Although great strides have been made in ability to identify risk markers for autism in younger infant/toddler samples, how and when to intervene during the prodromal state remains a critical question. Emerging evidence suggests that abnormal brain circuitry in autism precedes altered social behaviours; thus, an intervention designed to promote early social engagement and reciprocity potentially could steer brain development back toward the normal trajectory and remit or reduce the expression of symptoms.

Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

PubMed Central

Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

2013-01-01

In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid.

PubMed

Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E; Redhi, Godfrey H; Panlilio, Leigh V; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R

2013-11-01

In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse.

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography.

PubMed

Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M D; Rotenberg, Alexander; Daskalakis, Zafiris J; Pascual-Leone, Alvaro

2016-01-01

The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research.

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

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography

PubMed Central

Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M. D.; Rotenberg, Alexander; Daskalakis, Zafiris J.; Pascual-Leone, Alvaro

2016-01-01

The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research. PMID:27713691

Recovery of brain abscess-induced stuttering after neurosurgical intervention.

PubMed

Sudo, Daisuke; Doutake, Youichi; Yokota, Hidenori; Watanabe, Eiju

2018-05-12

Stuttering occurs in approximately 5% of all children and 1% of adults. One type, neurogenic stuttering, is usually attributable to strokes or other structural damages to the brain areas that are responsible for language fluency. Here, we present the first case of neurogenic stuttering caused by a brain abscess. The patient was a 60-year-old man admitted for a seizure and administered an anticonvulsant, after which he began stuttering. MRI revealed a brain abscess in the left frontal lobe that extended to the dorsolateral prefrontal cortex (BA (Brodmann's area) 9 and 46), frontal eye field (BA 8) and premotor cortex and supplementary motor area (BA 6). After neurosurgical drainage and antibiotic treatment, the symptoms had resolved. This case is unique in that the therapeutic effects and localisation of the cause of stuttering were rapidly identified, allowing for a more accurate description of the neural circuitry related to stuttering. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research.

PubMed

Kouzani, Abbas Z; Abulseoud, Osama A; Tye, Susannah J; Hosain, M D Kamal; Berk, Michael

2013-01-01

Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented.

The amusic brain: in tune, out of key, and unaware.

PubMed

Peretz, Isabelle; Brattico, Elvira; Järvenpää, Miika; Tervaniemi, Mari

2009-05-01

Like language, music engagement is universal, complex and present early in life. However, approximately 4% of the general population experiences a lifelong deficit in music perception that cannot be explained by hearing loss, brain damage, intellectual deficiencies or lack of exposure. This musical disorder, commonly known as tone-deafness and now termed congenital amusia, affects mostly the melodic pitch dimension. Congenital amusia is hereditary and is associated with abnormal grey and white matter in the auditory cortex and the inferior frontal cortex. In order to relate these anatomical anomalies to the behavioural expression of the disorder, we measured the electrical brain activity of amusic subjects and matched controls while they monitored melodies for the presence of pitch anomalies. Contrary to current reports, we show that the amusic brain can track quarter-tone pitch differences, exhibiting an early right-lateralized negative brain response. This suggests near-normal neural processing of musical pitch incongruities in congenital amusia. It is important because it reveals that the amusic brain is equipped with the essential neural circuitry to perceive fine-grained pitch differences. What distinguishes the amusic from the normal brain is the limited awareness of this ability and the lack of responsiveness to the semitone changes that violate musical keys. These findings suggest that, in the amusic brain, the neural pitch representation cannot make contact with musical pitch knowledge along the auditory-frontal neural pathway.

[Estrogens and feminine brain maturation during adolescence: emergency contraceptive pill].

PubMed

López Moratalla, Natalia; Errasti Alcalá, Tania; Santiago, Esteban

2011-01-01

In the period between puberty and maturity takes place the process of brain maturation. Hormone levels induce changes in neurons and direct the architecture and structural functionality thus affecting patterns of development of different brain areas. The onset of puberty brings with it the invasion of the female brain by high levels of hormones, cyclic surges of estrogen and progesterone in addition to steroids produced in situ. Control centers of emotions (amygdala), memory and learning (hippocampus) and sexual activity (hypothalamus) are modified according to the cyclical concentrations of both hormones. Sex hormones stimulate multimodal actions, both short and longer terms, because neurons in various brain areas have different types of receptors, membrane, cytoplasmic and nuclear. The composition of emergency contraceptive pill (postcoital pill) with high hormonal content raises the urgency of a thorough knowledge about the possible effect that the lack of control of the menstrual cycle in a time of consolidation of brain maturation, can bring in structuring and development of brain circuitry. Changes in the availability of sex steroids during puberty and adolescence underlie psychiatric disorders whose prevalence is typically feminine, such as depression, anxiety disorders. It is a fundamental ethical duty to present scientific data about the influence of estrogen in young female brain maturation, both for full information to potential users, and also to induce the appropriate public health measures.

Multimodal neuroimaging of male and female brain structure in health and disease across the life span.

PubMed

Jahanshad, Neda; Thompson, Paul M

2017-01-02

Sex differences in brain development and aging are important to identify, as they may help to understand risk factors and outcomes in brain disorders that are more prevalent in one sex compared with the other. Brain imaging techniques have advanced rapidly in recent years, yielding detailed structural and functional maps of the living brain. Even so, studies are often limited in sample size, and inconsistent findings emerge, one example being varying findings regarding sex differences in the size of the corpus callosum. More recently, large-scale neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium have formed, pooling together expertise, data, and resources from hundreds of institutions around the world to ensure adequate power and reproducibility. These initiatives are helping us to better understand how brain structure is affected by development, disease, and potential modulators of these effects, including sex. This review highlights some established and disputed sex differences in brain structure across the life span, as well as pitfalls related to interpreting sex differences in health and disease. We also describe sex-related findings from the ENIGMA consortium, and ongoing efforts to better understand sex differences in brain circuitry. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Birdsong and the neural production of steroids

PubMed Central

Remage-Healey, Luke; London, Sarah E.; Schinger, Barney A.

2009-01-01

The forebrain circuits involved in singing and audition (the ‘song system’) in songbirds exhibit a remarkable capacity to synthesize and respond to steroid hormones. This review considers how local brain steroid production impacts the development, sexual differentiation, and activity of song system circuitry. The songbird forebrain contains all of the enzymes necessary for the de novo synthesis of steroids - including neuroestrogens - from cholesterol. Steroid production enzymes are found in neuronal cell bodies, but they are also expressed in pre-synaptic terminals in the song system, indicating a novel mode of brain steroid delivery to local circuits. The song system expresses nuclear hormone receptors, consistent with local action of brain-derived steroids. Local steroid production also occurs in brain regions that do not express nuclear hormone receptors, suggesting a non-classical mode-of-action. Recent evidence indicates that local steroid levels can change rapidly within the forebrain, in a manner similar to traditional neuromodulators. Lastly, we consider growing evidence for modulatory interactions between brain-derived steroids and neurotransmitter/neuropeptide networks within the song system. Songbirds have therefore emerged as a rich and powerful model system to explore the neural and neurochemical regulation of social behavior. PMID:19589382

Variability of perceptual multistability: from brain state to individual trait

PubMed Central

Kleinschmidt, Andreas; Sterzer, Philipp; Rees, Geraint

2012-01-01

Few phenomena are as suitable as perceptual multistability to demonstrate that the brain constructively interprets sensory input. Several studies have outlined the neural circuitry involved in generating perceptual inference but only more recently has the individual variability of this inferential process been appreciated. Studies of the interaction of evoked and ongoing neural activity show that inference itself is not merely a stimulus-triggered process but is related to the context of the current brain state into which the processing of external stimulation is embedded. As brain states fluctuate, so does perception of a given sensory input. In multistability, perceptual fluctuation rates are consistent for a given individual but vary considerably between individuals. There has been some evidence for a genetic basis for these individual differences and recent morphometric studies of parietal lobe regions have identified neuroanatomical substrates for individual variability in spontaneous switching behaviour. Moreover, disrupting the function of these latter regions by transcranial magnetic stimulation yields systematic interference effects on switching behaviour, further arguing for a causal role of these regions in perceptual inference. Together, these studies have advanced our understanding of the biological mechanisms by which the brain constructs the contents of consciousness from sensory input. PMID:22371620

Profiles of Impaired, Spared, and Recovered Neuropsychological Processes in Alcoholism

PubMed Central

Oscar-Berman, Marlene; Valmas, Mary M.; Sawyer, Kayle S.; Ruiz, Susan Mosher; Luhar, Riya B.; Gravitz, Zoe R.

2015-01-01

Long-term chronic alcoholism is associated with disparate and widespread residual consequences for brain functioning and behavior, and alcoholics suffer a variety of cognitive deficiencies and emotional abnormalities. Alcoholism has heterogeneous origins and outcomes, depending upon factors such as family history, age, gender, and mental or physical health. Consequently, the neuropsychological profiles associated with alcoholism are not uniform among individuals. Moreover, within and across research studies, variability among participants is substantial and contributes to characteristics associated with differential treatment outcomes after detoxification. In order to refine our understanding of alcoholism-related impaired, spared, and recovered abilities, we focus on five specific functional domains: (1) memory, (2) executive functions, (3) emotion and psychosocial skills, (4) visuospatial cognition, and (5) psychomotor abilities. The brain systems that are most vulnerable to alcoholism are the frontocerebellar and mesocorticolimbic circuitries. Over time, with abstinence from alcohol, the brain appears to become reorganized to provide compensation for structural and behavioral deficits. By relying on a combination of clinical and scientific approaches, future research will help to refine the compensatory roles of healthy brain systems, the degree to which abstinence and treatment facilitate the reversal of brain atrophy and dysfunction, and the importance of individual differences to outcome. PMID:25307576