Restorative Neurology and Neuroscience - Volume 32, issue 1

Authors: Flor, Herta | Meyer-Lindenberg, Andreas

Article Type: Other

DOI: 10.3233/RNN-139017

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 1-3, 2014

Authors: Morris, Sarah E. | Rumsey, Judith M. | Cuthbert, Bruce N.

Article Type: Research Article

Abstract: Recent research in neurodevelopment, neuroplasticity and genetics is providing new insights into the etiogenesis of psychopathology, but progress in treatment development has been hampered by reliance on diagnostic categories that are characterized by heterogeneity and based primarily on phenomenology. The NIMH Research Domain Criteria (RDoC) initiative seeks to provide a neuroscience-based nosological framework for future research on psychopathology, categorizing individuals for research purposes using a dimensional approach that capitalizes on advances in modern neuroscience. These scientific advances and new approaches to classification can inform the development of novel, circuit-based interventions and the personalization of treatment. In this paper, we review …key advances areas in clinical neuroscience, describe the RDoC project and highlight some emerging treatment approaches that are consistent with these developments. Show more

Keywords: Psychiatric diagnosis, RDoC, neuroplasticity, psychiatric treatment

DOI: 10.3233/RNN-139015

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 5-23, 2014

Authors: Kuhn, Manuel | Popovic, Ana | Pezawas, Lukas

Article Type: Research Article

Abstract: A vast number of imaging studies have demonstrated the impact of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) on emotion and memory-related networks in the context of Major Depressive Disorder (MDD). Underlying molecular mechanisms that affect the functionality of these networks have been examined in detail in animals and corroborate imaging findings. The crucial role of 5-HT and BDNF signaling in the context of MDD is reflected in the etiologic models of MDD such as the monoamine or neuroplasticity hypothesis as well as in pharmacological models of antidepressant response. While antidepressant drug treatment has been primarily linked to the modulation …of emotion-related networks, cognitive behavioral therapy has been implicated in a top-down control of limbic structures. Initially, a simple lack of monoamines or BDNF has been proposed as causal factor of MDD etiology. However, recent findings suggest a much more complex neurobiology emphasizing epistatic and epigenetic mechanisms responsible for structural and functional changes observed in emotion and memory-related brain regions of healthy subjects and MDD patients. In this review, which focuses on neuroimaging studies in the context of MDD, the authors will provide a comprehensive overview of these networks as well as on the specific role of 5-HT and BDNF in their development and function. Show more

Keywords: Neuroimaging, functional magnetic resonance imaging, neuroplasticity, serotonin transporter, memory, learning, epistasis, major depressive disorder, selective serotonin re-uptake inhibitor, tryptophan, SLC6A4, BDNF

DOI: 10.3233/RNN-139005

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 25-49, 2014

Authors: Wessa, Michèle | Kanske, Philipp | Linke, Julia

Article Type: Research Article

Abstract: Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60–80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD patients and healthy individuals at risk …to develop BD. As a main result of our studies, we observed altered orbitofrontal and limbic activity and reduced connectivity between dorsal prefrontal and limbic brain regions, as well as reduced integrity of fiber tracts connecting prefrontal and subcortical brain structures in BD patients and high-risk individuals. Our results provide novel insights into pathophysiological mechanisms of bipolar disorder. The current laboratory review provides a specific view of our group on altered brain connectivity and underlying psychological processes in bipolar disorder based on our own work, integrating relevant findings from others. Thereby we attempt to advance neuropsychobiological models of BD. Show more

Keywords: Vulnerability, behavioral activation system, emotion regulation, amygdala, orbitofrontal cortex, reward, connectivity

DOI: 10.3233/RNN-139007

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 51-62, 2014

Authors: Lang, Peter J. | McTeague, Lisa M. | Bradley, Margaret M.

Article Type: Research Article

Abstract: 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. Show more

Keywords: Imagery, anxiety, specific phobia, social phobia, panic, GAD, comorbidity, depression, PTSD, trauma, chronicity, emotional reactivity, diagnostic subtypes, psychophysiology, startle, fMRI, real-time fMRI

DOI: 10.3233/RNN-139012

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 63-77, 2014

Authors: Hamm, Alfons O. | Richter, Jan | Pané-Farré, Christiane A.

Article Type: Research Article

Abstract: Unexpected, recurrent panic attacks and anxious apprehension are two distinct emotional phenomena that constitute the core symptoms for diagnosing panic disorder. Taking a neuroscience perspective the current review paper presents both epidemiological and experimental psychophysiological evidence suggesting that panic attacks can be conceptualized as an unconditioned circa defense response pattern to intense internal threat stimuli, characterized by strong autonomic surge and escape behavior and abnormal plastic changes of the brain. Anxious apprehension develops after the experience of such severe panic attacks as conditioned responses to mild body symptoms. Theoretically these conditioned fear responses can be considered as post-encounter defense characterized …by increased selective attention, increased threat appraisal and defensive freezing and startle potentiation evidencing altered brain circuits evoked by mild body symptoms. Agoraphobic avoidance starts very early during the defensive cascade and can be conceived as motivated behavior driven by the incentive to be in a safe context that is under control of the individual. Show more

Keywords: Panic disorder, anticipatory anxiety, defense cascade, startle potentiation, fear learning, phobic avoidance

DOI: 10.3233/RNN-139011

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 79-93, 2014

Authors: Flor, Herta | Nees, Frauke

Article Type: Research Article

Abstract: We review evidence from our laboratory that suggests that in addition to enhanced cue conditioning and delayed cue extinction disturbed contextual learning may play an important role in the development and maintenance of posttraumatic stress disorder. Based on data from a longitudinal sample of rescue workers at high risk for posttraumatic stress disorder and data on single trauma exposed persons with and without posttraumatic stress disorder we show the crucial role of the hippocampus for contextual memory and impaired contextual learning along with enhanced cue conditioning and delayed extinction in PTSD. Using structural and functional magnetic resonance imaging we confirmed …animal data on the role of the hippocampus in contextual and the importance of the amygdala in cue conditioning and the role of the frontal cortex in extinction. Genetic variants related to the modulation of the hypothalamus-pituitary-adrenal axis are associated with cue and genetic variants related to calcium signaling and memory processes and the regulation of the stress response are associated with context conditioning. These genes also play a role in PTSD. Further research needs to identify the predictive nature of these learning processes and plastic brain changes and their interaction with genetic characteristics changes for the transition into PTSD and its maintenance. A further focus needs to be on the identification of learning and memory mechanisms and the associated brain plasticity across disorders. Show more

Keywords: Posttraumatic stress disorder, cue conditioning, context conditioning, genetics, brain imaging

DOI: 10.3233/RNN-139013

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 95-102, 2014

Authors: Anderson, Nathaniel E. | Kiehl, Kent A.

Article Type: Research Article

Abstract: Psychopathy is a mental disorder marked by deficient emotional responses, lack of empathy, and poor behavioral controls, commonly resulting in persistent antisocial deviance and criminal behavior. Accumulating research suggests that psychopathy follows a developmental trajectory with strong genetic influences, and which precipitates deleterious effects on widespread functional networks, particularly within paralimbic regions of the brain. While traditional therapeutic interventions commonly administered in prisons and forensic institutions have been notoriously ineffective at combating these outcomes, alternative strategies informed by an understanding of these specific neuropsychological obstacles to healthy development, and which target younger individuals with nascent symptoms of psychopathy are more …promising. Here we review recent neurobehavioral and neuroimaging literature that informs our understanding of the brain systems compromised in psychopathy, and apply these data to a broader understanding of its developmental course, ultimately promoting more proactive intervention strategies profiting from adaptive neuroplasticity in youth. Show more

Keywords: Psychopathy, antisocial behavior, conduct disorder, callous unemotional traits, treatment

DOI: 10.3233/RNN-139001

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 103-117, 2014

Authors: Meyer-Lindenberg, Andreas | Tost, Heike

Article Type: Research Article

Abstract: Schizophrenia is a frequent and highly heritable brain disorder that typically manifests around or after puberty and has a fluctuating course. Multiple lines of evidence point to a neurodevelopmental origin of the illness and suggest that its (post) pubertal manifestation is related to genetic and environmental risk factors that interfere with the structural and functional reorganization of neural networks at this time. Longitudinal structural neuroimaging studies point to a progressive reduction in gray matter volume in many brain regions in schizophrenia. It has been proposed that these neuroimaging observations reflect an enduring disturbance of experience-dependent synaptic plasticity arising from developmental …abnormalities in key neural circuits implicated in schizophrenia, including dorsolateral prefrontal cortex and hippocampal formation. Recent work has identified genetic variants linked to neural plasticity that are associated with changes in these circuits. Furthermore, non-invasive interventions such as transcranial magnetic stimulation have been shown to impact some of these systems-level intermediate phenotypes, suggesting a modifiability of these core pathophysiological processes of schizophrenia that may be exploited by therapy. Show more

Keywords: Schizophrenia, plasticity, neurodevelopment, functional magnetic resonance imaging, graph theory, rapid transcranial magnetic stimulation

DOI: 10.3233/RNN-139014

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 119-127, 2014

Authors: Mansour, A.R. | Farmer, M.A. | Baliki, M.N. | Apkarian, A. Vania

Article Type: Research Article

Abstract: Based on theoretical considerations and recent observations, we argue that continued suffering of chronic pain is critically dependent on the state of motivational and emotional mesolimbic-prefrontal circuitry of the brain. The plastic changes that occur within this circuitry in relation to nociceptive inputs dictate the transition to chronic pain, rendering the pain less somatic and more affective in nature. This theoretical construct is a strong departure from the traditional scientific view of pain, which has focused on encoding and representation of nociceptive signals. We argue that the definition of chronic pain can be recast, within the associative learning and valuation …concept, as an inability to extinguish the associated memory trace, implying that supraspinal/cortical manipulations may be a more fruitful venue for adequately modulating suffering and related behavior for chronic pain. We briefly review the evidence generated to date for the proposed model and emphasize that the details of underlying mechanisms remain to be expounded. Show more

DOI: 10.3233/RNN-139003

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 129-139, 2014

Authors: Jensen, Jimmy | Walter, Henrik

Article Type: Research Article

Abstract: In this paper the concept of incentive motivational salience is briefly described, pioneering studies on the subject of the mesolimbic motivational system are reviewed, and studies we have been involved in conducting which elaborate on this subject are discussed. In particular, we aim to show that the mesolimbic motivational system is recruited as a reaction to primary and secondary reinforcers as a function of salience, that is independent of valence. Furthermore, studies showing that both psychological and pharmacological interventions can affect the function of the mesolimbic motivational system and how its' dysfunction is related to psychopathological phenomena with an emphasis …on psychosis are discussed. Show more

Keywords: Motivation, salience, ventral striatum, imaging, schizophrenia

DOI: 10.3233/RNN-139006

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 141-147, 2014

Authors: Ditzen, Beate | Heinrichs, Markus

Article Type: Research Article

Abstract: Social integration and social support have a substantial influence on individual health and longevity, an effect assumed to be mediated through reduced stress reactivity in support recipients. However, considerable variability in individual responses to social support has been documented, suggesting that the beneficial effect of social support interacts with early experiences, genetically influenced differences in biological systems mediating social behavior, personality traits, and psychopathology. Here we outline the historical background of social support research, including epidemiological studies, laboratory studies, and field studies on the subject of social support and health, with regard to different psychobiological effector systems. Most recent research …has focused on brain mechanisms which link social integration or social support with reduced neural threat responses. As numerous mental disorders are associated with considerable social impairment, understanding the potentially underlying mechanisms of neural plasticity in relation to social support, stress buffering and health in these disorders can help tailor new diagnostic and treatment strategies. Thus, theories of socially-driven emotional learning and memory, as presented in this review, might eventually lead to psychobiology-based treatment concepts for mental disorders involving social deficits. Show more

Keywords: Social support, stress, psychobiology, autonomic nervous system (ANS), hypothalamus pituitary adrenal (HPA) axis, cortisol, oxytocin, safety signals

DOI: 10.3233/RNN-139008

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 149-162, 2014

Authors: Paulzen, Michael | Veselinovic, Tanja | Gründer, Gerhard

Article Type: Research Article

Abstract: Although neurotransmitter-based hypotheses still prevail current thinking about the mechanism of action of psychotropic drugs, recent insight into the pathophysiology of psychiatric disorders has unveiled a range of new therapeutic actions of the drugs used to treat those disorders. Especially antidepressants seem to exert at least some of their effects via restoration of synaptic/neuronal plasticity. In addition, there is increasing evidence that several of the second-generation antipsychotics and some anticonvulsants affect neuronal survival/apoptosis as well as synaptic plasticity. Most of this evidence stems from work in animals. In this review, we will focus on the evidence for neuroplastic effects of …psychotropic drugs in humans being aware of the fact that most of the data are derived from animals and that volumetric studies in humans can only indicate structural plasticity and not necessarily functional plasticity. However, as the data from human studies are rather poor and inconclusive, and sometimes even conflicting, it seems impossible to draw general conclusions. Until now studies on neuroplasticity in humans can only explain small pieces of the effects of psychotropic drugs on brain plasticity in humans. Nevertheless, future prospects for the development of new drugs targeting brain plasticity will be of importance and will complete this overview. Show more

Keywords: Antidepressants, antipsychotics, mood stabilizer, neuroplasticity, plasticity, neuroprotection, synaptic plasticity

DOI: 10.3233/RNN-139004

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 163-181, 2014

Authors: Hofmann, Stefan G. | Fang, Angela | Gutner, Cassidy A.

Article Type: Research Article

Abstract: Traditional treatments for anxiety disorders include cognitive-behavioral therapy and anxiolytic medications. Although these treatments are more effective than placebo, there is still considerable room for further improvement. Unfortunately, combining these different modalities is generally not substantially better than monotherapies. Recently, researchers have turned their attention toward translating preclinical research on the neural circuitry underlying fear extinction to clinical applications for the treatment of anxiety disorders with the goal to augment the learning process during exposure-based procedures with cognitive enhancers. This review examines d-cycloserine, cortisol, catecholamines, yohimbine, oxytocin, modafinil, as well as nutrients and botanicals as agents to augment treatment for …anxiety disorders. D-cycloserine shows the most empirical support. Other promising agents include cortisol, catecholamines, yohimbine, and possibly oxytocin. Less support comes from studies that examined nutrients and botanicals, such as caffeine, nicotine, and omega-3 fatty acid. Limitations of the exiting literature and future research directions are discussed. Show more

Keywords: Cognitive enhancers, anxiety disorders, augmentation strategies

DOI: 10.3233/RNN-139002

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 183-195, 2014

Authors: Poustka, Luise | Brandeis, Daniel | Hohmann, Sarah | Holtmann, Martin | Bölte, Sven | Banaschewski, Tobias

Article Type: Research Article

Abstract: Autism spectrum disorders (ASD) are heterogeneous, neurodevelopmental disorders with early onset, characterized by a triad of impairments in reciprocal interaction and communication as well as repetitive and restricted interests and activities. Though underlying causes still remain largely unknown, there is now evidence for abnormal growth trajectories in the early brain development in ASD during vulnerable periods and subsequent impairment of neuronal organization and differentiation of neuronal networks. A growing number of studies over the last 10 years support the efficacy of behaviorally based interventions in ASD for the improvement of social communication and behavioral functioning. In contrast, research on neurobiologically …based therapies for ASD is still at its beginnings. In this article, we will provide a selective overview of novel interventions and trainings based on neurobiological principles. Directions and options for future research on treatment aiming at restoration of normal plasticity in disrupted brain circuits in ASD are discussed. Show more

Keywords: Autism spectrum disorder, intervention, novel treatments, neurofeedback, neural plasticity

DOI: 10.3233/RNN-139010

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 197-212, 2014

Authors: Degen, Christina | Schröder, Johannes

Article Type: Research Article

Abstract: As the demographic shift towards an aging population prevails, the improvement and/or maintenance of cognitive functioning appear increasingly important. To date, the effectiveness of cognitive, cardiovascular and sensorimotor training approaches in older adults has been demonstrated frequently using neuropsychological and behavioral performance measures. We present an overview of selected studies applying modern imaging techniques (fMRI, PET) to assess practice-induced structural and functional changes in the brain. Structurally, practice is associated with volumetric increases. Functionally, reorganization of neural network recruitment, overall decreases and increases in activity levels are found. Thus, the human brain retains a high degree of plasticity in old …age. Moreover, it seems that practice leads to more efficient processing, requiring less neural engagement to perform the same task. While the concept of economization finds widespread support in healthy populations, in patient groups this effect has proven to be absent or reversed. The concept of cognitive reserve and potentially compensatory mechanisms are discussed in this context. Show more

Keywords: Neuroimaging, plasticity, aging, cognition, training

DOI: 10.3233/RNN-139009

Citation: Restorative Neurology and Neuroscience, vol. 32, no. 1, pp. 213-221, 2014