179 research outputs found

    Age-differential relationships among dopamine D1 binding potential, fusiform BOLD signal, and face-recognition performance

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    Facial recognition ability declines in adult aging, but the neural basis for this decline remains unknown. Cortical areas involved in face recognition exhibit lower dopamine (DA) receptor availability and lower blood-oxygen-level-dependent (BOLD) signal during task performance with advancing adult age. We hypothesized that changes in the relationship between these two neural systems are related to age differences in face-recognition ability. To test this hypothesis, we leveraged positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to measure D1 receptor binding potential (BPND) and BOLD signal during facerecognition performance. Twenty younger and 20 older participants performed a face-recognition task during fMRI scanning. Face recognition accuracy was lower in older than in younger adults, as were D1 BPND and BOLD signal across the brain. Using linear regression, significant relationships between DA and BOLD were found in both age-groups in face-processing regions. Interestingly, although the relationship was positive in younger adults, it was negative in older adults (i.e., as D1 BPND decreased, BOLD signal increased). Ratios of BOLD:D1 BPND were calculated and relationships to face-recognition performance were tested. Multiple linear regression revealed a significant Group BOLD:D1 BPND Ratio interaction. These results suggest that, in the healthy system, synchrony between neurotransmitter (DA) and hemodynamic (BOLD) systems optimizes the level of BOLD activation evoked for a given DA input (i.e., the gain parameter of the DA input-neural activation function), facilitating task performance. In the aged system, however, desynchronization between these brain systems would reduce the gain parameter of this function, adversely impacting task performance and contributing to reduced face recognition in older adults

    Differential dopamine function in fibromyalgia

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    Approximately 30% of Americans suffer from chronic pain disorders, such as fibromyalgia (FM), which can cause debilitating pain. Many pain-killing drugs prescribed for chronic pain disorders are highly addictive, have limited clinical efficacy, and do not treat the cognitive symptoms reported by many patients. The neurobiological substrates of chronic pain are largely unknown, but evidence points to altered dopaminergic transmission in aberrant pain perception. We sought to characterize the dopamine (DA) system in individuals with FM. Positron emission tomography (PET) with [18F]fallypride (FAL) was used to assess changes in DA during a working memory challenge relative to a baseline task, and to test for associations between baseline D2/D3 availability and experimental pain measures. Twelve female subjects with FM and eleven female controls completed study procedures. Subjects received one FAL PET scan while performing a “2-back” task, and one while performing a “0-back” (attentional control, “baseline”) task. FM subjects had lower baseline FAL binding potential (BP) in several cortical regions relative to controls, including anterior cingulate cortex. In FM subjects, self-reported spontaneous pain negatively correlated with FAL BP in the left orbitofrontal cortex and parahippocampal gyrus. Baseline BP was significantly negatively correlated with experimental pain sensitivity and tolerance in both FM and CON subjects, although spatial patterns of these associations differed between groups. The data suggest that abnormal DA function may be associated with differential processing of pain perception in FM. Further studies are needed to explore the functional significance of DA in nociception and cognitive processing in chronic pain

    The Effects of SNCA rs894278 on Resting-State Brain Activity in Parkinson’s Disease

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    The pathogenesis of Parkinson’s disease (PD) is not well established. The rs894278 polymorphism of SNCA has been associated with PD. We performed this study to investigate the relationship between rs894278 and PD status on resting-state brain activity, by analyzing the amplitude of low-frequency fluctuation (ALFF). A total of 81 PD patients and 64 healthy controls were recruited. Disease severity and PD stage were evaluated in PD patients using the unified Parkinson’s disease rating scale (UPDRS) and the Hoehn and Yahr (HY) scale, while the cognitive function of all participants was assessed using the mini-mental state examination (MMSE). All participants were genotyped for the rs894278 SNP and underwent a resting state functional magnetic resonance imaging scan. We found that the ALFF values of PD patients in the lingual gyrus and left caudate were lower than those of HCs; and the ALFF values for the right fusiform of participants with G allele were lower than those of participants without G allele. And we further revealed higher ALFF values in bilateral fusiform in rs894278-G carriers than in rs894278-G non-carriers in the PD group and lower ALFF values in bilateral fusiform in rs894278-G carriers than in rs894278-G non-carriers in the HC group. Our findings show that rs894278 and PD status interactively affect the brain activity of PD patients and HCs, and changes in the brain connectomes may play a key role in the pathogenesis of PD. Thus, our work sheds light on the mechanism underlying PD pathogenesis

    Functional imaging in neuroenhancement

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    Increasingly demanding tasks, competition for competence and time pressure have lead to attempts of neuroenhancement (NE) among students and employees. NE is designed to increase cognitive abilities by modulating brain processes through the use of pharmaceutics. Substances such as methylphenidate (i.e. RitalinÂź), modafinil (i.e. VigilÂź) and caffeine are common candidates for enhancing cognitive abilities such as executive functions, inhibition control and memory (Wood et al., 2014). Until today, there has not been a study investigating memory enhancement in functional magnetic resonance imaging (fMRI). Using fMRI, 48 healthy participants were tested for drug effects in a single-dose, double-blind and randomized study using a declarative memory task. During memory recall, methylphenidate dependent deactivations were found in the fronto-parietal and temporal regions whereas no BOLD alterations were seen during encoding. On the behavioral level, methylphenidate enhanced subject’s judgement confidence and performance during late recall. During encoding, caffeine led to deactivations in the precentral gyrus whereas modafinil did not show any BOLD signal alterations at all. To get an overview over the existing neuroimaging literature, all published studies on the effects of the aforementioned drug agents were reviewed in addition. In line with this study, previous publications emphasized that methylphenidate seems to alter task relevant brain areas. Our main finding of task-related deactivations may point to the reduction of task-functioning distractions. Thereby, we conclude a drug-dependent increase of efficiency in data processing.Zunehmende Arbeitsbelastung, erhöhter Zeitdruck und grĂ¶ĂŸere Verantwortung haben dazu gefĂŒhrt, dass fĂŒr Studenten und Arbeitnehmer das PhĂ€nomen Neuroenhancement (NE) eine zunehmende Relevanz erlangt hat. Darunter wird die Steigerung der kognitiven Leistung durch pharmazeutischen Eingriff auf zentralnervöse Prozesse verstanden. Substanzen wie z.B. Methylphenidat (RitalinÂź), Modafinil (VigilÂź) und Koffein gelten als aussichtsreiche Kandidaten zur Leistungssteigerung, die möglicherweise Einfluss auf kognitive Prozesse, wie z.B. Exekutive Funktionen, Inhibitionskontrolle und GedĂ€chtnis ausĂŒben können (Wood et al., 2014). Keine bisher publizierte Studie hat den Fokus auf neuronale Korrelate der deklarativen GedĂ€chtnissteigerung gelegt. Aus dem Grund sind zusĂ€tzlich alle bisher veröffentlichten bildgebenden Studien zu Methylphenidat, Modafinil und Koffein zu einer strukturierten Übersicht zusammengefasst worden. Mittels funktionaler Magnetresonanztomographie (fMRT) wurden 48 gesunde Probanden, doppelt verblindet und randomisiert auf Steigerung der deklarativen GedĂ€chtnisleistung getestet. Obwohl die Wirksamkeit der drei Substanzen ausfĂŒhrlich fĂŒr klinische Patientenpopulationen untersucht wurde, gibt es kaum Wissen ĂŒber die möglichen behavioralen und neuronalen Auswirkungen auf gesunde, erwachsene Menschen. Entgegen der Erwartung, dass die getesteten Substanzen klassische GedĂ€chtnis assoziierte Regionen aktivieren, wurden unterschiedliche substanzspezifische Effekte gefunden. Wahrend des Abrufs von GedĂ€chtnisinhalten deaktivierte Methylphenidat fronto-parietale und temporale Regionen. Dagegen fĂŒhrte die Applikation von Koffein zu einer verringerten BOLD Antwort im Gyrus PrĂ€centralis wĂ€hrend der Lernphase. Modafinil fĂŒhrte zu keiner VerĂ€nderung im Vergleich zu Placebo. Auf Verhaltensebene förderte Methylphenidat den spĂ€ten Abruf von GedĂ€chtnisinhalten, wohingegen die beiden anderen Substanzen keine Effekte hinsichtlich der Lernleistung vorwiesen. Vor dem Hintergrund bisheriger bildgebender Studien zeigt die vorliegende Arbeit, dass Neuroenhancement neben der Aktivierung leistungsrelevanter Gehirnregionen auch durch Reduzierung von störenden Einwirkungen funktionieren kann und damit womöglich die EffektivitĂ€t der Informationsverarbeitung erhöht

    Neural mechanisms of social cognition – the mirror neuron system and beyond

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    In my PhD thesis, I present three functional magnetic resonance imaging studies aimed at investigating neurobiological mechanisms underlying social cognition. My thesis focuses on fast and automatic processes that are proposed to build the basis of social understanding, and might be activated in parallel to more effortful deliberate mechanisms. The proposed neural substrate of fast and automatic processes are mirror neurons, which according to the theory of embodied simulation allow humans to understand other individuals’ actions, and even emotions and intentions. Since non-invasive techniques cannot be applied to measure mirror neurons, but only neural populations assumed to constitute the mirror neuron system, experimental paradigms and analysis routines that allow approximation of mirror neuron functions need to be developed. In study 1, I demonstrated that different social cognitive skills, including imitation, affective empathy and theory of mind share a common neural basis, located in regions associated with the mirror neuron system. In addition to standard analyses, a shared voxel analysis was applied that revealed common activation for social-cognitive processes not only across, but also within participants. Study 2 was set up to investigate whether the mirror neuron system can distinguish the valence of facial configurations. The use of a functional magnetic resonance imaging adaptation paradigm allowed to determine neural populations sensitive to emotional valence. While the fusiform gyrus was sensitive to changes from fearful to smiling faces and also from smiling to fearful faces, Brodmann area 44 reaching into insula, and superior temporal sulcus, i.e. regions more commonly associated with the mirror neuron system and with the so called mentalizing network, showed particularly increased activation for switches from smiling to fearful faces. Study 3 was dedicated to the investigation of decision making in the context of ambiguous facial configurations. While probabilistic decision making on these facial configurations lead to activation in the executive control network, final decisions for an emotion resulted in nucleus accumbens activation. In addition, perceiving fear in a face lead to higher nucleus accumbens activation during final decisions than perceiving happiness. This finding can be linked to salience processing in the nucleus accumbens. In conclusion, all three studies show an involvement of fast and automatic processing regions for different social-cognitive processes. Study 3 additionally examined the interaction with slower and more deliberate processes, as involved in probabilistic decision making on ambiguous faces. The mirror neuron system seems to be critically involved in different social-cognitive tasks and also sensitive to emotional valence. In cases when automatic processing is not possible, as when presented with ambiguous facial configurations, brain regions commonly associated with probabilistic decision making assist, and the nucleus accumbens, possibly by directing salience, is involved in the final decision. These results deepen the understanding of the mechanisms of social cognition and encourage the use of sophisticated methods in experimental paradigms and analysis

    Neurofunctional Characterization of the At-Risk Mental State for Psychosis

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    <p>Schizophrenia is a complex and debilitating psychiatric illness characterized by positive symptoms like hallucinations and delusions and negative symptoms like blunting of affect, avolition, and poverty of thought. This constellation of symptoms is hypothesized to result from dopaminergic dysfunction, glutamatergic dysfunction, and dysfunctional stress-reactivity. Prior to the onset of schizophrenia there is a prodromal period when individuals begin to experience sub-clinical symptoms and decreased functioning. This period is important to study not only to help elucidate biologic mechanisms of the illness but also to potentially alter the course of the illness through early treatment. The difficulty of studying this period lies in its recognizing it prospectively. To address this researchers have begun to study the at-risk mental state, a state that is associated with a high but not inevitable risk of conversion to psychosis. The studies described in this dissertation are aimed at a neurofunctional characterization of the at-risk mental state in three primary domains: reward-anticipation, hippocampus-dependent learning, and stress-reactivity. Individuals at-risk for psychosis and age-matched healthy volunteers underwent functional magnetic resonance imaging while performing tasks targeting these domains. In the reward-anticipation task, at-risk individuals showed decreased ventral tegmental area (VTA) and dorsolateral prefrontal cortex (DLPFC) responses to reward anticipation. In the hippocampus-dependent learning task, at-risk individuals showed deficits in hippocampus-dependent memory, decreased VTA engagement, and increased DLPFC activation during learning of associations between items. In the stress-reactivity task, at-risk individuals showed increased activation in the bed nucleus of the stria terminalis/basal forebrain (BNST), anterior cingulate cortex (ACC), and medial prefrontal cortex (mPFC) in response to neutral faces. Collectively, these experiments show that neurofunctional deficits in reward-anticipation, hippocampus-dependent learning, and stress-reactivity are present in the putative prodrome, prior to the onset of psychosis. Regions implicated are those that would be expected based on current models of schizophrenia and neurofunctional studies in those with frank psychosis.</p>Dissertatio

    Effects of cholinesterase inhibition on brain function

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    Pharmacological-functional imaging provides a non-invasive method by which the actions of neurotropic drugs on the human brain can be explored. Simply put, it assesses how neural activity patterns associated with cognitive functions of interest are modified by a drug challenge. Since one of the most widely-used cognitive-enhancing drugs in clinical practice are cholinesterase inhibitors, this thesis applies pharmacological functional imaging to the question of understanding how such drugs work - both in healthy people and dementia. The experiments in this thesis describe how brain activations – as revealed by functional magnetic resonance imaging (fMRI) – are modulated by the cholinesterase inhibitor physostigmine, during tasks designed to isolate sensory, attentional, and memory processes. While non-human and human psychophysical studies suggest that all three of these cognitive functions are under the control of the endogenous cortical cholinergic system, understanding how neurobiological models of cholinergic function translate into human brain activation modulations is unclear. One main question that is particularly relevant in this regard, that recurs through all the experiments, is how physostigmine-induced neuromodulations differ between sensory-driven ‘bottom-up’, and task-driven ‘top-down’, brain activations. The results are discussed with reference both to non-human physiological data and to existing human cholinergic-functional imaging studies (fifty studies published to date), which are themselves reviewed at the outset. Furthermore, assumptions based upon the physical and physiological principles of pharmacological functional imaging, being critical to interpretation, are discussed in detail within a general methods section

    Social and Affective Neuroscience of Everyday Human Interaction

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    This Open Access book presents the current state of the art knowledge on social and affective neuroscience based on empirical findings. This volume is divided into several sections first guiding the reader through important theoretical topics within affective neuroscience, social neuroscience and moral emotions, and clinical neuroscience. Each chapter addresses everyday social interactions and various aspects of social interactions from a different angle taking the reader on a diverse journey. The last section of the book is of methodological nature. Basic information is presented for the reader to learn about common methodologies used in neuroscience alongside advanced input to deepen the understanding and usability of these methods in social and affective neuroscience for more experienced readers

    Obesity is associated with insufficient behavioral adaptation

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    Obesity is one of the major health concerns nowadays according to the World Health Organisation (WHO global status report on noncommunicable diseases 2010). Thus, there is an urgent need for understanding obesity-associated alterations in food-related and general cognition and their underlying structural and functional correlates within the central nervous system (CNS). Neuroscientific research of the past decade has mainly focussed on obesity-related differences within homeostatic and hedonic processing of food stimuli. Therein, alterations during anticipation and consumption of food-reward stimuli in obese compared with lean subjects have been highlighted. This points at an altered adaptation of eating behavior in obese individuals. This thesis investigates if adaptation of behavior is attenuated in obese compared to lean individuals in learning-related processes beyond the food domain. In five consecutive experimental studies, we show that obese participants reveal reduced adaptation of behavior within and outside the food context. With the help of MRI, we relate these behavioral findings to alterations in structure and function of the fronto-striatal dopaminergic system in obesity. In more detail, reduced behavioral adaptation seems to be associated with attenuated utilization of negative prediction errors in obese individuals. Within the brain, this relates to reduced functional coupling between subcortical dopaminergic target regions (ventral striatum) and executive cortical structures (supplementary motor area) in obesity, as revealed by fMRI analysis
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