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1.
Brain Sci ; 10(12)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33255604

RESUMO

Depression is a debilitating disorder with high prevalence and socioeconomic cost, but the brain-physiological processes that are altered during depressive states are not well understood. Here, we build on recent findings in macaques that indicate a direct causal relationship between pupil dilation and anterior cingulate cortex mediated arousal during anticipation of reward. We translated these findings to human subjects with concomitant pupillometry/fMRI in a sample of unmedicated participants diagnosed with major depression and healthy controls. We could show that the upregulation and maintenance of arousal in anticipation of reward was disrupted in patients in a symptom-load dependent manner. We could further show that the failure to maintain reward anticipatory arousal showed state-marker properties, as it tracked the load and impact of depressive symptoms independent of prior diagnosis status. Further, group differences of anticipatory arousal and continuous correlations with symptom load were not traceable only at the level of pupillometric responses, but were mirrored also at the neural level within salience network hubs. The upregulation and maintenance of arousal during reward anticipation is a novel translational and well-traceable process that could prove a promising gateway to a physiologically informed patient stratification and targeted interventions.

2.
BMC Psychiatry ; 20(1): 213, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393358

RESUMO

BACKGROUND: A major research finding in the field of Biological Psychiatry is that symptom-based categories of mental disorders map poorly onto dysfunctions in brain circuits or neurobiological pathways. Many of the identified (neuro) biological dysfunctions are "transdiagnostic", meaning that they do not reflect diagnostic boundaries but are shared by different ICD/DSM diagnoses. The compromised biological validity of the current classification system for mental disorders impedes rather than supports the development of treatments that not only target symptoms but also the underlying pathophysiological mechanisms. The Biological Classification of Mental Disorders (BeCOME) study aims to identify biology-based classes of mental disorders that improve the translation of novel biomedical findings into tailored clinical applications. METHODS: BeCOME intends to include at least 1000 individuals with a broad spectrum of affective, anxiety and stress-related mental disorders as well as 500 individuals unaffected by mental disorders. After a screening visit, all participants undergo in-depth phenotyping procedures and omics assessments on two consecutive days. Several validated paradigms (e.g., fear conditioning, reward anticipation, imaging stress test, social reward learning task) are applied to stimulate a response in a basic system of human functioning (e.g., acute threat response, reward processing, stress response or social reward learning) that plays a key role in the development of affective, anxiety and stress-related mental disorders. The response to this stimulation is then read out across multiple levels. Assessments comprise genetic, molecular, cellular, physiological, neuroimaging, neurocognitive, psychophysiological and psychometric measurements. The multilevel information collected in BeCOME will be used to identify data-driven biologically-informed categories of mental disorders using cluster analytical techniques. DISCUSSION: The novelty of BeCOME lies in the dynamic in-depth phenotyping and omics characterization of individuals with mental disorders from the depression and anxiety spectrum of varying severity. We believe that such biology-based subclasses of mental disorders will serve as better treatment targets than purely symptom-based disease entities, and help in tailoring the right treatment to the individual patient suffering from a mental disorder. BeCOME has the potential to contribute to a novel taxonomy of mental disorders that integrates the underlying pathomechanisms into diagnoses. TRIAL REGISTRATION: Retrospectively registered on June 12, 2019 on ClinicalTrials.gov (TRN: NCT03984084).

3.
Behav Res Ther ; 129: 103610, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32302820

RESUMO

Fear conditioning and extinction serve as a dominant model for the development and maintenance of pathological anxiety, particularly for phasic fear to specific stimuli or situations. The validity of this model would be supported by differences in the physiological or subjective fear response between patients with fear-related disorders and healthy controls, whereas the model's validity would be questioned by a lack of such differences. We derived pupillometry, skin conductance response and startle electromyography as well as unconditioned stimulus expectancy in a two-day fear acquisition, immediate extinction and recall task and compared an unmedicated group of patients (n = 73) with phobias or panic disorder and a group of patients with posttraumatic stress disorder (PTSD, n = 21) to a group of carefully screened healthy controls (n = 35). Bayesian statistics showed no convincing evidence for a difference in physiological and subjective responses between the groups during fear acquisition, extinction learning or recall. Only the PTSD subgroup had altered startle reactions during extinction learning. Our data do not provide evidence for general differences in associative fear or extinction learning in fear-related pathologies and thereby question the diagnostic validity of the associative fear learning model of these disorders.

4.
J Sleep Res ; : e13042, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32311167

RESUMO

The human brain has evolved to acquire novel information rapidly while serving the need to store long-term memories in a stable and lasting form. Presenting interfering information directly after learning can lead to forgetting of the original material. It has been suggested that sleep aids the stabilization of new memories and protects them from interference. Here, we aim to replicate in two separate experiments the claim that sleep protects memories from retroactive interference (Current Biology, 16, 2006 and 1290; PLoS ONE, 4, 2009 and e4117). We let participants study wordlists before letting them sleep for an afternoon nap or for a full night. In a control condition, subjects stayed awake for the same amount of time. After the consolidation interval, participants learnt an interfering wordlist and were tested on memory of the original wordlist. Sleep did not stabilize memory for the original wordlist in either study. We discuss our findings in the light of recent advances in computational neuroscience, and conclude that the stabilizing effect of sleep against interference has been overestimated.

5.
Curr Biol ; 28(19): R1129-R1130, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30300592

RESUMO

Schönauer and Pöhlchen introduce the reader to sleep spindles, brain oscillations that occur during nREM sleep that are thought to function in the stabilization of memories.


Assuntos
Ondas Encefálicas/fisiologia , Fases do Sono/fisiologia , Sono/fisiologia , Encéfalo/fisiologia , Cognição , Eletroencefalografia/métodos , Humanos , Memória
6.
Sleep ; 41(10)2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30113673

RESUMO

Solving a novel problem and finding innovative solutions requires a flexible and creative recombination of prior knowledge. It is thought that setting a problem aside before giving it another try aids problem-solving. The underlying mechanisms of such an incubation period could include unconscious processing that fosters spreading activation along associated networks and the restructuring of problem representations. Recently, it has been suggested that sleep may also support problem-solving by supporting the transformation and restructuring of memory elements. Since the effect of sleep on problem-solving has been mainly tested using the Remote Associates Test, we chose three different tasks-classical riddles, visual change detection, and anagrams-to examine various aspects of problem-solving and to pinpoint task-specific prerequisites for effects of sleep or incubation to emerge. Sixty-two participants were given two attempts to solve the problems. Both attempts either occurred consecutively or were spaced apart by a 3-hour incubation interval that was spent awake or asleep. We found that a period of incubation positively affected solutions rates in classical riddles, but not in visual change detection or anagram solving. Contrary to our hypothesis, spending the incubation period asleep, did not yield any additional benefit. Our study thus supports the notion that a period of letting a problem rest is beneficial for its solution and confines the role of sleep to memory transformations that do not directly impact on problem-solving ability.


Assuntos
Criatividade , Resolução de Problemas/fisiologia , Sono/fisiologia , Adulto , Feminino , Humanos , Masculino , Memória , Descanso , Pensamento , Inconsciente Psicológico , Vigília , Adulto Jovem
7.
Front Hum Neurosci ; 12: 72, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29535620

RESUMO

During creative problem solving, initial solution attempts often fail because of self-imposed constraints that prevent us from thinking out of the box. In order to solve a problem successfully, the problem representation has to be restructured by combining elements of available knowledge in novel and creative ways. It has been suggested that sleep supports the reorganization of memory representations, ultimately aiding problem solving. In this study, we systematically tested the effect of sleep and time on problem solving, using classical insight tasks and magic tricks. Solving these tasks explicitly requires a restructuring of the problem representation and may be accompanied by a subjective feeling of insight. In two sessions, 77 participants had to solve classical insight problems and magic tricks. The two sessions either occurred consecutively or were spaced 3 h apart, with the time in between spent either sleeping or awake. We found that sleep affected neither general solution rates nor the number of solutions accompanied by sudden subjective insight. Our study thus adds to accumulating evidence that sleep does not provide an environment that facilitates the qualitative restructuring of memory representations and enables problem solving.

8.
Proc Natl Acad Sci U S A ; 113(46): 13251-13256, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27803331

RESUMO

Previous evidence indicates that the brain stores memory in two complementary systems, allowing both rapid plasticity and stable representations at different sites. For memory to be established in a long-lasting neocortical store, many learning repetitions are considered necessary after initial encoding into hippocampal circuits. To elucidate the dynamics of hippocampal and neocortical contributions to the early phases of memory formation, we closely followed changes in human functional brain activity while volunteers navigated through two different, initially unknown virtual environments. In one condition, they were able to encode new information continuously about the spatial layout of the maze. In the control condition, no information could be learned because the layout changed constantly. Our results show that the posterior parietal cortex (PPC) encodes memories for spatial locations rapidly, beginning already with the first visit to a location and steadily increasing activity with each additional encounter. Hippocampal activity and connectivity between the PPC and hippocampus, on the other hand, are strongest during initial encoding, and both decline with additional encounters. Importantly, stronger PPC activity related to higher memory-based performance. Compared with the nonlearnable control condition, PPC activity in the learned environment remained elevated after a 24-h interval, indicating a stable change. Our findings reflect the rapid creation of a memory representation in the PPC, which belongs to a recently proposed parietal memory network. The emerging parietal representation is specific for individual episodes of experience, predicts behavior, and remains stable over offline periods, and must therefore hold a mnemonic function.


Assuntos
Memória/fisiologia , Lobo Parietal/fisiologia , Adulto , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/fisiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Lobo Parietal/diagnóstico por imagem , Aprendizagem Espacial , Realidade Virtual , Adulto Jovem
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