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ELife Nov 2021Theoretical accounts distinguish between motivational ('wanting') and hedonic ('liking') dimensions of rewards. Previous animal and human research linked wanting and... (Randomized Controlled Trial)
Randomized Controlled Trial
Theoretical accounts distinguish between motivational ('wanting') and hedonic ('liking') dimensions of rewards. Previous animal and human research linked wanting and liking to anatomically and neurochemically distinct brain mechanisms, but it remains unknown how the different brain regions and neurotransmitter systems interact in processing distinct reward dimensions. Here, we assessed how pharmacological manipulations of opioid and dopamine receptor activation modulate the neural processing of wanting and liking in humans in a randomized, placebo-controlled, double-blind clinical trial. Reducing opioid receptor activation with naltrexone selectively reduced wanting of rewards, which on a neural level was reflected by stronger coupling between dorsolateral prefrontal cortex and the striatum under naltrexone compared with placebo. In contrast, reducing dopaminergic neurotransmission with amisulpride revealed no robust effects on behavior or neural activity. Our findings thus provide insights into how opioid receptors mediate neural connectivity related to specifically motivational, not hedonic, aspects of rewards.
Topics: Adult; Amisulpride; Corpus Striatum; Dopamine Antagonists; Dorsolateral Prefrontal Cortex; Double-Blind Method; Female; Healthy Volunteers; Humans; Magnetic Resonance Imaging; Male; Motivation; Naltrexone; Narcotic Antagonists; Reward
PubMed: 34761749
DOI: 10.7554/eLife.71077 -
Proceedings of the National Academy of... May 2022Neurulation is the process in early vertebrate embryonic development during which the neural plate folds to form the neural tube. Spinal neural tube folding in the...
Neurulation is the process in early vertebrate embryonic development during which the neural plate folds to form the neural tube. Spinal neural tube folding in the posterior neuropore changes over time, first showing a median hinge point, then both the median hinge point and dorsolateral hinge points, followed by dorsolateral hinge points only. The biomechanical mechanism of hinge point formation in the mammalian neural tube is poorly understood. Here we employ a mechanical finite element model to study neural tube formation. The computational model mimics the mammalian neural tube using microscopy data from mouse and human embryos. While intrinsic curvature at the neural plate midline has been hypothesized to drive neural tube folding, intrinsic curvature was not sufficient for tube closure in our simulations. We achieved neural tube closure with an alternative model combining mesoderm expansion, nonneural ectoderm expansion, and neural plate adhesion to the notochord. Dorsolateral hinge points emerged in simulations with low mesoderm expansion and zippering. We propose that zippering provides the biomechanical force for dorsolateral hinge point formation in settings where the neural plate lateral sides extend above the mesoderm. Together, these results provide a perspective on the biomechanical and molecular mechanism of mammalian spinal neurulation.
Topics: Animals; Ectoderm; Humans; Mice; Neural Plate; Neural Tube; Neurulation; Notochord
PubMed: 35561223
DOI: 10.1073/pnas.2117075119 -
Cortex; a Journal Devoted To the Study... Oct 2023Reduplicative paramnesia refers to the delusional belief that there are identical places in different locations. In this case-control study we investigated the clinical,...
Reduplicative paramnesia refers to the delusional belief that there are identical places in different locations. In this case-control study we investigated the clinical, phenomenological, neuropsychological and neuroanatomical data of eleven patients with reduplicative paramnesia and compared them against a control group of eleven patients with severe spatial disorientation without signs of reduplicative paramnesia. We show that most patients with reduplicative paramnesia report that a current place is reduplicated and/or relocated to an other familiar place. Patients with reduplicative paramnesia show a higher prevalence of deficits in the executive functions compared to the control patients, while mnestic and visuo-spatial deficits were both frequent in patients with reduplicative paramnesia and the control group. Patients with reduplicative paramnesia mostly suffer from right hemispheric lesions with a maximal overlap in the dorsolateral prefrontal cortex. Using lesion network mapping we show that lesions causing reduplicative paramnesia are connected to bilateral anterior insula and the right cingulate cortex. We argue that patients with reduplicative paramnesia fail to integrate the actual context with visuo-spatial memories and personal relevant emotional information due to a disruption of the neural network within the anterior temporal lobe, the cingulate cortex and the anterior insula. Also patients with reduplicative paramnesia are not able to resolve this conflict due to the lesion of the dorsolateral prefrontal cortex and executive dysfunction.
Topics: Humans; Neuroanatomy; Delusions; Neuropsychology; Case-Control Studies; Memory Disorders
PubMed: 37515831
DOI: 10.1016/j.cortex.2023.06.006 -
Biomedical Papers of the Medical... Mar 2022In this study we evaluated the impact of location of deep brain stimulation electrode active contact in different parts of the subthalamic nucleus on improvement of...
BACKGROUND
In this study we evaluated the impact of location of deep brain stimulation electrode active contact in different parts of the subthalamic nucleus on improvement of non-motor symptoms in patients with Parkinson's disease.
METHODS
The subthalamic nucleus was divided into two (dorsolateral/ventromedial) and three (dorsolateral, medial, ventromedial) parts. 37 deep brain stimulation electrodes were divided according to their active contact location. Correlation between change in non-motor symptoms before and one and four months after deep brain stimulation electrode implantation and the location of active contact was made.
RESULTS
In dividing the subthalamic nucleus into three parts, no electrode active contact was placed ventromedially, 28 active contacts were located in the medial part and 9 contacts were placed dorsolaterally. After one and four months, no significant difference was found between medial and dorsolateral positions. In the division of the subthalamic nucleus into two parts, 13 contacts were located in the ventromedial part and 24 contacts were placed in the dorsolateral part. After one month, significantly greater improvement in the Non-motor Symptoms Scale for Parkinson's disease (P=0.045) was found on dorsolateral left-sided stimulation, but no significant differences between the ventromedial and dorsolateral positions were found on the right side.
CONCLUSION
This study demonstrated the relationship between improvement of non-motor symptoms and the side (hemisphere, left/right) of the deep brain stimulation electrode active contact, rather than its precise location within specific parts of the subthalamic nucleus in patients treated for advanced Parkinson's disease.
Topics: Deep Brain Stimulation; Electrodes; Humans; Parkinson Disease; Subthalamic Nucleus; Treatment Outcome
PubMed: 33883752
DOI: 10.5507/bp.2020.034 -
The International Journal of Clinical... 2021Meditation and hypnosis have both been found to attenuate pain; however, little is known about similarities and differences in the cognitive modulation of pain. Hypnotic... (Review)
Review
Meditation and hypnosis have both been found to attenuate pain; however, little is known about similarities and differences in the cognitive modulation of pain. Hypnotic and meditative states (e.g., mindfulness) reduce pain by sharing and overlapping multiple neuro-cognitive mechanisms, but they differ in many respects. While there are overlapping brain networks involved, the nature of these effects seems different. Both phenomena involve frontal modulation of pain-related areas. The role of the dorsolateral prefrontal cortex appears to depend, in hypnosis, on the type of suggestion given and, in meditation, on the level of practice. Whereas the anterior cingulate cortex seems to be a key node in both hypnosis and meditation, the dorsolateral prefrontal cortex appears to engage in hypnosis as a function of suggestion and, in meditation, as a function of proficiency.
Topics: Analgesia; Dorsolateral Prefrontal Cortex; Humans; Hypnosis; Meditation; Pain; Pain Management
PubMed: 33960912
DOI: 10.1080/00207144.2021.1917294 -
The Journal of Neuroscience : the... Nov 2020Several decades of research have established that different kinds of memories result from the activity of discrete neural networks. Studying how these networks process...
Several decades of research have established that different kinds of memories result from the activity of discrete neural networks. Studying how these networks process information in experiments that target specific types of mnemonic representations has provided deep insights into memory architecture and its neural underpinnings. However, in natural settings reality confronts organisms with problems that are not neatly compartmentalized. Thus, a critical problem in memory research that still needs to be addressed is how distinct types of memories are ultimately integrated. Here we demonstrate how two memory networks, the hippocampus and dorsolateral striatum, may accomplish such a goal. The hippocampus supports memory for facts and events, collectively known as declarative memory and often studied as spatial memory in rodents. The dorsolateral striatum provides the basis for habits that are assessed in stimulus-response types of tasks. Expanding previous findings, the current work revealed that in male Long-Evans rats, the hippocampus and dorsolateral striatum use time and space in distinct and largely complementary ways to integrate spatial and habitual representations. Specifically, the hippocampus supported both types of memories when they were formed in temporal juxtaposition, even if the learning took place in different environments. In contrast, the lateral striatum supported both types of memories if they were formed in the same environment, even at temporally distinct points. These results reveal for the first time that by using fundamental aspects of experience in specific ways, the hippocampus and dorsolateral striatum can transcend their attributed roles in information storage. The current paradigm in memory research postulates that different types of memories reflected in separate types of behavioral strategies result from activity in distinct neural circuits. However, recent data have shown that when rats concurrently acquired in the same environment of hippocampal-dependent spatial navigation and striatal-dependent approach of a visual cue, each of the two types of memories became dependent on both the hippocampus and dorsolateral striatum. The current work reveals that the hippocampus and dorsolateral striatum use distinct and complementary principles to integrate different types of memories in time and space: the hippocampus integrates memories formed in temporal proximity, while the lateral striatum integrates memories formed in the same space.
Topics: Animals; Corpus Striatum; Cues; Hippocampus; Male; Maze Learning; Memory; Psychomotor Performance; Rats; Rats, Long-Evans; Space Perception; Spatial Navigation; Time Perception
PubMed: 33051349
DOI: 10.1523/JNEUROSCI.1084-20.2020 -
Journal of Psychiatric Research Dec 2021and purpose of the study: Individuals with general anxiety disorder (GAD) have deficits in emotional and cognitive processing, including cognitive bias, which plays a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
and purpose of the study: Individuals with general anxiety disorder (GAD) have deficits in emotional and cognitive processing, including cognitive bias, which plays a causal role in anxiety. Hyperactivity of the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) is assumed to be involved in cognitive bias. We aimed to explore the causal contribution of the dorsolateral and ventromedial prefrontal cortices (dlPFC, vmPFC) on cognitive bias via non-invasive brain stimulation, and expected a bias-reducing effect of cortical activity enhancement over these areas in GAD, with a larger contribution of the vmPFC to perceptual, and of the dlPFC to interpretation bias.
MATERIAL AND METHODS
The study was conducted in a randomized, single-blinded, and complete crossover design. Thirty-four adults with GAD, received transcranial direct current stimulation (tDCS) in 5 separate sessions (1.5 mA, 20 min) with the following electrode montages: anodal dlPFC/cathodal vmPFC, anodal vmPFC/cathodal dlPFC, anodal dlPFC/cathodal right shoulder, anodal vmPFC/cathodal left shoulder, and sham stimulation. During stimulation, in each session, participants performed the Dot-Probe and Reading Mind from Eyes tests to measure attention and interpretation biases.
RESULTS
A significant effect of stimulation condition on attention and interpretation biases was observed. Anodal vmPFC and dlPFC stimulation coupled with an extracranial cathodal electrode reduced attention bias to threat-related stimuli in the dot-probe test. Furthermore, anodal dlPFC/cathodal vmPFC stimulation reduced negative interpretation bias in reading from eyes test.
CONCLUSION
As suggested by the results of this study, both dlPFC and vmPFC are involved in cognitive bias in GAD, but with partially different roles. Anodal stimulation over the right vmPFC and the left dlPFC reduced attention bias, supporting the relevance of these areas for attention bias. For interpretation bias, the significant effect of anodal dlPFC/cathodal vmPFC stimulation, but only trendwise effect of anodal tDCS over the dlPFC combined with an extracephalic return electrode is in accordance with a predominant effect of the dlPFC on interpretation bias, but does not rule out an additional minor involvement of the vmPFC. Based on these results, a new model is suggested for the neural underpinnings of anxiety symptoms.
Topics: Adult; Anxiety Disorders; Bias; Dorsolateral Prefrontal Cortex; Humans; Prefrontal Cortex; Transcranial Direct Current Stimulation
PubMed: 34710663
DOI: 10.1016/j.jpsychires.2021.10.034 -
Frontiers in Psychiatry 2022Major depressive disorder (MDD) has a high disability rate and brings a large disease burden to patients and the country. Significant sex differences exist in both the...
BACKGROUND
Major depressive disorder (MDD) has a high disability rate and brings a large disease burden to patients and the country. Significant sex differences exist in both the epidemiological and clinical features in MDD. The effect of sex on brain function in MDD is not clear now. Regional homogeneity (ReHo) and ALFF are widely used research method in the study of brain function. This research aimed to use ReHo and ALFF to explore gender differences in brain function images in MDD.
METHODS
Eighty first-episode drug-naive patients (47 women and 30 men) with MDD and 85 age, education matched healthy volunteers (47 women and 31 men) were recruited in our study and participated in resting-state functional magnetic resonance imaging scans. ReHo and ALFF were used to assess brain activity, two-way ANOVA and analysis was conducted to explore the sex difference in MDD. Correlation analysis was used to explore the relationship between abnormal brain functioning and clinical symptoms.
RESULTS
We observed sex-specific patterns and diagnostic differences in MDD Patients, further comparisons indicated that women with MDD showed decreased ALFF value in the right superior occipital gyrus and decreased ReHo value in the left calcarine and left dorsolateral superior frontal gyrus compared with HC females and men with MDD. Men with MDD showed decreased ReHo value in the right median cingulate gyrus compared with HC males and increased ReHo value in the left dorsolateral superior frontal gyrus compared with HC males, we also found that HC males showed higher ReHo value in the right median cingulate gyrus than HC females.
CONCLUSIONS
Men and women do have sex differences in brain function, the occipital lobe, calcarine, DLPFC, and DCG were the main different brain regions found between male and female in MDD, which may be the biomarker brain regions that can help diagnose and treat MDD in men and women.
PubMed: 36440430
DOI: 10.3389/fpsyt.2022.1025531 -
Advanced Science (Weinheim,... Mar 2024Locus coeruleus (LC) dysfunction is involved in the pathophysiology of depression; however, the neural circuits and specific molecular mechanisms responsible for this...
Locus coeruleus (LC) dysfunction is involved in the pathophysiology of depression; however, the neural circuits and specific molecular mechanisms responsible for this dysfunction remain unclear. Here, it is shown that activation of tyrosine hydroxylase (TH) neurons in the LC alleviates depression-like behaviors in susceptible mice. The dorsolateral septum (dLS) is the most physiologically relevant output from the LC under stress. Stimulation of the LC -dLS innervation with optogenetic and chemogenetic tools bidirectionally can regulate depression-like behaviors in both male and female mice. Mechanistically, it is found that brain-derived neurotrophic factor (BDNF), but not norepinephrine, is required for the circuit to produce antidepressant-like effects. Genetic overexpression of BDNF in the circuit or supplementation with BDNF protein in the dLS is sufficient to produce antidepressant-like effects. Furthermore, viral knockdown of BDNF in this circuit abolishes the antidepressant-like effect of ketamine, but not fluoxetine. Collectively, these findings underscore the notable antidepressant-like role of the LC -dLS pathway in depression via BDNF-TrkB signaling.
Topics: Mice; Animals; Male; Female; Depression; Locus Coeruleus; Norepinephrine; Brain-Derived Neurotrophic Factor; Antidepressive Agents
PubMed: 38155473
DOI: 10.1002/advs.202303503 -
Cell Reports Apr 2022Motor skill learning requires the activity of the dorsal striatum, with a differential global implication of the dorsomedial and dorsolateral territories. We investigate...
Motor skill learning requires the activity of the dorsal striatum, with a differential global implication of the dorsomedial and dorsolateral territories. We investigate here whether and how specific striatal neurons encode the acquisition and consolidation of a motor skill. Using ex vivo two-photon calcium imaging after rotarod training, we report that highly active (HA) striatal populations arise from distinct spatiotemporal reorganization in the dorsomedial (DMS) and dorsolateral (DLS) striatum networks and are correlated with learning performance. The DMS overall activity decreases in early training, with few and sparsely distributed HA cells, while the DLS shows a progressive and long-lasting formation of HA cell clusters. These reorganizations result from reinforcement of synaptic connections to the DMS and anatomical rearrangements to the DLS. Targeted silencing of DMS or DLS HA cells with the cFos-TRAP strategy strongly impairs individual performance. Our data reveal that discrete domains of striatal populations encode acquisition and long-lasting retention of a motor skill.
Topics: Corpus Striatum; Learning; Motor Skills; Neostriatum; Neurons
PubMed: 35385722
DOI: 10.1016/j.celrep.2022.110623