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Neuropsychopharmacology : Official... Apr 2023Brain dopamine may regulate the ability to maintain and manipulate sequential information online. However, the precise role of dopamine remains unclear. This... (Randomized Controlled Trial)
Randomized Controlled Trial
Brain dopamine may regulate the ability to maintain and manipulate sequential information online. However, the precise role of dopamine remains unclear. This pharmacological fMRI study examined whether and how the dopamine D2/3 receptor agonist pramipexole modulates fronto-subthalamic or fronto-striatal pathways during sequential working memory. This study used a double-blind, randomized crossover design. Twenty-two healthy male volunteers completed a digit ordering task during fMRI scanning after receiving a single oral dose of 0.5-mg pramipexole or placebo. The pramipexole effects on task performance, regional activity, activity pattern similarity, and functional connectivity were analyzed. Pramipexole impaired task performance, leading to less accurate and slower responses in the digit ordering task. Also, it downregulated the maintenance-related subthalamic and dorsolateral prefrontal activity, increasing reaction times for maintaining sequences. In contrast, pramipexole upregulated the manipulation-related subthalamic and dorsolateral prefrontal activity, increasing reaction time costs for manipulating sequences. In addition, it altered the dorsolateral prefrontal activity pattern similarity and fronto-subthalamic functional connectivity. Finally, pramipexole reduced maintenance-related striatal activity, which did not affect the behavior. This study confirms the role of the fronto-subthalamic pathway in sequential working memory. Furthermore, it shows that D2 transmission can regulate sequential working memory by modulating the fronto-subthalamic pathway.
Topics: Humans; Male; Pramipexole; Memory, Short-Term; Dopamine; Dopamine Agonists; Brain; Magnetic Resonance Imaging
PubMed: 36352204
DOI: 10.1038/s41386-022-01494-z -
International Journal of... Dec 2021An interoception model for the acute exercise-cognition interaction is presented. During exercise following the norepinephrine threshold, interoceptive feedback induces... (Review)
Review
An interoception model for the acute exercise-cognition interaction is presented. During exercise following the norepinephrine threshold, interoceptive feedback induces increased tonic release of extracellular catecholamines, facilitating phasic release hence better cognitive performance of executive functions. When exercise intensity increases to maximum, the nature of task-induced norepinephrine release from the locus coeruleus is dependent on interaction between motivation, perceived effort costs and perceived availability of resources. This is controlled by interaction between the rostral and dorsolateral prefrontal cortices, orbitofrontal cortex, anterior cingulate cortex and anterior insula cortex. If perceived available resources are sufficient to meet predicted effort costs and reward value is high, tonic release from the locus coeruleus is attenuated thus facilitating phasic release, therefore cognition is not inhibited. However, if perceived available resources are insufficient to meet predicted effort costs or reward value is low, tonic release from the locus coeruleus is induced, attenuating phasic release. As a result, cognition is inhibited, although long-term memory and tasks that require switching to new stimuli-response couplings are probably facilitated.
Topics: Catecholamines; Cognition; Dorsolateral Prefrontal Cortex; Exercise; Humans; Interoception
PubMed: 34666105
DOI: 10.1016/j.ijpsycho.2021.10.005 -
Cognitive, Affective & Behavioral... Aug 2020In this study, we employed a visuo-motor imagery task of alertness as a mental training to examine temporal processing of motor responses within healthy young adults....
In this study, we employed a visuo-motor imagery task of alertness as a mental training to examine temporal processing of motor responses within healthy young adults. Participants were divided into two groups (group 1; n = 20 who performed the mental training before the real physical task and a control group who performed the physical task without mental training). We vary the time interval between the imperative stimulus and the preceding one (fore-period) in which temporal preparation and arousal increase briefly. Our behavioural results provide clear evidence that mental training reinforces both temporal preparation and arousal, by shortening reaction time (RT), especially for the shortest fore-periods (FP) within exogenous "FP 250 ms" (p = 0.008) and endogenous alertness "FP 650 ms" (p = 0.001). We investigated how the brain controls such small temporal changes. We focus our neural hypothesis on three brain regions: anterior insula, dorsolateral prefrontal cortex, and anterior cingulate cortex and three putative circuits: one top-down (from dorsolateral prefrontal cortex to anterior cingulate cortex) and two bottom-up (from anterior insula to dorsolateral prefrontal cortex and anterior cingulate cortex). In fMRI, effective connectivity is strengthened during exogenous alertness between anterior insula and dorsolateral prefrontal cortex (p = 0.001), between anterior insula and cingulate cortex (p = 0.01), and during endogenous alertness between dorsolateral prefrontal cortex and anterior cingulate cortex (p = 0.05). We suggest that attentional reinforcement induced by an intensive and short session of mental training induces a temporal deployment of attention and allow optimizing the time pressure by maintaining a high state of arousal and ameliorating temporal preparation.
Topics: Adult; Attention; Brain Mapping; Female; Gyrus Cinguli; Humans; Imagination; Magnetic Resonance Imaging; Male; Practice, Psychological; Prefrontal Cortex; Psychomotor Performance; Reaction Time; Reinforcement, Psychology; Time Factors; Young Adult
PubMed: 32458391
DOI: 10.3758/s13415-020-00795-4 -
Biological Psychology Nov 2022Given the extensive neural networks connecting the dorsolateral prefrontal cortex (DLPFC) with other subcortical regions, the DLPFC has been implicated in a wide range... (Review)
Review
Given the extensive neural networks connecting the dorsolateral prefrontal cortex (DLPFC) with other subcortical regions, the DLPFC has been implicated in a wide range of psychological and physiological functions during execution of movements. The main objective of this narrative review is to provide a solid theoretical foundation to deepen our understanding of the functional significance of the DLPFC during exercise. Given the limited scientific evidence in this field of scientific enquiry, this review was primarily focused on fatiguing and exhaustive exercise modes. The authors reviewed the anatomical structure of this region, as well as its functional importance for physical tasks performed mainly at moderate and high intensities. The majority of the studies employed noninvasive brain assessment techniques, such as electroencephalography, functional near-infrared spectroscopy, and functional magnetic resonance imaging. Six main DLPFC functions were identified: 1) exercise tolerance, 2) executive function, 3) attention allocation, 4) emotion regulation, 5) reward seeking, and 6) memory formation. The most important neuromodulatory function exerted by the DLPFC pertains to the inhibitory influence of this region over the amygdala and the hypothalamic-pituitary-adrenal axis. This inhibitory function appears to be the primary possibility and is generally reliant upon connectivity with other subcortical regions. During exhaustive exercise, stress hormones appear to have an inhibitory effect on the DLPFC and hippocampus. The present authors hypothesize that the use of cognitive strategies to partially neutralize the amygdala may rely on the presence of rewards, which are then translated into motivation to action through the mesolimbic and mesocortical dopamine systems.
Topics: Humans; Prefrontal Cortex; Dorsolateral Prefrontal Cortex; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Amygdala; Magnetic Resonance Imaging
PubMed: 36243197
DOI: 10.1016/j.biopsycho.2022.108442 -
The Journal of Headache and Pain Jan 2022The precise underlying mechanisms of migraine remain unknown. Although we have previously shown acute orofacial pain evoked changes within the brainstem of individuals...
BACKGROUND
The precise underlying mechanisms of migraine remain unknown. Although we have previously shown acute orofacial pain evoked changes within the brainstem of individuals with migraine, we do not know if these brainstem alterations are driven by changes in higher cortical regions. The aim of this investigation is to extend our previous investigation to determine if higher brain centers display altered activation patterns and connectivity in migraineurs during acute orofacial noxious stimuli.
METHODS
Functional magnetic resonance imaging was performed in 29 healthy controls and 25 migraineurs during the interictal and immediately (within 24-h) prior to migraine phases. We assessed activation of higher cortical areas during noxious orofacial heat stimulation using a thermode device and assessed whole scan and pain-related changes in connectivity.
RESULTS
Despite similar overall pain intensity ratings between all three groups, migraineurs in the group immediately prior to migraine displayed greater activation of the ipsilateral nucleus accumbens, the contralateral ventrolateral prefrontal cortex and two clusters in the dorsolateral prefrontal cortex (dlPFC). Reduced whole scan dlPFC [Z + 44] connectivity with cortical/subcortical and brainstem regions involved in pain modulation such as the putamen and primary motor cortex was demonstrated in migraineurs. Pain-related changes in connectivity of the dlPFC and the hypothalamus immediately prior to migraine was also found to be reduced with brainstem pain modulatory areas such as the rostral ventromedial medulla and dorsolateral pons.
CONCLUSIONS
These data reveal that the modulation of brainstem pain modulatory areas by higher cortical regions may be aberrant during pain and these alterations in this descending pain modulatory pathway manifests exclusively prior to the development of a migraine attack.
Topics: Brain; Brain Stem; Dorsolateral Prefrontal Cortex; Humans; Magnetic Resonance Imaging; Migraine Disorders; Pain
PubMed: 35033014
DOI: 10.1186/s10194-021-01381-w -
Psychiatry Investigation Sep 2019The neuroimaging has been applied in the study of pathophysiology in major depressive disorder (MDD). In this review article, several kinds of methodologies of...
The neuroimaging has been applied in the study of pathophysiology in major depressive disorder (MDD). In this review article, several kinds of methodologies of neuroimaging would be discussed to summarize the promising biomarkers in MDD. For the magnetic resonance imaging (MRI) and magnetoencephalography field, the literature review showed the potentially promising roles of frontal lobes, such as anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). In addition, the limbic regions, such as hippocampus and amygdala, might be the potentially promising biomarkers for MDD. The structures and functions of ACC, DLPFC, OFC, amygdala and hippocampus might be confirmed as the biomarkers for the prediction of antidepressant treatment responses and for the pathophysiology of MDD. The functions of cognitive control and emotion regulation of these regions might be crucial for the establishment of biomarkers. The near-infrared spectroscopy studies demonstrated that blood flow in the frontal lobe, such as the DLPFC and OFC, might be the biomarkers for the field of near-infrared spectroscopy. The electroencephalography also supported the promising role of frontal regions, such as the ACC, DLPFC and OFC in the biomarker exploration, especially for the sleep electroencephalogram to detect biomarkers in MDD. The positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in MDD demonstrated the promising biomarkers for the frontal and limbic regions, such as ACC, DLPFC and amygdala. However, additional findings in brainstem and midbrain were also found in PET and SPECT. The promising neuroimaging biomarkers of MDD seemed focused in the fronto-limbic regions.
PubMed: 31550875
DOI: 10.30773/pi.2019.07.25.2 -
Neuropsychopharmacology : Official... Jan 2022Kraepelin, in his early descriptions of schizophrenia (SZ), characterized the illness as having "an orchestra without a conductor." Kraepelin further speculated that... (Review)
Review
Kraepelin, in his early descriptions of schizophrenia (SZ), characterized the illness as having "an orchestra without a conductor." Kraepelin further speculated that this "conductor" was situated in the frontal lobes. Findings from multiple studies over the following decades have clearly implicated pathology of the dorsolateral prefrontal cortex (DLPFC) as playing a central role in the pathophysiology of SZ, particularly with regard to key cognitive features such as deficits in working memory and cognitive control. Following an overview of the cognitive mechanisms associated with DLPFC function and how they are altered in SZ, we review evidence from an array of neuroscientific approaches addressing how these cognitive impairments may reflect the underlying pathophysiology of the illness. Specifically, we present evidence suggesting that alterations of the DLPFC in SZ are evident across a range of spatial and temporal resolutions: from its cellular and molecular architecture, to its gross structural and functional integrity, and from millisecond to longer timescales. We then present an integrative model based upon how microscale changes in neuronal signaling in the DLPFC can influence synchronized patterns of neural activity to produce macrocircuit-level alterations in DLPFC activation that ultimately influence cognition and behavior. We conclude with a discussion of initial efforts aimed at targeting DLPFC function in SZ, the clinical implications of those efforts, and potential avenues for future development.
Topics: Cognitive Dysfunction; Dorsolateral Prefrontal Cortex; Humans; Memory, Short-Term; Prefrontal Cortex; Schizophrenia
PubMed: 34285373
DOI: 10.1038/s41386-021-01089-0 -
Frontiers in Neuroscience 2022Neuropeptides are one of the largest and most diverse families of signaling molecules in animals and, accordingly, they regulate many physiological processes and...
Neuropeptides are one of the largest and most diverse families of signaling molecules in animals and, accordingly, they regulate many physiological processes and behaviors. Genome and transcriptome sequencing has enabled the identification of genes encoding neuropeptide precursor proteins in species from a growing variety of taxa, including bilaterian and non-bilaterian animals. Of particular interest are deuterostome invertebrates such as the phylum Echinodermata, which occupies a phylogenetic position that has facilitated reconstruction of the evolution of neuropeptide signaling systems in Bilateria. However, our knowledge of neuropeptide signaling in echinoderms is largely based on bioinformatic and experimental analysis of eleutherozoans-Asterozoa (starfish and brittle stars) and Echinozoa (sea urchins and sea cucumbers). Little is known about neuropeptide signaling in crinoids (feather stars and sea lilies), which are a sister clade to the Eleutherozoa. Therefore, we have analyzed transcriptome/genome sequence data from three feather star species, , and , to produce the first comprehensive identification of neuropeptide precursors in crinoids. These include representatives of bilaterian neuropeptide precursor families and several predicted crinoid neuropeptide precursors. Using as an experimental model, we have investigated the expression of selected neuropeptides in larvae (doliolaria), post-metamorphic pentacrinoids and adults, providing new insights into the cellular architecture of crinoid nervous systems. Thus, using mRNA hybridization F-type SALMFamide precursor transcripts were revealed in a previously undescribed population of peptidergic cells located dorso-laterally in doliolaria. Furthermore, using immunohistochemistry a calcitonin-type neuropeptide was revealed in the aboral nerve center, circumoral nerve ring and oral tube feet in pentacrinoids and in the ectoneural and entoneural compartments of the nervous system in adults. Moreover, functional analysis of a vasopressin/oxytocin-type neuropeptide (crinotocin), which is expressed in the brachial nerve of the arms in , revealed that this peptide causes a dose-dependent change in the mechanical behavior of arm preparations -the first reported biological action of a neuropeptide in a crinoid. In conclusion, our findings provide new perspectives on neuropeptide signaling in echinoderms and the foundations for further exploration of neuropeptide expression/function in crinoids as a sister clade to eleutherozoan echinoderms.
PubMed: 36583101
DOI: 10.3389/fnins.2022.1006594 -
Brain Communications 2021Relapse is one of the most perplexing problems of addiction. The dorsolateral prefrontal cortex is crucially involved in numerous cognitive and affective processes that...
Relapse is one of the most perplexing problems of addiction. The dorsolateral prefrontal cortex is crucially involved in numerous cognitive and affective processes that are implicated in the phenotypes of both substance use disorders and other neuropsychiatric diseases and has become the principal site to deliver transcranial magnetic stimulation for their treatment. However, the dorsolateral prefrontal cortex is an anatomically large and functionally heterogeneous region, and the specific dorsolateral prefrontal cortex locus and dorsolateral prefrontal cortex-based functional circuits that contribute to drug relapse and/or treatment outcome remain unknown. We systematically investigated the relationship of cocaine relapse with functional circuits from 98 dorsolateral prefrontal cortex regions-of-interest defined by evenly sampling the entire surface of bilateral dorsolateral prefrontal cortex in a cohort of cocaine dependent patients ( = 43, 5 Fr) following a psychosocial treatment intervention. Cox regression models were utilized to predict relapse likelihood based on dorsolateral prefrontal cortex functional connectivity strength. Functional connectivity from only 3 of the 98 dorsolateral prefrontal cortex loci, one in the left and two in the right hemisphere, significantly predicted cocaine relapse with an accuracy of 83.9%, 84.6% and 85.4%, respectively. Combining all three loci significantly improved prediction validity to 87.5%. Protective and risk circuits related to these dorsolateral prefrontal cortex loci were identified that have previously been implicated to support 'bottom up' drive to use drug and 'top down' control over behaviour together with social emotional, learning and memory processing. Three dorsolateral prefrontal cortex-centric circuits were identified that predict relapse to cocaine use with high accuracy. These functionally distinct dorsolateral prefrontal cortex-based circuits provide insights into the multiple roles played by the dorsolateral prefrontal cortex in cognitive and affective functioning that affects treatment outcome. The identified dorsolateral prefrontal cortex loci may serve as potential neuromodulation targets to be tested in subsequent clinical studies for addiction treatment and as clinically relevant biomarkers of its efficacy. Zhai et al. identify three dorsolateral prefrontal cortex (dlPFC)-centric circuits that predict cocaine relapse with high accuracy, providing insights into the multiple roles of the dlPFC in brain functioning that affects treatment outcome and suggesting the dlPFC loci as potential neuromodulation targets for addiction treatment.
PubMed: 34189458
DOI: 10.1093/braincomms/fcab120 -
Journal of Neurophysiology Jan 2021The marmoset monkey () has gained attention in neurophysiology research as a new primate model for visual processing and behavior. In particular, marmosets have a...
The marmoset monkey () has gained attention in neurophysiology research as a new primate model for visual processing and behavior. In particular, marmosets have a lissencephalic cortex, making multielectrode, optogenetic, and calcium-imaging techniques more accessible than other primate models. However, the degree of homology of brain circuits for visual behavior with those identified in macaques and humans is still being ascertained. For example, whereas the location of the frontal eye fields (FEF) within the dorsolateral frontal cortex has been proposed, it remains unclear whether neurons in the corresponding areas show visual responses-an important characteristic of FEF neurons in other species. Here, we provide the first description of receptive field properties and neural response latencies in the marmoset dorsolateral frontal cortex, based on recordings using Utah arrays in anesthetized animals. We find brisk visual responses in specific regions of the dorsolateral prefrontal cortex, particularly in areas 8aV, 8C, and 6DR. As in macaque FEF, the receptive fields were typically large (10°-30° in diameter) and the median responses latency was brisk (60 ms). These results constrain the possible interpretations about the location of the marmoset FEF and suggest that the marmoset model's significant advantages for the use of physiological techniques may be leveraged in the study of visuomotor cognition. Behavior and cognition in humans and other primates rely on networks of brain areas guided by the frontal cortex. The marmoset offers exciting new opportunities to study links between brain physiology and behavior, but the functions of frontal cortex areas are still being identified in this species. Here, we provide the first evidence of visual receptive fields in the marmoset dorsolateral frontal cortex, an important step toward future studies of visual cognitive behavior.
Topics: Animals; Callithrix; Evoked Potentials, Visual; Female; Frontal Lobe; Male; Visual Fields; Visual Perception
PubMed: 33326337
DOI: 10.1152/jn.00581.2020