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Cerebral Cortex (New York, N.Y. : 1991) Oct 2023Stress is a major external factor threatening creative activity. The study explored whether left-lateralized activation in the dorsolateral prefrontal cortex manipulated... (Randomized Controlled Trial)
Randomized Controlled Trial
Stress is a major external factor threatening creative activity. The study explored whether left-lateralized activation in the dorsolateral prefrontal cortex manipulated through transcranial direct current stimulation could alleviate stress-induced impairment in creativity. Functional near-infrared spectroscopy was used to explore the underlying neural mechanisms. Ninety female participants were randomly assigned to three groups that received stress induction with sham stimulation, stress induction with true stimulation (anode over the left and cathode over the right dorsolateral prefrontal cortex), and control manipulation with sham stimulation, respectively. Participants underwent the stress or control task after the transcranial direct current stimulation manipulation, and then completed the Alternative Uses Task to measure creativity. Behavioral results showed that transcranial direct current stimulation reduced stress responses in heart rate and anxiety. The functional near-infrared spectroscopy results revealed that transcranial direct current stimulation alleviated dysfunction of the prefrontal cortex under stress, as evidenced by higher activation of the dorsolateral prefrontal cortex and frontopolar cortex, as well as stronger inter-hemispheric and intra-hemispheric functional connectivity within the prefrontal cortex. Further analysis demonstrated that the cortical regulatory effect prevented creativity impairment induced by stress. The findings validated the hemispheric asymmetry hypothesis regarding stress and highlighted the potential for brain stimulation to alleviate stress-related mental disorders and enhance creativity.
Topics: Humans; Female; Transcranial Direct Current Stimulation; Prefrontal Cortex; Spectrum Analysis; Dorsolateral Prefrontal Cortex
PubMed: 37585735
DOI: 10.1093/cercor/bhad301 -
JAMA Psychiatry May 2024The risk of mental disorders is consistently associated with variants in CACNA1C (L-type calcium channel Cav1.2) but it is not known why these channels are critical to...
IMPORTANCE
The risk of mental disorders is consistently associated with variants in CACNA1C (L-type calcium channel Cav1.2) but it is not known why these channels are critical to cognition, and whether they affect the layer III pyramidal cells in the dorsolateral prefrontal cortex that are especially vulnerable in cognitive disorders.
OBJECTIVE
To examine the molecular mechanisms expressed in layer III pyramidal cells in primate dorsolateral prefrontal cortices.
DESIGN, SETTING, AND PARTICIPANTS
The design included transcriptomic analyses from human and macaque dorsolateral prefrontal cortex, and connectivity, protein expression, physiology, and cognitive behavior in macaques. The research was performed in academic laboratories at Yale, Harvard, Princeton, and the University of Pittsburgh. As dorsolateral prefrontal cortex only exists in primates, the work evaluated humans and macaques.
MAIN OUTCOMES AND MEASURES
Outcome measures included transcriptomic signatures of human and macaque pyramidal cells, protein expression and interactions in layer III macaque pyramidal cells using light and electron microscopy, changes in neuronal firing during spatial working memory, and working memory performance following pharmacological treatments.
RESULTS
Layer III pyramidal cells in dorsolateral prefrontal cortex coexpress a constellation of calcium-related proteins, delineated by CALB1 (calbindin), and high levels of CACNA1C (Cav1.2), GRIN2B (NMDA receptor GluN2B), and KCNN3 (SK3 potassium channel), concentrated in dendritic spines near the calcium-storing smooth endoplasmic reticulum. L-type calcium channels influenced neuronal firing needed for working memory, where either blockade or increased drive by β1-adrenoceptors, reduced neuronal firing by a mean (SD) 37.3% (5.5%) or 40% (6.3%), respectively, the latter via SK potassium channel opening. An L-type calcium channel blocker or β1-adrenoceptor antagonist protected working memory from stress.
CONCLUSIONS AND RELEVANCE
The layer III pyramidal cells in the dorsolateral prefrontal cortex especially vulnerable in cognitive disorders differentially express calbindin and a constellation of calcium-related proteins including L-type calcium channels Cav1.2 (CACNA1C), GluN2B-NMDA receptors (GRIN2B), and SK3 potassium channels (KCNN3), which influence memory-related neuronal firing. The finding that either inadequate or excessive L-type calcium channel activation reduced neuronal firing explains why either loss- or gain-of-function variants in CACNA1C were associated with increased risk of cognitive disorders. The selective expression of calbindin in these pyramidal cells highlights the importance of regulatory mechanisms in neurons with high calcium signaling, consistent with Alzheimer tau pathology emerging when calbindin is lost with age and/or inflammation.
PubMed: 38776078
DOI: 10.1001/jamapsychiatry.2024.1112 -
Neuroscience Letters Jun 2021Word retrieval may involve an inhibitory process in which a target word is activated and related words are suppressed. In the current functional magnetic resonance...
Word retrieval may involve an inhibitory process in which a target word is activated and related words are suppressed. In the current functional magnetic resonance imaging (fMRI) study, we examined the inhibition of language processing cortex by the left dorsolateral prefrontal cortex (DLPFC) during word retrieval using an anagram-solving paradigm. Participants were presented with a distractor that was read aloud followed by a to-be-solved anagram. Distractor types were defined relative to orthographic overlap with the subsequent anagram solution and included related words with one letter different (e.g., "gripe" for the anagram of "price"), related pseudo-words, and unrelated words (i.e., all five letters were different). The anagram solution reaction time was slower in both the related word and related pseudo-word distractor conditions as compared to the unrelated word distractor condition, which can be attributed to greater inhibition following related distractors. The contrast of related words and unrelated words produced one activation in the left DLPFC, a region that has been associated with memory inhibition. To identify the regions that were negatively correlated with activity in the left DLPFC for related distractors, we conducted a functional connectivity analysis between this left DLPFC region and the rest of the brain. We found negatively correlated activity between the DLPFC and language processing cortex for the related word distractor condition (and the related pseudo-word distractor condition at a relaxed threshold). These findings suggest that that the left DLPFC may inhibit related word (and pseudo-word) representations in language processing cortex.
Topics: Adult; Dorsolateral Prefrontal Cortex; Female; Humans; Inhibition, Psychological; Magnetic Resonance Imaging; Male; Memory; Mental Recall; Reaction Time; Vocabulary; Young Adult
PubMed: 33831498
DOI: 10.1016/j.neulet.2021.135876 -
International Journal of Clinical and... 2020Activation likelihood estimation meta-analysis was performed to examine the activation characteristics of cognition-related brain regions in patients with mild traumatic... (Review)
Review
Activation likelihood estimation meta-analysis was performed to examine the activation characteristics of cognition-related brain regions in patients with mild traumatic brain injury (mTBI). The databases PubMed, Ovid, Cochrane Library, Google Scholar, CNKI, WFSD, and VIP were systematically searched. The software Ginger-ALE 3.0.2 was used for coordinate unification and meta-analysis. Seven studies with a total of 314 subjects were included. Meta-analysis results indicated that compared with healthy subjects, mTBI patients had enhanced activation in the left anterior angular gyrus, left occipital joint visual, left midbrain, right temporal angular gyrus, right cerebellar tonsil, left frontal insula, and right inferior frontal gyrus. mTBI patients had attenuated activation in the right dorsolateral prefrontal lobe, left cerebellar anterior lobe, left dorsolateral prefrontal lobe, right middle frontal gyrus, right posterior cingulate gyrus, left joint visual, left supramarginal gyrus, left middle frontal gyrus, right precuneus, left dorsolateral prefrontal cortex, right frontal eye field, right lower parietal gyrus, corpus callosum, right frontal pole region, and left prefrontal lobe. Further joint analysis revealed that the dorsolateral prefrontal lobe of the right middle frontal gyrus was a region of attenuated co-activation. The dorsolateral prefrontal lobe of the right middle frontal gyrus showing attenuated activation was the main brain region distinguishing mTBI patients from healthy subjects. Cognitive deficits could be associated with attenuated activation in the dorsolateral prefrontal lobe of the right middle frontal gyrus, which could be due to a decline in the recruitment ability of the neural network involved in controlling attention.
PubMed: 33425093
DOI: No ID Found -
Brain Topography Nov 2022Empathic abilities have been shown to be linked with brain structural variations. Since psychotherapists constitute a population that tends to display greater empathic...
Empathic abilities have been shown to be linked with brain structural variations. Since psychotherapists constitute a population that tends to display greater empathic abilities, as shown in psychometric differences in cognitive empathy and emotional regulation, we aimed to identify cortical thickness (CT) differences between a group of professional psychotherapists and a control group. In line with the recently emphasized urge to employ more than a single workflow in cortical analyses, we utilized two cortical surface extraction and thickness estimation pipelines-CIVET and FreeSurfer. Eighteen psychotherapists and eighteen controls underwent MRI scanning and completed empathy-related psychometric assessments. We evaluated how CT measures differed between groups and if there was an association with individual empathy-related scores in a series of regions of interest (ROIs). Our analysis with CIVET shows that psychotherapists display a significantly greater CT at a ROI in the left dorsolateral prefrontal cortex (dlPFC; p < 0.05, FDR corrected). With FreeSurfer, a whole-brain vertex-wise analysis identified a statistically significant cluster in the left PFC that partially overlaps with the previous ROI. These results were reinforced by a structural covariance analysis revealing that, in psychotherapists, the left dlPFC ROI seemed to vary independently from the rest of the cortex. These findings are relevant because the dlPFC region importantly participates in the cognitive components of the empathic response, such as emotion regulation and perspective taking. Thus, our findings support the idea that empathic capacity is reflected by brain structural variations while also studying for the first time a sample of subjects for whom empathic responding is crucial in their profession.
Topics: Humans; Animals; Empathy; Emotional Regulation; Psychotherapists; Dorsolateral Prefrontal Cortex; Viverridae; Magnetic Resonance Imaging; Prefrontal Cortex
PubMed: 35988094
DOI: 10.1007/s10548-022-00910-3 -
The Journal of Physiology Aug 2018There are two electrophysiological dichotomous populations of parvalbumin (PV) interneurons located in the dorsal striatum. Striatal PV interneurons in medial and...
KEY POINTS
There are two electrophysiological dichotomous populations of parvalbumin (PV) interneurons located in the dorsal striatum. Striatal PV interneurons in medial and lateral regions differ significantly in their intrinsic excitability. Parvalbumin interneurons in the dorsomedial striatum, but not in the dorsolateral striatum, receive afferent glutamatergic input from cingulate cortex.
ABSTRACT
Dorsomedial striatum circuitry is involved in goal-directed actions or movements that become habits upon repetition, as encoded by the dorsolateral striatum. An inability to shift from habits can compromise action-control and prevent behavioural adaptation. Although these regions appear to be clearly behaviourally distinct, little is known about their distinct physiology. Parvalbumin (PV) interneurons are a major source of striatal inhibition and are usually considered as a homogeneous population in the entire dorsal striatum. In the present study, we recorded PV interneurons in dorsal striatum slices from wild-type male mice and suggest the existence of two electrophysiological dichotomous populations. We found that PV interneurons located at the dorsomedial striatum region have increased intrinsic excitability compared to PV interneurons in dorsolateral region. We also found that PV interneurons in the dorsomedial region, but not in the dorsolateral striatum region, receive short-latency excitatory inputs from cingulate cortex. Therefore, the results of the present study demonstrate the importance of considering region specific parvalbumin interneuron populations when studying dorsal striatal function.
Topics: Afferent Pathways; Animals; Corpus Striatum; Functional Laterality; Glutamic Acid; Interneurons; Male; Mice; Mice, Knockout; Parvalbumins
PubMed: 29808928
DOI: 10.1113/JP275936 -
Medicine Feb 2024Lateral medullary syndrome is caused by atherosclerosis or embolism of the vertebral artery and its branches or the posterior inferior cerebellar artery (PICA).The...
RATIONALE
Lateral medullary syndrome is caused by atherosclerosis or embolism of the vertebral artery and its branches or the posterior inferior cerebellar artery (PICA).The eight-and-a-half syndrome is a rare pontocerebellar nerve-ocular syndrome presenting as a one-and-a-half syndrome plus ipsilateral seventh cerebral nerve palsy. The dorsolateral medullary syndrome combined with the eight-and-a-half syndromes is even rarer, so it is important to recognize the features of the classical brainstem syndrome and the eight-and-a-half syndromes.
PATIENT CONCERNS
Most patients with dorsolateral medullary syndrome combined with eight-and-a-half syndromes have a good prognosis, with recovery occurring within a few weeks to a few months, although a few patients may take longer to recover.
DIAGNOSIS INTERVENTIONS
In the course of disease development, the patient developed dysarthria, dysphagia, hypothermia, ipsilateral Horner sign and ataxia. Computed tomography was performed which showed cerebral infarction in the left brainstem. Cranial diffusion-weighted imaging + magnetic resonance angiography showed acute infarction in the left cerebellar hemisphere, with a high probability of severe stenosis or occlusion in the intracranial and proximal segments of the basilar arteries. This supports the diagnosis of dorsolateral medullary syndrome. The patient's limited adduction and abduction of the left eye and limited adduction of the right eye, combined with peripheral paralysis of the affected lateral nerve, supported the diagnosis of eight-and-a-half syndromes. The administration of antiplatelet and anti-ester fixation treatment can effectively improve the symptoms and shorten the course of the disease.
OUTCOMES
After antiplatelet and anti-ester fixation treatment, the symptoms improved and the patient was discharged.
LESSONS
Dorsolateral medullary syndrome combined with eight-and-a-half syndromes is a rare clinical condition, and therefore more attention should be paid to the early diagnosis and treatment of such patients.
Topics: Humans; Lateral Medullary Syndrome; Cerebellum; Cerebral Infarction; Infarction; Vertebral Artery; Facial Paralysis
PubMed: 38335410
DOI: 10.1097/MD.0000000000034409 -
Neuron Sep 2014The basal ganglia are involved in sensorimotor functions and action selection, both of which require the integration of sensory information. In order to determine how...
The basal ganglia are involved in sensorimotor functions and action selection, both of which require the integration of sensory information. In order to determine how such sensory inputs are integrated, we obtained whole-cell recordings in mouse dorsal striatum during presentation of tactile and visual stimuli. All recorded neurons responded to bilateral whisker stimulation, and a subpopulation also responded to visual stimulation. Neurons responding to both visual and tactile stimuli were located in dorsomedial striatum, whereas those responding only to whisker deflections were located dorsolaterally. Responses were mediated by overlapping excitation and inhibition, with excitation onset preceding that of inhibition by several milliseconds. Responses differed according to the type of neuron, with direct pathway MSNs having larger responses and longer latencies between ipsilateral and contralateral responses than indirect pathway MSNs. Our results suggest that striatum acts as a sensory "hub" with specialized functional roles for the different neuron types.
Topics: Action Potentials; Afferent Pathways; Animals; Biotin; Cerebral Cortex; Corpus Striatum; Dextrans; Female; Functional Laterality; Green Fluorescent Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Patch-Clamp Techniques; Photic Stimulation; Receptors, Dopamine D1; Receptors, Dopamine D2; Vibrissae
PubMed: 25155959
DOI: 10.1016/j.neuron.2014.07.033 -
Dorsolateral and dorsomedial prefrontal cortex track distinct properties of dynamic social behavior.Social Cognitive and Affective... Jun 2020Understanding how humans make competitive decisions in complex environments is a key goal of decision neuroscience. Typical experimental paradigms constrain behavioral...
Understanding how humans make competitive decisions in complex environments is a key goal of decision neuroscience. Typical experimental paradigms constrain behavioral complexity (e.g. choices in discrete-play games), and thus, the underlying neural mechanisms of dynamic social interactions remain incompletely understood. Here, we collected fMRI data while humans played a competitive real-time video game against both human and computer opponents, and then, we used Bayesian non-parametric methods to link behavior to neural mechanisms. Two key cognitive processes characterized behavior in our task: (i) the coupling of one's actions to another's actions (i.e. opponent sensitivity) and (ii) the advantageous timing of a given strategic action. We found that the dorsolateral prefrontal cortex displayed selective activation when the subject's actions were highly sensitive to the opponent's actions, whereas activation in the dorsomedial prefrontal cortex increased proportionally to the advantageous timing of actions to defeat one's opponent. Moreover, the temporoparietal junction tracked both of these behavioral quantities as well as opponent social identity, indicating a more general role in monitoring other social agents. These results suggest that brain regions that are frequently implicated in social cognition and value-based decision-making also contribute to the strategic tracking of the value of social actions in dynamic, multi-agent contexts.
Topics: Adult; Bayes Theorem; Brain; Decision Making; Female; Humans; Magnetic Resonance Imaging; Male; Prefrontal Cortex; Social Behavior
PubMed: 32382757
DOI: 10.1093/scan/nsaa053 -
Brain and Neuroscience Advances 2018The prefrontal cortices play an essential role in cognitive-emotional and working memory processes through interactions with multiple brain regions.
Desirability, availability, credit assignment, category learning, and attention: Cognitive-emotional and working memory dynamics of orbitofrontal, ventrolateral, and dorsolateral prefrontal cortices.
BACKGROUND
The prefrontal cortices play an essential role in cognitive-emotional and working memory processes through interactions with multiple brain regions.
METHODS
This article further develops a unified neural architecture that explains many recent and classical data about prefrontal function and makes testable predictions.
RESULTS
Prefrontal properties of desirability, availability, credit assignment, category learning, and feature-based attention are explained. These properties arise through interactions of orbitofrontal, ventrolateral prefrontal, and dorsolateral prefrontal cortices with the inferotemporal cortex, perirhinal cortex, parahippocampal cortices; ventral bank of the principal sulcus, ventral prearcuate gyrus, frontal eye fields, hippocampus, amygdala, basal ganglia, hypothalamus, and visual cortical areas V1, V2, V3A, V4, middle temporal cortex, medial superior temporal area, lateral intraparietal cortex, and posterior parietal cortex. Model explanations also include how the value of visual objects and events is computed, which objects and events cause desired consequences and which may be ignored as predictively irrelevant, and how to plan and act to realise these consequences, including how to selectively filter expected versus unexpected events, leading to movements towards, and conscious perception of, expected events. Modelled processes include reinforcement learning and incentive motivational learning; object and spatial working memory dynamics; and category learning, including the learning of object categories, value categories, object-value categories, and sequence categories, or list chunks.
CONCLUSION
This article hereby proposes a unified neural theory of prefrontal cortex and its functions.
PubMed: 32166139
DOI: 10.1177/2398212818772179