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Human Brain Mapping Mar 2022The Self-Attention Network (SAN) has been proposed to describe the underlying neural mechanism of the self-prioritization effect, yet the roles of the key nodes in the...
The Self-Attention Network (SAN) has been proposed to describe the underlying neural mechanism of the self-prioritization effect, yet the roles of the key nodes in the SAN-the left posterior superior temporal sulcus (LpSTS) and the dorsolateral prefrontal cortex (DLPFC)-still need to be clarified. One hundred and nine participants were randomly assigned into the LpSTS group, the DLPFC group, or the sham group. We used the transcranial magnetic stimulation (TMS) technique to selectively disrupt the functions of the corresponding targeted region, and observed its impacts on self-prioritization effect based on the difference between the performance of the self-matching task before and after the targeted stimulation. We analyzed both model-free performance measures and HDDM-based performance measures for the self-matching task. The results showed that the inhibition of LpSTS could lead to reduced performance in processing self-related stimuli, which establishes a causal role for the LpSTS in self-related processing and provide direct evidence to support the SAN framework. However, the results of the DLPFC group from HDDM analysis were distinct from the results based on response efficiency. Our investigation further the understanding of the differentiated roles of key nodes in the SAN in supporting the self-salience in information processing.
Topics: Adult; Attention; Brain Mapping; Dorsolateral Prefrontal Cortex; Ego; Female; Humans; Male; Nerve Net; Psychomotor Performance; Social Perception; Temporal Lobe; Transcranial Magnetic Stimulation; Young Adult
PubMed: 34826160
DOI: 10.1002/hbm.25730 -
NeuroImage. Clinical 2013Cognitive control deficits have been consistently documented in patients with schizophrenia. Recent work in cognitive neuroscience has hypothesized a distinction between...
Cognitive control deficits have been consistently documented in patients with schizophrenia. Recent work in cognitive neuroscience has hypothesized a distinction between two theoretically separable modes of cognitive control-reactive and proactive. However, it remains unclear the extent to which these processes are uniquely associated with dysfunctional neural recruitment in individuals with schizophrenia. This functional magnetic resonance imaging (fMRI) study utilized the color word Stroop task and AX Continuous Performance Task (AX-CPT) to tap reactive and proactive control processes, respectively, in a sample of 54 healthy controls and 43 patients with first episode schizophrenia. Healthy controls demonstrated robust dorsolateral prefrontal, anterior cingulate, and parietal cortex activity on both tasks. In contrast, patients with schizophrenia did not show any significant activation during proactive control, while showing activation similar to control subjects during reactive control. Critically, an interaction analysis showed that the degree to which prefrontal activity was reduced in patients versus controls depended on the type of control process engaged. Controls showed increased dorsolateral prefrontal cortex (DLPFC) and parietal activity in the proactive compared to the reactive control task, whereas patients with schizophrenia did not demonstrate this increase. Additionally, patients' DLPFC activity and performance during proactive control was associated with disorganization symptoms, while no reactive control measures showed this association. Proactive control processes and concomitant dysfunctional recruitment of DLPFC represent robust features of schizophrenia that are also directly associated with symptoms of disorganization.
PubMed: 24179809
DOI: 10.1016/j.nicl.2013.04.010 -
Frontiers in Neuroscience 2022Transcranial magnetic stimulation (TMS) can depolarize cortical neurons through the intact skin and skull. The characteristics of the induced electric field (E-field)...
Transcranial magnetic stimulation (TMS) can depolarize cortical neurons through the intact skin and skull. The characteristics of the induced electric field (E-field) have a major impact on specific outcomes of TMS. Using multi-scale computational modeling, we explored whether the stimulation parameters derived from the primary motor cortex (M1) induce comparable macroscopic E-field strengths and subcellular/cellular responses in the dorsolateral prefrontal cortex (DLPFC). To this aim, we calculated the TMS-induced E-field in 16 anatomically realistic head models and simulated the changes in membrane voltage and intracellular calcium levels of morphologically and biophysically realistic human pyramidal cells in the M1 and DLPFC. We found that the conventional intensity selection methods (i.e., motor threshold and fixed intensities) produce variable macroscopic E-fields. Consequently, it was challenging to produce comparable subcellular/cellular responses across cortical regions with distinct folding characteristics. Prospectively, personalized stimulation intensity selection could standardize the E-fields and the subcellular/cellular responses to repetitive TMS across cortical regions and individuals. The suggested computational approach points to the shortcomings of the conventional intensity selection methods used in clinical settings. We propose that multi-scale modeling has the potential to overcome some of these limitations and broaden our understanding of the neuronal mechanisms for TMS.
PubMed: 35898411
DOI: 10.3389/fnins.2022.929814 -
Cerebral Cortex (New York, N.Y. : 1991) Apr 2023The dorsolateral prefrontal cortex has been shown to be associated with prosocial behavior. However, the direction of this relationship remains controversial. To resolve...
The dorsolateral prefrontal cortex has been shown to be associated with prosocial behavior. However, the direction of this relationship remains controversial. To resolve inconsistencies in the existing literature, we introduced the concept of default prosociality preference and hypothesized that this preference moderates the relationship between gray matter volume in the dorsolateral prefrontal cortex and prosocial behavior. This study analyzed the data of 168 participants obtained from voxel-based morphometry, 4 types of economic games, and 3 different measures of social value orientation that represent default prosociality preference. Here we show that, in individuals who were consistently classified as proself on the 3 social value orientation measures, gray matter volume in the right dorsolateral prefrontal cortex was positively associated with prosocial behavior. However, in individuals who were consistently classified as prosocial, the direction of this association was vice versa. These results indicate that the right dorsolateral prefrontal cortex regulates default prosociality preference.
Topics: Humans; Dorsolateral Prefrontal Cortex; Prefrontal Cortex; Magnetic Resonance Imaging; Gray Matter; Cerebral Cortex
PubMed: 36396873
DOI: 10.1093/cercor/bhac429 -
Neuropsychiatric Disease and Treatment 2021Previous studies suggested a link between serotonergic neurotransmission and impaired insight in schizophrenia. In this study, we examined the relationship between...
Association Between Lack of Insight and Prefrontal Serotonin Transporter Availability in Antipsychotic-Free Patients with Schizophrenia: A High-Resolution PET Study with [C]DASB.
BACKGROUND
Previous studies suggested a link between serotonergic neurotransmission and impaired insight in schizophrenia. In this study, we examined the relationship between serotonin transporter (SERT) availability in regions of the prefrontal cortex (dorsolateral, ventrolateral, ventromedial, and orbitofrontal cortices) and insight deficits in antipsychotic-free patients with schizophrenia using high-resolution positron emission tomography (PET) with [C]DASB.
METHODS
Nineteen patients underwent [C]DASB PET and 7-Tesla magnetic resonance imaging scans. To assess SERT availability, the binding potential with respect to non-displaceable compartment (BP) was derived using the simplified reference tissue model. Patients' level of insight was assessed using the Insight and Treatment Attitude Questionnaire (ITAQ). The relationship between ITAQ scores and [C]DASB BP values was examined using the region-of-interest (ROI)- and voxel-based analyses with relevant variables as covariates. The prefrontal cortex and its four subregions were selected as a priori ROIs since the prefrontal cortex has been implicated as the critical neuroanatomical substrate of impaired insight in schizophrenia.
RESULTS
The ROI-based analysis revealed that the ITAQ illness insight dimension had significant negative correlations with the [C]DASB BP in the left dorsolateral, left orbitofrontal, and bilateral ventrolateral prefrontal cortices. The ITAQ treatment insight dimension had significant negative correlations with the [C]DASB BP in the bilateral dorsolateral, left orbitofrontal, and bilateral ventrolateral prefrontal cortices. The ITAQ total score showed significant negative correlations with the [C]DASB BP in the bilateral prefrontal cortex and three subregions (dorsolateral, ventrolateral, and orbitofrontal cortices). A supplementary voxel-based analysis corroborated a significant negative association between the ITAQ score and the [C]DASB BP in the prefrontal cortices.
CONCLUSION
Our study provides in vivo evidence of significant negative correlations between insight deficits and prefrontal SERT availability in patients with schizophrenia, suggesting significant involvement of prefrontal serotonergic signaling in impaired insight, one of the core symptoms of schizophrenia.
PubMed: 34707358
DOI: 10.2147/NDT.S336126 -
The Journal of Neuroscience : the... Mar 2023A learned sensory-motor behavior engages multiple brain regions, including the neocortex and the basal ganglia. How a target stimulus is detected by these regions and...
A learned sensory-motor behavior engages multiple brain regions, including the neocortex and the basal ganglia. How a target stimulus is detected by these regions and converted to a motor response remains poorly understood. Here, we performed electrophysiological recordings and pharmacological inactivations of whisker motor cortex and dorsolateral striatum to determine the representations within, and functions of, each region during performance in a selective whisker detection task in male and female mice. From the recording experiments, we observed robust, lateralized sensory responses in both structures. We also observed bilateral choice probability and preresponse activity in both structures, with these features emerging earlier in whisker motor cortex than dorsolateral striatum. These findings establish both whisker motor cortex and dorsolateral striatum as potential contributors to the sensory-to-motor (sensorimotor) transformation. We performed pharmacological inactivation studies to determine the necessity of these brain regions for this task. We found that suppressing the dorsolateral striatum severely disrupts responding to task-relevant stimuli, without disrupting the ability to respond, whereas suppressing whisker motor cortex resulted in more subtle changes in sensory detection and response criterion. Together these data support the dorsolateral striatum as an essential node in the sensorimotor transformation of this whisker detection task. Selecting an item in a grocery store, hailing a cab - these daily practices require us to transform sensory stimuli into motor responses. Many decades of previous research have studied goal-directed sensory-to-motor transformations within various brain structures, including the neocortex and the basal ganglia. Yet, our understanding of how these regions coordinate to perform sensory-to-motor transformations is limited because these brain structures are often studied by different researchers and through different behavioral tasks. Here, we record and perturb specific regions of the neocortex and the basal ganglia and compare their contributions during performance of a goal-directed somatosensory detection task. We find notable differences in the activities and functions of these regions, which suggests specific contributions to the sensory-to-motor transformation process.
Topics: Mice; Male; Female; Animals; Vibrissae; Learning; Corpus Striatum; Neostriatum; Neocortex; Somatosensory Cortex
PubMed: 36810226
DOI: 10.1523/JNEUROSCI.1506-22.2023 -
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 -
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 -
Neurobiology of Disease Jun 2019Hypertension-induced microvascular brain injury is a major vascular contributor to cognitive impairment and dementia. We hypothesized that chronic hypoxia promotes the...
BACKGROUND
Hypertension-induced microvascular brain injury is a major vascular contributor to cognitive impairment and dementia. We hypothesized that chronic hypoxia promotes the hyperphosphorylation of tau and cell death in an accelerated spontaneously hypertensive stroke prone rat model of vascular cognitive impairment.
METHODS
Hypertensive male rats (n = 13) were fed a high salt, low protein Japanese permissive diet and were compared to Wistar Kyoto control rats (n = 5).
RESULTS
Using electron paramagnetic resonance oximetry to measure in vivo tissue oxygen levels and magnetic resonance imaging to assess structural brain damage, we found compromised gray (dorsolateral cortex: p = .018) and white matter (corpus callosum: p = .016; external capsule: p = .049) structural integrity, reduced cerebral blood flow (dorsolateral cortex: p = .005; hippocampus: p < .001; corpus callosum: p = .001; external capsule: p < .001) and a significant drop in cortical oxygen levels (p < .05). Consistently, we found reduced oxygen carrying neuronal neuroglobin (p = .008), suggestive of chronic cerebral hypoperfusion in high salt-fed rats. We also observed a corresponding increase in free radicals (NADPH oxidase: p = .013), p-Tau (pThr231) in dorsolateral cortex (p = .011) and hippocampus (p = .003), active interleukin-1β (p < .001) and neurodegeneration (dorsolateral cortex: p = .043, hippocampus: p = .044). Human patients with subcortical ischemic vascular disease, a type of vascular dementia (n = 38; mean age = 68; male/female ratio = 23/15) showed reduced hippocampal volumes and cortical shrinking (p < .05) consistent with the neuronal cell death observed in our hypertensive rat model as compared to healthy controls (n = 47; mean age = 63; male/female ratio = 18/29).
CONCLUSIONS
Our data support an association between hypertension-induced vascular dysfunction and the sporadic occurrence of phosphorylated tau and cell death in the rat model, correlating with patient brain atrophy, which is relevant to vascular disease.
Topics: Aged; Animals; Brain; Cell Hypoxia; Dementia, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Phosphorylation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; tau Proteins
PubMed: 30010004
DOI: 10.1016/j.nbd.2018.07.009 -
Frontiers in Neurology 2021Multiple studies have identified segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. It has been suggested that...
Multiple studies have identified segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. It has been suggested that in PD, preferential loss of dopamine in the posterior putamen may cause a major deficit in habitual control (mediated by the sensorimotor cortical-striatal loop), and the patients may therefore be forced into a progressive reliance on the goal-directed behavior (regulated by the associative cortical-striatal loop). Functional evidence supporting this point is scarce at present. This study aims to verify the functional connectivity changes within the sensorimotor, associative, and limbic cortical-striatal loops in PD. Resting-state fMRI of 70 PD patients and 30 controls were collected. Bilateral tripartite functional territories of basal ganglia and their associated cortical structures were chosen as regions of interest, including ventral striatum and ventromedial prefrontal cortex for limbic loop; dorsomedial striatum and dorsolateral prefrontal cortex for associative loop; dorsolateral striatum and sensorimotor cortex for sensorimotor loop. Pearson's correlation coefficients for each seed pair were calculated to obtain the functional connectivity. The relationships between functional connectivity and disease severity were further investigated. Functional connectivity between dorsolateral striatum and sensorimotor cortex is decreased in PD patients, and negatively correlated with disease duration; whereas functional connectivity between dorsomedial striatum and dorsolateral prefrontal cortex is also decreased but postitively correlated with disease duration. The functional connectivity within the sensorimotor loop is pathologically decreased in PD, while the altered connectivity within the associative loop may indicate a failed attempt to compensate for the loss of connectivity within the sensorimotor loop.
PubMed: 34764927
DOI: 10.3389/fneur.2021.720293