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Journal of Neurochemistry Sep 2022A distinct population of dopamine neurons in the substantia nigra pars lateralis (SNL) has a unique projection to the most caudolateral (tail) region of the striatum....
A distinct population of dopamine neurons in the substantia nigra pars lateralis (SNL) has a unique projection to the most caudolateral (tail) region of the striatum. Here, using two electrochemical techniques to measure basal dopamine and electrically evoked dopamine release in anesthetized rats, we characterized this pathway, and compared it with the 'classic' nigrostriatal pathway from neighboring substantia nigra pars compacta (SNc) dopamine neurons to the dorsolateral striatum. We found that the tail striatum constitutes a distinct dopamine domain compared with the dorsolateral striatum, with consistently lower basal and evoked dopamine, and diverse dopamine release kinetics. Importantly, electrical stimulation of the SNL and SNc evoked dopamine release in entirely separate striatal regions; the tail and dorsolateral striatum, respectively. Furthermore, we showed that stimulation of the subthalamic nucleus (STN) evoked dopamine release exclusively in the tail striatum, likely via the SNL, consistent with previous anatomical evidence of STN afferents to SNL dopamine neurons. Our work identifies the STN as an important modulator of dopamine release in a novel dopamine pathway to the tail striatum, largely independent of the classic nigrostriatal pathway, which necessitates a revision of the basal ganglia circuitry with the STN positioned as a central integrator of striatal information.
Topics: Animals; Basal Ganglia; Corpus Striatum; Dopamine; Dopaminergic Neurons; Rats; Substantia Nigra; Subthalamic Nucleus
PubMed: 35869680
DOI: 10.1111/jnc.15677 -
Neuron Feb 2023
PubMed: 36796328
DOI: 10.1016/j.neuron.2023.01.012 -
Brain : a Journal of Neurology Jul 2018While alterations in striatal dopamine in psychosis and stress have been well studied, the role of dopamine in prefrontal cortex is poorly understood. To date, no study...
While alterations in striatal dopamine in psychosis and stress have been well studied, the role of dopamine in prefrontal cortex is poorly understood. To date, no study has investigated the prefrontocortical dopamine response to stress in the psychosis spectrum, even though the dorsolateral and medial prefrontal cortices are key regions in cognitive and emotional regulation, respectively. The present study uses the high-affinity dopamine D2/3 receptor radiotracer 11C-FLB457 and PET together with a validated psychosocial stress challenge to investigate the dorsolateral and medial prefrontocortical dopamine response to stress in schizophrenia and clinical high risk for psychosis. Forty participants completed two 11C-FLB457 PET scans (14 antipsychotic-free schizophrenia, 14 clinical high risk for psychosis and 12 matched healthy volunteers), one while performing a Sensory Motor Control Task (control) and another while performing the Montreal Imaging Stress Task (stress). Binding potential (BPND) was estimated using Simplified Reference Tissue Model with cerebellar cortex as reference region. Dopamine release was defined as per cent change in BPND between control and stress scans (ΔBPND) using a novel correction for injected mass. Salivary cortisol response (ΔAUCI) was assessed throughout the tasks and its relationship with dopamine release examined. 11C-FLB457 binding at control conditions was significantly different between groups in medial [F(2,37) = 7.98, P = 0.0013] and dorsolateral [F(2,37) = 6.97, P = 0.0027] prefrontal cortex with schizophrenia patients having lower BPND than participants at clinical high risk for psychosis and healthy volunteers, but there was no difference in ΔBPND among groups [dorsolateral prefrontal cortex: F(2,37) = 1.07, P = 0.35; medial prefrontal cortex: F(2,37) = 0.54, P = 0.59]. We report a positive relationship between ΔAUCI and 11C-FLB457 ΔBPND in dorsolateral and medial prefrontal cortex in healthy volunteers (r = 0.72, P = 0.026; r = 0.76, P = 0.014, respectively) and in participants at clinical high risk for psychosis (r = 0.76, P = 0.0075; r = 0.72, P = 0.018, respectively), which was absent in schizophrenia (r = 0.46, P = 1.00; r = 0.19, P = 1.00, respectively). Furthermore, exploratory associations between ΔBPND or ΔAUCI and stress or anxiety measures observed in clinical high risk for psychosis were absent in schizophrenia. These findings provide first direct evidence of a disrupted prefrontocortical dopamine-stress regulation in schizophrenia.
Topics: Adult; Corpus Striatum; Dopamine; Female; Humans; Male; Positron-Emission Tomography; Prefrontal Cortex; Psychotic Disorders; Receptors, Dopamine D2; Risk Factors; Schizophrenia; Stress, Physiological; Young Adult
PubMed: 29860329
DOI: 10.1093/brain/awy133 -
Frontiers in Aging Neuroscience 2023Previous research has primarily focused on the association between muscle strength and global cognitive function in older adults, while the connection between muscle...
OBJECTIVE
Previous research has primarily focused on the association between muscle strength and global cognitive function in older adults, while the connection between muscle strength and advanced cognitive function such as inhibition and working memory (WM) remains unclear. This study aimed to investigate the relationship among muscle strength, WM, and task-related cortex hemodynamics.
METHODS
We recruited eighty-one older adults. Muscle strength was measured using a grip and lower limb strength protocol. We measured the WM performance by using reaction time (RT) and accuracy (ACC) in the N-back task and the cortical hemodynamics of the prefrontal cortex (PFC) by functional near-infrared spectroscopy (fNIRS).
RESULTS
We found positive correlations between grip strength ( < 0.05), 30-s sit-up ( < 0.05) and ACC, negative correlation between grip strength ( < 0.05) and RT. Furthermore, we observed positive correlations between grip strength and the level of oxygenated hemoglobin (HbO) in dorsolateral prefrontal cortex, frontopolar area, ventrolateral prefrontal cortex ( < 0.05), and negative correlations between grip strength and the level of deoxygenated hemoglobin (Hb) in left dorsolateral prefrontal cortex, frontopolar area, left ventrolateral prefrontal cortex ( < 0.05). Additionally, we noticed positive correlations between RT and the level of Hb in left dorsolateral prefrontal cortex, right frontopolar area ( < 0.05), and negative correlations between RT and the level of HbO in left dorsolateral prefrontal cortex, frontopolar area ( < 0.05). However, the cortical hemodynamics did not mediate the relationship between muscle strength and WM performance (RT, ACC).
CONCLUSION
The grip strength of older adults predicted WM in the cross-section study. The level of hemodynamics in PFC can serve as a predictor of WM.
PubMed: 37876877
DOI: 10.3389/fnagi.2023.1243283 -
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 -
Human Brain Mapping Feb 2021Three decades ago a series of parallel circuits were described involving the frontal cortex and deep grey matter structures, with putative roles in control of motor and... (Observational Study)
Observational Study
Three decades ago a series of parallel circuits were described involving the frontal cortex and deep grey matter structures, with putative roles in control of motor and oculomotor function, cognition, behaviour and emotion. The circuit comprising the dorsolateral prefrontal cortex, caudate, globus pallidus and thalamus has a putative role in regulating executive functions. The aim of this study is to investigate effective connectivity (EC) of the dorsolateral-prefrontal circuit and its association with PASAT-3 performance in people with multiple sclerosis(MS). We use Granger causality analysis of resting-state functional MRI from 52 people with MS and 36 healthy people to infer that reduced EC in the afferent limb of the dorsolateral prefrontal circuit occurs in the people with MS with cognitive dysfunction (left: p = .006; right: p = .029), with bilateral EC reductions in this circuit resulting in more severe cognitive dysfunction than unilateral reductions alone (p = .002). We show that reduced EC in the afferent limb of the dorsolateral prefrontal circuit mediates the relationship between cognitive performance and macrostrucutral and microstructural alterations of white matter tracts in components of the circuit. Specificity is shown by the absence of any relationship between cognition and EC in the analogous and anatomically proximal motor circuit. We demonstrate good stability of the EC measures in people with MS over an interval averaging 8-months. Key positive and negative results are replicated in an independent cohort of people with MS. Our findings identify the dorsolateral prefrontal circuit as a potential target for therapeutic strategies aimed at improving cognition in people with MS.
Topics: Adult; Cohort Studies; Dorsolateral Prefrontal Cortex; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Nerve Net; Neuropsychological Tests; Prospective Studies; White Matter
PubMed: 33073920
DOI: 10.1002/hbm.25239 -
Neuropsychopharmacology : Official... Jan 2021Compulsive alcohol consumption is a core, treatment-resistant feature of alcohol use disorder. The dorsomedial and dorsolateral striatum support goal-directed and...
Compulsive alcohol consumption is a core, treatment-resistant feature of alcohol use disorder. The dorsomedial and dorsolateral striatum support goal-directed and habitual action strategies, respectively. How ethanol targets dorsolateral striatum to drive compulsive consumption is poorly understood. Parvalbumin-expressing striatal fast-spiking interneurons comprise ~1% of the total neuronal striatal population, are enriched dorsolaterally and are functionally modulated by ethanol. To test whether fast-spiking interneurons are necessary for the development of compulsive ethanol consumption, we selectively ablated these neurons in adult male and female C57BL/6 J mice undergoing a voluntary chronic intermittent ethanol consumption paradigm followed by a compulsive ethanol drinking assay. Fast-spiking interneuron ablation curtailed the development of organized ethanol lick sequence behavior, reduced ethanol consumption, and abrogated compulsive consumption of ethanol with the added bitterant quinine. In contrast, fast-spiking interneuron ablation did not affect any index of water or sucrose consumption. These data causally implicate the minority striatal fast-spiking interneuron population as a key component of compulsive ethanol consumption.
Topics: Alcohol Drinking; Animals; Compulsive Behavior; Corpus Striatum; Female; Interneurons; Male; Mice; Mice, Inbred C57BL; Parvalbumins
PubMed: 32663841
DOI: 10.1038/s41386-020-0766-0 -
The Journal of Neuroscience : the... Oct 2017Declarative memory recall is thought to involve the reinstatement of neural activity patterns that occurred previously during encoding. Consistent with this view,...
Declarative memory recall is thought to involve the reinstatement of neural activity patterns that occurred previously during encoding. Consistent with this view, greater similarity between patterns of activity recorded during encoding and retrieval has been found to predict better memory performance in a number of studies. Recent models have argued that neural oscillations may be crucial to reinstatement for successful memory retrieval. However, to date, no causal evidence has been provided to support this theory, nor has the impact of oscillatory electrical brain stimulation during encoding and retrieval been assessed. To explore this we used transcranial alternating current stimulation over the left dorsolateral prefrontal cortex of human participants [ = 70, 45 females; age mean (SD) = 22.12 (2.16)] during a declarative memory task. Participants received either the same frequency during encoding and retrieval (60-60 or 90-90 Hz) or different frequencies (60-90 or 90-60 Hz). When frequencies matched there was a significant memory improvement (at both 60 and 90 Hz) relative to sham stimulation. No improvement occurred when frequencies mismatched. Our results provide support for the role of oscillatory reinstatement in memory retrieval. Recent neurobiological models of memory have argued that large-scale neural oscillations are reinstated to support successful memory retrieval. Here we used transcranial alternating current stimulation (tACS) to test these models. tACS has recently been shown to induce neural oscillations at the frequency stimulated. We stimulated over the left dorsolateral prefrontal cortex during a declarative memory task involving learning a set of words. We found that tACS applied at the same frequency during encoding and retrieval enhances memory. We also find no difference between the two applied frequencies. Thus our results are consistent with the proposal that reinstatement of neural oscillations during retrieval supports successful memory retrieval.
Topics: Brain; Female; Humans; Male; Memory; Mental Recall; Models, Neurological; Prefrontal Cortex; Psychomotor Performance; Transcranial Direct Current Stimulation; Young Adult
PubMed: 28912159
DOI: 10.1523/JNEUROSCI.0265-17.2017 -
Frontiers in Neuroscience 2021The efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression is nonuniform across patients. This study aims to determine whether baseline...
Functional and Structural Connectivity Between the Left Dorsolateral Prefrontal Cortex and Insula Could Predict the Antidepressant Effects of Repetitive Transcranial Magnetic Stimulation.
BACKGROUND
The efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression is nonuniform across patients. This study aims to determine whether baseline neuroimaging characters can provide a pretreatment predictive effect for rTMS.
METHODS
Twenty-seven treatment-naive patients with major depressive disorder (MDD) were enrolled and scanned with resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging. Clinical symptoms were assessed pre- and post-rTMS. Functional and structural connectivity between the left dorsolateral prefrontal cortex (DLPFC) and bilateral insula were measured, and the connectivity strength in each modality was then correlated to the clinical efficacy of rTMS.
RESULTS
When the coordinates of left DLPFC were located as a node in the central executive network, the clinical efficacy of rTMS was significantly correlated with the functional connectivity strength between left DLPFC and bilateral insula (left insula: = 0.66; right insula: = 0.65). The structural connectivity strength between the left DLPFC and left insular cortex also had a significantly positive correlation with symptom improvement ( = 0.458).
CONCLUSION
This study provides implications that rTMS might act more effectively when the pretreatment functional and structural connectivity between the insula and left DLPFC is stronger.
PubMed: 33841087
DOI: 10.3389/fnins.2021.645936 -
Neuroscience Bulletin Oct 2018An important and unresolved question is how human brain regions process information and interact with each other in intertemporal choice related to gains and losses....
An important and unresolved question is how human brain regions process information and interact with each other in intertemporal choice related to gains and losses. Using psychophysiological interaction and dynamic causal modeling analyses, we investigated the functional interactions between regions involved in the decision-making process while participants performed temporal discounting tasks in both the gains and losses domains. We found two distinct intrinsic valuation systems underlying temporal discounting in the gains and losses domains: gains were specifically evaluated in the medial regions, including the medial prefrontal and orbitofrontal cortices, and losses were evaluated in the lateral dorsolateral prefrontal cortex. In addition, immediate reward or punishment was found to modulate the functional interactions between the dorsolateral prefrontal cortex and distinct regions in both the gains and losses domains: in the gains domain, the mesolimbic regions; in the losses domain, the medial prefrontal cortex, anterior cingulate cortex, and insula. These findings suggest that intertemporal choice of gains and losses might involve distinct valuation systems, and more importantly, separate neural interactions may implement the intertemporal choices of gains and losses. These findings may provide a new biological perspective for understanding the neural mechanisms underlying intertemporal choice of gains and losses.
Topics: Adult; Brain; Brain Mapping; Delay Discounting; Female; Humans; Magnetic Resonance Imaging; Male; Neural Pathways; Neuropsychological Tests; Psychophysics; Reward; Young Adult
PubMed: 30088149
DOI: 10.1007/s12264-018-0267-x