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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 -
Addiction Biology Jul 2021Abstinence is one of the important measures for heroin addiction. However, it is unknown whether long-term abstinence (LA) would improve the coupling among three core...
Abstinence is one of the important measures for heroin addiction. However, it is unknown whether long-term abstinence (LA) would improve the coupling among three core brain networks (salience, default mode, and executive control) and decrease craving in treated heroin addicts. Forty-three heroin addicts with LA, 27 heroin addicts with short-term abstinence (SA), and 46 demographically matched healthy controls (HC) participated in the resting-state functional magnetic resonance imaging study. The authors compared the functional connectivity among the three groups and examined how the coupling among salience, default mode, and executive control networks related to duration of abstinence and craving before and after drug cue exposure among heroin addicts. Compared with the SA group, with a tendency toward the HC group, the LA group showed lower drug cue-induced craving, stronger connectivity between the dorsal anterior cingulate cortex (a key node of salience network) and left dorsolateral prefrontal cortex and right posterior parietal cortex (key nodes of executive control network), and stronger connectivity between the right dorsolateral prefrontal cortex and precuneus (a key node of default mode network). Meanwhile, the right dorsolateral prefrontal cortex-precuneus connectivity positively correlated with duration of abstinence. The LA and SA groups demonstrated lower connectivity between the left anterior insula (a key node of salience network) and dorsolateral prefrontal cortex and lower connectivity within the left dorsolateral prefrontal cortex, compared with the HC group. Our findings revealed that LA is associated with lower drug cue induced craving and improve the coupling among the three core brain networks in heroin addicts.
Topics: Adult; Brain; Brain Mapping; Craving; Cues; Dorsolateral Prefrontal Cortex; Gyrus Cinguli; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Young Adult
PubMed: 33142364
DOI: 10.1111/adb.12982 -
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 -
Frontiers in Neurology 2021Deep-brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor symptoms of advanced Parkinson's disease (PD). Due to a lack of...
Deep-brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor symptoms of advanced Parkinson's disease (PD). Due to a lack of detailed somatotopic organization in STN, the clinically most effective part of the STN for stimulation has already become one of the hot research focuses. At present, there are some reports about topographic distribution for different depths within the STN, but few about a mediolateral topography in this area. The objective was to investigate the local field potential (LFP) distribution patterns in dorsomedial and dorsolateral subparts of STN. In total, 18 PD patients eventually enrolled in this study. The DBS electrodes were initially located on the lateral portion of dorsolateral STN. Because of internal capsule side effects presented at low threshold (below 1.5 mA), the electrode was reimplanted more medially to the dorsomedial STN. In this process, intraoperative LFPs from dorsomedial and dorsolateral STN were recorded from the inserted electrode. Both beta power and gamma power of the LFPs were calculated using the power spectral density (PSD) for each DBS contact pair. Furthermore, coherence between any two pairs of contacts was computed in the dorsomedial and dorsolateral parts of STN, respectively. Meanwhile, the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) was monitored prior to surgery and at the 6-month follow-up. Compared to the dorsolateral part of STN, gamma oscillations ( < 0.01) and coherence ( < 0.05) were all weaker in the dorsomedial part. However, no obvious differences in beta oscillations and coherence were observed between the two groups ( > 0.05). Moreover, it should be noted that DBS of the dorsomedial STN resulted in significant improvement in the UPDRS-III in PD patients. There was a 61.50 ± 21.30% improvement in UPDRS-III scores in Med-off/Stim-on state relative to the Med-off state at baseline (from 15.44 ± 6.84 to 43.94 ± 15.79, < 0.01). The specific features of gamma activity may be used to differentiate STN subregions. Moreover, the dorsomedial part of STN might be a potential target for DBS in PD.
PubMed: 34557146
DOI: 10.3389/fneur.2021.710206 -
Journal of Molecular Histology Aug 2023Delayed cancer progression in the ventral prostate of the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model has been previously reported upon celecoxib and...
Delayed cancer progression in the ventral prostate of the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model has been previously reported upon celecoxib and nintedanib co-administration. Herein, we sought to further investigate the effects of these drugs association in some of their direct molecular targets (COX-2, VEGF and VEGFR-2) and in reactive stroma markers (TGF-β, αSMA, vimentin and pro-collagen 1) in the dorsolateral prostate, looking for lobe-specific responses. Male TRAMP mice were treated with celecoxib (10 mg/Kg, i.o.) and/or nintedanib (15 mg/Kg, i.o.) for 6 weeks and prostate was harvested for morphological and protein expression analyses. Results showed that combined therapy resulted in unique antitumor effects in dorsolateral prostate, especially due to the respective stromal or epithelial antiproliferative actions of these drugs, which altogether led to a complete inversion in high-grade (HGPIN) versus low-grade (LGPIN) premalignant lesion incidences in relation to controls. At the molecular level, this duality in drug action was paralleled by the differential down/upregulation of TGF-β signaling by celecoxib/nintedanib, thus leading to associated changes in stroma composition towards regression or quiescence, respectively. Additionally, combined therapy was able to promote decreased expression of inflammatory (COX-2) and angiogenesis (VEGF/VEGFR-2) mediators. Overall, celecoxib and nintedanib association provided enhanced antitumor effects in TRAMP dorsolateral as compared to former registers in ventral prostate, thus demonstrating lobe-specific responses of this combined chemoprevention approach. Among these responses, we highlight the ability in promoting TGF-β signaling and its associated stromal maturation/stabilization, thus yielding a more quiescent stromal milieu and resulting in greater epithelial proliferation impairment.
Topics: Humans; Mice; Animals; Male; Celecoxib; Prostate; Prostatic Neoplasms; Vascular Endothelial Growth Factor Receptor-2; Mice, Transgenic; Cyclooxygenase 2; Vascular Endothelial Growth Factor A; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 37335420
DOI: 10.1007/s10735-023-10130-z -
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 -
Frontiers in Behavioral Neuroscience 2022The dorsolateral prefrontal cortex (DLPFC) is a key node of the frontal cognitive circuit. It is involved in executive control and many cognitive processes. Abnormal... (Review)
Review
BACKGROUND
The dorsolateral prefrontal cortex (DLPFC) is a key node of the frontal cognitive circuit. It is involved in executive control and many cognitive processes. Abnormal activities of DLPFC are likely associated with many psychiatric diseases. Modulation of DLPFC may have potential beneficial effects in many neural and psychiatric diseases. One of the widely used non-invasive neuromodulation technique is called transcranial direct current stimulation (or tDCS), which is a portable and affordable brain stimulation approach that uses direct electrical currents to modulate brain functions.
OBJECTIVE
This review aims to discuss the results from the past two decades which have shown that tDCS can relieve clinical symptoms in various neurological and psychiatric diseases.
METHODS
Here, we performed searches on PubMed to collect clinical and preclinical studies that using tDCS as neuromodulation technique, DLPFC as the stimulation target in treating neuropsychiatric disorders. We summarized the stimulation sites, stimulation parameters, and the overall effects in these studies.
RESULTS
Overall, tDCS stimulation of DLPFC could alleviate the clinical symptoms of schizophrenia, depression, drug addiction, attention deficit hyperactivity disorder and other mental disorders.
CONCLUSION
The stimulation parameters used in these studies were different from each other. The lasting effect of stimulation was also not consistent. Nevertheless, DLPFC is a promising target for non-invasive stimulation in many psychiatric disorders. TDCS is a safe and affordable neuromodulation approach that has potential clinical uses. Larger clinical studies will be needed to determine the optimal stimulation parameters in each condition.
PubMed: 35711693
DOI: 10.3389/fnbeh.2022.893955 -
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 -
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 -
Psychoneuroendocrinology Feb 2021The left dorsolateral prefrontal cortex (dlPFC) has been implicated in the regulation of stress-related cognitive processes and physiological responses and is the...
The left dorsolateral prefrontal cortex (dlPFC) has been implicated in the regulation of stress-related cognitive processes and physiological responses and is the principal target of noninvasive brain stimulation techniques applied to psychiatric conditions. However, existing studies are mostly correlational and causal evidence on the role of this region in mediating specific psychophysiological mechanisms underpinning stress-related responses are needed to make the application of such techniques more efficient. To fill this gap, this study used inhibitory continuous theta burst stimulation (cTBS) in healthy individuals to examine the extent to which activity of the left dlPFC is associated with cognitive (subjective focus on a tracking task), behavioral (reaction times and variability), and physiological responses (heart rate and its variability and cortisol level) following induction of perseverative cognition. Compared to sham and left ventral PreMotor area stimulation (as active control area), inhibition of left dlPFC determined sustained autonomic and neuroendocrine activation and increased the subjective perception of being task-focused, while not changing the behavioral and self-reported stress-related responses. Adopting a causative approach, we describe a role of left dlPFC in inhibitory control of the physiological stress-response associated to perseverative thinking.
Topics: Cognition; Humans; Inhibition, Psychological; Prefrontal Cortex; Stress, Physiological; Transcranial Magnetic Stimulation
PubMed: 33310375
DOI: 10.1016/j.psyneuen.2020.105070