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Scientific Reports Jan 2021The ventromedial and dorsolateral prefrontal cortex are two major prefrontal regions that usually interact in serving different cognitive functions. On the other hand,...
The ventromedial and dorsolateral prefrontal cortex are two major prefrontal regions that usually interact in serving different cognitive functions. On the other hand, these regions are also involved in cognitive processing of emotions but their contribution to emotional processing is not well-studied. In the present study, we investigated the role of these regions in three dimensions (valence, arousal and dominance) of emotional processing of stimuli via ratings of visual stimuli performed by the study participants on these dimensions. Twenty- two healthy adult participants (mean age 25.21 ± 3.84 years) were recruited and received anodal and sham transcranial direct current stimulation (tDCS) (1.5 mA, 15 min) over the dorsolateral prefrontal cortex (dlPFC) and and ventromedial prefrontal cortex (vmPFC) in three separate sessions with an at least 72-h interval. During stimulation, participants underwent an emotional task in each stimulation condition. The task included 100 visual stimuli and participants were asked to rate them with respect to valence, arousal, and dominance. Results show a significant effect of stimulation condition on different aspects of emotional processing. Specifically, anodal tDCS over the dlPFC significantly reduced valence attribution for positive pictures. In contrast, anodal tDCS over the vmPFC significantly reduced arousal ratings. Dominance ratings were not affected by the intervention. Our results suggest that the dlPFC is involved in control and regulation of valence of emotional experiences, while the vmPFC might be involved in the extinction of arousal caused by emotional stimuli. Our findings implicate dimension-specific processing of emotions by different prefrontal areas which has implications for disorders characterized by emotional disturbances such as anxiety or mood disorders.
Topics: Adult; Arousal; Cognition; Emotions; Female; Humans; Male; Prefrontal Cortex; Transcranial Direct Current Stimulation; Young Adult
PubMed: 33479323
DOI: 10.1038/s41598-021-81454-7 -
Cerebral Cortex (New York, N.Y. : 1991) Aug 2023Prior experiences, conditioning cues, and expectations of improvement are essential for placebo analgesia expression. The dorsolateral prefrontal cortex is considered a...
Prior experiences, conditioning cues, and expectations of improvement are essential for placebo analgesia expression. The dorsolateral prefrontal cortex is considered a key region for converting these factors into placebo responses. Since dorsolateral prefrontal cortex neuromodulation can attenuate or amplify placebo, we sought to investigate dorsolateral prefrontal cortex biochemistry and function in 38 healthy individuals during placebo analgesia. After conditioning participants to expect pain relief from a placebo "lidocaine" cream, we collected baseline magnetic resonance spectroscopy (1H-MRS) at 7 Tesla over the right dorsolateral prefrontal cortex. Following this, functional magnetic resonance imaging scans were collected during which identical noxious heat stimuli were delivered to the control and placebo-treated forearm sites. There was no significant difference in the concentration of gamma-aminobutyric acid, glutamate, Myo-inositol, or N-acetylaspartate at the level of the right dorsolateral prefrontal cortex between placebo responders and nonresponders. However, we identified a significant inverse relationship between the excitatory neurotransmitter glutamate and pain rating variability during conditioning. Moreover, we found placebo-related activation within the right dorsolateral prefrontal cortex and altered functional magnetic resonance imaging coupling between the dorsolateral prefrontal cortex and the midbrain periaqueductal gray, which also correlated with dorsolateral prefrontal cortex glutamate. These data suggest that the dorsolateral prefrontal cortex formulates stimulus-response relationships during conditioning, which are then translated to altered cortico-brainstem functional relationships and placebo analgesia expression.
Topics: Humans; Dorsolateral Prefrontal Cortex; Pain; Analgesia; Brain Stem; Magnetic Resonance Imaging; Glutamates; Prefrontal Cortex
PubMed: 37415068
DOI: 10.1093/cercor/bhad247 -
Behavioral Neuroscience Jun 2023Both the medial temporal lobe and the dorsolateral prefrontal cortex have been implicated in learning and memory. However, it has been difficult to ascertain the degree...
Both the medial temporal lobe and the dorsolateral prefrontal cortex have been implicated in learning and memory. However, it has been difficult to ascertain the degree to which the two structures are dependent on each other or interact in subserving these cognitive functions. To investigate this question directly, we prepared two group of monkeys. First, the contralateral frontal-hippocampal split group (CFHS) received a unilateral lesion of the hippocampus and surrounding posterior parahippocampal cortices (H +), combined with a lesion of the dorsolateral prefrontal cortex (DLPFC) plus transection of the corpus callosum and anterior commissure. This preparation functionally "disconnects" the remaining intact H + from the sole intact DLPFC in the opposite hemisphere. As a surgical control group, a second set of animals, the ipsilateral frontal-hippocampal split group, was prepared with a lesion of the DLPFC and an H + lesion together plus transection of the corpus callosum and anterior commissure. This preparation matches the locus and extent of damage in the cross-lesion group but allows the intact H + and intact DLPFC to interact ipsilaterally. Following recovery from surgery, all animals were then tested on the delayed nonmatching to sample task (DNMS), a test of recognition memory. The crossed-lesion split-brain group (CFHS) was markedly impaired on DNMS in both acquisition (rule learning) and performance over delays (recognition memory). The results provide evidence of a functionally dependent interaction between the medial temporal lobe and the dorsolateral prefrontal cortex in learning and memory. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Topics: Animals; Macaca mulatta; Learning; Recognition, Psychology; Temporal Lobe; Cerebral Cortex; Hippocampus; Prefrontal Cortex
PubMed: 37023305
DOI: 10.1037/bne0000556 -
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 -
Translational Psychiatry Feb 2023Schizophrenia is a complex and multifactorial disorder associated with altered neurotransmission as well as numerous signaling pathway and protein trafficking...
Schizophrenia is a complex and multifactorial disorder associated with altered neurotransmission as well as numerous signaling pathway and protein trafficking disruptions. The pH of intracellular organelles involved in protein trafficking is tightly regulated and impacts their functioning. The SLC9A family of Na/H exchangers (NHEs) plays a fundamental role in cellular and intracellular pH homeostasis. Four organellar NHE isoforms (NHE6-NHE9) are targeted to intracellular organelles involved in protein trafficking. Increased interactions between organellar NHEs and receptor of activated protein C kinase 1 (RACK1) can lead to redistribution of NHEs to the plasma membrane and hyperacidification of target organelles. Given their role in organelle pH regulation, altered expression and/or localization of organellar NHEs could be an underlying cellular mechanism contributing to abnormal intracellular trafficking and disrupted neurotransmitter systems in schizophrenia. We thus characterized organellar NHE expression, co-immunoprecipitation with RACK1, and Triton X-114 (TX-114) phase partitioning in dorsolateral prefrontal cortex of 25 schizophrenia and 25 comparison subjects by Western blot analysis. In schizophrenia after controlling for subject age at time of death, postmortem interval, tissue pH, and sex, there was significantly decreased total expression of NHE8, decreased co-immunoprecipitation of NHE8 (64%) and NHE9 (56%) with RACK1, and increased TX-114 detergent phase partitioning of NHE6 (283%), NHE9 (75%), and RACK1 (367%). Importantly, none of these dependent measures was significantly impacted when comparing those in the schizophrenia group on antipsychotics to those off of antipsychotics for at least 6 weeks at their time of death and none of these same proteins were affected in rats chronically treated with haloperidol. In summary, we characterized organellar NHE expression and distribution in schizophrenia DLPFC and identified abnormalities that could represent a novel mechanism contributing to disruptions in protein trafficking and neurotransmission in schizophrenia.
Topics: Rats; Animals; Schizophrenia; Dorsolateral Prefrontal Cortex; Antipsychotic Agents; Sodium-Hydrogen Exchangers; Organelles; Protein Isoforms; Prefrontal Cortex; Receptors for Activated C Kinase
PubMed: 36732328
DOI: 10.1038/s41398-023-02336-2 -
The Journal of Neuroscience : the... May 2023Regional cellular heterogeneity is a fundamental feature of the human neocortex; however, details of this heterogeneity are still undefined. We used single-nucleus...
Regional cellular heterogeneity is a fundamental feature of the human neocortex; however, details of this heterogeneity are still undefined. We used single-nucleus RNA-sequencing to examine cell-specific transcriptional features in the dorsolateral PFC (DLPFC) and the subgenual anterior cingulate cortex (sgACC), regions implicated in major psychiatric disorders. Droplet-based nuclei-capture and library preparation were performed on replicate samples from 8 male donors without history of psychiatric or neurologic disorder. Unsupervised clustering identified major neural cell classes. Subsequent iterative clustering of neurons further revealed 20 excitatory and 22 inhibitory subclasses. Inhibitory cells were consistently more abundant in the sgACC and excitatory neuron subclusters exhibited considerable variability across brain regions. Excitatory cell subclasses also exhibited greater within-class transcriptional differences between the two regions. We used these molecular definitions to determine which cell classes might be enriched in loci carrying a genetic signal in genome-wide association studies or for differentially expressed genes in mental illness. We found that the heritable signals of psychiatric disorders were enriched in neurons and that, while the gene expression changes detected in bulk-RNA-sequencing studies were dominated by glial cells, some alterations could be identified in specific classes of excitatory and inhibitory neurons. Intriguingly, only two excitatory cell classes exhibited concomitant region-specific enrichment for both genome-wide association study loci and transcriptional dysregulation. In sum, by detailing the molecular and cellular diversity of the DLPFC and sgACC, we were able to generate hypotheses on regional and cell-specific dysfunctions that may contribute to the development of mental illness. Dysfunction of the subgenual anterior cingulate cortex has been implicated in mood disorders, particularly major depressive disorder, and the dorsolateral PFC, a subsection of the PFC involved in executive functioning, has been implicated in schizophrenia. Understanding the cellular composition of these regions is critical to elucidating the neurobiology underlying psychiatric and neurologic disorders. We studied cell type diversity of the subgenual anterior cingulate cortex and dorsolateral PFC of humans with no neuropsychiatric illness using a clustering analysis of single-nuclei RNA-sequencing data. Defining the transcriptomic profile of cellular subpopulations in these cortical regions is a first step to demystifying the cellular and molecular pathways involved in psychiatric disorders.
Topics: Humans; Male; Dorsolateral Prefrontal Cortex; Depressive Disorder, Major; Gyrus Cinguli; Prefrontal Cortex; Genome-Wide Association Study; Solitary Nucleus
PubMed: 37037607
DOI: 10.1523/JNEUROSCI.0830-22.2023 -
Cureus Mar 2021Introduction This study aimed to evaluate the clinical outcomes of 16 patients with capitellum and trochlea fractures that were treated using isolated headless...
Introduction This study aimed to evaluate the clinical outcomes of 16 patients with capitellum and trochlea fractures that were treated using isolated headless compression screws or a combination of dorsolateral locking plates and anterior-to-posterior screws. We also investigated the presence of lateral epicondyle fragments because this fragment is especially important when making decisions regarding the surgical approach and implants. Materials and methods We conducted a retrospective analysis of 16 patients with capitellum and trochlea fractures. Clinical, radiographic (based on CT scans), and elbow-specific outcomes, including the Mayo Elbow Performance Index (MEPI), were evaluated at a mean of 23.5 months postoperatively. Results The average MEPI scores in patients with Dubberley type A (non-posterior comminution) and type B (posterior comminution) fractures were 88 and 78, respectively (p=0.08). Headless compression screws were used in 10 cases of type A fracture and one case of type B fracture. A combination of dorsolateral locking plates and anterior-to-posterior screws was used in five cases of type B fracture. Hardware loosening was seen in one case of type B fracture with isolated screw fixation. The presence of a lateral epicondyle fragment was significantly associated with the type B group (6/6 patients; 100%). In contrast, patients in the type A group rarely had posterior comminution of the lateral epicondyle fragment (2/10 patients; 20%). Conclusions Capitellum and trochlea fractures with posterior comminution, which typically presented with lateral epicondylar fragments, were safely and effectively treated with a combination of dorsolateral locking plates and anterior-to-posterior screws through lateral approaches. Cases without posterior comminution were treated with headless compression screws with no complications. The Dubberley classification system provides helpful information to determine the fixation strategy.
PubMed: 33842118
DOI: 10.7759/cureus.13740 -
Frontiers in Psychiatry 2022The perimenopause is associated with an increased risk of developing a major depressive (MD) episode. The biological changes occurring during perimenopause responsible...
A comparative magnetic resonance spectroscopy study of GABA+ and glutamate referenced to creatine and phosphocreatine in the left dorsolateral prefrontal cortex of perimenopausal women and women of reproductive age.
OBJECTIVE
The perimenopause is associated with an increased risk of developing a major depressive (MD) episode. The biological changes occurring during perimenopause responsible for this increased risk of depression remain to be elucidated. Postmortem and magnetic resonance spectroscopy (MRS) studies have revealed decreased gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in the dorsolateral prefrontal cortex (DLPFC) of MD patients. The objective of this study was to compare LDLPFC GABA+ and Glu ratios (referenced to creatine and phosphocreatine) in healthy reproductive-aged (RD) and perimenopausal (PM) women.
MATERIALS AND METHODS
Eighteen healthy PM and 20 RD women were included in the study. Our dependent variables, LDLPFC Glu and GABA+ ratios which include homocarnosine and macromolecules, were measured MRS, using a 3 Tesla magnet. Absence of current or past psychiatric diagnosis was confirmed a structured interview. RD participants were scanned during the early follicular phase of the menstrual cycle (MC). PM women were scanned outside of ovulatory cycles.
RESULTS
Mean LDLPFC GABA+ and Glu ratios were not statistically different between the PM group and RD group (PM mean = 0.10 ± 0.06, RD mean = 0.11 ± 0.04, = -0.383, = 36, = -0.13, = 0.70) (PM mean = 0.56 ± 0.06, RD mean = 0.57 ± 0.05, = -0.794, = 36, = -0.26, = 0.43), respectively. The perimenopause demarcates the end of the reproductive life. Unsurprisingly PM women were older than RD women (PM women: 48.8 ± 3.55 years, range 41-53 years old; RD women: 31.5 ± 9.66 years, range 18-47 years old) ( < 0.001). This inherent entanglement of group and age is a limitation of our study.
CONCLUSION
Contrary to our previous findings of decreased GABA+ and Glu in the medial prefrontal cortex in perimenopausal women, the perimenopause is not associated with decreased GABA+ or Glu ratios in the LDLPFC. This suggests that brain areas playing a role in MD display different sensitivity to the female hormones fluctuations associated with perimenopause.
PubMed: 36386999
DOI: 10.3389/fpsyt.2022.989050 -
Learning & Memory (Cold Spring Harbor,... Oct 2020Most experimental preparations demonstrate a role for dorsolateral striatum (DLS) in stimulus-response, but not outcome-based, learning. Here, we assessed DLS...
Most experimental preparations demonstrate a role for dorsolateral striatum (DLS) in stimulus-response, but not outcome-based, learning. Here, we assessed DLS involvement in a touchscreen-based reversal task requiring mice to update choice following a change in stimulus-reward contingencies. In vivo single-unit recordings in the DLS showed reversal produced a population-level shift from excited to inhibited neuronal activity prior to choices being made. The larger the shift, the faster mice reversed. Furthermore, optogenetic photosilencing DLS neurons during choice increased early reversal errors. These findings suggest dynamic DLS engagement may facilitate reversal, possibly by signaling a change in contingencies to other striatal and cortical regions.
Topics: Animals; Conditioning, Operant; Corpus Striatum; Discrimination Learning; Male; Mice; Mice, Inbred C57BL; Photic Stimulation; Reversal Learning
PubMed: 32934094
DOI: 10.1101/lm.051714.120 -
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