scholarly journals Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association with Memory and Social Impairments and Abnormal Sensorimotor Gating

2019 ◽  
Author(s):  
Marquis P Vawter ◽  
Anton Schulmann ◽  
Lamees Alhassen ◽  
Wedad Alhassen ◽  
Abdul Rezzak Hamzeh ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Cognitive Functions ◽  
Repetitive Behavior ◽  
Detection Threshold ◽  
Sensorimotor Gating ◽  
Social Impairment ◽  
Behavioral Abnormalities ◽  
Potential Association ◽  
Dorsolateral Prefrontal ◽  
Melanin Concentrating Hormone

Abstract Background Evidence from anatomical, pharmacological, and genetic studies supports a role for the neuropeptide melanin concentrating hormone (MCH) system in modulating emotional and cognitive functions. Genome wide association (GWA) studies revealed a potential association between the MCH receptor (MCHR1) gene locus and schizophrenia and the largest GWA study conducted to date shows a credible GWA. Methods We analyze MCHR1 and pro-melanin concentrating hormone (PMCH) RNA-Seq expression in the prefrontal cortex in schizophrenia patients and healthy controls. Disruptions in the MCH system were modeled in the mouse brain by germline deletion of MCHR1 and by conditional ablation of MCH expressing neurons using a Cre-inducible diphtheria toxin (iDTR) system. Results MCHR1 expression is decreased in the prefrontal cortex of schizophrenia samples (FDR p< 0.05, CommonMind and PsychEncode combined datasets, N = 901) while PMCH is below the detection threshold. MCHR1 expression decreased with aging (p = 6.6E-57) in human dorsolateral prefrontal cortex. The deletion of MCHR1 was found to lead to behavioral abnormalities mimicking schizophrenia-like phenotypes: hyperactivity, increased stereotypic and repetitive behavior, social impairment, impaired sensorimotor gating, and disrupted cognitive functions. Conditional ablation of PMCH neurons increased repetitive behavior and produced a deficit in sensorimotor gating. Conclusions Our study indicates that early disruption of the MCH system interferes with neurodevelopmental processes which may contribute to the pathogenesis of schizophrenia. Further neurobiological research on the developmental timing and circuits that are affected by MCH may lead to a therapeutic target for early prevention of schizophrenia.

Evidence for the importance of dopamine for prefrontal cortex functions early in life

1996 ◽  
Vol 351 (1346) ◽  
pp. 1483-1494 ◽  
Keyword(s):  
Mental Retardation ◽  
Prefrontal Cortex ◽  
Amino Acid ◽  
Cognitive Functions ◽  
Cognitive Abilities ◽  
Dorsolateral Prefrontal Cortex ◽  
Dopamine Neurons ◽  
Dopamine Turnover ◽  
Severe Mental Retardation ◽  
Dorsolateral Prefrontal

There is considerable evidence that dorsolateral prefrontal cortex subserves critical cognitive abilities even during early infancy and that improvement in these abilities is evident over roughly the next 10 years. We also know that (a) in adult monkeys these cognitive abilities depend critically on the dopaminergic projection to prefrontal cortex and (b) the distribution of dopamine axons within dorsolateral prefrontal cortex changes, and the level of dopamine increases, during the period that infant monkeys are improving on tasks that require the cognitive abilities dependent on prefrontal cortex. To begin to look at whether these cognitive abilities depend critically on the prefrontal dopamine projection in humans even during infancy and early childhood we have been studying children who we hypothesized might have a selective reduction in the dopaminergic innervation of prefrontal cortex and a selective impairment in the cognitive functions subserved by dorsolateral prefrontal cortex. These are children treated early and continuously for the genetic disorder, phenylketonuria (PKU). In PKU the ability to convert the amino acid, phenylalanine (Phe), into another amino acid, tyrosine (Tyr), is impaired. This causes Phe to accumulate in the bloodstream to dangerously high levels and the plasma level of Tyr to fall. Widespread brain damage and severe mental retardation result. When PKU is moderately well controlled by a diet low in Phe (thus keeping the imbalance between Phe and Tyr in plasma within moderate limits) severe mental retardation is averted, but deficits remain in higher cognitive functions. In a four-year longitudinal study we have found these deficits to be in the working memory and inhibitory control functions dependent upon dorsolateral prefrontal cortex in PKU children with plasma Phe levels 3-5 times normal. The fact that even infants showed these impairments suggests that dopaminergic innervation to prefrontal cortex is critical for the proper expression of these abilities even during the first year of life. To test the hypothesis about the underlying biological mechanism we have created the first animal model of early and continuously treated PKU. As predicted, the experimental animals had reduced levels of dopamine and the dopamine metabolite, homovanillic acid (HVA), in prefrontal cortex and showed impaired performance on delayed alternation, a task dependent on prefrontal cortex function. Noradrenaline levels were unaffected; however some reduction in serotonin levels and in dopamine levels outside the prefrontal cortex was found. If prefrontal cortex functions are vulnerable in children with a moderate plasma Phe:Tyr imbalance because of the special properties of the dopamine neurons that project to prefrontal cortex, then other dopamine neurons that share those same properties should also be vulnerable in these children. The dopamine neurons in the retina share these properties (i.e. unusually high firing and dopamine turnover rates), and we have found that PKU children with plasma Phe levels 3-5 times normal are impaired in their contrast sensitivity, a behavioural measure sensitive to retinal dopamine levels.

scholarly journals Functional brain abnormalities associated with comorbid anxiety in autism spectrum disorder

2020 ◽  
Vol 32 (4) ◽  
pp. 1273-1286
Author(s):  
James Bartolotti ◽  
John A. Sweeney ◽  
Matthew W. Mosconi
Keyword(s):  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Anxiety Disorders ◽  
Data Exchange ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Anterior Cingulate ◽  
Social Impairment ◽  
Comorbid Anxiety

AbstractAnxiety disorders are common in autism spectrum disorder (ASD) and associated with social–communication impairment and repetitive behavior symptoms. The neurobiology of anxiety in ASD is unknown, but amygdala dysfunction has been implicated in both ASD and anxiety disorders. Using resting-state functional magnetic resonance imaging, we compared amygdala–prefrontal and amygdala–striatal connections across three demographically matched groups studied in the Autism Brain Imaging Data Exchange (ABIDE): ASD with a comorbid anxiety disorder (N = 25; ASD + Anxiety), ASD without a comorbid disorder (N = 68; ASD-NoAnx), and typically developing controls (N = 139; TD). Relative to ASD-NoAnx and TD controls, ASD + Anxiety individuals had decreased connectivity between the amygdala and dorsal/rostral anterior cingulate cortex (dACC/rACC). The functional connectivity of these connections was not affected in ASD-NoAnx, and amygdala connectivity with ventral ACC/medial prefrontal cortex (mPFC) circuits was not different in ASD + Anxiety or ASD-NoAnx relative to TD. Decreased amygdala–dorsomedial prefrontal cortex (dmPFC)/rACC connectivity was associated with more severe social impairment in ASD + Anxiety; amygdala–striatal connectivity was associated with restricted, repetitive behavior (RRB) symptom severity in ASD-NoAnx individuals. These findings suggest comorbid anxiety in ASD is associated with disrupted emotion-monitoring processes supported by amygdala–dACC/mPFC pathways, whereas emotion regulation systems involving amygdala–ventromedial prefrontal cortex (vmPFC) are relatively spared. Our results highlight the importance of accounting for comorbid anxiety for parsing ASD neurobiological heterogeneity.

scholarly journals Impact of Psychosocial Occupational Therapy Combined with Anodal Transcranial Direct Current Stimulation to the Left Dorsolateral Prefrontal Cortex on the Cognitive Performance of Patients with Schizophrenia: A Randomized Controlled Trial

2021 ◽  
pp. 156918612110651
Author(s):  
Elahe Fathi Azar ◽  
Samaneh Hosseinzadeh ◽  
Masoud Nosrat Abadi ◽  
Mohamad Sayad Nasiri ◽  
Hojjat Allah Haghgoo
Keyword(s):  
Prefrontal Cortex ◽  
Occupational Therapy ◽  
Cognitive Performance ◽  
Direct Current ◽  
Cognitive Functions ◽  
Visual Memory ◽  
Dorsolateral Prefrontal Cortex ◽  
Anodal Tdcs ◽  
Learning Abilities ◽  
Dorsolateral Prefrontal

Background The most common cognitive dysfunctions in patients with schizophrenia are information processing, memory, and learning. Based on the hypothesis of rehabilitation and brain stimulation in memory and learning, adding a form of neuromodulation to conventional rehabilitation might increase the effectiveness of treatments. Aims To explore the effects of psychosocial occupational therapy combined with anodal Transcranial Direct Current Stimulation (tDCS) on cognitive performance in patients with Schizophrenia. Methods Twenty-four patients diagnosed with schizophrenia were randomized into the experimental and control groups. We used The Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Loewenstein Occupational Therapy Cognitive Assessment battery (LOTCA) to assess spatial recognition, attention, visual memory, learning abilities, and high-level cognitive functions like problem-solving. All participants received customized psychosocial occupational therapy activities. Furthermore, the experimental group received 12 sessions of active anodal tDCS for 20 minutes with 2 mA intensity on the left dorsolateral prefrontal cortex (DLPFC) while the patients in the sham group received sham tDCS. Results Combining tDCS to conventional psychosocial occupational therapy resulted in a significant increase in spatial memory, visual learning, and attention. Conclusions Anodal tDCS on the left DLPFC improved visual memory, attention, and learning abilities. Contrary to our expectations, we could not find any changes in complex and more demanding cognitive functions.

scholarly journals Dorsolateral Prefrontal Cortex Activity during a Brain Training Game Predicts Cognitive Improvements after Four Weeks’ Brain Training Game Intervention: Evidence from a Randomized Controlled Trial

2020 ◽  
Vol 10 (8) ◽  
pp. 560
Author(s):  
Rui Nouchi ◽  
Natasha Yuriko dos Santos Kawata ◽  
Toshiki Saito ◽  
Robin Maximilian Himmelmeier ◽  
Ryo Nakamura ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Processing Speed ◽  
Cognitive Functions ◽  
Randomized Control Trial ◽  
Dorsolateral Prefrontal Cortex ◽  
Control Group ◽  
Brain Training ◽  
Intervention Period ◽  
Dorsolateral Prefrontal ◽  
Randomized Control

Background: Recent studies have demonstrated that brain activities using NIRS (near-infrared spectroscopy) at baseline during cognitive tasks (e.g., N-back task) can predict the cognitive benefits of a cognitive training. In this study, we investigated whether brain activities during brain training game (BT) at baseline would predict benefits to cognitive functions after the intervention period. Methods: In a four-week double-blinded randomized control trial (RCT) 72 young adults were randomly assigned to one of the two groups: participants in the BT group played specific game, called the Brain Age. Participants in an active control group (ACT) played the puzzle game Tetris. We measured brain activity during the training games using two channel NIRS before the intervention period. Cognitive functions were tested before and after the four-week intervention period. Results: The BT showed significant improvements in inhibition, processing speed, and working memory performance compared to ACT. The left and right DLPFC (dorsolateral prefrontal cortex) brain activities during the BT at baseline were associated with improvements in inhibition and processing speed. Discussion: This randomized control trial first provides scientific evidence that DLPFC activities during BT at baseline can predict cognitive improvements after a four-week intervention period.

Malfunctional Reorganization in the Developing Limbo-Prefrontal System in Animals: Implications for Human Psychoses?

2001 ◽  
Vol 12 (1) ◽  
pp. 8-14
Author(s):  
Gertraud Teuchert-Noodt ◽  
Ralf R. Dawirs
Keyword(s):  
Prefrontal Cortex ◽  
Mental Disorders ◽  
Dentate Gyrus ◽  
Cognitive Functions ◽  
Experimental Approach ◽  
Regulatory Mechanisms ◽  
Hippocampal Dentate Gyrus ◽  
Non Invasive ◽  
Invasive Method ◽  
Activity Dependent

Abstract: Neuroplasticity research in connection with mental disorders has recently bridged the gap between basic neurobiology and applied neuropsychology. A non-invasive method in the gerbil (Meriones unguiculus) - the restricted versus enriched breading and the systemically applied single methamphetamine dose - offers an experimental approach to investigate psychoses. Acts of intervening affirm an activity dependent malfunctional reorganization in the prefrontal cortex and in the hippocampal dentate gyrus and reveal the dopamine position as being critical for the disruption of interactions between the areas concerned. From the extent of plasticity effects the probability and risk of psycho-cognitive development may be derived. Advance may be expected from insights into regulatory mechanisms of neurogenesis in the hippocampal dentate gyrus which is obviously to meet the necessary requirements to promote psycho-cognitive functions/malfunctions via the limbo-prefrontal circuit.

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