Targeted Circuit Manipulations in the Modeling of OCD

Author(s):  
Susanne E. Ahmari

Work in animal models has great potential to shed light on the neural circuit perturbations that lead to OCD-related behaviors. Circuit-specific manipulations allow testing of the causal role of the brain network abnormalities observed in clinical imaging studies, with a precision that is not possible in investigations in humans. In recent years, circuit-specific manipulations in animals using a range of technologies have confirmed that abnormalities in the cortico-striatal circuitry can produce repetitive behaviors, such as excessive grooming. This chapter summarizes these advances. Refining our understanding of the contribution of particular neural circuits to OCD-relevant behaviors can inform the development of anatomically targeted treatments, such as deep brain stimulation.

1996 ◽  
Vol 76 (1) ◽  
pp. 193-244 ◽  
Author(s):  
P. B. Persson

It is generally held that the role of a specific control element can only be understood within its physiological environment. The reviewed studies make it clear that there is a potent interplay between locally produced substances such as adenosine, nitric oxide, prostaglandins, and various others all interacting with the central level of control. This can occur at central sites (e.g., nitric oxide in the brain) or in the periphery (e.g., neural influence on autoregulation). The interactions are more or less pronounced during specific physiological challenges. Furthermore, several of these interactions are altered under pathological circumstances, and in some cases, the interactions seem to maintain or even augment the severity of disease. When more than three parameters participate in an interaction, the resulting regulation may become extremely complex. If these parameters are nonlinearly coupled with each other, the only way to shed light onto the nature of control network is by treating it as a black box. With the use of spectral analysis or nonlinear methods, it is possible to disentangle the fundamental nature of the system in terms of the complexity and stability. Therefore, modern developments in cardiovascular physiology utilizing these techniques, some of which are derived from the "chaos theory," are reviewed.


2022 ◽  
pp. 109-126
Author(s):  
Omar El Hiba ◽  
Hicham Chatoui ◽  
Nadia Zouhairi ◽  
Lahoucine Bahi ◽  
Lhoussaine Ammouta ◽  
...  

Since December 2019, the world has been shaken by the spread of a highly pathogen virus, causing severe acute respiratory syndrome (SARS-Cov2), which emerged in Wuhan, China. SARS-Cov2 is known to cause acute pneumonia: the cardinal feature of coronavirus disease 2019 (COVID-19). Clinical features of the disease include respiratory distress, loss of spontaneous breathing, and sometimes neurologic signs such as headache and nausea and anosmia, leading to suppose a possible involvement of the nervous system as a potential target of SARS-CoV2. The chapter will shed light on the recent clinical and experimental data sustaining the involvement of the nervous system in the pathophysiology of COVID-19, based on several case reports and experimental data reporting the possible transmission of SARS-CoV2 throughout the peripheral nerves to the brain cardiorespiratory centers. Thus, understanding the role of the nervous system in the course of clinical symptoms of COVID-19 is important in determining the appropriate therapeutic approach to combat the disease.


CNS Spectrums ◽  
2016 ◽  
Vol 22 (3) ◽  
pp. 290-294 ◽  
Author(s):  
Donatella Marazziti ◽  
Stefano Baroni ◽  
Gino Giannaccini ◽  
Armando Piccinni ◽  
Federico Mucci ◽  
...  

ObjectiveThe role of dopamine (DA) in romantic love is suggested by different evidence and is supported by the findings of some brain imaging studies. The DA transporter (DAT) is a key structure in regulating the concentration of the neurotransmitter in the synaptic cleft. Given the presence of DAT in blood cells, the present study aimed to explore it in resting lymphocytes of 30 healthy subjects of both sexes in the early stage of romantic love (no longer than 6 months), as compared with 30 subjects involved in a long-lasting relationship.MethodsAll subjects had no physical or psychiatric illness. The DAT was measured by means of the [3H]-WIN 35,428 binding and the [3H]-DA reuptake to resting lymphocytes membranes. Romantic love was assessed by a specific questionnaire developed by us.ResultsThe results showed that the subjects in the early phase of romantic love had a global alteration of the lymphocyte DAT involving both a decreased number of proteins (Bmax) and a reduced functionality (Vmax).ConclusionsTaken together, these findings would indicate the presence of increased levels of DA in romantic love that, if paralleled by similar concentrations in the brain, would explain some peculiar features of this human feeling.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhibao Li ◽  
Chong Liu ◽  
Qiao Wang ◽  
Kun Liang ◽  
Chunlei Han ◽  
...  

Objective: The objective of this study was to use functional connectivity and graphic indicators to investigate the abnormal brain network topological characteristics caused by Parkinson's disease (PD) and the effect of acute deep brain stimulation (DBS) on those characteristics in patients with PD.Methods: We recorded high-density EEG (256 channels) data from 21 healthy controls (HC) and 20 patients with PD who were in the DBS-OFF state and DBS-ON state during the resting state with eyes closed. A high-density EEG source connectivity method was used to identify functional brain networks. Power spectral density (PSD) analysis was compared between the groups. Functional connectivity was calculated for 68 brain regions in the theta (4–8 Hz), alpha (8–13 Hz), beta1 (13–20 Hz), and beta2 (20–30 Hz) frequency bands. Network estimates were measured at both the global (network topology) and local (inter-regional connection) levels.Results: Compared with HC, PSD was significantly increased in the theta (p = 0.003) frequency band and was decreased in the beta1 (p = 0.009) and beta2 (p = 0.04) frequency bands in patients with PD. However, there were no differences in any frequency bands between patients with PD with DBS-OFF and DBS-ON. The clustering coefficient and local efficiency of patients with PD showed a significant decrease in the alpha, beta1, and beta2 frequency bands (p < 0.001). In addition, edgewise statistics showed a significant difference between the HC and patients with PD in all analyzed frequency bands (p < 0.005). However, there were no significant differences between the DBS-OFF state and DBS-ON state in the brain network, except for the functional connectivity in the beta2 frequency band (p < 0.05).Conclusion: Compared with HC, patients with PD showed the following characteristics: slowed EEG background activity, decreased clustering coefficient and local efficiency of the brain network, as well as both increased and decreased functional connectivity between different brain areas. Acute DBS induces a local response of the brain network in patients with PD, mainly showing decreased functional connectivity in a few brain regions in the beta2 frequency band.


SLEEP ◽  
2020 ◽  
Author(s):  
Kun-Hsien Chou ◽  
Pei-Lin Lee ◽  
Chih-Sung Liang ◽  
Jiunn-Tay Lee ◽  
Hung-Wen Kao ◽  
...  

Abstract Study Objectives While insomnia and migraine are often comorbid, the shared and distinct neuroanatomical substrates underlying these disorders and the brain structures associated with the comorbidity are unknown. We aimed to identify patterns of neuroanatomical substrate alterations associated with migraine and insomnia comorbidity. Methods High-resolution T1-weighted images were acquired from subjects with insomnia, migraine, and comorbid migraine and insomnia, respectively, and healthy controls (HC). Direct group comparisons with HC followed by conjunction analyses identified shared regional gray matter volume (GMV) alterations between the disorders. To further examine large-scale anatomical network changes, a seed-based structural covariance network (SCN) analysis was applied. Conjunction analyses also identified common SCN alterations in two disease groups, and we further evaluated these shared regional and global neuroanatomical signatures in the comorbid group. Results Compared with controls, patients with migraine and insomnia showed GMV changes in the cerebellum and the lingual, precentral, and postcentral gyri (PCG). The bilateral PCG were common GMV alteration sites in both groups, with decreased structural covariance integrity observed in the cerebellum. In patients with comorbid migraine and insomnia, shared regional GMV and global SCN changes were consistently observed. The GMV of the right PCG also correlated with sleep quality in these patients. Conclusion These findings highlight the specific role of the PCG in the shared pathophysiology of insomnia and migraine from a regional and global brain network perspective. These multilevel neuroanatomical changes could be used as potential image markers to decipher the comorbidity of the two disorders.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1124 ◽  
Author(s):  
Stephen Tisch

Within the field of movement disorders, the conceptual understanding of dystonia has continued to evolve. Clinical advances have included improvements in recognition of certain features of dystonia, such as tremor, and understanding of phenotypic spectrums in the genetic dystonias and dystonia terminology and classification. Progress has also been made in the understanding of underlying biological processes which characterize dystonia from discoveries using approaches such as neurophysiology, functional imaging, genetics, and animal models. Important advances include the role of the cerebellum in dystonia, the concept of dystonia as an aberrant brain network disorder, additional evidence supporting the concept of dystonia endophenotypes, and new insights into psychogenic dystonia. These discoveries have begun to shape treatment approaches as, in parallel, important new treatment modalities, including magnetic resonance imaging-guided focused ultrasound, have emerged and existing interventions such as deep brain stimulation have been further refined. In this review, these topics are explored and discussed.


2011 ◽  
Vol 7 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Rosa C. Paolicelli ◽  
Cornelius T. Gross

Microglia are enigmatic non-neuronal cells that infiltrate and take up residence in the brain during development and are thought to perform a surveillance function. An established literature has documented how microglia are activated by pathogenic stimuli and how they contribute to and resolve injuries to the brain. However, much less work has been aimed at understanding their function in the uninjured brain. A series of recent in vivo imaging studies shows that microglia in their resting state are highly motile and actively survey their neuronal surroundings. Furthermore, new data suggest that microglia in their resting state are able to phagocytose unwanted synapses and in this way contribute to synaptic pruning and maturation during development. Coupled with their exquisite sensitivity to pathogenic stimuli, these data suggest that microglia form a link that couples changes in brain environment to changes in brain wiring. Here we discuss this hypothesis and propose a model for the role of microglia during development in sculpting brain connectivity.


1997 ◽  
Vol 42 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Nancy C Andreasen

Background: Explaining the diversity of symptoms that occur in schizophrenia is a major conceptual challenge. Perhaps the most powerful strategy is to identify a fundamental cognitive process and/or a fundamental neural circuit. Methods: Convergent data from our research group in Iowa and from investigators in other centres are summarized. Results: The thalamus plays a key role in information processing. A defect in circuitry connecting the thalamus, frontal cortex, and cerebellum could explain a wide range of symptoms. Neuropathology and imaging studies suggest that patients with schizophrenia may have abnormalities in this circuitry. Conclusion: The fundamental deficit in schizophrenia may be conceptualized as a “cognitive dysmetria” characterized by impairments in coordinating the perception, encoding, retrieval, and prioritization of experience and information.


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