The Pathophysiology of Tics; An Evolving Story

2020 ◽  
Vol 15 (2) ◽  
pp. 92-123 ◽  
Author(s):  
Harvey S. Singer ◽  
Farhan Augustine
Keyword(s):  
Motor Control ◽  
Primary Motor Cortex ◽  
Scientific Data ◽  
Anatomical Site ◽  
Pathophysiological Mechanism ◽  
Model Studies ◽  
Complex Disorder ◽  
Complex Integration ◽  
Motor Movements

Background: Tics, defined as quick, rapid, sudden, recurrent, non-rhythmic motor movements or vocalizations are required components of Tourette Syndrome (TS) - a complex disorder characterized by the presence of fluctuating, chronic motor and vocal tics, and the presence of co-existing neuropsychological problems. Despite many advances, the underlying pathophysiology of tics/TS remains unknown. Objective: To address a variety of controversies surrounding the pathophysiology of TS. More specifically: 1) the configuration of circuits likely involved; 2) the role of inhibitory influences on motor control; 3) the classification of tics as either goal-directed or habitual behaviors; 4) the potential anatomical site of origin, e.g. cortex, striatum, thalamus, cerebellum, or other(s); and 5) the role of specific neurotransmitters (dopamine, glutamate, GABA, and others) as possible mechanisms (Abstract figure). Methods: Existing evidence from current clinical, basic science, and animal model studies are reviewed to provide: 1) an expanded understanding of individual components and the complex integration of the Cortico-Basal Ganglia-Thalamo-Cortical (CBGTC) circuit - the pathway involved with motor control; and 2) scientific data directly addressing each of the aforementioned controversies regarding pathways, inhibition, classification, anatomy, and neurotransmitters. Conclusion: Until a definitive pathophysiological mechanism is identified, one functional approach is to consider that a disruption anywhere within CBGTC circuitry, or a brain region inputting to the motor circuit, can lead to an aberrant message arriving at the primary motor cortex and enabling a tic. Pharmacologic modulation may be therapeutically beneficial, even though it might not be directed toward the primary abnormality.

Inhibitory Mechanisms in the Motor Cortical Circuit

2017 ◽  
pp. 67-74
Author(s):  
Hugo Merchant ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Motor Control ◽  
Primary Motor Cortex ◽  
Pyramidal Cells ◽  
Local Inhibition ◽  
Inhibitory Mechanisms ◽  
Gating Mechanism ◽  
Cortical Circuit ◽  
Motor Cortical ◽  
Behaving Monkeys

Inhibitory mechanisms are crucial for the integrated operation of the motor cortical circuit. Local inhibition is exerted by interneurons that are GABAergic, nonpyramidal cells with short, nonprojecting axons. Interneurons can be classified into at least two groups: fast-spiking (FS) neurons and instrinsic bursting (IB) neurons. In the primary motor cortex, FS cells may sculpe the tuning dispersion of directionally selective putative pyramidal cells during reaching in behaving monkeys. Analysis of putative interneuronal activity also allowed to discard the role of inhibition as a gating mechanism in motor control. The development of high-density, semichronic electrode systems for extracellular recordings in behaving primates will allow a closer investigation of the role of interneuronal inhibition in directional tuning and voluntary motor control. The results discussed in this chapter agree with the authors’ proposal that local inhibitory mechanisms may be intimately involved in controlling the directional accuracy and speed of the reaching movement.

Controversies Surrounding the Pathophysiology of Tics

2019 ◽  
Vol 34 (13) ◽  
pp. 851-862 ◽  
Author(s):  
Harvey S. Singer ◽  
Farhan Augustine
Keyword(s):  
Animal Model ◽  
Basal Ganglia ◽  
Tourette Syndrome ◽  
Model Studies ◽  
Complex Interactions ◽  
Motor Movements ◽  
Premonitory Urge ◽  
Underlying Pathophysiology

Tics are sudden, rapid, recurrent, nonrhythmic motor movements or vocalizations (phonic productions) that are commonly present in children and are required symptoms for the diagnosis of Tourette syndrome. Despite their frequency, the underlying pathophysiology of tics/Tourette syndrome remains unknown. In this review, we discuss a variety of controversies surrounding the pathophysiology of tics, including the following: Are tics voluntary or involuntary? What is the role of the premonitory urge? Are tics due to excess excitatory or deficient inhibition? Is it time to adopt the contemporary version of the cortico-basal ganglia-thalamocortical (CBGTC) circuit? and Do we know the primary abnormal neurotransmitter in Tourette syndrome? Data from convergent clinical and animal model studies support complex interactions among the various CBGTC sites and neurotransmitters. Advances are being made; however, numerous pathophysiologic questions persist.

The Effect of PDE5 Inhibitors on the Male Reproductive Tract

2020 ◽  
Vol 26 ◽  
Author(s):  
Nikolaos Sofikitis ◽  
Aris Kaltsas ◽  
Fotios Dimitriadis ◽  
Jens Rassweiler ◽  
Nikolaos Grivas ◽  
...  
Keyword(s):  
Male Infertility ◽  
Reproductive Tract ◽  
Tunica Albuginea ◽  
Scientific Data ◽  
Secretory Function ◽  
Pde5 Inhibitors ◽  
Male Reproductive Tract ◽  
Review Study ◽  
Phosphodiesterase 5

The therapeutic range of cyclic nucleotide phosphodiesterase 5 inhibitors (PDE5) inhibitors is getting wider in the last years. This review study focuses on the potential employment of PDE5 inhibitors as an adjunct tool for the therapeutic management of male infertility. The literature tends to suggest a beneficial effect of PDE5 inhibitors on Leydig and Sertoli cells secretory function. It also appears that PDE5 inhibitors play a role in the regulation of the contractility of the testicular tunica albuginea and the epididymis. Moreover scientific data suggest that PDE5 inhibitors enhance the prostatic secretory function leading to an improvement in sperm motility. Other studies additionally demonstrate a role of PDE5 inhibitors in the regulation of sperm capacitation process. Placebo-controlled, randomized, blind studies are necessary to unambiguously incorporate PDE5 inhibitors as an adjunct tool for the pharmaceutical treatment of semen disorders and male infertility.

scholarly journals The Association of Human Herpesviruses with Malignant Brain Tumor Pathology and Therapy: Two Sides of a Coin

2021 ◽  
Vol 22 (5) ◽  
pp. 2250
Author(s):  
Evita Athanasiou ◽  
Antonios N. Gargalionis ◽  
Fotini Boufidou ◽  
Athanassios Tsakris
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Comprehensive Evaluation ◽  
Tumor Development ◽  
Scientific Data ◽  
Malignant Brain Tumor ◽  
Direct Role ◽  
Tumor Pathology ◽  
Human Herpesviruses

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.

scholarly journals Cortical and Striatal Electroencephalograms and Apomorphine Effects in the FUS Mouse Model of Amyotrophic Lateral Sclerosis

2021 ◽  
pp. 1-15
Author(s):  
Vasily Vorobyov ◽  
Alexander Deev ◽  
Frank Sengpiel ◽  
Vladimir Nebogatikov ◽  
Aleksey A. Ustyugov
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Cortical Neurons ◽  
Primary Motor Cortex ◽  
Beta Activity ◽  
Systemic Injection ◽  
Eeg Spectra ◽  
Electroencephalogram Eeg ◽  
Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons resulting in muscle atrophy. In contrast to the lower motor neurons, the role of upper (cortical) neurons in ALS is yet unclear. Maturation of locomotor networks is supported by dopaminergic (DA) projections from substantia nigra to the spinal cord and striatum. Objective: To examine the contribution of DA mediation in the striatum-cortex networks in ALS progression. Methods: We studied electroencephalogram (EEG) from striatal putamen (Pt) and primary motor cortex (M1) in ΔFUS(1–359)-transgenic (Tg) mice, a model of ALS. EEG from M1 and Pt were recorded in freely moving young (2-month-old) and older (5-month-old) Tg and non-transgenic (nTg) mice. EEG spectra were analyzed for 30 min before and for 60 min after systemic injection of a DA mimetic, apomorphine (APO), and saline. Results: In young Tg versus nTg mice, baseline EEG spectra in M1 were comparable, whereas in Pt, beta activity in Tg mice was enhanced. In older Tg versus nTg mice, beta dominated in EEG from both M1 and Pt, whereas theta and delta 2 activities were reduced. In younger Tg versus nTg mice, APO increased theta and decreased beta 2 predominantly in M1. In older mice, APO effects in these frequency bands were inversed and accompanied by enhanced delta 2 and attenuated alpha in Tg versus nTg mice. Conclusion: We suggest that revealed EEG modifications in ΔFUS(1–359)-transgenic mice are associated with early alterations in the striatum-cortex interrelations and DA transmission followed by adaptive intracerebral transformations.

scholarly journals COVID-19 Pathogenesis: From Molecular Pathway to Vaccine Administration

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 903
Author(s):  
Francesco Nappi ◽  
Adelaide Iervolino ◽  
Sanjeet Singh Avtaar Singh
Keyword(s):  
Hospital Setting ◽  
Pathophysiological Mechanism ◽  
Systemic Response ◽  
Respiratory Complications ◽  
Thrombotic Risk ◽  
Global Pandemic ◽  
The Impact ◽  
Multiple Variants ◽  
Roll Out

The Coronavirus 2 (SARS-CoV-2) infection is a global pandemic that has affected millions of people worldwide. The advent of vaccines has permitted some restitution. Aside from the respiratory complications of the infection, there is also a thrombotic risk attributed to both the disease and the vaccine. There are no reliable data for the risk of thromboembolism in SARS-CoV-2 infection in patients managed out of the hospital setting. A literature review was performed to identify the pathophysiological mechanism of thrombosis from the SARS-CoV-2 infection including the role of Angiotensin-Converting Enzyme receptors. The impact of the vaccine and likely mechanisms of thrombosis following vaccination were also clarified. Finally, the utility of the vaccines available against the multiple variants is also highlighted. The systemic response to SARS-CoV-2 infection is still relatively poorly understood, but several risk factors have been identified. The roll-out of the vaccines worldwide has also allowed the lifting of lockdown measures and a reduction in the spread of the disease. The experience of the SARS-CoV-2 infection, however, has highlighted the crucial role of epidemiological research and the need for ongoing studies within this field.

scholarly journals Cerebellar Dysfunction in Adults with Prader Willi Syndrome

2021 ◽  
Vol 10 (15) ◽  
pp. 3320
Author(s):  
Laura Blanco-Hinojo ◽  
Laia Casamitjana ◽  
Jesus Pujol ◽  
Gerard Martínez-Vilavella ◽  
Susanna Esteba-Castillo ◽  
...  
Keyword(s):  
Motor Control ◽  
Motor Function ◽  
Motor Coordination ◽  
Task Demands ◽  
Functional Mobility ◽  
Prader Willi Syndrome ◽  
Pathophysiological Mechanism ◽  
Motor Tasks ◽  
Correlation Pattern ◽  
Motor Processing

Severe hypotonia during infancy is a hallmark feature of Prader Willi syndrome (PWS). Despite its transient expression, moto development is delayed and deficiencies in motor coordination are present at older ages, with no clear pathophysiological mechanism yet identified. The diverse motor coordination symptoms present in adult PWS patients could be, in part, the result of a common alteration(s) in basic motor control systems. We aimed to examine the motor system in PWS using functional MRI (fMRI) during motor challenge. Twenty-three adults with PWS and 22 matched healthy subjects participated in the study. fMRI testing involved three hand motor tasks of different complexity. Additional behavioral measurements of motor function were obtained by evaluating hand grip strength, functional mobility, and balance. Whole brain activation maps were compared between groups and correlated with behavioral measurements. Performance of the motor tasks in PWS engaged the neural elements typically involved in motor processing. While our data showed no group differences in the simplest task, increasing task demands evoked significantly weaker activation in patients in the cerebellum. Significant interaction between group and correlation pattern with measures of motor function were also observed. Our study provides novel insights into the neural substrates of motor control in PWS by demonstrating reduced cerebellar activation during movement coordination.

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