scholarly journals Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse

2021 ◽  
Vol 11 (10) ◽  
pp. 1353
Author(s):  
Eliana Lousada ◽  
Mathieu Boudreau ◽  
Julien Cohen-Adad ◽  
Brahim Nait Oumesmar ◽  
Eric Burguière ◽  
...  
Keyword(s):  
Open Source Software ◽  
Knockout Mouse ◽  
Structural Changes ◽  
Reference Model ◽  
Structural Connectivity ◽  
Repetitive Behaviours ◽  
Obsessive Compulsive ◽  
Structural Characterisation ◽  
Compulsive Disorder ◽  
Myelin Thickness

Pathological repetitive behaviours are a common feature of various neuropsychiatric disorders, including compulsions in obsessive–compulsive disorder or tics in Gilles de la Tourette syndrome. Clinical research suggests that compulsive-like symptoms are related to associative cortico-striatal dysfunctions, and tic-like symptoms to sensorimotor cortico-striatal dysfunctions. The Sapap3 knockout mouse (Sapap3-KO), the current reference model to study such repetitive behaviours, presents both associative as well as sensorimotor cortico-striatal dysfunctions. Previous findings point to deficits in both macro-, as well as micro-circuitry, both of which can be affected by neuronal structural changes. However, to date, structural connectivity has not been analysed. Hence, in the present study, we conducted a comprehensive structural characterisation of both associative and sensorimotor striatum as well as major cortical areas connecting onto these regions. Besides a thorough immunofluorescence study on oligodendrocytes, we applied AxonDeepSeg, an open source software, to automatically segment and characterise myelin thickness and axon area. We found that axon calibre, the main contributor to changes in conduction speed, is specifically reduced in the associative striatum of the Sapap3-KO mouse; myelination per se seems unaffected in associative and sensorimotor cortico-striatal circuits.

scholarly journals Reduced axon caliber in the associative striatum of the Sapap3 knockout mouse

2021 ◽  
Author(s):  
E. Lousada ◽  
M. Boudreau ◽  
J. Cohen-Adad ◽  
B. Nait Oumesmar ◽  
E. Burguière ◽  
...  
Keyword(s):  
Open Source Software ◽  
Knockout Mouse ◽  
Structural Changes ◽  
Reference Model ◽  
Research Literature ◽  
Repetitive Behaviors ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Fundamental Research ◽  
Myelin Thickness

AbstractPathological repetitive behaviors are a common feature of different neuropsychiatric disorders such as obsessive-compulsive disorder or Gilles de la Tourette syndrome. The Sapap3 knockout mouse (Sapap3-KO) is the current reference model used in translational psychiatry to study co-morbid repetitive behaviors, presenting both compulsive-like as well as tic-like behaviors. Consistent with clinical and fundamental research literature relating compulsive-like symptoms to associative cortico-striatal dysfunctions and tic-like symptoms to sensorimotor cortico-striatal dysfunctions, abnormalities comprising both circuits have been described in this mouse model. Findings reported on these mice point towards not only macro-, but also micro-circuitry deficits, both of which can be affected by neuronal structural changes. As such, in the present study, we aimed to investigate structural changes in associative and sensorimotor striatal areas that could affect information conduction. We used AxonDeepSeg, an open-source software to automatically segment and measure myelin thickness and axon caliber, and found that axon caliber, the main contributor for changes in conduction speed, is specifically reduced in the associative but not the sensorimotor striatum of the Sapap3-KO mouse. This smaller axon caliber in Sapap3-KO mice is not a general neuronal feature of this region, but specific to a subpopulation of axons with large caliber. These results point to a primary structural deficit in the associative striatum, affecting signal conduction and consequent connectivity.

OCD

2018 ◽  
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Intrusive Thoughts ◽  
Repetitive Behaviours ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

People with Obsessive Compulsive Disorder (OCD) experience unpleasant and intrusive thoughts, images, doubts or urges (called obsessions) and repetitive behaviours (called compulsions). Compulsions are usually carried out as a way of reducing the distress caused by obsessions. OCD takes many different forms and causes distress and interference to day-to-day life. 

scholarly journals Functional and structural connectivity of the amygdala in obsessive-compulsive disorder

2017 ◽  
Vol 13 ◽  
pp. 246-255 ◽  
Author(s):  
Oana Georgiana Rus ◽  
Tim Jonas Reess ◽  
Gerd Wagner ◽  
Claus Zimmer ◽  
Michael Zaudig ◽  
...  
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Structural Connectivity ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

on the Differential Diagnosis of Obsessive-compulsive Symptoms in Schizophrenia: A Conceptual and Clinical Analysis

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
P. Michalopoulou ◽  
P. Oulis ◽  
G. Konstantakopoulos ◽  
L. Lykouras
Keyword(s):  
Differential Diagnosis ◽  
Conceptual Analysis ◽  
A Priori ◽  
Clinical Analysis ◽  
Repetitive Behaviours ◽  
Obsessive Compulsive ◽  
General Psychopathology ◽  
Compulsive Disorder ◽  
Icd 10 ◽  
Dsm Iv

Several shortcomings of the current psychodiagnostic manuals (DSM-IV, ICD-10) with respect to obsessive-compulsive disorder, such as the diagnostic parity of obsessions and compulsions and the deficient conceptualization of compulsions might artificially inflate the clinical prevalence of obsessive-compulsive (OC) symptoms in the course of schizophrenic disorders. Still, one cannot exclude on purely a priori grounds the possibility of a genuine coexistence of OC symptoms along with delusions in patients with schizophrenia. the aim of the present study was to provide a contrastive conceptual analysis of typical features of obsessions versus those of delusions and correlatively of compulsions versus delusionally-motivated repetitive behaviours, supplemented by four relevant vignettes as clinical tests of its adequacy. Although preliminary, the results of our conceptual and illustrative analyses suggest that General Psychopathology can afford the conceptual resources for the accurate differential diagnosis obsession/compulsions from delusions/delusionally-motivated repetitive behaviours. in turn, this would provide a more solid clinical ground for the investigation of the epidemiology and the pathophysiology of OC symptoms in schizophrenic disorders.

scholarly journals Altered frontal interhemispheric and fronto‐limbic structural connectivity in unmedicated adults with obsessive‐compulsive disorder

2017 ◽  
Vol 39 (2) ◽  
pp. 803-810 ◽  
Author(s):  
Xiaofu He ◽  
Emily Steinberg ◽  
Mihaela Stefan ◽  
Martine Fontaine ◽  
H. Blair Simpson ◽  
...  
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Structural Connectivity ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

scholarly journals Maintained Visual-, Auditory-, and Multisensory-Guided Associative Learning Functions in Children With Obsessive–Compulsive Disorder

2020 ◽  
Vol 11 ◽  
Author(s):  
Ákos Pertich ◽  
Gabriella Eördegh ◽  
Laura Németh ◽  
Orsolya Hegedüs ◽  
Dorottya Öri ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Associative Learning ◽  
Obsessive Compulsive Disorder ◽  
Structural Changes ◽  
Reaction Times ◽  
Obsessive Compulsive ◽  
Sensory Stimuli ◽  
Compulsive Disorder ◽  
Acquired Equivalence ◽  
Learning Functions

Sensory-guided acquired equivalence learning, a specific kind of non-verbal associative learning, is associated with the frontal cortex–basal ganglia loops and hippocampi, which seem to be involved in the pathogenesis of obsessive–compulsive disorder (OCD). In this study, we asked whether visual-, auditory-, and multisensory-guided associative acquired equivalence learning is affected in children with OCD. The first part of the applied learning paradigm investigated association building between two different sensory stimuli (where feedback was given about the correctness of the choices), a task that critically depends upon the basal ganglia. During the test phases, which primarily depended upon the hippocampi, the earlier learned and hitherto not shown but predictable associations were asked about without feedback. This study involved 31 children diagnosed with OCD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria and 31 matched healthy control participants. The children suffering from OCD had the same performance as the control children in all phases of the applied visual-, auditory-, and multisensory-guided associative learning paradigms. Thus, both the acquisition and test phases were not negatively affected by OCD. The reaction times did not differ between the two groups, and the applied medication had no effect on the performances of the OCD patients. Our results support the findings that the structural changes of basal ganglia and hippocampi detected in adult OCD patients are not as pronounced in children, which could be the explanation of the maintained associative equivalence learning functions in children suffering from OCD.

145 Tractography-defined Subregions of Human Nucleus Accumbens Predict Acute Anxiolytic Response to Selective Stimulation

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 234-235
Author(s):  
Sam Cartmell ◽  
Qiyuan Tian ◽  
Nolan Williams ◽  
Kai Miller ◽  
Grant Yang ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Structural Connectivity ◽  
Brain Regions ◽  
Reward Processing ◽  
Clinical Effects ◽  
Obsessive Compulsive ◽  
Electrical Currents ◽  
Compulsive Disorder ◽  
Human Connectome Project ◽  
Monopolar Stimulation

Abstract INTRODUCTION The nucleus accumbens (NAc) serves as a key node in reward processing underlying motivated behavior, and its dysfunction is implicated in a host of psychiatric disorders that are amenable to deep brain stimulation (DBS). On the basis of histochemical and structural connectivity data most thoroughly conducted in animals, the NAc is divided into two primary subregions, core (dorsolateral) and shell (ventromedial), which have dissociable afferent and efferent connections and functions. To characterize NAc subregions, the current study used high-resolution diffusion tractography to delineate core and shell and assessed the immediate clinical implications. METHODS Multimodal MRI data from 245 healthy, unrelated subjects was obtained from the Human Connectome Project database. Freesurfer-generated brain regions were used to perform probabilistic tractography using every NAc voxel as seed and every other Freesurfer region as target. NAc voxels with similar connectivity fingerprints were grouped using k-means clustering. This procedure was also performed retrospectively on two other datasets of lesser quality, including that of one patient with obsessive-compulsive disorder who underwent bilateral DBS lead placement targeting the NAc. The final position of the DBS leads relative to tractography-defined subregions was determined, and the effect of monopolar stimulation on self-reported anxiety utilizing subregion-specific contacts was assessed utilizing a Likert scale. RESULTS >Tractography-based segmentation of the NAc produced ventromedial and dorsolateral subregions across subjects and datasets, consistent with prior histochemical evidence from humans. At electrical currents as low as 1.6 mA, monopolar stimulation of dorsolateral but not ventromedial subregions produced an acute reduction in self-reported anxiety. CONCLUSION NAc subregions that resemble histologically defined core and shell with dissociable acute clinical effects can be produced with tractography-based segmentation. These results have implications for DBS targeting of the NAc, and may help to explain variances in clinical outcome among patients receiving NAc DBS to date.

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