Cortico-striato-thalamo-cortical Circuit Research Articles

White matter integrity correlates with choline level in dorsal anterior cingulate cortex of obsessive compulsive disorder patients: A combined DTI-MRS study.

Structural and functional neuroimaging studies have indicated that the cortico-striato -thalamo-cortical (CSTC) circuit contributes to the pathophysiology of obsessive compulsive disorder (OCD). As an essential component of CSTC circuit, the dorsal anterior cingulate cortex (dACC) plays an important role for its advanced function in cognition and emotion control. A comprehensive understanding of the dACC disruption in OCD pathological mechanism is desired. In this study, we performed a combined diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) study in 15 OCD patients and 15 healthy controls to investigate the association between structural abnormality and metabolic alterations within the dACC area. We found a positive correlation between the dACC fractional anisotropy (FA) value and choline concentration in patients. Moreover, the FA was positively associated with OCD clinical symptom, especially the compulsive behavior, which showed the clinical relevance of dACC white matter integrity in OCD. To our knowledge, the present work is the first combined DTI-MRS study of OCD. Our findings demonstrated the co-occurrence of structural and metabolic changes within dACC in OCD patients. It was suggested that the disrupted white matter integrity might be accompanied with degraded cellular membrane turnover.

Intrinsic functional connectivity alteration of dorsal and rostral anterior cingulate cortex in obsessive-compulsive disorder: A resting fMRI study.

Cortico-striato-thalamo-cortical (CSTC) circuit has been implicated in OCD pathophysiology by converging neuroimaging findings. The anterior cingulate cortex (ACC), as an important part within CSTC circuit, plays a critical role in OCD etiology. The ACC can be divided into dorsal and rostral parts anatomically, which are involved in cognitive process and emotional function, respectively. However, the diverse function of intrinsic signals from dorsal and rostral ACC regions remains unclear in OCD study. In this work, we applied resting-state functional magnetic resonance imaging (rs-fMRI) technology to investigate and differentiate the functional connectivity (FC) characteristics between dACC and rACC in unmedicated OCD patients. Also, the correlation between the altered FC and clinical symptom severity was analyzed. Decreased FC of rACC-DLPFC and increased FC between dACC and caudate were found. Moreover, the altered dACC-caudate FC was positively correlated with total Y-BOCS and compulsion score in OCD patients. Our findings implied the crossed function of dorsal and rostral circuits in the pathophysiologic mechanism of OCD. The dorsal cingulate-striatum functional pathway served as a potential biomarker for OCD symptomatology and merits further investigations.

Clinical practice guidelines for Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a common psychiatric illness with lifetime prevalence of 1-3% [1]. It is the fourth-most common psychiatric illness and a leading cause of disability. OCD is associated with significant impairment in functioning, quality of life and disability. If untreated, OCD is a chronic illness with a waxing and waning of symptoms. A recent meta-analysis of long-term naturalistic prospective studies demonstrated that nearly a half of patients experience remission with much higher rates of remission in Indian patients compared to those in the west [2]. Early diagnosis and appropriate treatment may improve outcomes. Despite OCD being a common mental illness, most seek treatment after several years of suffering. Those who suffer from OCD tend to be secretive about their symptoms and suffer from shame and embarrassment. Less than a third of OCD sufferers receive appropriate pharmacotherapy and even less receive evidence-based psychotherapy. Symptoms The hallmarks of OCD are presence of obsessions and compulsions. Obsessions are repetitive, unwanted, intrusive thoughts, images or urges that are mostly ego-dystonic and cause severe distress or anxiety. Compulsions (or rituals) are repetitive behaviours or mental acts that are performed in response to an obsession to reduce anxiety/distress or prevent a dreaded consequence. Obsessions and compulsions are time consuming, distressing and are often resisted unsuccessfully. Clinical manifestations of OCD are remarkably similar across cultures and geographic locations. Common obsessions and compulsions and symptom dimensions identified through factor-analytical studies are shown in Table 1. Table 1 Common symptoms of OCD

Brain Gamma-Aminobutyric Acid (GABA) Concentration of the Prefrontal Lobe in Unmedicated Patients with Obsessive-Compulsive Disorder: A Research of Magnetic Resonance Spectroscopy.

BackgroundIn recent years, a large number of neuroimaging studies found that the Cortico-Striato- Thalamo-Cortical circuit (CSTC), including the prefrontal lobe, a significant part of CSTC, has disturbance metabolically in patients with Obsessive-Compulsive Disorder (OCD).AimExplore the correlation between the neuro-metabolic features and clinical characteristics of OCD patients using magnetic resonance spectroscopy technology.Methods88 patients with OCD who were not received medication and outpatient treatment for 8 weeks and 76 health controls were enrolled, there was no significant difference in gender, age or education level between the two groups. SIEMENS 3.0T MRI scanner was used to measure the spectral wave of Orbito Frontal Cortex (OFC) and Anterior Cingulate Cortex (ACC) of participants, setting mega-press sequences. Meanwhile, the concentrations of gamma-aminobutyric acid (GABA), glutamine/glutamate complex (Glx) and N-Acetyl Aspartate (NAA) were measured relative to concentration of water, on the ACC and OFC of participants, for statistical analysis via LC model version 6.3 software. The concentration of metabolic substances of the OCD group compared to the healthy control group was analyzed using two sample t-test. The correlation between substance concentration and scores on the scales, including Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety scale (HAMA) and Hamilton Depression scale (HAMD) was carried out using the Pearson correlation method.ResultsCompared with healthy controls, the GABA/W and NAA/W concentration in individuals with OCD are significantly decreased (p=0.031, t=2.193, p=0.002, t=3.223). Also, the concentration of GABA/W had a trend of decrease in the ACC. The GABA/W of the OFC had a negative correlation with Y-BOCS-O, Y-BOCS-C and Y-BOCS-T scores (p=0.037, r=0.221; p=0.007, r=0.283; p=0.014, r=0.259).ConclusionsThese results support that GABA concentration in the OFC area of patients with OCD is significantly decreased and the concentration in the ACC has a trend of decreasing. All of these indicate that there is a relationship between the GABA concentration and the psychopathology of OCD.

Cortico-Striato-Thalamo-Cortical Circuitry, Working Memory, and Obsessive-Compulsive Disorder.

Cortico-Striato-Thalamo-Cortical Circuitry, Working Memory, and Obsessive-Compulsive Disorder.

Altered intrinsic insular activity predicts symptom severity in unmedicated obsessive-compulsive disorder patients: a resting state functional magnetic resonance imaging study.

BackgroundPrevious neuroimaging data indicated that the dysfunction in cortico-striato-thalamo-cortical (CSTC) circuit contributed to the neuropathological mechanism of obsessive-compulsive disorder (OCD). Whereas, emerging work has shown that the pathophysiology of OCD might be related to more widely distributed large-scale brain systems including limbic system and the salience network. This study aims to investigate the aberrant spontaneous neuronal activity within the whole brain, and its association with the symptom severity for unmedicated OCD patients.MethodTwenty-eight unmedicated OCD adults and twenty-eight matched healthy controls were recruited for a resting state functional magnetic resonance imaging (fMRI) study. The amplitude of low-frequency fluctuation (ALFF) analysis over whole brain was performed to examine the intrinsic cerebral activity of subjects. In addition, we conducted the voxel-based Pearson’s correlative analysis to probe into the relationship between ALFF values and symptom severity for OCD patients.ResultsOur results showed that OCD patients had increased ALFF measures in the left frontopolar cortex and left orbital frontal cortex (OFC), with decreased ALFF values in the right insula. Moreover, the right insular intrinsic activity was significantly correlated with total YBOCS score (r = 0.611, p = 0.002) and compulsion score (r = 0.640, p = 0.001) for OCD patients.ConclusionThe results showed abnormal intrinsic neuronal activity within CSTC circuit and salience network of OCD patients. Our finding of aberrant insular activity advanced the understanding of OCD pathophysiology beyond the traditional CSTC circuit. To the best of our knowledge, it is the first finding about a reduced insular activity at the resting state for unmedicated OCD patients, which might serve as an informative biomarker for OCD pathophysiology.

Combining tract- and atlas-based analysis reveals microstructural abnormalities in early Tourette syndrome children.

Tourette syndrome (TS) is a neurological disorder that causes uncontrolled repetitive motor and vocal tics in children. Examining the neural basis of TS churned out different research studies that advanced our understanding of the brain pathways involved in its development. Particularly, growing evidence points to abnormalities within the fronto-striato-thalamic pathways. In this study, we combined Tract-Based Spatial Statistics (TBSS) and Atlas-based regions of interest (ROI) analysis approach, to investigate the microstructural diffusion changes in both deep and superficial white matter (SWM) in TS children. We then characterized the altered microstructure of white matter in 27 TS children in comparison with 27 age- and gender-matched healthy controls. We found that fractional anisotropy (FA) decreases and radial diffusivity (RD) increases in deep white matter (DWM) tracts in cortico-striato-thalamo-cortical (CSTC) circuit as well as SWM. Furthermore, we found that lower FA values and higher RD values in white matter regions are correlated with more severe tics, but not tics duration. Besides, we also found both axial diffusivity and mean diffusivity increase using Atlas-based ROI analysis. Our work may suggest that microstructural diffusion changes in white matter is not only restricted to the gray matter of CSTC circuit but also affects SWM within the primary motor and somatosensory cortex, commissural and association fibers. Hum Brain Mapp 37:1903-1919, 2016. © 2016 Wiley Periodicals, Inc.

Circuits regulating pleasure and happiness in major depression

The introduction of selective serotonin reuptake inhibitors has gradually changed the borders of the major depression disease class. Anhedonia was considered a cardinal symptom of endogenous depression, but the potential of selective serotonin reuptake inhibitors to treat anxiety disorders has increased the relevance of stress-induced morbidity. This shift has led to an important heterogeneity of current major depressive disorder. The complexity can be disentangled by postulating the existence of two different but mutually interacting neuronal circuits regulating the intensity of anhedonia (lack of pleasure) and dysphoria (lack of happiness). These circuits are functionally dominated by partly closed limbic (regulating misery-fleeing behaviour) and extrapyramidal (regulating reward-seeking behaviour) cortico-striato-thalamo-cortical (CSTC) circuits. The re-entry circuits include the shell and core parts of the accumbens nucleus, respectively. Pleasure can be considered to result from finding relief from the hypermotivation to exhibit rewarding behaviour, and happiness from finding relief from negative or conflicting circumstances. Hyperactivity of the extrapyramidal CSTC circuit results in craving, whereas hyperactivity of the limbic system results in dysphoria.

Abnormal functional connectivity of brain network hubs associated with symptom severity in treatment-naive patients with obsessive–compulsive disorder: A resting-state functional MRI study

ObjectiveAbnormal brain networks have been observed in patients with obsessive–compulsive disorder (OCD). However, detailed network hub and connectivity changes remained unclear in treatment-naive patients with OCD. Here, we sought to determine whether patients show hub-related connectivity changes in their whole-brain functional networks. MethodsWe used resting-state functional magnetic resonance imaging data and voxel-based graph-theoretic analysis to investigate functional connectivity strength and hubs of whole-brain networks in 29 treatment-naive patients with OCD and 29 age- and gender-matched healthy controls. Correlation analysis was applied for potential associations with OCD symptom severity. ResultsOCD selectively targeted brain regions of higher functional connectivity strength than the average including brain network hubs, mainly distributed in the cortico–striato–thalamo-cortical (CSTC) circuits and additionally parietal, occipital, temporal and cerebellar regions. Moreover, affected functional connectivity strength in the cerebellum, the medial orbitofrontal cortex and superior occipital cortex was significantly associated with global OCD symptom severity. ConclusionOur results provide the evidence about OCD-related brain network hub changes, not only in the CSTC circuits but more distributed in whole brain networks. Data suggest that whole brain network hub analysis is useful for understanding the pathophysiology of OCD.

Decreased thalamic glutamate level in unmedicated adult obsessive–compulsive disorder patients detected by proton magnetic resonance spectroscopy

BackgroundPrevious neuroimaging studies implied that the dysfunction of cortico–striato–thalamo–cortical (CSTC) circuit served as the neural basis for the pathophysiology of obsessive–compulsive disorder (OCD). The imbalances in neuronal metabolite and neurotransmitter within CSTC circuit have been shown as the leading reasons of the OCD onset. The aim of this study is to investigate the metabolic alterations, especially the glutamatergic signal dysfunction within CSTC circuit, and the relationships between neural metabolites and the symptom severity of OCD patients. MethodsSingle voxel magnetic resonance spectroscopy (MRS) was conducted in medial prefrontal cortex (mPFC) and bilateral thalamus areas for thirteen unmedicated adult OCD patients with age-, gender-, and education-matched healthy controls. Quantification and multivariate analysis were performed to identify vital metabolic biomarkers for patients and healthy controls group differentiation. Moreover, we performed Spearman׳s rank correlation analysis for OCD patients to examine the relationship between the metabolite concentration level and OCD symptomatology. ResultsPatients with OCD showed significantly decreased glutamate level in mPFC (p=0.021) and right thalamus (p=0.039), and significantly increased choline compounds in left thalamus (p=0.044).The glutamate in right thalamus was shown as the most important metabolite for group separation from multivariate analysis (Q2=0.134) and was significantly correlated with the patients׳ compulsion scores (Spearman r=−0.674, p=0.016). LimitationsLimited sample size, the use of creatine and phosphocreatine (Cr) ratios rather than absolute concentrations and unresolved glutamine (Gln) are limitations of the present study. ConclusionOur study results consolidated the hypothesis about glutamatergic signaling dysfunction in OCD. To our knowledge, it is the first finding about a reduced thalamic glutamate level in adult unmedicated OCD patients. The dysregulation of glutamate serves as a potential target for the OCD pharmacotherapy and the detailed mechanisms underlying the glutamate alterations within CSTC circuits merit further investigations.

The effects of methylphenidate on whole brain intrinsic functional connectivity.

Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that is used to treat attention deficit hyperactivity disorder and that has shown therapeutic potential in neuropsychiatric diseases such as depression, dementia, and Parkinson's disease. While effects of MPH on task-induced brain activation have been investigated, little is known about how MPH influences the resting brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional connectivity, we used resting state fMRI in 54 healthy male subjects in a double-blind, randomized, placebo-controlled study. Functional connectivity analysis employing ICA revealed seven resting state networks (RSN) of interest. Connectivity strength between the dorsal attention network and the thalamus was increased after MPH intake. Other RSN located in association cortex areas, such as the left and right frontoparietal networks and the executive control network, showed MPH-induced connectivity increase to sensory-motor and visual cortex regions and connectivity decrease to cortical and subcortical components of cortico-striato-thalamo-cortical circuits (CST). RSN located in sensory-motor cortex areas showed the opposite pattern with MPH-induced connectivity increase to CST components and connectivity decrease to sensory-motor and visual cortex regions. Our results provide evidence that MPH does not only alter intrinsic connectivity between brain areas involved in sustained attention, but that it also induces significant changes in the cortico-cortical and cortico-subcortical connectivity of many other cognitive and sensory-motor RSN.

Obsessive–Compulsive Disorder

Obsessive–compulsive disorder (OCD) is a common heterogeneous psychiatric disorder manifesting with obsessions and compulsions. Obsessions are intrusive, recurrent, and persistent unwanted thoughts. Compulsions are repetitive behaviors or mental acts that an individual feels driven to perform in response to the obsessions. The heterogeneity of OCD includes themes of obsessions, types of rituals, presence or absence of tics, etiology, genetics, and response to pharmacotherapy. Complications of OCD include interpersonal difficulties, unemployment, substance abuse, criminal justice issues, and physical injuries. Areas of the brain involved in the pathophysiology include the orbitofrontal cortex, anterior cingulate gyrus, and basal ganglia. Overall, OCD may be due to a malfunction in the cortico–striato–thalamo–cortical circuit in the brain. Neurotransmitters implicated in OCD include serotonin, dopamine, and glutamate. Numerous drugs such as atypical antipsychotics and dopaminergic agents can cause or exacerbate OCD symptoms. The etiology includes genetics and neurological insults. Treatment of OCD includes psychotherapy, pharmacotherapy, electroconvulsive therapy, transcranial magnetic simulation, and in extreme cases surgery. Exposure and response prevention is the most effective form of psychotherapy. Selective serotonin reuptake inhibitors (SSRIs) are the preferred pharmacotherapy. Higher doses than listed in the package insert and a longer trial are often needed for SSRIs than compared to other psychiatric disorders. Alternatives to SSRIs include clomipramine and serotonin/norepinephrine reuptake inhibitors. Treatment of resistant cases includes augmentation with atypical antipsychotics, pindolol, buspirone, and glutamate-blocking agents.

Reduction of N-acetylaspartate in the medial prefrontal cortex correlated with symptom severity in obsessive-compulsive disorder: meta-analyses of (1)H-MRS studies.

Structural and functional neuroimaging findings suggest that disturbance of the cortico–striato–thalamo–cortical (CSTC) circuits may underlie obsessive-compulsive disorder (OCD). However, some studies with 1H-magnetic resonance spectroscopy (1H-MRS) reported altered level of N-acetylaspartate (NAA), they yielded inconsistency in direction and location of abnormality within CSTC circuits. We conducted a comprehensive literature search and a meta-analysis of 1H-MRS studies in OCD. Seventeen met the inclusion criteria for a meta-analysis. Data were separated by frontal cortex region: medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex, orbitofrontal cortex, basal ganglia and thalamus. The mean and s.d. of the NAA measure were calculated for each region. A random effects model integrating 16 separate datasets with 225 OCD patients and 233 healthy comparison subjects demonstrated that OCD patients exhibit decreased NAA levels in the frontal cortex (P=0.025), but no significant changes in the basal ganglia (P=0.770) or thalamus (P=0.466). Sensitivity analysis in an anatomically specified subgroup consisting of datasets examining the mPFC demonstrated marginally significant reduction of NAA (P=0.061). Meta-regression revealed that NAA reduction in the mPFC was positively correlated with symptom severity measured by Yale–Brown Obsessive Compulsive Scale (P=0.011). The specific reduction of NAA in the mPFC and significant relationship between neurochemical alteration in the mPFC and symptom severity indicate that the mPFC is one of the brain regions that directly related to abnormal behavior in the pathophysiology of OCD. The current meta-analysis indicates that cortices and sub-cortices contribute in different ways to the etiology of OCD.

Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits

Deep brain stimulation (DBS) has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive compulsive disorder (OCD), which is characterized by recurrent unwanted thoughts or ideas (obsessions) and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions). Abnormal activity in cortico-striato-thalamo-cortical (CSTC) circuits including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), ventral striatum, and mediodorsal (MD) thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), ventral caudate nucleus, subthalamic nucleus (STN), and nucleus accumbens (NAc) have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level.

Sensorimotor network in cervical dystonia and the effect of botulinum toxin treatment: A functional MRI study

Background The evidence suggests that the origin of primary dystonia is at least partly associated with widespread dysfunction of the basal ganglia and cortico–striato–thalamo–cortical circuits. The aim of the study was to assess the sensorimotor activation pattern outside the circuits controlling the affected body part in cervical dystonia, as well as to determine task-related activation changes induced by botulinum toxin type A (BoNT-A) treatment. Methods Seven patients suffering from cervical dystonia and nine healthy controls were examined with functional MRI during skilled hand motor task; the examination was repeated 4 weeks after BoNT-A application to dystonic neck muscles. Results Functional MRI data demonstrated overall reduced extent of hand movement-related cortical activation but greater magnitude of blood oxygenation level dependent signal change in the contralateral secondary somatosensory cortex in patients compared to controls. Effective BoNT-A treatment led to reduced activation of the ipsilateral supplementary motor area and dorsal premotor cortex in patients. The patients' post-treatment sensorimotor maps showed significantly smaller basal ganglia activation compared to controls. Conclusions These results provide imaging evidence that abnormalities in sensorimotor activation extend beyond circuits controlling the affected body parts in cervical dystonia. The study also supports observations that BoNT-A effect has a correlate at central nervous system level, and such effect may not be limited to cortical and subcortical representations of the treated muscles.

Relationship of Cortical Atrophy to Fatigue in Patients With Multiple Sclerosis

Fatigue is a common and disabling symptom of multiple sclerosis (MS). Previous studies reported that damage of the corticostriatothalamocortical circuit is critical in its occurrence. To investigate the relationship between fatigue in MS and regional cortical and subcortical gray matter atrophy. Case-control study. National Institutes of Health. Twenty-four patients with MS and 24 matched healthy volunteers who underwent 3.0-T magnetic resonance imaging and evaluations of fatigue (Modified Fatigue Impact Scale) and depression (Center for Epidemiologic Studies Depression Scale). Relationship between thalamic and basal ganglia volume, cortical thickness of frontal and parietal lobes, and, in patients, T2 lesion volume and normal-appearing white matter volume and the extent of fatigue. Patients were more fatigued than healthy volunteers (P = .04), while controlling for the effect of depression. Modified Fatigue Impact Scale score correlated with cortical thickness of the parietal lobe (r = -0.50, P = .01), explaining 25% of its variance. The posterior parietal cortex was the only parietal area significantly associated with the Modified Fatigue Impact Scale scores. Cortical atrophy of the parietal lobe had the strongest relationship with fatigue. Given the implications of the posterior parietal cortex in motor planning and integration of information from different sources, our preliminary results suggest that dysfunctions in higher-order aspects of motor control may have a role in determining fatigue in MS.

Neural network processing of natural language: II. Towards a unified model of corticostriatal function in learning sentence comprehension and non-linguistic sequencing

A central issue in cognitive neuroscience today concerns how distributed neural networks in the brain that are used in language learning and processing can be involved in non-linguistic cognitive sequence learning. This issue is informed by a wealth of functional neurophysiology studies of sentence comprehension, along with a number of recent studies that examined the brain processes involved in learning non-linguistic sequences, or artificial grammar learning (AGL). The current research attempts to reconcile these data with several current neurophysiologically based models of sentence processing, through the specification of a neural network model whose architecture is constrained by the known cortico-striato-thalamo-cortical (CSTC) neuroanatomy of the human language system. The challenge is to develop simulation models that take into account constraints both from neuranatomical connectivity, and from functional imaging data, and that can actually learn and perform the same kind of language and artificial syntax tasks. In our proposed model, structural cues encoded in a recurrent cortical network in BA47 activate a CSTC circuit to modulate the flow of lexical semantic information from BA45 to an integrated representation of meaning at the sentence level in BA44/6. During language acquisition, corticostriatal plasticity is employed to allow closed class structure to drive thematic role assignment. From the AGL perspective, repetitive internal structure in the AGL strings is encoded in BA47, and activates the CSTC circuit to predict the next element in the sequence. Simulation results from Caplan’s [Caplan, D., Baker, C., & Dehaut, F. (1985). Syntactic determinants of sentence comprehension in aphasia. Cognition, 21, 117–175] test of syntactic comprehension, and from Gomez and Schvaneveldts’ [Gomez, R. L., & Schvaneveldt, R. W. (1994). What is learned from artificial grammars?. Transfer tests of simple association. Journal of Experimental Psychology: Learning, Memory and Cognition, 20, 396–410] artificial grammar learning experiments are presented. These results are discussed in the context of a brain architecture for learning grammatical structure for multiple natural languages, and non-linguistic sequences.

Tic Disorders: Neural Circuits, Neurochemistry, and Neuroimmunology

The neuroanatomy and neurochemistry underlying tic disorders are thought to involve corticostriatothalamocortical circuits and dysregulation of their component neurotransmitter systems. Tourette syndrome is a tic disorder that begins in childhood and follows a waxing and waning course of tic severity. Although it is generally believed to have a genetic component, its etiology has not been fully elucidated. The clinical entity pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) has led some to suggest that the pathophysiology of tics in some individuals might involve a postinfectious autoimmune component. We review the neural circuits and neurochemistry of Tourette syndrome and evaluate the evidence for and against a role for autoimmunity in the expression of tics.