Cingulate Cortex

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• Publisher: Elsevier
• Year: 2019
• Print ISBN: 9780444641960
• eBook ISBN: 9780444641977
• Topic: Medicine
• Subtopic: Neurology

Cingulate Cortex, Volume 166 summarizes research on the cingulate cortex, including its structure and function in health and how it is compromised in disease or trauma. Chapters discuss the cingulate organization by region and area, cover its function in consciousness, attention, social cognition and spatial orientation, review neurological disorders with cingulate involvement, including neurodegenerative disorders, movement disorders, Parkinson's, ADHD, Cognitive impairment, Palsy, Tourette's Syndrome, chronic pain, seizures, and more. Final sections discuss the relationship between the cingulate cortex, stress and psychiatric disorders. Coverage here includes PTSD, anxiety, depression, and evidence-based treatment for same.- Identifies the structure and function of all areas and regions of the cingulate cortex- Discusses its role in sensory-motor, cognitive and emotional processing- Covers cingulate-mediated neurological and psychiatric disorders- Supplies evidence-based treatment for cingulate mediated disorders

Section III

Cingulate neurological and movement disorders

Chapter 11

Cingulate role in Tourette syndrome

Joseph O'Neill^1,*; John C. Piacentini¹; Bradley S. Peterson^{2 1} Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, UCLA Department of Psychiatry & Biobehavioral Sciences, Los Angeles, CA, United States
² Institute for the Developing Mind, Children's Hospital Los Angeles, Keck School of Medicine at the University of Southern California, Los Angeles, CA, United States
^* Correspondence to: Joseph O'Neill, Division of Child & Adolescent Psychiatry, Jane & Terry Semel Institute for Neuroscience, UCLA Department of Psychiatry & Biobehavioral Sciences, 760 Westwood Plaza 58-227A, Los Angeles, CA 90024-1759, United States. Tel: + 1-310-825-5709, Fax: + 1-310-206-4446 email address: [email protected]

Abstract

This chapter comprehensively reviews the published record for neurosurgical, neurostimulatory, and neuroimaging evidence of the involvement of the cingulate gyrus in Gilles de la Tourette syndrome (TS). The most noteworthy evidence comes from neuroimaging. Neuroimaging findings were rarely exclusive to the cingulate cortex and tended to implicate multiple other cortices as well. Some results are reflective of obsessive–compulsive (OC) symptoms of TS. Copious findings, however, drawn from structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), resting-state functional magnetic resonance imaging (rsfMRI), task fMRI, and positron emission tomography (PET) implicate six of the eight cingulate subregions in TS. Gauged by MRI, cortical thinning and/or below-normal volume are seen in subgenual anterior cingulate cortex (sACC), pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and posterior middle cingulate cortex (pMCC), correlating with tic severity in sACC, pACC, and aMCC. Moreover, in pMCC, dorsal posterior cingulate cortex (dPCC), and ventral posterior cingulate cortex (vPCC), cortical thickness is a candidate biomarker shared across siblings with TS. Loss of cortex may reflect excitotoxicity secondary to insufficient local GABAergic inhibition, a notion supported by the few relevant MRS and PET studies conducted to date, recommending continued development of GABAergic and glutamatergic pharmacologic agents to treat TS. Measurements of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) obtained with DTI indicate that the white matter proximal to sACC, pACC, pMCC, and dPCC may also represent a seat of pathology in TS. rsfMRI reveals abnormal functional connectivity of pACC and dPCC with the globus pallidus internus, a favored target of therapeutic deep brain stimulation (DBS) for TS. In whole-brain network (graph theory) analysis, dPCC functional connectivity is related to the severity and complexity of tics. In task fMRI, in contrast, the pMCC seems to play a preeminent role in premonitory urges and preparation for tics as well as normal urges to urinate, swallow, and yawn. Strong monkey PET and EEG evidence ties vocal tics to spike discharges, α-activity, and regional blood flow in the pACC unleashed by failure of GABAergic inhibition in the ventral striatum. Tic suppression in fMRI scans is associated with increased blood oxygenation level-dependent activity in sACC, pACC, and aMCC, but decreased activity in pMCC and dPCC. Activity in the former three subregions may represent volitional effort, physical discomfort, and emotional distress that accompanies mounting tic urges; pMCC and dPCC may be more instrumental in amplifying than suppressing urges. Needs for future neuroimaging work in TS include longitudinal studies—particularly those striving to predict which individual pediatric patients will continue to suffer from TS as adults and studies of treatment response—particularly of behavioral therapies, which are as efficacious as pharmacology. Transcranial magnetic stimulation and related therapies such as cranial electrotherapy stimulation, which showed good efficacy in a recent trial, merit continued exploration. TS research using DTI, MRS, and PET will no doubt continue to benefit in coming years from technological advances such as ultrahigh-field scanners, multichannel head coils, and novel (including GABAergic and glutamatergic) ligands.

Keywords

Tourette's disorder; Cingulate cortex; Neurosurgery; Neurostimulation; Neuroimaging

Overview

This chapter reviews evidence for the involvement of the cingulate cortex in Tourette's syndrome (TS). Evidence stems predominantly from human neuroimaging with some contributions from clinical sources. There is little evidence from pathology or preclinical work. Neuropathology studies of TS of any kind are scarce, and we are aware of none involving the cingulate cortex. Indirectly, primate and rodent studies are highly informative in that they delineate much of the general structure, connectivity, and functions of the cingulate cortex (Vogt, 2009). There has also been much animal research specific to TS (reviewed, e.g., by Bronfeld et al., 2013; Hornig and Lipkin, 2013; McCairn and Isoda, 2013; Godar et al., 2014; Pappas et al., 2014). But the cingulate has rarely been a source of findings in these preclinical investigations. There is the work of McCairn et al. (2009, 2016, see later in this chapter) and Zalcman et al. (2012) who induced TS-like symptoms and increased c-fos protein immunoreactivity in the cingulate cortex of mice by injecting soluble IL-2 receptors. But these are exceptions, and our focus in the main will be on in vivo human neuroimaging studies.

The chapter begins with a brief clinical summary of TS followed by some key noncingulate neuroimaging findings. Then, after looking at cingulate-relevant neurosurgical and neurostimulatory findings, we examine those studies that found positive evidence implicating the cingulate in TS using various magnetic resonance (MR) and positron emission tomography (PET) modalities. We note here that numerous (typically noncingulate-targeted) negative studies remain unmentioned. We finish by drawing together a few plausible inferences on the cingulate role in TS and recommendations for future research.

A word on neuroanatomic nomenclature before proceeding. In this chapter, we adhere to Vogt's Eight-Subregion Model of the cingulate (Vogt, 2009; Fig. 11.12; for identification of the Vogt subregions on structural magnetic resonance imaging (MRI), see O’Neill et al., 2009). This model is consistent with all currently known histologic, anatomic, and neuroimaging data. In the Eight-Subregion Model, the cortex of both the cingulate and (to the extent present) paracingulate gyri is classified as “cingulate cortex.” Left and right cingulate cortices are each divided into four regions, each of which consists of two subregions. The total eight subregions of the cingulate gyrus from rostral to caudal are subgenual anterior cingulate cortex (sACC), pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), posterior middle cingulate cortex (pMCC), dorsal posterior cingulate cortex (dPCC), ventral posterior cingulate cortex (vPCC), dorsal retrosplenial cortex (dRSC), and ventral retrosplenial cortex (vRSC). The sACC and the pACC subregions together constitute the anterior cingulate cortex (ACC) region. Similarly, aMCC and pMCC constitute the middle cingulate cortex (MCC), dPCC and vPCC form the posterior cingulate cortex (PCC), and dRSC and vRSC make up the retrosplenial cortex (RSC). In reviewing each of the papers later, we employ this nomenclature, even if it was not used by the authors of those papers. For each cingulate finding, drawing from atlas coordinates, figures, or descriptions in the paper, we have, as far as possible, localized the finding to one or more subregions of the Model. In the (unfortunately plentiful) cases where indications in the paper were insufficiently precise, we resorted to the regional labels “ACC,” “MCC,” “PCC,” and “RSC.” Note particularly that we do not use the popular label “dACC” (dorsal anterior cingulate cortex); we call this region the “aMCC.” We have attempted to uphold the Eight-Subregion labeling throughout the chapter.

Tourette's Syndrome: Clinical Summary

Practice guidelines

Several excellent practi...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Handbook of Clinical Neurology 3rd Series
• Foreword
• Preface
• Contributors
• Section I: Overview
• Section II: Large scale networks and functions
• Section III: Cingulate neurological and movement disorders
• Section IV: Pain, epilepsy, stress and depression
• Index