Altered Fronto-Striatal Fiber Topography and Connectivity in Obsessive-Compulsive Disorder

Nakamae, Takashi; Abe, Yoshinari; Nishida, Seiji; Fukui, Kenji; Yamada, Kazuo; Kubota, Manabu; Denys, Damiaan; Narumoto, Jin

doi:10.1371/journal.pone.0112075

Cited by 26 publications

(22 citation statements)

References 61 publications

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“…In more than half of individuals with OCD, these symptoms may be severe enough to cause absence from work, school or social engagements; further, treatment of these severe cases is often more difficult (Bourne et al, 2012). Importantly, obsessions and compulsions represent dysfunctional cognitive and motor processes that become repetitive and disturbing; it is suggested that hyperactivation within CSTC circuits and changes to CSTC topography may underlie such ritualistic thoughts and behaviors (Graybiel and Rauch, 2000; Nakamae et al, 2014). …”

Section: Abnormalities Of Sn-cstc Loop Circuits In Psychiatric Illnessesmentioning

confidence: 99%

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

Peters

Dunlop

Downar³

2016

Front. Syst. Neurosci.

439

298

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The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network’s associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN’s cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders.

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Section: Abnormalities Of Sn-cstc Loop Circuits In Psychiatric Illnessesmentioning

confidence: 99%

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

Peters

Dunlop

Downar³

2016

Front. Syst. Neurosci.

439

298

View full text Add to dashboard Cite

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“…Determining whether striatal hyperactivity originates in striatum or in upstream cortical projections could help inform whether neuromodulatory treatments for OCD-related disorders should target cortical or subcortical regions. Although striatal deep brain stimulation has reported efficacy in OCD (Greenberg et al, 2010;Figee et al, 2013), studies demonstrating aberrant activity in corticostriatal circuits in OCD patients Menzies et al, 2008;Harrison et al, 2009;Del Casale et al, 2011;Figee et al, 2013;Nakamae et al, 2014) suggest that cortical regions may be useful targets for noninvasive neurostimulation via repetitive transcranial magnetic stimulation (rTMS), either through direct cortical effects or modulation of connected subcortical structures. Consistent with this idea, orbitofrontal cortex (OFC) and presupplementary motor area (pre-SMA), which are hyperactive in OCD patients (Maltby et al, 2005;Yücel et al, 2007;Leckman et al, 2010;Del Casale et al, 2011;de Wit et al, 2012;Grützmann et al, 2016), have been identified as promising targets for rTMS (Berlim et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Strengthened Inputs from Secondary Motor Cortex to Striatum in a Mouse Model of Compulsive Behavior

et al. 2019

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Hyperactivity in striatum is associated with compulsive behaviors in obsessive-compulsive disorder (OCD) and related illnesses, but it is unclear whether this hyperactivity is due to intrinsic striatal dysfunction or abnormalities in corticostriatal inputs. Understanding the cellular and circuit properties underlying striatal hyperactivity could help inform the optimization of targeted stimulation treatments for compulsive behavior disorders. To investigate the cellular and synaptic abnormalities that may underlie corticostriatal dysfunction relevant to OCD, we used the Sapap3 knock-out (Sapap3-KO) mouse model of compulsive behaviors, which also exhibits hyperactivity in central striatum. Ex vivo electrophysiology in double-transgenic mice was used to assess intrinsic excitability and functional synaptic input in spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in central striatum of Sapap3-KOs and wild-type (WT) littermates. While we found no differences in intrinsic excitability of SPNs or FSIs between Sapap3-KOs and WTs, excitatory drive to FSIs was significantly increased in KOs. Contrary to predictions, lateral orbitofrontal cortex-striatal synapses were not responsible for this increased drive; optogenetic stimulation revealed that lateral orbitofrontal cortex input to SPNs was reduced in KOs (ϳ3-fold) and unchanged in FSIs. However, secondary motor area (M2) postsynaptic responses in central striatum were significantly increased (ϳ6-fold) in strength and reliability in KOs relative to WTs. These results suggest that increased M2-striatal drive may contribute to both in vivo striatal hyperactivity and compulsive behaviors, and support a potential role for presupplementary/supplementary motor cortical regions in the pathology and treatment of compulsive behavior disorders.These findings highlight an unexpected contribution of M2 projections to striatal dysfunction in the Sapap3-KO obsessivecompulsive disorder (OCD)-relevant mouse model, with M2 inputs strengthened by at least sixfold onto both spiny projection neurons and fast-spiking interneurons in central striatum. Because M2 is thought to be homologous to presupplementary/ supplementary motor areas (pre-SMA/SMA) in humans, regions important for movement preparation and behavioral sequencing, these data are consistent with a model in which increased drive from M2 leads to excessive selection of sequenced motor patterns. Together with observations of hyperactivity in pre-SMA/SMA in both OCD and Tourette syndrome, and evidence that pre-SMA is a potential target for repetitive transcranial magnetic stimulation treatment in OCD, these results support further dissection of the role of M2 in compulsivity.

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“…Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2-3% 1 that is characterized by obsessions (recurrent intrusive thoughts with excessive anxiety) and compulsions (excessive repetitive actions for reducing obsessioninduced anxiety). Previous neuroimaging studies using structural and task-based functional magnetic resonance imaging (fMRI) have revealed neurobiological dysfunctions in OCD, most notably in the fronto-striatal circuit [2][3][4][5][6] . A meta-analysis of task-based fMRI studies using the symptom provocation paradigm revealed consistent increased activation within fronto-striatal regions 7 .…”

Section: Introductionmentioning

confidence: 99%

A Neural Marker of Obsessive-Compulsive Disorder from Whole-Brain Functional Connectivity

Takagi

Sakai

Lisi

et al. 2017

Sci Rep

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Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2–3%. Recently, brain activity in the resting state is gathering attention for exploring altered functional connectivity in psychiatric disorders. Although previous resting-state functional magnetic resonance imaging studies investigated the neurobiological abnormalities of patients with OCD, there are concerns that should be addressed. One concern is the validity of the hypothesis employed. Most studies used seed-based analysis of the fronto-striatal circuit, despite the potential for abnormalities in other regions. A hypothesis-free study is a promising approach in such a case, while it requires researchers to handle a dataset with large dimensions. Another concern is the reliability of biomarkers derived from a single dataset, which may be influenced by cohort-specific features. Here, our machine learning algorithm identified an OCD biomarker that achieves high accuracy for an internal dataset (AUC = 0.81; N = 108) and demonstrates generalizability to an external dataset (AUC = 0.70; N = 28). Our biomarker was unaffected by medication status, and the functional networks contributing to the biomarker were distributed widely, including the frontoparietal and default mode networks. Our biomarker has the potential to deepen our understanding of OCD and to be applied clinically.

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Altered Fronto-Striatal Fiber Topography and Connectivity in Obsessive-Compulsive Disorder

Cited by 26 publications

References 61 publications

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

Strengthened Inputs from Secondary Motor Cortex to Striatum in a Mouse Model of Compulsive Behavior

A Neural Marker of Obsessive-Compulsive Disorder from Whole-Brain Functional Connectivity

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