Cortico-Striatal-Thalamic Loop Circuits of the Orbitofrontal Cortex: Promising Therapeutic Targets in Psychiatric Illness

Fettes, Peter; Schulze, Laura; Downar, Jonathan

doi:10.3389/fnsys.2017.00025

Cited by 253 publications

(180 citation statements)

References 240 publications

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“…A significant case-control brain volume difference was observed for a brain component localized to bilateral fronto-striatal white matter, adjacent to the orbitofrontal cortex. Frontostriatal circuits are implicated in complex behaviors, such as reward processing, emotion regulation, inhibition, and motivational states (37), and the dysfunction of these circuits is implicated in several psychiatric disorders (37)(38)(39), including ADHD (40). Previous structural MRI studies have shown volume reductions in frontal lobes and the striatum (10,13) in individuals with ADHD compared to controls.…”

Section: Discussionmentioning

confidence: 99%

Reduced fronto-striatal volume in ADHD in two cohorts across the lifespan

Cupertino

Soheili-Nezhad

Grevet

et al. 2019

Preprint

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ObjectiveNeuroimaging studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with altered brain anatomy. However, small and heterogeneous study samples, and the use of region-of-interest and tissue-specific analyses have limited the consistency and replicability of these effects. The present study uses a fully data-driven multivariate approach to investigate alterations in both gray and white matter simultaneously, and capture neuroanatomical features associated with ADHD in two large, independent, demographically different cohorts.MethodsThe study comprised two ADHD cohorts with structural magnetic resonance imaging data: the Dutch NeuroIMAGE cohort (n=890, average age 17.2 years, discovery sample) and the Brazilian IMpACT cohort (n=180, average age 44.2 years, cross validation sample). Using independent component analysis of whole-brain morphometry images in the NeuroIMAGE cohort, 375 independent components of neuroanatomical variations were extracted and assessed their association with ADHD. Afterwards, ADHD-associated components were cross validated in the Brazilian IMpACT cohort.ResultsIn both discovery (corrected- p=0.020) and validation (p=0.033) cohorts, ADHD diagnosis was significantly associated with reduced brain volume in a component mapping to frontal lobes, striatum, and their interconnecting white-matter tracts. The most pronounced case-control differences were localized in white matter adjacent to the orbitofrontal cortex.ConclusionIndependent component analysis is a sensitive approach to uncover neuroanatomical alterations in ADHD and avoid bias attributable to a priori region-of-interest based methods. Current results provide further evidence for the role of the fronto-striatal circuit in ADHD. The fact that the two cohorts are from different continents and comprising different age ranges highlights the robustness of the findings.

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Section: Discussionmentioning

confidence: 99%

Reduced fronto-striatal volume in ADHD in two cohorts across the lifespan

Cupertino

Soheili-Nezhad

Grevet

et al. 2019

Preprint

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“…43 The DLPFC plays an essential role in emotional, motivational, attentional, and executive functions. 44 Gray matter volume reductions have also been found in the DLPFC in MDD patients compared to healthy controls. 2 Brain activity in the DLPFC was also found to be decreased 13 and could be increased to the average level after antidepressant treatment.…”

Section: Frontal Lobementioning

confidence: 99%

“…Fibers extending through the bilateral medial frontal lobe to the anterior corpus callosum and passing fibers connecting the medial frontal lobe to the amygdala via the uncinate fasciculus during stimulation of the “best” contacts have been deemed to be the switch in MDD . The DLPFC plays an essential role in emotional, motivational, attentional, and executive functions . Gray matter volume reductions have also been found in the DLPFC in MDD patients compared to healthy controls .…”

Section: Significant Structural Brain Alterations In Mddmentioning

confidence: 99%

Brain structure alterations in depression: Psychoradiological evidence

et al. 2018

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Depression is the leading cause of disability around the world, but little is known about its pathology. Currently, the diagnosis of depression is made based on clinical manifestations, with little objective evidence. Magnetic resonance imaging (MRI) has been used to investigate the pathological changes in brain anatomy associated with this disorder. MRI can identify structural alterations in depressive patients in vivo, which could make considerable contributions to clinical diagnosis and treatment. Numerous studies that focused on gray and white matter have found significant brain region alterations in major depressive disorder patients, such as in the frontal lobe, hippocampus, temporal lobe, thalamus, striatum, and amygdala. The results are inconsistent and controversial because of the different demographic and clinical characteristics. However, some regions overlapped; thus, we think that there may be a "hub" in MDD and that an impairment in these regions contributes to disease severity. Brain connections contain both structural connections and functional connections, which reflect disease from a different view and support that MDD may be caused by the interaction of multiple brain regions. According to previous reports, significant circuits include the frontal-subcortical circuit, the suicide circuit, and the reward circuit. As has been recognized, the pathophysiology of major depressive disorder is complex and changeable. The current review focuses on the significant alterations in the gray and white matter of patients with the depressive disorder to generate a better understanding of the circuits. Moreover, identifying the nuances of depressive disorder and finding a biomarker will make a significant contribution to the guidance of clinical diagnosis and treatment.

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“…One prototypical adaptive behaviour is value-guided decisionmaking, which relies on diverse neural systems thought to realise key computations, such as the assignment of value to specific stimulus-action pairs based on rewardhistory. Failure to adapt behaviour is a common symptom in many neurological disorders such as autism and schizophrenia 1 . In mammals, value-guided decisionmaking is governed by distributed neural circuits engaging cognitive primitives in prefrontal areas of the neocortex 2,3 .…”

Section: Main Textmentioning

confidence: 99%

Value-guided remapping of sensory circuits by lateral orbitofrontal cortex in reversal learning

Banerjee

Parente

Teutsch

et al. 2020

Preprint

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Flexible decision-making is crucial for adaptive behaviour. Such behaviour in mammals largely relies on the frontal cortex, and specifically, the orbitofrontal cortex (OFC). How OFC neurons encode decision variables and instruct sensory areas to guide adaptive behaviour is a key open question. Here we developed a reversal learning task for head-fixed mice together with twophoton calcium imaging to monitor the activity of lateral OFC neuronal populations and investigated their dynamic interaction with primary somatosensory cortex (S1). Mice trained on this task learned to discriminate go/no-go tactile stimuli and adapt their behaviour upon changes in stimulusreward contingencies ('rule-switch'). Longitudinal imaging at cellular resolution across weeks during all behavioural phases revealed a distinct engagement of S1 and lateral OFC neurons: S1 neural activity reflected task learning-related responses, while neurons in the lateral OFC saliently and transiently responded to the rule-switch. A subset of OFC neurons conveyed a value prediction error signal via feedback projections to S1, as direct anatomical long-range projections were revealed by retrograde tracing combined with whole-brain light-sheet microscopy. Top-down signals implemented an update of sensory representations and functionally reconfigured a small subpopulation of S1 neurons that were differentially modulated by reward-history. Functional remapping of these neurons crucially depended on top-down inputs, as chemogenetic silencing of lateral OFC neurons disrupted reversal learning and impaired plastic changes in these outcome-sensitive S1 neurons. Our results reveal the presence of long-range cortical interactions between cellular ensembles in higher and lower-order brain areas specifically recruited during context-dependent learning and taskswitching. Such interactions crucially implement history-dependent rewardvalue computations and error heuristics, which, in turn, help guide adaptive behaviour. analysed by C.L.). A.B and G.P. analysed data. F.F.V developed light-sheet microscope and imaged cleared brains together with A.B. A.B. and F.H. wrote the manuscript with comments from all authors.

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Cortico-Striatal-Thalamic Loop Circuits of the Orbitofrontal Cortex: Promising Therapeutic Targets in Psychiatric Illness

Cited by 253 publications

References 240 publications

Reduced fronto-striatal volume in ADHD in two cohorts across the lifespan

Reduced fronto-striatal volume in ADHD in two cohorts across the lifespan

Brain structure alterations in depression: Psychoradiological evidence

Value-guided remapping of sensory circuits by lateral orbitofrontal cortex in reversal learning

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