The involvement of the orbitofrontal cortex in psychiatric disorders: an update of neuroimaging findings

Jackowski, Andrea Parolin; Filho, Gerardo Maria de Araújo; Almeida, Amanda Galvão de; Araújo, Célia Maria de; Reis, Michel Silva; Nery, Fabiana; Batista, Ilza Rosa; Silva, Ivaldo; Lacerda, Acioly L.T.

doi:10.1016/s1516-4446(12)70040-5

Cited by 25 publications

(25 citation statements)

References 29 publications

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“…This idea is supported by studies that show that OFC has direct anatomical projections to the amygdala and hippocampus via the uncinate fasciculus in humans (Bach et al, 2011; Talairach and Tournoux, 1988) as well as in non-human primates (Carmichael and Price, 1995). It was also shown that such projections were abnormal in some psychiatric disorders such as conduct disorder (Passamonti et al, 2012), bipolar disorder (Benedetti et al, 2011), and schizophrenia (Jackowski et al, 2012). Further studies are needed to confirm whether disrupted interactions between OFC-amygdala may be implicated in PTSD.…”

Section: Discussionmentioning

confidence: 99%

Voxel-wise resting-state MEG source magnitude imaging study reveals neurocircuitry abnormality in active-duty service members and veterans with PTSD

Huang

Yurgil

Robb

et al. 2014

NeuroImage: Clinical

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Post-traumatic stress disorder (PTSD) is a leading cause of sustained impairment, distress, and poor quality of life in military personnel, veterans, and civilians. Indirect functional neuroimaging studies using PET or fMRI with fear-related stimuli support a PTSD neurocircuitry model that includes amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC). However, it is not clear if this model can fully account for PTSD abnormalities detected directly by electromagnetic-based source imaging techniques in resting-state. The present study examined resting-state magnetoencephalography (MEG) signals in 25 active-duty service members and veterans with PTSD and 30 healthy volunteers. In contrast to the healthy volunteers, individuals with PTSD showed: 1) hyperactivity from amygdala, hippocampus, posterolateral orbitofrontal cortex (OFC), dorsomedial prefrontal cortex (dmPFC), and insular cortex in high-frequency (i.e., beta, gamma, and high-gamma) bands; 2) hypoactivity from vmPFC, Frontal Pole (FP), and dorsolateral prefrontal cortex (dlPFC) in high-frequency bands; 3) extensive hypoactivity from dlPFC, FP, anterior temporal lobes, precuneous cortex, and sensorimotor cortex in alpha and low-frequency bands; and 4) in individuals with PTSD, MEG activity in the left amygdala and posterolateral OFC correlated positively with PTSD symptom scores, whereas MEG activity in vmPFC and precuneous correlated negatively with symptom score. The present study showed that MEG source imaging technique revealed new abnormalities in the resting-state electromagnetic signals from the PTSD neurocircuitry. Particularly, posterolateral OFC and precuneous may play important roles in the PTSD neurocircuitry model.

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Section: Discussionmentioning

confidence: 99%

Voxel-wise resting-state MEG source magnitude imaging study reveals neurocircuitry abnormality in active-duty service members and veterans with PTSD

Huang

Yurgil

Robb

et al. 2014

NeuroImage: Clinical

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“…Patients with BD or SCZ exhibit cognitive deficits related to OFC function with the most notable being disturbances in cognitive flexibility, which is the capacity to promptly adapt one's behavior when circumstances change [40][41][42]. Cognitive flexibility is best assessed through reversal learning tests, during which subjects are initially trained and rewarded to discriminate one visual cue from another until they reach a criterion level of performance.…”

Section: In Vivo Ofc Circhomer1a Knockdown Impairs Ofcmediated Behavimentioning

confidence: 99%

“…Using cutting-edge circRNA methodologies in postmortem brain samples from the orbitofrontal cortex (OFC), a region of the prefrontal cortex (PFC) implicated in psychiatric disorders and responsible for high order cognitive functions, including behavioral flexibility [40][41][42], we have identified an abundant and activity-dependent neuronalenriched circRNA [16,25], circHomer1a, that is robustly reduced in SCZ and BD. Furthermore, we report that cir-cHomer1a, which is generated from the backsplicing of four exons from the psychiatric disorder-related, synaptically expressed HOMER1 [13,43,44], is also significantly downregulated in iPS cell-derived neuronal cultures from SCZ and BD patients and the DLPFC of subjects with SCZ.…”

Section: Introductionmentioning

confidence: 99%

A psychiatric disease-related circular RNA controls synaptic gene expression and cognition

et al. 2020

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Although circular RNAs (circRNAs) are enriched in the mammalian brain, very little is known about their potential involvement in brain function and psychiatric disease. Here, we show that circHomer1a, a neuronal-enriched circRNA abundantly expressed in the frontal cortex, derived from Homer protein homolog 1 (HOMER1), is significantly reduced in both the prefrontal cortex (PFC) and induced pluripotent stem cell-derived neuronal cultures from patients with schizophrenia (SCZ) and bipolar disorder (BD). Moreover, alterations in circHomer1a were positively associated with the age of onset of SCZ in both the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). No correlations between the age of onset of SCZ and linear HOMER1 mRNA were observed, whose expression was mostly unaltered in BD and SCZ postmortem brain. Using in vivo circRNA-specific knockdown of circHomer1a in mouse PFC, we show that it modulates the expression of numerous alternative mRNA transcripts from genes involved in synaptic plasticity and psychiatric disease. Intriguingly, in vivo circHomer1a knockdown in mouse OFC resulted in specific deficits in OFCmediated cognitive flexibility. Lastly, we demonstrate that the neuronal RNA-binding protein HuD binds to circHomer1a and can influence its synaptic expression in the frontal cortex. Collectively, our data uncover a novel psychiatric diseaseassociated circRNA that regulates synaptic gene expression and cognitive flexibility.

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“…An animal‐based study found that the vmPFC is critical to detection of whether a stressor is controllable (i.e., escapable) and modulates the brainstem dorsal raphe nucleus and the stress response accordingly . It is proposed that the vmPFC within the mPFC provides “contextualization” of relayed information from the OFC and amygdala, and thus disruption of this area might play a key role in the generation of PTSD symptoms during nonthreatening situations. The OFC normally inhibits signals from the amygdala; however, research supports reduced OFC volumes in PTSD patients .…”

Section: Ptsd Neurophysiologymentioning

confidence: 99%

“…For this reason, a popular theory detailing PTSD pathophysiology maintains that intrusive symptoms observed in PTSD patients are due in part to a failure of the OFC to inhibit signals from a hyper‐responsive amygdala (Fig. A) . A diminished responsivity of the OFC and connected mPFC and exaggerated responsivity of the amygdala in individuals with PTSD (Fig.…”

Section: Ptsd Neurophysiologymentioning

confidence: 99%

Eye movement desensitization and reprocessing as a treatment for PTSD: current neurobiological theories and a new hypothesis

Calancie

Khalid‐Khan

Booij

et al. 2018

Annals of the New York Academy of Sciences

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Eye movement desensitization and reprocessing (EMDR), a form of psychotherapy for individuals with post-traumatic stress disorder (PTSD), has long been a controversial topic, hampered in part by a lack of understanding of the neural mechanisms that contribute to its remedial effect. Here, we review current theories describing EMDR's potential neurobiological mechanisms of action involving working memory, interhemispheric communication, de-arousal, and memory reconsolidation. We then discuss recent studies describing the temporal and spatial aspects of smooth pursuit and predictive saccades, which resemble those made during EMDR, and their neural correlates within the default mode network (DMN) and cerebellum. We hypothesize that if the production of bilateral predictive eye movements is supportive of DMN and cerebellum activation, then therapies that shift the brain towards this state correspondingly would benefit the processes regulated by these structures (i.e., memory retrieval, relaxation, and associative learning), all of which are essential components for PTSD recovery. We propose that the timing of sensory stimulation may be relevant to treatment effect and could be adapted across different patients depending on their baseline saccade metrics. Empirical data in support of this model are reviewed and experimental predictions are discussed.

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The involvement of the orbitofrontal cortex in psychiatric disorders: an update of neuroimaging findings

Cited by 25 publications

References 29 publications

Voxel-wise resting-state MEG source magnitude imaging study reveals neurocircuitry abnormality in active-duty service members and veterans with PTSD

Voxel-wise resting-state MEG source magnitude imaging study reveals neurocircuitry abnormality in active-duty service members and veterans with PTSD

A psychiatric disease-related circular RNA controls synaptic gene expression and cognition

Eye movement desensitization and reprocessing as a treatment for PTSD: current neurobiological theories and a new hypothesis

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