Decrease of Prefrontal Metabolism After Subthalamic Stimulation in Obsessive-Compulsive Disorder: A Positron Emission Tomography Study

Jeune, Florence Le; Vérin, Marc; N’Diaye, K.; Drapier, Dominique; Leray, Emmanuelle; Montcel, Sophie Tezenas du; Baup, Nicolas; Pélissolo, Antoine; Polosan, Mircea; Mallet, Luc; Yelnik, Jérôme; Devaux, Bertrand; Fontaine, Denys; Chéreau, Isabelle; Bourguignon, Anne; Péron, Julie Anne; Sauleau, Paul; Raoul, Sylvie; Garin, Étienne; Krebs, Marie‐Odile; Jaafari, Nématollah; Millet, Bruno

doi:10.1016/j.biopsych.2010.06.033

Cited by 111 publications

(82 citation statements)

References 39 publications

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“…Although we cannot conclude from task-related fMRI that the underlying neural deficit for these findings in OCD is vmPFC hyperactivation, findings from other task-independent studies using resting-state fMRI and positron emission tomography (PET) measures indicate this to be likely (29,30), emphasizing that the vmPFC is a key node in an overactive thalamo-corticostriatal pathway. We hypothesize that this sustained vmPFC hypermetabolism impedes safety learning in OCD.…”

Section: Discussionmentioning

confidence: 72%

“…In light of a recent study revealing that many fMRI results could reflect false positives (41), it is important to emphasize that our main findings were based on whole-brain group comparisons FEW-corrected at a significance level of P < 0.0001, indicative of convincing differences in vmPFC activation between OCD patients and controls. Moreover, a PET study had already implied a prominent role for the vmPFC in OCD, showing that deep brain stimulation of the subthalamic nucleus resulted in a strong decrease in vmPFC metabolism that correlated with an improvement in Yale Brown Obsessive Compulsive (Y-BOCS) scores (30).…”

Section: Discussionmentioning

confidence: 99%

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Neural basis of impaired safety signaling in Obsessive Compulsive Disorder

Apergis-Schoute

Gillan

Fineberg

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

140

152

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The ability to assign safety to stimuli in the environment is integral to everyday functioning. A key brain region for this evaluation is the ventromedial prefrontal cortex (vmPFC). To investigate the importance of vmPFC safety signaling, we used neuroimaging of Pavlovian fear reversal, a paradigm that involves flexible updating when the contingencies for a threatening (CS+) and safe (CS-) stimulus reverse, in a prototypical disorder of inflexible behavior influenced by anxiety, Obsessive Compulsive Disorder (OCD). Skin conductance responses in OCD patients (n = 43) failed to differentiate during reversal compared with healthy controls (n = 35), although significant differentiation did occur during early conditioning and amygdala BOLD signaling was unaffected in these patients. Increased vmPFC activation (for CS+ > CS-) during early conditioning predicted the degree of generalization in OCD patients during reversal, whereas vmPFC safety signals were absent throughout learning in these patients. Regions of the salience network (dorsal anterior cingulate, insula, and thalamus) showed early learning task-related hyperconnectivity with the vmPFC in OCD, consistent with biased processing of the CS+. Our findings reveal an absence of vmPFC safety signaling in OCD, undermining flexible threat updating and explicit contingency knowledge. Although differential threat learning can occur to some extent in the absence of vmPFC safety signals, effective CS-signaling becomes crucial during conflicting threat and safety cues. These results promote further investigation of vmPFC safety signaling in other anxiety disorders, with potential implications for the development of exposure-based therapies, in which safety signaling is likely to play a key role.Obsessive Compulsive Disorder | vmPFC | Pavlovian | fMRI | safety signals C urrent behavioral therapies in anxiety-related disorders are based on Pavlovian fear extinction models. As fear extinction relies on revaluation of threatening stimuli as safe, it is critical to address how the brain processes the safety of stimuli in the environment. The ventromedial prefrontal cortex (vmPFC) is known to play a multifaceted role in integrating affective evaluative processes while mediating flexible behavior and is implicated in fear learning and anxiety-related disorders (1-7). Prefrontal inflexibility in Obsessive Compulsive Disorder (OCD) suggests rigidity in threat estimation alongside a persistent urge to perform compulsive behaviors, yet only one study has examined the neural correlates of fear learning and extinction in this disorder, implicating a maladaptive vmPFC (8).Human fear learning studies usually involve contrasting a threatening (CS+) stimulus that is occasionally paired with a shock with a stimulus that is never paired with a shock and thus safe (CS-). When using the CS+ > CS-contrast, the vmPFC consistently exhibits negative activation values in healthy controls, indicating stronger activation to the CS-than to the CS+ in this region (1-3, 7, 9). Fear reversal (Fig. 1A)...

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Neural basis of impaired safety signaling in Obsessive Compulsive Disorder

Apergis-Schoute

Gillan

Fineberg

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

140

152

View full text Add to dashboard Cite

show abstract

“…Modulation of key parts of the limbic circuit has been demonstrated in a large series of patients; however, no resultant cognitive improvement was detected on neuropsychological testing except modest improvements in a card-sorting task (Le Jeune et al 2010). This result is potentially confounded because patients were tested who were still on medication in addition to DBS.…”

Section: Network Effects Of Subthalamic Nucleus Stimulationmentioning

confidence: 99%

“…A PET study showed that this therapy resulted in a decrease in metabolism of the left cingulate and medial gyrus of the left frontal lobe. Clinical improvement was correlated with a decrease of metabolic activity in the orbitofrontal cortex (OFC)-ventral medial prefrontal region in ON vs. OFF conditions (Le Jeune et al 2010).…”

Section: Network Effects Of Subthalamic Nucleus Stimulationmentioning

confidence: 99%

Network effects of deep brain stimulation

Alhourani

McDowell

Randazzo

et al. 2015

Journal of Neurophysiology

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The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies. deep brain stimulation; electrocorticography; magnetoencephalography DEEP BRAIN STIMULATION (DBS) provides a unique opportunity for further understanding of healthy and aberrant human brain function. DBS is the only paradigm in which specific deep brain regions may be manipulated through focal electrical stimulation while simultaneously recording brain activity. An emerging field of study has begun to elucidate how different DBS targets modulate network activity in connected brain regions.

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“…This effect was accompanied by a substantial increase in FC mainly between the left NBM and several regions of the paralimbic network. DBS is a powerful neuromodulatory therapeutic tool used in the treatment of neurological conditions, such as depression (Mayberg et al, 2005), addiction (Heinze et al, 2009), Parkinson's disease (Fasano et al, 2012;Odekerken et al, 2013), and obsessive compulsive disorder (Figee et al, 2013;Le Jeune et al, 2010). Moreover, there is tremendous potential for DBS-centered therapy in restoring arousal, goal-directed behaviors, communication, and consciousness in patients afflicted with disorders of consciousness (Schiff, 2012).…”

Section: Discussionmentioning

confidence: 99%

Brainstem Stimulation Increases Functional Connectivity of Basal Forebrain-Paralimbic Network in Isoflurane-Anesthetized Rats

et al. 2014

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Brain states and cognitive-behavioral functions are precisely controlled by subcortical neuromodulatory networks. Manipulating key components of the ascending arousal system (AAS), via deep-brain stimulation, may help facilitate global arousal in anesthetized animals. Here we test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) under light isoflurane anesthesia, associated with loss of consciousness, leads to cortical desynchronization and specific changes in blood-oxygenation-level-dependent (BOLD) functional connectivity (FC) of the brain. BOLD signals were acquired simultaneously with frontal epidural electroencephalogram before and after PnO stimulation. Whole-brain FC was mapped using correlation analysis with seeds in major centers of the AAS. PnO stimulation produced cortical desynchronization, a decrease in d-and h-band power, and an increase in approximate entropy. Significant increases in FC after PnO stimulation occurred between the left nucleus Basalis of Meynert (NBM) as seed and numerous regions of the paralimbic network. Smaller increases in FC were present between the central medial thalamic nucleus and retrosplenium seeds and the left caudate putamen and NBM. The results suggest that, during light anesthesia, PnO stimulation preferentially modulates basal forebrain-paralimbic networks. We speculate that this may be a reflection of disconnected awareness.

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Decrease of Prefrontal Metabolism After Subthalamic Stimulation in Obsessive-Compulsive Disorder: A Positron Emission Tomography Study

Cited by 111 publications

References 39 publications

Neural basis of impaired safety signaling in Obsessive Compulsive Disorder

Neural basis of impaired safety signaling in Obsessive Compulsive Disorder

Network effects of deep brain stimulation

Brainstem Stimulation Increases Functional Connectivity of Basal Forebrain-Paralimbic Network in Isoflurane-Anesthetized Rats

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