Nicolas Langbour

Neuronal activity correlated with checking behaviour in the subthalamic nucleus of patients with obsessive–compulsive disorder

Doubt, and its behavioural correlate, checking, is a normal phenomenon of human cognition that is dramatically exacerbated in obsessive-compulsive disorder. We recently showed that deep brain stimulation in the associative-limbic area of the subthalamic nucleus, a central core of the basal ganglia, improved obsessive-compulsive disorder. To understand the physiological bases of symptoms in such patients, we recorded the activity of individual neurons in the therapeutic target during surgery while subjects performed a cognitive task that gave them the possibility of unrestricted repetitive checking after they had made a choice. We postulated that the activity of neurons in this region could be influenced by doubt and checking behaviour. Among the 63/87 task-related neurons recorded in 10 patients, 60% responded to various combinations of instructions, delay, movement or feedback, thus highlighting their role in the integration of different types of information. In addition, task-related activity directed towards decision-making increased during trials with checking in comparison with those without checking. These results suggest that the associative-limbic subthalamic nucleus plays a role in doubt-related repetitive thoughts. Overall, our results not only provide new insight into the role of the subthalamic nucleus in human cognition but also support the fact that subthalamic nucleus modulation by deep brain stimulation reduced compulsive behaviour in patients with obsessive-compulsive disorder.

Evolution of brain gray matter loss in Huntington's disease: a meta-analysis.

Huntingtons disease is characterized by neuronal loss throughout the disease course. Voxel‐based morphometry studies have reported reductions in gray matter concentration (GMC) in many brain regions in patients with Huntington. The description of the time course of gray matter loss may help to identify some evolution markers. Here, we conducted a meta‐analysis of voxel‐based morphometry studies of Huntingtons disease to describe the evolution of brain gray matter loss.

Contextual and behavioral influences on uncertainty in obsessive-compulsive disorder

INTRODUCTION Behavioral adaptation generally follows the contextual changes arising from the consequences (rewards and punishments) of an action. According to the reciprocal determinism model, there is a mutual influence between external context, cognitive processes and behavior. The maladaptive behaviors observed in obsessive-compulsive disorder (OCD) have been hypothesized to result from the disruption of the interactions between these three entities. For this, we assessed the influence of error signals and checking behavior on prefrontal cortical functions during decision-making in 14 OCD patients and 14 matched healthy participants. METHODS We used a behavioral task designed to elicit intolerance of uncertainty (IU) followed by the free expression of checking behaviors, which was coupled with functional magnetic resonance imaging. RESULTS At the behavioral level, IU intensity was correlated to the number of checking behaviors in both checking OCD patients and healthy controls during decision-making. However, external error signals did not influence checking behaviors in OCD patients, whereas they appeared to trigger checking behaviors in healthy subjects. At the neural level, IU intensity was positively correlated with activation in the orbitofrontal cortex (OFC) in both the OCD and control groups. At the region of interest (ROI) level, error signals increased IU-related OFC activations; in contrast, checking behaviors contributed to decreasing these neural activations in the healthy subjects, but no such modulation was observed in the OCD patients. CONCLUSIONS Our results show that IU-related OFC dysfunctions are not under the influence of the context and the behavioral response in OCD, suggesting that alterations of the dynamic features for this neural network may contribute to the expression of OCD symptoms.

Electrophysiological Correlates of a Versatile Executive Control System in the Monkey Anterior Cingulate Cortex

When a subject faces conflicting situations, decision-making becomes uncertain. The human dorsal anterior cingulate cortex (dACC) has been repeatedly implicated in the monitoring of such situations, and its neural activity is thought to be involved in behavioral adjustment. However, this hypothesis is mainly based on neuroimaging results and is challenged by animal studies that failed to report any neuronal correlates of conflict monitoring. This discrepancy is thought be due either to methodological or more fundamental cross-species differences. In this study, we eliminated methodological biases and recorded single-neuron activity in monkeys performing a Stroop-like task. We found specific changes in dACC activity during incongruent trials but only in a small subpopulation of cells. Critically, these changes were not related to reaction time and were absent before any incorrect action was taken. A larger fraction of neurons exhibited sustained activity during the whole decision period, whereas another subpopulation of neurons was modulated by reaction time, with a gradual increase in their firing rate that peaked at movement onset. Most of the neurons found in these subpopulations exhibited activity after the delivery of an external negative feedback stimulus that indicated an error had been made. These findings, which are consistent with an executive control role, reconcile various theories of prefrontal cortex function and support the homology between human and monkey cognitive architectures.

Inverse relationship between thalamic and orbitofrontal volumes in obsessive-compulsive disorder.

Volumetric magnetic resonance imaging (MRI) studies in obsessive-compulsive disorder (OCD) have reported a smaller volume of the orbitofrontal cortex (OFC) and a larger volume of the thalamus compared with healthy controls. Both of these brain regions are strongly connected; therefore, it may be hypothesized that cortical and thalamic alterations are related. Here, we investigated the relationship between thalamic and orbitofrontal volumes in OCD patients relative to healthy controls. MRI volumetric measurements of the thalamus and the OFC were obtained in 16 OCD patients without comorbidity and 16 comparison subjects matched for age, sex and educational level. Partial correlation analyses that controlled for intracranial volume (ICV) were performed to explore relationships between thalamic and OFC volumes in each group. In order to assess the specificity of this relationship, we conducted similar analyses of the anterior cingulate cortex (ACC) as a non-OFC cortical volume. Finally, by using data from previously published volumetric MRI studies, we conducted a meta-regression to explore the relationships between volume changes in these regions of interest. Results showed that thalamic volumes were significantly negatively correlated with OFC volumes in OCD patients (r=-0.83, p<0.001), but not in healthy subjects (r=-0.15, p=0.59). A significant relationship between thalamic and ACC volumes was found neither in the OCD patients (r=0.03, p=0.91) nor in the comparison subjects (r=-0.23, p=0.40). Furthermore, meta-regression analyses showed that previously reported volume changes in the thalamus were significantly correlated with OFC volume changes (r=-0.71, p<0.05), but not with ACC volume changes (r=0.07, p=0.86). Although our results do not allow for any causal relationship to be established, they suggest that structural alterations of both the thalamus and the OFC are inversely and specifically related in OCD.

1H magnetic resonance spectroscopy suggests neural membrane alteration in specific regions involved in obsessive-compulsive disorder

Obsessive Compulsive Disorder (OCD) is the fourth most common psychiatric disorder, after phobias, addiction to alcohol and drugs, and depressive disorders, with prevalence between 1.2% to 2.4% (Karno et al., 1988; Robins et al., 1985; Ruscio et al., 2010). Recommended first-line treatment is based on cognitive behavioural therapy (CBT) combined with antidepressant treatments (primarily Serotonin Reuptake Inhibitors SRI antidepressants). However, 40–60% of OCD patients exhibit drug resistance, leaving them with a major handicap in everyday life (Jaafari et al., 2011). It is therefore essential to better understand the anatomical substrates and neurophysiopathologic mechanisms of OCD. Based on phenomenology and neuropsychology results, structural and functional neuroimaging studies have shown the involvement of the Cortico-StriatoThalamo-Cortical (CSTC) network in OCD including: the frontal cortex with the orbitofrontal cortex (OFC), the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC), and basal ganglia (striatum and thalamus) (Aouizerate et al., 2004; Menzies et al., 2008; Nakao et al., 2014; Pauls et al., 2014). Magnetic resonance spectroscopy (MRS) is a non-invasive technique that can assess biochemical alterations in the brain in vivo (Keshavan et al., 2000; Stanley, 2002). A dramatic increase of metabolic knowledge in psychiatric disorders has led to focus on the potential ability of spectroscopy to provide “in vivo” insights on this topic. In a specific way, proton (H) MRS can detect several metabolites implicated in neuronal viability and glial functions. First, N-acetylaspartate (NAA), which is a quantitative marker of neuronal suffering; then creatine (Cr), a marker of cellular energy metabolism; myo-ionositol (mI), a marker for glial density; the glutamatergic complex (Glx) divided into glutamate (excitation neurotransmitter), glutamine (derived from glutamate), and gamma-amino butyric acid (GABA) (inhibitory neurotransmitter); and finally, choline (Cho), a marker of membrane metabolism. Increased choline levels have been associated with either increased synthesis or degradation of the metabolism of cell membrane in Alzheimer and multiple sclerosis (McClure et al., 1994; Tartaglia et al., 2002). Considering CSTC network dysfunction, several studies using HMRS have found changes in neural metabolite concentrations among OCD patients in this area. The main results showed increased concentrations of N-Acetylaspartate (NAA) in frontal white matter (FWM) (Weber et al., 2014) and decreased NAA concentrations in ACC (Jang et al., 2006; O’Neill et al., 2013; Tükel et al., n.d.; Yücel et al., 2007), striatum (Bartha et al., 1998; Ebert et al., 1997), thalamus (Fitzgerald et al., 2000; Rosenberg et al., 2001) and hippocampus (Atmaca et al., 2009) in OCD patients. However, one study has found lower concentrations of NAA in the FWM along with increased rates in the ACC before treatment. Moreover, it is important to note that two MRS-H studies after treatment (SSRI or CBT) have shown normalization of NAA concentrations in the prefrontal cortex, FWM, ACC and caudate nucleus (Jang et al., 2006; Whiteside et al., 2012). These metabolite changes could therefore reflect not a definitive neuronal loss but rather a potentially reversible alteration. Therefore, decreased NAA in the CSTC circuit could indicate suffering involving neural structures. However, few studies have yielded significant results concerning Cho. Three of them found an increase of this metabolite in the FWM and the thalamus (Aoki et al., 2012; Fan et al., 2017; Mirza et al., 2006). Glutamate complex (Glx) variations in the caudate nucleus have been observed after treatment (SSRIs or CBT) (Bolton et al., 2001; Moore et al., 1998; O’Neill et al., 2013; Rosenberg et al., 2000; Whiteside et al., 2012). More recently, Park and al. found lower glutamine/glutamate concentration in OCD patients compared to healthy controls (Park et al., 2017). The results of those numerous previous studies remain inconsistent (Aoki et al., 2012; Brennan et al., 2013; O’Neill et al., 2016).

Identifying Oneself with the Face of Someone Else Impairs the Egocentered Visuo-spatial Mechanisms: A New Double Mirror Paradigm to Study Self–other Distinction and Interaction

Looking at our face in a mirror is one of the strongest phenomenological experiences of the Self in which we need to identify the face as reflected in the mirror as belonging to us. Recent behavioral and neuroimaging studies reported that self-face identification not only relies upon visual-mnemonic representation of one’s own face but also upon continuous updating and integration of visuo-tactile signals. Therefore, bodily self-consciousness plays a major role in self-face identification, with respect to interplay between unisensory and multisensory processing. However, if previous studies demonstrated that the integration of multisensory body-related signals contributes to the visual processing of one’s own face, there is so far no data regarding how self-face identification, inversely, contributes to bodily self-consciousness. In the present study, we tested whether self–other face identification impacts either the egocentered or heterocentered visuo-spatial mechanisms that are core processes of bodily self-consciousness and sustain self–other distinction. For that, we developed a new paradigm, named “Double Mirror.” This paradigm, consisting of a semi-transparent double mirror and computer-controlled Light Emitting Diodes, elicits self–other face merging illusory effect in ecologically more valid conditions, i.e., when participants are physically facing each other and interacting. Self-face identification was manipulated by exposing pairs of participants to an Interpersonal Visual Stimulation in which the reflection of their faces merged in the mirror. Participants simultaneously performed visuo-spatial and mental own-body transformation tasks centered on their own face (egocentered) or the face of their partner (heterocentered) in the pre- and post-stimulation phase. We show that self–other face identification altered the egocentered visuo-spatial mechanisms. Heterocentered coding was preserved. Our data suggest that changes in self-face identification induced a bottom-up conflict between the current visual representation and the stored mnemonic representation of one’s own face which, in turn, top-down impacted bodily self-consciousness.

Bruxism in craniocervical dystonia: a prospective study.

Aims: Bruxism pathophysiology remains unclear, and its occurrence has been poorly investigated in movement disorders. The aim of this study was to compare the frequency of bruxism in patients with craniocervical dystonia vs. normal controls and to determine its associated clinical features. Method: This is a prospective-control study. A total of 114 dystonic subjects (45 facial dystonia, 69 cervical dystonia) and 182 controls were included. Bruxism was diagnosed using a hetero-questionnaire and a clinical examination performed by trained dentists. Occurrence of bruxism was compared between the different study populations. A binomial logistic regression analysis was used to determine which clinical features influenced bruxism occurrence in each population. Results: The frequency of bruxism was significantly higher in the dystonic group than in normal controls but there was no difference between facial and cervical dystonia. It was also higher in women than in men. Bruxism features were similar between normal controls and dystonic patients except for a higher score of temporomandibular jaw pain in the dystonic group. Discussion: The higher frequency of bruxism in dystonic patients suggests that bruxism is increased in patients with basal ganglia dysfunction but that its nature does not differ from that seen in bruxers from the normal population.

Checking behavior in rhesus monkeys is related to anxiety and frontal activity

When facing doubt, humans can go back over a performed action in order to optimize subsequent performance. The present study aimed to establish and characterize physiological doubt and checking behavior in non-human primates (NHP). We trained two rhesus monkeys (Macaca mulatta) in a newly designed “Check-or-Go” task that allows the animal to repeatedly check and change the availability of a reward before making the final decision towards obtaining that reward. By manipulating the ambiguity of a visual cue in which the reward status is embedded, we successfully modulated animal certainty and created doubt that led the animals to check. This voluntary checking behavior was further characterized by making EEG recordings and measuring correlated changes in salivary cortisol. Our data show that monkeys have the metacognitive ability to express voluntary checking behavior similar to that observed in humans, which depends on uncertainty monitoring, relates to anxiety and involves brain frontal areas.