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Background: Transcranial ultrasound stimulation (TUS) is a non-invasive brain stimulation technique; when skull aberrations are compensated for, this technique allows, with millimetric accuracy, circumvention of the invasive surgical procedure associated with deep brain stimulation (DBS) and the limited spatial specificity of transcranial magnetic stimulation. Objective: /hypothesis: We hypothesize that MR-guided low-power TUS can induce a sustained decrease of tremor power in patients suffering from medically refractive essential tremor. Methods: The dominant hand only was targeted, and two anatomical sites were sonicated in this exploratory study: the ventral intermediate nucleus of the thalamus (VIM) and the dentato-rubro-thalamic tract (DRT). Patients (N = 9) were equipped with MR-compatible accelerometers attached to their hands to monitor their tremor in real-time during TUS. Results: VIM neurostimulations followed by a low-duty cycle (5 %) DRT stimulation induced a substantial decrease in the tremor power in four patients, with a minimum of 89.9 % reduction when compared with the baseline power a few minutes after the DRT stimulation. The only patient stimulated in the VIM only and with a low duty cycle (5 %) also experienced a sustained reduction of the tremor (up to 93.4 %). Four patients (N = 4) did not respond. The temperature at target was 37.2 ± 1.4 °C compared to 36.8 ± 1.4 °C for a 3 cm away control point. Conclusions: MR-guided low power TUS can induce a substantial and sustained decrease of tremor power. Follow-up studies need to be conducted to reproduce the effect and better to understand the variability of the response amongst patients. MR thermometry during neurostimulations showed no significant thermal rise, supporting a mechanical effect.

Abstract Background Catatonia is a psychomotor syndrome frequently observed in disorders with neurodevelopmental impairments, including psychiatric disorders such as schizophrenia. The orbitofrontal cortex (OFC) has been repeatedly associated with catatonia. It presents with an important interindividual morphological variability, with three distinct H-shaped sulcal patterns, types I, II, and III, based on the continuity of the medial and lateral orbital sulci. Types II and III have been identified as neurodevelopmental risk factors for schizophrenia. The sulcal pattern of the OFC has never been investigated in catatonia despite the role of the OFC in the pathophysiology and the neurodevelopmental component of catatonia. Methods In this context, we performed a retrospective analysis of the OFC sulcal pattern in carefully selected homogeneous and matched subgroups of schizophrenia patients with catatonia (N = 58) or without catatonia (N = 65), and healthy controls (N = 82). Results Logistic regression analyses revealed a group effect on OFC sulcal pattern in the left (χ 2 = 18.1; p

Transcranial ultrasound stimulation (TUS) has been shown to be a safe and effective technique for non-invasive superficial and deep brain stimulation. Safe and efficient translation to humans requires estimating the acoustic attenuation of the human skull. Nevertheless, there are no international guidelines for estimating the impact of the skull bone. A tissue independent, arbitrary derating was developed by the U.S. Food and Drug Administration to take into account tissue absorption (0.3 dB/cm-MHz) for diagnostic ultrasound. However, for the case of transcranial ultrasound imaging, the FDA model does not take into account the insertion loss induced by the skull bone, nor the absorption by brain tissue. Therefore, the estimated absorption is overly conservative which could potentially limit TUS applications if the same guidelines were to be adopted. Here we propose a three-layer model including bone absorption to calculate the maximum pressure transmission through the human skull for frequencies ranging between 100 kHz and 1.5 MHz. The calculated pressure transmission decreases with the frequency and the thickness of the bone, with peaks for each thickness corresponding to a multiple of half the wavelength. The 95th percentile maximum transmission was calculated over the accessible surface of 20 human skulls for 12 typical diameters of the ultrasound beam on the skull surface, and varies between 40% and 78%. To facilitate the safe adjustment of the acoustic pressure for short ultrasound pulses, such as transcranial imaging or transcranial ultrasound stimulation, a table summarizes the maximum pressure transmission for each ultrasound beam diameter and each frequency.

Major depressive disorder (MDD) is the psychiatric disorder with the highest prevalence in the world. Pharmacological antidepressant treatment (AD), such as selective serotonin reuptake inhibitors [SSRI, i.e., fluoxetine (Flx)] is the first line of treatment for MDD. Despite its efficacy, lack of AD response occurs in numerous patients characterizing Difficult-to-treat Depression. ElectroConvulsive Therapy (ECT) is a highly effective treatment inducing rapid improvement in depressive symptoms and high remission rates of ∼50–63% in patients with pharmaco-resistant depression. Nevertheless, the need to develop reliable treatment response predictors to guide personalized AD strategies and supplement clinical observation is becoming a pressing clinical objective. Here, we propose to establish a proteomic peripheral biomarkers signature of ECT response in an anxio/depressive animal model of non-response to AD. Using an emotionality score based on the analysis complementary behavioral tests of anxiety/depression (Elevated Plus Maze, Novelty Suppressed Feeding, Splash Test), we showed that a 4-week corticosterone treatment (35 μg/ml, Cort model) in C57BL/6JRj male mice induced an anxiety/depressive-like behavior. A 28-day chronic fluoxetine treatment (Flx, 18 mg/kg/day) reduced corticosterone-induced increase in emotional behavior. A 50% decrease in emotionality score threshold before and after Flx, was used to separate Flx-responding mice (Flx-R, n = 18), or Flx non-responder mice (Flx-NR, n = 7). Then, Flx-NR mice received seven sessions of electroconvulsive seizure (ECS, equivalent to ECT in humans) and blood was collected before and after ECS treatment. Chronic ECS normalized the elevated emotionality observed in Flx-NR mice. Then, proteins were extracted from peripheral blood mononuclear cells (PBMCs) and isolated for proteomic analysis using a high-resolution MS Orbitrap. Data are available via ProteomeXchange with identifier PXD037392. The proteomic analysis revealed a signature of 33 peripheral proteins associated with response to ECS (7 down and 26 upregulated). These proteins were previously associated with mental disorders and involved in regulating pathways which participate to the depressive disorder etiology.

Catatonia is a severe neuropsychiatric syndrome, usually treated by benzodiazepines and electroconvulsive therapy. However, therapeutic alternatives are limited, which is particularly critical in situations of treatment resistance or when electroconvulsive therapy is not available. Transcranial direct-current stimulation (tDCS) is a promising non-invasive neuromodulatory technique that has shown efficacy in other psychiatric conditions. We present the largest case series of tDCS use in catatonia, consisting of eight patients in whom tDCS targeting the left dorsolateral prefrontal cortex and temporoparietal junction was employed. We used a General Linear Mixed Model to isolate the effect of tDCS from other confounding factors such as time (spontaneous evolution) or co-prescriptions. The results indicate that tDCS, in addition to symptomatic pharmacotherapies such as lorazepam, seems to effectively reduce catatonic symptoms. These results corroborate a synthesis of five previous case reports of catatonia treated by tDCS in the literature. However, the specific efficacy of tDCS in catatonia remains to be demonstrated in a randomized controlled trial. The development of therapeutic alternatives in catatonia is of paramount importance.

Since the late 2010s, Transcranial Ultrasound Stimulation (TUS) has been used experimentally to carryout safe, non-invasive stimulation of the brain with better spatial resolution than Transcranial Magnetic Stimulation (TMS). This innovative stimulation method has emerged as a novel and valuable device for studying brain function in humans and animals. In particular, single pulses of TUS directed to oculomotor regions have been shown to modulate visuomotor behavior of non-human primates during 100 ms ultrasound pulses. In the present study, a sustained effect was induced by applying 20-s trains of neuronavigated repetitive Transcranial Ultrasound Stimulation (rTUS) to oculomotor regions of the frontal cortex in three non-human primates performing an antisaccade task. With the help of MRI imaging and a frame-less stereotactic neuronavigation system (SNS), we were able to demonstrate that neuronavigated TUS (outside of the MRI scanner) is an efficient tool to carry out neuromodulation procedures in non-human primates. We found that, following neuronavigated rTUS, saccades were significantly modified, resulting in shorter latencies compared to no-rTUS trials. This behavioral modulation was maintained for up to 20 min. Oculomotor behavior returned to baseline after 18–31 min and could not be significantly distinguished from the no-rTUS condition. This study is the first to show that neuronavigated rTUS can have a persistent effect on monkey behavior with a quantified return-time to baseline. The specificity of the effects could not be explained by auditory confounds.

Employment rate in psychiatry is around 10 to 30%. Cognitive remediation (CR) associated with psychosocial rehabilitation shows good functional outcomes, with a high level of satisfaction in participants provided by tailored CR. However, few studies looked at the long-term outcome in participants who experienced such a program. This retrospective survey examines the outcome of persons having psychiatric diseases 2 to 9 years after being treated with a personalized CR program. The survey included 12 domains with questions relevant to work, studies, before CR (T1) and at the moment of the survey (T2), questions about housing, relatedness, familiar relationships and daily activities at T2. Finally, a narrative interview was included to express feelings of the participants about CR. Sixty-six participants completed the survey, and were treated with neurocognitive or social cognition programs. Their diagnosis was: schizophrenia (80.3%), neurodevelopment disorder (autism as well as genetic or metabolic disease with psychiatric expression) (15.2%) and bipolar disorder (4.5%). The comparison between T1 and T2 showed significant difference for job employment (P < 0.001), even for competitive jobs (p < 0.007), for performing studies (p = 0.033), for practicing a physical activity (0.033) or reading (0.002). Outcome was also examined in reference to the delay from CR to highlight changes in patient characteristics and service delivery over the years. Hence, the total sample was split in two subgroups: CR delivered in 2009–2013 (n = 37); CR delivered in 2014–2016 (n = 29). While in the former group more participants were working (p = 0.037), in the latter group, which was younger (p = 0.04), more participants were studying (p = 0.02). At T2, a majority of persons experienced no relapse, three years (79.1%) to 8 years (56.8%) after CR, when referring to the anamnesis. Concerning subjective perception of CR, participants expressed feelings concerning positive impact on clarity of thought, on cognitive functions, self-confidence, perceiving CR as an efficient help for work and studies. To conclude, even long years after a personalized CR program, good benefits in terms of employment or studies emerge when compared to the status before CR, with good determinants for recovery in terms of leisure or physical activity practice.

Interactions between social cognition and symptoms of schizophrenia have been investigated, but mostly component by component. Here we tested the assumption that two categories of deficits exist depending on clinical profiles, one corresponding to a defect in social cognition – “under-social cognition” – and one corresponding to excessive attributions leading to social cognitive impairments – “over-social cognition”. To conduct the investigation, we performed a Hierarchical Clustering Analysis using positive and negative symptoms in seventy patients with schizophrenia and we compared the clusters obtained to a group of healthy controls on social cognitive measures. We distinguished two social cognitive profiles based on prevailing symptoms for emotion processes and Theory of Mind. Actually, patients with negative symptoms showed lower performances in emotion recognition task than both those with positive symptoms and controls. Concerning Theory of Mind, patients with positive symptoms had a significant tendency to make over interpretative errors than both patients with negative symptoms and controls. For other processes assessed, further explorations are needed. Actually, concerning social perception and knowledge both patients' groups presented significant impairments compared to controls. Assessment of attribution bias showed that patients in the positive group presented a significant hostility bias and a higher intentionality score compared to healthy controls. These results favor the existence of different categories of impairments depending more on the clinical characteristics of patients than on nosographical categories, but further investigations are now necessary to specify these profiles. It nevertheless showed the importance of assessing symptoms in relationship with cognitive functioning. Keywords: Social cognition, Schizophrenia, Symptoms, Emotion, Theory of mind, Attribution style