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Much attention is currently devoted to developing diagnostic classifiers for mental disorders. Complementing these efforts, we highlight the potential of machine learning to gain biological insights into the psychopathology and nosology of mental disorders. Studies to this end have mainly used brain imaging data, which can be obtained noninvasively from large cohorts and have repeatedly been argued to reveal potentially intermediate phenotypes. This may become particularly relevant in light of recent efforts to identify magnetic resonance imaging–derived biomarkers that yield insight into pathophysiological processes as well as to refine the taxonomy of mental illness. In particular, the accuracy of machine learning models may be used as dependent variables to identify features relevant to pathophysiology. Moreover, such approaches may help disentangle the dimensional (within diagnosis) and often overlapping (across diagnoses) symptomatology of psychiatric illness. We also point out a multiview perspective that combines data from different sources, bridging molecular and system-level information. Finally, we summarize recent efforts toward a data-driven definition of subtypes or disease entities through unsupervised and semisupervised approaches. The latter, blending unsupervised and supervised concepts, may represent a particularly promising avenue toward dissecting heterogeneous categories. Finally, we raise several technical and conceptual aspects related to the reviewed approaches. In particular, we discuss common pitfalls pertaining to flawed input data or analytic procedures that would likely lead to unreliable outputs.

WOS: 000335738000006 PubMed ID: 24768322 Background: Herpes simplex virus (HSV) is one of the most common causes of sporadic encephalitis worldwide. Objective: We aimed to determine clinical characteristics and prognosis of HSV encephalitis (HSVE) cases reviewed retrospectively from several collaborating centers. Study design: We searched hospital archives of the last 10 years for patients with HSVE diagnosis, i.e. clinical presentation compatible with encephalitis and brain involvement on magnetic resonance imaging (MRI) and/or detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction (PCR). Clinical characteristics were noted and patients were phone-interviewed. HSVE cases were grouped and analyzed as proven and probable, based on virological confirmation by PCR. Univariate and multivariate analyses were used to determine factors associated with prognosis. Results: A total of 106 patients (63 males and 43 females; mean age, 44 years; range, 18-83 years) were included. Most common symptoms were changes in mental status, fever, headache, and seizure. HSV PCR was positive in 69% of patients tested, while brain involvement was detected on MRI in 95%. Acyclovir was started mostly within five days of main symptom and continued for >= 14 days. Case fatality rate was 8%, while 69% of patients recovered with sequelae. Favorable prognosis was observed in 73% of patients. Multivariate analysis identified the duration of disease before hospital admission (odds ratio (OR) = 1.24) and the extent of brain involvement on MRI at the time of admission (OR = 37.22) as two independent risk factors associated with poor prognosis. Conclusions: Although HSVE fatality regressed considerably with acyclovir treatment, many patients survive with sequelae. Our results emphasize the importance of early diagnosis and prompt treatment of HSVE.

Background: Folate metabolism disorders can affect various organ systems, including the nervous system. 5,10-methenyltetrahydrofolate synthetase deficiency is a rare cerebral folate deficiency in which MTHFS activity is disrupted with low-normal cerebrospinal fluid (CSF) 5,10-methenyltetrahydrofolate levels, while peripheral folate levels are normal. Case report: We present here a female patient with developmental delay, microcephaly, hypotonia, nystagmus, and seizure in which a distinct brain MRI and CT showed restricted diffusion in the bilateral parietal and occipital lobes, and calcifications of the bilateral putamen, globus pallidus, and caudate nucleus, and the bilateral parietal and occipital lobes. Laboratory tests revealed macrocytic anemia, increased homocysteine, low-normal CSF 5,10-methenyltetrahydrofolate, and low CSF folate, but normal serum vitamin B12 and folate levels. A whole exome sequencing analysis verified the diagnosis of 5,10-methenyltetrahydrofolate synthetase deficiency. Conclusions: We have added novel knowledge which is nystagmus and hypotonia in the clinical findings, the involvement and restriction of bilateral putamen, globus pallidus, parietal and occipital lobes, and calcification of the bilateral putamen, globus pallidus, caudate nucleus, and parietal and occipital lobes in neuroimaging images and also low CSF folate in the metabolic investigation with the patient in 5,10-methenyltetrahydrofolate synthetase deficiency.(c) 2022 The Japanese Society of Child Neurology Published by Elsevier B.V. All rights reserved.

International audience; During development, when synapses start to be established, a primitive form of network-driven activity provides most of the synaptic activity. This pattern enables a high degree of synchrony in immature neurons in spite of the small number of functional synapses and could participate in activity-dependent growth and synapse formation. Relying on the giant depolarizing potentials that provide most of the synaptic activity in the developing hippocampus, this article reviews the common properties and generating mechanisms of these patterns, and particularly the role of the early depolarizing action of GABA(A) and glycine receptors and the sequential expression of GABA and glutamate synapses. Patterns similar to giant depolarizing potentials have been observed in a wide range of structures and species suggesting that there is a temporal template throughout evolution that constitutes an essential step in the formation of functional networks.

Background and Objectives: Emotion regulation involves attempts to influence emotion unfolding and may target experiential, expressive and physiological responses. Several strategies can be used, such as reappraisal (re-evaluating the emotional situation to reduce its emotional meaning) or distraction (turning the attention toward non-emotional aspects of the situation). Previous research on these regulation strategies produced contrasting results regarding their efficiency and we hypothesize that this could be due to individual differences such as trait anxiety. Design and Methods: Participants (N = 77) were confronted with negative pictures and we examined the differential emotional reactivity according to trait anxiety, followed by a comparison of the efficiency of reappraisal and distraction in reducing emotional responses. Results: Results show that trait anxiety has no impact on reactivity at the experiential and expressive levels, but has an impact at the physiological level, where high anxiety individuals show increased cardiac orienting effect, as well as higher skin conductance and respiratory rate. Regarding regulation, reappraisal and distraction successfully reduce emotional experience and expressivity, but not physiological arousal. Conclusions: Such contrasting results involve that high trait anxiety individuals might benefit from the use of other kinds of strategies than reappraisal and distraction, some that may successfully target physiological responses.

Objective: To investigate cerebral activity associated with allodynia in patients with neuropathic pain. Methods: The brain responses of 27 patients with peripheral (5), spinal (3), brainstem (4), thalamic (5), lenticular (5), or cortical (5) lesions were studied with fMRI as innocuous mechanical stimuli were addressed to either the allodynic territory or the homologous contralateral region. Results: When applied to the normal side, brush and cold rubbing stimuli did not evoke pain and activated a somatosensory “control” network including contralateral primary (SI) and secondary (SII) somatosensory cortices and insular regions. The same stimuli became severely painful when applied to the allodynic side and activated regions in the contralateral hemisphere that mirrored the “control” network, with, however, lesser activation of the SII and insular cortices. Increased activation volumes were found in contralateral SI and primary motor cortex (MI). Whereas ipsilateral responses appeared very small and restricted after control stimuli, they represented the most salient effect of allodynia and were observed mainly in the ipsilateral parietal operculum (SII), SI, and insula. Allodynic stimuli also recruited additional responses in motor/premotor areas (MI, supplementary motor area), in regions involved in spatial attention (posterior parietal cortices), and in regions linking attention and motor control (mid-anterior cingulate cortex). Conclusion: On a background of deafferentation in the hemisphere contralateral to stimuli, enhanced or additional responses to innocuous stimuli in the ipsilateral hemisphere may contribute to the shift of perception from innocuous toward painful and ill-defined sensations.

International audience; Using extracellular single unit recordings alone or in combination with neurobiotin juxtacellular labeling and orexin (hypocretin) immunohistochemistry in the mouse, we have recorded a total of 452 neurons in the orexin neuron field of the posterior hypothalamus. Of these, 76 exhibited tonic discharge highly specific to wakefulness, referred to as waking-active neurons. They showed differences from each other in terms of spike shape, activity profile, and response to an arousing sound stimulus and could be classified into three groups on the basis of spike shape as: 1) biphasic broad; 2) biphasic narrow; and 3) triphasic. Waking-active neurons characterized by biphasic broad spikes were orexin-immunopositive, whereas those characterized by either biphasic narrow or triphasic broad spikes were orexin-immunonegative. Unlike waking-specific histamine neurons, all orexin and non-orexin waking-active neurons exhibited slow (<10 Hz) tonic discharges during wakefulness and ceased firing shortly after the onset of electroencephalogram (EEG) synchronization (deactivation), the EEG sign of sleep (drowsy state). They remained virtually silent during slow-wave sleep, but displayed transient discharges during paradoxical (or rapid eye movement) sleep. During the transition from sleep to wakefulness, both orexin and triphasic non-orexin neurons fired in clusters prior to the onset of EEG activation, the EEG sign of wakefulness, and responded with a short latency to an arousing sound stimulus given during sleep. In contrast, the biphasic narrow non-orexin neurons fired in single spikes either prior to, or after, EEG activation during the same transition and responded to the stimulus with a longer latency. The activity of all waking-active neurons preceded the return of muscle tonus at the transition from paradoxical sleep to wakefulness. These data support the view that the activity of orexin and non-orexin waking-active neurons in the posterior hypothalamus plays an important wake-promoting role and that their activity antagonizes cortical deactivation and loss of muscle tone.

Orbitofrontal Reality Filtering (ORFi) denotes a cognitive process that allows our thoughts and behaviors to be congruent with the ongoing reality. ORFi appears to use a mechanism signaling when an anticipation is now invalid. It intervenes at an early stage of processing, at 200-300 ms, and is associated with activation of the posterior medial OFC. However, situations involving ambiguity may render it difficult to determine when previous anticipations are no longer valid. In the present thesis, we investigate how precisely the brain deals with such ambiguous situations. We first showed that the brain uses at least two distinct processes evaluating the absence of anticipated outcomes with unequivocal or ambiguous behavioral relevance. We next showed that the OFC flexibly adjusts the processing of outcomes depending on whether they require or not behavioral adaptation in the present context. Le filtre orbitofrontal de la réalité (ORFi) représente un processus cognitif qui permet à nos pensées et comportements d'être en accord avec la réalité. L'ORFi utilise un mécanisme permettant d'apprendre qu'une anticipation précédemment valide, ne l'est plus. Il apparaît très précocement dans le traitement cognitif, à 200-300 ms, et est associé à une activation de l'OFC médial postérieur. Néanmoins, des situations impliquant de l'ambiguïté peuvent induire des difficultés à déterminer lorsque ces anticipations ne sont plus valides. Dans cette thèse, nous cherchons alors à savoir précisément comment le cerveau gère ces situations d'ambiguïté. Premièrement, nous observons que le cerveau utilise au moins deux processus distincts évaluant une absence d'anticipations en fonction de sa pertinence comportementale, sans équivoque ou ambiguë. Nous notons également que l'OFC est particulièrement approprié pour déterminer si un même résultat implique ou non un changement de comportement, décidant si les pensées réfèrent ou non à la réalité selon le contexte actuel.