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In the last decades, planar multi-electrode arrays (MEAs) have been widely used to record activity from in vitro neuronal cell cultures and tissue slices. Though successful, this technique bears some limitations, particularly relevant when applied to three-dimensional (3D) tissue, such as brain slices, spheroids or organoids. For example, planar MEAs signals are informative on just one side of a 3D-organized structure. This limits the interpretation of the results in terms of network functions in a complex structured and hyperconnected brain tissue. Moreover, the side in contact with the MEAs often shows lower oxygenation rates and related vitality issues. To overcome these problems, we empowered a CMOS high-density multi-electrode array (HD-MEA) with thousands of microneedles (μneedles) of 65-90 μm height, able to penetrate and record in-tissue signals, providing for the first time a 3D HD-MEA chip. We propose a CMOS-compatible fabrication process to produce arrays of μneedles of different widths mounted on large pedestals to create microchannels underneath the tissue. By using cerebellar and cortico-hippocampal slices as a model, we show that the μneedles efficiently penetrate the 3D tissue while the microchannels allow the flowing of maintenance solutions to increase tissue vitality in the recording sites. These improvements are reflected by the increase in electrodes sensing capabilities, the number of sampled neuronal units (compared to matched planar technology), and the efficiency of compound effects. Importantly, each electrode can also be used to stimulate the tissue with optimal efficiency due to the 3D structure. Furthermore, we demonstrate how the 3D HD-MEA can efficiently penetrate and get outstanding signals from in vitro 3D cellular models as brain spheroids. In conclusion, we describe a new recording device characterized by the highest spatio-temporal resolution reported for a 3D MEA and significant improvements in the quality of recordings, with a high signal-to-noise ratio and improved tissue vitality. The applications of this game-changing technique are countless, opening unprecedented possibilities in the neuroscience field and beyond.

Objectives: To report a case series of children presenting with episodes of abrupt onset psychotic symptoms presumably linked to pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS). Methods: Children/adolescents were selected among the group of individuals affected by clinical diagnosis of PANDAS/PANS. One group was selected by affected individuals coming from the Center UMDNJ--New Jersey Medical School, New Jersey, USA and the other from the Department of Pediatrics Catania University, Italy. Child health Questionnaire Parent form 50 was given to parents to describe children's quality of life. Results: Among the group of individuals with PANDAS/PANS disorders, eight children/adolescents were selected, six coming from the UMDNJ--New Jersey and two from Catania, University centers showing among the other typical manifestations severe episodes of abrupt onset of psychotic symptoms. Conclusions: Severe psychotic symptoms may be considered one among the other neuropsychiatric clinical manifestations presenting in individuals with PANDAS/PANS syndromes.

Pediatric Autoimmune Neuropsychiatric Disorder associated with Streptococcal Infection (PANDAS) is characterized with main clinical features including obsessive-compulsive disorders and tics, acute-onset in prepubertal age, relapsing-remitting course, association with neurological abnormalities (mainly choreiform movements and motor hyperactivity), and temporal relationship with group A streptococcal infections. Thirty- four children with a serious- severe grade of PANDAS were enrolled in Italian Institutions with the aim to report clinical manifestations of the patients and their response to the intravenous immunoglobulin (IVIG) treatment. All patients were selected according to the Swedo‘s criteria and specific laboratory investigations as suggested by Chang for the PANS and treated with IVIG at the dosage of 2 g/kg/day for two consecutive days. At the onset, all patients presented with at least, one psychiatric manifestation including anxiety, emotional lability, bedwetting, enuresis, and phobia, and oppositional behavior including temper tantrums, personality changes, and deterioration in math skills and handwriting. At the laboratory investigations, positivity of pharyngeal swab for streptococcal infection in most of the patients and variable titers of anti-DNase B and ASO were found. In 29 patients reduction or disappearing of the motor symptoms were reached after 1 or 2 cycles of IVIG treatment, while in 5 patients the symptoms reappeared after the third cycle of IVIG. PANDAS may present with polymorphic clinical signs involving behavioral and psychiatric manifestations. In this study, IVIG has been shown to be effective in most of the cases and no complications have been reported during the treatment. Since there is no general agreement on PANDAS treatment, further more extensive researches in this topic are to be hoped.