Clinical and Family Implications of Cannabidiol (CBD)-Dominant Full-Spectrum Phytocannabinoid Extract in Children and Adolescents with Moderate to Severe Non-Syndromic Autism Spectrum Disorder (ASD): An Observational Study on Neurobehavioral Management.

Autism Spectrum Disorder (ASD) encompasses a wide range of neurodevelopmental conditions characterized by deficits in social interaction, communication and behavior. Current pharmacological options are limited and feature significant side effects. In this study, we conducted a retrospective, observational, and cross-sectional cohort study to evaluate the effects of Cannabidiol (CBD)-dominant, full-spectrum cannabis extract, containing Tetrahydrocannabinol (THC) in a ratio of 33:1 (CBD:THC), on non-syndromic children and adolescents (5-18 years old) with moderate to severe ASD. Thirty volunteers were recruited, underwent neuropsychological evaluations and were treated with individualized doses of CBD-dominant extract. Clinical assessments were conducted by the designated clinician. Additionally, parents or caregivers were independently interviewed to assess perceived treatment effects. We found significant improvements in various symptomatic and non-symptomatic aspects of ASD, with minimal untoward effects, as reported by both clinical assessments and parental perceptions. The observed improvements included increased communicative skills, attention, learning, eye contact, diminished aggression and irritability, and an overall increase in both the patient's and family's quality of life. Despite its limitations, our findings suggest that treatment with full-spectrum CBD-dominant extract may be a safe and effective option for core and comorbid symptoms of ASD, and it may also increase overall quality of life for individuals with ASD and their families.

Individually tailored dosage regimen of full-spectrum Cannabis extracts for autistic core and comorbid symptoms: a real-life report of multi-symptomatic benefits.

Autism Spectrum Disorders (ASD) may significantly impact the well-being of patients and their families. The therapeutic use of cannabis for ASD has gained interest due to its promising results and low side effects, but a consensus on treatment guidelines is lacking. In this study, we conducted a retrospective analysis of 20 patients with autistic symptoms who were treated with full-spectrum cannabis extracts (FCEs) in a response-based, individually-tailored dosage regimen. The daily dosage and relative proportions of cannabidiol (CBD) and tetrahydrocannabinol (THC) were adjusted based on treatment results following periodic clinical evaluation. Most patients (80%) were treated for a minimum of 6 months. We have used a novel, detailed online patient- or caregiver-reported outcome survey that inquired about core and comorbid symptoms, and quality of life. We also reviewed patients' clinical files, and no individual condition within the autistic spectrum was excluded. This real-life approach enabled us to gain a clearer appraisal of the ample scope of benefits that FCEs can provide for ASD patients and their families. Eighteen patients started with a CBD-rich FCE titrating protocol, and in three of them, the CBD-rich (CBD-dominant) FCE was gradually complemented with low doses of a THC-rich (THC-dominant) FCE based on observed effects. Two other patients have used throughout treatment a blend of two FCEs, one CBD-rich and the other THC-rich. The outcomes were mainly positive for most symptoms, and only one patient from each of the two above-mentioned situations displayed important side effects one who has used only CBD-rich FCE throughout the treatment, and another who has used a blend of CBD-Rich and THC-rich FCEs. Therefore, after FCE treatment, 18 out of 20 patients showed improvement in most core and comorbid symptoms of autism, and in quality of life for patients and their families. For them, side effects were mild and infrequent. Additionally, we show, for the first time, that allotriophagy (Pica) can be treated by FCEs. Other medications were reduced or completely discontinued in most cases. Based on our findings, we propose guidelines for individually tailored dosage regimens that may be adapted to locally available qualified FCEs and guide further clinical trials.

Bibliometric mapping of non-invasive brain stimulation techniques (NIBS) for fluent speech production.

Introduction: Language production is a finely regulated process, with many aspects which still elude comprehension. From a motor perspective, speech involves over a hundred different muscles functioning in coordination. As science and technology evolve, new approaches are used to study speech production and treat its disorders, and there is growing interest in the use of non-invasive modulation by means of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Methods: Here we analyzed data obtained from Scopus (Elsevier) using VOSViewer to provide an overview of bibliographic mapping of citation, co-occurrence of keywords, co-citation and bibliographic coupling of non-invasive brain stimulation (NIBS) use in speech research. Results: In total, 253 documents were found, being 55% from only three countries (USA, Germany and Italy), with emerging economies such as Brazil and China becoming relevant in this topic recently. Most documents were published in this last decade, with 2022 being the most productive yet, showing brain stimulation has untapped potential for the speech research field. Discussion: Keyword analysis indicates a move away from basic research on the motor control in healthy speech, toward clinical applications such as stuttering and aphasia treatment. We also observe a recent trend in cerebellar modulation for clinical treatment. Finally, we discuss how NIBS have established over the years and gained prominence as tools in speech therapy and research, and highlight potential methodological possibilities for future research.

Características psicométricas da versão brasileira do Sport Emotion Questionnaire (SEQ-BR) / Características psicométricas de la versión brasileña del Sport Emotion Questionnaire (SEQ-BR) / Psychometric characteristics of the Brazilian version of the Sport Emotion Questionnaire (SEQ-BR)

En este trabajo presentamos una versión traducida y adaptada del Sport Emotion Questionnaire (SEQ) en portugués brasileño, además de explorar sus características psicométricas. En el Estudio 1 se elaboró la versión brasileña del SEQ (SEQ-BR) de acuerdo con las directrices del proceso de adaptación transcultural, se evaluó la validez de contenido y el acuerdo entre evaluadores. La concordancia entre los evaluadores fue casi excelente (0.77 £ Kappa £ 0.89) y el instrumento se consideró válido desde el punto de vista de su contenido en cuanto a claridad (CVCt = 0.91) y pertinencia (CVCt = 0.93). En el Estudio 2, 895 atletas brasileños de diferentes deportes respondieron al SEQ-BR durante competiciones nacionales e internacionales. Se realizaron análisis factoriales para explorar y confirmar la estructura factorial del SEQ-BR. La estructura con cinco factores presentó un ajuste satisfactorio [χ2 (199) = 395.59; χ2/gl = 1.99; CFI = 0.98; TLI = 0.98; GFI = 0.98; RMSEA = 0.033], además de invarianza factorial entre grupos y consistencia interna adecuada en todos los factores (0.78 £ ω £ 0.85). Teniendo en cuenta lo anterior, el SEQ-BR presenta adecuación en cuanto a la validación del contenido y características psicométricas satisfactorias, proporcionando un instrumento estable, consistente y fiable para medir las emociones precompetitivas en atletas brasileños. (AU)

Neste trabalho apresentamos uma versão traduzida e adaptada doSport Emotion Questionnaire(SEQ) para o Português brasileiro, e exploramossuas características psicométricas. No Estudo 1 foi produzida a versão brasileira do SEQ (SEQ-BR)de acordo com as diretrizes para o processo de adaptação transcultural, eavaliadas a validade de conteúdo e a concordância entre os juízes. O julgamento quanto a concordância entre os juízes foi quase excelente (0.77£Kappa£0.89) e o instrumento foi considerado válido do ponto de vista do seu conteúdo quanto a clareza (CVCt= 0.91) e pertinência (CVCt= 0.93). No Estudo 2, 895 atletas brasileiros de diferentes modalidades esportivas responderam o SEQ-BR durante competições nacionais e internacionais. As análises fatoriais foram realizadas para explorar e confirmar a estrutura fatorial do SEQ-BR. Aestrutura com cinco fatores apresentou um ajuste satisfatório [χ2(199) = 395.59; χ2/gl = 1.99; CFI = 0.98;TLI = 0.98;GFI = 0.98;RMSEA = 0.033], além de invariância fatorial entre grupos e consistência interna adequada em todos os fatores (0.78£ω£0.85). Diante do exposto, o SEQ-BR apresenta adequação quanto à validação do conteúdo e características psicométricas satisfatórias, fornecendo um instrumento estável, consistente e confiável para mensurar emoções pré-competitivas em atletas brasileiros. (AU)

Here we present an adapted version oftheSport Emotion Questionnaire (SEQ)translated to Brazilian Portuguese, and exploreits psychometric characteristics. In Study 1, the Brazilian version of the SEQ (SEQ-BR) was produced according to the guidelines for the cross-cultural adaptation process, and the content validity and inter-rater agreement were evaluated. The agreement was almost excellent between judges (0.77£Kappa£0.89),and the instrument was considered valid from thecontent viewpoint, regarding clarity (CVCt= 0.91) and relevance (CVCt= 0.93). In Study 2, 895 Brazilian athletes from different types of sports answered the SEQ-BR during national and international competitions. Factor analysis were performed to exploreand confirm the factor structure of the SEQ-BR.The structure composed offive factors [χ2(199) = 395.59;χ2/df = 1.99; CFI = 0.98;TLI = 0.98;GFI = 0.98;RMSEA = 0.033], in addition to factorial invariance between groups and adequate internal consistency in all factors (0,78£ω£0,85). The SEQ-BR presents adequacy as to content validity,and satisfactory psychometric characteristics, providing a stable, consistent, and reliable instrument tomeasure pre-competitive emotions in Brazilian athletes. (AU)

Systematic review of visual illusions in schizophrenia.

Visual illusions have long been used as tools to investigate sensory-perceptual deficits in schizophrenia. Recent conflicting accounts have called into question the assumption of abnormal illusion perception in patients and, therefore, the validity of this approach. Here, we present a systematic review of the current evidence regarding visual illusion perception abnormalities in patients with schizophrenia. Relevant publications were identified by a systematic search of PubMed, Literatura LILACS, PsycINFO, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), IBECS, BIOSIS, and Web of Science. Forty-five studies were selected which included illusions classified as 'Motion illusions', 'Geometric-optical illusions', 'Illusory contours', 'Depth inversion illusion', and 'Non-specific'. There is concordant evidence of abnormal processing of illusions in patients for most categories, especially in facial Depth Inversion and Müller-Lyer illusions. There were significant methodological disparities and shortcomings, but risk of bias was overall low for individual studies. The usefulness of visual illusions as tools in clinical settings as well as in basic research may be contingent on significant methodological refinements.

Phase-sensitive radioluminescence and photoluminescence features in Tm3+-doped yttrium tantalates for cyan and white light generation.

Radioluminescence and visible photoluminescence tunability features from a single Tm3+-doped yttrium tantalate phosphor prepared by a soft sol-gel method designed to afford cubic Y3TaO7 and monoclinic M'-YTaO4 crystalline phases are reported. The annealing temperature influenced the crystallization kinetics and stabilized a preferential phase. To investigate how the crystalline phase affected the Tm3+ optical properties, excitation and emission spectra in the visible range were recorded for the samples annealed at 900 or 1100 °C. Inhomogeneous broadening in the emission spectra was due to the structural disorder of the Y3TaO7 phase. Energy transfer between the yttrium tantalate host and Tm3+ ions was observed upon CT band excitation. Under UV light, an intense and tunable cyan to blue emission ascribed to both the Tm3+ transitions 1D2 → 3F4 and 1G4 → 3H6 also emerged and could be observed by the naked eye. The lifetime decay curves demonstrated the occupation of distinct sites and that the symmetry sites occupied by Tm3+ ions in the Y3TaO7 host have higher lifetime values than in the M'-YTaO4 phase. A radioluminescence study was carried out to evaluate the yttrium tantalate scintillation performance, which was considerably enhanced in the presence of the M'-YTaO4 phase. Intense white light emission displaying a large color correlated temperature range could be obtained by controlling the delay time for the time-resolved measurements and upon an orange-emitting phosphor addition. All the above-mentioned structural and photoluminescence properties make these Tm3+-doped yttrium tantalates potential candidates for photonic applications, particularly integrated w-LED systems.

Super Broadband at Telecom Wavelengths From RE3+-Doped SiO2-Ta2O5 Glass Ceramics Planar Waveguides.

This paper reports on the preparation of Er3+/Yb3+/Tm3+, Er3+/Yb3+/Nd3+, and Er3+/Tm3+/Nd3+ triply doped and Er3+-doped SiO2-Ta2O5 glass ceramic nanocomposites and active planar waveguides by the sol-gel process using the dip-coating technique as deposition method. The investigation of their structural, morphological, and luminescent properties using XRD, AFM, and photoluminescence analysis, are reported here. The XRD results showed the presence of L-Ta2O5 nanocrystals dispersed in the SiO2-based amorphous host for all the nanocomposites and films. The rare earth ion (RE3+) doping concentration affected both the crystallinity, and the crystallite sizes of the Ta2O5 dispersed into SiO2-Ta2O5 nanocomposites and waveguides. AFM characterization revealed crack free and smooth surface roughness and differences in viscoelasticity on the Er3+-doped SiO2-Ta2O5 films surface, which allows the identification of Ta2O5 nanocrystals on the SiO2 amorphous host. The Er3+ doped and triply doped SiO2-Ta2O5 nanocomposites displayed broad- and super broadband NIR emissions with a FWHM up to 173 nm achieved in the telecom wavelengths. The lifetime of the 4I13/2 emitting level of the Er3+-doped SiO2-Ta2O5 waveguides is strongly dependent on Er3+ concentration and an emission quenching was negligible up to 0.81 mol%. The structural and luminescent investigations indicated that RE3+-doped SiO2-Ta2O5 glass ceramics are promising candidates for photonic applications in optical devices operating in wide wavelengths at the telecom bands.

The Perception of the Müller-Lyer Visual Illusion in Schizophrenics and Non-human Primates: A Translational Approach.

The Müller-Lyer Illusion (MLI) has been suggested as a potential marker for the perceptual impairments observed in schizophrenia patients. Along with some positive symptoms, these deficits are not easily modeled in rodent experiments, and novel animal models are warranted. Previously, MK-801 was shown to reduce susceptibility to MLI in monkeys, raising the prospects of an effective perception-based model. Here, we evaluate the translational feasibility of the MLI task under NMDA receptor blockage as a primate model for schizophrenia. In Experiment 1, eight capuchin monkeys (Sapajus spp.) were trained on a touchscreen MLI task. Upon reaching the learning criteria, the monkeys were given ketamine (0.3 mg/kg; i.m.) or saline on four consecutive days and then retested on the MLI task. In Experiment 2, eight chronic schizophrenia patients (and eight matching controls) were tested on the Brentano version of the MLI. Under saline treatment, monkeys were susceptible to MLI, similarly to healthy human participants. Repeated ketamine administrations, however, failed to improve their performance as previous results with MK-801 had shown. Schizophrenic patients, on the other hand, showed a higher susceptibility to MLI when compared to healthy controls. In light of the present and previous studies, the MLI task shows consistent results across monkeys and humans. In spite of potentially being an interesting translational model of schizophrenia, the MLI task warrants further refinement in non-human primates and a broader sample of schizophrenia subtypes.

Acute offline transcranial direct current stimulation does not change pain or anxiety produced by the cold pressor test.

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has an antalgic effect on acute experimental pain in healthy volunteers. Many published studies have used online stimulation (i.e., tDCS performed during painful stimulation). On the other hand, daily tDCS sessions have been proposed as a therapy for chronic pain (offline tDCS). In such cases, the therapeutic potential depends on the possible aftereffects of each tDCS session. We set out to investigate whether a single tDCS session before application of a classical experimental pain paradigm (the Cold Pressor Test, CPT) would be capable of modulating physiological measures of anxiety as well as pain perception. tDCS was applied to 30 healthy volunteers, 18-28 years old (mean 18.5), with the anode positioned over either the left M1 or the left dorsolateral prefrontal cortex (l-DLPFC), which has been linked to the affective aspects of experienced pain, including anxiety. All volunteers underwent the CPT procedure before and after a tDCS session. Real 2 mA tDCS sessions for 20 min were compared to sham stimulations. No significant difference was found for any variable after real tDCS sessions when compared to the sham stimulations. This result suggests that effective offline tDCS for chronic pain might have different mechanisms of action. Cumulative effects, functional targeting and the unintended simultaneous stimulation of both M1 and the l-DLPFC are likely responsible for the therapeutic effects of tDCS sessions in the clinical setting.

High Eu3+ concentration quenching in Y3TaO7 solid solution for orange-reddish emission in photonics.

We report the synthesis of a Y3TaO7 solid solution containing a high Eu3+ concentration (from 7 up to 50 mol%) and investigate how Eu3+ influences the Y3TaO7 crystallization process. To this end, we evaluate the Y3TaO7 structural features and photoluminescence properties after Eu3+ introduction into the Y3TaO7 lattice. The higher the Eu3+ ion concentration, the more stable the crystallization process of the Y3TaO7 phase seems to be. The Eu3+-containing Y3TaO7 displays intense orange-reddish, broad band emission because Eu3+ occupies different symmetry sites in the host and causes inhomogeneous broadening. Eu3+ emission quenching due to Eu3+ concentration is negligible up to 30 mol% and absolute quantum yield values of up to nearly 30% were obtained, making Eu3+-containing Y3TaO7 interesting materials for application as high-intensity emitters in photonics.

Effects of CBD-Enriched Cannabis sativa Extract on Autism Spectrum Disorder Symptoms: An Observational Study of 18 Participants Undergoing Compassionate Use.

Autism Spectrum Disorders comprise conditions that may affect cognitive development, motor skills, social interaction, communication, and behavior. This set of functional deficits often results in lack of independence for the diagnosed individuals, and severe distress for patients, families, and caregivers. There is a mounting body of evidence indicating the effectiveness of pure cannabidiol (CBD) and CBD-enriched Cannabis sativa extract (CE) for the treatment of autistic symptoms in refractory epilepsy patients. There is also increasing data support for the hypothesis that non-epileptic autism shares underlying etiological mechanisms with epilepsy. Here we report an observational study with a cohort of 18 autistic patients undergoing treatment with compassionate use of standardized CBD-enriched CE (with a CBD to THC ratio of 75/1). Among the 15 patients who adhered to the treatment (10 non-epileptic and five epileptic) only one patient showed lack of improvement in autistic symptoms. Due to adverse effects, three patients discontinued CE use before 1 month. After 6-9 months of treatment, most patients, including epileptic and non-epileptic, showed some level of improvement in more than one of the eight symptom categories evaluated: Attention Deficit/Hyperactivity Disorder; Behavioral Disorders; Motor Deficits; Autonomy Deficits; Communication and Social Interaction Deficits; Cognitive Deficits; Sleep Disorders and Seizures, with very infrequent and mild adverse effects. The strongest improvements were reported for Seizures, Attention Deficit/Hyperactivity Disorder, Sleep Disorders, and Communication and Social Interaction Deficits. This was especially true for the 10 non-epileptic patients, nine of which presented improvement equal to or above 30% in at least one of the eight categories, six presented improvement of 30% or more in at least two categories and four presented improvement equal to or above 30% in at least four symptom categories. Ten out of the 15 patients were using other medicines, and nine of these were able to keep the improvements even after reducing or withdrawing other medications. The results reported here are very promising and indicate that CBD-enriched CE may ameliorate multiple ASD symptoms even in non-epileptic patients, with substantial increase in life quality for both ASD patients and caretakers.

CB1 receptor antagonism in capuchin monkeys alters social interaction and aversive memory extinction.

RATIONALE: The endocannabinoid system (eCS) is an important modulator of social anxiety and social reward, as well as memory functions. OBJECTIVES: The present study evaluated the role of eCS in social interactions and aversive memory extinction in capuchin monkeys (Sapajus spp.) by blocking the cannabinoid type 1 receptor (CB1r). METHODS: In experiment 1, spontaneous social and non-social behaviors of five capuchin males, each one living in triads with two other females, were observed after AM251 treatment (vehicle, 0.3, 1.0, and 3.0 mg/kg; i.m.). In experiment 2, seven male capuchin monkeys were trained to reach for a reward inside a wooden box. After training, they were given either vehicle or a 3.0-mg/kg i.m. dose of AM251 before a single aversive encounter with a live snake in the box. The latency to return to reach the reward inside the box in subsequent trials was measured. RESULTS: The 3.0-mg/kg dose significantly increased the time spent performing self-directed behaviors, while decreasing that of social interactions. No changes were observed in vigilance or locomotion. AM251 increased the latency to reach the reward after the aversive encounter. CONCLUSION: Taken together, these results suggest that CB1r antagonism induces social deficits without increasing anxiety levels and impairs the extinction of aversive memories. This behavioral profile in monkeys underscores the potential involvement of eCS signaling in the deficits observed in autism spectrum disorders.

Characterization of Dmrt3-Derived Neurons Suggest a Role within Locomotor Circuits.

Neuronal networks within the spinal cord, collectively known as the central pattern generator (CPG), coordinate rhythmic movements underlying locomotion. The transcription factor doublesex and mab-3-related transcription factor 3 (DMRT3) is involved in the differentiation of the dorsal interneuron 6 class of spinal cord interneurons. In horses, a non-sense mutation in the Dmrt3 gene has major effects on gaiting ability, whereas mice lacking the Dmrt3 gene display impaired locomotor activity. Although the Dmrt3 gene is necessary for normal spinal network formation and function in mice, a direct role for Dmrt3-derived neurons in locomotor-related activities has not been demonstrated. Here we present the characteristics of the Dmrt3-derived spinal cord interneurons. Using transgenic mice of both sexes, we characterized interneurons labeled by their expression of Cre driven by the endogenous Dmrt3 promoter. We used molecular, retrograde tracing and electrophysiological techniques to examine the anatomical, morphological, and electrical properties of the Dmrt3-Cre neurons. We demonstrate that inhibitory Dmrt3-Cre neurons receive extensive synaptic inputs, innervate surrounding CPG neurons, intrinsically regulate CPG neuron's electrical activity, and are rhythmically active during fictive locomotion, bursting at frequencies independent to the ventral root output. The present study provides novel insights on the character of spinal Dmrt3-derived neurons, data demonstrating that these neurons participate in locomotor coordination.SIGNIFICANCE STATEMENT In this work, we provide evidence for a role of the Dmrt3 interneurons in spinal cord locomotor circuits as well as molecular and functional insights on the cellular and microcircuit level of the Dmrt3-expressing neurons in the spinal cord. Dmrt3 neurons provide the first example of an interneuron population displaying different oscillation frequencies. This study presents novel findings on an under-reported population of spinal cord neurons, which will aid in deciphering the locomotor network and will facilitate the design and development of therapeutics for spinal cord injury and motor disorders.

Neuron-specific inactivation of Wt1 alters locomotion in mice and changes interneuron composition in the spinal cord.

Locomotion is coordinated by neuronal circuits of the spinal cord. Recently, dI6 neurons were shown to participate in the control of locomotion. A subpopulation of dI6 neurons expresses the Wilms tumor suppressor gene Wt1. However, the function of Wt1 in these cells is not understood. Here, we aimed to identify behavioral changes and cellular alterations in the spinal cord associated with Wt1 deletion. Locomotion analyses of mice with neuron-specific Wt1 deletion revealed a slower walk with a decreased stride frequency and an increased stride length. These mice showed changes in their fore-/hindlimb coordination, which were accompanied by a loss of contralateral projections in the spinal cord. Neonates with Wt1 deletion displayed an increase in uncoordinated hindlimb movements and their motor neuron output was arrhythmic with a decreased frequency. The population size of dI6, V0, and V2a neurons in the developing spinal cord of conditional Wt1 mutants was significantly altered. These results show that the development of particular dI6 neurons depends on Wt1 expression and that loss of Wt1 is associated with alterations in locomotion.

The MINDVIEW project: First results.

We present the first results of the MINDVIEW project. An innovative imaging system for the human brain examination, allowing simultaneous acquisition of PET/MRI images, has been designed and constructed. It consists of a high sensitivity and high resolution PET scanner integrated in a novel, head-dedicated, radio frequency coil for a 3T MRI scanner. Preliminary measurements from the PET scanner show sensitivity 3 times higher than state-of-the-art PET systems that will allow safe repeated studies on the same patient. The achieved spatial resolution, close to 1 mm, will enable differentiation of relevant brain structures for schizophrenia. A cost-effective and simple method of radiopharmaceutical production from 11C-carbon monoxide and a mini-clean room has been demonstrated. It has been shown that 11C-raclopride has higher binding potential in a new VAAT null mutant mouse model of schizophrenia compared to wild type control animals. A significant reduction in TSPO binding has been found in gray matter in a small sample of drug-naïve, first episode psychosis patients, suggesting a reduced number or an altered function of immune cells in brain at early stage schizophrenia.

Undersampled critical branching processes on small-world and random networks fail to reproduce the statistics of spike avalanches.

The power-law size distributions obtained experimentally for neuronal avalanches are an important evidence of criticality in the brain. This evidence is supported by the fact that a critical branching process exhibits the same exponent [Formula: see text]. Models at criticality have been employed to mimic avalanche propagation and explain the statistics observed experimentally. However, a crucial aspect of neuronal recordings has been almost completely neglected in the models: undersampling. While in a typical multielectrode array hundreds of neurons are recorded, in the same area of neuronal tissue tens of thousands of neurons can be found. Here we investigate the consequences of undersampling in models with three different topologies (two-dimensional, small-world and random network) and three different dynamical regimes (subcritical, critical and supercritical). We found that undersampling modifies avalanche size distributions, extinguishing the power laws observed in critical systems. Distributions from subcritical systems are also modified, but the shape of the undersampled distributions is more similar to that of a fully sampled system. Undersampled supercritical systems can recover the general characteristics of the fully sampled version, provided that enough neurons are measured. Undersampling in two-dimensional and small-world networks leads to similar effects, while the random network is insensitive to sampling density due to the lack of a well-defined neighborhood. We conjecture that neuronal avalanches recorded from local field potentials avoid undersampling effects due to the nature of this signal, but the same does not hold for spike avalanches. We conclude that undersampled branching-process-like models in these topologies fail to reproduce the statistics of spike avalanches.

Ketamine alters oscillatory coupling in the hippocampus.

Recent studies show that higher order oscillatory interactions such as cross-frequency coupling are important for brain functions that are impaired in schizophrenia, including perception, attention and memory. Here we investigated the dynamics of oscillatory coupling in the hippocampus of awake rats upon NMDA receptor blockade by ketamine, a pharmacological model of schizophrenia. Ketamine (25, 50 and 75 mg/kg i.p.) increased gamma and high-frequency oscillations (HFO) in all depths of the CA1-dentate axis, while theta power changes depended on anatomical location and were independent of a transient increase of delta oscillations. Phase coherence of gamma and HFO increased across hippocampal layers. Phase-amplitude coupling between theta and fast oscillations was markedly altered in a dose-dependent manner: ketamine increased hippocampal theta-HFO coupling at all doses, while theta-gamma coupling increased at the lowest dose and was disrupted at the highest dose. Our results demonstrate that ketamine alters network interactions that underlie cognitively relevant theta-gamma coupling.

Theta phase modulates multiple layer-specific oscillations in the CA1 region.

It was recently proposed that fast gamma oscillations (60-150 Hz) convey spatial information from the medial entorhinal cortex (EC) to the CA1 region of the hippocampus. However, here we describe 2 functionally distinct oscillations within this frequency range, both coupled to the theta rhythm during active exploration and rapid eye movement sleep: an oscillation with peak activity at ∼80 Hz and a faster oscillation centered at ∼140 Hz. The 2 oscillations are differentially modulated by the phase of theta depending on the CA1 layer; theta-80 Hz coupling is strongest at stratum lacunosum-moleculare, while theta-140 Hz coupling is strongest at stratum oriens-alveus. This laminar profile suggests that the ∼80 Hz oscillation originates from EC inputs to deeper CA1 layers, while the ∼140 Hz oscillation reflects CA1 activity in superficial layers. We further show that the ∼140 Hz oscillation differs from sharp wave-associated ripple oscillations in several key characteristics. Our results demonstrate the existence of novel theta-associated high-frequency oscillations and suggest a redefinition of fast gamma oscillations.

Cross-modal responses in the primary visual cortex encode complex objects and correlate with tactile discrimination.

Cortical areas that directly receive sensory inputs from the thalamus were long thought to be exclusively dedicated to a single modality, originating separate labeled lines. In the past decade, however, several independent lines of research have demonstrated cross-modal responses in primary sensory areas. To investigate whether these responses represent behaviorally relevant information, we carried out neuronal recordings in the primary somatosensory cortex (S1) and primary visual cortex (V1) of rats as they performed whisker-based tasks in the dark. During the free exploration of novel objects, V1 and S1 responses carried comparable amounts of information about object identity. During execution of an aperture tactile discrimination task, tactile recruitment was slower and less robust in V1 than in S1. However, V1 tactile responses correlated significantly with performance across sessions. Altogether, the results support the notion that primary sensory areas have a preference for a given modality but can engage in meaningful cross-modal processing depending on task demand.