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Using a targeted transcriptomics approach, we have analyzed resected brain tissue from a cohort of 53 pediatric epilepsy surgery cases, and have found that there is a spectrum of involvement of both the innate and adaptive immune systems as evidenced by the differential expression of immune-specific genes in the affected brain tissue. The specimens with the highest expression of immune-specific genes were from two Rasmussen encephalitis cases, which is known to be a neuro-immunological disease, but also from tuberous sclerosis complex (TSC), focal cortical dysplasia, and hemimegalencephaly surgery cases. We obtained T cell receptor (TCR) Vβ chain sequence data from brain tissue and blood from patients with the highest levels of T cell transcripts. The clonality indices and the frequency of the top 50 Vβ clonotypes indicated that T cells in the brain were clonally restricted. The top 50 Vβ clonotypes comprised both public and private (patient specific) clonotypes, and the TCR Vβ chain third complementarity region (CDR3) of the most abundant public Vβ clonotype in each brain sample was strikingly similar to a CDR3 that recognizes an immunodominant epitope in either human cytomegalovirus or Epstein Barr virus, or influenza virus A. We found that the frequency of 14 of the top 50 brain Vβ clonotypes from a TSC surgery case had significantly increased in brain tissue removed to control recurrent seizures 11 months after the first surgery. Conversely, we found that the frequency in the blood of 18 of the top 50 brain clonotypes from a second TSC patient, who was seizure free, had significantly decreased 5 months after surgery indicating that T cell clones found in the brain had contracted in the periphery after removal of the brain area associated with seizure activity and inflammation. However, the frequency of a public and a private clonotype significantly increased in the brain after seizures recurred and the patient underwent a second surgery. Combined single cell gene expression and TCR sequencing of brain-infiltrating leukocytes from the second surgery showed that the two clones were CD8 effector T cells, indicating that they are likely to be pathologically relevant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chang, Reyes, Faure-Kumar, Lam, Lawlor, Leventer, Lew, Lockhart, Pope, Weiner, Salamon, Vinters, Mathern, Fallah and Owens.)

Two of the most commonly used substances by adolescents in the United States are cannabis and alcohol. Cannabis use disorder (CUD) and alcohol use disorder (AUD) are associated with impairments in decision-making processes. One mechanism for impaired decision-making in these individuals is thought to be an inability to adequately represent future events during decision-making. In the current study involving 112 adolescents, we used a comparative optimism task to examine the relationship between relative severity of CUD/AUD (as indexed by the CUD/AUD Identification Tests [CUDIT/AUDIT]) and atypical function within neural systems underlying affect-based neural represenation future events. Greater CUDIT scores were negatively related to responses within subgenual anterior and posterior cingulate cortex when processing high-intensity potential future positive and negative events. There was also a particularly marked negative relationship between CUD symptoms and blood oxygen level-dependent (BOLD) responses within visual and premotor cortices to high-intensity, negatively valenced potential future events. However, AUD symptom severity was not associated with dysfunction within these brain regions. These data indicate that relative risk/severity of CUD is associated with reduced responsiveness to future high-intensity events. This may impair decision-making where future significant consequences should guide response choice., (© 2020 Society for the Study of Addiction.)

Despite extensive behavioral evidence of impairments in face processing and expression recognition in adults with alcohol or cannabis use disorders (AUD/CUD), neuroimaging findings have been inconsistent. Moreover, relatively little work has examined the relationship of AUD or CUD symptoms with face or expression processing within adolescents. Given the high prevalence of alcohol and cannabis use during adolescence, understanding how these usage behaviors interact with neural mechanisms supporting face and expression processing could have important implications for youth social and emotional functioning. In this study, adolescents (N = 104) responded to morphed fearful and happy expressions during fMRI and their level of AUD and/or CUD symptoms were related to the BOLD response data. We found that AUD and CUD symptom severity were both negatively related to responses to faces generally. However, whereas this relationship was shown for AUD within ventromedial prefrontal cortex and lingual gyrus, it was shown for CUD within rostromedial prefrontal cortex including anterior cingulate cortex. Additionally, AUD symptom levels were associated with differential responses within medial temporal pole and inferior parietal lobule as a function of expression. These results have potential implications for understanding the social and emotional functioning of adolescents with AUD and CUD symptoms., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Importance: Childhood maltreatment is associated with serious developmental consequences that may be different depending on the form of maltreatment. However, relatively little research has investigated this issue despite implications for understanding the development of psychiatric disorders after maltreatment., Objective: To determine the association of childhood maltreatment and potential differential associations of childhood abuse or neglect with neural responsiveness within regions of the brain implicated in emotional responding and response control., Design, Setting, and Participants: In this cross-sectional study, participants aged 10 to 18 years with varying levels of prior maltreatment as indexed by the Childhood Trauma Questionnaire (CTQ) were recruited from a residential care facility and the surrounding community. Blood oxygen level-dependent response data were analyzed via 2 analyses of covariance that examined 2 (sex) × 3 (task condition [view, congruent, incongruent]) × 3 (valence [negative, neutral, positive]) with Blom-transformed covariates: (1) total CTQ score; and (2) abuse and neglect subscores. Data were collected from April 1, 2016, to June 30, 2018. Data analyses occurred from June 10, 2018, to October 31, 2018., Main Outcomes and Measures: Blood oxygenation level-dependent signals in response to an Affective Stroop task were measured via functional magnetic resonance imaging., Results: The sample included 116 youths (mean [SD] age, 15.0 [2.2] years; 70 [60.3%] male). Fifteen participants reported no prior maltreatment. The remaining 101 participants (87.1%) reported at least some prior maltreatment, and 55 (54.5%) reported significant maltreatment, ie, total CTQ scores were greater than the validated CTQ score threshold of 40. There were significant total CTQ score × task condition associations within the bilateral postcentral gyrus, left precentral gyrus, midcingulate cortex, middle temporal gyrus, and superior temporal gyrus (left postcentral gyrus: F = 11.73; partial η2 = 0.14; right postcentral and precentral gyrus: F = 9.81; partial η2 = 0.10; midcingulate cortex: F = 12.76; partial η2 = 0.12; middle temporal gyrus: F = 13.24; partial η2 = 0.10; superior temporal gyrus: F = 10.33; partial η2 = 0.11). In all examined regions of the brain, increased maltreatment was associated with decreased differential responsiveness to incongruent task trials compared with view trials (left postcentral gyrus: r = -0.34; 95% CI, -0.17 to -0.51; right postcentral and precentral gyrus: r = -0.31; 95% CI, -0.14 to -0.49; midcingulate cortex: r = -0.36; 95% CI, -0.18 to -0.53; middle temporal gyrus: r = -0.35; 95% CI, -0.17 to -0.52; superior temporal gyrus: r = -0.37; 95% CI, -0.20 to -0.55). These interactions were particularly associated with level of abuse rather than neglect. A second analysis of covariance revealed significant abuse × task condition (but not neglect × task) interactions within the midcingulate cortex (F = 13.96; partial η2 = 0.11), right postcentral gyrus and inferior parietal lobule (F = 15.21; partial η2 = 0.12), left postcentral and precentral gyri (F = 11.16; partial η2 = 0.12), and rostromedial frontal cortex (F = 10.36; partial η2 = 0.08)). In all examined regions of the brain, increased abuse was associated with decreased differential responsiveness to incongruent task trials compared with view trials (midcingulate cortex: partial r = -0.33; P < .001; right postcentral gyrus and inferior parietal lobule: partial r = -0.41; P < .001; left postcentral and precentral gyri: partial r = -0.40; P < .001; and rostromedial frontal cortex: partial r = -0.40; P < .001)., Conclusions and Relevance: These data document associations of different forms of childhood maltreatment with atypical neural response. This suggests that forms of maltreatment may differentially influence the development of psychiatric pathology.

Alcohol and cannabis are two of the most commonly used substances by adolescents and are associated with adverse medical and psychiatric outcomes. These adverse psychiatric outcomes may reflect the negative impact of alcohol and/or cannabis abuse on neural systems mediating reward and/or error detection. However, work indicative of this has mostly been conducted in adults with Alcohol and/or Cannabis Use Disorder (i.e., AUD and CUD), with relatively little work in adolescent patients. Furthermore, of the work that has been conducted in adolescents, groups were based on categorical diagnoses of AUD and/or CUD, so the relationship between AUD and/or CUD symptom severity in adolescents and neural dysfunction is unclear. We used a Monetary Incentive Delay (MID) task to examine the relationship between AUDIT and/or CUDIT scores and functional integrity of neuro-circuitries mediating reward processing and error detection within 150 adolescents. Our findings indicate that AUDIT score is negatively related to activity in reward processing neuro-circuitry in adolescents. However, CUDIT score is negatively related to activity in brain regions involved in error detection. Each of these relationships reflected a medium effect size (Partial-η 2 0.09-0.14). These data suggest differential impacts of AUD and CUD on reward versus error detection neuro-circuitries within the adolescent brain., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Alcohol and cannabis are two substances that are commonly abused by adolescents in the United States and which, when abused, are associated with negative medical and psychiatric outcomes across the lifespan. These negative psychiatric outcomes may reflect the detrimental impact of substance abuse on neural systems mediating emotion processing and executive attention. However, work indicative of this has mostly been conducted either in animal models or adults with Alcohol and/or Cannabis Use Disorder (AUD/CUD). Little work has been conducted in adolescent patients. In this study, we used the Affective Stroop task to examine the relationship in 82 adolescents between AUD and/or CUD symptom severity and the functional integrity of neural systems mediating emotional processing and executive attention. We found that AUD symptom severity was positively related to amygdala responsiveness to emotional stimuli and negatively related to responsiveness within regions implicated in executive attention and response control (i.e., dorsolateral prefrontal cortex, anterior cingulate cortex, precuneus) as a function of task performance. In contrast, CUD symptom severity was unrelated to amygdala responsiveness but positively related to responsiveness within regions including precuneus, posterior cingulate cortex, and inferior parietal lobule as a function of task performance. These data suggest differential impacts of alcohol and cannabis abuse on the adolescent brain.

Individuals with substance abuse (SA) histories show impairment in the computations necessary for decision-making, including expected value (EV) and prediction error (PE). Neuroimaging findings, however, have been inconsistent. Sixteen youth with (SA positive ) and 29 youth without (SA negative ) substance abuse histories completed a passive avoidance task while undergoing functional MRI. The groups did not significantly differ on age, gender composition or IQ. Behavioral results indicated that SA positive youth showed significantly less learning than SA negative youth over the task. SA positive youth show problems representing EV information when attempting to avoid sub-optimal choices in bilateral inferior frontal gyrus and striatum. Furthermore, SA positive youth showed a significantly increased differential response to reward versus punishment feedback modulated by PE in posterior cingulate cortex relative to SA negative youth. Disrupted decision-making is likely to exacerbate SA as a failure to represent EV during the avoidance of sub-optimal choices is likely to increase the likelihood of SA. With respect to the representation of PE, future work will be needed to clarify the impact of different substances on the neural systems underpinning PE representation. Moreover, interaction of age/development and substance abuse on PE signaling will need to be explored., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Electroencephalography (EEG) is challenged by high cost, immobility of equipment and the use of inconvenient conductive gels. We compared EEG recordings obtained from three systems that are inexpensive, wireless, and/or dry (no gel), against recordings made with a traditional, research-grade EEG system, in order to investigate the ability of these 'non-traditional' systems to produce recordings of comparable quality to a research-grade system. The systems compared were: Emotiv EPOC (inexpensive and wireless), B-Alert (wireless), g.Sahara (dry) and g.HIamp (research-grade). We compared the ability of the systems to demonstrate five well-studied neural phenomena: (1) enhanced alpha activity with eyes closed versus open; (2) visual steady-state response (VSSR); (3) mismatch negativity; (4) P300; and (5) event-related desynchronization/synchronization. All systems measured significant alpha augmentation with eye closure, and were able to measure VSSRs (although these were smaller with g.Sahara). The B-Alert and g.Sahara were able to measure the three time-locked phenomena equivalently to the g.HIamp. The Emotiv EPOC did not have suitably located electrodes for two of the tasks and synchronization considerations meant that data from the time-locked tasks were not assessed. The results show that inexpensive, wireless, or dry systems may be suitable for experimental studies using EEG, depending on the research paradigm, and within the constraints imposed by their limited electrode placement and number.

A study was performed to investigate and compare the relative performance of blind signal separation (BSS) algorithms at separating common types of contamination from EEG. The study develops a novel framework for investigating and comparing the relative performance of BSS algorithms that incorporates a realistic EEG simulation with a known mixture of known signals and an objective performance metric. The key finding is that although BSS is an effective and powerful tool for separating and removing contamination from EEG, the quality of the separation is highly dependant on the type of contamination, the degree of contamination, and the choice of BSS algorithm. BSS appears to be most effective at separating muscle and blink contamination and less effective at saccadic and tracking contamination. For all types of contamination, principal components analysis is a strong performer when the contamination is greater in amplitude than the brain signal whereas other algorithms such as second-order blind inference and Infomax are generally better for specific types of contamination of lower amplitude.

Objective: Gamma rhythms (30-100 Hz) have been shown to be associated with spindling activity induced by picrotoxin. To determine if gamma power is unique to picrotoxin spindles or is an integral part of physiological and pathological spindling activity we analysed and compared the strength and brain distribution of gamma EEG power during 4 spindling activities in the rat., Methods: The electroencephalogram (EEG) was recorded from rats with chronically implanted electrodes during natural sleep, barbiturate anaesthesia, during naturally occurring absence epilepsy spike and wave discharges and following the systemic application of picrotoxin. Spectral analysis was applied off-line to compare the strength and brain distribution of gamma EEG power during the 4 spindling activities., Results: Each spindle type contained significantly different levels of gamma power. Gamma power was significantly increased over background levels during picrotoxin spindles, slightly increased during absence spindles, slightly decreased during sleep spindles and significantly suppressed during barbiturate spindles, Conclusions: Changes in the power of gamma frequencies during spindle types suggest that gamma frequencies are neither the cause of nor an integral part of a spindle. They appear to be correlated with levels of consciousness and may contribute to the process of epileptogenesis., Significance: The findings are consistent with high frequency EEG activity being related to seizure-tendency.

This paper describes modelling and simulation of a had model which incorporates both the geometries and conductivities of the human head. It focuses on the inclusion of tissue conductivity inhomogeneity in a realistically-shaped head model, and investigates the impact of this inclusion on the potential distribution within the model. The result show that the impact, which has been neglected in realistic head models so far, is significant.

Objectives: It is unknown how generalised discharges in primary generalised epilepsy (PGE) develop from background brain electrical activity or how widespread these discharged are throughout the brain. Here we address this by determining which neural structures and rhythms lead to and participate in generalised discharges in the picrotoxin rat model of PGE., Methods: Rats with chronically implanted electrodes were infused with picrotoxin until a seizure occurred. This process we refer to as acute epileptogenesis. The electroencephalogram (EEG) was recorded and spectral analysis applied off-line to determine changes in the spectral power of contributing frequencies in 13 brain regions., Results: Two types of generalised discharge occurred, spindles and seizure, which were present in all brain regions studied. None of the frequencies (1-100 Hz) were significantly increased in background EEG before either spindles or seizure. Within the generalised discharges, power changes revealed significant increases in 6-8 Hz, most powerful in ventrolateral thalamus and neocortex. Gamma frequencies were increased significantly in neocortical structures during spindles with further increases in most structures at seizure onset. 1 Hz was significantly increased in parietal cortex during spindles with differential increases at seizure onset., Conclusions: We conclude that gamma, 1 and 6-8 Hz frequencies do not appear to contribute to picrotoxin epileptogenesis but do play a role in generalised seizures. The distribution of these frequencies during discharges suggests that the spindles are thalamocortical events and that the seizure is a cortical event with downstream effects on other brain regions.