The domain-variant indirect association between electrophysiological response to reward and ADHD presentations is moderated by dopaminergic polymorphisms.

BACKGROUND: Understanding the etiopathogenesis of attention-deficit/hyperactivity disorder (ADHD) may necessitate decomposition of the heterogeneous clinical phenotype into more homogeneous intermediate phenotypes. Reinforcement sensitivity is a promising candidate, but the exact nature of the ADHD-reward relation - including how, for whom, and to which ADHD dimensions atypicalities in reward processing are relevant - is equivocal. METHODS: Aims were to examine, in a carefully phenotyped sample of adolescents (N = 305; Mage = 15.30 years, SD = 1.07; 39.7% girls), whether functional dopaminergic polymorphisms implicated in both reward processing and ADHD (1) are differentially associated with event-related potentials (ERPs) of reward anticipation at distinct levels of ADHD risk (nno risk = 174, nat-risk = 131, ndiagnosed = 83); and (2) moderate the indirect effect of dispositional affectivity on the association between ERPs and ADHD domains. RESULTS: In adolescents at-risk for or with ADHD, carrying a hypodopaminergic allele was associated with enhanced ERPs of attention allocation to cue and attenuated ERPs of anticipatory attention to feedback. No associations were observed in adolescents not at-risk for or without ADHD. Controlling for age and sex, both the negative indirect effect of positive affectivity (PA) on the association between ERPs and inattention and the positive indirect effect of PA on the association between ERPs and hyperactivity/impulsivity were supported only for those with high activity dopamine transporter (DAT) alleles. CONCLUSIONS: Reward and affective processing are promising intermediate phenotypes relevant to disentangling ADHD developmental pathways. Consistent with developmental multifinality, through the successive effects of reward anticipation and positive affectivity, functional dopaminergic variants may confer protection against inattention or risk for hyperactivity/impulsivity.

A multimodal, implantable sensor array and measurement system to investigate the suppression of focal epileptic seizure using hypothermia.

Objective.Local cooling of the brain as a therapeutic intervention is a promising alternative for patients with epilepsy who do not respond to medication.In vitroandin vivostudies have demonstrated the seizure-suppressing effect of local cooling in various animal models. In our work, focal brain cooling in a bicuculline induced epilepsy model in rats is demonstrated and evaluated using a multimodal micro-electrocorticography (microECoG) device.Approach.We designed and experimentally tested a novel polyimide-based sensor array capable of recording microECoG and temperature signals concurrently from the cortical surface of rats. The effect of cortical cooling after seizure onset was evaluated using 32 electrophysiological sites and eight temperature sensing elements covering the brain hemisphere, where injection of the epileptic drug was performed. The focal cooling of the cortex right above the injection site was accomplished using a miniaturized Peltier chip combined with a heat pipe to transfer heat. Control of cooling and collection of sensor data was provided by a custom designed Arduino based electronic board. We tested the experimental setup using an agar gel modelin vitro, and thenin vivoin Wistar rats.Main results.Spatial variation of temperature during the Peltier controlled cooling was evaluated through calibrated, on-chip platinum temperature sensors. We found that frequency of epileptic discharges was not substantially reduced by cooling the cortical surface to 30 °C, but was suppressed efficiently at temperature values around 20 °C. The multimodal array revealed that seizure-like ictal events far from the focus and not exposed to high drop in temperature can be also inhibited at an extent like the directly cooled area.Significance.Our results imply that not only the absolute drop in temperature determines the efficacy of seizure suppression, and distant cortical areas not directly cooled can be influenced.

Two-dimensional multi-channel neural probes with electronic depth control.

This paper presents multi-electrode arrays for in vivo neural recording applications incorporating the principle of electronic depth control (EDC), i.e., the electronic selection of recording sites along slender probe shafts independently for multiple channels. Two-dimensional (2D) arrays were realized using a commercial 0.5- µm complementary-metal-oxide-semiconductor (CMOS) process for the EDC circuits combined with post-CMOS micromachining to pattern the comb-like probes and the corresponding electrode metallization. A dedicated CMOS integrated front-end circuit was developed for pre-amplification and multiplexing of the neural signals recorded using these probes.