Excitable Media Seminar

The simulation data presented here, and the conceptual framework developed for their interpretation are, both, in need of substantial refinement and extension. However, granting that they are initial pointers of some merit, and elementary indicators of general principles, several implications follow: the activity patterns of neurons and their assemblies are\ud interdependent with the extracellular milieu in which they are embedded, and to whose time varying composition they contribute. The complexity of this interdependence in the temporal dimension forecloses any time and context invariant relation between what the experimenter may consider stimulus input and its representation in neural activity. Hence, ideas of coding by (quasi)-digital neurons are called in question by the mutual interdependence of neurons and their\ud humoral milieu. Instead, concepts of 'mass action' in the Nervous system gain a new perspective: this time augmented by including the chemical medium surrounding neurons as part of the dynamics of the system as a whole. Accordingly, a meaningful way to describe activity in a neuron assembly would be in terms of a state space in which it can move along an infinite number of trajectories.\u

Cerebral blood flow predicts differential neurotransmitter activity

Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific neurotransmitter systems remains unclear. We address this question by probing cerebral blood flow in healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms of action. We use a novel framework aimed at disentangling the observed effects to contribution from underlying neurotransmitter systems. We find for all evaluated compounds a reliable spatial link of respective cerebral blood flow changes with underlying neurotransmitter receptor densities corresponding to their primary mechanisms of action. The strength of these associations with receptor density is mediated by respective drug affinities. These findings suggest that cerebral blood flow is a sensitive brain-wide in-vivo assay of metabolic demands across a variety of neurotransmitter systems in humans

Evidence for selective executive function deficits in ecstasy/polydrug users

Previous research has suggested that the separate aspects of executive functioning are differentially affected by ecstasy use. Although the inhibition process appears to be unaffected by ecstasy use, it is unclear whether this is true of heavy users under conditions of high demand. Tasks loading on the updating process have been shown to be adversely affected by ecstasy use. However, it remains unclear whether the deficits observed reflect the executive aspects of the tasks or whether they are domain general in nature affecting both verbal and visuo-spatial updating. Fourteen heavy ecstasy users (mean total lifetime use 1000 tablets), 39 light ecstasy users (mean total lifetime use 150 tablets) and 28 non-users were tested on tasks loading on the inhibition executive process (random letter generation) and the updating component process (letter updating, visuo-spatial updating and computation span). Heavy users were not impaired in random letter generation even under conditions designed to be more demanding. Ecstasy-related deficits were observed on all updating measures and were statistically significant for two of the three measures. Following controls for various aspects of cannabis use, statistically significant ecstasy-related deficits were obtained on all three updating measures. It was concluded that the inhibition process is unaffected by ecstasy use even among heavy users. By way of contrast, the updating process appears to be impaired in ecstasy users with the deficit apparently domain general in nature

A neurobiological perspective on social influence: Serotonin and social adaptation

Humans are inherently social beings. Being suggestible to each other's expectations enables pro-social skills that are crucial for social learning and adaptation. Despite their high relevance for psychiatry, the neurobiological mechanisms underlying social adaptation are still not well understood. This review, therefore, provides a conceptual framework covering various distinct mechanisms underlying social adaptation and explores the neuropharmacology — in particular the role of the serotonin (5-HT) system — in modulating these mechanisms. This article reviews empirical results on social influence processing and reconciles them with recent findings from psychedelic research on social processing to elucidate neurobiological and neuropharmacological underpinnings of social adaptation. Various computational, neurobiological, and neurochemical processes are involved in distinct mechanisms underlying social adaptation such as the multisensory process of social information integration that is crucial for the forming of self-representation and representations of social norms. This is again associated with self- and other-perception during social interactions as well as value-based decision-making that guides our behavior in daily interactions. We highlight the critical role of 5-HT in these processes and suggest that 5-HT can facilitate social learning and may represent an important target for treating psychiatric disorders characterized by impairments in social functioning. This framework also has important implications for psychedelic-assisted therapy as well as for the development of novel treatment approaches and future research directions

A Neural Correlate of Predicted and Actual Reward-Value Information in Monkey Pedunculopontine Tegmental and Dorsal Raphe Nucleus during Saccade Tasks

Dopamine, acetylcholine, and serotonin, the main modulators of the central nervous system, have been proposed to play important roles in the execution of movement, control of several forms of attentional behavior, and reinforcement learning. While the response pattern of midbrain dopaminergic neurons and its specific role in reinforcement learning have been revealed, the role of the other neuromodulators remains rather elusive. Here, we review our recent studies using extracellular recording from neurons in the pedunculopontine tegmental nucleus, where many cholinergic neurons exist, and the dorsal raphe nucleus, where many serotonergic neurons exist, while monkeys performed eye movement tasks to obtain different reward values. The firing patterns of these neurons are often tonic throughout the task period, while dopaminergic neurons exhibited a phasic activity pattern to the task event. The different modulation patterns, together with the activity of dopaminergic neurons, reveal dynamic information processing between these different neuromodulator systems