Analytic Background in the Neuroscience of the Potential Project "Hippocrates"

Abstract

This paper reviews the principles identified in analytic neuroscience that could be used in the setup of an international project, "Hippocrates" (H-project), named after the author of the endocrine theory of temperaments. The H-project can aim to summarize the findings in functional neurochemistry of consistent behavioural patterns (CBPs) in health (such as temperament traits) and psychopathology (symptoms of psychiatric disorders); to have systematically structured neurochemical investigations; to have an analysis of CBPs that include all ranges of behavioural histories and to have these modules complemented by regional contrasts related to climate, diets and other bio-environmental factors. The review highlights the benefits of constructivism and illustrates the contrast between constructivism and current approaches in terms of analytic and methodological aspects. (1) "Where" the neurochemical biomarkers should be measured: the review expands the range of needed measurements to out-of-brain systems, including environmental factors, and explores the concept of Specialized Extended Phenotype. (2) "What" should be measured but is missing: the review points to the need for measurement of the "Throw & Catch" neurochemical relays; behavioural and neuronal events contributing to the consistency of the CBPs but not documented in measurements. (3) Structuring the H-project's setup: the paper briefly describes a proposed earlier neurochemical framework, Functional Ensemble of Temperament that that accommodates the neurochemical continuum between temperament and symptoms of psychiatric disorders. This framework is in line with documented "Throw & Catch" neurochemical relays and can also be used to organize data about the personal and professional history of an individual.

Keywords: Specialized External Phenotype; constructivism; neurochemical framework FET; neurotransmitters; project Hippocrates; “Throw & Catch”.

Figure 1

Action as a result of the selection of degrees of freedom (DF). This Figure uses symbols as formal notations for behavioural aspects. Constructivism suggests that behaviour starts from the maintenance of current cycles (denoted as O), and if the current behavioural alternatives do not fit the needs for cycle maintenance, behavioural regulation launches the re-integration of prefab (previously learned) actions (marked as [[]]). If prefab elements are insufficient, an integration of a new program of actions starts (marked as []), and if a program cannot be composed, then orientation processes increase (denoted as //\\). All these blocks are active all the time but to a different degree that depends on the complexity, novelty and uncertainty of situations and capacities of the individual. The lower level highlights the brain structures involved in the relevant stages of action construction: RN –raphe nucleus; mPFC—medial) prefrontal cortex; HT—hypothalamus; HC—hippocampus; BF—basal forebrain; LC—locus coeruleus; (dL, V)TA—(dorsolateral, ventral) tegmental area; Th—thalamus; AM—amygdala; NAc—nucleus accumbens; Caud—caudate nucleus in ventral striatum; Put—putamen; STN—subthalamic nucleus; PPN—pedunculopontine nucleus; Crbm—cerebellum; GP—globus pallidium; SN—substantia nigra.

Figure 2

The contrast between the Perceptron and classic excitation-inhibition models (A) and the Throw & Catch (T&C) principle (B). (A): In common Perceptron-like models, perception is viewed as receptors (depicted as antennas) passively receiving and processing ALL surrounding information using sets of inhibitory and excitatory networks. Biases are given as weights added to the size of the signals. (B): In the T&C principle, the nervous system throws substances and actions towards relevant targets, similarly to a pencil technique looking for the dents on a paper sheet. The “Throw” processes proactively generate an additional variance to increase the visibility of details needed to select degrees of freedom. The “Catch” processes represent much more organized and complex parts of the nervous system compared to the “Throw” processes. The Catch systems use strategic placement of receptors (depicted as an antenna) to analyze the resulting “dents”. The directionality of “Throw” and the position of Catch follow the body- and experience-related biases. The coloured rectangular logo symbolizes the role of neurochemical systems in inducing these biases. Using T&C as a self-regulated “flashlight” to amplify the details of perceiving DFs allows nervous systems to save resources by not sensing the majority of surrounding stimuli and have a proactive search for the relevant information.

Figure 3

Neurochemical framework Functional Ensemble of Temperament (FET) summarizing the action of neurochemical systems in the regulation of 12 universal aspects of action construction. Red “?” and “!!” signs symbolize emotional amplifiers based on opioid receptor systems, as described in our earlier reviews. When selected DFs do not work, a further search for alternatives is increased (“?”), and if it does—the chosen alternatives are approved (“!!”). The “?” system that generates the release of the catecholamines (DA in familiar elements of behaviour and NE in novelty), as well as the HPA axis arousal in rough emotional response, is represented by KOR, some microbiota and cytokines systems. The “!!” system that generates the release of DA and suppresses the HPA axis activation is based on the action of MOR (in the ventral striatum), DOR (in dorsal striatum) and some microbiota. Note: ACh: acetylcholine; NE: noradrenaline; 5-HT: serotonin; DA: dopamine; OXY: oxytocin, VSP: vasopressin, Tstr: testosterone; Adr: adrenalin (and its deficient cycles); GC—glucocorticoids (including cortisol dysregulation); ORE: orexins; NP: neuropeptides; Glu—glutamate; GG—Gamma-Aminobutyric Acid and Glu; (M/D/K)OR: (mu/delta/kappa) opioid receptor systems; ANS—autonomic nervous system.