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Given the limitations of current models, this chapter takes us back to the structure and functioning of brain regions themselves, focussing first on on systems considered important for understanding consciousness from a representational viewpoint: corticothalamic systems, cerebellum, basal ganglia, and hypothalamus. It examines whether systems for processing different sensory modalities share common grounds, thereby offering clues about shared requirements for conscious representation. Both at the level of local circuits and area-to-area connectivity, differences between systems are considerable, making it hard to extract such requirements. Turning to subcortical regions such as the cerebellum, basal ganglia and hypothalamus, it is noted that they also harbor sensing and information-processing principles that have been previously considered essential for conscious representation (e.g., recurrency, statistical dependence, complexity). Departing from the concept of conscious experience as multimodal, situational representation, it is arguably important to frame-shift from a “columnar” and strictly hierarchical view of the neocortex to a more “horizontal” view that emphasizes the unique reverberatory and recursive properties of the cortical network. This paves the way for exploring whether such properties may support construction of higher aggregate (multi-area) forms of representation from lower-level forms operating at the level of single neurons and within-area groups of neurons.

What are the neural mechanisms that determine whether an individual cooperates or competes with another member of his or her species? In other words, what neural mechanisms determine whether perceived social stimuli are assigned a positive or a negative valence by the perceiver, with positive social stimuli activating neural pathways that cause contact seeking behaviors, acceptance, caregiving, and other prosocial behaviors, while negative social stimuli activate pathways that cause avoidance, rejection, competition or even attack (antisocial behaviors)? These questions form the overarching issue of this essay, which focuses on the neurobiological mechanisms that shift an individual away from antisocial behaviors and toward prosocial behaviors.

Beside their action at the genomic level, estrogens such as 17β-estradiol (E2) also activate rapid and transient cellular, physiological, and behavioral changes. Aromatase is the key limiting enzyme in the production of estrogens and the rapid modulation of this enzymatic activity could produce rapid changes in local E2 concentrations. The mechanisms that might mediate such rapid enzymatic changes are thus currently under intense scrutiny. Recent studies in our laboratory indicate that brain aromatase activity is rapidly inhibited by an increase in intracellular calcium concentration that results from potassium-induced depolarization or from the activation of glutamatergic receptors. Altogether, the phosphorylation/dephosphorylation processes affecting aromatase activity provide a new general mechanism by which the concentration of estrogens can be rapidly altered in the brain and other tissues.

The endcoannabinoid system is an important regulator of appetite, food preference and body weight. It not only regulates metabolic feeding related hormones (leptin, ghrelin) in the brain and gut, but also regulates the brain reward circuitry involved in palatability based feeding. One of the primary roles of the endocannabinoid system is in the homeostatic regulation of feeding behaviour. New treatments for obesity are being developed that attempt to harvest the anti-obesity effects of the CB₁ antagonist, rimonabant, but that are devoid of the psychiatric side effects that became clearly known only after it was widely prescribed.

In broad outline the brain’s subsystems can be understood in terms of specific functionality. This chapter introduces these subsystems and provides and overview of how they work together to provide the brain’s cognitive capabilities. The focus of the chapter is the mammalian forebrain, an elaborate complex of structures that take advantage of phylogenetically earlier brain systems to create explicit programs. Executing current programs is the primary responsibility of the Cortical-Basal Ganglia-Thalamus loop. Creating new programs is handled by the Hippocampus, which interprets new information in terms of deviations form a vast library of existing programs, and the Amygdala, whose circuitry marks a potential programs importance. Numerical rating of marked programs as to importance and risk is achieved with the Hypothalamus’s modulation of neurotransmitters.

The closest invertebrate relatives of vertebrates have brains that are smaller and organizationally much simpler that those of vertebrates, but there are similarities in basic architecture from which an evolutionary trajectory from simple to complex can be inferred. The molecular data show that many of the patterning signals are common to a range of taxa, including insects and annelids, indicating that some features are ancient and widely shared. Among protochordates, amphioxus provides the best model for the basic circuitry of the basal brainstem, including the hypothalamus and reticular formation. These have key roles in homeostasis and locomotory control, using circuits where paracrine transmission, neuropeptides, and open tract organization predominate. What is missing from amphioxus are the expanded dorsal centres, used by vertebrates for processing inputs from the paired sense organs of the head, which are themselves vertebrate innovations. Signals from these are routed through stacked arrays of cells in cortex and related structures that act as parallel array processors. In pallial derivatives in the forebrain, this has led to the emergence of primary consciousness, exemplified by awareness of the visual field, which is probably widespread in vertebrates. The function of consciousness is suggested here to relate to the adaptive advantage of generating a searchable display of sensory data, i.e. a searchable database.

Although ECT was developed as a treatment for schizophrenia, its ease of use, its safety, and the lack of effective treatments for many psychiatric conditions encouraged experimentation with this therapy to treat other disorders. These explorations define a cluster of conditions— acute and chronic psychosis, psychiatric disorders in pregnancy and the postpartum period, and intractable seizure disorders—in which ECT has a clinical role. Strongly held beliefs (delusions), abnormal sensory experiences (hallucinations, illusions) that are not based upon reality, and beliefs that others are paying special attention or plotting harm to the subject (paranoid thoughts) impair social functioning and disrupt family life. Thought disorders are the central peculiarity of schizophrenia but are also frequently found in patients with depression, mania, toxic states, and brain disorders. Regardless of the cause or the associated signs and symptoms, treatment can reduce the psychosis. This benefit is often given small notice, however, because ECT is widely regarded as an antidepressant, not an antipsychotic, treatment. The relief of psychosis afforded by ECT varies with the underlying condition. Disorders in thought in patients with depression or mania are readily relieved. Indeed, the more severe form of psychotic depression is relieved more rapidly than nonpsychotic depression. When ECT is used to treat patients with malignant catatonia and delirium, the psychosis is relieved at the same time as the toxic state. When psychosis dominates the clinical condition without other features, schizophrenia is the usual diagnosis. For acute schizophrenia dominated by the positive symptoms of paranoia, catatonia, or excitement, ECT is quite helpful. It is not helpful for the chronic varieties dominated by passivity and withdrawal, the negative signs of the illness. The clinical approach to the diagnosis of a psychotic condition is to exclude other causes for psychosis first and reserve the label “schizophrenia” for the residue of “not otherwise diagnosed” psychotic conditions. While we are able to ameliorate the psychoses in mood disorders and toxic states, palliation and symptom reduction are the best that we can offer other psychotic patients. Electroconvulsive therapy and insulin coma therapy were the main treatments for psychosis at the time when Thorazine and other new antipsychotic drugs were introduced in the 1950s.