KeywordsAutism Spectrum Disorder Transcranial Magnetic Stimulation Pyramidal Cell Gamma Oscillation Dopaminergic Tone
Definitions and Conclusions
Consciousness research is today one of the cornerstones in neuroscience. Almost all studies in the field have focused on identifying neural events accompanying appearences in the outer world, the “qualia,” like the redness of wine. These attemps have typically neglected the issue of the “Self.” Obviously, the self and qualia are two sides of the same coin. As formulated by Ramachandran (2004, p. 96):“You cannot have free-floating sensations, with no one to experience them.” Self-awareness is the essential tool for conscious metacognition. Metacognition monitors and controls behavior, the “self,” and thereby adjusts our beliefs of the world, essential for learning by conscious experience. This occurs not only within ourselves, but, importantly, also between individuals. Self-awareness is a primordial human capacity and is of decisive importance by giving humans an upper hand in phylogenetic development of culture and society (Frith 2012).
Self-awareness, or conscious self-monitoring, is the focus of this entry, based on a recent review (Lou et al. 2016a). It was until recently considered off-limits for the natural sciences. Neurobiological research shunned the “hard question of how consciousness and self-awareness arise from a physical basis,” influenced by the philosopher David Chalmers in the late 1990s (referenced by Lou et al. 2016a). Therefore, it has been fashionable to limit the quest for understanding the workings of the brain in consciousness and self-awareness to the task of identifying neural “correlates” of these mental functions. The limitation clearly involves the risk of arriving at two parallel worlds: a mental and a physical, without understanding how they interact. The consequence of this would be severe impediment of our understanding of the biological function of self-awareness and how it may account for disease in default.
However, using electrophysiological and pharmacological manipulations we have discovered that highly connected “hubs” of medial prefrontal and parietal are associated with self-awareness. They are not only linked to that function but indeed instrumental in its generation: Transcranial magnetic stimulation (TMS) targeting the hubs impedes specific aspects of self-awareness (Lou et al. 2004; Luber et al. 2012). Conversely, self-awareness is increased by dopaminergic challenge, primarily via GABA neurotransmission directly in the medial prefrontal cortex (Joensson et al. 2015; Lou et al. 2016b). The hubs are provided by an exceptionally rich assembly of fast-spiking parvalbumin interneurons assuring synchronization of their pyramidal cells for generation of self-awareness. The exceedingly high metabolic rate of these hubs makes them vulnerable in penuria of oxygen and/or glucose as a common final path in the pathophysiology of the many disorders with deficient self-awareness, like autism, attention deficit disorder, schizophrenia, and dementia.
Gallagher (2000), following Wittgenstein and the phenomenologists, claims that we are selfaware whenever we are conscious. Accordingly, self-awareness is an indispensible part of our experience of the world, whether it is minimal self-awareness (pre-reflective, with an automatic sense of ownership of the experience) or narrative (extended and reflective, based on retrieval of episodic (personal) memory). Minimal self-awarenes may be investigated using rapidly presented stimuli, which become aware to the observer when presentation time exceeds a certain threshold (Weiskrantz et al. 1995; Kjaer et al. 2001) or by comparing first person perspective with third person perspective (Vogeley et al. 2004). Narrative (extended) self-awareness may be investigated using retrieval of episodic memory of previous judgment of self versus another person (Lou et al. 2004). Both minimal and narrative self-awareness may be ranked according to the degree of self-reference (Craik et al. 1999).
The Paralimbic Network as a Signature of Self-Awareness and Conscious Self-Monitoring
From Association to Causality
Thus neural system, cellular, electromagnetic, and transmitter physiology all testify that the paralimbic system is instrumental in self-awareness. It is tantalizing how closely this discovery, based on experimental data, fits with suggestions based on bedside clinical observations by Ramachandran (2004, p. 112).
Ontogenesis of Self-Awareness and Metacognition
The infant is probably aware only of events in the present time, while the adult capacity to put these sensations into a time perspective, with ability to plan for the future, has to await later development (Lagercrantz and Changeux 2009). Similarly, the development of metacognition does not seem to occur until after 3 years of age.
This development occurs concomitantly with the development of resting state activity in the medial prefrontal and medial parietal hubs and insula, i.e., the paralimbic network (Fransson et al. 2011).
The widespread dysfunction of self-awareness in pathology is the result of the exceedingly high oxygen demand of the paralimbic default network (Kann 2016).This makes self-awareness, conscious self-monitoring, and metacognition particularly vulnerable to deficient oxygen and glucose supply. The high metabolic requirement is mainly due to dense concentrations of interneurons in the richly connected “hubs” of the paralimbic default network, their GABA-ergic synapses being instrumental for pyramidal cell synchronization in the paralimbic network. In particular, gamma oscillations are vulnerable to metabolic disruptions, a promising venue in the treatment and prevention of disorders of self-awareness.
Perspectives for Prevention and Treatment
The new understanding of the physiology and pathophysiology may lead to the application of novel or recently developed therapeutical strategies to increase dopaminergic activity and to improve neural interactions. These strategies may include meditation, which in independent studies have been shown to increase dopaminergic tone and induce growth in paralimbic structure, and targeted training aiming at increasing the availability of dopaminergic receptor. Also improvement of sensory input may be an important venue to increase dopaminergic tone and induce growth in relevant structures. Likewise frontal electromagnetic stimulation of oscillations may have a role. More generally, the new discoveries provide impetus to efforts to maintain oxygen homeostasis in neural tissue ranging from decreasing oxygen demand by cooling, for instance, in distressed neonates, to controlling cerebral perfusion pressure and autoregulation of cerebral blood flow, and obtaining optimal cerebral blood flow distribution via the capillary network (for review, see Lou et al. 2016a).
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