Excitation at widely dispersed loci in the cerebral cortex may represent a neural correlate of consciousness. Accordingly, each unique combination of excited neurons would determine the content of a conscious moment. This conceptualization would be strengthened if we could identify what orchestrates the various combinations of excited neurons. In the present paper, cholinergic afferents to the cerebral cortex are hypothesized to enhance activity at specific cortical circuits and determine the content of a conscious moment by activating certain combinations of (...) postsynaptic sites in select cortical modules. It is proposed that these selections are enabled by learning-related restructuring that simultaneously adjusts the cytoskeletal matrix at specific constellations of postsynaptic sites giving all a similar geometry. The underlying mechanism of conscious awareness hypothetically involves cholinergic mediation of linkages between microtubules and microtubule-associated protein-2 . The first reason for proposing this mechanism is that previous studies indicate cognitive-related changes in MAP-2 occur in cholinoceptive cells within discrete cortical modules. These cortical modules are found throughout the cerebral cortex, measure 1–2 mm2, and contain approximately 103–104cholinoceptive cells that are enriched with MAP-2. The subsectors of the hippocampus may function similarly to cortical modules. The second reason for proposing the current mechanism is that the MAP-2 rich cells throughout the cerebral cortex correspond almost exactly with the cortical cells containing muscarinic receptors. Many of these cholinoceptive, MAP-2 rich cells are large pyramidal cell types, but some are also small pyramidal cells and nonpyramidal types. The third reason for proposing the current mechanism is that cholinergic afferents are module-specific; cholinergic axons terminate wholly within individual cortical modules. The cholinergic afferents may be unique in this regard. Finally, the tapering apical dendrites of pyramidal cells are proposed as primary sites for cholinergic mediation of linkages between MAP-2 and microtubules because especially high amounts of MAP-2 are found here. Also, the possibility is raised that muscarinic actions on MAP-2 could modulate microtubular coherence and self-collapse, phenomena that have been suggested to underlie consciousness. (shrink)

The transplantation of cholinergic neurons into the hippocampal formation has been well characterized. We describe our studies on the effects of cholinergic transplants in the retrosplenial cortex. These transplants were capable of ameliorating spatial navigation deficits in rats with septohippocampal lesions. In addition, we provide evidence for the modulation of transplanted neurons by the host brain.

Robert Koch discovered the causal agents for tuberculosis, cholera, and anthrax. The 1905 Nobel Prize acknowledged Koch 's criteria for identifying the causal agent of an infectious disease. These criteria remain useful and the data reviewed below show that the cholinergic contributions to REM sleep control are confirmed by Koch 's postulates. [Hobson et al.].

The emergent Coronavirus Disease 2019 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 could produce a maternal immune activation via the inflammatory response during gestation that may impair fetal neurodevelopment and lead to postnatal and adulthood mental illness and behavioral dysfunctions. However, so far, limited evidence exists regarding long-term physiological, immunological, and neurodevelopmental modifications produced by the SARS-CoV-2 in the human maternal-fetal binomial and, particularly, in the offspring. Relevant findings derived from epidemiological and preclinical models show that a MIA (...) is indeed linked to an increased risk of neurodevelopmental disorders in the offspring. We hypothesize that a gestational infection triggered by SARS-CoV-2 increases the risks leading to neurodevelopmental disorders of the newborn, which can affect childhood and the long-term quality of life. In particular, disruption of either the maternal or the fetal cholinergic anti-inflammatory pathway could cause or exacerbate the severity of COVID-19 in the maternal-fetal binomial. From a translational perspective, in this paper, we discuss the possible manifestation of a MIA by SARS-CoV-2 and the subsequent neurodevelopmental disorders considering the role of the fetal-maternal cytokine cross-talk and the CAP. Specifically, we highlight the urgent need of preclinical studies as well as multicenter and international databanks of maternal-fetal psychophysiological data obtained pre-, during, and post-infection by SARS-CoV-2 from pregnant women and their offspring. (shrink)

Disturbances of consciousness, including fluctuations in attention and awareness, are a common and clinically important symptom in dementia with Lewy bodies. In the present study we investigate potential mechanisms of such disturbances of consciousness in a clinicopathological study evaluating specific components of the cholinergic system. [3H]Epibatidine binding to the high-affinity nicotinic receptor in the temporal cortex differentiated DLB cases with and without DOC, being 62–66% higher in those with DOC. The were no differences between DLB patients with or without (...) DOC in 125I-labeled α-bungaratoxin binding to the low-affinity nicotinic receptor, [3H]pirenzepine binding to the muscarinic M1 receptor, or in choline acetyltransferase activity. These findings provide support for the hypothesis that cholinergic activity is an important neural correlate if consciousness and suggest a mechanism of DOC in DLB involving alterations in the nicotinic receptor, composed of predominantly α4 and β2 subunits. (shrink)

As many as two million people in the United Kingdom repeatedly see people, animals, and objects that have no objective reality. Hallucinations on the border of sleep, dementing illnesses, delirium, eye disease, and schizophrenia account for 90% of these. The remainder have rarer disorders. We review existing models of recurrent complex visual hallucinations (RCVH) in the awake person, including cortical irritation, cortical hyperexcitability and cortical release, top-down activation, misperception, dream intrusion, and interactive models. We provide evidence that these can neither (...) fully account for the phenomenology of RCVH, nor for variations in the frequency of RCVH in different disorders. We propose a novel Perception and Attention Deficit (PAD) model for RCVH. A combination of impaired attentional binding and poor sensory activation of a correct proto-object, in conjunction with a relatively intact scene representation, bias perception to allow the intrusion of a hallucinatory proto-object into a scene perception. Incorporation of this image into a context-specific hallucinatory scene representation accounts for repetitive hallucinations. We suggest that these impairments are underpinned by disturbances in a lateral frontal cortex–ventral visual stream system. We show how the frequency of RCVH in different diseases is related to the coexistence of attentional and visual perceptual impairments; how attentional and perceptual processes can account for their phenomenology; and that diseases and other states with high rates of RCVH have cholinergic dysfunction in both frontal cortex and the ventral visual stream. Several tests of the model are indicated, together with a number of treatment options that it generates. Key Words: Blindness; Charles Bonnet; cholinergic; cortical release; delirium; dementia; dream intrusion; hallucination; Perception and Attention Deficit (PAD) model; schizophrenia. (shrink)

Cognitive deficits were produced in rats by different methods of damaging the brain: chronic ingestion of alcohol, causing widespread damage to diffuse cholinergic and aminergic projection systems; lesions (by local injection of the excitotoxins, ibotenate, quisqualate, and AMPA) of the nuclei of origin of the forebrain cholinergic projection system (FCPS), which innervates the neocortex and hippocampal formation; transient cerebral ischaemia, producing focal damage especially in the CA1 pyramidal cells of the dorsal hippocampus; and lesions (by local injection of (...) the neurotoxin, colchicine) of the granule cells of the dentate gyrus. Following chronic alcohol or lesions of the FCPS, transplants of cholinergically rich fetal brain tissue into the terminal areas (neocortex and/or hippocampus) restored performance almost to control levels, with a time course consistent with growth of the transplants and integration with host tissue; transplants of cholinergically poor fetal tissue (hippocampus) were without effect, as were transplants of cholinergically rich tissue into the region containing the nuclei of origin of the FCPS. Grafts of primary cells enriched in glia and cultured neuroblastoma cells into the terminal areas of the FCPS were equally effective, suggesting that there are multiple mechanisms by which neural transplants can restore cognitive function following diffuse cholinergic damage. In contrast, after ischaemia- or neurotoxin-induced damage to CA1 or dentate granule cells respectively, cholinergically rich fetal transplants into the damaged hippocampal formation were ineffective in restoring performance. After ischaemic damage, however, performance was restored by suspension grafts of CA1 cells but not by transplants containing CA3 pyramidal cells or granule cells; and after colchicine damage it was restored by solid grafts containing granule but not CA1 pyramidal cells. Furthermore, electrophysiological evidence has demonstrated functional, graft type-specific host-graft functional neuronal connectivity. Thus, restoration of cognitive function by neural transplants is possible after damage to either diffuse (cholinergic) or point-to-point (intrahippocampal) forebrain systems, but the transplant must be appropriate to the damage to be repaired. Because the different types of brain damage studied provide analogues of human alcoholic dementia, Alzheimer's disease, and heart attack, these results are encouraging with regard to the eventual application of neural transplant surgery to the treatment of cognitive deficits in humans. (shrink)

The cholinergic system is a good candidate for the role of determining the relative weight given in cortical information processing to new sensory information versus prior knowledge. We discuss the physiological data supporting this, and suggest that this Bayesian perspective can easily be reconciled with the dynamical framework proposed by Behrendt & Young.

Cholinergic-rich grafts have been shown to be effective in restoring maze-learning deficits in rats with lesions of the forebrain cholinergic projection system. However, the relevance of those studies to developing novel therapies for Alzheimer's disease is questioned.

A model of the neuropsychology of anxiety is proposed. The model is based in the first instance upon an analysis of the behavioural effects of the antianxiety drugs in animals. From such psychopharmacologi-cal experiments the concept of a “behavioural inhibition system” has been developed. This system responds to novel stimuli or to those associated with punishment or nonreward by inhibiting ongoing behaviour and increasing arousal and attention to the environment. It is activity in the BIS that constitutes anxiety and that (...) is reduced by antianxiety drugs. The effects of the antianxiety drugs in the brain also suggest hypotheses concerning the neural substrate of anxiety. Although the benzodiazepines and barbiturates facilitate the effects of γ-aminobutyrate, this is insufficient to explain their highly specific behavioural effects. Because of similarities between the behavioural effects of certain lesions and those of the antianxiety drugs, it is proposed that these drugs reduce anxiety by impairing the functioning of a widespread neural system including the septo-hippocampal system, the Papez circuit, the prefrontal cortex, and ascending monoaminergic and cholinergic pathways which innervate these forebrain structures. Analysis of the functions of this system suggests that it acts as a comparator: it compares predicted to actual sensory events and activates the outputs of the BIS when there is a mismatch or when the predicted event is aversive. Suggestions are made as to the functions of particular pathways within this overall brain system. The resulting theory is applied to the symptoms and treatment of anxiety in man, its relations to depression, and the personality of individuals who are susceptible to anxiety or depression. (shrink)

We present a theoretical view of the cellular foundations for network-level processes involved in producing our conscious experience. Inputs to apical synapses in layer 1 of a large subset of neocortical cells are summed at an integration zone near the top of their apical trunk. These inputs come from diverse sources and provide a context within which the transmission of information abstracted from sensory input to their basal and perisomatic synapses can be amplified when relevant. We argue that apical amplification (...) enables conscious perceptual experience and makes it more flexible, and thus more adaptive, by being sensitive to context. Apical amplification provides a possible mechanism for recurrent processing theory that avoids strong loops. It makes the broadcasting hypothesized by global neuronal workspace theories feasible while preserving the distinct contributions of the individual cells receiving the broadcast. It also provides mechanisms that contribute to the holistic aspects of integrated information theory. As apical amplification is highly dependent on cholinergic, aminergic, and other neuromodulators, it relates the specific contents of conscious experience to global mental states and to fluctuations in arousal when awake. We conclude that apical dendrites provide a cellular mechanism for the context-sensitive selective amplification that is a cardinal prerequisite of conscious perception. (shrink)

Empirical studies largely support the continuity hypothesis of dreaming. Despite of previous research efforts, the exact formulation of the continuity hypothesis remains vague. The present paper focuses on two aspects: the differential incorporation rate of different waking-life activities and the magnitude of which interindividual differences in waking-life activities are reflected in corresponding differences in dream content. Using a correlational design, a positive, non-zero correlation coefficient will support the continuity hypothesis. Although many researchers stress the importance of emotional involvement on the (...) incorporation rate of waking-life experiences into dreams, Hartmann formulated the hypothesis that highly focused cognitive processes such as reading, writing, etc. are rarely found in dreams due to the cholinergic activation of the brain during dreaming. The present findings based on dream diaries and the exact measurement of waking activities replicated two recent questionnaire studies. These findings indicate that it will be necessary to specify the continuity hypothesis more fully and include factors which modulate the incorporation rate of waking-life experiences into dreams. Whether the cholinergic state of the brain during REM sleep or other alterations of brain physiology are the underlying factors of the rare occurrence of highly focused cognitive processes in dreaming remains an open question. Although continuity between waking life and dreaming has been demonstrated, i.e., interindividual differences in the amount of time spent with specific waking-life activities are reflected in dream content, methodological issues have limited the capacity for detecting substantial relationships in all areas. Nevertheless, it might be concluded that the continuity hypothesis in its present general form is not valid and should be elaborated and tested in a more specific way. (shrink)

Clinical and experimental evidence suggests that hippocampal damage causes more severe disruption of episodic memories if those memories were encoded in the recent rather than the more distant past. This decrease in sensitivity to damage over time might reflect the formation of multiple traces within the hippocampus itself, or the formation of additional associative links in entorhinal and association cortices. Physiological evidence also supports a two-stage model of the encoding process in which the initial encoding occurs during active waking and (...) deeper consolidation occurs via the formation of additional memory traces during quiet waking or slow-wave sleep. In this article I will describe the changes in cholinergic tone within the hippocampus in different stages of the sleep-wake cycle and will propose that these changes modulate different stages of memory formation. In particular, I will suggest that the high levels of acetylcholine that are present during active waking might set the appropriate dynamics for encoding new information in the hippocampus, by partially suppressing excitatory feedback connections and so facilitating encoding without interference from previously stored information. By contrast, the lower levels of acetylcholine that are present during quiet waking and slow-wave sleep might release this suppression and thereby allow a stronger spread of activity within the hippocampus itself and from the hippocampus to the entorhinal cortex, thus facilitating the process of consolidation of separate memory traces. (shrink)

Dreaming: a process of self-organizationKahn and Hobson (1993) proposed that dreams are a product of self-organization of brain during sleep. As a complex system far from equilibrium state, the dreaming brain may form a new pattern by the interaction between components within this system. At REM sleep stage, signals from neuronal clusters self-organize and form image fragments, then the image fragments interact and produce images, and finally these materials are associated into a relatively continuous narrative (i.e., dreams). This process above (...) happens under a weak control of brain, and the conditions of this state mainly include: (a) the inhibition of external stimuli or feedback; (b) the changes of neuromodulatory systems (e.g., the governance of aminergic neurochemicals and the weakness of cholinergic neurochemicals); (c) the bombardment of PGO wave to the visual cortex; and (d) the changes of neural activity in brain (e.g., the activation of limbic system and the reduction of prefrontal regions). In this situation, the brain could focus on the internal world and integrate various psychological and physiological changes into dream content (Kahn et al., 2002, 2000). However, self-organization mechanism could not determine which memories will be activated and incorporated into dream content (Kahn, 2013), although it provides an approach how an ordered structure, behavior or pattern spontaneously emerges from the interaction between components or subsystems without an e... (shrink)

Background: Short latency afferent inhibition provides a method to investigate mechanisms of sensorimotor integration. Cholinergic involvement in the SAI phenomena suggests that SAI may provide a marker of cognitive influence over implicit sensorimotor processes. Consistent with this hypothesis, we previously demonstrated that visual attention load suppresses SAI circuits preferentially recruited by anterior-to-posterior -, but not posterior-to-anterior -current induced by transcranial magnetic stimulation. However, cerebellar modulation can also modulate these same AP-sensitive SAI circuits. Yet, the consequences of concurrent cognitive and (...) implicit cerebellar influences over these AP circuits are unknown.Objective: We used cerebellar intermittent theta-burst stimulation to determine whether the cerebellar modulation of sensory to motor projections interacts with the attentional modulation of sensory to motor circuits probed by SAI.Methods: We assessed AP-SAI and PA-SAI during a concurrent visual detection task of varying attention load before and after cerebellar iTBS.Results: Before cerebellar iTBS, a higher visual attention load suppressed AP-SAI, but not PA-SAI, compared to a lower visual attention load. Post-cerebellar iTBS, the pattern of AP-SAI in response to visual attention load, was reversed; a higher visual attention load enhanced AP-SAI compared to a lower visual attention load. Cerebellar iTBS did not affect PA-SAI regardless of visual attention load.Conclusion: These findings suggest that attention and cerebellar networks converge on overlapping AP-sensitive circuitry to influence motor output by controlling the strength of the afferent projections to the motor cortex. This interaction has important implications for understanding the mechanisms of motor performance and learning. (shrink)

Adenosine 5′-triphosphate (ATP) was identified in 1970 as the transmitter responsible for non-adrenergic, non-cholinergic neurotransmission in the gut and bladder and the term ‘purinergic’ was coined. Purinergic cotransmission was proposed in 1976 and ATP is now recognized as a cotransmitter in all nerves in the peripheral and central nervous systems. P1 (adenosine) and P2 (ATP) receptors were distinguished in 1978. Cloning of these receptors in the early 1990s was a turning point in the acceptance of the purinergic signalling hypothesis. (...) There are both short-term purinergic signalling in neurotransmission, neuromodulation and secretion and long-term (trophic) purinergic signalling of cell proliferation, differentiation and death in development and regeneration. Much is known about the mechanisms of ATP release and its breakdown by ectonucleotidases. Recently, there has been emphasis on purinergic pathophysiology, including neurodegenerative and neuropsychiatric disorders. Purinergic therapeutic strategies are being developed for treatment of gut, kidney, bladder, lung, skeletal and reproductive system disorders, pain and cancer. (shrink)

The neural correlates of rapid eye movements (REMs) in sleep are extraordinarily robust; including REM-locked activation in the retrosplenial cortex, the supplementary eye field and areas overlapping cholinergic basal nucleus. The phenomenology of REMs speaks to the notion that perceptual experience in both sleep and wakefulness is a constructive process – in which we generate predictions of sensory inputs and then test those predictions through actively sampling the sensorium with eye movements. On this view, REMs during sleep may index (...) an internalized active sampling or ‘scanning’ of self-generated visual constructs that are not constrained by visual input. If this view is correct, it renders REMs an ideal probe to study consciousness as “an exclusively internal affair” (Metzinger 2009). In other words, REMs offer a probe of active inference – in the sense of predictive coding – when the brain is isolated from the sensorium in virtue of the natural blockade of sensory input during REM sleep. REMs are temporally precise events that enable powerful inferences based on timeseries analyses. As a natural, task-free probe, [REMs] could be used in non-compliant subjects, including infants and animals. In short, REM constitutes a promising probe to study the ontogenetic and phylogenetic development of consciousness and perhaps its abnormal development in schizophrenia and autism, which have been considered in terms of aberrant predictive coding. (shrink)

What we perceive is the product of an intrinsic process and not part of external physical reality. This notion is consistent with the philosophical position of transcendental idealism but also agrees with physiological findings on the thalamocortical system. -Frequency rhythms of discharge activity from thalamic and cortical neurons are facilitated by cholinergic arousal and resonate in thalamocortical networks, thereby transiently forming assemblies of coherent oscillations under constraints of sensory input and prefrontal attentional mechanisms. Perception and conscious experience may be (...) based on such assemblies and sensory input to thalamic nuclei plays merely a constraining role in their formation. In schizophrenia, the ability of sensory input to modulate self-organisation of thalamocortical activity may be generally reduced. If during arousal thalamocortical self-organisation is underconstrained by sensory input, then attentional mechanisms alone may determine the content of perception and hallucinations may arise. (shrink)

This commentary takes a closer look at how “constructive models of subjective perception,” referred to by Collerton et al. (sect. 2), might contribute to the Perception and Attention Deficit (PAD) model. It focuses on the neuronal mechanisms that could mediate hallucinations, or false inference – in particular, the role of cholinergic systems in encoding uncertainty in the context of hierarchical Bayesian models of perceptual inference (Friston 2002b; Yu & Dayan 2002).

If both waking and dreaming consciousness are functional, their de-differentiation would be doubly detrimental. Differentiation between waking and dreaming is achieved through neuromodulation. During dreaming, without external sensory data and with mesolimbic dopaminergic input, hyper-cholinergic input almost totally suppresses the aminergic system. During waking, with sensory gates open, aminergic modulation inhibits cholinergic and mesocortical dopaminergic suppresses mesolimbic. These neuromodulatory systems are reciprocally interactive and self-organizing. As a consequence of neuromodulatory reciprocity, phenomenologically, the self and the world that appear (...) during dreaming differ from those that emerge during waking. As a result of self-organizing, the self and the world in both states are integrated.Some loss of self-organization would precipitate a degree of de-differentiation between waking and dreaming, resulting in a hybrid state which would be expressed heterogeneously, both neurobiologically and phenomenologically. As a consequence of progressive de-differentiation, certain identifiable psychiatric disorders may emerge. Ultimately, schizophrenia, a disorganized-fragmented self, may result. (shrink)

Based on recent insight into the thalamocortical system and its role in perception and conscious experience, a unified pathophysiological framework for hallucinations in neurological and psychiatric conditions is proposed, which integrates previously unrelated neurobiological and psychological findings. Gamma-frequency rhythms of discharge activity from thalamic and cortical neurons are facilitated by cholinergic arousal and resonate in networks of thalamocortical circuits, thereby transiently forming assemblies of coherent gamma oscillations under constraints of afferent sensory input and prefrontal attentional mechanisms. If perception is (...) based on synchronisation of intrinsic gamma activity in the thalamocortical system, then sensory input to specific thalamic nuclei may merely play a constraining role. Hallucinations can be regarded as underconstrained perceptions that arise when the impact of sensory input on activation of thalamocortical circuits and synchronisation of thalamocortical gamma activity is reduced. In conditions that are accompanied by hallucinations, factors such as cortical hyperexcitability, cortical attentional mechanisms, hyperarousal, increased noise in specific thalamic nuclei, and random sensory input to specific thalamic nuclei may, to a varying degree, contribute to underconstrained activation of thalamocortical circuits. The reticular thalamic nucleus plays an important role in suppressing random activity of relay cells in specific thalamic nuclei, and its dysfunction may be implicated in the biological vulnerability to hallucinations in schizophrenia. Combined with general activation during cholinergic arousal, this leads to excessive disinhibition in specific thalamic nuclei, which may allow cortical attentional mechanisms to recruit thalamic relay cells into resonant assemblies of gamma oscillations, regardless of their actual sensory input, thereby producing an underconstrained perceptual experience. Key Words: Charles Bonnet syndrome; gamma oscillations; hallucinations; late paraphrenia; Lewy body dementia; perception; schizophrenia; thalamocortical system. (shrink)

The paradigmatic assumption that REM sleep is the physiological equivalent of dreaming is in need of fundamental revision. A mounting body of evidence suggests that dreaming and REM sleep are dissociable states, and that dreaming is controlled by forebrain mechanisms. Recent neuropsychological, radiological, and pharmacological findings suggest that the cholinergic brain stem mechanisms that control the REM state can only generate the psychological phenomena of dreaming through the mediation of a second, probably dopaminergic, forebrain mechanism. The latter mechanism (and (...) thus dreaming itself) can also be activated by a variety of nonREM triggers. Dreaming can be manipulated by dopamine agonists and antagonists with no concomitant change in REM frequency, duration, and density. Dreaming can also be induced by focal forebrain stimulation and by complex partial (forebrain) seizures during nonREM sleep, when the involvement of brainstem REM mechanisms is precluded. Likewise, dreaming is obliterated by focal lesions along a specific (probably dopaminergic) forebrain pathway, and these lesions do not have any appreciable effects on REM frequency, duration, and density. These findings suggest that the forebrain mechanism in question is the final common path to dreaming and that the brainstem oscillator that controls the REM state is just one of the many arousal triggers that can activate this forebrain mechanism. The “REM-on” mechanism (like its various NREM equivalents) therefore stands outside the dream process itself, which is mediated by an independent, forebrain “dream-on” mechanism. Key Words: acetylcholine; brainstem; dopamine; dreaming; forebrain; NREM; REM; sleep. (shrink)

Toward illuminating the structure of Llewellyn's dream theory, I compare it in formal terms to Freud's dream theory. An alternative to both of these dream machines, grounded in the distribution of cholinergic activation in the central nervous system, is presented. It is suggested that neither nor dream theory is sufficient to account for the properties of dreams.

We argue that the rapid eye movement dream experiences owe their structure and meaning to inherent self-organizing properties of the brain itself. Thus, we offer a common meeting ground for brain based studies of dreaming and traditional psychological dream theory. Our view is that the dreaming brain is a self-organizing system highly sensitive to internally generated influences. Several lines of evidence support a process view of the brain as a system near the edge of chaos, one that is highly sensitive (...) to internal influences. Such sensitivity is due to several factors. First, the dreaming brain normally gates out external input and thus operates without the stabilizing influences of external feedback. Second, the pre-frontal cortex is only minimally activated during REM sleep, and hence the brain operates with weakened volition, reduced logic, and diminished self-reflection. Third, because the neuromodulatory inhibition mechanism is turned off during REM, the brain responds spontaneously to the least provocation. In addition, the dreaming brain is also subject to powerful intermittent cholinergic stimulation which may stimulate creative patterns of dream activity. (shrink)

What we perceive is the product of an intrinsic process and not part of external physical reality. This notion is consistent with the philosophical position of transcendental idealism but also agrees with physiological findings on the thalamocortical system. -Frequency rhythms of discharge activity from thalamic and cortical neurons are facilitated by cholinergic arousal and resonate in thalamocortical networks, thereby transiently forming assemblies of coherent oscillations under constraints of sensory input and prefrontal attentional mechanisms. Perception and conscious experience may be (...) based on such assemblies and sensory input to thalamic nuclei plays merely a constraining role in their formation. In schizophrenia, the ability of sensory input to modulate self-organisation of thalamocortical activity may be generally reduced. If during arousal thalamocortical self-organisation is underconstrained by sensory input, then attentional mechanisms alone may determine the content of perception and hallucinations may arise. (shrink)