Consciousness.pdf

CONSCIOUSNESS Shafiq Dexter Abou Zaki Internist - Neurologist What is Consciousness? ◦ Consciousness is classically described as emerging from brain systems that make up the content of consciousness, regulated by distinct systems that control the level of consciousness ◦ The content of c...

CONSCIOUSNESS Shafiq Dexter Abou Zaki Internist - Neurologist What is Consciousness? ◦ Consciousness is classically described as emerging from brain systems that make up the content of consciousness, regulated by distinct systems that control the level of consciousness ◦ The content of consciousness is the substrate upon which levels of consciousness act. ◦ This content includes all the various types of information processed by hierarchically organized sensory, motor, emotional, and memory systems in the brain What is Consciousness? ◦ Level of consciousness can affect all of these specific functions. ◦ The level of consciousness is controlled by specialized cortical and subcortical systems that determine the amount of alertness, attention, and awareness (mnemonic, AAA) ◦ Alertne ss (arousal, wakefulne ss) is necessar y for any mea ningf ul response s to occur. ◦ Attent ion ena ble s selective or susta ined inf or ma tion to be p rocessed. ◦ Awarene ss is the abilit y to form exp erience s t ha t can pote ntially b e reporte d later. The Consciousness System ◦ The specialized brain networks controlling the level of consciousness ◦ The level of consciousness depends critically on both cortical and subcortical structures The Consciousness System ◦ Cortical components of the consciousness system include the major regions of the higher-order “heteromodal” association cortex. ◦ On the medial brain surface, important components are the medial frontal, anterior cingulate, posterior cingulate, and medial parietal (precuneus, retrosplenial) cortex ◦ On the lateral surface, major consciousness system networks include the lateral frontal, anterior insula, orbital frontal, and lateral temporal -parietal association cortex The Consciousness System ◦ It is important to recognize that individual components of the higher -order association cortex play important and well -studied roles in specific cognitive functions in the dominant and non -dominant hemispheres ◦ These same association cortex regions have also been described as participating in either so called task-positive networks based on their activation during externally oriented attention or task-negative networks, also known as the “default mode” based on activity at rest ◦ It is the collective activity of widespread areas of bilateral association cortex that determines the level of consciousness The Consciousness System ◦ Subcortical components of the consciousness system include the upper brainstem activating systems, thalamus, hypothalamus, and basal forebrain ◦ Other subcortical structures also participate, including portions of the basal ganglia, cerebellum, amygdala, and claustrum ◦ Multiple parallel neurotransmitter systems participate in subcortical arousal including acetylcholine, glutamate, gamma amino butyric acid (GABA), norepinephrine, serotonin, dopamine, histamine, and orexin The Consciousness System ◦ Recent proposed physiological mechanisms for consciousness include synchronized oscillations, slow cortical potentials, connectivity, information integration, population neuroenergetics, and recurrent or global neuronal processing among others. ◦ Much additional work is needed before the physiological mechanisms of consciousness are more definitely known. SUBCORTICAL NETWORKS AND CONSCIOUSNESS Subcortical Networks and Consciousness ◦ Alertness and Arousal ◦ midbrain and up pe r p ons, t ha la mus, hy pothalamus, a nd basal fore brain ◦ Attention and Awareness ◦ midbrain and up pe r p ons, t ha la mus, hy pothalamus, a nd basal fore brain, as we ll as by ot he r sub cortical ne tworks including t he supe rior colliculi, cereb ellum, amygdala , basal ganglia , cla ustrum, and t ha lamic re ticular nucleus Coma ◦ a state of unarousable unresponsiveness in which the eyes are closed, and no purposeful responses can be elicited ◦ occurs either through bilateral damage to widespread cortical areas, or via lesions in a core set of structures lying in upper brainstem and medial diencephalon ◦ Lesions in this small but critical region of the upper pons and midbrain produce profound coma Subcortical Networks and Consciousness ◦ The core brainstem arousal systems lie in the tegmentum and include a variety of nuclei embedded within the brainstem reticular formation. ◦ The tegmentum is sandwiched between the more ventral brainstem basis — containing ascending and descending white matter pathways; and the more dorsal tectum—lying dorsal to the cerebral aqueduct or fourth ventricle. ◦ Bilateral lesions of the thalamus, particularly in the intralaminar and midline thalamic nuclei , can also produce profound suppression of arousal Subcortical Networks and Consciousness ◦ Subsequent work has revealed that the subcortical arousal systems consist of multiple parallel neurotransmitter systems and pathways ◦ The projection systems arising from the upper brainstem including the midbrain and upper pons (pontomesencephalic reticular formation) tend to project upward to the cortex, diencephalon, and basal forebrain ◦ The upward projecting systems were originally called the “ ascending reticular activating system” (ARAS) ◦ the se “aro usal syste m s” ar is e fro m a vari e ty of spe c if ic nuc l ei rathe r than from what was form e rl y consi de red a si ngl e di ff usel y o rgani zed system Subcortical Networks and Consciousness ◦ The subcortical arousal systems in the midbrain and upper pons have three main targets: ◦ (i) Put at ive gluta ma tergic ne urons from the reticul ar formatio n and cholinergic neurons from the pedun culop ontin e tegmental nucleus (PPT N) an d la terod orsa l tegmental n ucl eus (LDTN ) project mainly to t he thalamus, part icula rly to the thal amic intralami nar nuclei which, in turn, increase cor tical arousal. ◦ (ii) Other ne urons p roje ct to the nucleus basalis (of Mey nert) and hyp othalamus, which aga in relay arousal inf luen ces to the corte x. ◦ (iii) Finally, the monoa minergic neurot ra nsmitte r systems (norep ine phrine , dop amine , serotonin) p roje ct dire ctly to the ent ire fore bra in including t he cortex and subcortical struct ures. Subcortical Networks and Consciousness ◦ The upper brainstem arousal systems are inf luenced by a variety of inputs including numerous regions of the association cortex and limbic cortex, as well as sensory pathways such as the anterolateral pain transmission pathways. ◦ Inhibitory inf luences arise from the thalamic reticular nucleus (modulatory function) as well as other GABAergic inputs ◦ The arousal systems are also strongly regulated by brainstem and hypothalamic circuits controlling circadian sleep rhythms The Thalamus and Consciousness ◦ Main relay station of all input and output signals to and from the cortex ◦ The rostral intralaminar nuclei (central lateral, paracentral, central medial nuclei) and midline thalamic nuclei are thought to be particularly important for activating the cortex ◦ The thalamic reticular nucleus forms a thin shell of predominantly GABAergic inhibitory neurons on the lateral thalamus ◦ As axons traverse this nucleus traveling from thalamus to cortex or from cortex back to thalamus, they give off collateral branches to the thalamic reticular neurons The Thalamus and Consciousness ◦ The thalamic reticular neurons, in turn, project to the thalamus and inhibit the specific thalamocortical neurons corresponding to individual corticothalamic loops ◦ The reciprocal connections between thalamic relay nuclei and the thalamic reticular nucleus are thought to play an important role in generating corticothalamic rhythms during normal sleep and waking activity, as well as in pathological rhythms such as epilepsy The Thalamus and Consciousness ◦ These physiological rhythms are crucial for regulating the level of consciousness. ◦ In addition, the thalamic reticular nucleus inf luences arousal through long- range inhibitory projections to the pontomesencephalic reticular formation ◦ Selective attention may also be mediated through the arrangement of reticular thalamic neurons and their directed inhibitory projections to the thalamus, which can generate an inhibitory surround around a “searchlight” of focused attention in a narrow band of thalamocortical channels Glutamatergic and Related Arousal Systems ◦ Glutamate is the most prevalent excitatory neurotransmitter of the central nervous system ◦ Arousal system pathways probably mediated by glutamate include those arising from the midbrain and upper pontine reticular formation that project to the thalamus and basal forebrain as well as the widespread projections from the thalamic intralaminar nuclei to the cortex Cholinergic Arousal Systems ◦ Acetylcholine is the major neurotransmitter of the peripheral nervous system, but in the central nervous system it has a more neuromodulatory function, where its role in arousal has been studied extensively ◦ Two main sources of cholinergic projections neurons in the central nervous system lie in the brainstem pontomesencephalic reticular formation and in the basal forebrain Cholinergic Arousal Systems ◦ At the junction of the midbrain and pons, the pedunculopontine nucleus is located in the lateral reticular formation, while the laterodorsal tegmental nucleus lies in the periaqueductal gray ◦ The pedunculopontine nucleus stretches from the caudal midbrain substantia nigra pars reticulata into the rostral pons towards the superior cerebellar peduncle ◦ Cholinergic neurons from these brainstem nuclei project to the thalamus, including the intralaminar nuclei, playing an important role in arousal Cholinergic Arousal Systems ◦ Brainstem cholinergic arousal is thought to act synergistically with noncholinergic putative glutamatergic pontomesencephalic neurons that project to intralaminar thalamus and basal forebrain ◦ In sleep, pontogeniculate waves arise from cholinergic brainstem neurons projecting to thalamocortical neurons in the lateral geniculate nucleus Cholinergic Arousal Systems ◦ The brainstem has very few direct cholinergic projections to the cortex and nearly all facilitatory effects of the brainstem cholinergic systems on cortex are mediated via the thalamus ◦ The major source of cholinergic input to the cortex is the basal forebrain ◦ Cholinergic neurons in the nucleus basalis of Meynert and surrounding regions (substantia innominata, globus pallidus, and preoptic magnocellular nucleus) not only project to almost the entire neocortex but also innervate some nuclei in the thalamus (reticular thalamic, mediodorsal, anteroventral/ anteromedial, and ventromedial nuclei) Cholinergic Arousal Systems ◦ The brainstem and basal forebrain cholinergic systems work together to abolish cortical slow wave activity and promote an alert state ◦ Cholinergic arousal in the central nervous system is mediated predominantly by muscarinic acetylcholine receptors, although nicotinic receptors may also play an important role in arousal and attention ◦ Pharmacological blockade of central cholinergic neurotransmission produces an acute state of delirium and memory loss GABAergic Arousal Systems ◦ Found in local inhibitory interneurons throughout the cortex and subcortical structures, GABA is the most prevalent inhibitory neurotransmitter in the central nervous system and plays a major role in regulating arousal. ◦ Some GABAergic neurons in the basal forebrain are thought to promote arousal because these inhibitory neurons in turn project to cortical inhibitory interneurons but others speculate these effects may be variable GABAergic Arousal Systems ◦ Other important long-range GABAergic projections mainly inhibit arousal ◦ These include neurons in ◦ ventral lateral preoptic nucleus , which have w idesprea d inhibitory proj ections to virt ua lly a ll sub cortical arousal syste ms ◦ la teral septal GABAergic neurons thought to inhibit the basal foreb ra in and hy pothalamus ◦ thal amic reticula r n ucl eus which cont ains GABAergic neurons proj ecting both to the remainder of the t ha la mus a nd to the b ra instem reticular format ion ◦ In addition, GABAergic neurons in the globus pallidus internal segment inhibit regions of the thalamus including the intralaminar nuclei Noradrenergic Arousal Systems ◦ Norepinephrine (noradrenaline)-containing neurons are in the locus ceruleus in the rostral pons adjacent to the fourth ventricle, as well as in the nearby lateral tegmental area extending into the more caudal pons and medulla ◦ Ascending noradrenergic projections reach the cortex, thalamus and hypothalamus to regulate sleep -wake cycles, attention, and mood ◦ Descending projections to the brainstem, cerebellum, and spinal cord modulate autonomic function and gating of pain ◦ Selective removal or blockade of noradrenergic neurons affects arousal but does not produce coma Serotoninergic Arousal Systems ◦ Serotonergic neurons are found predominantly in the midline raphe nuclei of the midbrain, pons, and medulla ◦ The more rostral serotonergic neurons in the midbrain and upper pontine raphe nuclei project to the entire forebrain, participating in sleep -wake regulation ◦ More caudal serotonergic neurons in the pons and medulla are important for modulation of breathing, pain, temperature control, cardiovascular, and motor function Serotoninergic Arousal Systems ◦ The most important rostral raphe nuclei participating in arousal are the dorsal raphe and median raphe ◦ Rostral brainstem serotonergic neurons have been proposed to promote arousal in response to hypoventilation and increased carbon dioxide levels, Dopaminergic Arousal Systems ◦ Most dopaminergic neurons are located in the ventral midbrain, either in the substantia nigra pars compacta or in the adjacent ventral tegmental area ◦ These mesencephalic nuclei give rise to the following three ascending dopaminergic projection systems: ◦ (i) t he mesostriat al (nigrost ria ta l) p athway project s from t he subst antia nigra to t he cauda te and puta me n ◦ (ii) t he mesolimb ic pa thw ay arises mainly f rom t he ve nt ra l tegment al area a nd project s to limbic struct ures including the medial temp oral lobe , amygdala, cingulate g yrus, sept al nucle i, and nucle us accumbens ◦ (iii) t he mesocortical pa thway arises mainly f rom t he ve nt ra l tegment al area a s well as sca ttered ne urons in the vicinity of the substa nt ia nigra a nd ve ntral pe ria queducta l gray, p roje cting to t he prefronta l cortex a nd thalamus Dopaminergic Arousal Systems ◦ Dopamine may contribute to maintaining the waking state at least in part through effects on other subcortical arousal circuits ◦ Effects of dopamine on the thalamus and cortex can be either excitatory or inhibitory ◦ Impaired dopaminergic transmission to the prefrontal cortex has been proposed to be important for the apathetic negative symptoms of schizophrenia, and may also contribute to states of markedly reduced motivation, initiative and action/intention seen in frontal lobe disorders, abulia, and akinetic mutism Histaminergic Arousal Systems ◦ Histamine-containing neurons are found mainly in the tuberomamillary nucleus of the posterior hypothalamus, although a few scattered histaminergic neurons are also found in the midbrain reticular formation ◦ Widespread ascending projections of histaminergic neurons from the tuberomamillary nucleus reach nearly the entire forebrain including cortex and thalamus, while descending projections target the brainstem and spinal cord Histaminergic Arousal Systems ◦ Histamine can produce arousal effects on cortex and thalamus ◦ Arousal actions of histamine may be mediated by activation of other subcortical arousal systems including other hypothalamic nuclei, the basal forebrain, brainstem cholinergic, and noradrenergic nuclei ◦ Effects of histamine are receptor -dependent as activation of H1 receptors promotes wakefulness, whereas H3 -receptors appear to have the opposite role Orexinergic Arousal Systems ◦ Orexin (hypocretin) is a peptide produced in neurons of the perifornical, lateral, and posterior hypothalamus , which project to both cortex and virtually all subcortical arousal systems to promote the awake state. ◦ The arousal effects of orexin likely arise from both cortical and subcortical mechanisms ◦ Abnormalities of the orexin system are thought to play a role in narcolepsy, a disorder characterized by excessive daytime sleepiness and pathological transitions into rapid eye movement sleep Adenosine and Arousal ◦ Although the neuroanatomical sources of adenosine are not well characterized, this neuromodulator may be important in mechanisms of conscious arousal ◦ The effects of adenosine on arousal are generally inhibitory, and circadian f luctuations in adenosine levels peak just prior to the initiation of sleep. ◦ Adenosine receptors are found in both cortex and thalamus, where they have an overall inhibitory function on arousal. ◦ Caffeine blocks adenosine receptors and this may be one important mechanism whereby coffee promotes alertness Amygdala and Arousal ◦ The amygdala, located in the anteromedial temporal lobe, has widespread and reciprocal cortical-subcortical connections that contribute to arousal particularly in response to emotions ◦ The main components of the amygdaloid nuclear complex are the corticomedial, basolateral, and central nuclei, as well as the bed nucleus of the stria terminalis. ◦ The basolateral nucleus is la rgest in huma ns and ha s wide sp re ad direct a nd indire ct connect ions to the cortex , basal f ore bra in, and medial tha lamus ◦ The smaller cor ticomedial nucleus - ap pet itive sta tes v ia the hyp othalamus, and olf action. ◦ The central nucleus, a lt hough sma llest, has conne ctions with t he hy pothalamus and brainste m part icipa ting in arousal a nd a utonomic control Attention and Awareness: Roles of Subcortical Arousal Systems, Tectal Region, Basal Ganglia, Claustrum, and Cerebellum ◦ The thalamus and other multiple parallel subcortical arousal systems in the upper brainstem, hypothalamus, and basal forebrain are essential for maintaining the alert state ◦ These same systems also play a key role in controlling attention and awareness not only in a permissive sense, but also by facilitating the additional processing in cortical and subcortical networks necessary for attention and for awareness. Attention and Awareness: Roles of Subcortical Arousal Systems, Tectal Region, Basal Ganglia, Claustrum, and Cerebellum ◦ Components of the tectal region, specifically the superior colliculi and pretectal area form an important circuit along with the pulvinar of the thalamus to direct saccadic eye movements towards salient stimuli, and the same circuits also participate in directed attention ◦ The basal ganglia have major reciprocal connections with the thalamic intralaminar nuclei and this circuit as well as other basal ganglia connections may contribute to arousal and attention functions Attention and Awareness: Roles of Subcortical Arousal Systems, Tectal Region, Basal Ganglia, Claustrum, and Cerebellum ◦ The claustrum is a thin layer of neurons located in the white matter between the putamen and insula, with widespread cortical connections that have been proposed to play an important role in the attention and awareness aspects of consciousness ◦ Finally, the cerebellum has major reciprocal connections with the prefrontal cortex and has also been proposed to participate in attention, although this remains somewhat controversial CORTICAL NETWORKS AND CONSCIOUSNESS Cortical Networks and Consciousness ◦ The cortical components of the consciousness system include widespread regions of association cortex in the bilateral cerebral hemispheres, particularly in the lateral frontal, anterior insula, lateral parietal (and adjacent temporal-occipital cortex), medial frontal, medial parietal (precuneus) and cingulate cortex ◦ It is the collective action of widespread bilateral association cortex regions that gives rise to regulation of the level of alertness, attention, and conscious awareness. The Cortex and Arousal ◦ The most important input to subcortical arousal systems, including the thalamus, hypothalamus, basal forebrain, and the multiple brainstem arousal systems is the cerebral cortex itself ◦ It has long been known that stimulation of the higher -order heteromodal frontoparietal association cortex increases arousal ◦ Unilateral cortical lesions usually do not markedly depress level of consciousness, but bilateral lesions of the association cortex can produce coma Attention and Consciousness ◦ Ideas of Attention vs Consciousness ◦ Both are the sa me ◦ Both are dif ferent ◦ Attent ion is necessa ry for but not identical to consciousness ◦ Models of Attention ◦ He mispheric Dominance of Attent ion ◦ Aff ect, Motiva tion a nd Attention ◦ The Binding Problem ◦ Top-down and Bottom-up Attention Net works ◦ Task-posit ive a nd Ta sk -nega tive Networks Hemispheric Dominance of Attention ◦ Large majority of individuals have dominant spatial attention in the right hemisphere ◦ Lesions of the right parietal and right frontal lobes may cause hemineglect of the left side of the body sometimes extending to the ipsilateral side ◦ The left hemisphere (left inferior frontal lobe) is more involved with language (Broca’s Area) making language an important component of the content of consciousness not a regulator of it Affect, Motivation and Attention ◦ One important aspect of cortical attention networks that should not be overlooked is the major role of affect and motivational drives ◦ Subjects who are emotionally motivated, for example, by seeking a reward, are clearly more successful in attention tasks ◦ The orbital frontal cortex and other limbic circuits have been implicated and are likely to be crucial for the motivational aspects of attention The Binding Problem ◦ Where and how do the diverse aspects of any particular percept come together to form a unified conscious experience? ◦ Many potential solutions have been proposed for how different components of sensory input are bound together into a single percept, including coherent high-frequency oscillations, lateral connections between neurons in particular cortical layers, among others ◦ One mechanism for attentional binding may be the interaction of primary cortices or unimodal association cortex with higher -order (heteromodal) parietal or other association cortices Top-down and Bottom-up Attention Networks ◦ Two separate but interacting systems mediating the top -down and bottom- up aspects of attention ◦ In this scheme, goal-oriented selection of stimuli and responses is controlled by dorsal regions of the frontal and parietal association cortex bilaterally, including the frontal eye fields and intraparietal sulcus. (Top- down) = LOGIC ◦ A second attention system serves a stimulus -driven “circuit-breaking” role for grabbing and reorienting attention in response to salient or changing sensory stimuli. ( Bottom-up) [more ventrally in the temporal-parietal junction and the ventral frontal cortex (including the frontal operculum), and is strongly lateralized to the right hemisphere] = EMOTION Task-Positive and Task-Negative Networks ◦ Regardless of the specific task, a particular set of regions tends to show reduced activity during task blocks when functional neuroimaging data are analyzed by conventional block-design analyses contrasting task versus rest (Task-Negative) ◦ Regions showing relatively increased activity during task blocks show greater variability depending on the specific task, but do show some general similarities between studies —particularly those involving attention (Task- Positive) Task-Positive and Task-Negative Networks Tas k-Negative Network s Tas k-Po sitive Networks ◦ precuneus/poste rior cingula te ◦ anter io r ins ula/f ront al o p erc ulum ◦ posterior-inferior p ariet al lobule ◦ s upp lem entar y moto r/do rsal m edial (angular gy rus) f ro ntal lo be ◦ lateral p remo tor co rtex ◦ vent ra l-ante rior medial f ronta l ◦ anter io r m id dle f ro ntal g yrus ◦ middle te mp ora l gyrus ◦ s uper io r p arietal ◦ media l temporal corte x ◦ lob ule/an terior inferio r p arietal lob ule ◦ lateral inferio r p os terior tem p oral g y rus Task-Positive and Task-Negative Networks ◦ In summary, a large number of cortical networks have been shown to participate in different aspects of attention and to modulate their activity in relation to onset and end of attention tasks. Memory Systems and Consciousness ◦ Alertness (arousal, wakefulness) can be tested based on responses to simple questions or commands, and attention based on tasks requiring selective responses ◦ Awareness, on the other hand, is demonstrated when a subject reports being aware of a particular stimulus or event - testing of conscious awareness requires memory ◦ In fact, it may be useful to define awareness as the attentive (process) and other processes necessary for events to be selected, handed off and encoded into memory for subsequent report. Volition and Conscious Free Will ◦ Conscious action can be divided into planning, “premeditation” or initiation of future activities, and awareness of ongoing or completed deeds ◦ Conscious planning and initiation of voluntary movement as well as decision making on the other hand, likely involve other neuroanatomical circuits ◦ Motor planning depends on a distributed network including the premotor, supplementary motor and other frontal cortical circuits, interacting with parietal association cortex and subcortical networks especially in the basal ganglia Volition and Conscious Free Will ◦ Stimu lation of the parietal cortex is accompanie d by an awareness of voluntary movement initiation or urge to move even if no actual motion takes place ◦ On the other hand, stimulation of the pre motor c ortex of the fronta l lobe can pro duce actual movement even when the subject is u naware of the movement ◦ Finally, stimulation of the supplem entary motor area produces an urge to move that may feel compu lsory or involuntary ◦ Spontaneous volu ntary movements are preced ed 1 -2 secs earlier by a “readiness potenti al” or “Bereitschafts potenti al” that can be record ed from the scalp near the midline and has subsequ ently been localized to the su pplementary motor area based on intracranial measu rements Self-Awareness and Embodiment ◦ Some consider self-awareness to be the defining sine qua non of consciousness, while others view awareness of self to be just one example of the many things that an individual can be aware of ◦ Awareness of self can be drastically and selectively impaired in certain neurological disorders ◦ A series of investigations using patients with out -of-body experience, or functional neuroimaging and behavioral interventions to create an out -of- body experience in normal subjects, have revealed that the right temporal- parietal junction plays a crucial role in this unusual condition. Awareness: Conscious Report and Contrastive Analysis ◦ Philosophers and scientists have long enjoyed a debate about whether or not consciousness can be understood through scientific investigation. ◦ First-Person Experience vs Second-Person Experience ◦ Taking this approach, a large number of studies have investigated the contrast between brain activity when a conscious event is reported or is not reported under very similar circumstances. Awareness: Conscious Report and Contrastive Analysis ◦ In summary, multiple studies using contrastive analysis have demonstrated that events reported as consciously perceived give rise to greater activity in the bilateral frontal and parietal association cortex. ◦ These findings support the idea that the anatomical regions constituting the consciousness system play an important role in regulating conscious awareness. CONSCIOUSNESS Shafiq Dexter Abou Zaki Internist - Neurologist