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\def\RunningAuthor{Yuvaraj Babu K et al.}
\firstPage{659}
\articleType{Review Article}
\receivedDate{23 Jul 2020}
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\title{Engine of Consciousness in Brain - A Review}
\author{Aldrin~Joshua~A\textsuperscript{1},  
            Yuvaraj~Babu~K\textsuperscript{*}\textsuperscript{1}, 
            Gifrina~Jayaraj\textsuperscript{2}~\\[5pt]{\textsuperscript{1}Department of Anatomy, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 77, Tamil Nadu, India}~\\{\textsuperscript{2}Department of Oral Pathology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 77, Tamil Nadu, India}}

\begin{abstract}
Consciousness is the cognitive faculty which is evolved by natural selection and it has designed a sense of ourselves and our surroundings. The cerebral cortex is `the seat of consciousness' in humans and mammals. The salient features of consciousness, they are human consciousness exists, involves short term memory, it occurs independently of sensory inputs, it displays steerable attentions, has capacity for attentive interpretations of complex or ambiguous data, consciousness disappears in a deep sleep and finally, it harbours the contents of several basic modalities within a single unified experience. The consciousness depends on the ascending projections from the dorsal brainstem that form the ascending reticular activating system. The engine of consciousness depends mainly on the brain's activity of sustaining rich dynamics in neural activity. The aim of the present review is to study the neuroscientific aspects of consciousness and thereby, the present scope of retrieving people out of consciousness and to consciousness disorders. This research was conceived as a scoping literature review. This review has accessed existing reviews and researches in the last decade mostly, through PMC database, MeSH, Google Scholar, Pubmed, Medline, CrossRef. Considered research was limited to manuscripts related to English, to consciousness, anaesthetic drugs relations, and Alzheimer's disease. This review excluded non-english researches, other neurological disorders not related to consciousness, physiological impairment of consciousness. Quality of articles used was assessed using Quality assessment tools and graded as strong, moderate and weak. The description of the included studies for the review is tabulated. 
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Consciousness,\newline Anaesthetic drugs,\newline Psychedelic drugs,\newline Alzheimer's disease
\end{keywords}
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\section{Introduction}
Consciousness is the cognitive division of the brain which is evolved by natural selection and it has designed a sense of ourselves and our surroundings. The cerebral cortex is `the seat of consciousness' in humans and mammals. There are seven salient features of consciousness. They are human consciousness exists, involves short term memory, it occurs independently of sensory inputs, it displays steerable attentions, has capacity for attentive interpretations of complex or ambiguous data, consciousness disappears in deep sleep which reappears in dreaming state when at-least in muted or disjointed form and finally it harbours the contents of several basic modalities within single unified experience \unskip~\citep{872543:20207465}. The consciousness depends on the ascending projections from the dorsal brainstem that form the ascending reticular activating system \unskip~\citep{872543:20207535}. The engine of consciousness depends mainly on the brain's activity of sustaining rich dynamics in neural activity \unskip~\citep{872543:20207469}. 

 Previous research models for consciousness was studied by \unskip~\citet{872543:20207477}. The study divided consciousness as brain-based and organism-based models. The neuroscientists claim that consciousness can also be reduced to the electrical pattern in specific brain modules. It helps in recording the responses of neurons to stimuli. Another recent study by \unskip~\citet{872543:20207493}, conducted on monkeys, found that electrically stimulating a certain part of forebrain's central lateral thalamus which wakes the monkeys from anaesthesia with minimum mechanisms that will be necessary for consciousness. The study concluded that these findings might someday be used to bring people out of coma, treat consciousness disorders and will ensure patients to stay anaesthetised during intensive procedures. If these researchers hope to find a network of neurons that satisfy the conditions for a neural correlate of consciousness and need convenient terms, it has a multitude of characteristics with specificity which will be a significant advantage. 

Over the past years various research done by our team was on osteology \unskip~\citep{872543:20207466}, foramens in middle cranial fossa \unskip~\citep{872543:20207473}, styloid process \unskip~\citep{872543:20207478}, foramen of Huschke \unskip~\citep{872543:20207479}, foramen meningo-orbitale \unskip~\citep{872543:20207490}, girdy's tubercle \unskip~\citep{872543:20207485}, Occipital emissary formanen \unskip~\citep{872543:20207537}, stature estimation \unskip~\citep{872543:20207481},  radiation effects of mobile phone \unskip~\citep{872543:20207536}, use of i-pads in education \unskip~\citep{872543:20207540}, on micro RNA \unskip~\citep{872543:20207474}, microRNA especially on preeclampsia patients \unskip~\citep{872543:20207533}, animal studies \unskip~\citep{872543:20207534}, and in few other fields like thyroid function \unskip~\citep{872543:20207483}, and amblyopia \unskip~\citep{872543:20207492}. There was not much work done on neurosciences hence the aim of the present review is to study the neuroscientific aspects of consciousness and updates on the latest research in it thereby presenting the scope of retrieving people out of unconsciousness and other related consciousness disorders. 
    
\section{Materials and Methods}
This research was conceived as a scoping literature review. This review has accessed existing reviews and researches in the last decade mostly, through PMC database, MeSH, Google Scholar, Pubmed, Medline, CrossRef and the search terms included were, 'consciousness', 'engine of consciousness', 'anaesthetic drugs', 'Alzheimer's disease', 'seat of consciousness'. Considered research was limited to manuscripts related to English, to consciousness, anaesthetic drugs relations, and Alzheimer's disease. This review excluded non-English researches, other neurological disorders not related to consciousness, physiological impairment of consciousness. The period of duration considered is 1909 to 2020. The total number of articles found on typing the topic is 6,840 and the number of articles actually relevant to the topic is 56 found by searching using keywords. The number of research articles that are used in writing the review is 35. Quality of articles used was assessed using Quality assessment tools and graded as strong, moderate and weak. The level of evidence of the reviewed articles was categorised according to the criteria of Centre for Evidence-Based Medicine, Oxford, UK and graded as strong, moderate and weak (Table~\ref{tw-4584248b76b7}).

\textbf{Consciousness}

\textbf{Definition of consciousness}

Consciousness is the cognitive faculty that is evolved during natural selection which has designed a sense of ourselves and our surrounding \unskip~\citep{872543:20207465}. Consciousness is the awareness by the sentience of external or internal existence. There are many definitions of consciousness in both scientific and psychological field. The real definition is still a mystery, but we can accept a few definitions \unskip~\citep{872543:20207482}. 

\textbf{Region of the brain concerned with Consciousness}

Consciousness mainly depends on ascending projections of the dorsal brainstem as ascending reticular activating system \unskip~\citep{872543:20207535}. Consciousness has a dependency on deep layer neurons which gives feedback to superficial layers. The neurons in the thalamus in deep cortical layers are more sensitive to the changes in consciousness level.So, for every change in consciousness level, it is due to neurons in the thalamus \unskip~\citep{872543:20207493}. The consciousness has the ability to retrieve information of attributes that are present in the multimodal sensory environment of relevant elements of the past \unskip~\citep{872543:20207475}. 


\begingroup
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\begin{longtable}{p{\dimexpr.07009999999999998\linewidth-2\tabcolsep}p{\dimexpr.19730000000000004\linewidth-2\tabcolsep}p{\dimexpr.10889999999999999\linewidth-2\tabcolsep}p{\dimexpr.17939999999999998\linewidth-2\tabcolsep}p{\dimexpr.2443\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}}
\caption{\boldmath {Descriptionand Quality of included studies} }
\label{tw-4584248b76b7}
\def\arraystretch{1.1}\\\endfirsthead \hline \noalign{\vskip3pt} \noalign{\textit{Table \thetable\ continued}} \noalign{\vskip3pt} \hline \endhead \hline \noalign{\vskip3pt} \noalign{\textit{\hfill Continued on next page}} \noalign{\vskip3pt} \endfoot \endlastfoot 
\tbltoprule \rowcolor{kwdboxcolor}No. & Author & Year  & Type of study & Key Points & Quality of study\\
\tblmidrule 
1 &
  \unskip~\cite{872543:20207465} &
  1996 &
  Systematic review &
  Consciousness is cognitive faculty that is evolved during natural selection. &
  Moderate\\
2 &
  \unskip~\cite{872543:20207482} &
  2010 &
  Systematic review &
  Consciousness is awareness by sentience by external or internal existence. &
  Moderate\\
3 &
  \unskip~\cite{872543:20207535} &
  2020 &
  Randomised controlled trial &
  Consciousness depends on ascending projections of dorsal brainstem. &
  Strong\\
4 &
  \unskip~\cite{872543:20207493} &
  2020 &
  Randomised controlled trial  &
  Certain part of the brain wakes monkeys from anaesthesia which is the central lateral thalamus of the forebrain &
  Moderate\\
5 &
  \unskip~\cite{872543:20207474} &
  2002 &
  Systematic review &
  Consciousness has the ability to retrieve information of attributes that are present in the multimodal sensory environment of relevant elements of the past.  &
  Moderate\\
6 &
  \unskip~\cite{872543:20207487} &
  1995 &
  Case controlled study &
  High frequency by EEG activation causes alert state of intactness which is from reticular formation of the brainstem. &
  Moderate\\
7 &
  \unskip~\cite{872543:20207488} &
  1908 &
  Systematic review  &
  Basal ganglia have the level of consciousness. &
  Moderate\\
8 &
  \unskip~\cite{872543:20207470} &
  2014 &
  Expert opinion &
  The consciousness will have direct influence on our behaviour,it moulds the behaviour. &
  Weak\\
9 &
  \unskip~\cite{872543:20207539} &
  2016 &
  Systematic review &
  Consciousness has dissociation from other brain functions. &
  Moderate\\
10 &
  \unskip~\cite{872543:20207477} &
  2004 &
  Systematic review &
  The consciousness is divided into brain based and organism based models. The neuroscientist claims that consciousness can be reduced to the electrical patterns in specific brain modules. &
  Moderate\\
11 &
  \unskip~\cite{872543:20207471} &
  2005 &
  Prospective study &
  In animals,consciousness is present in subcortical nuclei, reticular formation in midbrain and thalamus. &
  Strong\\
12 &
  \unskip~\cite{872543:20207545} &
  2000 &
  Expert opinion &
  Salient features of consciousness are explained. &
  Weak\\
13 &
  \unskip~\cite{872543:20207480} &
  2018 &
  Systematic review &
  Consciousness is useful in making voluntary decisions. &
  Moderate\\
14 &
  \unskip~\cite{872543:20207472} &
  2001 &
  Prospective study &
  Alzheimer's disease induces heterogeneous impairment. &
  Strong\\
15 &
  \unskip~\cite{872543:20207469} &
  2019 &
  Systematic review &
  Engine of consciousness depends mainly on the brain's activity of sustaining rich dynamics in neural activity. &
  Strong\\
16 &
  \unskip~\cite{872543:20207489} &
  2017 &
  Systematic review &
  Split brain does not cause the individual as two independent conscious perceivers. &
  Strong\\
17 &
  \unskip~\cite{872543:20207541} &
  2002 &
  Systematic review &
  Split brain patient is epileptic patient whose corpus callosum is severed. &
  Moderate\\
18 &
  \unskip~\cite{872543:20207486} &
  1999 &
  Case controlled study &
  The Cholinergic system has modulatory neurotransmitter systems which is an essential component of conscious awareness. Without this system, consciousness would be impaired. &
  Moderate\\
19 &
  \unskip~\cite{872543:20207538} &
  2020 &
  Systematic review &
  Current pharmacotherapy concentrated on drugs which improves cerebral acetylcholine level by facilitation of cholinergic neurotransmission by inhibiting cholinesterase. &
  Moderate \\
20 &
  \unskip~\cite{872543:20207462} &
  2020 &
  Prospective study &
  Physiological monitoring determines the depth of consciousness through EEG sensors. &
  Strong\\
21 &
  \unskip~\cite{872543:20207532} &
  2017 &
  Systematic review &
  State of consciousness is higher when psychedelic drugs are used. &
  Moderate \\
22 &
  \unskip~\cite{872543:20207542} &
  2020 &
  Randomised controlled trial &
  Anaesthetic drugs like GABA ergic agonist propofol, it is the way to control and reversibly modulate the brain's state of consciousness. &
  Strong \\
23 &
  \unskip~\cite{872543:20207464} &
  2020 &
  Systematic review &
  The stage of Anaesthesia, a type of anaesthesia, has a direct influence on EEG expression. &
  moderate\\
24 &
  \unskip~\cite{872543:20207494} &
  2020 &
  Systematic review &
  The consciousness disorder is due to damage to the brain cortex. &
  strong\\
25 &
  \unskip~\cite{872543:20207463} &
  2017 &
  Prospective study &
  Link between the sensor level connectivity and alpha bond of conscious states that will be indexed by behaviour. &
  Strong \\
26 &
  \unskip~\cite{872543:20207544} &
  2007 &
  Case controlled study &
  Increased consciousness will have lower risk of Alzheimer's disease. &
  Moderate \\
27 &
  \unskip~\cite{872543:20207543} &
  2003 &
  Case controlled study &
  Attempts to decode the natural correlate the single unified entity for the unity of consciousness. &
  Moderate \\
28 &
  \unskip~\cite{872543:20207461} &
  2020 &
  Systematic review &
  The vasovagal syncope in fainting is due to impaired consciousness. &
  Moderate \\
29 &
  \unskip~\cite{872543:20207484} &
  2010 &
  Systematic review &
  The brain activation consists of some awareness in cognition of vegetative or minimally conscious state. &
  Moderate \\
30 &
  \unskip~\cite{872543:20207468} &
  2017 &
  Randomised controlled study &
  Sometimes, overdose of painkillers, tranquilizers cause impaired consciousness. So, use of painkillers should be monitored. &
  Strong \\
\tblbottomrule 
\end{longtable}
\endgroup
\makeatletter\@ifundefined{TwoColDocument}{}{\twocolumn}\makeatother 
\textbf{Origin of consciousness}

In the 19th century, the neocortex was considered as the `seat of consciousness' and it is proven wrong. Recent studies state when high frequency by EEG activation causes an alert state of intactness which is from reticular formation of brainstem \unskip~\citep{872543:20207487}. The seat of consciousness is present in basal ganglia; having asleep, wake centres contribute to level of consciousness when there is no cerebral development due to damage of cerebral substance making consciousness unimpaired \unskip~\citep{872543:20207488}. 

\textbf{Function of consciousness}

Consciousness has a high biological value that benefits the organism, by changing its behaviour, in adaptation, to single representation parts of the brain. Consciousness will have a direct influence on our behaviour. It moulds the behaviour. If a person has a high consciousness level of himself, then the behaviour would be of a high standard \unskip~\citep{872543:20207470}. Consciousness has dissociation from other brain functions, including the language, memory, attention, language of the body and the self \unskip~\citep{872543:20207539}. 

\textbf{\textbf{Previous Researches}}

\textbf{Division of consciousness}

The consciousness is divided into brain-based and organism-based models. The neuroscientist claims that consciousness can be reduced to the electrical patterns in specific brain modules. It helps in recording the responses to stimuli of neurons. This type of division of consciousness would be helpful to treat certain brain problems like progressive brain damage, traumatic and non-traumatic brain damage \unskip~\citep{872543:20207477}. 

\textbf{Can it make patients come out of a coma?}

It has been proven that on electrically stimulating a certain part of the brain in monkeys, wakes them from anaesthesia. Similarly, stimulating a certain part of the central lateral thalamus of the forebrain in humans can retrieve patients from coma or consciousness disorders during intensive procedures. There is no research done on humans to verify the retrieval of coma of patients \unskip~\citep{872543:20207493}. These studies need to progress forward for the benefit of humans.

\textbf{Salient features of consciousness}

The salient features of consciousness involve short term memory by consciousness. It gives steerable attention, disappears in a deep sleep, it harbours the contents of basic sensory modalities within a single unified experience; it occurs independently of sensory inputs \unskip~\citep{872543:20207545}. Consciousness will be useful for voluntary decision making. So, the consciousness level should be high for making better voluntary decisions \unskip~\citep{872543:20207480}. Consciousness has many features to explore and to study.

\textbf{Engine of Consciousness}

\textbf{Depends on}

Consciousness depends on the interactions of thalamocortical and corticocortical tracts. So, the tracts from the thalamus to brain cortex and between fibres of brain cortex have a greater dependence on consciousness \unskip~\citep{872543:20207493}. Consciousness also depends on brains ability to sustain rich dynamics on neural activity \unskip~\citep{872543:20207469}. 

\textbf{Split-brain}

There are many theories behind the split-brain but does not cause the individual as two independent conscious perceivers \unskip~\citep{872543:20207489}. The split-brain patient is the epileptic patient (individual) whose corpus callosum is severed in order to minimise the spread of seizure activity. This is the most accepted theory behind the split-brain \unskip~\citep{872543:20207541}.

\textbf{Cholinergic systems}

 The Cholinergic system has modulatory neurotransmitter systems which are an essential component of consciousness, without which, consciousness would be impaired \unskip~\citep{872543:20207486}. Current pharmacotherapy concentrated on drugs which improve cerebral acetylcholine level by facilitation of cholinergic neurotransmissions by inhibiting cholinesterase which is recognised as cholinesterase inhibitors which have a modest influence on the improvement of Alzheimer's disease \unskip~\citep{872543:20207538}. 

\textbf{Current Advances}

\textbf{Depth of consciousness}

Physiological monitoring of the depth of consciousness through EEG sensors gives the treatment data \unskip~\citep{872543:20207462}. So, normal EEG is enough to measure the depth of consciousness. The depth of consciousness is needed to know the level of consciousness and the treatment procedure. 

\textbf{Psychedelic drugs involvement}

State of consciousness is higher when psychedelic drugs are used. So, the use of these drugs will definitely increase the consciousness level \unskip~\citep{872543:20207532}. These drugs will be useful in treating consciousness disorders.

\textbf{Anaesthetic drugs}

 Anaesthetic drugs like GABAergic agonist propofol is the way to control and reversibly modulate the brain's state of consciousness \unskip~\citep{872543:20207542}. EEG expression is based on the type of anaesthesia and the stage at which anaesthesia is given. The anaesthetic drugs have a greater impact on consciousness \unskip~\citep{872543:20207464}. 

\textbf{Disorders}

Disorders of consciousness is a set of clinical conditions where consciousness is affected by brain damage to the cerebral cortex \unskip~\citep{872543:20207494}. The brain activation consists of some awareness in the cognition of vegetative or minimally conscious state \unskip~\citep{872543:20207484}. Leaves of Mucuna pruriens contain dopamine used for the treatment of epilepsy which is a group of CNS disorders \unskip~\citep{872543:20207534}. 

\textbf{Behavioural consciousness}

The link between the sensor level connectivity and alpha bond of conscious states that will be indexed by behaviour. So, behavioural consciousness is necessary for us in every part of life \unskip~\citep{872543:20207463}. 

\textbf{The relation between consciousness and Alzheimer's disease}

 Increased consciousness will have a lower risk of Alzheimer's disease. So, the consciousness if increased by any treatment of drugs, especially psychedelic drugs, will lower the risk of Alzheimer's disease \unskip~\citep{872543:20207544}. Pulmonary arterial hypertension has been implicated in the pathogenesis of Alzheimer's disease \unskip~\citep{872543:20207474} and due to high blood pressure, the blood supply to the brain can be blocked causing preeclampsia which causes fainting of the individual \unskip~\citep{872543:20207533}. 

\textbf{Decoding}

 Attempts have been made to decode the neural correlate of consciousness, acknowledging the fact that consciousness is not a single entity and that there are instead many consciousnesses that are distributed in time and space. These multiple consciousnesses are called the 'synthetic, transcend' unified consciousness which constitutes a hierarchy. Thus the process of decoding will be helpful to access the part of the brain for retrieval of any information \unskip~\citep{872543:20207543}. 

\textbf{Factors affecting consciousness}

 The vasovagal syncope in fainting is due to impaired consciousness \unskip~\citep{872543:20207461}. Sometimes, overdose of painkillers, tranquilizers cause impaired consciousness. So, the use of painkillers should be monitored \unskip~\citep{872543:20207468}. Limitations of most previous researches are they only review articles. Most studies have been targeted in animals; such studies have not been studied on humans. These previous researches also did not find out the correct location of consciousness in the brain.
    
\section{Results and Discussion }
 The engine of consciousness mainly depends on interactions between thalamocortical and corticocortical nerve tracts \unskip~\citep{872543:20207493} and depends on the brain's ability of dynamics in neural activity \unskip~\citep{872543:20207469}. The seat of consciousness is in the reticular formation \unskip~\citep{872543:20207487}; basal ganglia has a level of consciousness \unskip~\citep{872543:20207488}. Alzheimer's disease has a lower risk due to increased consciousness \unskip~\citep{872543:20207544}. It induces heterogeneous impairment, consciousness has a convergence of many neural networks, the neuronal alterations that are lacking or distributed by the sequential order of successive stimuli cannot be maintained by heteromodal association cortex. The supramodal associative cortex has neural, cognitive networks \unskip~\citep{872543:20207472}. Anaesthetic drugs like GABAergic agonist propofol modulates the brain's state of consciousness. It is supported by cholinergic and GABAergics which affects sensory and associated cortical areas through altered arousal and cognition. In animals, consciousness is present in subcortical nuclei, reticular formation in midbrain and thalamus \unskip~\citep{872543:20207471}. The dexmedetomidine and propofol at equisedative doses have a greater impact on effects on visual stimulus induced GBR, has visual evoked responses and PMBR has effects on human consciousness \unskip~\citep{872543:20207491}. Cholinergic systems have modulatory neurotransmitter systems that are an essential component in conscious awareness \unskip~\citep{872543:20207486} and are advanced by current pharmacotherapy, the level of cerebral acetylcholine improved by drugs that inhibit cholinesterase \unskip~\citep{872543:20207538}. A certain part of the brain wakes monkeys from anaesthesia which is the central lateral thalamus of the forebrain. It is used for coma retrieval during intensive procedures \unskip~\citep{872543:20207493}. It is different from the midcingulate cortex, which has a critical role in the integrator of brain activity which vanishes in an altered state of consciousness \unskip~\citep{872543:20207494}.

 The limitations of the present review are that only recent studies have been included, mostly older studies have not been included. The study population of previous researches are different, like monkeys, rats, etc. The review should have larger, deeper research{\textemdash}more research needed in invivo studies and more elaborative studies to be included.

 Future scope of the review is future studies to be conducted on humans of consciousness which will provide the practice of reviving from a coma during trauma. 
    
\section{Conclusion}
More research has to be extended in humans so that for knowing the exact location of seat consciousness, methods can be devised to arouse the consciousness in patients going to an unconsciousness state as a result of trauma, health issues, faulty medical procedures and treatments, thereby many lives can be saved. 

\textbf{Funding Support }

The authors declare no funding support for this study 

\textbf{Conflict of Interest }

The authors reported the conflict of interest while performing this study to be nil.
    

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