Literature Review: Restoration Processes of the Brain

By Mohammad R. Emami,

student of the Master in Applied Neuroscience

Mohammad R. Emami evaluates in his Master´s Thesis the restoration process of the brain by analyzing various recovery routs taken by the brain itself, either by utilizing neurogenesis or by shuffling its modulatory using functioning pathways and regions or even both, to compensate for the loss of vital information it suffers by losing a sensory system, such as sight. His thesis offers an overall vision of how valid and reliable scientific research are and examines, chronologically and rationality, scientific research in curative medicine since 1950s.

 

Methods: Descriptive overview of the current literature, synthesizing the conclusion and findings of the academic papers retrieved from on line database, such as PubMed, relevant journals, and published books on the subject.

 

Results: Injuries to the brain are a very perplexing practice, to diagnose, nurse and restore, depending on the nature of the damage, be it structural or alternations of synapses functionality.

 

Any degree of peripheral nerve impairment initiates a complicated cellular and molecular signalling alteration, and the amount of efficient recovery closely relates to the molecular feedbacks that struggle to sort-out and recondition the nerves to their pre-injury state. Nearly all sensory data reaches cortex through thalamus, and these signals to various cortex regions are able to initiate major changes in cortical wiring structure. The quality of recovery of TBI is not only burdened by CNS only, but also influence by external rehabilitation practices.

Introduction

 

Today, cognitive neurology considers the brain as an interconnected network, rather than as a group of regions functioning individually. Other studies indicate that the intensity of modularity network depends directly on the amount of performed cognitive tasks (Qiuhai et al., 2017).

 

Alterations due to injuries in nervous system provoke alterations in neural sub-structures at sub-cortical and cortical planes in CNS (Kaas et al., 2003). The underlying mechanisms of this central plasticity are largely unknown, but a heightened excitability is often observed in cortical regions that remodel in response to nerve injury (Navarro et al., 2007).

 

In 1928, Santiago Ramón y Cajal, the father of modern neuroscience, proclaimed that the brains of adult humans never make new neurons. “Once development was ended,” he wrote: “The founts of growth and regeneration … dried up irrevocably. In the adult CNS the nerve paths are something fixed, ended and immutable. Everything must die, nothing may be regenerated.” Ninety years later, it’s still unclear if his statement is true.

 

Similar to other parts of body, such as skin, Central Nervous System (CNS) has its own distinctive restorative process, newly termed as neuroplasticity. In 2007, Norman Doidge, a researcher psychiatrist at the university of Toronto puts neuroplasticity in the spotlight by publishing his book, The Brain That Changes Itself (Doidge, 2007).

 

Also, from his recent book, The Brain’s Way of Healing (Doidge, 2015): Remarkable Discoveries and Recoveries from the Frontiers of Neuroplasticity, reflects actual stories of patients provoking neuroplasticity and curing their disorders with no medicines or operations. In disorders from multiple sclerosis, Parkinson’s disease to autism and ADHD, brain’s overall neuronal and wiring shape goes wrong, as the result of inflammation, toxicity or genetic reasons behind abnormalities. Neural pathways may fail or become inactive or even fire at unbalanced rates.

 

Doidge terms this disorder a ‘noisy brain’. People with various disorders have limitations because neural circuits are inactive, but there exist other regions of the brain that are over active, which through practice, these healthy parts of cortex can be trained to undertake other functions. Triggering neuropathic growth, and brain regions would heal over a period of time, adds Dr. Doidge.

 

Methodology

 

Topics on neurology and brain impairments are vast and extremely complicated as there are genetics and epigenetic factors involved. This review is a collection of current substantive research-based knowledge, plus theoretical works offered on the subject matter, to indicate the current state of understanding, how this complicated cluster of neurons function when facing a major injury. The selected reviewed literature is the work of the most prominent scholars and researches of our time. This paper, within its limited scope, is a summary of major researches conclusions, with valid examples of what is firmly established knowledge so far, and how brain, bolted in cranium, zealous to be in touch with outside environment, alters itself accordingly to by-pass the impairment as much as possible. The organizational pattern of this review begins with wiring structure of various regions of the CNS and the impact of injuries on these regions, for example, visual, as studied by the scientist, retrieved from relevant journals.

 

In controversial cases such as neurogenesis, both sides of disputes by the scholars are reflected to signify the complexity and relativity of the subject matter, which largely depends on the vision of the researcher, category of their examined specimens, as well as quality of their scanners.

For this reason, this literature review ends with an annex, to also assess how contextual and dependent scientific research is.

 

Results

 

Based on the nature of impairments, disorders and injuries to CNS is a challenging exercise, beginning with correct diagnose and long-term healing process. The range of injuries depends on the severity and depth of the trauma, which could be mild, such as temporary concussions or deep CNS wounds causing coma or later amnesia, treatments differ depending on adequate diagnosis. It is now a well-known fact that brain, among other organs, is the most self-conscious structure, able to acknowledge damages and to some degree alter and adapt an ancillary means to the trauma, based on its nature of plasticity and cognitive reserve, or even the controversial notion of neurogenesis in some rare cases, together with an ample amount of rehabilitation support.

 

From early development, almost all incoming data touches the cortex through thalamus, a fairly large gray matter sensory relay station, incorporated within cortical regions of the brain, it is responsible for safety, security and haemostasis of the body. Sealed in cranium, thalamus has to be in touch with the outside environment, to perform its duties well according to its genetic instructions. Prognoses of restoration today, is promising and encouraging, despite the fact that the exact retrieval machinery of brain is not yet fully understood. There are now many curative possibilities offered by therapists to support and initiate neuroplasticity, upgrade of synaptic connections, as well as Brain Computer Interface supporting devices.

 

Although, similar to other organs, CNS has its own genetically programmed ability to recover wounds to certain level, but this ability gradually decreases with time and age. A recognised fact and practiced strategy to effective rehabilitation is involvement of close families and friends, to encourage the instinct healing process, burdened by brain alone.

 

Discussion

 

Brain has a stipulated structure, genetically, and an adaptive structure, epigenetically, depending on the living environment. The organ we know and study, today in our era, as brain, was much smaller with different (adapted) wiring structure in our ancestors Homo sapiens cranium.

 

We begin with an overview of some general structural details regarding cortical landscape of brain. A comparison in numbers is made between macaques and human neocortex.

 

Neocortex of cerebral brain is a similar to a sheet of ~105 cm2 per hemisphere, with ~ 1.4 billion neurons in each hemisphere, same size as a couple of ~12cm diameter cookies (Collins et al., 2010; Van Essen et al., 2012b). While, human cortex has four times more neurons (~8billions per hemisphere) and the surface area of the cortex is nine times bigger surface area (~973 ± 88 2 cm /hemisphere), which make it look like a pair of pizzas with 35 cm diameter (Azevedo et al., 2009; Van Essen et al., 2012c).The average quantity of neurons beneath each two millimetre of cortical sheet is less in humans (8 ×103) than it is in macaque (1.4 × 104). Density of neurones is also less in humans as the neocortex is typically slightly thicker in humans than in macaques (2.44 mm, from Van Essen et al., 2012c; 2.68 ± 0.40 mm for 196 HCP subjects—Glasser et al., 2013b) than in macaques (1.86 ± 0.40 mm from 19 macaques—Glasser et al. 2013b).

 

The layers of brain cortex, histologically, consist of grey panes of specialized neurons with no apparent boundaries, dedicated to specific sensory processing and movement roles.

 

The architect of the region’s borders can only be observed in cross section by staining for cells myelin. The occipital cortex, V1 to V8 (below picture) is among the largest and highest neuron dense areas. At the first glance, it seems neurons of each area are assigned to a limited specific function. Neurons of visual system, in occipital cortex, are tuned to respond to particular aspects of visual data, for instant, brightness, orientation and location within the field of eye view. It could be that the neurons of each layer of visual region have evolved and adapted to perform a specific task and are unable to do anything else. Or, it is also possible that any layer of this cortex can be re-trained to perform a different task, or somewhere in between these two extremes (Bedny, et al., 2015).

 

 

parts of parietal lobe

 

Crucial to understanding how prefrontal cortex functions is understanding the cortical architect and connectivity. Three dimensions of prefrontal cortex are examined:

 

Within frontal lobe, local projections, post-Rolandic projections and major fibre trajectories pathways. Organization of local connections are related to dorsal hippocampal source and ventral paleo cortical base development traces. Based on the theory of a “dual origin of cerebral cortex” cortical regions originate from hippocampal archi-cortex and also from the paleocortex, gradually (Sanides 1969, Pandya and Yeterian, 1985).

 

“Prefrontal cortex within each trend, are connected with less architectonically differentiated areas, and also with more differentiated areas. Such organization may allow for the systematic exchange of information within each architectonic trend” (Yeterain et al., 2011).

 

How nature and nurture form and guide brain development is by studying various brain regions of the blind and blindness. Occipital regions of the blind are activated by sensory inputs from other modalities, such as sound and touch. This cortex also contributes to tactile perception and sound localization, when it is not utilized as visual sensory perception area. (Merabet et al., 2004; Poirier et al., 2006; Collignon et al., 2011).

 

Brain cortex in human consists of many specified regions with different functionality, such as occipital, auditory, olfactory, plus regions for processing language. Question is; how genome and life style experience influence these special areas? Research on plasticity of brain indicate that these cortical areas alter their inherited function from one to another modality, in order to adapt. We demonstrate that in coming sensory data, throughout development changes cortical area functionality even more radically. For example, in blind individual a subdivision of visual cortex takes up the task of language processing. Remarkably, we noticed that this visual area also reacts to very specific features of language and sentence coordination, which is uniquely human. The obtained results propose that cortical area of human brain has a wide functional capability, during growth and development, inputs from outside environment play a key role in defining the functional specific adaptation. Adapted from “Visual Cortex of Congenitally Blind Adults Responds to Syntactic Movement” (Lane et al., 2015).

 

Above clearly indicates the readiness and plastic adaptability of neurobiology in developing brain, which despite its uniformity among individuals, still may be reformed and adjusted by other experiences outside linguistic involvement. Within the evolutionary distinctions between language and vision as we are aware of, involvement of visual cortex in language is outstanding and surprising. This wide range of brain flexibility and the key to its functionality can reflect vital information regarding how brain improves and matures. Most research on plasticity of occipital region are on adults, and plasticity during development is not yet looked into. One assumption is the period and timing of visual participation in language, which could develop in adolescence, requiring a long period of blindness to re-train or rewire the visual region to perform other functions. An important and distinct capacity of human CNS that emerges from its complex cognition is its capability to reconstruct its natural wiring arrangement, willingly, to adapt to environmental conditions, exploiting all sensory inputs at its disposal. Survival and advance cognitive performance seem to be the main force behind this flexibility. It is important to distinguish between sensory impairments and brain impairments. Sensory disorders have a profound effect on a healthy brain function and intellectual ability of the CNS. Brain impairments can also change the sensory (sight, hearing, touch and smell) capabilities and subsequent responsiveness to sensory information.

 

Below is an example of sensory impairments impact on cortical regions and brains determination to be in touch with the outside world as well as possible, by altering its structure accordingly.

 

In an article, in Wired Magazine, March 25, 2015, Adam Piore writes the story of Pat Fletcher, who lost her eyes more than thirty years ago, but gradually became able to see what she was hearing simultaneously, with ears. Obviously, her brain had reconfigured and re-trained her visual cortex to make sense of auditory inputs through ears. Although, seeing with ears experience seems illogical relative to what we acknowledge as logical and scientifically normal. But Pat Fletcher’s ability to see with her ears were tested and confirmed by prominent neuroscientists at Harvard Medical School. She has no eyeballs to look at the outside world, but after hearing her “soundscapes” her occipital cortex showed intense activity, when inside the MRI machine, and her auditory cortex responded to other sounds as normal. Surprisingly, her brain had learned to distinguish between incoming various sounds by directing them to configured regions, such as vision, despite of the fact that they did not enter the brain through eyes, but ears (Piore A. 2015).

 

The question here is the role of consciousness in this process, in other words, how much, conscious you, demand and push your sub-conscious brain to connect, YOU, to the outside world. At the other extreme, occipital responses to speech might be present at birth. Over time, vision might eliminate these non-visual responses in sighted children, whereas they are maintained in children who are blind. An intermediate possibility is that blindness causes responses to spoken language to emerge in visual cortex during early childhood (Bedny, et al., 2015).

 

The time course of plasticity also provides insight into its mechanism. How does occipital cortex come to respond to speech? According to one hypothesis, spoken language reaches occipital circuits from primary auditory areas or the auditory nucleus of the thalamus (Miller and Vogt, 1984; Falchier et al., 2002; Clavagnier et al., 2004). During development, occipital cortex initially responds to sound and, subsequently, gradually specializes for common or highly practiced sounds, such as speech. Cellular community of brain, the neurons, seem to function similar to bacteria in a biofilm via quorum sensing, which is cell to cell chemical communication to harmonise gene expression and behaviour, adaptively.

 

In a 1996 innovative study of those who were blinded early in life, neurologists proved that occipital cortex is capable of tasks other than visual such as reading Braille.

 

In order to better understand the neural processing of Braille, we can look to the literature on reading and writing in the sighted. Given its complex and dynamic nature, sighted reading has been shown to involve an expansive network of regions throughout the brain, many of which are concentrated in the left hemisphere (Dehaene et al., 2009). Early pre-lexical visual processing of the letters occurs in low-level occipital-temporal regions, including the “visual word form area” (Bolger et al., 2005) and the “grapheme area” in the left fusiform gyrus where the form and identity of the letters are assessed, respectively (Beeson et al., 2003). Meaning is then assigned to these letter forms in temporal regions including the left middle temporal gyrus and the left anterior fusiform gyrus, parietal regions including the left angular gyrus, and frontal regions including the left inferior frontal gyrus (Jobard et al., 2003; Dehaene, 2009).

 

The left Inferior Frontal Gyrus(IFG), also referred to as “Broca’s area,” has also been shown to be involved in the production and articulation of speech that occurs during reading.

 

Other areas implicated in production and articulation include the inferior precentral gyrus, the supra-marginal gyrus, and the superior temporal gyrus, all in the left hemisphere. Lastly, other parietal regions, including the posterior superior parietal lobule and the inferior parietal sulcus (Dehaene 2009; Jobard et al., 2003), are recruited during the serial allocation of spatial attention needed while reading (Likova et al., 2016).

 

Flexible connections

 

functional attributions of each network keyed by colour

 

Network for sighted reading: Image based on Figure 2.2 in Dehaene (2009), with functional attributions of each network keyed by colour.

 

The Broca’s and Wernicke’s language specialized regions of brain, to construct and understand language respectively, are well known to neuroscientist for over a century. To process language, these regions have essential properties, such as synaptic organization of neurons and connectivity with the rest of the brain, which gives them distinctive ability to process language.

 

Within the sensory cortices, other areas like occipital, auditory and olfactory have their own specialized regions. However, it seems that in assigning various functions of brain there is certain flexibility rather than a solid pre-determined decision. Animal studies by MIT professor Mriganka, have indicate that, each brain region can also process data from a different sense, when early in life it is rewired to them surgically. For instance, vision nerves to the auditory region activates auditory to process images rather than sound.

 

Studies and research have verified the query of gene and epigenetics involvement in regional functional properties of brain, in experience-based plasticity. For example, the visual area of the blind responds to tactile and auditory inputs (Hyvärinen et al., 1981). Also, areas of visual cortices show activity when blind adults locate sound or hear audio motions and distinguish tactile forms (Weeks et al., 2000; Merabet et al., 2004; Saenz et al., 2008). The auditory region, similarly, functions in respond to stimuli from visual and somatosensory (Finney et al., 2001, 2003; Karns et al., 2012).

 

So far, the flexibility in the areas of language processing has not been investigated, except some activity in the left occipital area of blind cognitive adults, during verbal tasks, but its development into language processing was not displayed. Rebecca Sax, an assistant professor of cognitive science, and Alvaro Pascal of Harvard Medical school, with Bendy and he colleagues, initiated a research to see if visual area in blind could be more involved in complicated tasks of language processing, like meaning of words and sentence structures. To start with, they scanned blind subjects (MRI) while they were performing a sentence comprehension task. The researchers were expecting activities in visual cortex, if this area was involved at all in processing language, similar to Broca’s and Wernicke’s area. To their surprise, that was the case and the visual area showed sensitivity to word meaning and structure of sentences, similar to typical language areas.

 

Bedny says: “The idea that these brain regions could go from vision to language is just crazy, she adds: It suggests that the intrinsic function of a brain area is constrained only loosely, and that experience can have really a big impact on the function of a piece of brain tissue (Saxe and Bedny, 2011).”

 

Another study by MIT neuroscientists indicate that, in blind born individuals, the task of language processing is assigned to some parts of occipital cortex, meaning that, visual area of brain can go through radical transformations to function other jobs. Secondly, the findings prove that the specialized areas of language processing are not genetically permanent and can diverge due to experience (Trafton 2011).

 

Marina Bendy, a MIT postdoctoral associate in Brain Cognitive asserts that: “Brain is not a pre-packed organ and does not grow along a permanent course; instead it is a self-made tool kit. This process of building is greatly influenced by the outside experience during growth and development.” The question is the “self-building” who is the self, and what is being built?

 

One thing is certain that, brain is an active vibrant organ, willing and able to change according to experience and life style. Age of course, and epigenetics such as nutrition, mental activity, and other social endeavours have vital influence in moulding the brain.

 

Traumatic brain injuries

 

After a traumatic brain injury, the degree of recovery is very variable dependent, which can last for weeks or months. The evidence-based knowledge regarding brain architect, involved in repairing impairments is so far limited. But the role of thalamus and its complicated attachment to the rest of brain is of importance and fundamental. Activation of thalamic nuclei, naturally or through rehabilitation in impaired brains can improve posttraumatic symptoms (Munivenkatappa & Agrawal 2016).

 

Also, a possible and likely reason for dementia is various injuries of brain, which can become even worse long after the damage, this process of neurodegeneration is not yet clearly understood. Long periods of neuroinflammation, initiated by microglial cells is linked to many neurodegenerative syndromes. Inflammation of thalamus for up to 17 years was detected by using PK11195(PK) PET, which is an indication of translocator protein (TSPO), secreted by activation of microglia cells. Question here is inflammation of thalamus, being distant from centre of injury (Scott et al., 2015).

 

Thalamus

 

Thalamus is a dense cluster of gray matter at the top end of brain stem, it is the central relay station for most of sensory signals to all other regions of cerebral cortex, regulating consciousness, alertness, sleep and homeostasis. Thalamus, being a well attentive entry access of almost all sensory information to related regions of cortical brain can be a serious candidate for consciousness locality. Also, during early brain development, communicative nerve supplies or innervations between rear thalamic region and cerebral hemispheres, an example of that is the thalamic reticular nucleus (TRN).

 

This nucleus is a strong controlling station in brain, such as sending back to thalamus the inhibitory axons, almost to the same area where they received afferent (Min B. K., 2010). Thalamus has other significant assignments through distinctive states of brain. For example, in intervals of alertness, neurons in thalamus produce strong chains of action potentials, in order to ease transmission of received sensory signals from eye, ear, skin… to cerebral cortex for decisive processing of each information received.

 

The important role of thalamic involvements and pathways has been deeply researched, towards the structures of thalamocortical wiring arrangement and connections of inter-cortical. A lot of evidence reveals for the thalamic role in innervation. On the other hand, the activity pattern of spatial-temporal, shows an informative function for future developments, like the arrangements of inter-cortical diagram (Mrigank Sur and Catherine A. Leamey 2001).

 

A schematic diagram of the connections between thalamic relay nuclei and their corresponding cortical areas

 

A schematic diagram of the connections between thalamic relay nuclei and their corresponding cortical areas (of the same colour) through the thalamic reticular nucleus(Min B. K. 2010, a thalamic reticular networking model of consciousness). Black lines indicate corticothalamic connections, and coloured lines indicate thalamocortical connections. A: anterior thalamic nucleus, M: medial thalamic nucleus, VA: ventral anterior nucleus, VL: ventral lateral nucleus, VP: ventral posterior nucleus, LP: lateral posterior nucleus, Pu: pulvinar, C: Centro medial nucleus, P: Para fascicular nucleus, LGN: lateral geniculate nucleus, MGN: medial geniculate nucleus, TRN: thalamic reticular nucleus (courtesy of Wolfgang Klimesch, with permission).

 

Relative to conscious mind, subconscious mind ascending from thalamic region, is somehow illogical and autonomic. Also, thoughts and deeds by conscious mind, are sometimes fearfully rejected or inhibited by thalamic subconsciousness.

 

For instance, Lamme agrees to the view that feedback pathways to the primary occipital region are needed for visual mindfulness he suggested that advanced pile up of frequent connections consequences to conscious awareness. Dehaene et al., in their ‘global workspace’ model of consciousness, suggested that conscious perception is systematically associated with parieto-frontal activity, causing top-down amplification. while, Zeki argued against a single entity of consciousness, claiming that there are multiple hierarchical consciousnesses (the micro-consciousnesses).

 

Thalamus and brain injuries

 

Thalamus, as the central conductor of brain and whole-body homeostasis functionality, is in touch via intense circuits with almost all sensory regions of brain. With such responsibility and ability, it is expected and considered to be the sub-seat of consciousness. Slightest injuries to thalamus nuclei cause severe coma, while disturbance of prefrontal cortex area (performed by lobotomy) only reduces consciousness. With all its vital importance and duties, it is still anatomically, chemically/electronic driven, and naively superficial in other mental functions.

 

Thalamus role in awakening system of brain is certain and critical, emotionally, and in various movement coordination. That is why it is an important centre for further in-depth studies, according to current detailed knowledge of its non-sensory nuclei and how it contributes to healthy or disordered cognitive functions (Lawrence 2013).

 

Covert consciousness

 

On the other hand, there is now enough evidence for covert consciousness, despite of the fact that behavioural examination may indicate otherwise. MRI and EEG screening of people with severe brain injuries indicate that they are they are covertly conscious. Typical brain analysis of clients with serious head injuries, normally and mistakenly suggest that the person is unconsciously in coma. Although, the patient is not able to respond, speak or move, but they seem to be, a majority of them, covertly conscious, meaning that the reptilian consciousness is still intact but unable to communicate due to injuries of higher brain regions.

 

In “Brain, a journal of neurology,” volume 140, issue 9 of September 2017 we read: A pioneering work in 2006, proved that fMRI (functional MRI) is able to identify consciousness in subjects in vegetative state (unresponsive wakefulness), according to behavioural clinical analysis (Owen et al., 2006), since then, in order to detect covert consciousness, or cognitive motor dissociation (CMD), in similar cases, functional imaging methods have been widely utilized (Schiff, 2015). Recent studies using EEG, active motor imagery and fMRI have shown a small number of subjects with chronic traumatic disorders of wakefulness and consciousness reflect signs of cognitive motor dissociation, verified through assignments of command-following (Monti et al., 2010; Cruse et al., 2011). Also, researches using music and passive language as stimuli have proved that people with consciousness disorders exhibit association cortex reactions, in the absence of language or comprehension behaviour (Coleman et al., 2009; Okumura et al., 2014). Although, evidence have proved that EEG and fMRI can, in some patients, with consciousness disorders detect cognitive motor dissociation, but there are no studies on patients in ICU suffering from severe brain Injuries. Detection of consciousness and cortical activity in early stages of injury is decisive for prognoses and neurological recovery (Giacino and Kalmar, 1997; Whyte et al., 2001; Coleman et al., 2009; Stender et al., 2014).

 

An analogy of covert consciousness would be, when for example, on line, in virtual reality, if my computer suddenly crashes or slows down and I can’t respond to emails and messages, don’t quickly assume that I am dead, wait, I, the conscious me, am trying to fix the computer. It may take a long while, but “I am” still there and appreciate any assistance from outside to pull “me” out, I need to be in touch with the out-side world. In the meantime, while in coma, please keep talking to me and play the music, I like it and helps me feel alive.

 

Consciousness is not entirely in the brain, within the wide spectrum of human consciousness, from ultimate to low sub consciousness. It is critical to recognize the position of thalamus as the meeting point, between spiritual high and inner thalamic (reptilian) consciousness. Similarly, in the universe above, where energy and matter meet.

 

Cognitive reserve

 

Cognitive reserve suggests that every individual has a different neural connectivity and network, depending on their life style and events such as dynamic education and physical activities,

 

which then results in different tolerance and handling various brain damages, relative to others with less reserve. Cognitive reserve theory was initiated by Dr. Yaakov Stern (2002, 2006 2009),  a professor of Neuropsychology at Columbia University, he asserts that; people with greater reserve are able to optimize or increase functioning through various recruitment of brain wiring network, this may reveal utilization of alternate cognitive strategies (Stern, 2002). The notion of cognitive reserve has been suggested to address the interruption caused by brain damage or pathology and its clinical manifestations. For example, a head injury of the same magnitude can result in different levels of cognitive impairment, and that impairment can vary in its rate of recovery. Similarly, several prospective studies of aging have reported that up to 25% of elders whose neuropsychological testing is unimpaired prior to death meet full pathologic criteria for Alzheimer’s disease (Ince, 2001), suggesting that this degree of pathology does not invariably result in clinical dementia (Stern,  2009).

 

threshold of brain reserve idea

 

Above picture indicates the threshold of brain reserve idea, in 2 subjects, who have different brain reserve capacities, an impairment large enough results in clinical irregularity in subject 2 with less amount of brain reserve. On the other hand, the same injury in subject 1 with more reserve reflects no clinical deficit. Picture revised from Stern 2002.

 

To recognize cognitive reserve, anatomic factors such as brain size, head circumference, synaptic numbers, or dendritic densities are applicable knowhow of reserve. Based on the epidemiologic data evaluated in the following, a variety of life experience are usually applied as proxies for cognitive reserve. These include measures of socio-economic position, and occupational accomplishment, educational achievement and relaxation activity. In other societies, quality  of literacy could be better indication for CR than the period of academic education, as it is a direct indicator of educational attainment (Manly, Touradji, Tang, & Stern, 2003Manly, Schupf, Tang, & Stern, 2005). Ultimately, particular counted aspects have been used as indicators of cognitive reserve, specifically IQ.

 

Education can be an important sign of intrinsic intelligence, which could be genetically based or a result of experience. Other research propose that an evaluation of IQ, could in fact be a stronger test for reserve in specific situations (Albert & Teresi, 1999Alexander et al., 1997).

 

Still, schooling and other active life practises have proved to reveal cognitive reserve better and beyond that gained from inherent intelligence. A potential study revealed that at age 53, IQ was distinctly related to early life cognition, education and adult occupation (Richards & Sacker, 2003). These explanations emphasize that CR is not a fixed phenomenon and at any point in person’s life, and it is the outcome from a combination of experiences (Stern 2009).

 

Both cognitive reserve and brain plasticity are related in the way that they are important measures of person’s intelligence, relative to conventional assessment of intelligence. Plasticity is the freedom and capacity of neural structure to redefine and restructure itself adaptively during a life time, this capacity includes gradual anatomical alternations of nervous wiring diagram, at different cortical levels. While, cognitive reserve is the tangible operating developments related to academic intelligence, social and physical activities people go through their lives. For this reason, in neuroscience, cognitive reserve and neural plasticity are diligently related and dependent. Overall, daily cognitive and other intellectual activities have a profound quantitative and qualitive effect on brain that makes it more resilient to impairments (Cabrera Pescador, 2018).

 

Thus, considering the above, to generalize, we may conclude that It is now a well-known fact that we don’t have brain but brains, very much like finger prints. People are born and raised in a different environmental circumstance that form their brain anatomically, accordingly. Therefore, brain impairments have different manifestations in each individual depending on a lot of factors such as cognitive reserve which is the measure of brain plasticity and self-consciousness which enforces the brain to adopt by converting to adequate neural network. Obviously, the higher the self-consciousness, the better the plasticity and ability to bypass impairments.

 

Consciousness

 

One of the core questions of neuroscience today, philosophically, historically is still what constitutes consciousness. In a study, reflected in “Science Advances” February 2019, which was a collective work between scientists from France, the US, Canada, Belgium, France and the UK, 159 people were put through functional MRI. Although their findings do not define what consciousness is, but what it does to brain by creating certain patterns, in healthy conscious individuals. These various objective patterns of cortical connections may assist a great deal in recognising amount of awareness during coma.

 

This research and findings confirm the hypothesis of the “Global Neuronal Workplace” asserting that various streams of information regions in brain compete with others for the overall separation from a united widespread of regional network, related to conscious access. With regards to fMRI BOLD (Blood Oxygen Level Dependent) signals, this may reflect, among communal inhibition activity at various regions of cortical brain, defining an anti-correlated dynamic (Demertzi et al., 2019)

 

interareal coordination of ongoing brain dynamics

 

The interareal coordination of ongoing brain dynamics is differentially orchestrated as a function of the state of consciousness. Picture by Demertzi et al.,2019.

 

There is today an insistent need to at least define consciousness, globally, before even attaining it, a seemingly impossible task as it depends firstly, on what we perceive as “consciousness” which differs person to person, scientist to scientist. One thing is clear that, to learn or to know we must be conscious, now we want to comprehend what this state of being is. For example, to see, we need to shed light on objects, to understand this necessary “tool” of seeing, the “light” we are looking for another light to shed on it, which does not work. Consciousness is the higher energy and the light, within, and the only way to understand it, is to have it, or better to say to be it, to be enlightened and conscious. Study shows that, there exist a biological, autonomic, computer like consciousness, arising from inner brain, involving thalamus, hypothalamus and hippocampus, and as we ascend towards cortical regions, awareness and mindfulness increases. One way to “be” conscious is to practice controlling this biological subconscious part of being, by for instance, braking the daily habit of eating or not eating for a certain period of time, which induces a mild controlled stress on the sub-conscious brain, by our conscious decision.

 

On the other hand, history has witnessed sages and transparent hearts, who spent years learning how to control this biological creature within, rather than examining it on a dish at school, and by controlling it they understood it much deeper and better, instead of finding the brain a complicated tangle of cells, they found it a naive adaptable lizard like simple pet, if well-ordered it will be your best friend and ride of life. It is nothing but a plastic and soft pathway with a genetic print, supplied to us so far today, patiently, through eons of a precisely selective evolution, which can even be altered and rewired as we wish. Similar to the universe, where matter and energy meet and transfer into each other, brain is where ultimate consciousness and sub-consciousness interact to constitute the extremely wide spectrum of human awareness.

 

Florian Mormann, one of the authors of a study published in Current Biology 2017 specifies that: The results of our study reveal the existence of an intermediate state between unconscious and consciousness within brain, on the neuron level (Reber et al., 2017).

 

This instrument of thoughts, brain, can play its own music anatomically, as programmed genetically and epigenetically, but sometimes it falls fully, as a tool, into the hands of a greater conscious artist and creator.

 

Diagnosis

 

Accurate diagnosis of the causal pathology is the key to effective and positive neurological restoration and healing. Recognizing the main effect of the injury on neural structure and regional network is an important factor prior to rehabilitation process. Today, the availability of advanced neuroimaging equipment offers a wide and deep vision of neural structure, to various levels of brain cortical configuration (Hu et al., 2014).

 

The main focus of healing and rehabilitation is to re-establish brain’s health and function as it was before the injury or as well as possible and improve the living quality of individuals. There is a verity of treatment options from endogenous to exogenous, by relying on brains own effort to heal or bypass impairments to pharmacological and rehabilitation physical exercises. Within the last decade, a new kind of treatment called Neural Interface Technology has gained much attention by neuroscientists, which is due to fast rate of developments in electronic and brain – computer devices. From deep brain stimulation to transcranial magnetic stimulation (TMS), this non-invasively stimulates or inhibits neural cells within the brain.

 

Brain Computer Interface

 

The primary goal of brain-computer interface (BCI) devices is to launch an uninterrupted contact and interaction route between brain and computer devices allowing a firm and more innate interaction and control for patients with motor incapacities of for example, spinal cord injury, limb amputation, and neurological disorders. Therefore, BCI is an auxiliary and assisting apparatus, what distinguishes BCI from classical devices is that, person’s will and thoughts are copied directly from the brain neural activity, without needing to use extra physical movements (Wang et al., 2010).

 

Consequently, BCI is a brain -computer system that utilises signals from brain, processes the signals and then interprets them into various commands that are fed into a device which functions accordingly, so, BCI by passes the normal brain-muscle pathway, which is impaired due to injuries. This limits the definition of BCI to any system that receives, analyzes and utilises CNS signals. For instance, a system that activates voice, or muscles is not a BCI, or an electroencephalogram (EEG) device is not considered a BCI system, as it only records signals produced by brain without further actions generated by the signals.

 

BCI equipment, are sometimes misunderstood as mind reading computers, as they do not collect mind information but assist the user in a convenient way, by reading command signals. It does take a period of training for the user to generate distinguished command signals translatable by the system to operate the intended action (Shih, et al., 2012).

 

BCI technology, among other similar gadgets have their pros and cons, such as cost and reliability. Not every person can afford a high-tech device nor medical insurances would cover such expenses, plus the reliability of a man made, imperfect computer program to control and conduct living activity of an impaired person is another problem to acknowledge.

 

BCI, similar to other gadgets have their own relative pros and cons, high cost and dependability is among the most important. Medical insurances normally don’t cover such high-tech devices, and there are many aspects of this system to be developed and modified yet (Shih, et al., 2012).

 

Neurogenesis

 

A hot debatable phenomenon, best is to leave it to the test of time, but for now, some research findings indicate generation of new neurons in adult hippocampal area of dentate gyrus and other suggest possibilities of very few neurons. Although, the main assumption is that; some go into forest looking for berries, a few find berries, and a few don’t, so there is berries in the forest, in some areas.

 

In brain, neural stem cells are cells capable of renewal and proliferate, to regenerate the main structure of the nervous system. In principle, they divide into various neurons, astrocytes or oligodendrocytes (Alenzi., 2011), via a diversity of differentiation. These cells are termed as adult stem cells, being limited in their capability to distribute and the fact that they are generated along an adult life long, in a process termed as neurogenesis. The brain region known for neurogenesis is the subventricular zone (SVZ) of lateral ventricles, which has the highest quantities of neural stem cells, with a capacity to produce glial cells as well (Clark.,2000). Within the SVZ region, ependymal cells and astrocytes, could secret certain molecules that guides the stem cell into neural or glial ending (Paspala., 2011).

 

olfactory bulb

 

Concerning neurogenesis in the adult brain, Gage (2002) argues: “A milestone is marked in our understanding of the brain with the recent acceptance, contrary to early dogma, that the adult nervous system can generate new neurons. One could wonder how this dogma originally came about, particularly because all organisms have some cells that continue to divide, adding to the size of the organism and repairing damage.”

 

Gage argues that; mammals are able to reproduce cells in many of their organs, such as blood and stem cells are present for a lifelong, and there is neurogenesis in insects, fish and amphibians. He adds that microglia and astrocytes are able to divide, and neurons were thought to be unable to replicate, now we know that there is neurogenesis in important areas of the brain like, hippocampus and subventricular zone. Gage also brings up a vital question that why other neurons are not programmed to replicate. One reason he points out is that the dendrites complexity and synaptic branches make it difficult, logically, for new neurons to grow and integrate in an already established network.

 

In “Science News Magazine” December 2018 Laura Sanders Wrote: “The battle over new nerve cells in adults intensifies just a generation ago, common wisdom held that once a person reaches adulthood, the brain stops producing new nerve cells. Scientists countered that depressing prospect 20 years ago with signs that a grown-up brain can in fact replenish itself. The implications were huge: Maybe that process would offer a way to fight disorders such as depression and Alzheimer’s disease. This year, though, several pieces of contradictory evidence surfaced, and a heated debate once again flared up.”

 

Sanders also adds that; although there are negative outcomes for new neurons growth, there are still many scientists who still believe new growth occurs. The evidence against neurogenesis in human brain seems to be weak and not convincing enough to totally abandon the theory, considering the difficulties in measuring and detecting neuron birth, and all studies depend on post-mortem tissues, which are not reliable enough to conclude. All agree that new methods are needed.

 

Up to now nobody knows for sure if a mature cultivates new neurons. The opening speech was from a controversial report in Nature, disputing some breakthrough discoveries that had influenced the scientific atmosphere that brain in adulthood is able to grow new neurons. A response came after a month from another research group offered many newly born neurons in post-mortem brains of adults, published in April 5th edition of Cell Stem Cell(SN: 5/12/18, p. 10). This on-going play of brain’s ability to regenerate new neurons into adulthood is still debatable and unresolved, a question yet to be firmly addressed (Sanders 2018).

 

Conclusion

 

Injuries to the brain are a very challenging practice, to diagnose and to heal, depending on the nature of the damage, be it structural or alternations of synapses functionality. The range of injuries depends on the severity and depth of the trauma, which could be mild, such as temporary concussions or deep CNS wounds causing coma or later amnesia, treatments differ depending on adequate diagnosis. In this paper we discussed the ability of CNS to alter and adapt an ancillary means to the trauma, based on its nature of plasticity and cognitive reserve, or even neurogenesis, in some rare cases. Plastic brain, specifically young ones, have an outstanding self-conscious capacity to recognize and rewire itself, and the way it functions, to cope with challenges.

 

As examined in this paper, thalamus, a fairly large gray matter sensory relay station, which is attentively incorporated within cortical regions of the brain, is responsible for safety, security and haemostasis of the body. From early development, nearly all data reaches cortex through thalamus, these signals to various cortex regions are able to initiate major changes in cortical wiring structure. Although, locked in cranium, thalamus needs to be in touch with the outside environment, to perform its duties well.

 

Full recovery is normally lengthy, depending on the nature of trauma and age of the brain, but the forecasts of recovery today is promising and encouraging, despite the fact that the exact retrieval machinery of brain is not yet fully understood. There are now many curative possibilities offered by therapists to support and initiate neuroplasticity and instinct healing process of the brain. From upgrading synaptic connections, cellular propagation to the alternation of inflammatory reactions of neurons. As well as pharmacological treatments, there are today Brain Computer Interface BCI devices, which collect signals from CNS, and interpret them into instruction, that are communicated with devises to perform the required function.

 

While, CNS has its own genetically programmed ability to repair injuries, to certain level, but this ability gradually reduces with time, there are many other factors that can and should be considered as part of rehabilitation process. A well-known fact and practiced strategy to effective rehabilitation is involvement of close families and friends, as there could be a long period before improvements, continues care and exercise is an important factor, supporting and encouraging the healing process of the sub-conscious brain, which desperately needs positive and inspiring signals from outside. The quality of recovery of TBI is not only burdened by CNS only, but also influence by external rehabilitation practices.

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