Brain asymmetry

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In human neuroanatomy, brain asymmetry can refer to at least two quite distinct findings:

Contents

A stereotypical image of brain lateralisation - demonstrated to be false in neuroscientific research. Brain Lateralization.svg
A stereotypical image of brain lateralisation - demonstrated to be false in neuroscientific research.

Neuroanatomical differences themselves exist on different scales, from neuronal densities, to the size of regions such as the planum temporale, toat the largest scalethe torsion or "wind" in the human brain, reflected shape of the skull, which reflects a backward (posterior) protrusion of the left occipital bone and a forward (anterior) protrusion of the right frontal bone. [2] In addition to gross size differences, both neurochemical and structural differences have been found between the hemispheres. Asymmetries appear in the spacing of cortical columns, as well as dendritic structure and complexity. Larger cell sizes are also found in layer III of Broca's area.

The human brain has an overall leftward posterior and rightward anterior asymmetry (or brain torque). There are particularly large asymmetries in the frontal, temporal and occipital lobes, which increase in asymmetry in the antero-posterior direction beginning at the central region. Leftward asymmetry can be seen in the Heschl gyrus, parietal operculum, Silvian fissure, left cingulate gyrus, temporo-parietal region and planum temporale. Rightward asymmetry can be seen in the right central sulcus (potentially suggesting increased connectivity between motor and somatosensory cortices in the left side of the brain), lateral ventricle, entorhinal cortex, amygdala and temporo-parieto-occipital area. Sex-dependent brain asymmetries are also common. For example, human male brains are more asymmetrically lateralized than those of females. However, gene expression studies done by Hawrylycz and colleagues and Pletikos and colleagues, were not able to detect asymmetry between the hemispheres on the population level. [3] [4]

People with autism have much more symmetrical brains than people without it. [5] [6]

History

In the mid-19th century scientists first began to make discoveries regarding lateralization of the brain, or differences in anatomy and corresponding function between the brain's two hemispheres. Franz Gall, a German anatomist, was the first to describe what is now known as the Doctrine of Cerebral Localization. Gall believed that, rather than the brain operating as a single, whole entity, different mental functions could be attributed to different parts of the brain. He was also the first to suggest language processing happened in the frontal lobes. [7] However, Gall's theories were controversial among many scientists at the time. Others were convinced by experiments such as those conducted by Marie-Jean-Pierre Flourens, in which he demonstrated lesions to bird brains caused irreparable damage to vital functions. [8] Flourens's methods, however, were not precise; the crude methodology employed in his experiments actually caused damage to several areas of the tiny brains of the avian models.

Paul Broca was among the first to offer compelling evidence for localization of function when he identified an area of the brain related to speech. Paul Broca.jpg
Paul Broca was among the first to offer compelling evidence for localization of function when he identified an area of the brain related to speech.

In 1861 surgeon Paul Broca provided evidence that supported Gall's theories. Broca discovered that two of his patients who had suffered from speech loss had similar lesions in the same area of the left frontal lobe. [7] While this was compelling evidence for localization of function, the connection to “sidedness” was not made immediately. As Broca continued to study similar patients, he made the connection that all of the cases involved damage to the left hemisphere, and in 1864 noted the significance of these findings—that this must be a specialized region. He also—incorrectly—proposed theories about the relationship of speech areas to “handedness”.

Accordingly, some of the most famous early studies on brain asymmetry involved speech processing. Asymmetry in the Sylvian fissure (also known as the lateral sulcus), which separates the frontal and parietal lobes from the temporal lobe, was one of the first incongruencies to be discovered. Its anatomical variances are related to the size and location of two areas of the human brain that are important for language processing, Broca's area and Wernicke's area, both in the left hemisphere. [9]

Around the same time that Broca and Wernicke made their discoveries, neurologist Hughlings Jackson suggested the idea of a “leading hemisphere”—or, one side of the brain that played a more significant role in overall function—which would eventually pave the way for understanding hemispheric “dominance” for various processes. Several years later, in the mid-20th century, critical understanding of hemispheric lateralization for visuospatial, attention and perception, auditory, linguistic and emotional processing came from patients who underwent split-brain procedures to treat disorders such as epilepsy. In split-brain patients, the corpus callosum is cut, severing the main structure for communication between the two hemispheres. The first modern split-brain patient was a war veteran known as Patient W.J., [10] whose case contributed to further understanding of asymmetry.

Brain asymmetry is not unique to humans. In addition to studies on human patients with various diseases of the brain, much of what is understood today about asymmetries and lateralization of function has been learned through both invertebrate and vertebrate animal models, including zebrafish, pigeons, rats, and many others. For example, more recent studies revealing sexual dimorphism in brain asymmetries in the cerebral cortex and hypothalamus of rats show that sex differences emerging from hormonal signaling can be an important influence on brain structure and function. [11] Work with zebrafish has been especially informative because this species provides the best model for directly linking asymmetric gene expression with asymmetric morphology, and for behavioral analyses. [12]

In humans

Lateralized functional differences and significant regions in each side of the brain and their function

The left and right hemispheres operate the contralateral sides of the body. Each hemisphere contains sections of all 4 lobes: the frontal lobe, parietal lobe, temporal lobe, and occipital lobe. The two hemispheres are separated along the mediated longitudinal fissure and are connected by the corpus callosum which allows for communication and coordination of stimuli and information. [13] The corpus callosum is the largest collective pathway of white matter tissue in the body that is made of more than 200 million nerve fibers. [14] The left and right hemispheres are associated with different functions and specialize in interpreting the same data in different ways, referred to as lateralization of the brain. The left hemisphere is associated with language and calculations, while the right hemisphere is more closely associated with visual-spatial recognition and facial recognition. This lateralization of brain function results in some specialized regions being only present in a certain hemisphere or being dominant in one hemisphere versus the other. Some of the significant regions included in each hemisphere are listed below. [15]

Left Hemisphere

Broca's Area
Broca's area is located in the left hemisphere prefrontal cortex above the cingulate gyrus in the third frontal convolution. [16] Broca's area was discovered by Paul Broca in 1865. This area handles speech production. Damage to this area would result in Broca aphasia which causes the patient to become unable to formulate coherent appropriate sentences. [17]
Wernicke's Area
Wernicke's area was discovered in 1976 by Carl Wernicke and was found to be the site of language comprehension. Wernicke's area is also found in the left hemisphere in the temporal lobe. Damage to this area of the brain results in the individual losing the ability to understand language. However, they are still able to produce sounds, words, and sentence although they are not used in the appropriate context. [18]

Right Hemisphere

Fusiform Face Area
The Fusiform Face Area (FFA) is an area that has been studied to be highly active when faces are being attended to in the visual field. A FFA is found to be present in both hemispheres, however, studies have found that the FFA is predominantly lateralized in the right hemisphere where a more in-depth cognitive processing of faces is conducted. [19] [20] The left hemisphere FFA is associated with rapid processing of faces and their features. [19]

Other regions and associated diseases

Some significant regions that can present as asymmetrical in the brain can result in either of the hemispheres due to factors such as genetics. An example would include handedness. Handedness can result from asymmetry in the motor cortex of one hemisphere. For right handed individuals, since the brain operates the contralateral side of the body, they could have a more induced motor cortex in the left hemisphere.

Several diseases have been found to exacerbate brain asymmetries that are already present in the brain. Researchers are starting to look into the effect and relationship of brain asymmetries to diseases such as schizophrenia and dyslexia.

Schizophrenia
Schizophrenia is a complex long-term mental disorder that causes hallucinations, delusions and a lack of concentration, thinking, and motivation in an individual. Studies have found that individuals with schizophrenia have a lack in brain asymmetry thus reducing the functional efficiency of affected regions such as the frontal lobe. [21] Conditions include leftward functional hemispheric lateralization, loss of laterality for language comprehension, a reduction in gyrification, brain torsion etc. [22] [23]
Dyslexia
As studied earlier, language is usually dominant in the left hemisphere. Developmental language disorders, such as dyslexia, have been researched using brain imaging techniques to understand the neuronal or structural changes associated with the disorder. Past research has exhibited that hemispheric asymmetries that are usually found in healthy adults such as the size of the temporal lobe is not present in adult patients with dyslexia. In conjunction, past research has exhibited that patients with dyslexia lack a lateralization of language in their brain compared to healthy patients. Instead patients with dyslexia showed to have a bilateral hemispheric dominance for language. [24] [25]

Current research

Lateralization of function and asymmetry in the human brain continues to propel a popular branch of neuroscientific and psychological inquiry. Technological advancements for brain mapping have enabled researchers to see more parts of the brain more clearly, which has illuminated previously undetected lateralization differences that occur during different life stages. [9] As more information emerges, researchers are finding insights into how and why early human brains may have evolved the way that they did to adapt to social, environmental and pathological changes. This information provides clues regarding plasticity, or how different parts of the brain can sometimes be recruited for different functions. [26]

Continued study of brain asymmetry also contributes to the understanding and treatment of complex diseases. Neuroimaging in patients with Alzheimer's disease, for example, shows significant deterioration in the left hemisphere, along with a rightward hemispheric dominance—which could relate to recruitment of resources to that side of the brain in the face of damage to the left. [27] These hemispheric changes have been connected to performance on memory tasks. [28]

As has been the case in the past, studies on language processing and the implications of left- and right- handedness also dominate current research on brain asymmetry.

See also

Related Research Articles

Language center speech processing in the brain

In neuroscience and psychology, the term language center refers collectively to the areas of the brain which serve a particular function for speech processing and production. Language is a core system, which gives humans the capacity to solve difficult problems and provides them with a unique type of social interaction. Language allows individuals to attribute symbols to specific concepts and display them through sentences and phrases that follow proper grammatical rules. Moreover, speech is the mechanism in which language is orally expressed.

Corpus callosum White matter tract connecting the two cerebral hemispheres

The corpus callosum, also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental mammals. It spans part of the longitudinal fissure, connecting the left and right cerebral hemispheres, enabling communication between them. It is the largest white matter structure in the human brain, about ten centimetres in length and consisting of 200–300 million axonal projections.

Cerebral hemisphere The left and right cerebral hemispheres of the brain

The vertebrate cerebrum (brain) is formed by two cerebral hemispheres that are separated by a groove, the longitudinal fissure. The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres has an outer layer of grey matter, the cerebral cortex, that is supported by an inner layer of white matter. In eutherian (placental) mammals, the hemispheres are linked by the corpus callosum, a very large bundle of nerve fibers. Smaller commissures, including the anterior commissure, the posterior commissure and the fornix, also join the hemispheres and these are also present in other vertebrates. These commissures transfer information between the two hemispheres to coordinate localized functions.

Cingulate cortex Part of the brain within the cerebral cortex

The cingulate cortex is a part of the brain situated in the medial aspect of the cerebral cortex. The cingulate cortex includes the entire cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the cingulate sulcus. The cingulate cortex is usually considered part of the limbic lobe.

Parietal lobe

The parietal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The parietal lobe is positioned above the temporal lobe and behind the frontal lobe and central sulcus.

Temporal lobe One of the four lobes of the mammalian brain

The temporal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain.

Frontal lobe Part of the brain

The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere. It is parted from the parietal lobe by a groove between tissues called the central sulcus and from the temporal lobe by a deeper groove called the lateral sulcus. The most anterior rounded part of the frontal lobe is known as the frontal pole, one of the three poles of the cerebrum.

Cerebrum Large part of the brain containing the cerebral cortex

The cerebrum or telencephalon is the largest part of the brain containing the cerebral cortex, as well as several subcortical structures, including the hippocampus, basal ganglia, and olfactory bulb. In the human brain, the cerebrum is the uppermost region of the central nervous system. The cerebrum develops prenatally from the forebrain (prosencephalon). In mammals, the dorsal telencephalon, or pallium, develops into the cerebral cortex, and the ventral telencephalon, or subpallium, becomes the basal ganglia. The cerebrum is also divided into approximately symmetric left and right cerebral hemispheres.

Brodmann area 45

Brodmann area 45 (BA45), is part of the frontal cortex in the human brain. It is situated on the lateral surface, inferior to BA9 and adjacent to BA46.

Wernickes area Speech comprehension region in the dominant hemisphere of the hominid brain

Wernicke's area, also called Wernicke's speech area, is one of the two parts of the cerebral cortex that are linked to speech, the other being Broca's area. It is involved in the comprehension of written and spoken language, in contrast to Broca's area, which is involved in the production of language. It is traditionally thought to reside in Brodmann area 22, which is located in the superior temporal gyrus in the dominant cerebral hemisphere, which is the left hemisphere in about 95% of right-handed individuals and 70% of left-handed individuals.

Longitudinal fissure

The longitudinal fissure is the deep groove that separates the two cerebral hemispheres of the vertebrate brain. Lying within it is a continuation of the dura mater called the falx cerebri. The inner surfaces of the two hemispheres are convoluted by gyri and sulci just as is the outer surface of the brain.

Arcuate fasciculus

The arcuate fasciculus (AF) is a bundle of axons that generally connects the Broca's area and the Wernicke's area in the brain. It is an association fiber tract connecting caudal temporal cortex and inferior frontal lobe. Fasciculus arcuatus is latin for curved bundle.

Planum temporale

The planum temporale is the cortical area just posterior to the auditory cortex within the Sylvian fissure. It is a triangular region which forms the heart of Wernicke's area, one of the most important functional areas for language. Original studies on this area found that the planum temporale was one of the most asymmetric regions in the brain, with this area being up to ten times larger in the left cerebral hemisphere than the right.

Lateral ventricles Two largest ventricles in each cerebral hemisphere

The lateral ventricles are the two largest ventricles of the brain and contain cerebrospinal fluid (CSF). Each cerebral hemisphere contains a lateral ventricle, known as the left or right ventricle, respectively.

Brodmann area 22

Brodmann area 22 is a Brodmann's area that is cytoarchitecturally located in the posterior superior temporal gyrus of the brain. In the left cerebral hemisphere, it is one portion of Wernicke's area. The left hemisphere BA22 helps with generation and understanding of individual words. On the right side of the brain, BA22 helps to discriminate pitch and sound intensity, both of which are necessary to perceive melody and prosody. Wernicke's area is active in processing language and consists of the left Brodmann area 22 and Brodmann area 40, the supramarginal gyrus.

Lateralization of brain function Specialization of some cognitive functions in one side of the brain

The lateralization of brain function is the tendency for some neural functions or cognitive processes to be specialized to one side of the brain or the other. The medial longitudinal fissure separates the human brain into two distinct cerebral hemispheres, connected by the corpus callosum. Although the macrostructure of the two hemispheres appears to be almost identical, different composition of neuronal networks allows for specialized function that is different in each hemisphere.

Frontal lobe disorder Brain disorder

Frontal lobe disorder, also frontal lobe syndrome, is an impairment of the frontal lobe that occurs due to disease or frontal lobe injury. The frontal lobe of the brain plays a key role in executive functions such as motivation, planning, social behaviour, and speech production. Frontal lobe syndrome can be caused by a range of conditions including head trauma, tumours, neurodegenerative diseases, neurosurgery and cerebrovascular disease. Frontal lobe impairment can be detected by recognition of typical signs and symptoms, use of simple screening tests, and specialist neurological testing.

Dichotic listening is a psychological test commonly used to investigate selective attention and the lateralization of brain function within the auditory system. It is used within the fields of cognitive psychology and neuroscience.

Disconnection syndrome

Disconnection syndrome is a general term for a collection of neurological symptoms caused -- via lesions to associational or commissural nerve fibres -- by damage to the white matter axons of communication pathways in the cerebrum, independent of any lesions to the cortex. The behavioral effects of such disconnections are relatively predictable in adults. Disconnection syndromes usually reflect circumstances where regions A and B still have their functional specializations except in domains that depend on the interconnections between the two regions.

An estimated 90% of the world's human population consider themselves to be right-handed. The human brain's control of motor function is a mirror image in terms of connectivity; the left hemisphere controls the right hand and vice versa. This theoretically means that the hemisphere contralateral to the dominant hand tends to be more dominant than the ipsilateral hemisphere, however this is not always the case and there are numerous other factors which contribute in complex ways to physical hand preference.

References

  1. Nielsen, J. A., Zielinski, B. A., Ferguson, M. A., Lainhart, J. E., & Anderson, J. S. (2013). An evaluation of the left-brain vs. right-brain hypothesis with resting state functional connectivity magnetic resonance imaging. PLOS ONE, 8(8), e71275.
  2. LeMay M (June 1977). "Asymmetries of the skull and handedness. Phrenology revisited". Journal of the Neurological Sciences. 32 (2): 243–53. doi:10.1016/0022-510X(77)90239-8. PMID   874523. S2CID   24210069.
  3. Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, et al. (September 2012). "An anatomically comprehensive atlas of the adult human brain transcriptome". Nature. 489 (7416): 391–399. Bibcode:2012Natur.489..391H. doi:10.1038/nature11405. PMC   4243026 . PMID   22996553.
  4. Pletikos M, Sousa AM, Sedmak G, Meyer KA, Zhu Y, Cheng F, Li M, Kawasawa YI, Sestan N (January 2014). "Temporal specification and bilaterality of human neocortical topographic gene expression". Neuron. 81 (2): 321–32. doi:10.1016/j.neuron.2013.11.018. PMC   3931000 . PMID   24373884.
  5. Herbert, M. R. (2004-11-17). "Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis". Brain. Oxford University Press (OUP). 128 (1): 213–226. doi: 10.1093/brain/awh330 . ISSN   1460-2156. PMID   15563515.
  6. Postema, Merel C.; et al. (2019-10-31). "Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets". Nature Communications. 10 (1): 4958. Bibcode:2019NatCo..10.4958P. doi:10.1038/s41467-019-13005-8. ISSN   2041-1723. PMC   6823355 . PMID   31673008 . Retrieved 2021-03-22.
  7. 1 2 Springer S, Deutsch G (1997). Left Brain Right Brain: Perspectives from Cognitive Neuroscience. New York: W.H. Freeman & Company.
  8. Pearce, J. M. S. (2009). "Marie-Jean-Pierre Flourens (1794–1867) and Cortical Localization". European Neurology. 61 (5): 311–314. doi: 10.1159/000206858 . ISSN   0014-3022. PMID   19295220.
  9. 1 2 Toga AW, Thompson PM (January 2003). "Mapping brain asymmetry". Nature Reviews. Neuroscience. 4 (1): 37–48. doi:10.1038/nrn1009. PMID   12511860. S2CID   15867592.
  10. Gazzaniga MS, Ivry RB, Mangun GR (2002). "Cerebral Lateralization and Specialization" . Cognitive neuroscience : the biology of the mind (2nd ed.). New York: Norton. ISBN   978-0393977776. OCLC   47767271.
  11. Lewis DW, Diamond MC (1995). "The Influence of Gonadal Steroids on the Asymmetry of the Cerebral Cortex". In Davidson R, Hugdahl K (eds.). Brain asymmetry (2nd print ed.). Cambridge, Mass.: MIT Press. pp. 31–50. ISBN   978-0585326634. OCLC   45844419.
  12. Concha ML (August 2004). "The dorsal diencephalic conduction system of zebrafish as a model of vertebrate brain lateralisation". NeuroReport. 15 (12): 1843–6. doi:10.1097/00001756-200408260-00001. PMC   1350661 . PMID   15305121.
  13. Paul M. Thompson; Toga, Arthur W. (January 2003). "Mapping brain asymmetry". Nature Reviews Neuroscience. 4 (1): 37–48. doi:10.1038/nrn1009. ISSN   1471-0048. PMID   12511860. S2CID   15867592.
  14. "National Organization of Disorders of the Corpus Callosum National Organization of Disorders of the Corpus Callosum » National Organization of Disorders of the Corpus Callosum » Corpus Callosum DisordersNational Organization of Disorders of the Corpus Callosum National Organization of Disorders of the Corpus Callosum » National Organization of Disorders of the Corpus Callosum". nodcc.org. Retrieved 2019-04-11.
  15. Alqadah, Amel; Hsieh, Yi-Wen; Morrissey, Zachery D.; Chuang, Chiou-Fen (January 2018). "Asymmetric development of the nervous system". Developmental Dynamics. 247 (1): 124–137. doi:10.1002/dvdy.24595. ISSN   1097-0177. PMC   5743440 . PMID   28940676.
  16. "Broca area | anatomy". Encyclopedia Britannica. Retrieved 2019-04-11.
  17. "Broca's Area Is the Brain's Scriptwriter, Shaping Speech, Study Finds - 02/17/2015". www.hopkinsmedicine.org. Retrieved 2019-04-11.
  18. Binder, Jeffrey R. (2015-12-15). "The Wernicke area: Modern evidence and a reinterpretation". Neurology. 85 (24): 2170–2175. doi:10.1212/WNL.0000000000002219. ISSN   0028-3878. PMC   4691684 . PMID   26567270.
  19. 1 2 Kanwisher, Nancy; Yovel, Galit (2006-12-29). "The fusiform face area: a cortical region specialized for the perception of faces". Philosophical Transactions of the Royal Society B: Biological Sciences. 361 (1476): 2109–2128. doi:10.1098/rstb.2006.1934. ISSN   0962-8436. PMC   1857737 . PMID   17118927.
  20. Meng, Ming; Cherian, Tharian; Singal, Gaurav; Sinha, Pawan (2012-05-22). "Lateralization of face processing in the human brain". Proceedings of the Royal Society B: Biological Sciences. 279 (1735): 2052–2061. doi:10.1098/rspb.2011.1784. ISSN   0962-8452. PMC   3311882 . PMID   22217726.
  21. Sim, Kang; Bezerianos, Anastasios; Collinson, Simon L.; Chen, Yu; Sun, Yu (2017-01-01). "Reduced Hemispheric Asymmetry of Brain Anatomical Networks Is Linked to Schizophrenia: A Connectome Study". Cerebral Cortex. 27 (1): 602–615. doi: 10.1093/cercor/bhv255 . ISSN   1047-3211. PMID   26503264.
  22. Ribolsi, Michele; Daskalakis, Zafiris J.; Siracusano, Alberto; Koch, Giacomo (2014-12-22). "Abnormal Asymmetry of Brain Connectivity in Schizophrenia". Frontiers in Human Neuroscience. 8: 1010. doi:10.3389/fnhum.2014.01010. ISSN   1662-5161. PMC   4273663 . PMID   25566030.
  23. Royer, Céline; Delcroix, Nicolas; Leroux, Elise; Alary, Mathieu; Razafimandimby, Annick; Brazo, Perrine; Delamillieure, Pascal; Dollfus, Sonia (February 2015). "Functional and structural brain asymmetries in patients with schizophrenia and bipolar disorders". Schizophrenia Research. 161 (2–3): 210–214. doi:10.1016/j.schres.2014.11.014. PMID   25476118. S2CID   18134633.
  24. Helland, Turid; Asbjørnsen, Arve (October 2001). "Brain asymmetry for language in dyslexic children". Laterality: Asymmetries of Body, Brain and Cognition. 6 (4): 289–301. doi:10.1080/713754422. ISSN   1357-650X. PMID   15513177. S2CID   30457618.
  25. Leonard, Christiana M.; Eckert, Mark A. (2008). "Asymmetry and Dyslexia". Developmental Neuropsychology. 33 (6): 663–681. doi:10.1080/87565640802418597. ISSN   8756-5641. PMC   2586924 . PMID   19005910.
  26. Gómez-Robles A, Hopkins WD, Sherwood CC (June 2013). "Increased morphological asymmetry, evolvability and plasticity in human brain evolution". Proceedings. Biological Sciences. 280 (1761): 20130575. doi:10.1098/rspb.2013.0575. PMC   3652445 . PMID   23615289.
  27. Liu H, Zhang L, Xi Q, Zhao X, Wang F, Wang X, Men W, Lin Q (2018). "Changes in Brain Lateralization in Patients with Mild Cognitive Impairment and Alzheimer's Disease: A Resting-State Functional Magnetic Resonance Study from Alzheimer's Disease Neuroimaging Initiative". Frontiers in Neurology. 9: 3. doi:10.3389/fneur.2018.00003. PMC   5810419 . PMID   29472886.
  28. Yang C, Zhong S, Zhou X, Wei L, Wang L, Nie S (2017). "The Abnormality of Topological Asymmetry between Hemispheric Brain White Matter Networks in Alzheimer's Disease and Mild Cognitive Impairment". Frontiers in Aging Neuroscience. 9: 261. doi:10.3389/fnagi.2017.00261. PMC   5545578 . PMID   28824422.

Further reading