Editing Human brain (section)

==Research==
The brain is not fully understood, and research is ongoing.<ref name=HCP2009 /> [[Neuroscientist]]s, along with researchers from allied disciplines, study how the human brain works. The boundaries between the specialties of [[neuroscience]], [[neurology]] and other disciplines such as [[psychiatry]] have faded as they are all influenced by [[basic research]] in neuroscience.

Neuroscience research has expanded considerably. The "[[Decade of the Brain]]", an initiative of the United States Government in the 1990s, is considered to have marked much of this increase in research,<ref>{{Cite journal |first1=E.G. |last1=Jones |author-link1=Edward G. Jones |first2=L.M. |last2=Mendell |title=Assessing the Decade of the Brain |journal=Science |doi=10.1126/science.284.5415.739 |date=April 30, 1999 |volume=284 |issue=5415 |page=739 |pmid=10336393 |bibcode = 1999Sci...284..739J|s2cid=13261978 }}</ref> and was followed in 2013 by the [[BRAIN Initiative]].<ref>{{cite web |title=A $4.5 Billion Price Tag for the BRAIN Initiative? |url=https://www.science.org/content/article/45-billion-price-tag-brain-initiative |website=Science {{!}} AAAS |date=June 5, 2014 |url-status=live |archive-url=https://web.archive.org/web/20170618154752/http://www.sciencemag.org/news/2014/06/45-billion-price-tag-brain-initiative |archive-date=June 18, 2017  }}</ref> The [[Human Connectome Project]] was a five-year study launched in 2009 to analyse the anatomical and functional connections of parts of the brain, and has provided much data.<ref name=HCP2009>{{cite journal |last1=Van Essen |first1=D.C. |display-authors=etal |title=The Human Connectome Project: A data acquisition perspective |journal=NeuroImage |date=October 2012 |volume=62 |issue=4 |pages=2222–2231 |doi=10.1016/j.neuroimage.2012.02.018|pmid=22366334 |pmc=3606888 }}</ref>
 
An emerging phase in research may be that of [[simulation|simulating]] brain activity.<ref>{{Cite journal|last1=Fan|first1=Xue|last2=Markram|first2=Henry|date=2019-05-07|title=A Brief History of Simulation Neuroscience|journal=Frontiers in Neuroinformatics|volume=13|page=32|doi=10.3389/fninf.2019.00032|pmid=31133838|pmc=6513977|issn=1662-5196|doi-access=free}}</ref>

===Methods===
Information about the structure and function of the human brain comes from a variety of experimental methods, including animals and humans. Information about brain trauma and stroke has provided information about the function of parts of the brain and the effects of [[brain damage]]. [[Neuroimaging]] is used to visualise the brain and record brain activity. [[Electrophysiology]] is used to measure, record and monitor the electrical activity of the cortex. Measurements may be of [[local field potential]]s of cortical areas, or of the activity of a single neuron. An [[electroencephalography|electroencephalogram]] can record the electrical activity of the cortex using [[electrode]]s placed non-invasively on the [[scalp]].<ref>{{cite journal | last1=Towle |first1=V.L. |display-authors=etal |title=The spatial location of EEG electrodes: locating the best-fitting sphere relative to cortical anatomy |journal=Electroencephalography and Clinical Neurophysiology |date=January 1993 |volume=86 |issue=1 |pages=1–6 |pmid=7678386 |doi=10.1016/0013-4694(93)90061-y}}</ref>{{sfn|Purves|2012|pp=632–633}}

Invasive measures include [[electrocorticography]], which uses electrodes placed directly on the exposed surface of the brain. This method is used in [[cortical stimulation mapping]], used in the study of the relationship between cortical areas and their systemic function.<ref>{{cite journal |last1=Silverstein |first1=J. |title=Mapping the Motor and Sensory Cortices: A Historical Look and a Current Case Study in Sensorimotor Localization and Direct Cortical Motor Stimulation |journal=The Neurodiagnostic Journal |pmid=22558647 |url=http://www.readperiodicals.com/201203/2662763741.html |year=2012 |volume=52 |issue=1 |pages=54–68 |url-status=live |archive-url=https://web.archive.org/web/20121117021132/http://www.readperiodicals.com/201203/2662763741.html |archive-date=November 17, 2012  }}</ref> By using much smaller [[microelectrode]]s, [[single-unit recording]]s can be made from a single neuron that give a high [[Angular resolution|spatial resolution]] and high [[temporal resolution]]. This has enabled the linking of brain activity to behaviour, and the creation of neuronal maps.<ref>{{cite journal |last1=Boraud |first1=T. |last2=Bezard |first2=E. | year=2002 | title=From single extracellular unit recording in experimental and human Parkinsonism to the development of a functional concept of the role played by the basal ganglia in motor control | journal=Progress in Neurobiology | volume=66 | issue=4 | pages=265–283 | doi=10.1016/s0301-0082(01)00033-8 |pmid=11960681 |s2cid=23389986 |display-authors=etal}}</ref>

The development of [[cerebral organoid]]s has opened ways for studying the growth of the brain, and of the cortex, and for understanding disease development, offering further implications for therapeutic applications.<ref name="Lancaster">{{cite journal |last1=Lancaster |first1=MA |last2=Renner |first2=M |last3=Martin |first3=CA |last4=Wenzel |first4=D |last5=Bicknell |first5=LS |last6=Hurles |first6=ME |last7=Homfray |first7=T |last8=Penninger |first8=JM |last9=Jackson |first9=AP |last10=Knoblich |first10=JA |title=Cerebral organoids model human brain development and microcephaly. |journal=Nature |date=September 19, 2013 |volume=501 |issue=7467 |pages=373–9 |doi=10.1038/nature12517 |pmid=23995685|pmc=3817409 |bibcode=2013Natur.501..373L }}</ref><ref name="Lee">{{cite journal |last1=Lee |first1=CT |last2=Bendriem |first2=RM |last3=Wu |first3=WW |last4=Shen |first4=RF |title=3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders. |journal=Journal of Biomedical Science |date=August 20, 2017 |volume=24 |issue=1 |page=59 |doi=10.1186/s12929-017-0362-8 |pmid=28822354|pmc=5563385 |doi-access=free }}</ref>

===Imaging===
{{Further |Magnetic resonance imaging of the brain}}
[[File:Human-brain-mri-gif-brain-mri-gif.gif|thumb|FMRI of healthy human brain]]
[[Functional neuroimaging]] techniques show changes in brain activity that relate to the function of specific brain areas. One technique is [[functional magnetic resonance imaging]] (fMRI) which has the advantages over earlier methods of [[SPECT]] and [[positron emission tomography|PET]] of not needing the use of [[Nuclear medicine|radioactive materials]] and of offering a higher resolution.<ref>{{cite web |title=Magnetic Resonance, a critical peer-reviewed introduction; functional MRI |publisher=European Magnetic Resonance Forum |access-date=June 30, 2017 |url=http://www.magnetic-resonance.org/ch/11-03.html |url-status=live |archive-url=https://web.archive.org/web/20170602035337/http://www.magnetic-resonance.org/ch/11-03.html |archive-date=June 2, 2017  }}</ref> Another technique is [[functional near-infrared spectroscopy]]. These methods rely on the [[haemodynamic response]] that shows changes in brain activity in relation to changes in [[cerebral circulation|blood flow]], useful in [[brain mapping|mapping functions to brain areas]].<ref>{{cite journal |last1=Buxton |first1=R. |last2=Uludag |first2=K. |last3=Liu |first3=T. | year= 2004| title=Modeling the haemodynamic response to brain activation | journal=NeuroImage | volume= 23 | pages=S220–S233 | doi=10.1016/j.neuroimage.2004.07.013|pmid=15501093 |citeseerx=10.1.1.329.29 |s2cid=8736954 }}</ref> [[Resting state fMRI]]
looks at the interaction of brain regions whilst the brain is not performing a specific task.<ref>{{cite journal |last1=Biswal |first1=B.B. |title=Resting state fMRI: a personal history |journal=NeuroImage|date=August 15, 2012|volume=62|issue=2|pages=938–44|pmid=22326802|doi=10.1016/j.neuroimage.2012.01.090|s2cid=93823 }}</ref> This is also used to show the [[default mode network]].

Any electrical current generates a magnetic field; [[neural oscillation]]s induce weak magnetic fields, and in functional [[magnetoencephalography]] the current produced can show localised brain function in high resolution.{{sfn|Purves|2012|p=20}} [[Tractography]] uses [[MRI]] and [[image analysis]] to create [[3D modeling|3D images]] of the [[nerve tract]]s of the brain. [[Connectogram]]s give a graphical representation of the [[connectome|neural connections]] of the brain.<ref name="Kane">{{cite book |last1=Kane |first1=R.L. |last2=Parsons |first2=T.D. |title=The Role of Technology in Clinical Neuropsychology |isbn=978-0-19-023473-7 |publisher=[[Oxford University Press]] |year=2017 |page=399 |url=https://books.google.com/books?id=iuAwDgAAQBAJ |quote=Irimia, Chambers, Torgerson, and Van Horn (2012) provide a first-step graphic on how best to display connectivity findings, as is presented in Figure 13.15. This is referred to as a connectogram.}}</ref>

Differences in [[brain morphometry|brain structure can be measured]] in some disorders, notably [[schizophrenia]] and [[dementia]]. Different biological approaches using imaging have given more insight for example into the disorders of [[biology of depression|depression]] and [[biology of obsessive-compulsive disorder|obsessive-compulsive disorder]]. A key source of information about the function of brain regions is the effects of damage to them.<ref>{{cite book | url=https://books.google.com/books?id=kiCtU8wBTfwC | title=Neuropsychology | last=Andrews | first=D.G. | publisher=Psychology Press | year=2001 | isbn=978-1-84169-103-9}}</ref>

Advances in [[neuroimaging]] have enabled objective insights into mental disorders, leading to faster diagnosis, more accurate prognosis, and better monitoring.<ref>{{cite web |author=Lepage, M. |date=2010 |title=Research at the Brain Imaging Centre |work=Douglas Mental Health University Institute |url=http://www.douglas.qc.ca/page/imagerie-cerebrale?locale=en |url-status=dead |archive-url=https://web.archive.org/web/20120305042011/http://www.douglas.qc.ca/page/imagerie-cerebrale?locale=en |archive-date=March 5, 2012 }}</ref>

===Gene and protein expression===
{{Main|Bioinformatics}}
{{See also |List of neuroscience databases}}
[[Bioinformatics]] is a field of study that includes the creation and advancement of databases, and computational and statistical techniques, that can be used in studies of the human brain, particularly in the areas of [[Bioinformatics#Gene and protein expression|gene and protein expression]]. Bioinformatics and studies in [[genomics]], and [[functional genomics]], generated the need for [[DNA annotation]], a [[Transcriptomics technologies|transcriptome technology]], identifying [[gene]]s, their locations and functions.<ref name="Steward">{{cite journal | title=Genome annotation for clinical genomic diagnostics: strengths and weaknesses | author=Steward, C.A. |display-authors=etal | pmid=28558813 | doi=10.1186/s13073-017-0441-1 | volume=9 | issue=1 | pmc=5448149 | year=2017 | journal=Genome Med | page=49 | doi-access=free }}</ref><ref>{{cite journal | title=GENCODE: the reference human genome annotation for The ENCODE Project. | author=Harrow, J. |display-authors=etal | pmid=22955987 | doi=10.1101/gr.135350.111 | pmc=3431492 | volume=22 | issue=9 | date=September 2012 | journal=Genome Res. | pages=1760–74}}</ref><ref name="Gibson and Muse">{{cite book|title=A primer of genome science|vauthors=Gibson G, Muse SV|date=April 20, 2009 |publisher=Sinauer Associates|isbn=9780878932368|edition=3rd|location=Sunderland, MA}}</ref> [[GeneCards]] is a major database.

{{as of|2017}}, just under 20,000 [[Human genome#Coding sequences (protein-coding genes)|protein-coding genes]] are seen to be expressed in the human,<ref name="Steward"/> and some 400 of these genes are brain-specific.<ref>{{Cite web|url=https://www.proteinatlas.org/humanproteome/brain|title=The human proteome in brain – The Human Protein Atlas|website=www.proteinatlas.org|access-date=September 29, 2017|url-status=live|archive-url=https://web.archive.org/web/20170929231550/https://www.proteinatlas.org/humanproteome/brain|archive-date=September 29, 2017}}</ref><ref>{{Cite journal|last1=Uhlén|first1=Mathias|last2=Fagerberg|first2=Linn|last3=Hallström|first3=Björn M.|last4=Lindskog|first4=Cecilia|last5=Oksvold|first5=Per|last6=Mardinoglu|first6=Adil|last7=Sivertsson|first7=Åsa|last8=Kampf|first8=Caroline|last9=Sjöstedt|first9=Evelina|date=January 23, 2015|title=Tissue-based map of the human proteome|journal=Science|volume=347|issue=6220|page=1260419|doi=10.1126/science.1260419|issn=0036-8075|pmid=25613900|s2cid=802377}}</ref> The data that has been provided on [[gene expression]] in the brain has fuelled further research into a number of disorders. The long term use of alcohol for example, has shown altered gene expression in the brain, and cell-type specific changes that may relate to [[alcoholism|alcohol use disorder]].<ref>{{cite journal|last=Warden|first=A|year=2017|title=Gene expression profiling in the human alcoholic brain.|journal=Neuropharmacology|volume=122|pages=161–174|pmid=28254370|doi=10.1016/j.neuropharm.2017.02.017|pmc=5479716}}</ref> These changes have been noted in the [[Synapse|synaptic]] [[transcriptome]] in the prefrontal cortex, and are seen as a factor causing the drive to alcohol dependence, and also to other [[substance abuse]]s.<ref>{{cite journal | title=Applying the new genomics to alcohol dependence. | author=Farris, S.P. |display-authors=etal | journal=Alcohol | year=2015 | pmid=25896098 | doi=10.1016/j.alcohol.2015.03.001 | volume=49 | issue=8 | pmc=4586299 | pages=825–36}}</ref>

Other related studies have also shown evidence of synaptic alterations and their loss, in the [[ageing brain]]. Changes in gene expression alter the levels of proteins in various neural pathways and this has been shown to be evident in synaptic contact dysfunction or loss. This dysfunction has been seen to affect many structures of the brain and has a marked effect on inhibitory neurons resulting in a decreased level of neurotransmission, and subsequent cognitive decline and disease.<ref name="Rozycka">{{cite journal|last1=Rozycka|first1=A|last2=Liguz-Lecznar|first2=M|title=The space where aging acts: focus on the GABAergic synapse.|journal=Aging Cell|date=August 2017|volume=16|issue=4|pages=634–643|doi=10.1111/acel.12605|pmid=28497576|pmc=5506442}}</ref><ref>{{cite journal|last1=Flores|first1=CE|last2=Méndez|first2=P|title=Shaping inhibition: activity dependent structural plasticity of GABAergic synapses.|journal=Frontiers in Cellular Neuroscience|date=2014|volume=8|page=327|doi=10.3389/fncel.2014.00327|pmid=25386117|pmc=4209871|doi-access=free}}</ref>