Editing Working memory (section)

=== Neural mechanisms of maintaining information ===
The first insights into the neuronal and neurotransmitter basis of working memory came from animal research. The work of Jacobsen<ref>{{Cite journal| vauthors = Jacobsen CF |title= Studies of cerebral function in primates |journal=Comparative Psychology Monographs |volume=13 |issue=3 |pages=1–68 |year=1938 |oclc=250695441 }}</ref> and Fulton in the 1930s first showed that lesions to the PFC impaired spatial working memory performance in monkeys. The later work of [[Joaquin Fuster]]<ref>{{cite journal | vauthors = Fuster JM | title = Unit activity in prefrontal cortex during delayed-response performance: neuronal correlates of transient memory | journal = Journal of Neurophysiology | volume = 36 | issue = 1 | pages = 61–78 | date = January 1973 | pmid = 4196203 | doi = 10.1152/jn.1973.36.1.61 | s2cid = 17534879 | doi-access = free }}</ref> recorded the electrical activity of neurons in the PFC of monkeys while they were doing a delayed matching task. In that task, the monkey sees how the experimenter places a bit of food under one of two identical-looking cups. A shutter is then lowered for a variable delay period, screening off the cups from the monkey's view. After the delay, the shutter opens and the monkey is allowed to retrieve the food from under the cups. Successful retrieval in the first attempt – something the animal can achieve after some training on the task – requires holding the location of the food in memory over the delay period. Fuster found neurons in the PFC that fired mostly during the delay period, suggesting that they were involved in representing the food location while it was invisible. Later research has shown similar delay-active neurons also in the posterior [[parietal cortex]], the [[thalamus]], the [[Caudate nucleus|caudate]], and the [[globus pallidus]].<ref>{{cite journal | vauthors = Ashby FG, Ell SW, Valentin VV, Casale MB | title = FROST: a distributed neurocomputational model of working memory maintenance | journal = Journal of Cognitive Neuroscience | volume = 17 | issue = 11 | pages = 1728–1743 | date = November 2005 | pmid = 16269109 | doi = 10.1162/089892905774589271 | s2cid = 12765957 }}</ref> The work of [[Patricia Goldman-Rakic|Goldman-Rakic]] and others showed that principal sulcal, dorsolateral PFC interconnects with all of these brain regions, and that neuronal microcircuits within PFC are able to maintain information in working memory through recurrent excitatory glutamate networks of pyramidal cells that continue to fire throughout the delay period.<ref>{{cite journal | vauthors = Goldman-Rakic PS | title = Cellular basis of working memory | journal = Neuron | volume = 14 | issue = 3 | pages = 477–485 | date = March 1995 | pmid = 7695894 | doi = 10.1016/0896-6273(95)90304-6 | s2cid = 2972281 | doi-access = free }}</ref> These circuits are tuned by lateral inhibition from GABAergic interneurons.<ref>{{cite journal | vauthors = Rao SG, Williams GV, Goldman-Rakic PS | title = Destruction and creation of spatial tuning by disinhibition: GABA(A) blockade of prefrontal cortical neurons engaged by working memory | journal = The Journal of Neuroscience | volume = 20 | issue = 1 | pages = 485–494 | date = January 2000 | pmid = 10627624 | pmc = 6774140 | doi = 10.1523/JNEUROSCI.20-01-00485.2000 }}</ref> The neuromodulatory arousal systems markedly alter PFC working memory function; for example, either too little or too much dopamine or norepinephrine impairs PFC network firing<ref>{{cite journal | vauthors = Arnsten AF, Paspalas CD, Gamo NJ, Yang Y, Wang M | title = Dynamic Network Connectivity: A new form of neuroplasticity | journal = Trends in Cognitive Sciences | volume = 14 | issue = 8 | pages = 365–375 | date = August 2010 | pmid = 20554470 | pmc = 2914830 | doi = 10.1016/j.tics.2010.05.003 }}</ref> and working memory performance.<ref>{{cite journal | vauthors = Robbins TW, Arnsten AF | title = The neuropsychopharmacology of fronto-executive function: monoaminergic modulation | journal = Annual Review of Neuroscience | volume = 32 | pages = 267–287 | year = 2009 | pmid = 19555290 | pmc = 2863127 | doi = 10.1146/annurev.neuro.051508.135535 }}</ref> A brain network analysis demonstrates that the FPC network requires less induced energy during working memory tasks than other functional brain networks. This finding underscores the efficient processing of the FPC network and highlights its crucial role in supporting working memory processes.<ref name="10.1038/s41598-024-83696-7">{{cite journal | vauthors = Saberi M, Rieck JR, Golafshan S, Grady CL, Misic B, Dunkley BT, Khatibi A | title = The brain selectively allocates energy to functional brain networks under cognitive control | journal = Scientific Reports | date = 2024 | volume = 14 | issue = 1 | pages = 32032 | doi = 10.1038/s41598-024-83696-7 | pmid = 39738735 | url = https://doi.org/10.1038/s41598-024-83696-7 | pmc = 11686059 | bibcode = 2024NatSR..1432032S }}</ref>

The research described above on persistent firing of certain neurons in the delay period of working memory tasks shows that the brain has a mechanism of keeping representations active without external input. Keeping representations active, however, is not enough if the task demands maintaining more than one chunk of information. In addition, the components and features of each chunk must be bound together to prevent them from being mixed up. For example, if a red triangle and a green square must be remembered at the same time, one must make sure that "red" is bound to "triangle" and "green" is bound to "square". One way of establishing such bindings is by having the neurons that represent features of the same chunk fire in synchrony, and those that represent features belonging to different chunks fire out of sync.<ref>{{cite journal | vauthors = Raffone A, Wolters G | title = A cortical mechanism for binding in visual working memory | journal = Journal of Cognitive Neuroscience | volume = 13 | issue = 6 | pages = 766–785 | date = August 2001 | pmid = 11564321 | doi = 10.1162/08989290152541430 | s2cid = 23241633 }}</ref> In the example, neurons representing redness would fire in synchrony with neurons representing the triangular shape, but out of sync with those representing the square shape. So far, there is no direct evidence that working memory uses this binding mechanism, and other mechanisms have been proposed as well.<ref>{{cite book |doi=10.1093/acprof:oso/9780198508571.003.0009 |chapter=Three forms of binding and their neural substrates: Alternatives to temporal synchrony |title=The Unity of ConsciousnessBinding, Integration, and Dissociation |date=2003 |last1=Oʼreilly |first1=Randall C. |last2=Busby |first2=Richard S. |last3=Soto |first3=Rodolfo |pages=168–190 |isbn=978-0-19-850857-1 }}</ref> It has been speculated that synchronous firing of neurons involved in working memory oscillate with frequencies in the [[theta rhythm|theta]] band (4 to 8&nbsp;Hz). Indeed, the power of theta frequency in the EEG increases with working memory load,<ref>{{Cite book|title=Handbook of binding and memory|publisher=Oxford University Press|year=2006|location=Oxford|pages=115–144|chapter=Binding principles in the theta frequency range| vauthors = Klimesch W | veditors = Zimmer HD, Mecklinger A, Lindenberger U }}</ref> and oscillations in the theta band measured over different parts of the skull become more coordinated when the person tries to remember the binding between two components of information.<ref>{{cite journal | vauthors = Wu X, Chen X, Li Z, Han S, Zhang D | title = Binding of verbal and spatial information in human working memory involves large-scale neural synchronization at theta frequency | journal = NeuroImage | volume = 35 | issue = 4 | pages = 1654–1662 | date = May 2007 | pmid = 17379539 | doi = 10.1016/j.neuroimage.2007.02.011 | s2cid = 7676564 }}</ref>