{{Short description|Abnormal EEG pattern}} thumb|Electroencephalogram (EEG) displaying burst suppression patterns. Onset of bursts are indicated by solid arrows; offset, by open arrows. In both A and B, the interval between each vertical dotted line is one second. '''Burst suppression''' is an electroencephalography (EEG) pattern that is characterized by periods of high-voltage electrical activity alternating with periods of no activity in the brain. The pattern is found in patients with inactivated brain states, such as from general anesthesia, coma, or hypothermia.<ref name=Ching>{{cite journal|last=Ching|first=S.|author2=Purdon, P. L. |author3=Vijayan, S. |author4=Kopell, N. J. |author5= Brown, E. N. |title=A neurophysiological-metabolic model for burst suppression|journal=Proceedings of the National Academy of Sciences|date=7 February 2012|volume=109|issue=8|pages=3095–3100|doi=10.1073/pnas.1121461109 |pmid=22323592 |pmc=3286963|bibcode=2012PNAS..109.3095C|doi-access=free}}</ref> This pattern can be physiological, as during early development, or pathological, as in diseases such as Ohtahara syndrome.<ref name=Hofmeijer>{{cite journal|last=Hofmeijer|first=Jeannette |author2=Tjepkema-Cloostermans, Marleen C. |author3=van Putten, Michel J.A.M. |title=Burst-suppression with Identical Bursts: a distinct EEG pattern with poor outcome in postanoxic coma|journal=Clinical Neurophysiology|date=October 2013|doi=10.1016/j.clinph.2013.10.017 |pmid=24286857 |volume=125 |issue=5 |pages=947–954|s2cid=5101630 |url=https://ris.utwente.nl/ws/files/6825668/Hofmeijer%202013%20identical%20bursts.pdf }}</ref>
== History == The burst suppression pattern was first observed by Derbyshire et al. while studying effects of anesthetics on feline cerebral cortices in 1936, where the researchers noticed mixed slow and fast electrical activity with decreasing amplitude as anesthesia deepened.<ref name=Niedermeyer>{{cite journal|last=Niedermeyer|first=E|title=The burst-suppression electroencephalogram.|journal=American Journal of Electroneurodiagnostic Technology|date=December 2009|volume=49|issue=4|pages=333–41|pmid=20073416|doi=10.1080/1086508X.2009.11079736|s2cid=8752000}}</ref> In 1948, Swank and Watson coined the term "burst-suppression pattern" to describe the alternation of spikes and flatlines in electrical activity in deep anesthesia.<ref name=Amzica>{{cite journal|last=Amzica|first=Florin|title=Basic physiology of burst-suppression|journal=Epilepsia|date=1 December 2009|volume=50|pages=38–39|doi=10.1111/j.1528-1167.2009.02345.x|pmid=19941521|doi-access=free}}</ref> It wasn't until after the early 1960s that the burst suppression pattern began being used in medical settings; it had been primarily observed in animal studies and psychosurgeries.<ref name=Liley>{{cite journal|last=Liley|first=David T. J.|author2=Walsh, Matthew|title=The Mesoscopic Modeling of Burst Suppression during Anesthesia|journal=Frontiers in Computational Neuroscience|year=2013|volume=7|page=46|doi=10.3389/fncom.2013.00046|pmid=23641211|pmc=3639728|doi-access=free}}</ref>
== Mechanisms == A paper published in 2023 showed that burst suppression and epilepsy may share the same ephaptic coupling mechanism.<ref name="ephaptic burst">{{cite journal |last1=Doubovikov |first1=Evan D. |last2=Serdyukova |first2=Natalya A. |last3=Greenberg |first3=Steven B. |last4=Gascoigne |first4=David A. |last5=Minhaj |first5=Mohammed M. |last6=Aksenov |first6=Daniil P. |title=Electric Field Effects on Brain Activity: Implications for Epilepsy and Burst Suppression |journal=Cells |date=September 2023 |volume=12 |issue=18 |page=2229 |doi=10.3390/cells12182229 |pmid=37759452 |pmc=10527339 |language=en |issn=2073-4409 |doi-access=free }}</ref> When inhibitory control is sufficiently low, as in the case of certain general anesthetics such as sevoflurane (due to a decrease in the firing of interneurons<ref name="Inhibition Anesthesia">{{cite journal |last1=Aksenov |first1=Daniil P. |last2=Miller |first2=Michael J. |last3=Dixon |first3=Conor J. |last4=Wyrwicz |first4=Alice M. |title=The effect of sevoflurane and isoflurane anesthesia on single unit and local field potentials |journal=Experimental Brain Research |date=June 2019 |volume=237 |issue=6 |pages=1521–1529 |doi=10.1007/s00221-019-05528-9 |pmid=30919011 |pmc=6526065 |issn=1432-1106}}</ref>), electric fields are able to recruit neighboring cells to fire synchronously, in a burst suppression pattern. This same mechanism also underlies epileptic bursts, but the magnitude of bursts is comparatively weaker in burst suppression, as the neuronal network still retains partial inhibitory control under the effects of anesthesia.
== Characteristics == The pseudo-rhythmic pattern of burst suppression is dictated by extracellular calcium depletion and the ability of neurons to restore the concentration.<ref name=Amzica /> Bursts are accompanied by depletion of extracellular cortical calcium ions to levels that inhibit synaptic transmission, which leads to suppression periods.<ref name=Amzica /> During suppression, neuronal pumps restore the calcium ion concentrations to normal levels, thus causing the cortex to be subject to the process again.<ref name=Amzica /> As the brain becomes more inactive, burst periods become shorter and suppression periods become longer.<ref name=Tetrault>{{cite journal|last=Tétrault|first=Samuel|author2=Chever, Oana |author3=Sik, Attila |author4= Amzica, Florin |title=Opening of the blood–brain barrier during isoflurane anaesthesia|journal=European Journal of Neuroscience|date=1 October 2008|volume=28|issue=7|pages=1330–1341|doi=10.1111/j.1460-9568.2008.06443.x|pmid=18973560|s2cid=28555021 |doi-access=}}</ref> The shortening of bursts and lengthening of suppression is caused by the central nervous system's inability to properly regulate calcium levels due to increased blood–brain permeability.<ref name=Tetrault />
At the cellular level, hyperpolarization of the membrane potential of cortical neurons reliably precedes any overt electroencephalographic activity of burst suppression.<ref name=Steriade /> This hyperpolarization, which has been attributed to an increase in neuronal membrane potassium conductance,<ref name=Steriade /> has been hypothesized to play a major role in the induction of burst suppression, supported by the induction of burst suppression through the application of a direct acting GABA<sub>A</sub> agonist, muscimol.<ref name=Liley /> In contrast, inhibition is diminished when burst suppression is induced through the use of isoflurane.<ref name=Ferron>{{cite journal|last=Ferron|first=JF|author2=Kroeger, D |author3=Chever, O |author4= Amzica, F |title=Cortical inhibition during burst suppression induced with isoflurane anesthesia.|journal=The Journal of Neuroscience |date=Aug 5, 2009|volume=29|issue=31|pages=9850–60|pmid=19657037 |pmc=6666595|doi=10.1523/jneurosci.5176-08.2009}}</ref> Another theory is that alterations in brain metabolism regulate activity dependent slow modulation of ATP-gated potassium channel conductance which induces burst suppression.<ref name=Ching /> However, modulating inhibitory activity alone may not be sufficient for burst suppression, and modulation in excitatory synaptic efficiency, stemming from the depletion and subsequent recovery of interstitial calcium levels, could contribute to the induction of burst suppression.<ref name=Liley />
Burst episodes are associated with excitatory activity in cortical neurons.<ref name=Kroeger>{{cite journal|last=Kroeger|first=Daniel|author2=Florea, Bogdan |author3=Amzica, Florin |author4= Dickson, Clayton T. |title=Human Brain Activity Patterns beyond the Isoelectric Line of Extreme Deep Coma|journal=PLOS ONE|date=18 September 2013|volume=8|issue=9|article-number=e75257|doi=10.1371/journal.pone.0075257 |pmid=24058669 |pmc=3776755|bibcode=2013PLoSO...875257K|doi-access=free}}</ref> Suppression is caused by the absence of synaptic activity of cortical neurons; however, some thalamocortical neurons exhibit oscillations in the delta frequency range during these periods.<ref name=Steriade>{{cite journal|last=Steriade|first=M|author2=Amzica, F |author3=Contreras, D |title=Cortical and thalamic cellular correlates of electroencephalographic burst-suppression.|journal=Electroencephalography and Clinical Neurophysiology|date=January 1994|volume=90|issue=1|pages=1–16|pmid=7509269|doi=10.1016/0013-4694(94)90108-2}}</ref> The burst suppression pattern varies with the brain anesthetic concentration when pharmacologically inducing coma.<ref name=Westover /> Level of suppression is adjustable by decreasing or increasing anesthetic infusion rate, thus adjusting the level of inactivation.<ref name=Shanechi>{{cite journal|last=Shanechi|first=Maryam M.|author2=Chemali, Jessica J. |author3=Liberman, Max |author4=Solt, Ken |author5=Brown, Emery N. |author6= Sporns, Olaf |title=A Brain–Machine Interface for Control of Medically-Induced Coma|journal=PLOS Computational Biology|date=31 October 2013|volume=9|issue=10|article-number=e1003284|doi=10.1371/journal.pcbi.1003284 |pmid=24204231 |pmc=3814408|bibcode=2013PLSCB...9E3284S |doi-access=free }}</ref>
While burst suppression has typically been viewed as a homogeneous brain state, recent studies have shown that bursts and suppressions can occur in specific regions while other regions are unaffected.<ref name=Lewis>{{cite journal|last=Lewis|first=L. D.|author2=Ching, S. |author3=Weiner, V. S. |author4=Peterfreund, R. A. |author5=Eskandar, E. N. |author6=Cash, S. S. |author7=Brown, E. N. |author8= Purdon, P. L. |title=Local cortical dynamics of burst suppression in the anaesthetized brain|journal=Brain|date=25 July 2013|volume=136|issue=9|pages=2727–2737|doi=10.1093/brain/awt174 |pmid=23887187 |pmc=3754454}}</ref> The fact that the burst suppression pattern persists after a patient undergoes cortical deafferentation indicates that burst suppression represents an intrinsic dynamic mode of cortex.<ref name=Liley /> Even when a burst appears to be homogeneous across the brain, the timing of the bursts in different regions may differ.<ref name=Lewis />
Burst suppression patterns can be classified through comparisons of burst duration and inter-burst intervals, maximum peak to peak voltage, and the ratio of power in high versus low frequencies. (Akrawi et al., 1996)<ref>{{cite journal|last=Akrawi|first=WP|author2=Drummond, JC |author3=Kalkman, CJ |author4= Patel, PM |title=A comparison of the electrophysiologic characteristics of EEG burst-suppression as produced by isoflurane, thiopental, etomidate, and propofol.|journal=Journal of Neurosurgical Anesthesiology|date=January 1996|volume=8|issue=1|pages=40–6|pmid=8719192 |doi=10.1097/00008506-199601000-00010}}</ref> Burst suppression with identical bursts suggests a deterministic process of burst generation, whereas other burst suppression patterns depend on stochastic processes.<ref name=Hofmeijer /> Burst suppression with identical bursts is a distinct pathological EEG pattern that is typical in diffuse cerebral ischemia and is associated with poor outcomes in comatose patients after cardiac arrest.<ref name=Hofmeijer />
== Electrophysiology == Bursts are identifiable on EEG readings by their high amplitude (75-250μV), typically short period of 1–10 seconds, and have frequency ranges of 0–4 Hz (δ) and 4–7 Hz (θ).<ref name=Bhattacharyya>{{cite journal|last=Bhattacharyya|first=Sourya|author2=Biswas, Arunava |author3=Mukherjee, Jayanta |author4=Majumdar, Arun Kumar |author5=Majumdar, Bandana |author6=Mukherjee, Suchandra |author7= Singh, Arun Kumar |title=Detection of artifacts from high energy bursts in neonatal EEG|journal=Computers in Biology and Medicine|date=1 November 2013|volume=43|issue=11|pages=1804–1814|doi=10.1016/j.compbiomed.2013.07.031|pmid=24209926}}</ref> Suppression episodes are identifiable by their low amplitude (< 5μV) and typically long period (> 10s).<ref name=Bhattacharyya />
EEG recordings of burst-suppression pattern differ between adults and neonates because of diverse pattern fluctuations found in the EEG of neonates.<ref name=Bhattacharyya /> These fluctuations, along with sudden changes in synchronous neuron firing, are caused by development of the newborn's brain.<ref name=Bhattacharyya /> Burst suppression patterns also occur spontaneously during neonatal development, rather than as a characteristic of inactivated brains as in adults.<ref name=Westover>{{cite journal|last=Brandon Westover|first=M.|author2=Shafi, Mouhsin M. |author3=Ching, ShiNung |author4=Chemali, Jessica J. |author5=Purdon, Patrick L. |author6=Cash, Sydney S. |author7= Brown, Emery N. |title=Real-time segmentation of burst suppression patterns in critical care EEG monitoring|journal=Journal of Neuroscience Methods|date=1 September 2013|volume=219|issue=1|pages=131–141|doi=10.1016/j.jneumeth.2013.07.003|pmid=23891828|pmc=3939433|url=http://dspace.mit.edu/bitstream/1721.1/102246/1/Brown_Real-time%20segmentation.pdf|hdl=1721.1/102246}}</ref>
=== Quantification === In order to quantify the burst suppression pattern, the EEG signal must be subject to segmentation.<ref name=Chemali>{{cite journal|last=Chemali|first=Jessica|author2=Ching, ShiNung |author3=Purdon, Patrick L |author4=Solt, Ken |author5= Brown, Emery N |title=Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression|journal=Journal of Neural Engineering|date=1 October 2013|volume=10|issue=5|article-number=056017|doi=10.1088/1741-2560/10/5/056017 |pmid=24018288 |pmc=3793904|bibcode=2013JNEng..10e6017C}}</ref> The first segmentation used a fixed voltage-threshold, and various methods for segmentation or burst detection have developed in time domain,<ref name=Westover /> frequency (Fourier) domain, and both.<ref name=Lee>{{cite journal|last=Lee|first=Jaeyun|author2= Song, Woo-Jin|author3 = Lee, Hyang-Woon|author4 = Shin, Hyun-Chool|title= Novel Burst Suppression Segmentation in the Joint Time-Frequency Domain for EEG in Treatment of Status Epilepticus|journal=Computational and Mathematical Methods in Medicine|date=2016|doi=10.1155/2016/2684731|pmid=27872655|pmc=5107253|volume=2016|article-number=2684731|doi-access=free}}</ref> These processes separates burst and suppression episodes based on EEG features such as entropies, non-linear-energy-operator, voltage variance, or adaptation of constant false alarm rate (CFAR) algorithm,<ref name=Lee2>{{cite journal|last=Lee|first=Jaeyun|author2= Shin, Hyun-Chool|title= Burst Suppression Segmentation of EEG Using Adaptive Binarization in Time and Frequency Domains|journal=IEEE Access|date=2019|doi=10.1109/ACCESS.2019.2910869|volume=7|pages=54550–54561|bibcode=2019IEEEA...754550L |doi-access=free}}</ref> etc. When the features represent distinguishable patterns of burst and suppression, a fixed threshold using ROC-curve or machine learning methods<ref name=Lee /> are used for segmentation.
Quantifying the burst suppression pattern allows for calculation of the burst suppression ratio (BSR) by assigning binary values of 0 to bursts and 1 to suppression episodes.<ref name=Chemali /> Thus, a burst suppression ratio of 1 is associated with a state of the brain that shows no electrical activity, while a ratio of 0 indicates that the brain is active. The burst suppression ratio measures the amount of time within an interval spent in the suppressed state.<ref name=Westover /> This ratio increases as the brain becomes increasingly inactive until the brain's EEG signal flatlines, represented by a burst suppression ratio equal to 1.<ref name=Vijn>{{cite journal|last=Vijn|first=P. C.|author2=Sneyd, J. R.|title=I.v. anaesthesia and EEG burst suppression in rats: bolus injections and closed-loop infusions.|journal=British Journal of Anaesthesia|date=1 September 1998|volume=81|issue=3|pages=415–421|doi=10.1093/bja/81.3.415|pmid=9861133|doi-access=free}}</ref> Because of the direct relationship between burst suppression ratio and brain inactivity, the ratio is an indicator of suppression intensity.<ref name=Westover />
Using the same binary assignments to the burst suppression pattern, another measure of the depth of burst suppression, the burst suppression probability (BSP), can be determined.<ref name=Westover /> Mathematically, the instantaneous probability of being suppressed, is :<math> p_i = \frac{e^{x_i}}{1+e^{x_i}}, </math> BSR = (Total time of suppression/epoch length) × 100%.<ref name="Vijn"/> where ''x<sub>i</sub>'' is the brain's suppression state at time ''i''Δ, with Δ representing intervals for analysis, and ranges across all real numbers.<ref name=Chemali />
== Clinical benefits == thumb|Patients with a high burst suppression ratio (yellow circles) show significantly better recovery from coma (traumatic etiologies) as measured by the Glasgow Outcome Scale extended (GOSe) 6 months post-injury (histogram on vertical axis). Figure from Frohlich et al. 2021 Frontiers in Neurology. Because the burst suppression pattern is characteristic of inactivated brains, the pattern can be used as a marker for the level of coma a patient is in, with persistence of the pattern commonly associated with poor prognosis.<ref name=Chemali /> Note, however, that there is evidence linking sedation-induced burst suppression with positive outcomes in patients recovering from coma following traumatic brain injury, suggesting a neuroprotective effect.<ref>{{Cite journal |last1=Frohlich |first1=Joel |last2=Johnson |first2=Micah A. |last3=McArthur |first3=David L. |last4=Lutkenhoff |first4=Evan S. |last5=Dell'Italia |first5=John |last6=Real |first6=Courtney |last7=Shrestha |first7=Vikesh |last8=Spivak |first8=Norman M. |last9=Ruiz Tejeda |first9=Jesús E. |last10=Vespa |first10=Paul M. |last11=Monti |first11=Martin M. |date=2021 |title=Sedation-Induced Burst Suppression Predicts Positive Outcome Following Traumatic Brain Injury |journal=Frontiers in Neurology |volume=12 |article-number=750667 |doi=10.3389/fneur.2021.750667 |pmid=35002918 |pmc=8727767 |issn=1664-2295|doi-access=free }}</ref> When inducing coma to protect the brain post trauma, the pattern assists in maintaining the necessary level of coma so that no further damage occurs to the brain.<ref name=Shanechi /> The pattern is also used to test the ability of anesthetic arousal agents to induce emergence from comas.<ref name=Chemali /> The burst suppression pattern can also be used to track ascent into and descent out of hypothermia through observing changes in the pattern.<ref name=Chemali />
Monitoring the burst suppression ratio aids medical personnel in adjusting suppression intensity for therapeutic purposes; however, medical personnel currently rely on visually monitoring the EEG and arbitrarily assessing the depth of burst suppression.<ref name=Westover /> Not only is the evaluation of the EEG signal for burst suppression done manually, but also the infusion rate of anesthetic to adjust suppression intensity.<ref name=Shanechi /> The introduction of machines makes maintaining proper levels of inactivity more precise through the use of algorithms. This is done through the use of measures such as burst suppression probability<ref name=Westover /> for real-time tracking of burst suppression or brain–machine interfaces to automate maintaining proper levels of inactivity.<ref name=Shanechi />
== References == {{reflist}}
{{Seizures and epilepsy}}
Category:Electroencephalography Category:Neurological disorders