Editing Retrograde amnesia (section)

== Causes ==
RA commonly results from damage to regions of the brain that are associated with episodic and declarative memory, including [[autobiographical]] information. In extreme cases, individuals may completely forget who they are. Generally, this is a more severe type of amnesia known as [[global amnesia|global]], or generalized amnesia.<ref name="Vaidya_1998">{{cite journal | vauthors = Vaidya CJ, Gabrieli JD, Verfaellie M, Fleischman D, Askari N | title = Font-specific priming following global amnesia and occipital lobe damage | journal = Neuropsychology | volume = 12 | issue = 2 | pages = 183–92 | date = April 1998 | pmid = 9556765 | doi = 10.1037/0894-4105.12.2.183 }}</ref> However, memory loss can also be selective or categorical, manifested by a person's inability to remember events related to a specific incident or topic. Patients also differ in durations of RA (how long they can't recall information) and durations of what is forgotten (past time frame for which information is unavailable).

During consolidation, the hippocampus acts as an intermediate tool that quickly stores new information until it is transferred to the [[neocortex]] for the long-term. The temporal lobe, which holds the hippocampus, [[entorhinal]], [[perirhinal]] and parahippocampal cortices, has a reciprocal connection with the neocortex.<ref name="Squire_1995" /> The temporal lobe is temporarily needed when consolidating new information; as the learning becomes stronger, the neocortex becomes more independent of the temporal lobe.<ref name="Squire_1995" />

Studies on specific cases demonstrate how particular impaired areas of the hippocampus are associated with the severity of RA. Damage can be limited to the CA1 field of the hippocampus, causing very limited RA for about one to two years.<ref name="Squire_1995" /> More extensive damage limited to the hippocampus causes temporally graded amnesia for 15 to 25 years.<ref name="Squire_1995" /> Another study suggests that large medial temporal lobe lesions, that extend laterally to include other regions, produce more extensive RA, covering 40 to 50 years.<ref name="Squire_1995" /> These findings suggest that density of RA becomes more severe and long-term as the damage extends beyond the hippocampus to surrounding structures.

=== Traumatic brain injury (TBI) ===
Traumatic brain injury (TBI) occurs from an external force that causes structural damage to the brain, such as a sharp blow to the head, a [[diffuse axonal injury]],<ref name="Wolf_2001">{{cite journal | vauthors = Wolf JA, Stys PK, Lusardi T, Meaney D, Smith DH | title = Traumatic axonal injury induces calcium influx modulated by tetrodotoxin-sensitive sodium channels | journal = The Journal of Neuroscience| volume = 21 | issue = 6 | pages = 1923–30 | date = March 2001 | pmid = 11245677 | pmc = 6762603 | doi = 10.1523/JNEUROSCI.21-06-01923.2001 }}</ref> or childhood brain damage (e.g., [[shaken baby syndrome]]).<ref name="Wolf_2001"/> In cases of sudden rapid acceleration, the brain continues moving around in the skull, harming brain tissue as it hits internal protrusions.<ref name="Hardman_2002">{{cite journal | vauthors = Hardman JM, Manoukian A | title = Pathology of head trauma | journal = Neuroimaging Clinics of North America | volume = 12 | issue = 2 | pages = 175–87, vii | date = May 2002 | pmid = 12391630 | doi = 10.1016/s1052-5149(02)00009-6 }}</ref>

TBI varies according to impact of external forces, location of structural damage, and severity of damage ranging from mild to severe.<ref name="Winocur_2001">{{cite journal | vauthors = Winocur G, McDonald RM, Moscovitch M | title = Anterograde and retrograde amnesia in rats with large hippocampal lesions | journal = Hippocampus | volume = 11 | issue = 1 | pages = 18–26 | date = 2001 | pmid = 11261769 | doi = 10.1002/1098-1063(2001)11:1<18::AID-HIPO1016>3.0.CO;2-5 | s2cid = 4079756 }}</ref><ref name="Wolf_2001"/><ref name="Hardman_2002"/> Retrograde amnesia can be one of the many consequences of brain injury but it is not always the outcome of TBI. An example of a subgroup of people who are often exposed to TBI are individuals who are involved in high-contact sports. Research on football players takes a closer look at some of the implications to their high-contact activities. Enduring consistent head injuries can have an effect on the neural consolidation of memory.<ref name="YarnellLynch">{{cite journal | vauthors = Yarnell PR, Lynch S | title = Retrograde memory immediately after concussion | journal = Lancet | volume = 1 | issue = 7652 | pages = 863–864 | date = April 1970 | pmid = 4191508 | doi = 10.1016/S0140-6736(70)91691-0 }}</ref>

Specific cases, such as that of patient ML, support the evidence that severe blows to the head can cause the onset of RA.<ref name="Levin_1998">{{cite journal | vauthors = Levine B, Black SE, Cabeza R, Sinden M, Mcintosh AR, Toth JP, Tulving E, Stuss DT | display-authors = 6 | title = Episodic memory and the self in a case of isolated retrograde amnesia | journal = Brain | volume = 121 | issue = Pt 10 | pages = 1951–1973 | date = October 1998 | pmid = 9798749 | doi = 10.1093/brain/121.10.1951 | doi-access = free }}</ref> In this specific case there was an onset of isolated RA following a severe head injury. The brain damage did not affect the person's ability to form new memories. Therefore, the idea that specific sections of retrograde memory are independent of anterograde is supported. Normally, there is a very gradual recovery, however, a dense period of amnesia immediately preceding the trauma usually persists.<ref name="YarnellLynch"/>

=== Traumatic events ===
RA can occur without any anatomical damage to the brain, lacking an observable neurobiological basis.<ref name="Stanilour_2010">{{cite journal | vauthors = Staniloiu A, Markowitsch HJ, Brand M | title = Psychogenic amnesia--a malady of the constricted self | journal = Consciousness and Cognition | volume = 19 | issue = 3 | pages = 778–801 | date = September 2010 | pmid = 20655759 | doi = 10.1016/j.concog.2010.06.024 | s2cid = 19950039 }}</ref> Primarily referred to as [[psychogenic amnesia]] or [[psychogenic fugue]], it often occurs due to a traumatic situation that individuals wish to consciously or unconsciously avoid through intrapsychic conflicts or unconscious repressions.<ref name="Markowitsch_2003">{{cite journal | vauthors = Markowitsch HJ | title = Psychogenic amnesia | journal = NeuroImage | volume = 20 | issue = Suppl 1 | pages = S132–S138 | date = November 2003 | pmid = 14597306 | doi = 10.1016/j.neuroimage.2003.09.010 | s2cid = 18671395 }}</ref> The onset of psychogenic amnesia can be either global (i.e., individual forgets all history) or situation specific (i.e., individual is unable to retrieve memories of specific situations).<ref name="Diamond_2004">{{cite journal | vauthors = Diamond DM, Park CR, Woodson JC | title = Stress generates emotional memories and retrograde amnesia by inducing an endogenous form of hippocampal LTP | journal = Hippocampus | volume = 14 | issue = 3 | pages = 281–91 | date = 2004 | pmid = 15132427 | doi = 10.1002/hipo.10186 | s2cid = 45819426 }}</ref>

Patients experiencing psychogenic amnesia have impaired episodic memory, instances of wandering and traveling, and acceptance of a new identity as a result of inaccessible memories pertaining to their previous identity.<ref name="Markowitsch_2003"/>

Recent research has begun to investigate the effects of stress and fear-inducing situations with the onset of RA. [[Long-term potentiation]] (LTP) is the process by which there is a signal transmission between neurons after the activation of a neuron, which has been known to play a strong role in the hippocampus in learning and memory.<ref name="Diamond_2004"/> Common changes in the hippocampus have been found to be related to stress and induced LTP.<ref name="Diamond_2004"/> The commonalities support the idea that variations of stress can play a role in producing new memories as well as the onset of RA for other memories.<ref name="Diamond_2004"/> The [[amygdala]] plays a crucial role in memory and can be affected by emotional stimuli, evoking RA.<ref name="Strange_2003">{{cite journal | vauthors = Strange BA, Hurlemann R, Dolan RJ | title = An emotion-induced retrograde amnesia in humans is amygdala- and beta-adrenergic-dependent | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 23 | pages = 13626–13631 | date = November 2003 | pmid = 14595032 | doi = 10.1073/pnas.1635116100 | pmc = 263864 | doi-access = free }}</ref>

Studies of specific cases, such as 'AMN', support evidence  of traumatic experiences as a plausible cause of RA. AMN escaped a small fire in his house, did not inhale any smoke, and had no brain damage. Nevertheless, he was unable to recall autobiographical knowledge the next day. This case shows that RA can occur in the absence of structural brain damage.<ref name="Markowitsch_1998">{{cite journal | vauthors = Markowitsch HJ, Kessler J, Van Der Ven C, Weber-Luxenburger G, Albers M, Heiss WD | title = Psychic trauma causing grossly reduced brain metabolism and cognitive deterioration | journal = Neuropsychologia | volume = 36 | issue = 1 | pages = 77–82 | date = January 1998 | pmid = 9533390 | doi = 10.1016/s0028-3932(97)00093-6 | s2cid = 19174159 }}</ref>

After a traumatic head injury, emotional disturbances can occur at three different levels: neurological, reactionary, and long-term disturbances. Neurological disturbances can change emotional and motivational responses. Reactionary disturbances effect emotional and motivational responses as well, but reflect the failure to cope with environmental demands. Someone with this might withdraw from the environment that they are placed in because they no longer know how to handle the cognitive resources.<ref name="Prigatano_1987">{{cite book | vauthors = Prigatano GP | date = 1987 | chapter = Psychiatric aspects of head injury: Problem areas and suggested guidelines for research | title = Neurobehavioral Recovery from Head Injury | pages = 217–218 | location = New York | publisher = Oxford University Press }}</ref>

=== Nutritional deficiency ===
RA has been found among alcohol-dependent patients who have [[Korsakoff's syndrome]].<ref name="De_Bellis_2000">{{cite journal | vauthors = De Bellis MD, Clark DB, Beers SR, Soloff PH, Boring AM, Hall J, Kersh A, Keshavan MS | title = Hippocampal volume in adolescent-onset alcohol use disorders | journal = The American Journal of Psychiatry | volume = 157 | issue = 5 | pages = 737–44 | date = May 2000 | pmid = 10784466 | doi = 10.1176/appi.ajp.157.5.737 | s2cid = 1668456 }}</ref> Korsakoff's syndrome patients develop retrograde amnesia due to a [[thiamine]] deficiency (lack of vitamin B1).<ref name="McEntee_1990">{{cite journal | vauthors = McEntee WJ, Mair RG | title = The Korsakoff syndrome: a neurochemical perspective | journal = Trends in Neurosciences | volume = 13 | issue = 8 | pages = 340–4 | date = August 1990 | pmid = 1699320 | doi = 10.1016/0166-2236(90)90146-2 | s2cid = 31404753 }}</ref> Also, chronic alcohol use disorders are associated with a decrease in the volume of the left and right hippocampus.<ref name="De_Bellis_2000"/>

These patients' regular diet consists mostly of hard alcohol intake, which lacks the necessary nutrients for typical development and maintenance.<ref name="McEntee_1990" /> Therefore, after a prolonged time consuming primarily alcohol, these people undergo memory difficulties and ultimately develop RA. However, some of the drawbacks of using Korsakoff patients to study RA is the progressive nature of the illness and the unknown time of onset.<ref name="Squire_1995"/>

=== Infections ===
Infections that pass the [[blood–brain barrier]] can cause brain damage ([[encephalitis]]), sometimes resulting in the onset of RA. In the case of patient 'SS', the infection led to focal or isolated retrograde amnesia where there was an absence of or limited AA. Brain scans show abnormalities in the bilateral medial temporal lobes, including two thirds of the hippocampal formation and the posterior part of the amygdala.<ref name="Fujiietal">{{cite journal | vauthors = Fujii T, Yamadori A, Endo K, Suzuki K, Fukatsu R | title = Disproportionate retrograde amnesia in a patient with herpes simplex encephalitis | journal = Cortex; A Journal Devoted to the Study of the Nervous System and Behavior | volume = 35 | issue = 5 | pages = 599–614 | date = December 1999 | pmid = 10656630 | doi = 10.1016/S0010-9452(08)70822-0 | s2cid = 4480119 }}</ref>

=== Surgery ===
[[Henry Molaison]] had epilepsy that progressed and worsened by his late twenties. The severity of his condition caused him to undergo surgery in an effort to prevent his seizures. Unfortunately, due to a lack of overall known neurological knowledge, Molaison's surgeons removed his bilateral medial temporal lobe, causing profound AA and RA.<ref name="HMpap">{{cite journal | vauthors = Squire LR | title = The legacy of patient H.M. for neuroscience | journal = Neuron | volume = 61 | issue = 1 | pages = 6–9 | date = January 2009 | pmid = 19146808 | doi = 10.1016/j.neuron.2008.12.023 | pmc = 2649674 | s2cid = 643599 }}</ref> The removed brain structures included the hippocampus, the amygdala, and the [[parahippocampal gyrus]], now called the medial temporal lobe memory system.<ref name="HMpap"/> HM was one of the most studied memory cases to date and started the examination of neurological structures in relation to memory.

Patients who have RA due to surgery are "P.B." and "F.C." who had unilateral removal of the medial areas in the left temporal lobe.<ref name="HMpap"/>

=== Controlled induction ===
Clinically induced RA has been achieved using different forms of electrical induction.
* [[Electroconvulsive therapy]] (ECT), used as a depression therapy, can cause impairments in memory.<ref name="Ottosson_1960">{{cite journal | vauthors = Ottosson J | title = Experimental studies of the mode of action of electroconvulsive therapy. | journal = Acta Psychiatrica Scandinavica | date = 1960 | volume = 145 | pages = 1–41 | doi = 10.1111/j.1600-0447.1960.tb08352.x| s2cid = 29773758 }}</ref> Tests show that information from days and weeks before the ECT can be permanently lost.<ref name="Donahue_2000">{{cite journal | vauthors = Donahue AB | title = Electroconvulsive therapy and memory loss: a personal journey | journal = The Journal of ECT | volume = 16 | issue = 2 | pages = 133–43 | date = June 2000 | pmid = 10868323 | doi = 10.1097/00124509-200006000-00005 | s2cid = 28318459 | url = }}</ref> The results of this study also show that severity of RA is more extreme in cases of bilateral ECT rather than unilateral ECT. Impairments can also be more intense if ECT is administered repetitively (sine wave simulation) as opposed to a single pulse (brief-pulse stimulation).<ref name="Squire_1986">{{cite journal | vauthors = Squire LR | title = Memory functions as affected by electroconvulsive therapy | journal = Annals of the New York Academy of Sciences | date = 1986 | volume = 462 | issue = 1 | pages = 307–314 | pmid = 3458411 | doi = 10.1111/j.1749-6632.1986.tb51265.x | bibcode = 1986NYASA.462..307S | s2cid = 28060335 | doi-access = free }}</ref>
* [[Electroconvulsive shock]] (ECS): The research in this field has been advanced by using animals as subjects.<ref name="Misanin_2002">{{cite journal | vauthors = Rao SK, Andrade C, Reddy K, Madappa KN, Thyagarajan S, Chandra S | title = Memory protective effect of indomethacin against electroconvulsive shock-induced retrograde amnesia in rats | journal = Biological Psychiatry | volume = 51 | issue = 9 | pages = 770–773 | date = May 2002 | pmid = 11983192 | doi = 10.1016/S0006-3223(01)01219-7 | s2cid = 29560202 }}</ref> This is done to further understand RA.