View source for Retrograde amnesia

{{short description|Permanent loss of long-term memory}}
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In [[neurology]], '''retrograde amnesia''' ('''RA''') is the inability to access memories or information from before an injury or disease occurred.<ref name="Hunkin_1995" /> RA differs from a similar condition called [[anterograde amnesia]] (AA), which is the inability to form new memories following injury or disease onset.<ref name="Lafleche_2017">{{cite book | vauthors = Lafleche G, Verfaellie M | chapter = Anterograde Amnesia |date=2017 | title = Encyclopedia of Clinical Neuropsychology |pages=1–5 | veditors = Kreutzer J, DeLuca J, Caplan B |place=Cham |publisher=Springer International Publishing |language=en |doi=10.1007/978-3-319-56782-2_1106-2 |isbn=978-3-319-56782-2 }}</ref> Although an individual can have both RA and AA at the same time, RA can also occur on its own; this 'pure' form of RA can be further divided into three types: focal, isolated, and pure RA.<ref name="Lafleche_2011">{{cite book | vauthors = Lafleche G, Verfaellie M | chapter = Retrograde Amnesia |date=2011 | veditors = Kreutzer J, DeLuca J, Caplan B | title = Encyclopedia of Clinical Neuropsychology |pages=2167–2170 |place=New York, NY |publisher=Springer New York |language=en |doi=10.1007/978-0-387-79948-3_1152 |isbn=978-0-387-79947-6 }}</ref> RA negatively affects an individual's [[Episodic memory|episodic]], [[Autobiographical memory|autobiographical]], and [[declarative memory]], but they can still form new memories because RA leaves [[procedural memory]] intact.<ref name="Lafleche_2011" /> Depending on its severity, RA can result in either temporally graded or more permanent memory loss.<ref name="Lafleche_2011" /> However, memory loss usually follows [[Ribot's law]], which states that individuals are more likely to lose recent memories than older memories.<ref name="Wixted_2004">{{cite journal | vauthors = Wixted JT | title = The psychology and neuroscience of forgetting | date = February 2004| journal = Annual Review of Psychology | volume = 55 | pages = 235–269 | pmid = 14744216 | doi = 10.1146/annurev.psych.55.090902.141555 | s2cid = 3057114 }}</ref> Diagnosing RA generally requires using an Autobiographical Memory Interview (AMI) and observing brain structure through [[magnetic resonance imaging]] (MRI), a [[computed tomography scan]] (CT), or [[electroencephalography]] (EEG).<ref name="Lafleche_2011" /><ref name="Reed_19982">{{cite journal |vauthors=Reed JM, Squire LR |date=May 1998 |title=Retrograde amnesia for facts and events: findings from four new cases |journal=The Journal of Neuroscience|volume=18 |issue=10 |pages=3943–54 |doi=10.1523/JNEUROSCI.18-10-03943.1998 |pmc=6793126 |pmid=9570821}}</ref><ref name=":0" />

== Types ==
[[File:Types of Retrograde Amnesia Flowchart.svg|thumb|upright=2|Types of RA can be divided into two main categories: temporally graded RA and pure forms of RA. Individuals with pure forms of RA like focal, isolated, and pure RA do not have anterograde amnesia (AA).]]

=== Temporally graded RA ===
Memory loss in patients with temporally graded RA strongly follows [[Ribot's law]], meaning that one will experience more memory loss for events closer to the injury or disease onset.<ref name="Wixted_2004" /> This type of RA is commonly triggered in individuals with [[Korsakoff syndrome]] due to a combination of long-term alcohol use and [[Wernicke encephalopathy]].<ref>{{cite book | vauthors = Bauer RM, Asken B | veditors = Morgan JE, Ricker JH | chapter = Chapter 28: The Three Amnesias |date= 2008 | doi = 10.4324/9781315537511-51 | title = Textbook of Clinical Neuropsychology | edition = 2nd | pages = 678–700 | location = New York, NY | publisher = Rutlidge |isbn = 978-1-351-98599-4 }}</ref> Debate has risen about why this temporal gradient forms in the first place. Initial theories proposed that the [[hippocampus]] and [[medial temporal lobe]] are not nearly as important for long-term memories compared to short-term memories.<ref name="Lafleche_2011" /> As memory processing occurs in the brain over time, neocortical regions can directly communicate with each other, so they do not rely as heavily on the hippocampus for long-term memory storage.<ref name="Lafleche_2011" /> Therefore, if an individual experiences RA that damages the hippocampus, they will lose more short-term memories according to this theory. However, this theory has been challenged by the multiple-trace theory, which claims that the brain develops a hippocampal trace each time a memory is retrieved.<ref name="Lafleche_2011" /> Since more hippocampal traces are present for older memories, it is easier for older memories to remain intact when RA occurs.<ref name="Lafleche_2011" />

=== Focal, isolated, and pure RA ===
An absence of anterograde amnesia (AA) characterizes pure forms of RA, which fall into three main categories: focal, isolated, and pure RA.<ref name="Lafleche_2011" /> Slight differences in the use of these terms to describe a pure form of RA are summarized below:
{| class="wikitable"
|+Pure Forms of RA
!width=42%|Focal RA
!width=29%|Isolated RA
!width=29%|Pure RA
|-
|Focal RA generally results from neurological problems like epilepsy and is characterized by memory loss prior to – but not after – injury or disease onset.<ref>{{cite journal | vauthors = Sehm B, Frisch S, Thöne-Otto A, Horstmann A, Villringer A, Obrig H | title = Focal retrograde amnesia: voxel-based morphometry findings in a case without MRI lesions | journal = PLOS ONE | volume = 6 | issue = 10 | article-number = e26538 | date = 2011-10-19 | pmid = 22028902 | pmc = 3197527 | doi = 10.1371/journal.pone.0026538 | bibcode = 2011PLoSO...626538S | veditors = de Beeck HP | doi-access = free }}</ref> When an individual experiences focal RA, a combination of their episodic and semantic memories may be affected.<ref name="Wheeler_2001">{{cite journal | vauthors = Wheeler MA, McMillan CT | title = Focal retrograde amnesia and the episodic-semantic distinction | journal = Cognitive, Affective & Behavioral Neuroscience | volume = 1 | issue = 1 | pages = 22–36 | date = March 2001 | pmid = 12467101 | doi = 10.3758/CABN.1.1.22 | s2cid = 20269516 | doi-access = free }}</ref> In one case study, a middle-aged female experienced focal RA after significant head trauma.<ref name="Wheeler_2001" /> Although she could be re-taught information from her past, these memories were not episodic, but rather, semantic.<ref name="Wheeler_2001" /> With focal RA, the details of a patient's life prior to amnesia onset can be reintroduced, but they are unable to recall how they perceived the experience.<ref name="Wheeler_2001" />
|Isolated RA is usually associated with a visible [[Thalamus|thalamic]] lesion.<ref name="Miller_2001">{{cite journal | vauthors = Miller LA, Caine D, Harding A, Thompson EJ, Large M, Watson JD | title = Right medial thalamic lesion causes isolated retrograde amnesia | journal = Neuropsychologia | volume = 39 | issue = 10 | pages = 1037–46 | date = 2001 | pmid = 11440756 | doi = 10.1016/s0028-3932(01)00041-0 | s2cid = 18021762 }}</ref> Similar to other forms of RA, the inability to recall past information characterizes the isolated form.<ref name="Miller_2001" /> In one case study, a middle-aged man, identified as JG, had a thalamic lesion which expanded as he grew older.<ref name="Miller_2001" /> This lesion growth induced his isolated RA, resulting in both autobiographical memory loss and the inability to recognize information from popular culture.<ref name="Miller_2001" />
|Pure RA (PRA) is caused by a range of factors such as vascular diseases, encephalitis, and head injuries.<ref name="Lucchelli_1998">{{cite journal |vauthors=Lucchelli F, Muggia S, Spinnler H |date=1998 |title=The Syndrome of Pure Retrograde Amnesia |journal=Cognitive Neuropsychiatry |volume=3 |issue=2 |pages=91–118 |doi=10.1080/135468098396189}}</ref> It is often confused with peritraumatic amnesia that commonly follows mild concussions, but the severity and duration of PRA differs from that of peritraumatic amnesia.<ref name="Lucchelli_1998" /> Current discussion in neuropsychiatry literature centers on whether PRA is possibly [[Psychogenic disease|psychogenic]] in nature.<ref name="Lucchelli_1998" />
|}

== 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.

==Diagnosis ==

Since RA affects people's memories to varying degrees, testing is required to fully diagnose RA; these tests, however, are inherently limited if a patient's previous [[Neuropathology|neuropathological]] medical history is unknown.<ref name="Reed_19982"/> As a result, some clinicians diagnose RA by testing patients about factual knowledge, such as current public events.<ref name="Reed_19982" /> This testing is limited, however, because people's knowledge about current events differs.<ref name="Reed_19982" /> Furthermore, these tests must be adjusted to account for the time period that a patient is alive, which affects the amount of detail included in the questions.<ref name="Baddeley_20152">{{cite book |title=Memory |vauthors=Baddeley A, Eysenck MW, Anderson MC |publisher=Psychology Press |year=2015 |location=New York |pages=444–48}}</ref> Since some information obtained from this testing is subjective, it is difficult to verify how accurately memories are recalled; this difficulty is especially true for memories from the distant past.<ref name="Reed_19982" />

To avoid these issues, many researchers test for RA using the Autobiographical Memory Interview (AMI).<ref name="Reed_19982" /><ref name=":4">{{Cite journal |last1=Kopelman |first1=M. D. |last2=Wilson |first2=B. A. |last3=Baddeley |first3=A. D. |date=1989 |title=The autobiographical memory interview: A new assessment of autobiographical and personal semantic memory in amnesic patients |url=https://www.tandfonline.com/doi/full/10.1080/01688638908400928 |journal=Journal of Clinical and Experimental Neuropsychology |language=en |volume=11 |issue=5 |pages=724–744 |doi=10.1080/01688638908400928 |pmid=2808661 |issn=0168-8634|url-access=subscription }}</ref> The AMI asks patients targeted questions about three different portions of their life: childhood, early adult life, and recent life.<ref name="Reed_19982" /> For each period of that individual's life, researchers ask questions that require the patient to use either their autobiographical or semantic memory.<ref name=":4" /> Through the AMI, researchers can better understand the types of memories affected, as well as the degree of a patient's RA.<ref name="Reed_19982" /> These AMIs can then be used alongside functional brain imaging techniques like [[magnetic resonance imaging]] (MRI), [[computed tomography scan]]s (CT) and [[electroencephalography]] (EEG) that detect brain damage in patients with RA.<ref name=":0">{{Cite journal |date=2006-12-01 |title=Functional Brain Imaging |journal=Ontario Health Technology Assessment Series |volume=6 |issue=22 |pages=1–79 |issn=1915-7398 |pmc=3379170 |pmid=23074493|last1=Medical Advisory |first1=Secretariat }}</ref>

== Brain structures ==
The most commonly affected areas are associated with [[episodic memory|episodic]] and [[declarative memory]] such as the [[hippocampus]],<ref name="Cipolotti_2001">{{cite journal | vauthors = Cipolotti L, Shallice T, Chan D, Fox N, Scahill R, Harrison G, Stevens J, Rudge P | title = Long-term retrograde amnesia...the crucial role of the hippocampus | journal = Neuropsychologia | volume = 39 | issue = 2 | pages = 151–72 | date = 2001 | pmid = 11163373 | doi = 10.1016/s0028-3932(00)00103-2 | s2cid = 7428309 | url = }}</ref> the [[diencephalon]],<ref name="Dusoiretal"/> and the [[temporal lobe]]s.<ref name="Buccione_2008">{{cite journal | vauthors = Buccione I, Fadda L, Serra L, Caltagirone C, Carlesimo GA | title = Retrograde episodic and semantic memory impairment correlates with side of temporal lobe damage | journal = Journal of the International Neuropsychological Society| volume = 14 | issue = 6 | pages = 1083–94 | date = November 2008 | pmid = 18954490 | doi = 10.1017/S1355617708080922 | s2cid = 12905302 | url = | doi-access = free }}</ref>
* The [[hippocampus]] deals largely with [[memory consolidation]],<ref name="Cipolotti_2001"/> where information from the [[working memory]] and [[short-term memory]] is encoded into [[long-term memory|long-term]] storage for future retrieval. Amnesic patients with damage to the hippocampus are able to demonstrate some degree of unimpaired [[semantic memory]], despite a loss of [[episodic memory]], due to spared [[parahippocampal cortex]].<ref name="Nadel_1997">{{cite journal | vauthors = Nadel L, Moscovitch M | title = Memory consolidation, retrograde amnesia and the hippocampal complex | journal = Current Opinion in Neurobiology | volume = 7 | issue = 2 | pages = 217–227 | date = April 1997 | pmid = 9142752 | doi = 10.1016/S0959-4388(97)80010-4 | s2cid = 4802179 }}</ref> In other words, retrograde amnesics "know" about information or skill, but cannot "remember" how they do.
* The [[diencephalon]] and the surrounding areas' role in memory is not well understood. However, this structure appears to be involved in episodic memory recall.<ref name="Dusoiretal">{{cite journal | vauthors = Dusoir H, Kapur N, Byrnes DP, McKinstry S, Hoare RD | title = The role of diencephalic pathology in human memory disorder. Evidence from a penetrating paranasal brain injury | journal = Brain | volume = 113 | issue = Pt 6 | pages = 1695–1706 | date = December 1990 | pmid = 2276041 | doi = 10.1093/brain/113.6.1695 }}</ref> 
* The [[temporal lobe]]s are essential for semantic and factual memory processing. Aside from helping to consolidate memory with the [[hippocampus]],<ref name="Buccione_2008"/> the temporal lobes are extremely important for [[semantic memory]]. Damage to this region of the brain can result in the impaired organization and categorization of verbal material, disturbance of language comprehension, and impaired long-term memory. The right frontal lobe is critical for the retrieval of episodic information, while the left frontal region is more active for the retrieval of semantic information.<ref name = "Reinvang_2000">{{cite journal | vauthors = Reinvang I, Nielsen CS, Gjerstad L, Bakke SJ | title = Isolated retrograde amnesia: Evidence for preservation of implicit memory. An event-related potential investigation. | journal = Neurocase | date = September 2000 | volume = 6 | issue = 5 | pages = 423–433 | doi = 10.1080/13554790008402713 | s2cid = 145665210 }}</ref> Lesions in the right hemisphere and right frontal lobes result in the impaired recall of non-verbal material, such as music and drawings.<ref name="Milner_1968">{{cite journal | vauthors = Milner B | date = 1968 | title = Visual recognition and recall after right temporal lobe excision in man | journal = Neuropsychologia | volume = 6 | issue = 3 | pages = 191–209 | doi = 10.1016/0028-3932(68)90019-5 }}</ref> Difficulties in studying this region of the brain extends to its duties in comprehension, naming objects, [[verbal memory]], and other language functions.<ref name = "Kolb_1990">{{cite book | vauthors = Kolb B, Whishaw I |title=Fundamentals of Human Neuropsychology | edition = 3rd |date=1990 |publisher=Freeman |location=New York |isbn=978-0-7167-1973-1 }}{{page needed|date=September 2021}}</ref>

[[Neuroplasticity|Brain plasticity]] has helped explain the recovery process of brain damage induced retrograde amnesia, where neuro-structures use different neural pathways to avoid the damaged areas while still performing their tasks.<ref name="Kolb_2003">{{cite journal | vauthors = Kolb B, Gibb R, Robinson TE | title = Brain plasticity and behavior. | journal = Current Directions in Psychological Science | date = February 2003 | volume = 12 | issue = 1 | pages = 1–5 | doi = 10.1111/1467-8721.01210 | hdl = 2027.42/74427 | s2cid = 11271886 | hdl-access = free }}</ref> Thus, the brain can learn to be independent of the impaired hippocampus, but only to a certain extent.<ref name="Squire_1995"/>
For example, older memories are consolidated over time and in various structures of the brain, including [[Wernicke's area]] and the neocortex, making retrieval through alternate pathways possible.<ref name="Wixted_2004"/>

== Case studies ==
Since researchers are interested in examining the effects of disrupted brain areas and conducting experiments for further understanding of an unaffected, normal brain,<ref name="Esclapez_1994">{{cite journal | vauthors = Esclapez M, Tillakaratne NJ, Kaufman DL, Tobin AJ, Houser CR | title = Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms | journal = The Journal of Neuroscience| volume = 14 | issue = 3 Pt 2 | pages = 1834–1855 | date = March 1994 | pmid = 8126575 | pmc = 6577546 | doi = 10.1523/JNEUROSCI.14-03-01834.1994 }}</ref> many individuals with brain damage have volunteered to undergo countless tests to advance our scientific knowledge of the human brain. For example, [[Henry Molaison]] (HM) was someone with significant brain damage and participated in a lot of neurological research. Furthermore, he was also the most tested person in [[neuropsychology]].<ref name="Corkin_1997">{{cite journal | vauthors = Corkin S, Amaral DG, González RG, Johnson KA, Hyman BT | title = H. M.'s medial temporal lobe lesion: findings from magnetic resonance imaging | journal = The Journal of Neuroscience| volume = 17 | issue = 10 | pages = 3964–79 | date = May 1997 | pmid = 9133414 | pmc = 6573687 | doi = 10.1523/JNEUROSCI.17-10-03964.1997 }}</ref> All living people who participate are referred to in literature using only their initials to protect privacy.

Each case of RA has led to different symptoms and durations, where some patients have exhibited an inability to describe future plans, whether in the near future (e.g., this afternoon) or in the distant future (e.g., next summer)<ref name="Tulving_1988">{{cite journal | vauthors = Tulving E, Schacter DL, McLachlan DR, Moscovitch M | title = Priming of semantic autobiographical knowledge: a case study of retrograde amnesia | journal = Brain and Cognition | volume = 8 | issue = 1 | pages = 3–20 | date = August 1988 | pmid = 3166816 | doi = 10.1016/0278-2626(88)90035-8 | s2cid = 17125951 }}</ref> because of their inability to consolidate memories.<ref name="Squire_1995"/> Furthermore, researchers have also found that some patients can identify themselves and loved ones in photographs, but cannot determine the time or place the photo was taken.<ref name="Tulving_1988"/> It has also been found that patients with RA greatly differ from the general population in remembering past events.<ref name="Kwan_2010">{{cite journal | vauthors = Kwan D, Carson N, Addis DR, Rosenbaum RS | title = Deficits in past remembering extend to future imagining in a case of developmental amnesia | journal = Neuropsychologia | volume = 48 | issue = 11 | pages = 3179–3186 | date = September 2010 | pmid = 20561535 | doi = 10.1016/j.neuropsychologia.2010.06.011 | s2cid = 565582 }}</ref>

A few case examples are:
* After a head injury, '''AB''' had to relearn personal information.<ref name="Fujiwara_2008">{{cite journal | vauthors = Fujiwara E, Brand M, Kracht L, Kessler J, Diebel A, Netz J, Markowitsch HJ | title = Functional retrograde amnesia: a multiple case study | journal = Cortex; A Journal Devoted to the Study of the Nervous System and Behavior | volume = 44 | issue = 1 | pages = 29–45 | date = January 2008 | pmid = 18387529 | doi = 10.1016/j.cortex.2005.09.001 | s2cid = 206982684 }}</ref> Many of AB's habits had also changed.<ref name="Fujiwara_2008"/>
* Patient '''CD''' reported disorientation of place and time following his injuries as well as relearning previously learned information and activities (e.g., using a razor).<ref name="Fujiwara_2008"/>
* '''EF''' was examined and found to be very confused about social norms (e.g., appropriate attire outside his home). EF exhibited memory loss of his personal experiences (e.g., childhood), and the impaired ability to recognize his wife and parents.<ref name="Fujiwara_2008"/>
* '''JG''' is the first recorded patient with isolated RA.<ref name="Miller_2001" />
* '''GH''', a mother and a wife, had surgery in August 2002. When GH woke up after the surgery, she believed it was May 1989.<ref name="Fujiwara_2008"/> Due to her amnesia, GH experienced great difficulty in her social environment, being overwhelmed by relationships to others.<ref name="Fujiwara_2008"/>
* '''DH''', a learning disabilities instructor and husband, sustained a closed head injury. He did not show any normal signs of memory loss but he could not recall anything prior to the accident.<ref name="Hunkin_1995">{{cite journal | vauthors = Hunkin NM, Parkin AJ, Bradley VA, Burrows EH, Aldrich FK, Jansari A, Burdon-Cooper C | title = Focal retrograde amnesia following closed head injury: a case study and theoretical account | journal = Neuropsychologia | volume = 33 | issue = 4 | pages = 509–523 | date = April 1995 | pmid = 7617158 | doi = 10.1016/0028-3932(94)00136-D | s2cid = 21295568 }}</ref>
* '''CDA''' is a 20-year-old man who fell and experienced head trauma after being unconscious for a little less than an hour. He had a self-identity loss and a retrograde deficit limited to the autobiographical events 5 years before the trauma. He often showed signs of spontaneous speech that was iterative and sometimes incoherent. When he saw his family and friends, he was shocked at how old they looked because he remembered them from 5 years earlier. This case also included amnesia for procedural skills like the fear of shaving or driving, which ultimately was overcome. There were no psychological, neuropsychological, or brain damage problems. His recovery of memory was progressive and spontaneous, where after several months the amnesia was limited to the two years preceding the trauma. This was a classic case of PRA.<ref name="Lucchelli_1998" />
* '''GC''' was a 38 year old accountant that was found in a town square unable to remember anything about himself and unaware of where he was and how he got there. He was eventually able to recall basic information about himself and his family, but could not recall emotionally charged autobiographical events pertaining to the last 7 years of his life. Within 3–4 days, it was determined that his autobiographical amnesia was clearly and strictly selective for professional events, as he could remember everything that was not related to his job. It was ultimately learned that the job had created severe emotional stress and anxiety due to the extreme hours that triggered a sudden fugue state. He was eventually able to recover most of his memories minus a single work event where he had stolen money from the company. This was a classic case of [[psychogenic amnesia]].<ref name="Lucchelli_1998" />
* '''AF''' is a 15-year-old boy who hit his head and lost consciousness. He could not remember anything but was able to play songs on the piano, showing that his procedural memory was still intact. He gradually recovered some memories within the first 2–3 days but had autobiographical amnesia as well as significant memory loss for famous public facts and events for the 2 years prior to the injury.<ref name="Lucchelli_1998" />
* '''L''' is 19-year-old student who was left with the inability to recall episodic memories after experiencing a [[fugue state]] in December 2020. However, he was able to recall things such as his birthday and the street names of Nantes, the city where he resides in. L was part of a case study that associated reduced pupil size as a possible indicator of RA.<ref>{{Cite journal |last1=El Haj |first1=Mohamad |last2=Lamy |first2=Estelle |last3=Janssen |first3=Steve M. J. |last4=Boutoleau-Bretonnière |first4=Claire |date=2021-03-04 |title=Amnesia in your pupils: decreased pupil size during autobiographical retrieval in a case of retrograde amnesia |journal=Neurocase |volume=27 |issue=2 |pages=155–159 |doi=10.1080/13554794.2021.1902539 |issn=1355-4794 |pmid=33739239|s2cid=232299779 }}</ref>

Although it may seem that people living with brain damage have great difficulty continuing the usual day-to-day aspects, they still can accomplish many feats. People with RA are able to lead a normal life. For instance, '''KC''' is a man who has many functional aspects intact; normal intelligence, unaffected perceptual and linguistic skills, short-term memory, social skills, and reasoning abilities.<ref name="Tulving_1988"/> All of these things are necessary in everyday life and contribute to normal living. KC also is fully capable of scripted activities (e.g., making reservations or changing a flat tire).<ref name="Tulving_1988"/>
In addition, patient '''HC''' graduated high school and continued into post-secondary studies,<ref name="Kwan_2010"/> an obvious accomplishment despite her condition. '''DH''' relearned his childhood memories from his parents and can retell the stories, but cannot recall specifics other than what has been told to him.<ref name="Hunkin_1995" />

== Other forms of amnesia ==
Other forms of amnesia exist and may be confused with RA. For instance, [[anterograde amnesia]] (AA) is the inability to learn new information.<ref name="Dworetzky">{{cite journal | vauthors = Dworetzky BA | title = The neurology of memory | journal = Seminars in Speech and Language | year = 2001 | volume = 22 | issue = 2 | pages = 95–105 | pmid = 11373070 | doi = 10.1055/s-2001-13934 | s2cid = 25906826 }}</ref> This describes a problem encoding, storing, or retrieving information that can be used in the future.<ref name="encoding">{{cite book | vauthors = Markowitsch HJ, Calabrese P | date = 1999 | chapter = Neuroanatomy of memory | title = The Oxford Handbook of Memory | veditors = Tulving E, Craik FI | pages = 465–484 | publisher = Oxford University Press }}</ref> It is important to note that these two conditions can, and often do both occur in the same patient simultaneously,<ref name="Winocur_2001"/> but are otherwise separate forms of amnesia.

RA can also be an inherent aspect of other forms of amnesia, namely [[transient global amnesia]] (TGA). TGA is the sudden onset of AA and RA caused by a traumatic event, however it is short lived, typically lasting only 4 to 8 hours<ref name="Fisher_1982">{{cite journal | vauthors = Fisher CM | title = Transient global amnesia. Precipitating activities and other observations | journal = Archives of Neurology | volume = 39 | issue = 10 | pages = 605–8 | date = October 1982 | pmid = 7125972 | doi = 10.1001/archneur.1982.00510220003001 }}</ref> TGA is very difficult to study because of the patients' quick recovery.<ref name="Guillery-Girardetal">{{cite journal | vauthors = Guillery-Girard B, Desgranges B, Urban C, Piolino P, de la Sayette V, Eustache F | title = The dynamic time course of memory recovery in transient global amnesia | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 75 | issue = 11 | pages = 1532–1540 | date = November 2004 | pmid = 15489382 | doi = 10.1136/jnnp.2003.024968 | pmc = 1738827 | s2cid = 16685800 }}</ref> This form of amnesia, like AA, remains distinct from RA.<ref name="Squire_1995">{{cite journal | vauthors = Squire LR, Alvarez P | title = Retrograde amnesia and memory consolidation: a neurobiological perspective | journal = Current Opinion in Neurobiology | volume = 5 | issue = 2 | pages = 169–177 | date = April 1995 | pmid = 7620304 | doi = 10.1016/0959-4388(95)80023-9 | s2cid = 9080102 }}</ref>

[[Post-traumatic amnesia|Post-traumatic amnesia (PTA)]] is a state of [[Mental confusion|confusion]] that occurs immediately following a [[traumatic brain injury]] in which the injured person is [[Orientation (mental)|disoriented]] and unable to remember events that occur after the [[Physical injury|injury]].

[[Psychogenic amnesia]], or dissociative amnesia, is a [[memory disorder]] characterized by sudden retrograde [[autobiographical memory]] loss, said to occur for a period of time ranging from hours to years.

== See also ==
* [[Amnesia]]
* [[Anterograde amnesia]]
* [[Dissociative amnesia]]
* [[Scott Bolzan]] – One of the most severe cases of retrograde amnesia on record<ref>{{cite web | title = Man With Amnesia Lost 46 Years in Workplace Slip: Scott Bolzan Interviews Wife for Details on Their 25-Plus Year Marriage, Past Life | vauthors = Woodruff B, Patria M | publisher = ABC News | work = Nightline | date = 19 April 2010 | url = https://abcnews.go.com/Nightline/amnesia-man-hits-head-loses-memories/story?id=10396719 }}</ref>

== References ==
{{reflist}}

== External links ==
* [http://www.jneurosci.org/cgi/content/abstract/9/3/828 Journal of Neuroscience]
* [http://www.rnw.nl/english/article/retrograde-amnesia-strange-case-jonathan-overfeld The strange case of Jonathan Overfeld from The State We're In radio show ] {{Webarchive|url=https://web.archive.org/web/20110724165657/http://www.rnw.nl/english/article/retrograde-amnesia-strange-case-jonathan-overfeld |date=2011-07-24 }}
{{Medical resources
|  ICD10       = {{ICD10|R|41|2|r|40}}  
|  ICD9        = {{ICD9|780.9}}  
}}

{{Cognition, perception, emotional state and behaviour symptoms and signs}}
{{memory}}

{{DEFAULTSORT:Retrograde Amnesia}}
[[Category:Amnesia]]
[[Category:Symptoms, signs or clinical findings involving cognition]]