Memory Disorders –Amnesias

Anterograde Amnesia

 loss of the ability to create new memories

 leading to a partial or complete inability to recall the recent past
o Repeat comments or questions several times, for example, or fail to
recognize people they met just minutes before.
 Long-term memories before the event remain intact.
 WHY?
o Anterograde amnesia results from a failure of memory encoding and storage.
o New information = processed normally
 but = immediately forgotten, never making it into the regions of the
brain where long-term memories are stored.
o Normal Memory:
 Neurons in the mammillary bodies of the hypothalamus make
connections with the thalamus, which in turn makes connections with
the cortex of the brain, where long-term memories are stored.
o Anterograde amnesia
 Result from damage to the hypothalamus and thalamus and the
surrounding cortical structures, so that encoded memories are never
stored since connections between hippocampus and cortex are
disrupted.

 Anterograde amnesia
o lose declarative memory (the recollection of facts)
o Retain non-declarative, or procedural memory (the learning of skills and
habits)
 may remember or learn how to do things:
 talking on the phone or riding a bicycle
 BUT may not remember what they had eaten for lunch earlier
that day.
o This is because procedural memory does not rely on the hippocampus and
medial temporal lobe memory system in the same way as declarative
memory.
 There have, however, been cases where anterograde amnesia patients lose only the
episodic part of their declarative memory (that part which relates to
autobiographical information with a temporal and/or spatial context), and not the
semantic part (factual information, such as language, history, geography, etc, with
autobiographical association).

 ETIOLOGY:
o drug-induced
  several benzodiazepines, antihistamines, sleeping tablets are known
to have powerful amnesic effects
 alcohol intoxication
o traumatic brain injury
o surgery
 damage to the hippocampus or medial temporal lobe
o Acute event: a concussion, a heart attack, oxygen deprivation or an epileptic
attack.
o Shock or an emotional disorder.

NOTE: When there is damage to just one side of the medial temporal lobe, the
neuroplasticity of the brain (its ability to re-map its neural connections when necessary) can
often allow the opportunity for normal, or near-normal, functioning for memories with time.

However, if the damage is bilateral, as in the case of H.M. then a return to functioning is not
always possible.

Case Study
H.M.
Bilateral damage to the hippocampus results in anterograde amnesia (PatientH.M.).

 Generalised epileptic seizures

 Grown worse in frequency and severity (despite high doses of medication)
 23 August, 1953 – William Scoville performed bilateral medial-temporal-lobe
resection (temporal lobectomy)
 Severe anterograde amnesia
o Persisted to this day
 I.Q. = > average
 Normal performance on perceptual tests
 Memory of events BEFORE surgery = good
o Recalls remote incidents from school days / jobs held in his teens
o slight retrograde amnesia surrounding few years prior to surgery
 socially = quiet and well-mannered
o speaks in monotone
o articulates words well
o vocab = normal in keeping with IQ
o language comprehension = normal
 understand complex verbal material (incl. jokes)
 dresses nearly – needs to be REMINDED TO SHAVE
 = protective employment (monotonous work)
 CANNOT GIVE DESCRIPTION OF PLACE OF WORK, NATURE OF JOB, ROUTE TAKEN TO
GET THERE
 Can draw plan of bungalow he has lived in for past 8 years
 Thought to have GLOBAL ANTEROGRADE AMNESIA
o Impaired in spatial and topographic learning
o Learning about all events that take place around him
o Remembers only a few events / people who have made news since his injury
 o BUT kept procedural memory:
 e.g. mirror drawing. Improved his proficiency on mirror drawing (as is
to be expected in a normal patient) despite his lack of recall of ever
doing the task. Therefore procedural memory = often intact.

“Everyday is alone in itself, whatever enjoyment I’ve had, and whatever sorrow I’ve had.”
(Kolb & Whishaw, 2009, p. 491)

Wernicke-Korsakoff’s Syndrome
History
 Late 1800s
 Russian Physician Sergei Korsakoff
o Called attention to syndrome that = found to accompany chronic alcoholism
 Most obvious symptom = severe loss of memory
 Memory of recent events, those that just happened = chiefly
disturbed
 Sanders & Warrington (1971) article:
o 6 MAJOR SYMPTOMS
 Anterograde amnesia
 Retrograde amnesia
 Confabulation
 people glibly produce plausible stories about past events
rather than admit memory loss
 stories = plausible because they = based on past experiences
 meagre content in conversation
 lack of insights
 apathy
 lose interest in things quickly
 generally appear indifferent to change

Overview
 ETIOLOGY:
o Thiamine / vitamin B₁ deficiency
 Result of prolonged intake of large quantities of alcohol
 Alcohol abuse (malnutrition)
 Alcohol affects the breakdown of thiamine in the body – most of
thiamine is not absorbed
o Avitaminosis
 secondary to malabsorption syndromes
o Refusal to eat
 Psychiatric disorder (anorexia nervousa)
 Stages of Illness
o Wernicke's encephalopathy is characterized by:
 confusion
 nystagmus (involuntary eye movement)
 ophthalmoplegia (impaired eye movement)
  anisocoria (unequal size of pupils)
 ataxia (lack of muscle coordination)
 sluggish pupillary reflexes
 coma and death if untreated
o Korsakoff's psychosis is characterized by:
 anterograde amnesia (inability to form new memories)
 retrograde amnesia (loss of existing memories)
 confabulation (false perceptions or memories)
 hallucinations
o Amnesia
 Persists as permanent symptom
 Symptoms – can appear suddenly within the space of a few days
o Severe anterograde
o Extensively temporally graded retrograde
o Confabulation of memories
o Anosognosia for amnesia
 They are unaware of memory loss and therefore confabulate as a
compensation mechanism
 Damage:
o Controversial
 Medial nuclei of thalamus
 Diencephalic lesions of anterior thalamic nuclei
 Mamillary bodies
 Generalised cerebral atrophy
 Syndrome can be arrested = massive doses of vitamin B₁ BUT CANNOT BE REVERSED
 Prognosis:
o Poor
o Roughly 20% of patients show recovery in a year on B₁-enriched diets
o Many patients = no recovery even after 10 – 20 years

Neuroimaging
 Caulo et al. 2005
 Functional MRI study of diencephalic amnesia in Wernicke-Korsakoff syndrome
o Anterograde amnesia in Wernicke–Korsakoff syndrome is associated with
diencephalic lesions, mainly in the anterior thalamic nuclei.
o Whether diencephalic and temporal lobe amnesias are distinct entities is still
not clear.
 NOTE: diencephalon is the region of the embryonic vertebrate neural tube that gives
rise to posterior forebrain structures including the thalamus, hypothalamus,
posterior portion of the pituitary gland, and pineal gland.
 Investigated episodic memory for faces using functional MRI (fMRI) in eight controls
and in a 34-yearold man with Wernicke–Korsakoff syndrome and diencephalic
lesions but without medial temporal lobe (MTL) involvement at MRI.
 All activation was greater in the right hemisphere. In controls both the encoding and
recognition tasks activated two hippocampal regions (anterior and posterior). The
anterior hippocampal region was more activated during recognition. Activation in
the prefrontal cortex was greater during recognition. In the subject with Wernicke–
 Korsakoff syndrome, fMRI did not show hippocampal activation during either
encoding or recognition. During recognition, although behavioural data showed
defective retrieval, the prefrontal regions were activated as in controls, except for
the ventrolateral prefrontal cortex.

Presentation
 1979 film made by Drs Ken Shaw and Allan Thomson
 In-patient treatment of chronic alcohol users.
o In this clip Dr Shaw talks about the symptoms, treatment and prevention of
Wernicke-Korsakoff syndrome.

Herpes Simplex Encephalitis

Overview
 Herpes causes:
o Inflammation & necrosis particularly in orbitofrontal & inferior temporal
regions
o Involves limbic structures – hippocampus, parahippocampal gyrus, amygdale
& overlying cortex, polar limbic cortex, cingulated gyrus and orbitofrontal
cortex.
 Patients present with:
o Personality changes
o Confusion
o Headache
o Fever
o Seizures
o Often amnesic
 Treatment:
o Antiviral agent = control illness
o Full recovery = possible
 BUT damage to brain structures often leaves person with SEVERE
anterograde and retrograde amnesia

Case Study
 e.g. D.R.B / Boswell
o Damasio et al.
o Damage to temporal lobes = accompanied by severe memory impairments
o Extensive anterograde amnesia
o Normal intelligence and language abilities
o Performs normally on implicit-memory tests
o BUT
 Have retrograde amnesia that = > severe than most temporal-lobe
patients
 Unable to retrieve information from any part of his life history.
 Damage to medial temporal cortex = contributes to
anterograde amnesia
 
Damage to lateral temporal cortex = contributes to retrograde
amnesia
o INSULA may be especially implicated in retrograde amnesia
 Accesses previously acquired memories
 Posner & Raichle research on insula and practiced vs novel verbal
tasks

Presentation
 The British musician Clive Wearing suffers from an acute and long-lasting case of
both anterograde amnesia and retrograde amnesia.
 Limbic System:
o The left hippocampus was completely destroyed
o Parts of the right hippocampus were destroyed
 Cerebral Cortex:
o Some of the left temporal lobe was damaged
o Some of the frontal lobe was destroyed (parts of the "inferior frontal lobe")
 In a diary provided by his caretakers, Clive was encouraged to record his thoughts.
Page after page is filled with entries similar to the following:

8:31 AM: Now I am really, completely awake.

9:06 AM: Now I am perfectly, overwhelmingly awake.

9:34 AM: Now I am superlatively, actually awake.

New Research
 NEW RESEARCH: human herpes virus-6 (HHV-6)
o Can also target limbic system
o Present with amnesic syndromes, confusion, sleep disorders, seizures
o Wainwright et al., 2001

Transient Global Amnesia

 TGA
 Middle age / older
 Distinctive type of amnesia
o Acute onset
o Short course
 Begins suddenly and typically resolves within a day
 8 hours or so
 Loss of old memories & inability to form new memories
 Severe impairment in learning and patchy loss of information learned prior to onset
= seen
 NOTE: some memory loss can be permanent (depending on severity of etiology)
 Patient often asks repetitive questions and may be aware of the memory deficit
 After resolution of amnesia: neuropsychological testing = normal except for amnesia
for episode
 ETIOLOGY:
 o Epilepsy
o Concussion
o Hypoglycemia (glucose in the brain = necessary for proper brain function
therefore reduced glucose means reduced function and possible cell death)
o Emotional stress (fugue)
o Occlusive cerebrovascular disease
 Ischemic stroke / embolism
o Migrainous vasospasm
o Vertebrobasilar dyscontrol
o Venous insufficiency

New Research
 Lesions in CA1 of the hippocampus in patients with TGA within the first 48 hours
 Sander & Sander et al, 2004.

Neuroimaging

Presentation

TBI and the Glasgow Coma Scale

 Severity of anterograde and retrograde amnesia correlates with severity of injury as
measured by the GCS / duration of unconsciousness.
 Retrograde amnesia typically improves along with improvement in anterograde
amnesia
o = evidence that a retrieval deficit = responsible for the portion of the
retrograde memory loss that recovers.
 Residual memory impairment = usually a feature of broader cognitive and
attentional impairment (but can = prominent in severe injuries)
 Pathological changes = variable and widespread
 Memory dysfunction may = caused by:
o Anterior temporal lobe contusions
o Temporal lobe white matter necrosis
o Diffuse axonal disruption

Special Memory Abilities

 Luria’s ‘The Mind of a Mnemonist’
o ‘S’
o Newspaper reporter
o Form explicit memories he couldn’t forget
o Memory skills = 3 processes:
 Visualise stimuli mentally
 Multisensory impressions of sensations (synaesthesia)
 ‘Pegboard’ technique
o ‘S’ = little aim in life
 o Dull & superficial
o Not able to reason / categorise / see order in things as other people
o < / X understanding of metaphors
 Interpreted everything literally and therefore couldn’t figure out what
they meant
 No understanding of poetry

o Explanation?
 Multiple memory systems?
 Memory systems compete with one another
 Result = ordinary memory is not excellent – too much
interference
 Competition of left hemisphere restrains right hemisphere
o Without this competition (either from surgery or insult)
the right hemisphere is able to ‘over-function’
 Jill Price
 Hyperthymestic syndrome
o Autobiographical memory = excessive
o Recall almost every day of their lives in near perfect detail
o Public events that hold some personal significance to them (flash bulb
memory)
o Memories = uncontrollable associations
 Encounter a date, they "see" a vivid depiction of that day in their
heads.
 Recollection occurs without hesitation or conscious effort.
o Approximately 20 cases reported
 Of the 4 most famous, 3 are men and all 3 are left-handed.
 OCD – and hyperthymesia
o hoarding. Hoards physical / material objects and memories.
 Depressed
 Weight Gain – can say exact dates that mother commented on her weight
 Never forgets an insult
 Individuals with hyperthymesia can

Neuroimaging
 Two abnormally large areas
o Caudate nuclei
 Typically used when forming automatic habits
o Part of temporal lobe
 Stores facts, dates, events

Temporal lobes & Hippocampus transfer information from STM to LTM. Therefore damage
in these areas = deficits in explicit memory.
Damage in thalamus and hypothalamus / diencephalon = Korsakoff’s syndrome.
Reference List

Caulo, M., van Hecke, J., Toma, L., Ferretti, A., Tartaro, A., Colosimo, C., et al. (2005).
Functional MRI study of diencephalic amnesia in Wernicke-Korsakoff syndrome. Brain , 128,
1584-1594.

Corkin, S., Amaral, D. G., Gonzalez, R. G., Johnson, K. A., & Hyman, B. T. (1997). H.M.'s
medial temporal lobe lesion: Findings from magnetic resonance imaging. Journal of
Neuroscience , 17 (10), 3964-3979.

Darby, D., & Walsh, K. (2005). Walsh's neuropsychology. A clinical approach (5th ed.).
Sydney: Elsevier.

Heilman, K. M., & Valenstein, E. (2012). Clinical neuropsychology (5th ed.). New York:
Oxford.

Kolb, B., & Whishaw, I. Q. (2009). Fundamentals of human neuropsychology (6th ed.). USA:
Worth.

Salat, D. H., van der Kouwe, A. J., Tuch, D. S., Quinn, B. T., Fischl, B., Dale, A. M., et al. (2006).
Neuroimaging H.M.: A 10 year follow-up examination. Hippocampus , 16, 936-945.

Sander, K., & Sander, D. (2005). New insights into transient global amnesia: Recent imaging
and clinical findings. Lancet Neurology , 4, 437-444.

Zillmer, E. A., Spiers, M. V., & Culbertson, W. C. (2008). Principles of neuropsychology (2nd
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