NEUROBIOLOGY OF

MEMORY – RECENT
DEVELOPMENTS

Presenter: Suchitra Banerjee

Chairperson: Dr. Shweta Rai
 CONTENTS
 Brief History

 Types of Memory

 Role of the Hippocampus in Memory

 Multiple Memory Systems

 STM and the Temporal and Frontal Lobes

 Current research focus

 Conclusion
LEARNING AND MEMORY
 Both these processes are fundamental to human experience.

 We can acquire new information about the world because the

experiences we have, modify our brain.

 And once learned we can hold the new knowledge in our

memories, often for a very long time, because aspects of these
modifications are retained in our brains.

 Memory is the process by which what is learned persists across

time. In this sense, learning and memory are inextricably
connected.
PSYCHOLOGICAL INVESTIGATIONS OF
MEMORY:

Memory involves three processes:

 the act of committing something to memory involves ‘encoding’

(input);
 holding the material in memory requires ‘storage’; and
 remembering (recalling) that material involves ‘retrieval’ (output)
MEMORY
 Memory can thus be defined as the process of storing and
retaining information for possible recall/use at some later date.

 Its fundamental importance for psychological functioning was

recognised more than a century ago by William James (1890).
BRIEF HISTORY

 PHILOSOPHY – Use of non-experimental methods

 PSYCHOLOGY – Empirical studies of the mind (Ebbinghaus, etc.)

 BIOLOGY – In the 1960s the revolution involved two major

components: Molecular component (cellular and molecular
mechanisms of memory storage) and the Systems component
(concerned with the neural systems of the brain important for
memory).

(Squire and Kandel, 1999)

 The molecular component (end of the nineteenth and the
beginning of the twentieth century) with the work of Gregor
Mendel, William Bateson, and Thomas Hunt Morgan. These three
showed that hereditary information is passed from parent to
offspring by means of genes. This framework would enable
scientists to study, on a molecular level, the internal representation
of complex cognitive processes in the mammalian brain.
 The second, or systems component of the biological revolution,
has been concerned with mapping elements of cognitive functions
onto specific brain areas.

 Thus, the biology of memory can now be studied at two different

levels, one aimed at nerve cells and the molecules within nerve
cells, and the other aimed at brain structures, circuitry, and
behaviour.
(Squire and Kandel, 1999)
WHERE ARE MEMORIES STORED…?

Since the beginning of the 19th century two contrasting ideas have
been advanced about the localization of mental functions:

 All mental functions can be localized to specific regions in the brain.

 Different mental functions are not localized but instead are global
properties that arise from the integrated activity of the entire brain.
TYPES OF MEMORY
TYPES OF MEMORY

The two broadest categories are: explicit and implicit memory

(Tulving, Schacter, and Stark, 1982).

 Explicit memory is the conscious, intentional recollection of

previous experiences.
 Implicit memory is an unconscious, nonintentional form of
memory.

 Explicit memory is further divided into Semantic memory and

Episodic memory.
 In the historical case of H.M., whose surgery involved removal of
most of the temporal lobe, it has been found that:

 His explicit memory is extremely impaired while his implicit

memory is largely intact
 This played an important role in the discovery that these two forms
of memory are distinct.
 This dissociation between explicit and implicit memory implies that
implicit memory is stored independently of the temporal lobe.
THE NEURAL BASIS OF EXPLICIT MEMORY

The key strutures involved in this circuit are:

 The Amygdala
 The Hippocampus
 The Rhinal cortex
 The Prefrontal cortex
 Nuclei in the Thalamus
 The Neocortex
 The brainstem systems, including acetylcholine, serotonin, and
noradrenaline systems

(Kolb and Whishaw, 2007)

ANATOMICAL AREAS OF EXPLICIT MEMORY

Basal
Forebrain Thalamus

Neocortex

Prefrontal
Cortex

Amygdala
Hippocampus
Rhinal Cortex
THE NEURAL BASIS OF IMPLICIT MEMORY

The key structures in this proposed circuit are :

 Neocortex
 Basal ganglia
 Premotor cortex
 Substantia nigra
 The neurotransmitter Dopamine

(Petri and Mishkin, 1994)

ANATOMICAL AREAS OF IMPLICIT MEMORY
Premotor Cortex

Basal Ganglia
Thalamus

Substantia
nigra
THE CASE OF H.M.
 H. M. had been experiencing generalized epileptic seizures that had
grown progressively greater in frequency and severity over the years.

 In 1953, a bilateral medial-temporal-lobectomy was performed on

him, in an attempt to stop the seizures.

 After the surgery, H. M. was almost completely cured of his seizures,

but experienced a severe anterograde amnesia that was lasting and
complete.

 H. M.’s remote memory was largely intact. His language

comprehension was normal, as was his social functioning and self-
care.
 It was initially believed that the loss of H.M.’s hippocampus,
specifically, was responsible for his memory deficits.

 However, H. M.’s surgery was not a selective lesion of the

hippocampus but a removal of most of the medial temporal lobe.

 Furthermore, Corkin et al. (1984) found that his hippocampal lesion

was not complete. In fact, about 40% of his hippocampus was
spared.

 This led researchers to extend their focus of study to other areas

within the temporal lobes.
CASE STUDIES OF HIPPOCAMPAL
FUNCTION

A number of research groups have described other amnesic

patients whose symptoms are somewhat like those of H. M.
1.

 Squire at al. (1982) report the results of various case studies that
suggest that the retrograde amnesia of most patients is time
dependent and that larger lesions produce retrograde amnesia that
goes back farther in time.

 They also suggest that memories formed early in life may be spared by
hippocampal lesions but may be lost if the lesions extend into
structures surrounding the hippocampus.
 Patient R. B. whose lesions are limited to a specific region of the
hippocampus, has a limited retrograde amnesia covering perhaps 1
or 2 years.
 Patient L. M. has more extensive hippocampal damage, and his
retrograde amnesia covers from 15 to 25 years.
 Patient E. P., with complete hippocampal damage plus some
damage to surrounding structures, has retrograde amnesia covering
from 40 to 50 years.
 All of these patients have access to memories from early life, as
does H. M.
 Squire et al. (1982) concluded that the hippocampus itself
is important for memory for a relatively short period of time
after learning and that adjacent cortexes are responsible for
memory that extends farther back in time.

 Additionally, they proposed that the earliest memories can

be accessed directly in the neocortex and so survive
temporal-lobe lesions.
2.
 Cipolottie et al. (2001) report that a patient, V. C., whose
hippocampus was entirely removed, though surrounding structures
were undamaged, has retrograde amnesia that covers his entire life
before the lesion was incurred.

 His performance in a number of tests of memory was studied. It

was found that he was almost completely unable to respond to any
autobiographical questions for any time period. His performance
was better on factual questions. But even that ability was impaired
relative to that of control subjects.
 In short, V. C.’s case suggests that the complete loss of the
hippocampus results in complete retrograde and anterograde
amnesia for explicit information for all age periods of life.
3.

 Some researchers hypothesized that, if hippocampal damage

occurred in infancy, the persons would be described not as amnesic
but as severely retarded.

 That is, they would be unable to speak, being unable to learn new
words; be unable to socialize, being unable to recognize other people;
and be unable to develop problem-solving abilities, being unable to
remember solutions to problems.
 Vargha-Khadem et al. (1997) report on three cases in which
hippocampal damage was incurred early in life: for one subject just
after birth, for another at 4 years of age, and for the third at 9 years
of age.

 None of these people can reliably find his or her way in familiar
surroundings, or remember where objects are usually located.
None is well oriented in date and time, and all must frequently be
reminded of regularly scheduled appointments and events.
THE ROLE OF THE HIPPOCAMPUS IN MEMORY
There are at least four theories of the role of the hippocampus in
memory:

1.
 The first theory describes the hippocampus as a storage site for
memory.

 However , based on this theory, it is difficult to reconcile the

time-dependent effects of retrograde amnesia with a storage
theory. If memories were stored there, presumably remote
memories should be as likely to be lost as recent memories.
2.

 The role of the hippocampus is to consolidate new memories.

According to this notion, memories are held in the hippocampus
for a period of time, undergoing consolidation before transfer to
the neocortex.

 This theory explains why older memories tend to be preserved

in cases of hippocampal damage (they have been transferred
elsewhere for storage), whereas more-recent memories are likely
to be lost (they are still in the hippocampus).
 A difficulty with this theory is that retrograde amnesia sometimes
extends back for decades, which, according to the theory, means
that the hippocampus would have to hold the memories for storage
for an exceedingly long time and the consolidation process would
have to be exceedingly slow.
3.
 The hippocampus plays the role of a librarian for
memories. It knows how and where memories are stored
elsewhere in the brain and can retrieve them when
required.

 A problem with this theory is that it does not explain why

explicit memories cannot be retrieved, whereas implicit
memories can be retrieved.
4.
 The hippocampus is responsible for tagging memories with
respect to context—that is, with the location and time of
their occurrence.

 According to this notion, the hippocampus has a special

role in storing memories that are meaningful only if their
context also is recalled.

 Episodic, or autobiographical, memory is especially context

dependent.
MULTIPLE MEMORY SYSTEMS
MULTIPLE MEMORY SYSTEMS

 The Temporal Cortex

 The Amygdala

 The Perirhinal Cortex

 The Diencephalon

 Ascending Systems
THE TEMPORAL CORTEX
 The results of several studies suggest that there are significant
differences in the memory impairments stemming from damage to
the left and right hemispheres, and that the temporal neocortex
makes a significant contribution to these functional impairments.
 After right-temporal-lobe removal, patients are impaired on face-
recognition, spatial-position, and maze-learning tests.

 Left-temporal-lobe lesions are followed by functional

impairments in the recall of word lists, recall of consonant
trigrams, and nonspatial associations.

(Milner et al., 1970)

 Milner et al. (1968) studied the effects of damage to the
neocortex of the temporal lobe of each hemisphere on several
memory tasks.

 They conclude that lesions of the right temporal lobe result in

impaired memory of nonverbal material. Lesions of the left
temporal lobe, on the other hand, produce deficits on verbal tests
such as the recall of previously presented stories and word pairs, as
well as the recognition of words or numbers.
 The results of these studies indicate not only that the medial
temporal lobe is associated with severe deficits of memory but also
that the adjacent temporal neocortex also is associated with
memory disturbance.
THE AMYGDALA
 The amygdala is composed of a number of separate nuclei, each
of which probably has specific functions, and so it is not entirely
correct to consider them together.

 These nuclei have been associated with emotional, olfactory,

and visceral events.
 Sarter and Markowitsch (1985), in reviewing the literature on
studies of animals and humans, suggest that the amygdala has a
role in memory processes associated with events that have
emotional significance in a subject’s life.
THE PERIRHINAL CORTEX
 These regions project to the hippocampus, and so conventional
surgeries and many forms of brain injury that affect the
hippocampus may also damage the rhinal cortex or the pathways
from the rhinal cortex to the hippocampus.

 In consequence, discriminating between deficits that stem from

rhinal-cortex damage and deficits that result from disconnection of
the hippocampus or damage to it can be difficult.
 Squire et al. (1998) found that the perirhinal cortex plays an
important role in visual recognition memory.
THE DIENCEPHALON

Diencephalon
 Long-term alcoholism, especially when accompanied by thiamine
deficiency, has long been known to produce defects of memory.
The diencephalon has been implicated in producing these defects
(Korsakoff’s Syndrome).

 The diencephalon plays a critical role the recall of knowledge

about facts and events (Gold, 2006).
ASCENDING SYSTEMS

 The loss of cholinergic cells projecting to areas in the cortex, has

been proposed to be responsible for, the amnesia displayed by
patients with Alzheimer’s disease.

 There are also serotonergic cells in the midbrain, projecting to

the limbic system and cortex. Profound amnesia can be produced if
the serotonergic cells in the midbrain and the cholinergic cells in
the basal forebrain are damaged together.
 Cell loss in more than one of the cholinergic, serotonergic, or
noradrenergic systems, could be a cause of amnesia even when
cortical or limbic structures are intact.
SHORT TERM MEMORY
SHORT TERM MEMORY (STM) AND THE
TEMPORAL LOBES

 Warrington et al. (1978) found that patients who received a left

posterior temporal lesion experienced an almost total inability to
repeat verbal stimuli such as letters, words, and sentences.

 In contrast, their long-term recall of paired-associates words or

short stories was nearly normal.

 On the other hand, patients who display anterograde amnesia for

explicit information do not show impairments in short-term
memory.
SHORT TERM MEMORY (STM) AND THE
FRONTAL LOBES

 Damage to the frontal cortex is recognized to be the cause of

many impairments of STM for tasks in which subjects must
remember the temporary location of stimuli.

 Prisko (1963), using a “compound stimulus” task, found that

patients with unilateral frontal-lobe removals showed a marked
impairment in matching the first and second items of each pair.
MORE RECENT FINDINGS…
SEX INFLUENCES ON THE NEUROBIOLOGY OF
MEMORY…
 Neurobiological sex differences in brain regions
implicated in memory exist at multiple levels of analysis,
from gross neuroanatomy to circuit properties to the
molecular mechanisms underlying them.
NEUROANATOMY

 Multiple studies report larger whole brain volumes in men than

women (Allen et al., 2002; Cosgrove et al., 2007), as well as a larger
percentage of brain volume in CSF (Agartz et al., 1992) and a higher
ratio of white to gray matter (Gur et al., 1999).

 Other studies have found that relative to brain size, women have
larger volume in the hippocampus (Filipek et al., 1994).

 In contrast, the relative volume of the amygdala (Giedd et al.,

1996) is consistently larger in men.
NEUROCHEMISTRY

 The largest sex difference in neurochemistry can be found in

circulating sex hormone levels.
NEUROCHEMISTRY…
 The pharmacological suppression of ovarian hormone release
can affect verbal memory (Sherwin and Tulandi, 1996), and
working memory (Grigorova et al., 2006) in women, and these
deficits can be reversed with hormone replacement.

 In older men, testosterone replacement has been shown to

modulate spatial, verbal, and working memory, suggesting that
the hormone plays a role in maintaining these abilities (Martin et
al., 2008).
SPATIAL MEMORY

 Studies of spatial working memory have found significantly more

activation in parietal areas in men; however in women, these
studies indicate significant activity in frontal regions (Hugdahl et al.,
2006).

 This has been interpreted as evidence of a different cognitive

strategy used by men and women in solving problems of spatial
working memory. Research data favours men on this ability.
SPATIAL MEMORY…

 It has been suggested that these superior frontal regions may

indicate conscious recall (Gizewski et al. 2006) or internal
verbalization, suggesting a more effortful, ‘‘serial’’ approach
compared to the ‘‘gestalt’’ approach employed by men (Hugdahl et
al. 2006).
NAVIGATION

 Large male advantages have been observed on tests of spatial

navigation, in which participants are asked to reconstruct a path
through a map (Postma et al., 2004), a virtual environment (Iaria et
al., 2003), or real world space (Saucier et al., 2002).

 Many studies of navigation have suggested that men tend to

favour a more allocentric strategy, while women are more
frequently egocentric navigators (Maguire et al., 1999).
OBJECT LOCATION

 Significant female advantages have been observed in studies of

object location memory (Silverman et al., 2007). Women reported
using a verbal strategy significantly more often than did men to
solve the task.

 Further, fMRI showed more left-lateralized activity in women,

consistent with verbal activity, and men showed right-lateralized
activity (Frings et al., 2006).
VERBAL MEMORY

 Substantial evidence indicates a female advantage on tests of

verbal memory, as measured by both word recall and fluency. This
advantage has been observed throughout the life span.
VERBAL MEMORY…

 It has been suggested that language abilities are distributed

across the brain differently in men and women, specifically
indicating that language processing is more bilateral in women, but
more left lateralized in men (Kimura, 1983).

 Following left temporal lobectomy, women’s verbal memory is

spared, whereas verbal memory in men declines significantly
(McGlone, 1978).
EPISODIC AND AUTOBIOGRAPHICAL MEMORY

 Numerous studies of recall of life events reveal a female

advantage in autobiographical memory.

 Compared to men, women’s recall is more accurate (Bloise and

Johnson, 2007) and more specifically detailed (Pillemer et al.,
2003).
EPISODIC AND AUTOBIOGRAPHICAL
MEMORY…

 When not specifically prompted, women’s accounts are longer

than are men’s (Friedman and Pines, 1991).

 They recall their first event more quickly, recall more life events,
and the first items recalled come significantly earlier in life (Davis,
1999). Women have also been shown to date events in their lives
more accurately (Skowronski et al., 1991).
THE AFFECTIVE INTENSITY HYPOTHESIS

 It has been frequently suggested that women’s autobiographical

advantage is attributable to an enhancement of emotional recall.
Women use significantly more emotional terms, and describe
internal states significantly more, when producing autobiographical
accounts (Bauer et al., 2003).
THE AFFECTIVE INTENSITY HYPOTHESIS…

 In one study examining both neutral and emotional memory, it

was found that although women recalled significantly more
emotional information than did men, they showed no advantage
for neutral memory (Davis, 1999).
THE NEUROSCIENCE OF REMOTE
MEMORIES…
 The available evidence describes different profiles of retrograde
amnesia for factual information (Cipolotti et al., 2001), as well as
recall of personal episodes (Bayley et al., 2005), based on the
extent of the lesions.

 Neuroimaging studies have generally reported greater activity in

the right hippocampus or right entorhinal cortex for recently
learned material than for more remotely learned material. (Douville
K, et al., 2005)
….

 Most studies of recent and remote autobiographical memory

have found that when volunteers recalled recent memories, activity
was greater in the hippocampal region bilaterally (Piefke et al.,
2003), or in the right hippocampus (Maguire and Frith, 2003) than
when the volunteers recalled remote memories.
THE PARIETAL LOBE’S CONTRIBUTION TO
MEMORY…
 Recent reviews have reflected that (Rugg, et al., 2002; Wagner, et
al., 2005), several studies in the mid-1990s reported greater
activity in lateral and medial parietal cortex during blocks of
memory trials than during other conditions.

 A further finding has been greater activation in parietal cortex

when recognition is accompanied by retrieval of details concerning
the context in which old items were previously encountered,
suggesting that the region may be particularly important for
conscious recollection (Henson, et al., 1999).
REM SLEEP AND THE CONSOLIDATION OF
HUMAN EMOTIONAL MEMORY…
 In a study by Nishida et al., (2008) it was explored whether rapid
eye movement (REM) sleep, and aspects of its unique
neurophysiology, underlie the influence of emotion on memory.

 Subjects that napped showed a consolidation benefit for

emotional but not neutral memories. The No-Nap control group
showed no evidence of a consolidation benefit for either memory
type.

 Further, within the Nap group, the extent of emotional memory

facilitation was significantly correlated with the amount of REM
sleep.
RETROGRADE AMNESIA IN PATIENTS WITH
HIPPOCAMPAL, MEDIAL TEMPORAL, TEMPORAL
LOBE OR FRONTAL PATHOLOGY..
 Bright et al., (2006) made a comparison between medial
temporal, medial plus lateral temporal, and frontal lesion patients
on a new autobiographical memory task and measures of the more
semantic aspects of memory.

 Only those patients with damage extending beyond the medial

temporal cortex into the lateral temporal regions showed severe
impairment on free recall remote memory tasks.
….

 Based on the findings it was suggested that a widely distributed

network of regions underlies the retrieval of past memories, and
that the extent of lateral temporal damage appears to be critical to
the emergence of a severe remote memory impairment.
CONCLUSION
The most important areas of the brain involved in the neurobiology of
memory are:

 the amygdala & the hippocampus

 the rhinal cortex, the prefrontal cortex, & the neocortex
 the thalamus
 the basal ganglia
 the substantia nigra
 the diencephalon
 the acetylcholine, serotonin, and noradrenaline systems.

 The frontal lobe has also been found to play a role in the process of
memory (STM).
 Present literature focuses on :

 Sex influences on the neurobiology of memory

 The neuroscience of remote memory
 The parietal lobe’s contribution to human memory
 REM sleep and the consolidation of human emotional memory
 Retrograde amnesia in patients with hippocampal, medial
temporal, temporal lobe, or frontal pathology.
THANK YOU…