THEORIES OF

MEMORY
AND
ITS
NEUROPSYCHIAT
RIC
IMPLICATIONS
Presenters : Dr. Akhila I and Dr. Monika
Chairperson : Dr Aditya Somani
 OUTLINE
• Introduction
• Types of Memory
• Neurobiology of Memory
• Theories of Memory
• Memory and Neuropsychiatric Disorders
• Clinical implications
• Future directions
• Conclusion
 INTRODUCTION
• Memory - The process by which, what is experienced or learned is established as a
record in the CNS, where it persists with a variable degree of permanence, and
can be recalled or recollected from storage at will.

Processes involved in memory function-

• Encoding

• Storage

• Retrieval
 TYPES OF MEMORY
• Temporal: Short-term memory (STM)
Long-term memory (LTM)

• Form: Visual memory

Verbal memory
Non-verbal memory
• Process:
Declarative vs Non- declarative (Cohen and Squire, 1980)
Explicit vs implicit (Tulving, Schacter and Stark, 1982)
 TYPES OF MEMORY

Declarative Non-declarative
• Facts (semantic) Procedural memory
priming
• Events(episodic) Classical conditioning
Non-associative conditioning
 NEUROBIOLOGY OF MEMORY
• Neuroanatomy
• Neurophysiology
• Neuropathology and clinical implications
NEUROANATOMY OF DECLARATIVE MEMORY
1. Medial Temporal Lobe
Key structures within the MTL include:
• Hippocampus: dentate gyrus, CA1, CA2, CA3 fields, and the subiculum.
• Entorhinal, Perirhinal, and Parahippocampal Cortices

These adjacent cortical regions are involved in the processing and consolidation of
episodic memory.
They receive and integrate high-level information from various sensory modalities and
relay it to the hippocampus​.
• Eichenbaum et al., (2007) proposed a functional organization of memory’s medial

temporal lobe system: “Neocortical input regarding the object features (“what”)

converges in the PRC (perirhinal cortex) and lateral entorhinal area (LEA), whereas

details about the location (“where”) of objects converge in the PHC( parahippocampal)

and medial entorhinal area (MEA). These streams converge in the hippocampus, which

represents items in the context in which they were experienced.

2. Inferior temporal lobe
Involved in fact based memory

3. Diencephalon ( especially medial part)

• Mammillary Bodies: Part of the hypothalamus, these structures are involved in
recollective memory.
• Thalamus: dorsomedial and anterior nuclei
• Diencephalic amnesia: seen in conditions like Korsakoff syndrome, which often involves
both diencephalic and frontal lobe damage.
 4. Frontal Lobes

• The frontal lobes contribute to memory by aiding in the organization and retrieval
processes.

• Although limited frontal damage does not cause amnesia, it can lead to difficulties in
memory retrieval, particularly in tasks requiring strategic thinking and evaluation.
5. Amygdala

• involved in emotional memory.

• It helps enhance the recall of emotionally charged events and is critical for associative
learning of emotional stimuli.

• Abnormalities in the amygdala are linked to conditions like PTSD​

The ventral temporal cortex, including fusiform gyrus, is commonly engaged when
pictures of visual objects are presented, and the lateral temporal cortex including
superior temporal gyrus is typically engaged during the encoding of auditory
information.
NEUROANATOMY OF NON-DECLARATIVE
MEMORY

• Basal Ganglia and Neostriatum: Important

for habit learning and procedural memory.

• Cerebellum: Involved in conditioning of

skeletal musculature.

• Neocortex: Supports perceptual priming

and long-term storage of memories once
they have been consolidated.
 NEUROPHYSIOLOGY
Cellular mechanism :

Synaptic Plasticity
• Synaptic plasticity, the ability of synapses to strengthen or weaken over time.

• It is fundamental to memory formation.

• Two major forms of synaptic plasticity : long-term potentiation (LTP)

long-term depression (LTD).
• Long-Term Potentiation (LTP):

• This is a long-lasting increase in synaptic strength following high-frequency stimulation of

a synapse.

• LTP is most prominently observed in the hippocampus, particularly in the CA1 region, and
is crucial for the consolidation of new memories.

• It involves the activation of NMDA receptors, which allows calcium ions to enter the
neuron and trigger signaling pathways that enhance synaptic transmission​.
• Long-Term Depression (LTD):

• This is a long-lasting decrease in synaptic strength following low-frequency stimulation.

• LTD is important for synaptic pruning and the forgetting process, ensuring that only
relevant information is retained.

• It also involves NMDA receptors but leads to different intracellular pathways that reduce
synaptic efficacy​
 NEUROTRANSMITTERS
• Glutamate:

• The primary excitatory neurotransmitter in the brain, glutamate is essential for

synaptic plasticity.

• It activates NMDA and AMPA receptors, which are critical for LTP and LTD​​.
 NEUROTRANSMITTERS
• Dopamine:
• Involved in reward-based learning and memory.

• Dopamine modulates synaptic plasticity in the hippocampus and prefrontal

cortex, influencing the consolidation and retrieval of memories​​.
 NEUROTRANSMITTERS
• Acetylcholine:
• Important for attention and memory encoding.

• Acetylcholine enhances synaptic plasticity and modulates cortical and

hippocampal activity, facilitating learning and memory processes​​.
 Molecular mechanisms

• Calcium Signaling:

• Calcium ions play a pivotal role in both LTP and LTD by activating various enzymes
such as calmodulin-dependent kinase (CaMKII) and protein phosphatases. These
enzymes modify synaptic proteins, leading to changes in synaptic strength)​.
 Molecular mechanisms

• Second Messengers:

• Molecules like cyclic AMP (cAMP) and inositol triphosphate (IP3) act as second
messengers, propagating the signal from activated receptors to intracellular
targets. These messengers activate protein kinases and phosphatases that
modulate synaptic plasticity​.
 Molecular mechanisms

• Gene Expression and Protein Synthesis:

• Long-lasting changes in synaptic strength require new protein synthesis.

Transcription factors such as CREB (cAMP response element-binding protein) are
activated by calcium signaling and other pathways, leading to the expression of
genes involved in synaptic growth and modification​.
 FACTORS INFLUENCING MEMORY

INTRINSIC FACTORS-
• Age- Memory span increases between 16-26 years of age.
• Maturity
• Will to learn
• Interest and attention
• Intelligence
• Rest and sleep
• Medical disorders- hypothyroidism, ADHD,Alzheimer’s
• Emotional factors like anxiety stress and fear
 FACTORS INFLUENCING MEMORY
EXTERNAL FACTORS-

• Amount of material
• Distraction
• Effective learning
• Liking of the place/person teaching
• Monotonous nature of print material
METHODS OF MEMORIZING –

• Recitation method- learner reads content then recites and recall.

• Whole and part method- Memorizing from start to end in parts.

• Spaced and Unspaced methods- After memorizing a part , some rest is given
followed by continued memorization.
THEORIES OF MEMORY
• Information Processing Model-

• (Atkinson and Shiffrin 1968)

• This model is one of the most prominent and influential model.

Sensory memory/ sensory register-

• Starts with sensory input from environment.

• This input is held for a very brief time- several seconds at most- in a sensory register
associated with the sensory channel ( vision, hearing, touch ,and so forth), and it can
hold at least 11 to 16 items of information during the second before it lose the
information through decay.
Sensory memory/ sensory register-

• Visual sensory register- about 1 second ( Sperling, 1960)

• Auditory( hearing) register- longer upto about 4-5 seconds ( Darwin et al., 1972 )

• Most of the information briefly held in the sensory register is lost, however if we pay
attention to and recognize some of the information from sensory register, it is passed to
short term memory.
Short term memory-

• Holds information received from the sensory register upto about 30 seconds because it is
displaced by upcoming items of information.

• In addition to its transient quality it also has very limited storage capacity, estimated
about 7 items plus minus 2.

• storage capacity increased by chunking (Ericason and Chase , 1992)

Long term memory-

• May last for days, months, years or even lifetime.

• Storage capacity has no known limit.

• There is no true forgetting for LTM ,when we seem to forget, it is because it has not been
stored in organized fashion or because we are not searching for it in right part of the
memory storehouse.
Rehearsal

• Roughly refers to keeping information at the centre of attention

• Maintenance rehearsal(simply repeating the information)

• Elaborative rehearsal( degree to which incoming information is processed so that it

can be tied to , or integrated with existing memories)
• Levels of Processing model-
(Craig and Lockhart 1972, Craig and Tulving 1975)

• Incoming information can be worked on at different levels of analysis, the deeper the
analysis goes, the better the memory.

• First level is simple perception of input which gives us immediate awareness of

environment , at a somewhat deeper level , the structural features of input( for
example,what it sounds like) are analyzed and finally at the deepest level of processing the
meaning of the input is analyzed.
• Working Memory model- (Baddley and Hitch 1974)

• Is a combination of fields of attention, concentration and short-term memory

• Refers to ability to temporarily maintain and manipulate information that one needs to
keep in mind

• As it requires active and conscious participation, it is an explicit and declarative memory

system
• Phonologic information - keeping phone number “in your head”

• Spatial information - mentally following a route

• Executive system - allocates attentional resources

• Episodic buffer -integrate information from different resources , likely controlled by central
executive.
 MEMORY
AND
NEUROPSYCHIATRIC
DISORDERS
 SCHIZOPHRENIA
• Deficits in working memory and episodic memory - - - > disrupted plasticity in the
hippocampus and prefrontal cortex.

• Ability to form new memories is impaired - reflecting dysfunction in synaptic plasticity.

 SCHIZOPHRENIA
•Deficits in verbal episodic memory and in recollection vs. familiarity-based memory
have also been reported for individuals with schizophrenia.
• Verbal episodic memory deficits -
Decreased hippocampus recruitment during verbal episodic memory retrieval
Increased hippocampus baseline activity
 SCHIZOPHRENIA

• One hypothesis regarding the aetiology of the disease - N-methyl-d-aspartate

receptor hypofunction in individuals with schizophrenia which also makes it possible
that the episodic memory deficits in individuals with schizophrenia might be due to
alterations in the expression, subunit composition, subcellular location and/ or
sensitivity of N-methyl-d-aspartate receptors in the hippocampus and prefrontal
cortex.
 DEPRESSION

• Depression is associated with hippocampal atrophy and reduced neurogenesis.

Problems in memory consolidation

Retrieval
Formation of new memories
 DEPRESSION

• Patients with major depression can exhibit difficulties with explicit memory, especially
recollection memory.

• Difficulty in retrieving specific autobiographical memories.

• Intrusive negative autobiographical memories.

 DEPRESSION

• Chronic stress has numerous effects on plasticity-associated processes throughout the

brain in rodent models.

• In the hippocampus, chronic stress produces dendritic atrophy, especially in the CA3
region.
 DEPRESSION

• Prolonged pharmacological elevation of glucocorticoids, the principal adrenal stress

hormones can lead to cell death.

• Severe stress can also inhibit long-term potentiation (LTP) and enhance long-term
depression in the hippocampus.
 DEPRESSION

• A significant correlation between depression and episodic memory ability as assessed

by the auditory verbal learning test was found by re-analyzing data from a major
epidemiological research including over 3,000 elderly Dutch individuals.

• A linear relationship between depression symptoms and cognitive function was

found. Higher scores on a depression scale were associated with worse episodic
memory performance.
 BIPOLAR DISORDER
• Both manic and depressive episodes in bipolar disorder can disrupt cognitive
function, including memory.

• During manic phases, patients may exhibit heightened distractibility, while depressive
episodes can impair memory recall and attention.
POST-TRAUMATIC STRESS DISORDER (PTSD)

• Flashbacks and nightmares - one of the cardinal symptoms of PTSD.

• Pathologically enhanced memories contribute to acute stress disorder and PTSD, in

which excessively strong associations with traumatic events lead to their disruptive
recall and generalization.
POST-TRAUMATIC STRESS DISORDER (PTSD)

• Memory consolidation is disrupted, leading to difficulty distinguishing between past

and present experiences.

• The amygdala's reaction to fear-inducing stimuli is heightened in people with PTSD.

• PTSD patients also have dysregulation of the hippocampus and parts of the
prefrontal cortex, which typically regulate amygdala activity.
 ALZHEIMER’S DISEASE
• Major histopathological hallmarks of Alzheimer’s disease -

Loss of synapses

Extracellular amyloid plaque deposits

Intracellular neurofibrillary tangles

Amyloid plaque (top right), neurofibrillary tangles (bottom left) and
granulovacuolar degeneration (bottom center)
 ALZHEIMER’S DISEASE

• Pre-clinical phase of the disease mainly involves episodic memory.

• Cognitive impairment in the early stages of the disease mainly involves episodic
memory and spatial orientation.
 ALZHEIMER’S DISEASE

• Compared to individuals with the E3/4, E3/3, or E2/3 genotype with Alzheimer's
disease, those who had a higher frequency of the apolipoprotein E4 allele (E4/4
genotype) showed reduced volumes of the hippocampus and the amygdala very early
in the course of the disease.

• In a list learning test, individuals with the E4/4 genotype varied from E3/3, 3/2 patients
and also had the lowest results on delayed memory tests.
 ALZHEIMER’S DISEASE

• Degeneration of the amygdala is thought to begin very early in the course of

Alzheimer’s disease.

• At later stages of the disease, neurodegeneration in the frontal cortex, hippocampus

and basal forebrain might lead to the more global learning and memory impairment.
ormative models of Alzheimer’s disease progression shown at 4 Alzheimer Age with estimated time until/from diagnosis.
ottom to top rows show alteration of brain glucose metabolism, hippocampus atrophy, cortical thinning and onset of cognitive declin
Igor et al., 2021
EPILEPSY
 EPILEPSY
• Organic memory deficits take many forms depending on which regions or systems of
the brain are functionally compromised due to epilepsy.

• Restrictions involving uniquely specialized neocortical systems may produce highly

select deficits in familiar face recognition, recall of unique category exemplars (eg,
makes of automobiles), or familiar name recognition.

• Lateralized, material-specific memory deficits due to left or right temporal lobe

dysfunction - - - > inability to recall verbal vs visuospatial information, respectively.
 EPILEPSY

• In a community-based survey of more than 1000 people with epilepsy in the United
States, cognitive difficulties were ranked at the top of a list of patient complaints.

• Approximately half of all respondents rated school performance, memory,

concentration, mental and emotional well-being, and the ability to think clearly as
being adversely affected by seizures.
MMPs (Matrix Metalloproteases) in Neuropsychiatric Disorders
MMPs (Matrix Metalloproteases) in Neuropsychiatric Disorders
Schizophrenia

• Dysregulated MMP activity, particularly increased MMP-9 levels, has been linked to
cognitive deficits observed in schizophrenia, such as impairments in memory and
attention.
MMPs (Matrix Metalloproteases) in Neuropsychiatric Disorders
Depression

• Changes in MMP expression, especially MMP-9, have been associated with depressive
symptoms.

• Altered MMP activity may contribute to neuroinflammation and synaptic

dysfunction, both of which are implicated in the pathophysiology of depression.
MMPs (Matrix Metalloproteases) in Neuropsychiatric Disorders
Post-Traumatic Stress Disorder (PTSD)

• MMPs are involved in the brain’s response to stress.

• Altered MMP activity can contribute to the formation of maladaptive memories and
exacerbate PTSD symptoms by affecting synaptic remodeling in stress-related brain
regions, such as the hippocampus and amygdala.
MMPs (Matrix Metalloproteases) in Neuropsychiatric Disorders
Alzheimer's Disease

• MMPs are implicated in neurodegenerative processes.

• Dysregulation of MMPs can contribute to the breakdown of the blood-brain barrier

and the accumulation of amyloid plaques, which are characteristic of Alzheimer’s
disease.
CLINICAL IMPLICATIONS
 VAGUS NERVE STIMULATION

• Vagus Nerve Stimulation (VNS) involves the application of electrical impulses to the
vagus nerve, which influences brain areas involved in cognition and emotion regulation,
such as the prefrontal cortex and hippocampus.

• Studies indicate that VNS can enhance attention and working memory in people with
certain neuropsychiatric conditions, potentially by improving neural plasticity and
modulating brain circuits involved in cognition.
 VAGUS NERVE STIMULATION

• It can also help in improving attention and working memory in individuals with

neuropsychiatric disorders, particularly in conditions like depression and epilepsy.

 MEDICATIONS
• AEDs and psychotropic drugs are among the many medications that frequently cause

cognitive inefficiencies as a side effect.

•They can significantly impair attention and memory encoding; some, like long-term

phenytoin, cause structural harm that results in insidious and irreversible cognitive

impairment and thus should be cautiously used.

•They are especially detrimental when more than one AED is used for treatment of

epilepsy and in certain patient populations including older adults and children.
 GLUCOCORTICOIDS
• Glucocorticoids, including cortisol, affect hippocampal function, which is crucial for

memory formation and consolidation.

• Acute, short-term increases in cortisol can enhance memory, but chronic elevations

impair hippocampal neurogenesis and synaptic plasticity.

• Both the hippocampus and the prefrontal cortex contain high concentrations of

glucocorticoid receptors. Chronic activation of these receptors can result in structural

and functional changes in neurons - - - > memory deficits.

 GLUCOCORTICOIDS
• Chronic glucocorticoid exposure can also accelerate neurodegenerative processes,

contributing to diseases like Alzheimer’s disease.

• In depression, chronic stress leads to persistently high cortisol levels, contributing to

hippocampal atrophy.- - - > cognitive deficits such as memory problems.

 GLUCOCORTICOIDS
• Modulating glucocorticoid levels - a potential therapeutic avenue

• Strategies might include the use of corticosteroid antagonists or other drugs that

block glucocorticoid receptors.

• Psychological interventions such as cognitive-behavioral therapy (CBT) may help

reduce stress and lower glucocorticoid levels.

FUTURE DIRECTIONS
 Future Directions
• Computational models of memory that simulate neural processes in greater detail may

allow for better predictions of memory disorders.

• Artificial intelligence and machine learning techniques to analyze large-scale brain data

for insights into memory encoding and retrieval.

• Promote collaboration between neuroscience, psychology, genetics, and psychiatry to

 Future Directions
• Neuroimaging advancements (e.g., fMRI, PET, EEG) to track memory processes in

real-time and observe the dynamic interactions between brain regions during memory

encoding and recall can be promising.

• Early biomarkers and intervention strategies for neurodegenerative diseases that

impair memory could be explored.

 Future Directions
• Therapeutic approaches for treating trauma-related disorders, such as PTSD, through

targeting specific memory systems could be researched on.

• Ethical considerations surrounding interventions aimed at enhancing or altering

memory, such as neurostimulation or memory-modifying drugs can be an interesting

topic for discussion and debate.

 CONCLUSION

• Memory is a complex process involving encoding, storage, and retrieval of

information, and it relies on multiple brain systems.

• Declarative memory, crucial for facts and events, primarily involves the medial

temporal lobe structures, while non-declarative memory, related to skills and habits,

relies on systems such as the basal ganglia and cerebellum.

 CONCLUSION

• Synaptic plasticity, neurotransmitters like glutamate, dopamine, and acetylcholine,

and molecular mechanisms such as calcium signaling play critical roles in memory

formation and consolidation.

 CONCLUSION
• Various neuropsychiatric disorders, including schizophrenia, depression, bipolar

disorder, PTSD, and Alzheimer's disease, affect memory functioning, with disruptions in

brain areas like the hippocampus and prefrontal cortex.

• Memory impairments in these disorders often reflect changes in synaptic plasticity,

structural brain damage, and neurochemical imbalances, emphasizing the importance

of early diagnosis and intervention.

 CONCLUSION
• Treatments like vagus nerve stimulation, medications, and managing glucocorticoid

levels show potential in improving memory function in neuropsychiatric disorders.

 CONCLUSION
• Future research should focus on computational models, AI, neuroimaging, and

interdisciplinary collaboration to advance our understanding of memory processes and

therapeutic strategies.

• The ethical implications of enhancing or modifying memory through neurostimulation

or drugs will remain a key topic for future debate and research.
 REFERENCES
•Pittenger C. Disorders of memory and plasticity in psychiatric disease. (1958-5969 (Electronic)).

• Beroun A, Mitra S, Michaluk P, Pijet B, Stefaniuk M, Kaczmarek L. MMPs in learning and memory

and neuropsychiatric disorders. Cellular and Molecular Life Sciences. 2019;76:3207-28.

• Dere E, Pause BM, Pietrowsky R. Emotion and episodic memory in neuropsychiatric disorders.
Behavioural brain research. 2010;215(2):162-71.
 REFERENCES
•Bortz JJ, editor Neuropsychiatric and memory issues in epilepsy. Mayo Clinic Proceedings; 2003:

Elsevier.

• Alderson AL, Novack TA. Neurophysiological and clinical aspects of glucocorticoids and

memory: a review. Journal of clinical and experimental neuropsychology. 2002;24(3):335-55.

• Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. 10th

ed. Philadelphia: Wolters Kluwer; 2017.

• King L, Morgan D. Textbook of Psychology. 8th ed. New York: McGraw-Hill Education; 2017.