Chapter 5 Notes: Learning, Memory and Amnesia
Learning and Memory: Overview
Learning – deals with how experience changes the brain.
Memory – deals with how these changes are stored and subsequently reactivated.
Objective Tests of Memory
Digit Span +1 Test: classic test of verbal long-term memory where the patient should recite the series of digits first spoken by the neuropsychologist or doctor.
Block-tapping memory-span test: an array of 9 blocks spread out on a board in front of the patient; the patient watches the neuropsychologist touch a sequence and then repeats the same sequence by tapping.
Objective Tests of Memory (cont.)
Mirror-Drawing Test – used for anterograde amnesia. Patient is asked to draw a line within the boundaries of a star-shaped target by watching his hand in a mirror. Trace the star 10 times on each of 3 consecutive days.
Rotary-Pursuit Test – the subject tries to keep the tip of a stylus in contact with a target that rotates on a revolving turntable.
Incomplete-Pictures Test – a nonsensorimotor memory test with five sets of fragmented drawings. Each set contains drawings of the same 20 objects, but sets differ in sketchiness (Set 1 most fragmented to Set 5 complete). The subject identifies the 20 objects from the sketchiest set (Set 1); those not recognized are shown in Set 2, and so on until all 20 are identified.
Pavlovian Conditioning – formation of an association between thoughts, feelings, or behaviors and an event or emotional state (skill learning).
Henry Gustav Molaison (HM) – the world’s most important brain science patient; studied for over 50 years (ages 27 to 82).
HM suffered profound amnesia and could not remember the researchers’ names or experiments.
As a child, HM had epilepsy (likely from a head injury at age 7); seizures worsened after age 16; by 27 he was unable to work.
In 1953, neurosurgeon Dr. William Beecher Scoville performed bilateral medial temporal lobe resection (removal of portions of the temporal lobes, including parts of the hippocampus and amygdala, from both sides).
After surgery, HM woke with severe amnesia. He could remember his childhood and the stock market crash of 1929, but could not remember events from the years immediately before or after surgery (up to about 11 years prior in some cases).
HM also had severe anterograde amnesia – difficulty forming new memories.
He described his condition as being “like waking from a dream…every day is alone in itself.”
HM: Amnesic Effects of Bilateral Medial Temporal Lobectomy
HM’s seizures were dramatically reduced but so was his long-term memory.
Mild retrograde amnesia and severe anterograde amnesia.
HM’s amnesia was global across modalities (not limited to one sensory system).
Anterograde Amnesia: Discovery of Unconscious Memories
HM’s digit span and block-tapping tests showed that his short-term memory systems were intact but that his ability to form new long-term memories was profoundly impaired.
HM improves with practice on sensorimotor tasks (mirror-drawing, rotary-pursuit) and on a nonsensorimotor task (incomplete-pictures) without recalling prior practice sessions.
HM readily learns responses through classical (Pavlovian) conditioning but has no memory of the conditioning trials themselves.
This demonstrates that memory for performance can improve without conscious recollection (explicit memory) and that memory systems can operate unconsciously (implicit memory).
Explicit vs. Implicit Memory
Explicit memories: conscious memories (declarative).
Implicit memories: unconscious memories (procedural memory).
Repetition priming tests (e.g., identifying word fragments) show implicit memory benefits from prior exposure even when conscious recall is absent.
Three Major Scientific Contributions of HM’s Case
Medial temporal lobes are involved in memory.
STM, remote memory, and LTM are distinct; HM’s case shows a dissociation, with a problem in moving memories from STM to LTM (memory consolidation).
Memory may exist but not be recalled; explicit vs implicit memory; motor learning can be retained even when explicit memory is impaired.
A form of memory (motor learning) must be distinct from the system that records new facts and experiences and may be located in brain regions unaffected by HM’s operation.
There are multiple memory systems located in different brain areas; damage to one region does not eliminate all forms of memory.
Medial Temporal Lobe Amnesia
Characteristics: difficulty forming explicit long-term memories while retaining the ability to form implicit long-term memories.
Not all patients with medial temporal lobe amnesia are unable to form new explicit long-term memories; semantic memory (general facts) may function normally while episodic memory (events) does not.
Medial temporal lobe amnesia may also involve difficulty imagining future events.
Semantic vs. Episodic Memories: explicit long-term memories subdivide into semantic (facts) and episodic (life events).
Cerebral Ischemia – interruption of blood supply to the brain.
Patients with cerebral ischemia often experience medial temporal lobe amnesia.
R.B.’s case suggested that hippocampal damage alone can produce amnesia; HM’s damage and amnesia were more severe.
Korsakoff’s syndrome – memory disorder common in heavy alcohol use or thiamine deficiency; characterized by amnesia, confusion, personality changes, and physical problems; damage often in medial thalamus and medial hypothalamus; advanced stages include sensory/motor problems and higher mortality risks.
Korsakoff’s syndrome amnesia resembles medial temporal lobe amnesia in some respects.
Alzheimer’s disease (AD) – another major cause of amnesia; memory decline often begins mildly and is progressive and terminal.
Damage in AD is associated with decreased acetylcholine due to basal forebrain degeneration.
Retrograde Amnesia and Memory Consolidation
Concussions disrupt the consolidation (storage) of recent memories.
Hebb’s theory: memories are stored in the short term by neural activity; interference with this activity prevents consolidation.
Examples: concussions, ECS (electroconvulsive shock).
Posttraumatic amnesia: retrograde amnesia caused by concussions; severity correlates with duration of coma in non-penetrating head injuries.
Periods of anterograde amnesia reflect temporary failure of memory consolidation.
Reconsolidation: each time a memory is retrieved from LTM, it is temporarily held in STM and is susceptible to disruption until reconsolidated.
Where Are Memories Stored?
Memories are stored diffusely across brain structures, so destruction of a single structure does not erase all memories.
Some brain structures have particular roles in memory storage:
Hippocampus – spatial location
Perirhinal cortex – object recognition
Medial dorsal nucleus – Korsakoff’s symptoms
Basal forebrain – Alzheimer’s symptoms
Inferotemporal cortex – visual perception of objects
Additional structures:
Amygdala – emotional learning; changes in activity during visual recall; lesions disrupt fear learning.
Prefrontal cortex – temporal order of events and working memory; tasks requiring sequences of responses.
Cerebellum – stores memories of sensorimotor skills.
Striatum – habit formation.
Biopsychology of Memory and You
Infantile amnesia – the common inability to remember events from early childhood.
Nootropics – substances claimed to affect memory and cognitive function (contextual mention of memory-enhancing agents).
Some Concepts about Memory You Should Know (three stages of memory):
The Three Stages of Memory
Sensory register/buffer – stores information for about a second or so.
Short-term memory (STM) – lasts about 15-30\text{ seconds}; also called working memory because we can consciously use that information.
Long-term memory (LTM) – lasts a lifetime.
Rehearsal, Primacy, and Recency
Rehearsal (conscious repetition) helps retain information in STM and may aid consolidation into LTM.
Primacy effect – improved recall of the beginning of a list; reflects greater consolidation into LTM.
Recency effect – improved recall of the end of a list; reflects items still present in STM.
Forgetting: information may disappear from LTM, but most forgetting is due to retrieval difficulties.
Cued Recall – provided with hints about the desired information.
Free Recall – must retrieve items without cues.
Proactive interference – prior memories hinder learning new material.
Retroactive interference – learning new information makes it harder to recall old memories.
Retrieved memories can be distorted; Misinformation effect – memory traces can be altered and reconsolidated in distorted form.
Flashbulb memories – highly detailed memories of momentous events that can become distorted when recounted to others.
Notes on Practical and Real-World Relevance
The HM case demonstrates the brain’s modular memory organization and the existence of explicit vs. implicit learning systems.
Memory consolidation processes have practical implications for head injuries, anesthesia, and therapeutic interventions.
Understanding memory storage locations helps explain differential effects of brain injuries and neurodegenerative diseases on various memory types.
The distinction between semantic and episodic memory has implications for education, aging, and conditions like Alzheimer’s disease.
Ethical considerations arise in early neurosurgical interventions when patients have severe incapacitation and the long-term memory consequences are profound; informed consent and weighing risks vs. benefits are central.
Concepts like reconsolidation highlight why memories can change over time and under suggestion, important in legal, educational, and clinical contexts.
Learning and Memory: Overview
Learning – The process by which experience leads to relatively permanent changes in our brain, affecting behavior, knowledge, and skills. This often involves changes at the synaptic level (synaptic plasticity).
Memory – The mechanisms by which these learned changes are encoded, stored, and then retrieved or reactivated when needed, allowing us to recall past experiences, information, and skills.
Objective Tests of Memory
Digit Span +1 Test: A classic neuropsychological test used to assess verbal long-term memory and the capacity of short-term memory. The patient is asked to repeat a series of digits spoken by the neuropsychologist. For the "+1" variation, the series length is gradually increased until the patient can no longer repeat it correctly, often in reverse order or one digit longer than previously mastered. This tests the ability to hold and manipulate information actively.
Block-tapping memory-span test: This test measures spatial short-term memory. An array of 9 blocks is spread out on a board. The patient observes the neuropsychologist tap a sequence of blocks and then attempts to replicate the exact sequence by tapping the blocks themselves. Similar to the digit span test, the sequence length is progressively increased to determine the patient's spatial memory span. Patients like HM showed normal performance on this, indicating intact short-term memory systems.
Objective Tests of Memory (cont.)
Mirror-Drawing Test – This test is primarily used to assess sensorimotor skill learning and is particularly sensitive for detecting implicit memory abilities in patients with anterograde amnesia. The patient is instructed to draw a line within the boundaries of a star-shaped target while only observing their hand's reflection in a mirror. The task is typically performed multiple times (e.g., 10 trials on each of 3 consecutive days), and improvement in accuracy and speed over these trials indicates motor skill learning, even if the patient has no conscious recall of previous practice sessions.
Rotary-Pursuit Test – Another sensorimotor skill learning task where the subject attempts to keep the tip of a stylus in continuous contact with a small target that rotates on a revolving turntable. Like the mirror-drawing test, improvement in performance over trials, even without explicit memory of prior practice, demonstrates implicit motor learning.
Incomplete-Pictures Test – A nonsensorimotor memory test specifically designed to assess implicit perceptual memory. It involves five sets of fragmented line drawings. Each set contains drawings of the same 20 objects, but the sets vary in their level of completeness, from highly fragmented (Set 1) to complete (Set 5). The subject is asked to identify the objects starting with the sketchiest set; any unidentified objects are then shown in the next, less fragmented set, and so on. A reduction in the number of fragments needed to identify an object on subsequent exposures indicates implicit memory for the perceptual form of the objects.
Pavlovian Conditioning – Also known as classical conditioning, this involves the formation of an association between a neutral stimulus and a stimulus that naturally elicits a response. It is a fundamental process of associative learning and a form of implicit memory (skill learning). For example, if a tone (neutral stimulus) is repeatedly paired with an air puff to the eye (eliciting a blink), eventually the tone alone will cause the subject to blink.
Henry Gustav Molaison (HM) – Universally recognized as the most influential patient in the history of brain science and memory research. His case was studied extensively for over 50 years, from the age of 27 until his death at age 82.
HM suffered from profound amnesia, rendering him unable to remember the names of researchers, the details of experiments he had just participated in, or any new events after his surgery.
As a child, HM developed severe epilepsy, which was likely caused by a head injury sustained at age 7. His seizures became progressively worse after age 16, escalating to the point where he was completely incapacitated and unable to work by age 27.
In 1953, neurosurgeon Dr. William Beecher Scoville performed a highly experimental bilateral medial temporal lobe resection. This radical surgical procedure involved the removal of significant portions of HM's medial temporal lobes from both hemispheres, including about two-thirds of the hippocampus, portions of the amygdala, and adjacent parahippocampal gyrus.
Following the surgery, HM woke up with a dramatically reduced seizure frequency, but also suffered from severe and pervasive amnesia. While he retained memories from his childhood and long-past events (like the stock market crash of 1929), he could not remember events from the years immediately preceding the surgery (retrograde amnesia, extending back 1-11 years in some reports) or form any new memories (severe anterograde amnesia).
HM vividly described his condition as being “like waking from a dream…every day is alone in itself,” highlighting his inability to integrate new experiences into a coherent narrative of his life.
HM: Amnesic Effects of Bilateral Medial Temporal Lobectomy
HM’s severe debilitating seizures were indeed dramatically reduced after the bilateral medial temporal lobectomy, achieving the primary goal of the surgery. However, this came at the profound cost of his long-term memory capacity.
He exhibited mild retrograde amnesia, meaning he had difficulty recalling some events that occurred in the years leading up to his surgery, but older, remote memories (from childhood) remained largely intact.
Critically, he developed severe anterograde amnesia, an incapacitating inability to form any new explicit long-term memories. This meant he could not learn new facts, remember new faces, or recall daily occurrences.
A significant characteristic of HM’s amnesia was its global nature, meaning it was not confined to a specific sensory modality (e.g., only visual or only auditory memory loss) but affected all forms of new explicit learning, regardless of the information's sensory input.
Anterograde Amnesia: Discovery of Unconscious Memories
Despite his profound anterograde amnesia, HM’s performance on tests like the digit span and block-tapping tasks demonstrated that his short-term memory (STM) systems were largely intact. He could hold immediate information for brief periods, but this information could not be transferred into long-term storage.
Crucially, HM showed significant improvement with practice on sensorimotor tasks such as the mirror-drawing test and the rotary-pursuit test, and also on a nonsensorimotor task like the incomplete-pictures test. Yet, remarkably, he had absolutely no conscious recollection of having practiced these tasks before; each session felt entirely new to him, creating a profound dissociation.
Similarly, HM readily learned new responses through classical (Pavlovian) conditioning, demonstrating the formation of new associations at an unconscious level. However, when asked, he had no memory whatsoever of the conditioning trials themselves, nor could he explain why he was responding in a certain way.
This collection of observations from HM’s case was groundbreaking. It unequivocally demonstrated that memory for performance and skills (procedural knowledge) can improve without any accompanying conscious recollection (explicit memory). This crucial finding led to the understanding that memory systems can operate unconsciously, giving rise to the concepts of implicit memory and the existence of multiple, distinct memory systems within the brain.
Explicit vs. Implicit Memory
Explicit memories: These are conscious, intentional, and retrievable memories that can be verbally declared. They are often referred to as declarative memories because we can consciously recall and state the information. Examples include remembering a specific event (e.g., your last birthday party) or recalling learned facts (e.g., the capital of France).
Implicit memories: These are unconscious, non-intentional memories that are expressed through performance rather than conscious recall. Often referred to as procedural memories or non-declarative memories, they influence our behavior without our awareness. Examples include riding a bicycle, typing on a keyboard, or tying a shoelace. Skill learning, priming, and classical conditioning are all forms of implicit memory.
Repetition priming tests (e.g., the incomplete-pictures test or tasks requiring identification of word fragments) provide strong evidence for implicit memory. These tests show that prior exposure to a stimulus (e.g., seeing a truncated word) significantly benefits subsequent performance (e.g., easier identification of the fragmented word), even when the individual has no conscious recall of the initial exposure.
Three Major Scientific Contributions of HM’s Case
HM’s case revolutionized our understanding of memory and provided empirical evidence for concepts previously only theorized:
The medial temporal lobes (including the hippocampus) are critically involved in the formation of new long-term memories. Before HM, the exact role of these structures in memory was poorly understood. His specific and severe deficits following the targeted lesion clearly implicated these regions as essential for memory consolidation.
Short-term memory (STM), remote memory (very old LTM), and the process of forming new long-term memory (LTM) are distinct and operate via separable neural processes. HM’s intact STM, preserved remote LTM, but severely impaired ability to transfer new information from STM to LTM (a process known as memory consolidation) demonstrated a clear dissociation between these memory stages. This challenged earlier unitary views of memory.
Memory can exist and be expressed even without conscious recollection; thus, there are distinct explicit and implicit memory systems. HM's ability to learn and improve on motor skills and perceptual tasks (like mirror-drawing or the incomplete-pictures test) without consciously remembering any prior practice sessions provided definitive evidence for the existence of implicit (unconscious/procedural) memory, separate from explicit (conscious/declarative) memory. This showed that motor learning, for instance, must be governed by a system distinct from the one responsible for recording new facts and experiences, and that this motor learning system was located in brain regions unaffected by HM’s operation (e.g., the cerebellum and striatum). This concept of multiple memory systems operating in different brain areas was a paradigm shift in neuroscience.
Medial Temporal Lobe Amnesia
Characteristics: This type of amnesia is primarily defined by a significant difficulty in forming new explicit long-term memories (anterograde amnesia) alongside varying degrees of retrograde amnesia, while typically retaining the ability to form implicit long-term memories. Patients often experience a severe impairment in daily functioning due to their inability to remember new information or events.
Not all patients with medial temporal lobe damage present identically. Some, unlike HM, may retain a limited ability to form new semantic memories (general facts, knowledge about the world) while their episodic memory (memory for specific personal events and experiences, often tied to a time and place) remains profoundly impaired. This highlights a further dissociation within explicit memory.
Semantic memory: Refers to our general knowledge about the world, concepts, facts, and vocabulary, independent of personal experience (e.g., knowing that Paris is the capital of France).
Episodic memory: Refers to memories of specific personal experiences, events, and their associated contextual details (e.g., remembering your last birthday party and what you did).
Medial temporal lobe amnesia may also involve difficulty in imagining future events, suggesting that the brain regions involved in recalling past episodic events are also crucial for constructing hypothetical future scenarios.
Cerebral Ischemia – This condition results from an interruption of blood supply to the brain, which deprives brain tissue of oxygen and glucose, leading to neuronal damage. Brief periods of cerebral ischemia, particularly those affecting the CA1 subfield of the hippocampus, can cause severe medial temporal lobe amnesia.
R.B.’s case: R.B. was a patient who suffered ischemic brain damage primarily restricted to the CA1 pyramidal cell layer of the hippocampus. His case suggested that even relatively selective hippocampal damage alone can produce significant amnesia, although his amnesia was less severe and more specific than HM's, whose damage was more extensive.
Korsakoff’s syndrome – A severe memory disorder primarily associated with chronic heavy alcohol use, often coupled with a thiamine (vitamin B1) deficiency. It is characterized by devastating amnesia (both anterograde and retrograde), profound confusion, personality changes, and various physical problems (e.g., ataxia, ophthalmoplegia). Neuropathological studies indicate brain damage often in the medial diencephalon (medial thalamus and medial hypothalamus) as well as diffuse damage to other brain areas like the prefrontal cortex. In its advanced stages, Korsakoff’s syndrome can lead to significant sensory and motor problems and carries a higher risk of mortality.
Korsakoff’s syndrome amnesia, particularly its profound anterograde component and variable retrograde memory loss, resembles medial temporal lobe amnesia in several respects, suggesting shared underlying neural circuits for memory consolidation.
Alzheimer’s disease (AD) – The most common neurodegenerative cause of amnesia and dementia, particularly in the elderly. Memory decline in AD typically begins mildly, often with difficulty remembering recent events, and progressively worsens over time, ultimately becoming a terminal illness. Early symptoms often involve episodic memory loss, followed by semantic memory and executive function deficits.
The widespread cerebral damage in AD is significantly associated with reductions in the neurotransmitter acetylcholine, mainly due to the degeneration of cholinergic neurons in the basal forebrain. This region provides cholinergic input to the cortex and hippocampus, which is critical for attention, learning, and memory.
Retrograde Amnesia and Memory Consolidation
Concussions – Traumatic brain injuries resulting from a blow to the head, often disrupt the neural activity underpinning recently formed memories. This interference can prevent the successful consolidation (the physiological process of converting short-term memories into more stable, long-term forms) of those memories.
Hebb’s theory of memory consolidation: Donald Hebb proposed that memories are initially stored in the short term by patterns of neural activity reverberating in closed-circuit neuronal loops. If this activity persists long enough, it leads to enduring structural changes at the synapses (e.g., increased synaptic strength, formation of new synapses), thereby permanently storing the memory in the long term. Any event that disrupts this ongoing neural activity (e.g., a concussion or electroconvulsive shock) within a critical period after learning will prevent consolidation.
Examples of disruption: Events like concussions, seizures, or electroconvulsive shock (ECS), which cause widespread disruption of brain electrical activity, physically interfere with the neural reverberations necessary for consolidation, leading to amnesia for events immediately preceding the disruptive event.
Posttraumatic amnesia (PTA): This refers to the period of confusion and disorientation following a brain injury, characterized by a combination of retrograde amnesia (for events before the injury) and anterograde amnesia (for events after the injury). The severity and duration of retrograde amnesia caused by concussions are often correlated with the duration of the coma or period of unconsciousness observed in non-penetrating head injuries.
Periods of anterograde amnesia observed after a concussion or brain trauma are thought to reflect a temporary failure of the memory consolidation process, preventing the encoding of new experiences into stable long-term memories during the acute recovery phase.
Reconsolidation: A dynamic process proposed to explain why retrieved memories can be altered. Each time a consolidated memory is retrieved from long-term memory (LTM) into working memory (STM), it is temporarily rendered labile, similar to how it was during its initial consolidation. During this labile phase, the memory is once again susceptible to disruption, modification, or enhancement before it is restabilized or reconsolidated back into LTM. This process has significant implications for therapeutic interventions for PTSD and explains how memories can change over time.
Where Are Memories Stored?
Modern neuroscience indicates that memories are not stored in a single, localized brain structure but are distributed diffusely across various brain regions in a network. Consequently, the destruction of a single brain structure typically does not erase all memories, though it can hinder specific types of memory formation or retrieval.
While memories are distributed, some brain structures have particular and well-defined roles in different aspects of memory storage and processing:
Hippocampus – Crucial for the formation of new explicit long-term memories, particularly spatial memory (e.g., navigation, remembering routes, forming cognitive maps of an environment, place cells). It binds together different features of an experience from various cortical areas to form a cohesive memory.
Perirhinal cortex – Located adjacent to the hippocampus, this region is a key component of the medial temporal lobe memory system and is critically involved in object recognition memory (i.e., remembering what objects are and their properties).
Medial dorsal nucleus (of the thalamus) – Damage to this thalamic nucleus, along with the medial hypothalamus, is strongly associated with the memory deficits and other symptoms observed in Korsakoff’s syndrome.
Basal forebrain – A critical source of cholinergic projections to the cortex and hippocampus. Its degeneration, leading to a significant decrease in acetylcholine, is a hallmark pathology related to Alzheimer’s disease symptoms and cognitive decline, particularly in memory and attention.
Inferotemporal cortex – Located in the ventral stream of visual processing, this area is involved in the high-level processing of visual information, especially for the visual perception and memory of objects.
Additional structures contributing to memory systems include:
Amygdala – While not directly involved in storing explicit facts or events, the amygdala plays a central role in emotional learning and encoding the emotional significance of experiences. It modulates the strength and vividness of memories, especially fear memories, and shows changes in activity during emotionally charged visual recall tasks. Lesions to the amygdala severely disrupt fear conditioning and emotionally motivated learning.
Prefrontal cortex – Critically involved in working memory (the active maintenance and manipulation of information over short periods), the temporal order of events (remembering when things happened), and tasks requiring sequences of responses or strategic retrieval of memories. It helps in organizing and executing goal-directed behaviors that rely on memory.
Cerebellum – Primarily known for its role in motor control, the cerebellum also plays a vital role in storing memories of sensorimotor skills (e.g., riding a bike, playing a musical instrument) and classically conditioned motor responses, such as eyelid conditioning.
Striatum (part of the basal ganglia) – Essential for habit formation and stimulus-response learning. It supports incremental learning of procedural routines and motor habits, often operating unconsciously and independently of explicit memory.
Biopsychology of Memory and You
Infantile amnesia – The common and pervasive inability of adults to recall episodic memories (specific personal events and experiences) from the first few years of their lives (typically before age 2-4). Several theories attempt to explain this phenomenon, including brain immaturity (especially the hippocampus and prefrontal cortex), lack of language development, and differences in self-concept in early childhood.
Nootropics – Also known as