Lectures 16-18 Flashcards

Question

What do heterogeneity models propose about medial temporal lobe (MTL) components?

Answer 1

Different memory processes (i.e. algorithms) distinguish MTL components

Answer 2

Lesions should impair recollection and familiarity somewhat selectively, depending on which MTL component is damaged

Answer 3

fMRI activation patterns should differentiate recollection and familiarity processes

Answer 4

It is not recognition memory processes that distinguish MTL components Differences between MTL structures are not due to separate memory algorithms

Answer 5

Hippocampal lesions should impair recollection and familiarity somewhat equivalently Following MTL damage, no selective deficit between the two processes

Answer 6

Activation patterns should show similar MTL engagement across both recollection and familiarity

Answer 7

In neuroscience we need to be able to tell them apart to understand the neural basis of each of them.

Answer 8

Presents one stimulus at a time, so direct comparison between items is impossible Depends primarily on recollection of contextual or episodic details Often impaired by hippocampal damage due to reliance on recollective processes

Answer 9

Presents multiple stimuli simultaneously, enabling direct comparison Can be solved using familiarity judgements alone (“which one feels most known”) Remains intact in individuals lacking a hippocampus because familiarity is preserved

Answer 10

Encoding: participants study a series of stimuli Test: items presented one at a time; participant first judges whether they have seen each item before If “yes,” they report “Remember” if they recall specific details (recollection) or “Know” if it merely feels familiar (familiarity) Subjective, introspective method in use for 30–40 years

Answer 11

Encoding: each stimulus is presented with a distinct source cue (e.g. screen location or background colour) Test: for recognised items, participants indicate the original source attribute Correct source identification indexes recollection of contextual detail Incorrect or guessed source responses may reflect reliance on familiarity

Answer 12

Participants must introspectively distinguish detailed recall from mere familiarity Both R/K and source memory tasks depend on subjective judgements Despite this, these methods are essential to reveal distinct neural bases of each process

Answer 13

Memory for individual stimuli Typically tested with a yes/no recognition task, where each item is judged as “old” or “new”

Answer 14

Memory for the relationship between two or more items (e.g. arbitrary pairs) Tested by presenting item pairs at test and asking whether the combination matches the originally studied pairing

Answer 15

MTL cortices (perirhinal, entorhinal, parahippocampal) support item familiarity Hippocampus supports binding of distinct elements into associative memories

Answer 16

Hippocampus is necessary for associating or “binding” separate elements into a unified memory trace MTL cortical regions do not perform this binding but relay item information to the hippocampus

Answer 17

Associative recognition should depend exclusively on recollection and thus on hippocampal integrity Item recognition may be supported by familiarity and hence remain relatively preserved after hippocampal damage

Answer 18

Use a yes/no recognition task for individual items (item recognition) Use a paired-comparison or forced-choice associative test for studied item pairs (associative recognition)

Answer 19

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Answer 20

Hippocampus: sparse, non-overlapping ensembles that minimise interference Perirhinal (PRC) and parahippocampal (PHC) cortices: dense, overlapping ensembles that capture similarity

Answer 21

The process of forming distinct neural codes for similar inputs to reduce memory interference Implemented by the hippocampus via sparse, orthogonalised representations

Answer 22

Retrieving a complete memory trace from a partial or degraded cue Supported by hippocampal auto-associative networks using the separated representations

Answer 23

Shared neural units across inputs emphasise common features Enable extraction of statistical regularities and rapid “sense” of prior encounter

Answer 24

Perirhinal cortex (PRC) and parahippocampal cortex (PHC) Support item familiarity and generalisation across exemplars via overlapping codes

Answer 25

Task demands determine whether differences or commonalities between inputs are emphasised Hippocampus emphasises distinctions (pattern separation) when precise recall is needed Cortical regions emphasise overlap (generalisation) when rapid familiarity or categorisation suffices

Answer 26

Input representations with any degree of overlap are mapped to identical outputs No pattern separation or generalisation occurs Neural similarity between outputs remains the same as between inputs

Answer 27

Partial cues prompt the hippocampus to reconstruct the full memory via its auto‐associative network Behavioural analogue: in a cued‐recall task, a reminder fragment reliably elicits retrieval of the entire event Everyday example: parking in the same car park each day but slightly different spot - returning to the lot cues recall of exactly where you left your car

Answer 28

Lesions provide direct evidence of necessity by showing which functions are lost when a region is damaged Complement correlational data from fMRI with causal inference

Answer 29

Lesions are incidental and cannot be experimentally controlled Damage rarely respects neuroanatomical boundaries, especially in densely packed regions like the MTL Patient heterogeneity: lesion extent, location and aetiology vary across individuals

Answer 30

Ensures precise mapping of lesion location and extent Clinical MRI scans alone are often insufficient for detailed neuroanatomical delineation

Answer 31

Administer standardised tests to rule out non-mnemonic deficits (e.g. IQ, language) Compare patient performance to a matched control group (typically ≥15 participants matched on age, IQ, etc.)

Answer 32

Experienced a cerebrovascular incident in 1986 Sustained relatively focal, bilateral hippocampal damage along its full anterior–posterior extent

Answer 33

Employed high-resolution structural MRI to measure hippocampal cross-sectional areas at successive coronal slices Compared each measurement to a matched healthy control sample YR’s hippocampal volumes were consistently more than two standard deviations below the control mean

Answer 34

MRI scans were acquired circa 2000 with lower spatial resolution than current standards Lesion delineation relied on manual segmentation protocols that may vary between operators Despite these factors, the volume reductions are large and specific to the hippocampus, supporting a focal lesion interpretation

Answer 35

METHODS: * Study phase: eight object silhouettes (e.g. anchor, frog, horse) presented once each * Test phase: * Forced‐choice: four-item arrays containing one target and three similar foils (familiarity sufficient) * Yes/no: single-item probes judged as “old” or “new” (recollection required for high foil similarity) RESULTS: * Forced‐choice (familiarity): YR performed within ~1 SD of control mean, indicating preserved familiarity * Yes/no (recollection): YR scored >3 SD below control mean, reflecting a profound recollection deficit INTERPRETATION: * Selective hippocampal damage abolished recollection‐based recognition while sparing familiarity‐based performance

Answer 36

METHODS: * N = 5 patients with confirmed bilateral hippocampal lesions * Forced‐choice: 12 studied items, 12 test trials each with 4 alternatives (target + 3 similar foils) * Yes/No: 12 studied items, 60 single‐item test trials (target and foil trials intermixed) RESULTS: * Patients were impaired on both tests but showed disproportionately poorer performance on the yes/no test INTERPRETATION: * Argued that the larger number of yes/no trials (and greater time/difficulty) accounts for the performance gap * Concluded that task difficulty, not selective hippocampal involvement in recollection, explains the differential deficit

Answer 37

Both recognition and recall were similarly impaired, suggesting no dissociation between familiarity and recollection in this sample (Manns et al 2003)

Answer 38

Observed the same pattern of deficits across both forced-choice and yes/no recognition tasks Provided converging evidence that task difficulty did not uniquely account for performance differences (Jeneson et al 2010)

Answer 39

Confirms that different recognition tasks reliably evoke the same pattern of impairment Does not increase the independence of data points, since patient samples substantially overlap

Answer 40

* Intra-item associative recognition – recognising a modified version of the same item (e.g. “sandstorm” ↔ “snowstorm”), minimal cross-item binding * Within-domain inter-item associative recognition – recognising pairs drawn from the same stimulus class (e.g. two faces), moderate binding demands within a single domain * Between-domain inter-item associative recognition – recognising pairs drawn from different domains (e.g. face + object), high binding demands across distinct representational systems

Answer 41

METHODS: * Study phase: sets of four stimuli or stimulus pairs (intra-item, within-domain, between-domain) * Test phase: forced-choice arrays requiring identification of intact versus recombined or modified pairs RESULTS: * Intra-item: performance within normal range relative to controls * Within-domain inter-item: performance within normal range, indicating preserved same-domain binding * Between-domain inter-item: profound impairment (well below control mean), indicating a selective deficit in cross-domain binding INTERPRETATION: * Selective hippocampal damage spares simple and same-domain associative judgements but abolishes the ability to bind across distinct stimulus domains

Answer 42

Proposes that perirhinal cortex (PRC) and hippocampus both contribute to item memory and within-domain associations but via different algorithms Suggests that only the hippocampus supports binding across distinct domains

Answer 43

Perirhinal cortex (PRC) Uses overlapping, dense neural representations to generalise across similar stimuli, yielding a familiarity signal for single items and same-domain pairs

Answer 44

Forms sparse, orthogonalised codes that enable pattern separation at encoding Utilises auto-associative pattern completion at retrieval to reinstate detailed memories (recollection) for items and same-domain pairs

Answer 45

Between-domain associations (e.g. face–object pairs) Requires hippocampal binding because PRC representations of distinct domains do not overlap sufficiently to support familiarity‐based association

Answer 46

Similar stimuli converge earlier into PRC, permitting some degree of associative binding for within-domain pairs Different-domain inputs converge later in hippocampus, making cross-domain binding reliant on hippocampal circuitry

Answer 47

The fornix

Answer 48

Surgery often produces a focal disconnection of the fornix Provides a larger, more homogenous patient cohort than typical incidental hippocampal lesions Allows direct testing of recollection deficits without neocortical damage

Answer 49

Lesions to these diencephalic structures yield profound recall/recollection impairments Highlight necessity of the subcortical loop beyond the hippocampus alone

Answer 50

Surgical sectioning or thinning of the fornix produces profound anterograde amnesia characterised by impaired recall and recollection Memory deficits arise despite intact neocortex and MTL cortical regions

Answer 51

Coronal MRI slices show comparison between healthy controls (intact fornix) and patients with bilaterally sectioned or unilaterally thinned fornix Focal disruption of the C-shaped fornix bundle evident beneath the corpus callosum

Answer 52

Even slight damage to the fornix fibres leads to severe memory impairment Preserving the fornix minimises postoperative amnesia while allowing cyst removal

Answer 53

Major white-matter tract conveying hippocampal outputs to mammillary bodies and anterior thalamus Integral link in the hippocampus → fornix → mammillary body → mammillothalamic tract → anterior thalamus → retrosplenial cortex loop supporting detailed recollection

Answer 54

The fornix fibres project directly into the mammillary bodies Surgical disruption of the fornix leads to secondary shrinkage of the mammillary bodies

Answer 55

Mammillary bodies have a distinctive shape that allows reliable volumetric measurement on MRI Fornix damage and mammillary body atrophy correlate strongly across patients

Answer 56

Coronal structural MRI slices to visualise the C-shaped fornix and the pill-shaped mammillary bodies Manual or semi-automated segmentation of each structure to derive normalised volume estimates Box-plot comparisons between patients and matched controls to identify significant atrophy

Answer 57

Disruption of the hippocampus→fornix→mammillary bodies→anterior thalamus loop abolishes detailed recollection Severity of memory impairment scales with the degree of mammillary body shrinkage, reflecting fornix disconnection

Answer 58

Patients with smaller normalised mammillary body volumes exhibit poorer recall scores Linear regression shows R² ≈ 0.41, indicating that ~41 % of recall variance is explained by mammillary body atrophy Demonstrates that the integrity of the fornix→mammillary body pathway is critical for detailed recollection

Answer 59

Remember / Know probability estimation Structured equation modelling (SEM) of latent recollection and familiarity constructs Receiver operating characteristic (ROC) curve modelling

Answer 60

Severe atrophy group (SMB) showed a marked reduction in recollection estimates (*** p < 0.001) Familiarity estimates were comparable or modestly elevated in the severe atrophy group

Answer 61

ROC-derived recollection parameter was significantly reduced in the severe atrophy group (** p < 0.01) ROC-derived familiarity parameter did not differ between groups, indicating preserved familiarity despite mammillary body shrinkage

Answer 62

Stimuli of the same condition (A or B) are presented continuously in long blocks (e.g. 30 s per condition) BOLD responses are averaged over each block, limiting temporal resolution Poor sensitivity to isolate activity evoked by individual memory events, especially in deeper MTL structures

Answer 63

Presents stimuli in a randomised, time-jittered sequence so each trial’s BOLD response can be modelled separately Enables linking of specific behavioural outcomes (e.g. remembered vs forgotten trials) to their neural signature Allows deconvolution of overlapping haemodynamic responses, revealing MTL activations associated with recollection and familiarity

Answer 64

* Development of statistical deconvolution methods to estimate trial-specific haemodynamic responses * Introduction of general linear model frameworks accommodating rapid event sampling * Optimisation of experimental timing (jittered inter-trial intervals) to enhance design efficiency and detection power

Answer 65

Scan‐Encoding * Participants encode stimuli while inside the scanner * Memory is tested behaviourally outside the scanner afterwards * Used to identify neural bases of successful encoding Scan‐Retrieval * Participants study stimuli before scanning * Retrieval is tested inside the scanner * Used to identify neural bases of successful retrieval

Answer 66

* Necessitates a very long total scan time * Increases participant fatigue and movement artefacts * May require splitting into multiple sessions to maintain data quality

Answer 67

Have participants perform a free-recall test after they exit the scanner Only feasible when scanning during encoding, since recollection must be probed later

Answer 68

A low-level encoding task that restricts conceptual or semantic processing (e.g. simple perceptual judgements) Reduces the encoding of rich contextual details, suppressing recollection and highlighting familiarity signals

Answer 69

Use a forced-choice or relative-judgement paradigm that requires only a sense of prior encounter Avoid tasks demanding explicit recall of context, thereby limiting engagement of recollective mechanisms

Answer 70

METHODS: * Event‐related fMRI with very slow trial timing (one word every 20 s) to isolate individual haemodynamic responses * Subjects made Remember/Know judgments for each old/new word probe while in the scanner * Regions of interest defined in left and right hippocampus RESULTS: * “Remember” (recollection) trials elicited a clear hippocampal BOLD increase (~0.15–0.25 % signal change peaking ~5 s post-cue) in both hemispheres * “Know” (familiarity) trials produced little or no hippocampal BOLD signal above baseline * Correct rejections and misses showed distinct hippocampal signal profiles different from “Remember” trials INTERPRETATION: * First fMRI evidence that hippocampal activation selectively tracks recollection rather than mere familiarity Eldridge et al. 2000

Answer 71

Bilateral hippocampus Left parahippocampal cortex These regions show higher BOLD signal for items subsequently recognised with correct source details Davachi et al. 2003

Answer 72

Perirhinal cortex Exhibits increased activation for items later recognised as “old” but lacking source‐detail recollection Davachi et al. 2003

Answer 73

METHODS: * Healthy adult volunteers studied a list of words outside the scanner * During fMRI, single‐word probes appeared every 20 s; participants made old/new judgments and then classified each “old” item as “Remember” (recollection) or “Know” (familiarity) * Regions of interest manually delineated in left and right hippocampus RESULTS: * “Remember” trials evoked a clear hippocampal BOLD increase (~0.15–0.25 % signal change peaking ~5 s post‐cue) in both hemispheres * “Know” trials produced no significant hippocampal response above baseline * Correct rejections and misses showed distinct, lower‐amplitude hippocampal signal profiles INTERPRETATION: * Hippocampal activation selectively tracks recollection rather than a general familiarity signal

Answer 74

METHODS: * Participants studied words under two encoding tasks: generate a mental image versus silently pronounce each word backward * Memory test after scanning required old/new judgments plus identification of the encoding task (source) if “old” * Encoding‐phase BOLD signal was modelled for trials later (a) recognised with correct source (recollection), (b) recognised without correct source (familiarity), (c) forgotten RESULTS: * Trials later recognised with correct source elicited greater encoding‐phase activation in bilateral hippocampus and left parahippocampal cortex * Trials later recognised without correct source (item only) showed increased activation selectively in perirhinal cortex * Forgotten items showed minimal MTL activation INTERPRETATION: * Distinct MTL subregions support different memory processes: hippocampus/parahippocampal cortex for recollection of contextual details, perirhinal cortex for familiarity‐based item recognition

Answer 75

Parametric confidence and source modelling * Used a 6-point old/new confidence scale plus separate colour-source judgments * Treated recollection strength as a continuous variable rather than a binary outcome Finer anatomical precision along the MTL axis * Demonstrated that posterior hippocampus and parahippocampal/fusiform cortex predict later source-correct recognition (recollection) * Showed perirhinal cortex activation selectively predicts later item-only recognition (familiarity) Whole-brain network mapping * Identified lateral parietal and prefrontal regions whose encoding-phase activity covaries with subsequent recollection versus familiarity Ranganath et al. 2004

Answer 76

Meta-analysis of multiple event-related fMRI studies contrasting New versus Old item recognition Showed consistent perirhinal cortex clusters exhibiting relative deactivation to Old stimuli (New>Old BOLD response) Demonstrates that perirhinal cortex reliably tracks familiarity signals across tasks and is distinct from recollection-related regions

Answer 77

METHODS: * Event-related fMRI during word encoding with two semantic tasks (size judgement vs animate/inanimate decision) * Later recognition test with confidence ratings and source-colour judgments * Analysed hippocampal BOLD as a function of item-confidence, collapsing across correct and incorrect source RESULTS & CONCLUSION: * When high-confidence “old” trials were equated for source correctness, hippocampal activation did not differ between source-correct and source-incorrect items * Argued that hippocampal BOLD reflects memory strength (confidence) rather than the retrieval of specific contextual details

Answer 78

Pointed out that high-confidence source-incorrect trials may still involve recollection of non-target details (e.g. semantic or perceptual aspects) Argued that matching confidence does not guarantee absence of recollection, since confidence increases with the amount of retrieved detail, not solely target source Concluded that hippocampal activation likely still indexes qualitative recollection processes rather than a generic strength signal

Answer 79

Source-correctness only indexes recall of the target context (e.g. colour), not all retrieved details High confidence increases as more contextual information—target or non-target—is recollected Participants may recollect alternative features (semantic, perceptual) on “source-incorrect” trials Thus, hippocampal BOLD on confident non-source trials could reflect residual recollection rather than pure familiarity

Answer 80

Participants viewed one “target” picture above and two “choice” pictures below, and had 4 s to select which bottom image was identical to the top Stimuli were everyday scenes differing only in fine perceptual details (e.g. chimney size) Short decision window minimised semantic or contextual processing, preventing formation of rich episodic traces.

Answer 81

Familiarity arises from generalised perceptual overlap—participants need only detect coarse pattern similarity Recollection requires hippocampal binding of contextual details, which time-limited shallow encoding disrupts By forcing rapid, detail-focused judgements, the task ensures memory decisions rely on perirhinal‐mediated familiarity signals rather than hippocampal recollection

Answer 82

Encoding task: Perceptual matching of natural scene triplets (choose which of two bottom images matched the top image on subtle visual features) Retention interval: 48-hour delay between encoding and scanning Training: Participants received explicit recollection-vs-familiarity instruction and practice before scanning In-scanner test: * Rate familiarity of each scene on a six-point scale (CR, M/F0, F1, F2, F3, R) * Do not attempt deliberate recollection * Report any spontaneous recollection that occurs

Answer 83

CR (Correct Rejection): “Definitely new” images correctly identified as new M (Miss, F0): Old images incorrectly judged new F1 (Weak Familiarity): Old images judged “weakly old” F2 (Medium Familiarity): Old images judged “moderately old” F3 (Strong Familiarity): Old images judged “strongly old” R (Recollection): Old images for which spontaneous recollection was reported

Answer 84

Parametric deactivation: Left and right PRc signal decreased progressively from F1 through F3 (significant parametric modulation of the old>new contrast) Recollection (R): Produced PRc activity equivalent to the highest familiarity level (F3), not an additional increase Implication: PRc is sensitive to the strength of familiarity but does not differentiate recollection from very strong familiarity

Answer 85

Selective activation: Both left and right hippocampi showed significantly greater BOLD response for R than for F3 (p < 0.05 for R > F3 contrast) No graded familiarity effect: Hippocampal activity did not increase across F1–F3 levels Conclusion: The hippocampus supports recollection-specific retrieval processes, not graded familiarity memory

Answer 86

Response definitions: * F3 (strong familiarity): Old items judged “definitely old” without spontaneous recollection * R (recollection): Old items with reported episodic recall Accuracy results: * F1 (weak familiarity): ~0.54 * F2 (medium familiarity): ~0.65 * F3: ~0.88 * R: ~0.89 Reaction-time results (ms): * F1: ~2100 ms * F2: ~1940 ms * F3: ~1850 ms * R: ~1850 ms Key finding: No significant difference in accuracy or RT between F3 and R, demonstrating that strong familiarity and recollection can be equated on behavioural strength metrics.

Answer 87

Hippocampus * Confidence 1–4: flat, minimal BOLD change * Confidence 5–6: sharp, non-linear surge in activity Perirhinal cortex * Highest activity at lowest confidence (novelty/low-strength detection) * Monotonic decline in BOLD as confidence increases from 1 → 6 Confound * High-confidence (5–6) items also have greatest memory strength and accuracy demands, so the hippocampal “spike” may reflect strength effects rather than discrete recollection processes.

Answer 88

METHODS: * Adult human volunteers encoded scene photographs using a perceptual‐matching task (minimising semantic elaboration) * Retention interval of 48 hours before memory test * In‐scanner test: * Rate item familiarity on a three-point scale (F1–F3) * Report any spontaneous recollection (R) without being prompted to recollect * Behavioural matching: select F3 and R trials such that mean recognition accuracy was equated (F3 ≈ 0.88; R ≈ 0.89) and mean reaction time was equated (both ≈ 1 850 ms) RESULTS: * Hippocampal BOLD signal was significantly greater for R than for F3—even though F3 and R were identical in accuracy and RT CONCLUSION: * Hippocampal engagement reflects a specific role in episodic recollection rather than a general response to high memory strength.

Answer 89

When participants recognise items based solely on a feeling of familiarity (without recalling contextual details), the hippocampus shows no significant activation. In contrast, when participants report recollection (retrieval of contextual/source details), hippocampal activity is robustly increased.

Answer 90

Parametric increases in familiarity strength (F1 → F3) produce no systematic change in hippocampal BOLD signal. This absence of modulation indicates that the hippocampus is not engaged by familiarity, regardless of confidence level, when accuracy is held constant.

Answer 91

Perirhinal cortex supports familiarity-based recognition (sensitivity to old/new contrasts and graded familiarity). Hippocampus supports recollection-based recognition (retrieval of contextual/source details), with no engagement by familiarity memory.

Answer 92

Methods (brief): * Adult humans first encoded 90 scenes, 90 faces and 90 objects using a matching‐to‐sample task. * During fMRI retrieval, 135 items of each category were presented (fixation 800 ms → stimulus 3 000 ms → implicit baseline 3 000 ms). * On each trial participants rated familiarity (New, F1–F3) and reported any spontaneous recollection (R). * Behavioural F3 and R trials were equated for accuracy and reaction time. Results (familiarity slope): * Scenes: PRC/entorhinal cortex and parahippocampal cortex (PHC) activity rose linearly from F1 → F3. * Faces: Amygdala and fusiform gyrus activity rose linearly with increasing familiarity. * Objects: Perirhinal cortex (PRC) and PHC activity declined linearly as familiarity increased.

Answer 93

Design control: F3 and R trials matched for recognition accuracy (~0.80–0.90) and reaction time (~1 800 ms). Hippocampal result: Robust BOLD increases for R but no activation for F3 in all three stimulus categories. Inference: Hippocampus is selectively engaged by episodic recollection, regardless of stimulus type or overall memory strength.

Answer 94

METHODS: * Healthy adult volunteers encoded 90 objects, 90 faces and 90 scenes in a matching-to-sample task before scanning. * Retrieval session in the MRI: 135 trials per category (fixation 800 ms → stimulus 3 000 ms → implicit baseline 3 000 ms). * On each trial participants rated familiarity (New, F1–F3) and reported spontaneous recollection (R). * F3 and R trials were selected to equate mean recognition accuracy and reaction time. RESULTS: * Anterior thalamus (AT): significant activation for R > F3, but no parametric change across F1→F3. * Mediodorsal thalamus (MD): activity increased linearly with familiarity strength (F1→F3) for all stimulus types. * Ventrolateral thalamus (VL): parametric familiarity effect only for faces (F1→F3). * Posterior thalamus (PT): parametric familiarity effect only for scenes (F1→F3). CONCLUSION: * AT supports episodic recollection specifically, whereas MD integrates familiarity signals across domains, with VL and PT showing material-specific familiarity responses.

Answer 95

METHODS: * Seed region: MD thalamus peak from the familiarity contrast (F1–F3). * PPI analysis examined MD connectivity with perirhinal cortex (PRC) and parahippocampal cortex (PHC) during familiarity trials. * Familiarity strength indexed by hits minus false alarms across F1–F3. RESULTS: * Objects: MD–PRC connectivity increased with familiarity strength (R² = 0.42, p < 0.01). * Faces: MD–PRC connectivity increased with familiarity (R² = 0.30, p < 0.05). * Scenes: MD–PHC connectivity increased with familiarity (R² = 0.32, p < 0.05). CONCLUSION: * The mediodorsal thalamus serves as a hub, functionally coupling with material-specific MTL cortices in proportion to familiarity strength, thus orchestrating the subjective experience of familiarity.

Answer 96

Anterior thalamus (AT): * Significant activation for recollection (R > F3) * No parametric modulation across familiarity levels (F1→F3) Mediodorsal thalamus (MD): * Domain-general linear increase in activity with rising familiarity (F1→F3) for all stimulus types Ventrolateral thalamus (VL): * Familiarity-strength modulation (F1→F3) only for faces Posterior thalamus (PT): * Familiarity-strength modulation (F1→F3) only for scenes

Answer 97

Objects: MD–perirhinal cortex (PRC) connectivity increased with object familiarity (R² = 0.42, p < 0.01) Faces: MD–PRC connectivity increased with face familiarity (R² = 0.30, p < 0.05) Scenes: MD–parahippocampal cortex (PHC) connectivity increased with scene familiarity (R² = 0.32, p < 0.05)

Answer 98

Acts as a hub that functionally couples with material-specific MTL cortices in direct proportion to familiarity strength Orchestrates the subjective experience of familiarity across objects, faces and scenes

Answer 99

Lateral nucleus: receives CS (conditioned stimulus) and US (unconditioned stimulus) inputs Basolateral & accessory basal nuclei: integrate and refine associative signals Central nucleus: final common output specifying fear responses

Answer 100

Periaqueductal gray: orchestrates defensive behaviours (e.g. freezing) Lateral hypothalamus: drives autonomic responses (heart rate, blood pressure) Bed nucleus of the stria terminalis: regulates hormonal stress responses (e.g. HPA axis)

Answer 101

Cue-based conditioning: * Procedure: pair discrete CS (tone/light) with aversive US (shock) * Neural substrate: amygdala circuits alone * Measure: freezing or startle to CS Contextual conditioning: * Procedure: expose animal to context paired with US * Neural substrates: hippocampal context representation plus amygdala * Measure: freezing when returned to same context

Answer 102

Freezing (cessation of all movement except respiration) is a robust, quantifiable defensive behaviour Longer freezing indicates stronger associative fear memory Applicable across sensory modalities and experimental setups

Answer 103

CS pathway: auditory thalamus → lateral amygdala (LA), with a parallel route via auditory cortex → LA US pathway: somatosensory thalamus → LA, with additional input from somatosensory cortex → LA

Answer 104

Pavlovian (cue) conditioning: rat freezes when the tone CS is presented alone Contextual conditioning: rat freezes when returned to the training context without any tone or shock

Answer 105

Rats retain the conditioned fear response lifelong, demonstrating remarkably durable one‐trial learning

Answer 106

Enables rapid detection and recall of danger signals Increases an animal’s chance of survival by promoting immediate defensive behaviours (e.g. freezing) on re‐encountering the cue or context

Answer 107

METHODS: * Simultaneous extracellular recordings from 4 LA neurons during: * Ten CS‐only trials (tone alone) before conditioning * Ten CS–US pairings (tone co‐terminating with footshock) * Ten CS‐only trials after conditioning RESULTS: * Before conditioning: tone evoked modest, sparse spiking across LA units * After conditioning: tone evoked a robust, large increase in spike rate in all recorded LA neurons

Answer 108

METHODS: * Simultaneous extracellular recordings from four LA neurons * Phase 1 (Pre-test): ten trials of tone CS alone (3 sec tone; inter-trial interval ~30 sec) * Phase 2 (Unpaired “conditioning”): ten tone CS presentations and ten footshock US presentations, pseudorandomly interleaved so that CS and US never co-occur * Phase 3 (Post-test): ten trials of tone CS alone, identical to Phase 1 RESULTS: * No increase in tone‐evoked firing after unpaired presentations; some neurons even showed a decrease in spiking * Indicates that LA potentiation requires temporal CS–US association, not mere exposure to both stimuli

Answer 109

METHODS: * Adult rats underwent differential fear conditioning: CS– tone never paired; CS+ tone paired with footshock. * During retrieval, simultaneous extracellular recordings from LA neurons. * Temporary CE inactivation via lidocaine infusion before CS+ presentation. * Measured CS-evoked LA spiking and freezing. RESULTS: * LA firing: CS+ still evoked a large increase in LA spike rate despite CE inactivation. * Freezing: CE‐lidocaine abolished freezing to CS+ (no conditioned response). CONCLUSION: * LA activity reflects associative fear memory retrieval, whereas CE is required to transform that memory signal into overt defensive behaviour.

Answer 110

METHODS: * Rats conditioned to freeze in Context A (shock context) but never heard CS– tone there. * During retrieval in Context A, presented CS– tone while recording LA neurons and measuring freezing. RESULTS: * Freezing: High levels of contextual freezing on CS– trials. * LA firing: No increase in CS–‐evoked LA spike rate above baseline. CONCLUSION: * Contextual fear engages downstream fear circuits to drive freezing without LA spiking to the novel tone, confirming LA responses are CS associative, not behavioural per se.

Answer 111

LA: encodes the presence of learned CS+ associations (memory trace), showing robust spiking on CS+ retrieval regardless of freezing CE: acts as the behavioural effector node; CE inactivation prevents freezing even though LA memory representations remain intact OVERALL: The amygdala’s memory‐behaviour circuit separates storage (LA) from expression (CE), ensuring that learned fear associations can be retrieved independently of immediate behavioural output.

Answer 112

METHODS: * Adult rats first underwent auditory fear conditioning: 3 blocks of 10 tone–footshock pairings (CS+ → US). * Immediately afterwards, extinction comprised 3 blocks of 10 tone-only trials (CS alone; 3 sec tone; ~30 sec inter-trial interval). * Simultaneous measurements of: * Freezing behaviour (percentage time immobile per block) * Extracellular spiking from LA neurons during each CS presentation RESULTS: * Freezing: peaked by the end of conditioning then declined progressively across extinction blocks. * LA firing: CS-evoked spike rates likewise rose during conditioning but fell in parallel during extinction. INTERPRETATION: * Extinction does not erase the CS–US memory in LA; rather, it forms a new CS→no-US memory that inhibits expression of the original trace (via prefrontal control), causing both behavioural and neural responses to diminish.

Answer 113

Methods: * Adult rats received bilateral excitotoxic lesions of infralimbic cortex (vmPFC) or sham surgery. * Day 1: all animals underwent auditory fear conditioning (tone CS + footshock US) followed immediately by extinction training (tone alone, 20 trials). * Day 2: extinction recall test (tone alone, 20 trials) without any further extinction training. Results: * Extinction learning (Day 1): both lesion and sham groups showed equivalent decreases in freezing across extinction trials. * Extinction recall (Day 2): sham rats exhibited low freezing to the tone, whereas vmPFC-lesioned rats continued to show high freezing. Conclusion: * Infralimbic/vmPFC is necessary for recall of the extinction memory but not for initial extinction learning of the CS–US association.

Answer 114

Methods: * Chronic single-unit recordings from infralimbic cortex in awake rats. * Day 1: habituation, fear conditioning (tone + shock), then extinction training (tone alone). * Day 2: extinction recall (tone alone) in the same context. Results: * Conditioning & extinction learning (Day 1): infralimbic neurons showed minimal tone-evoked changes. * Extinction recall (Day 2): a subset of infralimbic neurons exhibited a marked increase in firing rate time-locked to tone onset. Conclusion: * Infralimbic cortex neurons selectively encode recall of the extinction (“safety”) memory.

Answer 115

Conceptual basis: extinction does not erase the original CS→US trace in lateral amygdala (LA) but instead creates a new CS→no-US memory. Evidence: * LA neurons still retain potentiated responses to the CS after extinction, but behavioural freezing and LA spiking are suppressed by infralimbic inputs. * Infralimbic lesion or inactivation unmasks the original fear response without altering LA plasticity. Conclusion: * Extinction establishes a parallel “safety” memory in infralimbic/vmPFC that inhibits retrieval of the original fear memory in the amygdala.

Answer 116

Anatomy: infralimbic cortex sends glutamatergic projections to inhibitory interneurons in the lateral and basal nuclei of the amygdala. Function: activation of this pathway during extinction recall suppresses output from the central nucleus, thereby preventing freezing. Supportive data: optogenetic or chemogenetic stimulation of infralimbic→LA projections reduces conditioned freezing, while pathway blockade impairs extinction recall.

Answer 117

Clinical observations: patients with PTSD display impaired recall of extinction and persistent fear responses to trauma-related cues. Neuroimaging: reduced ventromedial PFC (homologous to rodent infralimbic) activation during extinction recall in PTSD patients. Interpretation: failure to engage vmPFC “safety” circuits may underlie pathological persistence of fear in PTSD.

Answer 118

Prelimbic cortex (PL): * Drives expression of conditioned fear by exciting the central nucleus of the amygdala (CE) * Lesions or inactivation reduce freezing to the CS+ without affecting extinction learning Infralimbic cortex (IL): * Encodes and recalls extinction (“safety”) memories that suppress LA/CE output * Lesions or inactivation impair extinction recall, resulting in persistent freezing

Answer 119

Hippocampus → Fornix → Mammillary bodies → Anterior thalamus → Retrosplenial cortex → back to Hippocampus

Answer 120

4‐alternative forced‐choice recognition: * YR performs at control levels, relying on preserved familiarity processes Yes/no recognition with similar foils: * YR is severely impaired (>3 SD below control mean), indicating recollection deficits

Answer 121

Shows relative deactivation for previously seen (“old”) items compared to novel (“new”) items Reflects sensitivity to graded familiarity strength rather than simple novelty detection