Module Four Flashcards
(191 cards)
1
Q
Define behaviorist stimulus–response approach.
A
Early 20th-century approach focused solely on external stimuli directly evoking observable responses.
2
Q
What did Tolman propose in 1948?
A
Internal spatial representations (‘cognitive maps’) based on rat navigation experiments.
3
Q
Who revived Tolman’s cognitive map idea with electrophysiology?
A
O’Keefe & Nadel in 1978.
4
Q
Define place cells.
A
Hippocampal neurons that fire when an animal occupies specific locations, forming a neural map.
5
Q
Define head direction cells.
A
Neurons firing according to the animal’s facing direction, acting like an internal compass.
6
Q
Define grid cells.
A
Neurons in medial entorhinal cortex firing in a hexagonal pattern, providing metric for distance and direction.
7
Q
What additional spatial neurons exist beyond place, head-direction, and grid cells?
A
Cortical and subcortical spatially tuned neurons aiding spatial encoding.
8
Q
Who was Henry Molaison (H.M.) and his significance?
A
Patient with bilateral hippocampal removal causing severe anterograde amnesia and spatial impairments.
9
Q
What did the radial-arm maze demonstrate about hippocampus?
A
Its involvement in spatial working memory tasks.
10
Q
What does the Morris water maze test?
A
Spatial mapping ability independent of explicit working-memory demands.
11
Q
What happens to Morris water maze performance after hippocampal lesions?
A
Performance abolished, confirming deficits due to impaired spatial mapping.
12
Q
Discovery of place cells occurred through what method?
A
Single-unit hippocampal neuron recordings in freely moving rats by O’Keefe & Dostrovsky (1971).
13
Q
Do primates and humans have place cells?
A
Yes, but fewer, often encoding conjunctive spatial features.
14
Q
What ensures long-term stability of place fields?
A
Place fields persist days to weeks, although some cells show turnover for temporal coding.
15
Q
Do place cells rely solely on visual cues?
A
No, they integrate olfactory, tactile, and self-motion inputs, remaining stable in darkness.
16
Q
What is place-cell remapping?
A
Reorganization of place fields forming a distinct spatial code when environment changes.
17
Q
How do primates differ from rodents in navigation strategies?
A
Primates emphasize visual landmarks; rodents require direct exploration.
18
Q
Describe head-direction cell firing.
A
Cells fire maximally when head points in specific directions, independent of location.
19
Q
What circuitry generates head-direction signals?
A
Angular-velocity neurons in DTN and LMN relayed through thalamic and cortical structures.
20
Q
Grid cell identification location?
A
Medial entorhinal cortex, pre- and parasubiculum.
21
Q
What happens to grid cells during external cue rotation?
A
Grid fields rotate coherently with distal landmarks.
22
Q
Grid cells’ role in path integration?
A
Persist in darkness using self-motion computation; lesions impair path integration.
23
Q
Identify supporting cell types for grid cells.
A
Speed cells encoding locomotor velocity and band cells potentially scaffolding grid formation.
24
Q
Define interneurons.
A
Diverse, GABAergic inhibitory neurons modulating circuitry throughout hippocampal and cortical regions.
25
Spatial modulation of interneurons?
Interneurons exhibit coarse, stable spatial fields complementary to place cells.
26
Theta rhythm definition?
Brain oscillations (~4-12 Hz) prominent in hippocampus during movement and REM sleep.
27
Relationship between theta rhythm and running speed?
Theta rhythm frequency linked to running speed, affecting motor coordination.
28
What are extrahippocampal place cells?
Spatially tuned neurons outside hippocampus, typically less selective or conjunctive.
29
Medial entorhinal cortex (mEC) place-like cells?
Cells alongside grid cells, possibly vertices of grids or deeper-layer non-grid spatial cells.
30
Striatum’s spatial neuron evidence?
Weak, often conflated with motor or task-related signals.
31
Boundary vector cell (BVC) model?
Cells firing relative to boundary distance and allocentric direction, shaping place-cell activity.
32
Identify areas with boundary cells.
Subiculum, presubiculum, parasubiculum, medial entorhinal cortex, rostral thalamus, claustrum.
33
Object cell functional significance?
Combine object and spatial information for episodic-like memories.
34
Object-cell locations and traits?
Anterior claustrum and lateral entorhinal cortex with persistent object-location coding.
35
Goal cells definition?
Hypothetical neurons firing based on distance/direction to navigational goals.
36
Rodent explicit goal cells?
Rare; subtle place-cell modulation near goals; clear evidence mainly from bats.
37
Goal-related signals in medial prefrontal cortex (mPFC)?
Fire selectively at goal initiation sites; possibly related to task-relevant cues.
38
What are conjunctive cells?
Neurons simultaneously encoding multiple spatial features (e.g., location and direction).
39
Define theta-modulated place-by-direction cells.
Presubiculum/parasubiculum cells firing based on both location and head direction.
40
Role of movement/action-sensitive cells?
Integrate motor/spatial info supporting dynamic navigation and path integration.
41
'Big three' spatial neurons?
Place, head-direction, and grid cells foundational to spatial coding discovery.
42
Spatially modulated activity scope?
Extends beyond hippocampus and entorhinal cortex, throughout cortical/subcortical regions.
43
Doeller et al. (2010) study significance?
Identified human fMRI signatures matching rodent grid-cell firing patterns.
44
Cognitive spaces framework (Bellmund et al., 2018)?
Proposes spatial-coding mechanisms underpin domain-general cognition.
45
AD spatial deficits cause (Silva & Martínez, 2023)?
Grid-cell dysfunction precedes place-cell deficits in Alzheimer's Disease.
46
Biomarkers for AD diagnosis?
MEC-targeted imaging and oscillatory measures combined with VR navigation tests.
47
What was the focus of early 20th-century behaviorist research in spatial learning?
It focused solely on external stimuli evoking responses (Watson, 1919; Hull, 1950).
48
Who proposed the concept of a cognitive map and what did it entail?
Tolman in 1948 proposed an internal spatial representation based on rat navigation experiments.
49
Which researchers integrated behavioral evidence with emerging electrophysiology to support the cognitive map concept in 1978?
O’Keefe & Nadel.
50
What are place cells and who discovered them?
Hippocampal neurons that fire when the animal occupies specific locations in its environment, discovered by O’Keefe & Dostrovsky (1971).
51
What is the function of head direction cells and who first reported them?
They fire based on the animal’s facing direction like an internal compass; first reported by Ranck Jr. (1984) and characterized by Taube et al. (1990a,b).
52
Where are grid cells located and what is their firing pattern?
In the medial entorhinal cortex; they fire in a hexagonal lattice pattern, providing a metric for distance and direction traveled (Fyhn et al., 2004; Hafting et al., 2005).
53
What did the case of Henry Molaison (H.M.) demonstrate about the hippocampus?
His bilateral hippocampal removal led to profound anterograde amnesia and severe spatial memory impairments, showing the hippocampus is crucial for forming new spatial memories.
54
What does performance in the radial-arm maze suggest about hippocampal function?
That working-memory performance in the radial-arm maze is highly hippocampus-dependent, indicating hippocampal involvement in spatial working memory.
55
How do Morris water maze experiments demonstrate the hippocampus’s role in spatial mapping?
Rats with hippocampal lesions cannot locate the hidden platform using distal cues, indicating spatial mapping deficits rather than working-memory loss.
56
What is a place cell’s “place field”?
The specific region in the environment where a place cell fires maximally, regardless of head direction.
57
How stable are place fields over time?
They persist across days to weeks, though some cells show turnover, reflecting potential temporal coding.
58
How do visual and non-visual cues contribute to place cell activity?
Visual distal landmarks determine place field locations, but in darkness or blind rats, place fields remain stable via olfactory, tactile, and self-motion inputs.
59
What is remapping in place cells?
When the environment is altered or new, place cells reorganize their place fields to form a distinct spatial code.
60
How do primate place-encoding neurons differ from rodents?
In primates, place-encoding neurons are a minority (11–25%) of hippocampal/parahippocampal cells, many encoding spatial view or conjunctive features, unlike rodents where direct exploration is required for stable place fields.
61
What characterizes head direction cell population coding?
Different cells have uniformly distributed preferred directions, providing an unbiased representation of all headings.
62
How do head direction cells maintain alignment with the environment?
They rely on external cues like landmarks to stay aligned; their preferred directions rotate coherently with cue rotations and maintain tuning without external cues if not disoriented.
63
What is the anatomical circuitry underlying head direction signals?
Angular-velocity-sensitive neurons in dorsal tegmental nuclei (DTN) and lateral mammillary nuclei (LMN) relay through anterior dorsal thalamic nucleus (ADN), projecting to postsubiculum, retrosplenial cortex, entorhinal cortex, parasubiculum, posterior parietal cortex, and other thalamic nuclei.
64
What is distinctive about the firing pattern of grid cells in the mEC?
They fire in multiple locations forming a regular triangular or hexagonal lattice.
65
How do grid cells respond to manipulations of external cues and environments?
Their grid fields rotate with distal landmark rotations, deform partially with geometric distortions, and maintain coordinated alignment and spacing in novel settings.
66
What role do grid cells play in path integration?
They persist in darkness if the animal remains oriented, suggesting self-motion computation, and medial entorhinal lesions impair path integration performance.
67
Which animal species besides rats have grid cells been recorded in?
Mice, bats, and suggested by human single-unit recordings and fMRI signatures.
68
What are speed and band cells and their roles?
Speed cells in mEC encode locomotor velocity; band cells fire in periodic bands and may scaffold hexagonal grid formation.
69
What defines interneurons in the hippocampus?
They are GABAergic inhibitory cells, morphologically diverse, high-firing-rate neurons modulating local circuitry.
70
Approximately what percentage of neurons in hippocampal CA1 are interneurons?
About 10%, with at least 21 distinct types in CA1.
71
How do interneurons exhibit spatial tuning?
They show coarse but reliable spatial firing fields that rotate with visual landmarks, with some showing off-fields like suppressed activity near place-cell fields.
72
What is theta-phase locking in interneurons?
Different interneurons fire at specific phases of the hippocampal theta rhythm (\~4–12 Hz), coordinating timing during movement, exploration, and REM sleep.
73
How do medial septum inputs affect interneurons and theta rhythms?
Septal GABAergic inputs regulate the theta rhythm, acting as a pacemaker for the hippocampus, coordinating interneurons.
74
What is the relationship between running speed and theta rhythm frequency?
The speed at which an animal runs is connected to the frequency of the theta rhythm; changing theta frequency can affect running speed, showing coordination of movement control.
75
What are speed-tuned interneurons?
Pure speed cells identified in medial entorhinal cortex whose firing scales linearly with running velocity, feeding speed signals into self-localization and path integration computations.
76
What must computational models of navigation incorporate regarding interneurons?
The diversity of interneuron types, their timing, and spatial functions, given their active contribution to shaping place- and grid-cell activity and encoding dynamic variables.
77
What characterizes extrahippocampal place-like cells in mEC?
Place-like cells recorded alongside grid cells; debates exist whether they are true place units or vertices of grid fields, and deeper layers contain non-grid spatial cells with multiple firing fields.
78
What has research in the striatum revealed about spatial encoding?
Early reports suggested head-direction and location-sensitive neurons, but later studies failed to replicate true spatial encoding, indicating motor- or action-related firing that covaries with location and context.
79
What are spatially tuned cells in the lateral septum and their potential function?
LS contains cells resembling place fields with orthogonal codes across environments that later converge, hinting at pattern-completion roles, but LS lesions produce minimal behavioral deficits.
80
Does the medial septum contain place-like cells?
No, medial septum is critical for entorhinal theta and grid firing, but place-like cells have not been reported there.
81
How do subicular place-like cells differ from CA1 place cells?
They have lower spatial specificity and often encode combinations of position, heading, and speed, with some representing boundaries or supporting path integration.
82
What place-like units are found in the rostral thalamus?
Highly selective, stable place-like units in parataenial, anteromedial, and reuniens nuclei, linked to episodic and long-term memory.
83
What are the characteristics of anterior claustrum place-like cells?
Small population (\~4.3%) of place-like cells alongside directionally tuned units, integrating visual/spatial and other cortical inputs rather than pure place encoding.
84
How do lateral entorhinal cortex object-dependent place fields function?
Cells fire only in presence of objects, losing spatial tuning when objects are absent, supplying non-spatial information to hippocampal place cells.
85
What spatial modulation is observed in the postrhinal cortex?
Spatially modulated firing without stable place fields or coherent cue-rotations, possibly representing an intermediate stage in developing full place selectivity.
86
How does the orbitofrontal cortex (OFC) encode spatial information?
Neurons discriminate locations of odor ports mixed with task phase and behavior, with pure location coding rare, likely reflecting integration of spatial context with actions.
87
What is the Boundary Vector Cell (BVC) model?
A model predicting neurons that fire relative to the distance and allocentric direction of environmental boundaries, whose collective input generates place-cell activity.
88
Where have boundary/border cells been identified?
In subiculum (true BVCs), presubiculum & parasubiculum (BVC-like), mEC (border cells firing within \~10 cm of walls), rostral thalamus & anterior claustrum (BVCs and perimeter cells).
89
How do BVCs respond to boundaries?
They fire when a boundary lies at a preferred distance and allocentric direction, irrespective of the animal’s location or behavior, driven by internal path-integration-based memory.
90
What distinguishes distance-tuned vs proximal border cells?
Subicular BVCs fire at considerable distances from walls, while mEC and claustral border cells respond only within \~10 cm of boundaries.
91
What are “boundary-off” and “perimeter” cells?
Boundary-off cells show suppressed firing near one or all boundaries, while perimeter cells fire uniformly along every boundary or exclusively in central areas away from walls.
92
What role do boundary cells play in spatial mapping?
They likely provide geometric inputs that shape and stabilize hippocampal place fields, forming a rich boundary-processing network.
93
Why are object cells important for spatial representation?
Object recognition is vital for survival and underpins the “what” component of episodic memory alongside “where” information, integrating spatial and non-spatial inputs.
94
Through which pathway does non-spatial object information reach the hippocampus?
Via perirhinal cortex → lateral entorhinal cortex (lEC) → hippocampus.
95
How are true object cells distinguished from sensory-encoding neurons?
True object cells combine object sensitivity with spatial specificity, persisting in darkness and following object removal.
96
What characterizes object cells in the anterior claustrum?
\~5.5% of neurons fire upon encountering an object, cease when removed, remain active in darkness or with object substitution, indicating encoding of object location rather than mere sensory cues.
97
What is the memory trace response of lEC object cells?
They maintain firing at the former location of a removed object, indicating lasting spatial memory for object positions.
98
What are ACC trace cells and their characteristics?
Cells in mouse anterior cingulate cortex fire at the precise location of a missing object for up to 30 days after exposure, mirroring lEC trace responses.
99
What is the proposed function of object-sensitive spatial cells in claustrum, lEC, and ACC?
To convey object-place associations to the hippocampus for episodic encoding, as supported by lEC lesions impairing object recognition.
100
Why are goal representations necessary for navigation?
Animals need neural signals specifying “where” to go to reach specific goals like food or shelter, not just “where” they are.
101
Do hippocampal place cells explicitly encode goal locations?
Early work showed they do not reliably fire for goal locations alone; remapping reflects planned trajectory rather than goal.
102
How do place fields change near rewarded locations?
Place fields can skew toward rewarded locations, overrepresenting goal zones, and some neurons increase activity before reward receipt.
103
What did computational models predict about goal cells?
Neurons whose firing scales with distance to a designated goal to aid navigation, with subiculum as a candidate locus.
104
What goal-related signals are found in the medial prefrontal cortex (mPFC)?
Many prelimbic/infralimbic neurons fire selectively at goal zones where rats initiate reward release, forming large goal-centered fields.
105
Does mPFC inactivation abolish hippocampal goal-related firing?
No, suggesting hippocampal-to-mPFC information flow or parallel processing.
106
How does the orbitofrontal cortex (OFC) relate to goal encoding?
OFC neurons encode reward expectation, and any spatial modulation likely reflects reward-related or task-contingent signals rather than pure goal coding.
107
What alternative mechanism could encode goal information without explicit goal cells?
A population gradient of grid-cell activity could encode distance to goal, supported by human fMRI patterns showing goal-related signals.
108
What evidence exists for goal-bearing neurons in bats?
Egyptian fruit bats have hippocampal neurons that fire for the precise allocentric direction and distance of a hidden goal, even when obscured.
109
What remains an open question regarding goal cells?
Direct electrophysiological identification of canonical goal cells in rodents and humans, and how goal signals are formed, routed, and integrated with spatial maps.
110
What are conjunctive cells?
Neurons that simultaneously encode multiple spatial features, like location and direction or location and speed.
111
What are theta-modulated place-by-direction (TPD) cells and where are they found?
TPD cells fire only when the animal is in a specific place and facing a specific direction, found in presubiculum and parasubiculum.
112
What conjunctive cells exist in the retrosplenial cortex?
Retrosplenial conjunctive cells combine spatial location with head-direction tuning, integrating allocentric cues with self-motion information.
113
How do some mEC grid cells demonstrate conjunctive encoding?
Some grid cells also carry head-direction signals, and some head-direction cells exhibit spatial tuning.
114
Why are conjunctive cells important for navigation models?
They provide integrated self-motion and environmental information necessary for computational models requiring simultaneous encoding of location and movement.
115
What role do movement- or action-sensitive cells play in navigation?
They integrate internal self-motion cues—proprioceptive, vestibular, motor efference—for path integration and update position estimates.
116
How do place and head-direction cells exhibit velocity encoding?
Their firing rate and timing modulate based on running speed or angular velocity, with some head-direction cells firing in anticipation of future orientation.
117
How does the striatum contribute to action-sensitive encoding?
It underlies habitual or repetitive behaviors, with neurons firing in relation to specific movements and task phases, often at particular locations.
118
What spatial coding functions does the posterior parietal cortex (PPC) serve?
PPC cells encode sequences of movements or egocentric cue positions, facilitating transformation to allocentric frames; lesions impair orientation to proximal cues and spatial tasks.
119
How does the retrosplenial cortex (RSC) contribute to navigation?
RSC cells conjunctively code location, head direction, and action sequences, linking egocentric movements with an allocentric map.
120
How do movement-sensitive and conjunctive cells support dynamic navigation?
They collaborate across regions to integrate motor and spatial information, enabling conversion between reference frames and supporting flexible navigation.
121
What three cell types inaugurated the field of neural spatial coding?
Place cells, head-direction cells, and grid cells.
122
How has the repertoire of spatially tuned cells expanded beyond the “big three”?
Additional types include interneurons, boundary cells, object cells, goal cells, conjunctive cells, and movement-sensitive neurons, forming a heterogeneous network.
123
In which brain regions does spatially modulated activity occur beyond hippocampus and mEC?
Many neocortical, thalamic, and subcortical regions.
124
How does hippocampal place coding exhibit resilience?
It arises from multiple inputs (grid, boundary, head-direction, object, self-motion) and remains robust even when some inputs are disrupted.
125
What is the nature of the reciprocal connections in spatial circuits?
Many structures both send spatial signals to and receive outputs from the hippocampus, creating a dense, bidirectional network of maps.
126
What challenge does the complexity of spatial representations pose to researchers?
It demands advanced electrophysiology, behavioral paradigms, and sophisticated data-analysis methods to disentangle conjunctive representations.
127
What is a future research direction regarding interneurons and lesser-studied spatial cells?
Comprehensive electrophysiological profiling across brain regions to systematically map interneuron types and spatial cell diversity.
128
What question remains about object cells?
What sensory attributes distinguish “objects” from other cues and how do they drive object cell responses?
129
What question remains about boundary cells?
Do they encode physical barriers, drops, impedance to locomotion, or abstract linear features, and how do “perimeter” and “boundary-off” cells relate?
130
What remains to be understood about goal representation in spatial navigation?
How spatial goals are encoded, stored, and retrieved—whether via dedicated goal cells, grid-cell gradients, or prefrontal–hippocampal circuits.
131
How could virtual and multimodal environments advance spatial coding research?
By testing boundary and object tuning in non-physical spaces (e.g., acoustic, virtual) to probe abstraction levels.
132
Why is mapping inter-regional dynamics important for understanding spatial navigation?
To track the flow of spatial information through reciprocal pathways (e.g., hippocampus ↔ mPFC ↔ thalamus) during navigation and memory tasks.
133
What role could computational and deep-learning frameworks play in spatial navigation research?
They can integrate the full diversity of spatial and conjunctive signals to predict navigational behavior and neural dynamics.
134
Which understudied areas could reveal new insights into the brain’s positioning system?
Claustrum, ACC, septal nuclei, and postrhinal cortex.
135
What distinguishes normal age-related memory changes from pathological aging?
Normal aging involves variable, modest memory decline, whereas pathological aging (e.g., MCI or Alzheimer’s) is marked by progressive cognitive deterioration.
136
What are the three hallmark features of Alzheimer’s disease (AD)?
(1) Brain atrophy (volume reduction), (2) Amyloid-β plaques from APP cleavage forming toxic oligomers and fibrils, (3) Hyperphosphorylated tau tangles causing microtubule destabilization and pathology spread.
137
How is Alzheimer’s disease definitively diagnosed?
Definitive diagnosis requires post-mortem confirmation of both amyloid-β plaques and tau tangles; clinically, diagnosis relies on cognitive decline tests and PET imaging, but PET can show plaques in asymptomatic older adults.
138
Why must PET imaging for amyloid-β be interpreted cautiously in older adults?
Because up to 50% of 70–80-year-olds can have plaques without cognitive symptoms, so PET findings need contextual clinical correlation.
139
What proportion of AD patients exhibit spatial-memory deficits and wandering behaviors early in the disease?
Over 60% of Alzheimer’s patients show spatial-memory deficits and wandering behaviors as an early feature.
140
What is the primary focus of the reviewed scope regarding Alzheimer’s and spatial memory?
Examining rodent transgenic AD models that alter hippocampal–entorhinal firing leading to disrupted cognitive maps and spatial deficits, and human VR studies for early diagnosis and rehabilitation.
141
Who first proposed the cognitive map concept and what does it entail?
Tolman (1940) proposed that animals build an internal representation of space, or cognitive map, from multisensory inputs.
142
Which cell types in the hippocampal–entorhinal circuit contribute to cognitive map formation?
Place cells, grid cells, band cells, head-direction cells, border/boundary cells, object cells, speed cells, goal cells, reward cells, and conspecific-location cells.
143
What are place cells and where are they located?
Hippocampal neurons that fire at specific spatial coordinates, encoding the animal’s current location.
144
What are grid cells and what role do they play?
Medial entorhinal cortex neurons that fire on a triangular lattice, providing a spatial metric for navigation.
145
What is global remapping in the context of place/grid cells?
An orthogonal reorganization of place and grid fields when the animal moves between distinct contexts, supporting pattern separation of overlapping inputs.
146
What is rate remapping and how does it differ from global remapping?
Rate remapping involves changes in firing rate without relocating place fields under subtle context changes, whereas global remapping changes field locations entirely.
147
How do landmark cues affect place and grid cell alignment?
On first exposure, place and grid fields anchor to external cues; they reorganize when environmental boundaries are altered.
148
In what way do place cells encode added barriers or compartmentalization?
They flexibly remap their fields to encode new barriers or compartmentalization but do not encode changes in environmental connectivity.
149
What evidence exists for place cells in humans from single-unit recordings?
Frontal and medial temporal electrodes in epilepsy patients performing VR navigation tasks show neurons responding specifically to particular locations and landmark views.
150
What are path cells and where have they been recorded in humans?
Entorhinal neurons recorded in epilepsy patients that fire along specific paths rather than fixed locations during navigation.
151
How do fMRI studies reveal grid-like activity in humans?
By detecting hexadirectional BOLD modulation in entorhinal cortex during virtual foraging and imagined navigation tasks.
152
In which non-topographic tasks have grid-like codes been observed in humans?
During odor-landscape association tasks in entorhinal and medial prefrontal cortices, and in nonspatial relational memory tasks.
153
What dual functions do HP-EC map-like neurons serve?
They support spatial navigation and episodic memory by providing pattern separation and completion of similar memories.
154
Why are HP-EC map-forming cells particularly relevant to AD pathology?
Because their disruption likely underlies early spatial-memory deficits and wandering seen in AD, making them targets for diagnosis and intervention.
155
Do any animal models fully recapitulate Alzheimer’s disease?
No, but transgenic rodents expressing amyloid-β and/or tau in the hippocampal–entorhinal circuit consistently show spatial-coding dysfunctions resembling early AD features.
156
In AD transgenic models, which dysfunction appears first: grid-cell or place-cell impairment?
Grid-cell dysfunction typically occurs before place-cell breakdown, mirroring the early vulnerability of the entorhinal cortex in human AD.
157
What is network oscillopathy and how does it relate to AD models?
A condition characterized by reduced theta and gamma oscillations across AD models, potentially causing cognitive fluctuations and contributing to spatial deficits.
158
Why is medial entorhinal cortex (MEC) degeneration significant in Alzheimer’s pathology?
Because early MEC degeneration leads to grid-cell dysfunction, driving spatial disorientation and wandering observed in early AD.
159
How do fMRI + VR studies contribute to our understanding of AD-related spatial deficits?
They reveal grid-like brain activity in the entorhinal cortex during navigation tasks, paralleling rodent grid coding, and help identify navigational impairments in at-risk individuals.
160
Can VR tasks detect Alzheimer’s-related navigational deficits before clinical symptoms appear?
Yes, VR-based assessments can identify navigational impairments in individuals at risk for AD decades before clinical diagnosis.
161
What are the advantages of using virtual reality for assessing and rehabilitating spatial memory in AD?
VR offers high ecological validity, engages key cognitive systems, is culturally scalable, and allows for safe, standardized, repeatable rehabilitation exercises.
162
What limitation should be considered when using VR to assess spatial disorientation in AD patients?
VR performance may not accurately reflect real-world disorientation and wandering behaviors in individuals with AD.
163
According to the review, which neurons are among the first to degenerate in Alzheimer’s disease?
Medial entorhinal cortex (MEC) grid cells are among the first to degenerate in AD.
164
How do hippocampal place cells decline following grid-cell dysfunction in AD?
Place-cell deficits arise after grid-cell impairment, as hippocampal mapping loses its entorhinal metric anchor, leading to broader spatial-memory loss.
165
What combination of biomarkers and assessments holds promise for preclinical AD diagnosis?
MEC-targeted imaging, oscillatory (theta/gamma) measures, and VR-based navigation tests combined may allow for early AD detection before symptoms manifest.
166
Why might VR-based rehabilitation be beneficial for spatial-memory deficits in AD?
Because VR can provide controlled, ecologically valid navigation experiences that engage and potentially strengthen cognitive mapping circuits in a safe setting.
167
How does global remapping enable pattern separation in memory encoding?
By orthogonally reorganizing place and grid cell fields across different contexts, it ensures overlapping events are represented by distinct neural codes, reducing interference.
168
What role do band cells play in spatial coding within the HP-EC circuit?
Band cells fire in periodic bands and may contribute to scaffolding the hexagonal grid firing patterns of grid cells.
169
How are boundary or border cells defined in the cognitive map framework?
Neurons that fire in relation to environmental edges or boundaries, providing geometric inputs that shape place-cell firing fields.
170
What evidence supports human hippocampal pattern separation/completion dynamics?
fMRI studies show distinct hippocampal activation patterns when participants discriminate similar scenes or complete partially occluded memories, reflecting pattern separation and completion.
171
Describe ‘rate remapping’ of place cells in subtle context changes.
Rate remapping occurs when place cells change their firing rates without shifting the location of their place fields in response to minor environmental or task alterations.
172
What finding in transgenic AD models mirrors early human spatial disorientation?
MEC degeneration and grid-cell dysfunction precede broader hippocampal pathology, similar to early spatial disorientation and wandering in AD patients.
173
How do VR-based assessments differentiate at-risk individuals from healthy controls decades before AD onset?
At-risk individuals show subtle impairments in VR navigation tasks—such as less efficient pathfinding or reduced grid-like fMRI signals—long before clinical cognitive decline appears.
174
What aspect of MEC function is critical for stabilizing hippocampal place fields?
Grid-cell metric input from the MEC provides the spatial scaffold that anchors hippocampal place fields; loss of this input leads to hippocampal mapping failures.
175
How does septal input influence network oscillations relevant to spatial coding?
Septal GABAergic projections modulate hippocampal theta rhythms, coordinating interneuron timing and affecting place/grid cell plasticity relevant to spatial coding.
176
What evidence links oscillatory deficits to cognitive fluctuations in AD models?
Many AD models show reduced theta and gamma power, correlating with memory lapses and inconsistent spatial behavior, suggesting oscillopathies underlie cognitive instability.
177
What key benefit does VR offer for cross-cultural spatial-assessment studies in AD?
VR can standardize tasks and stimuli across different languages and cultures, ensuring comparable metrics of spatial performance globally.
178
What potential pitfall arises when using VR to predict real-world wandering in AD patients?
Performance improvements in VR may not translate to real-world navigation abilities due to differences in sensory feedback and environmental complexity.
179
Explain how global remapping supports the disambiguation of overlapping episodic memories.
By generating orthogonal place-field patterns for different contexts, global remapping ensures similar experiences in different settings are encoded as separate memories.
180
Which combination of neural measures could serve as early AD biomarkers according to the review?
MEC-specific imaging of grid-like firing properties, measures of theta/gamma oscillations, and behavioral VR performance metrics.
181
What factor makes place-cell deficits a downstream consequence of grid-cell degeneration in AD?
Without grid-cell input to provide the spatial metric, hippocampal place cells lose the coordinate reference necessary for stable firing fields, leading to deficit.
182
In AD transgenic rodent models, how is the progression from grid-cell dysfunction to spatial behavior deficits observed?
Early MEC grid-cell breakdown occurs before observable place-cell impairment, followed by spatial navigation deficits in tasks like the Morris water maze.
183
What implication does early grid-cell dysfunction in AD models have for human intervention?
Therapeutic strategies targeting entorhinal grid-cell function or oscillatory network stability may delay or mitigate spatial-memory decline in prodromal AD.
184
How do hippocampal band cells and speed cells contribute to spatial coding?
Band cells help organize periodic inputs that support grid formation, while speed cells modulate firing rates based on locomotor velocity, aiding path integration.
185
Why is the medial entorhinal cortex especially vulnerable in Alzheimer’s disease?
Because MEC neurons—including grid cells—are among the first to accumulate amyloid-β and tau pathology, disrupting the spatial metric system essential for navigation.
186
Describe the relationship between network oscillopathy and spatial-memory impairment in AD models.
Reduced theta/gamma rhythms impair the timing coordination of place/grid cells, leading to unstable spatial representations and corresponding memory deficits.
187
What advantage does VR have for spatial-memory rehabilitation over traditional methods?
VR allows immersive, repeatable practice in simulated environments that directly engage spatial circuits, potentially restoring cognitive map function without real-world risk.
188
In what way do transgenic AD models demonstrate oscillatory changes before behavioral symptoms?
Many AD models show decreased theta and gamma oscillation power in hippocampal–entorhinal circuits prior to measurable deficits in spatial-task performance.
189
How might MEC-targeted imaging improve early AD diagnosis?
By detecting disrupted grid-cell signals via high-resolution fMRI or other modalities, clinicians could identify preclinical AD before overt cognitive symptoms emerge.
190
What is the significance of VR-based grid-like fMRI signals in at-risk human cohorts?
They indicate the integrity of entorhinal spatial coding; reductions or inconsistencies in six-fold modulation may predict future AD-related cognitive decline.
191
In summary, why are MEC grid cells considered prime targets for AD intervention?
Their early degeneration precipitates hippocampal network breakdown and spatial-memory loss; preserving or restoring grid-cell function could maintain cognitive mapping and delay disease progression.
