Interrupt Cycle
An Overview of Spatial Representation and Cognitive Mapping in Alzheimer's Disease
INTRODUCTION
Alongside the deterioration of episodic and semantic memory [1], spatial disorientation and spatial learning problems are key symptoms of Alzheimer’s disease (AD) and are among the first to develop.[2] This paper firstly provides an overview of the neural basis for spatial representation and cognitive mapping and further examines the impact of Alzheimer’s disease upon these functions.
SPATIAL REPRESENTATION AND COGNITIVE MAPPING
The processing of sensory data to create spatial representations is necessary for spatial memory. [3] Two types of spatial representation are used in navigation strategies; egocentric and allocentric. [4]
Egocentric navigation follows a polar coordinate – or self to object – system, measuring the distance between the individual and the target at any given moment, where the bearing of the individual is directly related to the intrinsic axis of orientation imposed by their physical configuration within the environment. [5] Allocentric navigation is based on knowledge of the spatial relationships between objects, where the individual is able to reach their target destination using a mental representation of the environment, which incorporates the distances and directions between the target and relevant landmarks along the route. From this mental representation, the individual is able to move from one place to another by following an appropriate path. [6] This type of navigation follows a Cartesian coordinate – or object to object – system, whereby the spatial relationships between each landmark in the mental representation are registered and remembered independent of the position of the individual. [7] This type of representation is known as a cognitive map.
Depending on the complexity of the route and environment, both forms of spatial representation may be used in navigational strategies. Egocentric navigation may be useful for direct point to point navigation, whereas allocentric navigation may be more useful in complex environments where obstructions prevent direct navigation. [8]
Alongside the deterioration of episodic and semantic memory [1], spatial disorientation and spatial learning problems are key symptoms of Alzheimer’s disease (AD) and are among the first to develop.[2] This paper firstly provides an overview of the neural basis for spatial representation and cognitive mapping and further examines the impact of Alzheimer’s disease upon these functions.
SPATIAL REPRESENTATION AND COGNITIVE MAPPING
The processing of sensory data to create spatial representations is necessary for spatial memory. [3] Two types of spatial representation are used in navigation strategies; egocentric and allocentric. [4]
Egocentric navigation follows a polar coordinate – or self to object – system, measuring the distance between the individual and the target at any given moment, where the bearing of the individual is directly related to the intrinsic axis of orientation imposed by their physical configuration within the environment. [5] Allocentric navigation is based on knowledge of the spatial relationships between objects, where the individual is able to reach their target destination using a mental representation of the environment, which incorporates the distances and directions between the target and relevant landmarks along the route. From this mental representation, the individual is able to move from one place to another by following an appropriate path. [6] This type of navigation follows a Cartesian coordinate – or object to object – system, whereby the spatial relationships between each landmark in the mental representation are registered and remembered independent of the position of the individual. [7] This type of representation is known as a cognitive map.
Depending on the complexity of the route and environment, both forms of spatial representation may be used in navigational strategies. Egocentric navigation may be useful for direct point to point navigation, whereas allocentric navigation may be more useful in complex environments where obstructions prevent direct navigation. [8]
THE INVOLVEMENT OF THE HIPPOCAMPUS
A large amount of the processing necessary for spatial representation takes place within the hippocampal formation, a part of the brain located in the medial temporal lobes, which has long been regarded in its importance to episodic memory and learning. The hippocampus comprises the entorhinal cortex and the hippocampus proper, which is further divided into the dentate gyrus and Cornu Ammonis (CA) subfields. [9] Specific cells within the hippocampus are responsible for different aspects of spatial representation.
A large amount of the processing necessary for spatial representation takes place within the hippocampal formation, a part of the brain located in the medial temporal lobes, which has long been regarded in its importance to episodic memory and learning. The hippocampus comprises the entorhinal cortex and the hippocampus proper, which is further divided into the dentate gyrus and Cornu Ammonis (CA) subfields. [9] Specific cells within the hippocampus are responsible for different aspects of spatial representation.
PLACE CELLS AND GRID CELLS IN SPATIAL REPRESENTATION
The first evidence of allocentric spatial representation within mammalian brains was the discovery of place cells, which are pyramidal neurons found in the CA1 and CA3 regions of the hippocampus. [10] [11] Place cells fire in a specific location in any given environment, which encodes the individuals’ location: the location in which a place cell fires is known as its place field [12] and the combined firing of place cells within a place field creates an internal neural map of the environment. [13] Following the discovery of place cells, subsequent clinical studies have demonstrated a strong positive correlation between place cell firing and spatial memory, supporting evidence that place cell firing is integral to encoding in spatial memory. [14]
However, place cells do not contain information about the distances between objects or direction, which are required to form a cognitive map of an environment. O’Keefe and Nadel proposed that this information was also located within the hippocampal formation. [15] This hypothesis led to the later discovery of grid cells within the entorhinal cortex by May-Britt and Edvard Moser.
Single grid cells are active in different places in an environment. These points of activation form a hexagonal grid pattern, resembling a honeycomb structure. Different grid cells fire with the same spacing, but in a different phasing, so that every point of an environment is covered. [16] This allows the individual to encode and recall the distances between themselves and other objects in an environment. Several other types of cell have been discovered relating to spatial orientation. Head direction cells fire when an individual faces in a particular direction and boundary vector cells fire when an individual reaches the proximity of a boundary, such as the edge of an environment. [17]
The combined information these cells collect provide the neural basis for cognitive mapping.
The first evidence of allocentric spatial representation within mammalian brains was the discovery of place cells, which are pyramidal neurons found in the CA1 and CA3 regions of the hippocampus. [10] [11] Place cells fire in a specific location in any given environment, which encodes the individuals’ location: the location in which a place cell fires is known as its place field [12] and the combined firing of place cells within a place field creates an internal neural map of the environment. [13] Following the discovery of place cells, subsequent clinical studies have demonstrated a strong positive correlation between place cell firing and spatial memory, supporting evidence that place cell firing is integral to encoding in spatial memory. [14]
However, place cells do not contain information about the distances between objects or direction, which are required to form a cognitive map of an environment. O’Keefe and Nadel proposed that this information was also located within the hippocampal formation. [15] This hypothesis led to the later discovery of grid cells within the entorhinal cortex by May-Britt and Edvard Moser.
Single grid cells are active in different places in an environment. These points of activation form a hexagonal grid pattern, resembling a honeycomb structure. Different grid cells fire with the same spacing, but in a different phasing, so that every point of an environment is covered. [16] This allows the individual to encode and recall the distances between themselves and other objects in an environment. Several other types of cell have been discovered relating to spatial orientation. Head direction cells fire when an individual faces in a particular direction and boundary vector cells fire when an individual reaches the proximity of a boundary, such as the edge of an environment. [17]
The combined information these cells collect provide the neural basis for cognitive mapping.
SPATIAL REPRESENTATION AND ALZHEIMER’S DISEASE
Spatial disorientation is one of the earliest features to manifest in the pathology of Alzheimer’s disease. In the earliest stages of the disease, this presents as an individuals’ inability to cope with new environments. Despite poor orientation and a degree of memory loss, in the early stages individuals with AD are often able to maintain an impressive social façade. [18] These symptoms may only become evident to those around them when they are placed in a strange environment, such as a friend or relative’s home or a new city. [19] However, as the disease progresses, the disorientation extends to more familiar surroundings, including the individual’s own home. [20]
THE IMPACT OF ALZHEIMER'S DISEASE ON SPATIAL MEMORY
Several studies have demonstrated the impairment of spatial memory in Alzheimer’s disease, using route learning tests and memory for scenes. [21] [22] AD has been shown to damage both egocentric and allocentric spatial memory, [23] [24] although one study has suggested that AD has a greater impact on allocentric memory.[25]
During the pathology of Alzheimer’s disease, the hippocampus is the first part of the brain to exhibit neurodegeneration, causing damage to the place and grid cells within this part of the brain. Given the importance of place and grid cells to spatial memory, it is clear that this early damage to the hippocampus is a significant contributing factor to the spatial memory deficits that individuals with AD exhibit early on in the condition. Structure-function studies support this, demonstrating a positive correlation between spatial memory performance and hippocampal volume in AD patients [26] and in a transgenic mouse model of AD, the disruption of place cell firing was found to correlate with spatial memory impairment.[27] The correlation between hippocampal decay and spatial representation has implications for early diagnosis of AD and therapeutic strategies. Tests for spatial memory impairment can help identify individuals who may be developing AD at an early stage, and by identifying the types of cells that contribute to spatial memory, focused developments can be made towards treatments that may protect these cells against damage.
Spatial disorientation is one of the earliest features to manifest in the pathology of Alzheimer’s disease. In the earliest stages of the disease, this presents as an individuals’ inability to cope with new environments. Despite poor orientation and a degree of memory loss, in the early stages individuals with AD are often able to maintain an impressive social façade. [18] These symptoms may only become evident to those around them when they are placed in a strange environment, such as a friend or relative’s home or a new city. [19] However, as the disease progresses, the disorientation extends to more familiar surroundings, including the individual’s own home. [20]
THE IMPACT OF ALZHEIMER'S DISEASE ON SPATIAL MEMORY
Several studies have demonstrated the impairment of spatial memory in Alzheimer’s disease, using route learning tests and memory for scenes. [21] [22] AD has been shown to damage both egocentric and allocentric spatial memory, [23] [24] although one study has suggested that AD has a greater impact on allocentric memory.[25]
During the pathology of Alzheimer’s disease, the hippocampus is the first part of the brain to exhibit neurodegeneration, causing damage to the place and grid cells within this part of the brain. Given the importance of place and grid cells to spatial memory, it is clear that this early damage to the hippocampus is a significant contributing factor to the spatial memory deficits that individuals with AD exhibit early on in the condition. Structure-function studies support this, demonstrating a positive correlation between spatial memory performance and hippocampal volume in AD patients [26] and in a transgenic mouse model of AD, the disruption of place cell firing was found to correlate with spatial memory impairment.[27] The correlation between hippocampal decay and spatial representation has implications for early diagnosis of AD and therapeutic strategies. Tests for spatial memory impairment can help identify individuals who may be developing AD at an early stage, and by identifying the types of cells that contribute to spatial memory, focused developments can be made towards treatments that may protect these cells against damage.
[1] SS. Jheng and MC. Pai, Cognitive map in patients with mild Alzheimer’s disease: A computer-generated arena study, Behavioural Brain Research 200 (2009) 42–47, p.42.
[2] E. Kalova, K. Vlcek, E. Jarolimova and J. Bures, Allothetic orientation and sequential ordering of places is impaired in early stages of Alzheimer’s disease: corresponding results in real space tests and computer tests, Behavioural Brain Research 159 (2005) 175–186, p.175.
[3] R. Wood and D. Chan, The Hippocampus, Spatial Memory and Alzheimer’s Disease, Advances in Clinical Neuroscience and Rehabilitation, < http://www.acnr.co.uk/wp-content/uploads/2015/07/05-07_ACNRMJ15.pdf> [Accessed: 10/1/2016].
[4] Jheng and Pai, Cognitive map in patients with mild Alzheimer’s disease: A computer-generated arena study, p.42.
[5] Wood and Chan, The Hippocampus, Spatial Memory and Alzheimer’s Disease, Advances in Clinical Neuroscience and Rehabilitation, < http://www.acnr.co.uk/wp-content/uploads/2015/07/05-07_ACNRMJ15.pdf>
[6] Jheng and Pai, Cognitive map in patients with mild Alzheimer’s disease: A computer-generated arena study, p.42.
[7] Wood and Chan, The Hippocampus, Spatial Memory and Alzheimer’s Disease, Advances in Clinical Neuroscience and Rehabilitation, < http://www.acnr.co.uk/wp-content/uploads/2015/07/05-07_ACNRMJ15.pdf>
[8] Ibid.
[9] Ibid.
[10] B. Poucet, PP. Lenck-Santini, V. Paz-Villagran, E. Save, Place cells, neocortex and spatial navigation: a short review, Journal of Physiology - Paris 97 (2003) 537–546, p.537.
[11] J. O’Keefe and J. Dostrovsky, The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. (1971) 34(1): 171-5, pp.171-5.
[12] Wood and Chan, The Hippocampus, Spatial Memory and Alzheimer’s Disease, Advances in Clinical Neuroscience and Rehabilitation, < http://www.acnr.co.uk/wp-content/uploads/2015/07/05-07_ACNRMJ15.pdf>
[13] O. Kiehn and H. Forssberg, Scientific Background: The Brain’s Navigational Place and Grid Cell System, <https://www.nobelprize.org/nobel_prizes/medicine/laureates/2014/advanced-medicineprize2014.pdf> [Accessed 10/1/2016], p2.
[14] J. O’Keefe, A. Speakman, Single unit activity in the rat hippocampus during a spatial memory task. Exp Brain Res. (1987) 68(1): 1-27, pp.1-27.
[15] J. O’Keefe and L. Nadel, The Hippocampus as a Cognitive Map, [Oxford: Oxford University Press, 1978].
[16] Kiehn and Forssberg, Scientific Background: The Brain’s Navigational Place and Grid Cell System, <https://www.nobelprize.org/nobel_prizes/medicine/laureates/2014/advanced-medicineprize2014.pdf> p.3-4.
[17] Wood and Chan, The Hippocampus, Spatial Memory and Alzheimer’s Disease, Advances in Clinical Neuroscience and Rehabilitation, < http://www.acnr.co.uk/wp-content/uploads/2015/07/05-07_ACNRMJ15.pdf>
[18] Ibid., p.36.
[19] A. Burns, R. Howard and W. Pettit, Alzheimer’s Disease: A Medical Companion, [Oxford: Alden Press, 1995], pp.35-36.
[20] Ibid., pp.35-36.
[21] MM. Cherrier, M. Mendez and K. Perryman. Route learning performance in Alzheimer disease patients, Neuropsychiatry Neuropsychology Behavioural Neurology, (2001) 14(3): 159-68, pp.159-68.
[22] AR. DeIpolyi, KP. Rankin, L. Mucke, BL. Miller and ML. Gorno-Tempini. Spatial cognition and the human navigation network in AD and MCI. Neurology (2007) 69(10): 986-97, pp. 986-97.
[23] Cherrier, Mendez and Perryman. Route learning performance in Alzheimer disease patients, pp.159-68.
[24] J. Laczo, K. Vlcek, M. Vyhnalek, O. Vajnerova, M. Ort, I. Holmerova, et al. Spatial navigation testing discriminates two types of amnestic mild cognitive impairment. Behavioural Brain Research (2009) 202(2): 252-9, pp.252-9.
[25] Kalova, Vlcek, Jarolimova and Bures, Allothetic orientation and sequential ordering of places is impaired in early stages of Alzheimer’s disease: corresponding results in real space tests and computer tests, p.175.
[26] KK. Moodley, L. Minati, VE. Contarino, S. Prioni, R. Wood, R. Cooper, et al. Diagnostic differentiation of mild cognitive impairment due to Alzheimer’s disease using a hippocampus-dependent test of spatial memory. Hippocampus (2015) Jan 20. doi: 10.1002/hipo.22417. [Epub ahead of print].
[27] F. Cacucci, M. Yi, TJ. Wills, P. Chapman, and J. O’Keefe, Place cell firing correlates with memory deficits and amyloid plaque burden in Tg2576 Alzheimer mouse model. Proc Natl Acad Sci U.S.A. (2008) 105(22): 7863-8, pp.7863-8.