Cognitive mapping deficits in schizophrenia: a critical overview.

Hippocampal deficits are an established feature of schizophrenia and are complementary with recent evidences of marked allocentric processing deficits being reported in this disorder. By "Cognitive mapping" we intend to refer to the concepts from the seminal works of O'Keefe and Nadel (1978) that led to the development of cognitive map theory of hippocampal function. In this review, we summarize emerging evidences and issues that indicate that "Cognitive mapping deficits" form one of the important cognitive aberrations in schizophrenia. The importance has been placed upon hippocampally mediated allocentric processing deficits and their role in pathology of schizophrenia, for spatial/representational cognitive deficits and positive symptoms in particular. It is modestly summarized that emerging evidences point toward a web of spatial and cognitive representation errors concurrent with pronounced hippocampal dysfunction. In general, it can be stated that there are clear and consistent evidences that favor the cognitive mapping theory in explaining certain deficits of schizophrenia and for drawing out a possible and promising endophenotype/biomarkers. Further research in this regard demands attention.

INTRODUCTION

Understanding the cognitive basis for schizophrenia has been challenging because it is characterized by a wide array of aberrations. One of the major difficulties in understanding the nature of deficits exhibited in schizophrenia emanates from the fact that sufficient research literature e.g., see[1] reflects that the deficits observed can be dissociable in terms of psychological and neural pathophysiology. Yet this pathophysiological dissociation does little in achieving an understanding of this disorder.[2] Nonetheless, it has been postulated that the wide-ranging pattern of cognitive aberrations in schizophrenia could potentially be narrowed down to a set of “core” deficits. The significant cross-task correlation[3] within the “context-sensitive” conditions of several cognitive tasks seem to support the theory that schizophrenia is characterized by “an impairment in using representations of context” to govern appropriate behavior.[4]

Disparate lines of evidence suggest that a primary function of the hippocampus is to bind previously experienced item and context information to construct detailed item-in-context memories.[56] Hippocampal formation and medial temporal lobe (MTL) see[7] have been proposed to be critically involved in the pathogenesis of schizophrenia.[78] Hippocampus figures prominently in meta-analyses of brain abnormalities associated with schizophrenia[9101112] and pathophysiological theories of schizophrenia.[13141516] In this review, we focus our attention to the deficits in context representation with specific emphasis on egocentricity-allocentricity (which explains both visuospatial frame of reference[1718] and social frame of reference),[1920] their relation to the hippocampus and the resultant dysfunction that is manifested at several levels as features of schizophrenia.

Current models of visuospatial abilities (encompassing constructs like navigation, spatial learning and spatial memory) are explained by two perspectives of visual space: Allocentric (object or environment centered) reference and egocentric (self-centered or body-centered) reference. The visual space is thus delineated into egocentric and allocentric frames of references. Egocentrism is the ability to see the world from one's own perspective and allocentrism is the capacity to experience the world from a non-egocentric/environment or object-centered point of view. Observations from lesion studies and single unit recordings in animals and humans, as well as from functional imaging studies in humans e.g.,[2122232425] have established the role of hippocampal and parahippocampal cortices in mediating allocentric abilities. Further, learning allocentric i.e., object – location associations has been particularly related to hippocampal function across species.[26272829] Hippocampal and parahippocampal activation occurs during the computation of spatial body positions, complex geometric scenes, or 3-dimensional (3D) navigation.[3031] These evidences yield conclusive indications confirming the critical role for the hippocampus in cognitive mapping as discussed below.

The cognitive map theory was developed from the seminal works of O’Keefe and Nadel and was published in their book “Hippocampus as a cognitive map.” As per this postulate, “hippocampus represents the environments, locations within those environments and their contents and thus mediates spatial memory processes and flexible navigation.”[32] This model posits that, in humans, spatial maps are built in the right hippocampus whereas semantic maps are located in the left hippocampus. The former is responsible for encoding spatial relationships, while the latter provides semantic links and structure for comprehension and production of discourse. Evidences from the study of patients with amnesia support this theory.[33] Furthermore, one or both hippocampi integrate temporal information derived from the frontal lobes, this allows to timestamp each individual visit to a location and provides the basis for a spatio-temporal contextual or episodic memory system. Hippocampus also mediates “declarative memory”[34] and “flexible relational memory”[35] in humans and some animals. Most importantly, the cognitive map theory states that hippocampus specifically supports allocentric processing of space; while egocentric processing, the conceptual polar opposite of allocentric cognition, is supported by the parietal neocortex.[32] Conclusively, based on research evidences, the hippocampus has been hypothesized as essential to construction and storage of spatial information in the form of allocentric spatial cognitive maps;[36] declarative (explicit information) rather than procedural (implicit information) memory;[37] and disambiguation of the relations between stimuli that combine to form unique representations during the encoding and recall of information.[383940] All of these hypotheses predict a spatial impairment after hippocampal damage.[41] This also implies that accurate mental representations are invariably dependent on adequate hippocampal function. In summary, this discussion implies hippocampal role in visual and spatial encoding, representation, recall, manipulation, memory and learning. In this article, attempting to expand on the original proposition of “The cognitive mapping theory” as proposed by O’Keefe and Nadel, we intend to summarize the observations to support the view that cognitive mapping deficits (hippocampal dysfunction and associated allocentric deficits) are among the critical contributors to schizophrenia disease process; more importantly, these deficits can be linked with certain important clinical manifestations of this disorder. To emphasize this, we have reviewed the contributions of the hippocampus and associated structures in this regard. Furthermore, we have illustrated the utility of allocentric and egocentric concepts (subsumed under the broader framework of our proposed cognitive mapping theory implicating hippocampal function) of understanding visuospatial and social frames of reference in explaining symptomatic expressions of schizophrenia by recent research findings.

COGNITIVE MAPPING DEFICITS IN SCHIZOPHRENIA

Studies that have evaluated egocentric/allocentric cognitive functions in schizophrenia are summarized in Table 1. Several paradigms are widely employed in the investigation of visuospatial representation (with specific focus on assessment of egocentricity-allocentricity) among both patients with schizophrenia and normal controls [Table 1]. In the following sections, we have attempted to relate these observations with the clinical manifestations of the schizophrenia.

Table 1

Studies that have evaluated egocentric/allocentric cognitive functions in schizophrenia*

Deficits in source monitoring and clinical symptomatology

One crucial cognitive deficit in schizophrenia patients could be their inability to monitor their own actions[4243] and differentiating between imagination and reality.[4445] Several studies report a general impairment of action monitoring in schizophrenia patients.[42434647] Evidences suggest that errors of source memory, free recall and recognition are positively correlated with positive symptoms and inversely correlated with negative symptoms reflecting emotional and social deficits.[48] Additional support towards this paradigm for understanding the pathogenetic basis for hallucinations in schizophrenia comes from literature on “source monitoring,” which refers to the ability to remember the origin of information.[49] Positive symptoms such as hallucinations may thus be interpreted as a deficit of self-monitoring associated with a kind of over-activity of mental imagery: Patients’ inner life is particularly intense and vivid and the patients are unable to realize that their mental images come from themselves rather from the external world.[5051] This function is impaired in patients with schizophrenia and underlies several positive[5253] and negative symptoms see.[48] It has been proposed that episodic memory and source monitoring are closely interlinked so much so that brain structures implicated in the former (for the encoding process, storage and retrieval of memory trace) are also associated with the latter[54] vouching for a central role of the hippocampus in the entire process. Further, source monitoring has been shown to be associated with hippocampal activation (in storage of source memory,[55] correct retrieval of source information[56] and external source monitoring i.e., identifying and remembering external sources-persons from whom information is acquired).[57]

The three-component model-the binding of the item and context model[5859] – is in tune with these observations and this model postulates that different functions are performed by the sub-structures of the hippocampal system. The perirhinal cortex processes item information, the parahippocampal cortex processes context information and the hippocampus binds the item and the context. This has been partially supported by recent evidences. The perirhinal cortex is indeed related to the processing of status (i.e., familiar or novel) of item information and the hippocampus associated to the retrieval of the relationship between items and their sources. However, it is probable that the hippocampus plays roles in both the recognition processes.[57] Furthermore, recent evidences implicate sub-regions within MTL,[57] pre-frontal cortex (PFC) and posterior cortex in representing and/or processing source features see[60] for details. Taken together, these evidences indicate that source monitoring deficits are the outcome of a hippocampal dysfunction-binding failure between the item and its respective context. Further this deficit in source monitoring mediates positive and negative symptoms of schizophrenia.

Delusions and hallucinations

Perception[61] and memory[62] are substantially constructive and our perception and recollections are strongly influenced by our prior experiences and expectancies. Our memories are subject to experience-dependent biases[63] and are highly mutable by nature.[6465] This can be explained by the discrepancy-attribution hypothesis.[6667] Both true and false familiarities are experienced when a comparison between expectations and outcomes within a processing episode elicits a surprise or prediction error. This motivates the person to seek an explanation, attributing the surprise to some plausible source in the current environment or to similar features in the past.[68] This kind of processing errors seems to involve aberrant perceptions (representation of context and/or content of one's environment) and/or attributions (meta-representations) mediated by declarative memory system (semantic and episodic). These processes seem to explain reality alteration underlying positive symptoms of schizophrenia, such as hallucinations and delusions, which involve gross alterations in the experience of reality. It is also conceived that the drive to explain away odd experiences, in schizophrenia and related conditions, can result in delusion formation.[6970] This then sculpts and vitiates future experiences and attributions.[717273] Recent studies have demonstrated an association between illusory memories, perceptual aberrations and odd beliefs.[68] Structural abnormality in hippocampus (reduction in the dentate gyrus) has been reported to increase the prevalence of illusory pattern completion and reduce discrimination between present and past events as stored in memory.[16] Evidences indicate inappropriate engagement of the right PFC (pre-frontal cortex) in mediating false memory formation, odd perceptions and unusual beliefs by signaling inappropriate mismatches between expectancy and experience which engage new learning.[74] Such interactions among neural networks leads to the formation of novel associations, which may have adaptive advantages,[7576] but in its extreme form, hyperactivity of such associations ultimately leads to psychotic symptoms.[68] Furthermore, role of the hippocampus in new learning and real time association formations hippocampal damage results in the inability to recall recent events; for models see;[77] the hippocampus as a possible mediator of accessing previously stored rigid scene information to permit its flexible engagement[78] and construction of mental images[79] lends it a more central role in mediating aberrant associations, which manifest as positive symptoms of delusions and hallucinations.

Deficits in context processing

The processing of stimuli in a spatiotemporal context is dependent on the hippocampus. The hippocampus is implicated in conjunctive coding of stimulus features.[8081] This includes conjunctions between object identity and position[828384] and temporal conjunctions.[8586] Context processing deficits in schizophrenia are manifested as severe context insensitivity, associated with impairments in choosing subordinate over dominant responses based on context cues, high false alarm rates in object recognition and deficient retrieval of context information in source monitoring.[87] These deficits could be resulting from reduced connectivity in parahippocampal regions, leading to the formation of abnormal episodic representations, with poor binding of the object and spatial features and a predominance of object information, at the expense of spatial information. This bias causes the object cues to tend to override the context cues, which place only weak constraints on MTL processing. In addition, the poorly integrated entorhinal representations result in reduced retrieval during use of the paradigms that strongly draw on links between the different aspects of an episode, for instance source monitoring and free recall.[8788] Further the reduced entorhinohippocampal connectivity leads to increased representational overlap in the system. This implies that some patterns are not stored in a distinctive episodic representation and cannot be retrieved at all. On the other hand, increased overlap enhances formation of so-called spurious attractors: Strong patterns-connected to many inputs and outputs. Such patterns may get inappropriately activated; especially in paradigms that enhance formation of overlapping representations through the presentation of similar stimuli (e.g., source monitoring).[87] It has been suggested that context processing and episodic memory share same underlying binding deficit.[87] Space and time allow us to determine “when and where” of our recent memories and are thus crucial to episodic memory formation. Recent study suggests hippocampal activation in both spatial and temporal order processing, at least in the context of navigation while parahippocampal and PFC, play largely distinct roles in spatial and temporal order processing, respectively.[89] Taken together, these evidences support the role of hippocampal system in binding deficits that lead to faulty context processing and construing of false memories or aberrant episodic memory snippets; signifying a deficiency probably explainable by cognitive mapping theory of hippocampal function.

Impairments of social cognition: False memory, empathy and theory of mind

Human relationships are contingent on the memories of social interactions. Nonverbal cues (such as gesture, body orientation and eye gaze) are essential in social situations: They allow an individual to recognize that he or she is being directly addressed e.g.,[90] and consequently define the egocentric or allocentric context in which communication occurs. The ability to recall if a past conversation occurred in an egocentric or allocentric context is undoubtedly important for maintaining interpersonal relationships and information about the neural processes responsible for encoding the context of a social communication are inadequate. Past research indicates that left inferior frontal, posterior temporal, premotor and hippocampal brain regions are involved in creating memories of speech and gesture communication.[91] False recognition is a phenomenon whereby people sometimes believe they recognize things that they have never actually encountered, for example, confusing a stranger with an old acquaintance. This often occurs in everyday situations. It has been reported that memories of social interactions are egocentrically biased. Further at the neural level, activations of specific cortical and hippocampal regions during encoding have been reflective of accurate and inaccurate recollections of social contextual information. Activity in the right hippocampus was associated with successful encoding of speech, gesture and their social context. This supports the hippocampal theories of relational associative memories.[92] Though these findings come from studies on healthy participants and specific studies probing false recognition or false contextual memories of social interactions have not been reported for schizophrenia patients; yet it is quite conceivable that pronounced allocentric deficits[93] together with hippocampal abnormalities could be contributing to the outstanding deficits in encoding social contexts and forming false memories of social interactions among schizophrenia patients.

A major aspect of “Empathy” involves adopting psychological perspective of another person and is related to the ability of taking another person's visuo-spatial perspective. Some studies have reported the role of visuospatial abilities in cognitive and affective empathy in schizotypy and schizophrenia patients.[9495] Lower self-reported cognitive, but not affective, empathy has been reported in individuals diagnosed with schizophrenia[95] and impaired theory of mind has been extensively documented in patients with schizophrenia see[96] for review. These deficits co-occur in schizophrenia and are mediated through shared neural pathways; as in, there is evidence for parietal cortex and the temporoparietal junction being involved in both empathy and visuospatial processing.[979899] Many studies have reported both reduced empathy[9596100101] and subtle differences in spatial attention[102103104105106] and visuospatial transformation ability[107108] in schizophrenia patients and among those found high in schizophrenia-like traits. These findings thus indicate that visuospatial representational deficits (in all probability involving hippocampal dysfunction) interfere with social representation and social perspective taking that are subsumed under empathy.

Theory of mind refers to the ability to attribute mental states like beliefs, intents, desires, knowledge, pretension, etc., to self and to others.[109] According to Langdon et al.[93] and Langdon and Coltheart[112], “theory of mind” impairments in mental states attribution in schizophrenia spectrum disorders are due to inefficient abilities to reconstruct another first-person experience (allocentric simulation). A study done by Langdon et al.[93112] found that ability to take another person's perspective is impaired in schizophrenia patients. In relational frame theory terms, the ability to respond in accordance with the deictic frame of I-YOU would be impaired when additional relational responding is necessitated by the inclusion of the IF-THEN frame (i.e., “If I were you then I would believe that”). Several studies have demonstrated that schizophrenia patients perform less accurate than controls when required to reverse the frame of I-YOU (attribution of belief to another) and/or to respond in accordance with the frame of logical note (attribution of a false-belief).[110] These growing literature on mental states attribution in schizophrenia shows that patients with schizophrenia present a deficit in attributing false-belief.[96111] It also supports the idea that these patients have an important disability of adopting another's point of view.[93] It has been shown that hippocampus mediates errors in construction of mental images[79] and may thus reflect inefficient abilities to reconstruct another first-person experience (allocentric simulation) underlying deficits of false-belief attribution.

Some studies have reported disturbed visuo-spatial perspective taking in normal adults with high scores on self-reported measures of schizotypy.[112] Since schizotypy refers to the personality traits that are related to symptoms of schizophrenia and imply a latent liability for the disorder,[94] such results are insightful. Those high on schizotypy are poor mentalizers, hence it is highly suggestive that poor mentalizing among normal adults may be better conceived as an impairment of perspective taking (visual and/or cognitive).[112]

Disorganization symptoms and excessive egocentricity processing in schizophrenia

Differential symptom picture of schizophrenia is associated with varying visuo-spatial performance profile among patients. Schizophrenia subjects with stronger disorganization symptoms have been found to perform poorly on egocentric processing tasks than their counterparts with lesser disorganization symptom.[94113] Thakkar and Park[94] reported that greater accuracy on the perspective-taking task in the condition that required a self–other transformation was associated with increased positive syndrome schizotypy, suggesting that those individuals who tend to have anomalous cognitive and perceptual experiences are better at inhibiting their own perspective. Enhanced egocentric manipulations may be just as problematic as an inability to imagine another person's viewpoint and either way lead to reduced empathic understanding. This data when taken together with evidences supporting allocentric deficit hypothesis of schizophrenia[93] indicate that-in general, schizophrenia patients demonstrate allocentric deficits; but those with pronounced cognitive and perceptual processing deficits are further impaired on mental representation. They may demonstrate lesser deficits on allocentric perspective taking task, but their corresponding poorer performance on cognitive empathy indicates more deteriorated mental representations of complex (like social) environments.

SYNTHESIZING THE COGNITIVE MAPPING DEFICITS IN SCHIZOPHRENIA

Several studies have reported that allocentric processing is impaired, but egocentric processing is preserved among schizophrenia patients.[113114] Allocentric simulation hypothesis posits that pathological referencing in schizophrenia results from the difficulty in adopting a world-centered – inter-subjective –reference frame. In reiterating this hypothesis, experimental data has shown intact reaction time (RT) and learning rate during egocentric referencing among patients with schizophrenia. Interestingly, this study further reported “a certain improvement in RT associated with task progression in the stable allocentric (landmark-centered) condition in patients; though the correlation between RT and set did not reach statistical significance.”[114] This partially preserved stable allocentric (landmark-centered) task related RT improvement in patients could reflect the possibility that the egocentric and stable allocentric (landmark-centered) conditions reinforce structural representations of a stable body position or a stable environment respectively and are thus relatively preserved. The RT during unstable allocentric (object-centered) referencing that depends on the transient intrinsic nature of the object the ball always changes its position in the task used by[114] thus shows no improvement over time. This evidence seems to support the notion that “task-specific mechanisms prominently contribute to visuospatial cognitive dysfunctions in schizophrenia.”[115] Further another recent study demonstrated that the posterior superior parietal cortex/precuneus play an important role in allocentric representation while the hippocampus and interactions between the hippocampus and these parietal areas, are important for flexible utilization of these representations[78] implicating a more central role of the hippocampus in mediating allocentric processing. However it should be noted that parietal neocortex has been implicated in egocentric processing. Egocentric and allocentric process have been found to demonstrate an enormous amount of overlap of underlying neural circuits[116117118119].

In their translational study, Girard et al.[121] examined allocentric and egocentric memory for spatial locations and recent event memory (EM) and reference memory (RM) among schizophrenia patients using the Virtual water morris task employed in animal models (rats). RM refers to information that is important and invariant across several problems, like general task rules and procedures, whereas recent EM refers to a flexible and dynamic memory for context-specific information unique to trials within task problems like in delayed-(non) matching tasks. Schizophrenia patients demonstrated pronounced allocentric memory deficits for spatial location and RM; and egocentric memory for spatial location and recent EM were relatively preserved. These findings were consistent with previous research studies.[113] Somewhat weaker but consistent differences reported between EM versus RM deficit in schizophrenia patients are that cognitive mapping theories of hippocampal function may be more relevant than EM-RM distinctions among humans.[120] The associative memory deficit in schizophrenia is also consistent with hippocampus mediated impairment. These findings bridge the gaps between animal models and human studies and also establish hippocampal dysfunction as central deficit of this pattern.[121]

In their study with a very large sample size, Thakkar and Park (2010)[94] reported impaired maintenance and spared manipulation of representations in working memory (WM). They found that mental manipulation of visual stimuli was spared in sample of patients and they observed a well-replicated impairment in passive maintenance of the location of stimuli. Further they reported that patients were more accurate than controls on the allocentric mental rotation at the largest degree of rotation, which placed the greatest demand on mental manipulation. The counterintuitive nature of this finding can be explained on several grounds. One potential reason behind this discrepancy is that tasks that purport to index WM manipulation ability do not isolate the component processes of WM.[94] Maintenance and manipulation are two interdependent but dissociable components of WM and thus it is possible to have one relatively preserved while the other is impaired as reported in these findings. The observation made here is novel and demands further investigation. This also suggests that a pocket of cognitive function might be enhanced in schizophrenia patients. Another possibility behind these observations could be-brain's compensatory mechanisms. Since the WM maintenance is impaired, the WM manipulation component could have been over exercised in everyday tasks and as a result of repeated usage, this feature could have led to a strengthened information processing pathway. As a result WM manipulation becomes enhanced among such patients. This finding favors our previously visited position on “a need for examining the task specific mechanisms that seem to make a prominent contribution to visuo-spatial cognitive dysfunction in schizophrenia.”[115]

Several studies propose alternate explanation to these observed allocentric deficits. They propose that allocentric deficits might be the result of excessive egocentric referencing or inability inhibit one's own perspective; this proposition is in tandem with the disruption in visuo-spatial information processing and perception observed in patients with schizophrenia.[94114122123124125] Recently allocentric processing deficits have been given more central concern. In these studies, it was demonstrated that perspective-taking difficulty (as reflected by performance deficits on theory of mind tasks with “indirect instructions”) impairs insight in schizophrenia. Further Lysaker et al.[127] showed that reduced ability to organize and interpret ambiguous stimuli, to differentiate between self and other's perspectives and to formulate logical accounts of behavior and social exchange predicted poorer awareness of psychiatric symptoms among schizophrenia patients. They further suggested that replication of these results would indicate that in order to achieve awareness of their condition; patients with schizophrenia may need assistance with making sense of their environment and organizing their experience of the illness. These observations imply that, non-egocentric referencing, as a higher order cognitive function, is associated with decentration, functionality and disease outcome[126127] and plays a crucial role in manifestation of schizophrenia.

Some useful evidence in this regard comes from “visuospatial perspective switch tasks.” Schizophrenia patients demonstrate increased switch cost when switching from egocentric referencing to allocentric referencing but not vice-versa.[114] This finding is supported by research showing that switching towards a dominant (in case of schizophrenia patients’-egocentric) response requires greater effort than switching towards a less dominant (in case of schizophrenia patients’-allocentric) response.[128] The problem that patients with schizophrenia face is-undoing the inhibition for stimulus-response relation when switching egocentric to allocentric as the former is dominant in their case.[114] These findings suggest allocentric deficits as a stable feature of schizophrenia and give plausible explanations underneath these deficits.

In summary, recent evidences are expanding the scope of the cognitive mapping theory of hippocampal function. In their seminal work, O’Keefe and Nadel proposed role of hippocampus in encoding spatial relationship (right hippocampi), semantic maps (left hippocampi), integration of temporal information from frontal lobe and allocentric processing. We examined how emerging evidences point towards a broader role of hippocampus by indicating its role in source monitoring, false memories resulting for aberrant perception and attribution, contextual binding and social cognition (empathy and meta-representative abilities like Theory of mind). Furthermore, allocentric processing deficits have been found central to information processing in schizophrenia. Recent evidences indicate that circuitry for allocentric processing is not limited to hippocampal system. Both egocentric and allocentric processing share a remarkable overlap of neural circuitry e.g., regions of parietal lobe have been implicated in both egocentric[33] and allocentric processing).[78] Thus, these evidences merit a closer scrutiny and further investigations for concrete conclusions are drawn.

CRITIQUE ON COGNITIVE MAPPING THEORY FOR SCHIZOPHRENIA PATHOGENESIS

The critical limitation arise from the fact that current evidences indicate complementary roles of allocentric and egocentric representations of space depending on the number of locations/landmarks to be remembered and the size and familiarity of the environment.[129] Further egocentric and allocentric referencing have been found to closely interrelate on the behavioral and neuronal level. We have discussed evidences from studies of spatial WM in favor of our position, but WM being a constructive and compartmentalized concept, is yet to be studied in terms of its components to yield definitive conclusions. Further, discrepancies in RT while performing visuospatial perspective oriented tasks have raised some concerns about the nature of allocentric and egocentric processing (in relation to task complexity). We review these findings and discuss the challenge they posit to our proposition.

The egocentric and allocentric referencing are not entirely independent of each other. On the neural level, they share a fronto-parietal network with an overlap of up to 88%.[116117118119] Egocentric tasks recruit posterior parietal and frontal premotor areas. In addition to these regions, allocentric processing also activates occipito-temporal and retrosplenial cortices. A study by Committeri et al.[116] contrasted cortical activity during viewer-centered, object-centered and landmark-centered referencing with a non-spatial condition. Egocentric referencing (viewer-centered) activated the dorsal stream and frontal areas. The unstable (object-centered) and stable (landmark-centered) allocentric conditions were associated with ventrolateral and medial occipito-temporal activation, respectively. Interestingly, the parahippocampal gyri were bilaterally activated exclusively in the landmark-centered condition, where subjects had to consider the surrounding's geometrical structure as a spatial reference. In fact, parahippocampal activity has been associated with contextual retrieval of extra-personal global structures from memory.[130131] Further, the “two-system models” propose that transient “ego” and more sustained “allo” representations are processed in parallel, with preferential use of one system likely depending on self-motion, environmental structure and experience-dependent factors.[131] In addition, the multiple memory systems studied are relative versus mutually exclusive and may compete or support each other.[129132133] This data presents allocentric and egocentric processing as non-exclusive and dependent phenomena and complicates our claim of one being impaired and other preserved in patients with schizophrenia.

Finally, most of the current research has successfully explained positive symptoms of schizophrenia through deficits of source monitoring, meta-representation and context binding. Research evidences exploring the role of hippocampal pathology and allocentric deficits in relation to negative symptoms are too limited to indicate a conclusion.

SOME DIRECTIONS FOR FUTURE RESEARCH

There are some emerging issues that should be taken into consideration while interpreting current literature and these may play a crucial part in directing future research. One of them could be effects of medication. Studies on treatment naïve and treated patients are required to guide emerging findings and address discrepancies. Antipsychotics are expected to interfere with visuomotor learning; however the study by Weniger and Irle found no relationship between antipsychotic dosage and allocentric or egocentric task performance. Further clinical studies have shown that among schizophrenia patients, atypical antipsychotics have favorable effects on cognitive and motor functions.[134135] Some studies have reported a protective effect of olanzapine on implicit but not explicit visual learning in schizophrenia subjects.[136137] This could possibly give psychopharmacological explanation behind preserved egocentric abilities in schizophrenia patients. However, such findings, in absence of longitudinal studies reflecting on visuospatial abilities at different stages of the schizophrenia disease process, may at best be speculative and demand further investigation. Furthermore, in future, studies should also show whether preserved egocentric memory in recent-onset schizophrenia is a feature of the disease or rather reflects the beneficial properties of some or all atypical antipsychotic drugs.[113]

CONCLUSIONS

In this review, we have summarized studies supporting a consistent pattern of mapping deficits among patients with schizophrenia. These observations support the view that deficits in mental representations and mental constructions that are vital for cognitive mapping are among the critically impaired functions in schizophrenia. Visuospatial processing deficits and hippocampal abnormalities are robust and could possibly be a trait-marker for this disorder. A cognitive mapping viewpoint, drawn from these premises, can explain a wide range of deficits characterizing the schizophrenia disease process. Positive symptoms such as delusion, illusion and hallucinations in particular along with higher cognitive processes of empathy, false-belief attribution and other forms of meta-representation can be all explained by a single principle. Such theoretical unity facilitates comprehensive framework for conceptualizing the diversity of deficits expressed in schizophrenia disease process. In this light, unsurprisingly, research on visuospatial processing, meta-representation abilities and similar cognitive mapping constructs are catching momentum.

Although presented as intriguing, a lot remains to be desired from current research paradigms. Longitudinal studies with large sample size (to allow statistical rigor), differentiating between medicated and treatment naïve participants with positive and negative symptom picture over different phases would allow more clarity. Further, studies testing for allocentric deficits’ specificity to schizophrenia are inadequate. Future researches need to focus on relatives of patients with schizophrenia and prodromal individuals; this will help determine if visuospatial impairments may serve as phenomenological markers for the disease. Future studies should also explore further possibilities of recruiting virtual reality paradigms in investigating allocentric and egocentric processing as they seem promising in providing-translational comparisons with animal models, 3D first person environment for simulating real-life like experimental contexts and are well tolerated by patients. Though research findings are not yet adequate in establishing schizophrenia as a disorder of cognitive mapping, this proposition may prove to be a comprehensive framework on further deliberation and deserves disciplined attention.

Supplementary Table 1

Experimental paradigms of investigating mental representation