The brain dynamics of visuospatial perspective-taking captured by intracranial EEG.

Visuospatial perspective-taking (VPT) is the ability to imagine a scene from a position different from the one used in self-perspective judgments (SPJ). We typically use VPT to understand how others see the environment. VPT requires overcoming the self-perspective, and impairments in this process are implicated in various brain disorders, such as schizophrenia and autism. However, the underlying brain areas of VPT are not well distinguished from SPJ-related ones and from domain-general responses to both perspectives. In addition, hierarchical processing theory suggests that domain-specific processes emerge over time from domain-general ones. It mainly focuses on the sensory system, but outside of it, support for this hypothesis is lacking. Therefore, we aimed to spatiotemporally distinguish brain responses domain-specific to VPT from the specific ones to self-perspective, and domain-general responses to both perspectives. In particular, we intended to test whether VPT- and SPJ specific responses begin later than the general ones. We recorded intracranial EEG data from 30 patients with epilepsy who performed a task requiring laterality judgments during VPT and SPJ, and analyzed the spatiotemporal features of responses in the broad gamma band (50-150 Hz). We found VPT-specific processing in a more extensive brain network than SPJ-specific processing. Their dynamics were similar, but both differed from the general responses, which began earlier and lasted longer. Our results anatomically distinguish VPT-specific from SPJ-specific processing. Furthermore, we temporally differentiate between domain-specific and domain-general processes both inside and outside the sensory system, which serves as a novel example of hierarchical processing.

Timing of Allocentric and Egocentric Spatial Processing in Human Intracranial EEG.

Spatial reference frames (RFs) play a key role in spatial cognition, especially in perception, spatial memory, and navigation. There are two main types of RFs: egocentric (self-centered) and allocentric (object-centered). Although many fMRI studies examined the neural correlates of egocentric and allocentric RFs, they could not sample the fast temporal dynamics of the underlying cognitive processes. Therefore, the interaction and timing between these two RFs remain unclear. Taking advantage of the high temporal resolution of intracranial EEG (iEEG), we aimed to determine the timing of egocentric and allocentric information processing and describe the brain areas involved. We recorded iEEG and analyzed broad gamma activity (50-150 Hz) in 37 epilepsy patients performing a spatial judgment task in a three-dimensional circular virtual arena. We found overlapping activation for egocentric and allocentric RFs in many brain regions, with several additional egocentric- and allocentric-selective areas. In contrast to the egocentric responses, the allocentric responses peaked later than the control ones in frontal regions with overlapping selectivity. Also, across several egocentric or allocentric selective areas, the egocentric selectivity appeared earlier than the allocentric one. We identified the maximum number of egocentric-selective channels in the medial occipito-temporal region and allocentric-selective channels around the intraparietal sulcus in the parietal cortex. Our findings favor the hypothesis that egocentric spatial coding is a more primary process, and allocentric representations may be derived from egocentric ones. They also broaden the dominant view of the dorsal and ventral streams supporting egocentric and allocentric space coding, respectively.

Is Central Europe Safe from Environmental Lead Intoxications? A Case Series.

Preventive measures in Central Europe were successful in suppressing both occupational and environmental lead exposure so that they did not constitute a severe public health problem. However, rare lead intoxications still appear. We report on lead intoxication in four family members where the source was removed lead ceiling paint. The symptoms of the lead intoxication started several weeks after removal and the inhalational exposure to the minimum dust residues lasted for more than three months before the poisoning was diagnosed. Father developed anaemia and saturnine colics. He and his two daughters received antidotal treatment which had to be repeated in the children. Finally, all recovered completely.Lead intoxication may be easily overlooked due to the unspecific symptoms. It is necessary to think of this rare poisoning which may be caused by old paints, historical ceramics and lead shots, in addition to commercial products imported from abroad.

Spatial navigation impairment is proportional to right hippocampal volume.

Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (n = 23) or mild and moderate AD (n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real-space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (ß = -0.62, P < 0.001) and virtual (ß = -0.43, P = 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (P ≤ 0.05) but not in cognitively healthy (P > 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present.

Risk factors for spatial memory impairment in patients with temporal lobe epilepsy.

At present, the risk factors for world-centered (allocentric) navigation impairment in patients with temporal lobe epilepsy (TLE) are not known. There is some evidence on the importance of the right hippocampus but other clinical features have not been investigated yet. In this study, we used an experimental human equivalent to the Morris water maze to examine spatial navigation performance in patients with drug-refractory unilateral TLE. We included 47 left-hemisphere speech dominant patients (25 right sided; 22 left sided). The aim of our study was to identify clinical and demographic characteristics of TLE patients who performed poorly in allocentric spatial memory tests. Our results demonstrate that poor spatial navigation is significantly associated with younger age at epilepsy onset, longer disease duration, and lower intelligence level. Allocentric navigation in TLE patients was impaired irrespective of epilepsy lateralization. Good and poor navigators did not differ in their age, gender, or preoperative/postoperative status. This study provides evidence on risk factors that increase the likelihood of allocentric navigation impairment in TLE patients. The results indicate that not only temporal lobe dysfunction itself but also low general cognitive abilities may contribute to the navigation impairment.

Tackling the challenges of group network inference from intracranial EEG data.

Introduction: Intracranial EEG (iEEG) data is a powerful way to map brain function, characterized by high temporal and spatial resolution, allowing the study of interactions among neuronal populations that orchestrate cognitive processing. However, the statistical inference and analysis of brain networks using iEEG data faces many challenges related to its sparse brain coverage, and its inhomogeneity across patients. Methods: We review these challenges and develop a methodological pipeline for estimation of network structure not obtainable from any single patient, illustrated on the inference of the interaction among visual streams using a dataset of 27 human iEEG recordings from a visual experiment employing visual scene stimuli. 100 ms sliding window and multiple band-pass filtered signals are used to provide temporal and spectral resolution. For the connectivity analysis we showcase two connectivity measures reflecting different types of interaction between regions of interest (ROI): Phase Locking Value as a symmetric measure of synchrony, and Directed Transfer Function-asymmetric measure describing causal interaction. For each two channels, initial uncorrected significance testing at p < 0.05 for every time-frequency point is carried out by comparison of the data-derived connectivity to a baseline surrogate-based null distribution, providing a binary time-frequency connectivity map. For each ROI pair, a connectivity density map is obtained by averaging across all pairs of channels spanning them, effectively agglomerating data across relevant channels and subjects. Finally, the difference of the mean map value after and before the stimulation is compared to the same statistic in surrogate data to assess link significance. Results: The analysis confirmed the function of the parieto-medial temporal pathway, mediating visuospatial information between dorsal and ventral visual streams during visual scene analysis. Moreover, we observed the anterior hippocampal connectivity with more posterior areas in the medial temporal lobe, and found the reciprocal information flow between early processing areas and medial place area. Discussion: To summarize, we developed an approach for estimating network connectivity, dealing with the challenge of sparse individual coverage of intracranial EEG electrodes. Its application provided new insights into the interaction between the dorsal and ventral visual streams, one of the iconic dualities in human cognition.

Spatial navigation and APOE in amnestic mild cognitive impairment.

BACKGROUND: The effect of APOE ε4 allele (ε4) on spatial navigation in amnestic mild cognitive impairment (aMCI) is unknown. OBJECTIVE: Our purpose was to examine the characteristics of spatial navigation impairment in ε4-positive (ε4+) and ε4-negative (ε4-) aMCI subgroups. METHODS: Blood samples were collected to determine the APOE genotype. A total of 34 aMCI patients were stratified into aMCI-ε4- (n = 23) and aMCI-ε4+ (n = 11) groups. Control (n = 28) and mild Alzheimer's disease (AD; n = 16) groups were also used. We used a human analogue of the Morris water maze (enclosed arena 2.9 m in diameter) to examine body-centered (egocentric) and world-centered (allocentric) spatial navigation. RESULTS: The aMCI-ε4+ group performed poorer on spatial navigation than the aMCI-ε4- group in both egocentric and allocentric tasks even though these 2 groups did not differ in global cognitive functioning or neuropsychological tests. The aMCI-ε4+ and mild AD groups performed similarly on all Morris Water Maze tasks and were outperformed by the aMCI-ε4- group, which also resembled the control group in performance on the egocentric tasks. The aMCI groups showed poor spatial navigation learning regardless of their ε4 positivity. CONCLUSION: We found more profound deficits in spatial navigation in aMCI-ε4+ relative to aMCI-ε4- patients. The aMCI-ε4+ group resembled the mild AD group in spatial navigation performance. Although the ε4 genotype was indicative of spatial navigation performance, it was not indicative of the aMCI patients' ability to learn the tasks. Spatial navigation testing represents a promising area with respect to identifying individuals at higher risk for AD among the heterogeneous MCI population.

Brain mechanisms of visuospatial perspective-taking in relation to object mental rotation and the theory of mind.

Visuospatial perspective-taking (VPT) is a process of imagining what can be seen and how a scene looks from a location and orientation in space that differs from one's own. It comprises two levels that are underpinned by distinct neurocognitive processes. Level-2 VPT is often studied in relation to two other cognitive phenomena, object mental rotation (oMR) and theory of mind (ToM). With the aim to describe the broad picture of neurocognitive processes underlying level-2 VPT, here we give an overview of the recent behavioral and neuroscientific findings of level-2 VPT. We discuss its relation to level-1 VPT, which is also referred to as perspective-tracking, and the neighboring topics, oMR and ToM. Neuroscientific research shows that level-2 VPT is a diverse cognitive process, encompassing functionally distinct neural circuits. It shares brain substrates with oMR, especially those parietal brain areas that are specialized in spatial reasoning. However, compared to oMR, level-2 VPT involves additional activations in brain structures that are typically involved in ToM tasks and deal with self/other distinctions. In addition, level-2 VPT has been suggested to engage brain areas coding for internal representations of the body. Thus, the neurocognitive model underpinning level-2 VPT can be understood as a combination of visuospatial processing with social cognition and body schema representations.

Mapping the Scene and Object Processing Networks by Intracranial EEG.

Human perception and cognition are based predominantly on visual information processing. Much of the information regarding neuronal correlates of visual processing has been derived from functional imaging studies, which have identified a variety of brain areas contributing to visual analysis, recognition, and processing of objects and scenes. However, only two of these areas, namely the parahippocampal place area (PPA) and the lateral occipital complex (LOC), were verified and further characterized by intracranial electroencephalogram (iEEG). iEEG is a unique measurement technique that samples a local neuronal population with high temporal and anatomical resolution. In the present study, we aimed to expand on previous reports and examine brain activity for selectivity of scenes and objects in the broadband high-gamma frequency range (50-150 Hz). We collected iEEG data from 27 epileptic patients while they watched a series of images, containing objects and scenes, and we identified 375 bipolar channels responding to at least one of these two categories. Using K-means clustering, we delineated their brain localization. In addition to the two areas described previously, we detected significant responses in two other scene-selective areas, not yet reported by any electrophysiological studies; namely the occipital place area (OPA) and the retrosplenial complex. Moreover, using iEEG we revealed a much broader network underlying visual processing than that described to date, using specialized functional imaging experimental designs. Here, we report the selective brain areas for scene processing include the posterior collateral sulcus and the anterior temporal region, which were already shown to be related to scene novelty and landmark naming. The object-selective responses appeared in the parietal, frontal, and temporal regions connected with tool use and object recognition. The temporal analyses specified the time course of the category selectivity through the dorsal and ventral visual streams. The receiver operating characteristic analyses identified the PPA and the fusiform portion of the LOC as being the most selective for scenes and objects, respectively. Our findings represent a valuable overview of visual processing selectivity for scenes and objects based on iEEG analyses and thus, contribute to a better understanding of visual processing in the human brain.

Spatial navigation deficits in amnestic mild cognitive impairment with neuropsychiatric comorbidity.

AIMS: To find out whether neuropsychiatric comorbidity (comMCI) influences spatial navigation performance in amnestic mild cognitive impairment (aMCI). METHODS: We recruited aMCI patients with (n = 21) and without (n = 21) neuropsychiatric comorbidity or alcohol abuse, matched for global cognitive impairment and cognitively healthy elderly participants (HE, n = 22). They completed the Mini-Mental State Examination and a virtual Hidden Goal Task in egocentric, allocentric, and delayed recall subtests. RESULTS: In allocentric navigation, aMCI and comMCI performed significantly worse than HE and similarly to each other. Although aMCI performed significantly worse at egocentric navigation than HE, they performed significantly better than patients with comMCI. CONCLUSIONS: Despite the growing burden of dementia and the prevalence of neuropsychiatric symptoms in the elderly population, comMCI remains under-studied. Since trials often assess "pure" aMCI, we may underestimate patients' navigation and other deficits. This finding emphasizes the importance of taking account of the cognitive effects of psychiatric disorders in aMCI.

Exploring the contribution of spatial navigation to cognitive functioning in older adults.

Spatial navigation (SN) impairment is present early in Alzheimer's disease (AD). We tested whether SN performance, self-centered (egocentric) and world-centered (allocentric), was distinguishable from performance on established cognitive functions-verbal and nonverbal memory, executive and visuospatial function, attention/working memory, and language function. 108 older adults (53 cognitively normal [CN] and 55 with amnestic mild cognitive impairment [aMCI]) underwent neuropsychological examination and real-space navigation testing. Subset (n = 63) had automated hippocampal volumetry. In a factor analysis, allocentric and egocentric navigation tasks loaded highly onto the same factor with low loadings on other factors comprising other cognitive functions. In linear regression, performance on other cognitive functions was not, or was only marginally, associated with spatial navigation performance in CN or aMCI groups. After adjustment for age, gender, and education, right hippocampal volume explained 26% of the variance in allocentric navigation in aMCI group. In conclusion, spatial navigation, a known cognitive marker of early AD, may be distinguished from other cognitive functions. Therefore, its assessment along with other major cognitive functions may be highly beneficial in terms of obtaining a comprehensive neuropsychological profile.

Is Chelation Therapy Efficient for the Treatment of Intravenous Metallic Mercury Intoxication?

The efficacy of treatment for intravenous elemental mercury intoxication has not been fully studied with regard to clinical outcome, and treatment recommendations vary. We treated a 41-year-old man with a history of drug abuse and depression who attempted suicide using 1 mL (13.53 g) metallic Hg i.v. He was admitted to the hospital 2 months later for dyspnoea and thoracic pain and was diagnosed with pneumonia. Hg deposits were seen in the lungs and extra-pulmonary organs. His blood level (372 µg/L) exceeded the population level of 5 µg/L by more than 70 times. Dimercaptopropane sulphonate sodium (DMPS; 600 mg/day orally) was administered for 14 days. One year later, the patient presented with dyspnoea on exertion, fatigue, depression and impaired sleep. His chest X-ray showed multiple opacities (size up to 2.8 cm), and psychological testing revealed a selective cognitive deficit in the area of visual attentiveness, flexibility, source memory and impairment of the motor speed of the dominant upper extremity. Mercury blood level was 158 µg/L and mercury urine output was 1380 µg/24 hr. DMPS (800 mg/day orally) was administered for 40 days; the patient eliminated up to 18 mg Hg/day. His Hg blood level and Hg urine output belong to the highest among reported cases. In spite of the therapy, the patient's blood Hg, complaints and psychological tests showed no improvement. This case report confirms that DMPS does not effectively remove intravenous deposits of metallic Hg.

Scopolamine disrupts place navigation in rats and humans: a translational validation of the Hidden Goal Task in the Morris water maze and a real maze for humans.

RATIONALE: Development of new drugs for treatment of Alzheimer's disease (AD) requires valid paradigms for testing their efficacy and sensitive tests validated in translational research. OBJECTIVES: We present validation of a place-navigation task, a Hidden Goal Task (HGT) based on the Morris water maze (MWM), in comparable animal and human protocols. METHODS: We used scopolamine to model cognitive dysfunction similar to that seen in AD and donepezil, a symptomatic medication for AD, to assess its potential reversible effect on this scopolamine-induced cognitive dysfunction. We tested the effects of scopolamine and the combination of scopolamine and donepezil on place navigation and compared their effects in human and rat versions of the HGT. Place navigation testing consisted of 4 sessions of HGT performed at baseline, 2, 4, and 8 h after dosing in humans or 1, 2.5, and 5 h in rats. RESULTS: Scopolamine worsened performance in both animals and humans. In the animal experiment, co-administration of donepezil alleviated the negative effect of scopolamine. In the human experiment, subjects co-administered with scopolamine and donepezil performed similarly to subjects on placebo and scopolamine, indicating a partial ameliorative effect of donepezil. CONCLUSIONS: In the task based on the MWM, scopolamine impaired place navigation, while co-administration of donepezil alleviated this effect in comparable animal and human protocols. Using scopolamine and donepezil to challenge place navigation testing can be studied concurrently in animals and humans and may be a valid and reliable model for translational research, as well as for preclinical and clinical phases of drug trials.

Molecular mechanism of pregnenolone sulfate action at NR1/NR2B receptors.

NMDA receptors are highly expressed in the CNS and are involved in excitatory synaptic transmission and synaptic plasticity as well as excitotoxicity. They have several binding sites for allosteric modulators, including neurosteroids, endogenous compounds synthesized by the nervous tissue and expected to act locally. Whole-cell patch-clamp recording from human embryonic kidney 293 cells expressing NR1-1a/NR2B receptors revealed that neurosteroid pregnenolone sulfate (PS) (300 microm), when applied to resting NMDA receptors, potentiates the amplitude of subsequent responses to 1 mm glutamate fivefold and slows their deactivation twofold. The same concentration of PS, when applied during NMDA receptor activation by 1 mm glutamate, has only a small effect. The association and dissociation rate constants of PS binding and unbinding from resting NMDA receptors are estimated to be 3.3 +/- 2.0 mm(-1)sec(-1) and 0.12 +/- 0.02 sec(-1), respectively, corresponding to an apparent affinity K(d) of 37 microm. The results of experiments indicate that the molecular mechanism of PS potentiation of NMDA receptor responses is attributable to an increase in the peak channel open probability (P(o)). Responses to glutamate recorded in the continuous presence of PS exhibit marked time-dependent decline. Our results indicate that the decline is induced by a change of the NMDA receptor affinity for PS after receptor activation. These results suggest that the PS is a modulator of NMDA receptor P(o), the effectiveness of which is lowered by glutamate binding. This modulation may have important consequences for the neuronal excitability.

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.

Spatial disorientation and learning problems belong to the integral symptoms of Alzheimer's disease (AD). A circular arena for human subjects (2.9 m diameter, 3 m high) was equipped with a computerized tracking system, similar to that used in animals. We studied navigation in 11 subjects diagnosed with early stages of Alzheimer's disease (AD), 27 subjects with subjective problems with memory or concentration, and 10 controls. The task was to locate one or several unmarked goals using the arena geometry, starting position and/or cues on the arena wall. Navigation in a real version and a computer map view version of the tests yielded similar results. The AD group was severely impaired relative to controls in navigation to one hidden goal in eight rotated positions. The impairment was largest when only the cues on the wall could be used for orientation. Also, the AD group recalled worse than controls the order of six sequentially presented locations, though they recalled similarly to controls the positions of the locations. The group with subjective problems was not impaired in any of the tests. Our results document the spatial navigation and non-verbal episodic memory impairment in the AD. Similar results in real and map view computer tests support the use of computer tests in diagnosis of cognitive disturbances.

Perspective taking abilities in amnestic mild cognitive impairment and Alzheimer's disease.

Perspective taking is the ability to imagine what a scene looks like from a different viewpoint, which has been reported to be impaired in Alzheimer's disease (AD). This study compared overhead and first-person view perspective taking abilities in patients with mild cognitive impairment (MCI) and AD. A newly developed Arena Perspective Taking Task (APTT), using an environment of a circular arena, was used to compare 23 AD patients and 38 amnestic MCI patients with 18 healthy controls. The results were contrasted with a published perspective taking test (Standardized Road-Map Test of Direction Sense, RMTDS). The AD group was impaired in both overhead and first-person view APTT versions, but the impairment in the overhead view version applied specifically to women. Patients with aMCI were impaired in the first-person view but not in the overhead view version. Substantial sexual differences were found in the overhead but not in the first-person view APTT version. The RMTDS resembled both APTT versions: patients with aMCI were impaired in this test and also women in both patient groups were less accurate than men. Using the receiver operating characteristic analysis, the highest predictive power for MCI and AD patients diagnosis versus controls was observed for their success rate in the first-person view version. The results suggest distinction between overhead and first-person view perspective taking in the impairment of aMCI patients and the sex differences. The first-person view perspective taking is a potentially important candidate psychological marker for AD.

Comparison of Visuospatial and Verbal Abilities in First Psychotic Episode of Schizophrenia Spectrum Disorder: Impact on Global Functioning and Quality of Life.

OBJECTIVES: Deficit in visuospatial functions can influence both simple and complex daily life activities. Despite the fact that visuospatial deficit was reported in schizophrenia, research on visuospatial functions as an independent entity is limited. Our study aims to elucidate the impact of visuospatial deficit in comparison with verbal deficit on global functioning and quality of life in the first psychotic episode of schizophrenia spectrum disorder (FES). The significance of clinical symptoms and antipsychotic medication was also studied. METHODS: Thirty-six FES patients and a matched group of healthy controls (HC group) were assessed with a neuropsychological battery focused on visuospatial (VIS) and verbal (VERB) functions. Using multiple regression analysis, we evaluated the cumulative effect of VERB and VIS functions, psychiatric symptoms (PANSS) and antipsychotic medication on global functioning (GAF) and quality of life (WHOQOL-BREF) in the FES group. RESULTS: The FES group demonstrated significant impairment both in VIS and VERB cognitive abilities compared to the HC group. Antipsychotic medication did not significantly affect either VIS or VERB functioning. PANSS was not related to cognitive functioning, apart from the Trail Making Test B. In the FES group, the GAF score was significantly affected by the severity of positive symptoms and VERB functioning, explaining together 60% of GAF variability. The severity of negative and positive symptoms affected only the Physical health domain of WHOQOL-BREF. The degree of VERB deficit was associated with both Physical and Psychological health. Although we did not find any relation between VIS functioning, GAF, and WHOQOL-BREF, a paradoxical finding emerged in the Environment quality domain, where a worse quality of the environment was associated with better VIS functioning. CONCLUSIONS: Our results suggest that the deficit in VIS functions is an integral part of cognitive deficit in schizophrenia spectrum disorders, rather than a side effect of symptomatology or antipsychotic medication. Moreover, VERB functioning was a better predictor of GAF and WHOQOL-BREF than VIS functioning. Given the findings of negative or missing effect of VIS deficit on WHOQOL-BREF and GAF, the accuracy of these measures in evaluating the impact of global cognitive deficit on everyday life in schizophrenia could be questioned.

Neural correlates of spatial navigation changes in mild cognitive impairment and Alzheimer's disease.

Although the memory impairment is a hallmark of Alzheimer's disease (AD), AD has also been characterized by spatial disorientation, which is present from its early stages. Spatial disorientation in AD manifests itself in getting lost in familiar and unfamiliar places and have been characterized more specifically using spatial navigation tests in both real space and virtual environments as an impairment in multiple spatial abilities, including allocentric and egocentric navigation strategies, visuo-spatial perception, or selection of relevant information for successful navigation. Patients suffering mild cognitive impairment (MCI), who are at a high risk of development of dementia, show impairment in a subset of these abilities, mainly connected with allocentric and egocentric processing. While spatial disorientation in typical AD patients probably reflects neurodegenerative changes in medial and posterior temporal, parietal, and frontal lobes, and retrosplenial cortex, the impairment of spatial navigation in MCI seem to be connected mainly with the medial temporal and also parietal brain changes. In this review, we will summarize the signs of brain disease in most MCI and AD patients showing in various tasks of spatial memory and navigation.

Famous landmark identification in amnestic mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Identification of famous landmarks (FLI), famous faces (FFI) and recognition of facial emotions (FER) is affected early in the course of Alzheimer's disease (AD). FFI, FER and FLI may represent domain specific tasks relying on activation of distinct regions of the medial temporal lobe, which are affected successively during the course of AD. However, the data on FFI and FER in MCI are controversial and FLI domain remains almost unexplored. OBJECTIVES: To determine whether and how are these three specific domains impaired in head to head comparison of patients with amnestic MCI (aMCI) single domain (SD-aMCI) and multiple domain (MD-aMCI). We propose that FLI might be most reliable in differentiating SD-aMCI, which is considered to be an earlier stage of AD pathology spread out, from the controls. PATIENTS AND METHODS: A total of 114 patients, 13 with single domain (SD-aMCI) and 30 with multiple domains (MD-aMCI), 29 with mild AD and 42 controls underwent standard neurological and neuropsychological evaluations as well as tests of FLI, FER and FFI. RESULTS: Compared to the control group, AD subjects performed worse on FFI (p = 0.020), FER (p<0.001) and FLI (p<0.001), MD-aMCI group had significantly worse scores only on FLI (p = 0.002) and approached statistical significance on FER (0.053). SD-aMCI group performed significantly worse only on FLI (p = 0.028) compared to controls. CONCLUSIONS: Patients with SD-aMCI had an isolated impairment restricted to FLI, while patients with MD-aMCI showed impairment in FLI as well as in FER. Patients with mild dementia due to AD have more extensive impairment of higher visual perception. The results suggest that FLI testing may contribute to identification of patients at risk of AD. We hypothesize that clinical examination of all three domains might reflect the spread of the disease from transentorhinal cortex, over amygdala to fusiform gyrus.