Distinct grey and white matter changes are associated with the phenomenology of visual hallucinations in Lewy Body Disease.

Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a variety of phenomena, such as illusions, presence and passage hallucinations occurring at early stages of LBD. The neural mechanisms of visual hallucinations are largely unknown. The hodotopic model posits that the hallucination state is due to abnormal activity in specialized visual areas, that occurs in the context of wider network connectivity alterations and that phenomenology of VH, including content and temporal characteristics, may help identify brain regions underpinning these phenomena. Here we investigated both the topological and hodological neural basis of visual hallucinations integrating grey and white matter imaging analyses. We studied LBD patients with VH and age matched healthy controls (HC). VH were assessed using a North-East-Visual-Hallucinations-Interview that captures phenomenological detail. Then we applied voxel-based morphometry and tract based spatial statistics approaches to identify grey and white matter changes. First, we compared LBD patients and HC. We found a reduced grey matter volume and a widespread damage of white tracts in LBD compared to HC. Then we tested the association between CVH and MVH and grey and white matter indices. We found that CVH duration was associated with decreased grey matter volume in the fusiform gyrus suggesting that LBD neurodegeneration-related abnormal activity in this area is responsible for CVH. An unexpected finding was that MVH severity was associated with a greater integrity of white matter tracts, specifically those connecting dorsal, ventral attention networks and visual areas. Our results suggest that networks underlying MVH need to be partly intact and functional for MVH experiences to occur, while CVH occur when cortical areas are damaged. The findings support the hodotopic view and the hypothesis that MVH and CVH relate to different neural mechanisms, with wider implications for the treatment of these symptoms in a clinical context.

Common and specific activations supporting optic flow processing and navigation as revealed by a meta-analysis of neuroimaging studies.

Optic flow provides useful information in service of spatial navigation. However, whether brain networks supporting these two functions overlap is still unclear. Here we used Activation Likelihood Estimation (ALE) to assess the correspondence between brain correlates of optic flow processing and spatial navigation and their specific neural activations. Since computational and connectivity evidence suggests that visual input from optic flow provides information mainly during egocentric navigation, we further tested the correspondence between brain correlates of optic flow processing and that of both egocentric and allocentric navigation. Optic flow processing shared activation with egocentric (but not allocentric) navigation in the anterior precuneus, suggesting its role in providing information about self-motion, as derived from the analysis of optic flow, in service of egocentric navigation. We further documented that optic flow perception and navigation are partially segregated into two functional and anatomical networks, i.e., the dorsal and the ventromedial networks. Present results point to a dynamic interplay between the dorsal and ventral visual pathways aimed at coordinating visually guided navigation in the environment.

Brain connectivity patterns associated with individual differences in the access to experience-near personal semantics: a resting-state fMRI study.

It has been proposed that a continuum of specificity exists between episodic and semantic autobiographical memory. Personal semantics have been theorized to situate intermediately on this continuum, with more "experience-near" personal semantics (enPS) closer to the episodic end. We used individual differences in behavior as a model to investigate brain networks associated with the access to episodic autobiographical (EAM) and enPS information, assessing the relation between performance in the EAM and enPS conditions of the Autobiographical Fluency Task (AFT) and intrinsic brain connectivity. Results of an intrinsic connectivity contrast analysis showed that the global connectivity of two clusters in the left and right posterior cingulate cortex (PCC) was predicted by performance in the enPS conditions. Moreover, enPS scores predicted the connectivity strength of the right PCC with the bilateral anterior hippocampus (aHC), anterior middle temporal gyrus (aMTG) and medial orbitofrontal cortex, and the left aMTG and PCC. enPS scores also predicted the connectivity strength of the left PCC with the bilateral HC and MTG. The network highlighted involves parts of the core and of the dorsal medial subsystems of the Default Mode Network, in line with the proposal that enPS represents an intermediate entity between episodic and semantic memory.

Multidimensional assessment of time perception along the continuum of Alzheimer's Disease and evidence of alterations in subjective cognitive decline.

Timing alterations occur in Alzheimer's disease (AD), even in early stages (mild cognitive impairment, MCI). Moreover, a stage named subjective cognitive decline (SCD), in which individuals perceive a change in cognitive performance not revealed by neuropsychological tests, has been identified as a preclinical phase of AD. However, no study to date has investigated different dimensions of time processing along the continuum from physiological to pathological aging, and whether timing alterations occur in SCD. Here a sample of participants with SCD, MCI, AD and healthy controls (HC) performed tasks assessing prospective duration estimation, production, reproduction, implicit temporal learning in conditions dependent from external cues (externally-cued learning, ECL) or independent from external cues (internally-based learning, IBL), retrospective duration estimation, the subjective experience of time and the temporal collocation of events. AD patients performed worse than HC and SCD in prospective timing, and in collocating events in time. The subjective experience of time did not differ between groups. Concerning temporal learning, AD performed worse in ECL than in IBL, whereas SCD performed worse in IBL than in ECL. SCD, MCI and AD patients all showed errors greater than HC in retrospective duration estimation. Results point to implicit temporal learning in externally-cued conditions and retrospective time estimation as possible early markers of cognitive decline.

The autobiographical fluency task: Validity and reliability of a tool to assess episodic autobiographical memory and experience-near personal semantics.

The assessment of autobiographical memory is challenging in clinical settings. The Autobiographical Fluency Task (AFT) - that is designed to test both Episodic Autobiographical Memory (EAM) and experience-near Personal Semantics (enPS) - may represent a feasible and rapid method to test access to autobiographical memories. Here we tested the reliability and the construct validity of the AFT. A total number of 51 individuals participated in the present study, with 24 included in Experiment 1 and 27 in Experiment 2. In Experiment 1, participants performed both the AFT and the Survey of Autobiographical Memory (SAM). In Experiment 2, participants completed the AFT and the Autobiographical Interview (AI). The AFT showed a moderate-to-high reliability. Also, EAM and enPS scores significantly correlated with the episodic subscale of the SAM. Results of Experiment 1 were replicated and expanded in Experiment 2. Again, the AFT showed a high reliability. Both EAM and enPS showed a significant correlation with the number of internal details produced during the AI; enPS also correlated with the number of external details. Overall, the present results show that the AFT may be a feasible instrument to assess autobiographical memory, especially for testing episodic autobiographical memory and experience-near personal semantics in clinical settings.

Combining the Inner Self with the Map of the Body: Evidence for White Matter Contribution to the Relation Between Interoceptive Sensibility and Nonaction-oriented Body Representation.

Very recent studies on healthy individuals suggest that changes in the sensibility toward internal bodily sensations across the lifespan affect the ability to mentally represent one's body, in terms of action-oriented and nonaction-oriented body representation (BR). Little is known about the neural correlates of this relation. Here we fill this gap using the neuropsychological model provided by focal brain damage. Sixty-five patients with unilateral stroke (20 with left and 45 with right brain damage, LBD and RBD, respectively) participated in this study. Both action-oriented BR and nonaction-oriented BR were tested; interoceptive sensibility was assessed as well. First, we tested whether interoceptive sensibility predicted action-oriented BR and nonaction-oriented BR, in RBD and LBD separately. Then, a track-wise hodological lesion-deficit analysis was performed in a subsample of twenty-four patients to test the brain network supporting this relation. We found that interoceptive sensibility predicted the performances in the task tapping nonaction-oriented BR. The higher interoceptive sensibility was, the worse patients performed. This relation was associated with the disconnection probability of the corticospinal tract, the fronto-insular tract, and the pons. We expand over the previous findings on healthy individuals, supporting the idea that high levels of interoceptive sensibility negatively affect BR. Specific frontal projections and frontal u-shaped tracts may play a pivotal role in such an effect, likely affecting the development of a first-order representation of the self within the brainstem autoregulatory centers and posterior insula and of a second-order representation of the self within the anterior insula and higher-order prefrontal areas.

Lifelong impairment in episodic re-experiencing: Neuropsychological and neuroimaging examination of a new case of Severely Deficient Autobiographical Memory.

Autobiographical memory (AM) represents a complex and multimodal cognitive function, that allows an individual to collect and retrieve personal events and facts, enabling to develop and maintain the continuity of the self over time. Here we describe the case of DR (acronym of the fictional name Doriana Rossi), a 53-year-old woman, who complains of a specific and lifelong deficit in recalling autobiographical episodes. Along with an extensive neuropsychological assessment, DR underwent a structural and functional MRI examination to further define this impairment. The neuropsychological assessment revealed a deficit in episodic re-experiencing of her own personal life events. DR showed reduced cortical thickness in the Retrosplenial Complex in the left hemisphere, and in the Lateral Occipital Cortex, in the Prostriate Cortex and the Angular Gyrus in the right hemisphere. An altered pattern of activity in the calcarine cortex was detected during ordering of autobiographical events according to her own personal timeline. The present study provides further evidence about the existence of a severely deficient autobiographical memory condition in neurologically healthy people, with otherwise preserved cognitive functioning. Furthermore, the present data provide new important insights into neurocognitive mechanisms underpinning such a developmental condition.

Neural substrates of interoceptive sensibility: An integrated study in normal and pathological functioning.

In early studies interoception strictly referred to the awareness of visceral sensations, but recent theories have expanded this concept to denote the ongoing status of the body, including somatosensory feelings. Here, we integrated data from normal and pathological functioning to disclose neural underpinnings of interoceptive sensibility, taking into account the crucial distinction between visceral and somatosensory feelings. Twenty-seven healthy young individuals underwent structural MRI (including T1w images and DTI). Voxel-wise analyses of the gyrification index (GI) and fractional anisotropy (FA) data were performed to assess the relation between interoceptive sensibility and surface morphometry and anatomical connectivity. Thirty-three unilateral brain-damaged patients took part in this study for Voxel-Based Lesion-Symptom Mapping (VLSM) and track-wise hodological lesion-deficit analysis (TWH). All participants completed the Self-Awareness Questionnaire (SAQ), a self-report tool assessing interoceptive sensibility of visceral (F1) and somatosensory feelings (F2). Tract-Based Spatial Statistics showed that F2 was positively associated with FA in the bilateral anterior thalamic radiation, corticospinal tract, cingulum, forceps, inferior longitudinal, fronto-occipital, superior longitudinal, and uncinate fasciculi; no significant association was detected for F1. However, F1 was positively associated with GI in the left anterior cingulate cortex. VLSM showed that F1 mainly relies on the right posterior insula, whereas F2 is related mostly to subcortical nuclei and surrounding white matter in the right hemisphere. Accordingly, patients with disconnection of the anterior thalamic projection, corticospinal tract, inferior fronto-occipital, inferior longitudinal, uncinate and superior longitudinal fasciculus III showed lower scores on F2. Overall, results support the dissociation between interoceptive sensibility of visceral and somatosensory feelings.

Intrinsic hippocampal connectivity is associated with individual differences in retrospective duration processing.

The estimation of incidentally encoded durations of time intervals (retrospective duration processing) is thought to rely on the retrieval of contextual information associated with a sequence of events, automatically encoded in medial temporal lobe regions. "Time cells" have been described in the hippocampus (HC), encoding the temporal progression of events and their duration. However, whether the HC supports explicit retrospective duration judgments in humans, and which neural dynamics are involved, is still poorly understood. Here we used resting-state fMRI to test the relation between variations in intrinsic connectivity patterns of the HC, and individual differences in retrospective duration processing, assessed using a novel task involving the presentation of ecological stimuli. Results showed that retrospective duration discrimination performance predicted variations in the intrinsic connectivity of the bilateral HC with the right precentral gyrus; follow-up exploratory analyses suggested a role of the CA1 and CA4/DG subfields in driving the observed pattern. Findings provide insights on neural networks associated with implicit processing of durations in the second range.

Temporal learning in the suprasecond range: insights from cognitive style.

The acquisition of information on the timing of events or actions (temporal learning) occurs in both the subsecond and suprasecond range. However, although relevant differences between participants have been reported in temporal learning, the role of dimensions of individual variability in affecting performance in such tasks is still unclear. Here we investigated this issue, assessing the effect of field-dependent/independent cognitive style on temporal learning in the suprasecond range. Since different mechanisms mediate timing when a temporal representation is self-generated, and when it depends on an external referent, temporal learning was assessed in two conditions. Participants observed a stimulus across six repetitions and reproduced it. Unbeknownst to them, in an internally-based learning (IBL) condition, the stimulus duration was fixed within a trial, although the number of events defining it varied; in an externally-cued learning (ECL) condition, the stimulus was defined by the same number of events within each trial, although its duration varied. The effect of the reproduction modality was also assessed (motor vs. perceptual). Error scores were higher in IBL compared to ECL; the reverse was true for variability. Field-independent individuals performed better than field-dependent ones only in IBL, as further confirmed by correlation analyses. Findings provide evidence that differences in dimensions of variability in high-level cognitive functioning, such as field dependence/independence, significantly affect temporal learning in the suprasecond range, and that this effect depends on the type of temporal representation fostered by the specific task demands.

Temporal Organization of Episodic and Experience-near Semantic Autobiographical Memories: Neural Correlates and Context-dependent Connectivity.

Autobiographical memory includes a representation of personal life events with a unique spatiotemporal context (episodic autobiographical memory) and factual self-knowledge (personal semantics). Whereas "experience-far" personal semantics have undergone complete abstraction, "experience-near" personal semantics are still linked to a spatiotemporal context. The representation of one's own past involves an autobiographical knowledge base, in the form of a personal timeline, along which autobiographical information is temporally organized into different lifetime periods. Commonalities and differences between brain networks supporting this temporal organization for autobiographical information with different contextual specificity, however, have not been investigated to date. Here, we used task-based fMRI to assess neural substrates of temporal ordering along the personal timeline for real autobiographical episodic and experience-near personal semantic memories. Within a distributed network, the left calcarine cortex was more strongly activated for episodic autobiographical memory than personal semantics, whereas the left ventromedial pFC and right posterior cingulate cortex (PCC), angular gyrus (AG), and anterior middle temporal gyrus (aMTG) showed stronger activation for personal semantics than episodic autobiographical memory. Findings were confirmed by analyses in independently derived ROIs. Generalized psychophysiological interaction analyses between the same regions showed that, during personal semantics compared with episodic autobiographical memory, memory category modulated activity in the left PCC and right PCC, AG, and aMTG. Findings provide insights on how personal events and facts are represented in the timescale of years, suggesting that the temporal organization of autobiographical memory exploits properties of situation models developed within posteromedial, lateral parietal, and medial prefrontal regions.

Testing a Model of Human Spatial Navigation Attitudes towards Global Navigation Satellite Systems.

Global navigation satellite systems (GNSS) can provide better data quality for different purposes; however, some age groups might lie outside its use. Understanding the barriers to its adoption is of interest in different fields. This work aims at developing a measurement instrument of the adoption attitudes towards this technology and examining the relationship of variables such as age and gender. A UTAUT model was tested on 350 participants. The main results can be summarised as follows: (i) the proposed GNSS scale on human spatial navigation attitudes towards geopositioning technology showed optimal psychometric properties; (ii) although statistically significant differences were found in the Wayfinding Questionnaire (WQ) between men and women, these did not reach the level of statistical significance for the scores on attitudes towards GNSS; (iii) by testing a model on human spatial navigation attitudes towards geopositioning technology, it was possible to show a higher relationship with age in women.

DiaNe: A New First-Level Computerized Tool Assessing Memory, Attention, and Visuospatial Processing to Detect Early Pathological Cognitive Decline.

BACKGROUND: Detecting the beginning of cognitive decay is crucial to guarantee good management and the possible prevention of dementia progression. The present study arises from observations collected during an educational event to promote mental and physical health in which incidental neuropsychological data gathered on 290 citizens showed the importance of routine neuropsychological examination in detecting early signs of cognitive decay, since many individuals were unaware of the decrease in their cognitive efficiency. Accordingly, the availability of a screening tool that is computerized, portable, self-administrable, and sensitive to the main neurocognitive changes testifying the progression towards pathological aging is critical. OBJECTIVE: To this aim, we developed a computerized battery for the early, preclinical Diagnosis of Neurocognitive disease (DiaNe), that can be self-administered and performed autonomously by using a tablet. METHODS: DiaNe includes tests expected to evaluate the main cognitive domains involved in neurodegenerative diseases (memory, attention, executive functions) with a detailed assessment of visuospatial memory in particular. RESULTS: DiaNe is not just the translation of standard tests into telematics, rather it is a new tool that provides both accuracy and response time measurements, aimed to screen cognitive profile and monitor it over time, being able to detect changes in still normal performances that may be suggestive of an ongoing onset of neurocognitive disorders. CONCLUSION: Here we present an investigation of DiaNe concurrent validity showing that its results are comparable to those obtained by existing paper-and-pencil neuropsychological tests, and propose that DiaNe could be a useful, quick, and economical instrument for the monitoring of cognitive aging.

The Verbal Judgement Task: Normative data of verbal abstract reasoning in a sample of 18- to 40-years old.

In this study, normative data for the age-range 18-40 years have been provided for the Verbal Judgment Test (VJT), which underpins abstract reasoning on the basis of four subtests: "Differences", "Proverbs", "Absurdities" and "Classifications". 554 participants (280 males and 274 females) were recruited and the following data were provided: means and standard deviations divided by gender, educational level (8, 13 and 18 years) and age group (18-20 years, 21-25 years, 26-30 years, 31-35 years and 36-40 years) for each subtest and the total score; percentiles for each subtest, divided by age group, and, when appropriate, educational level and/or gender; Rho correlations between age group, gender, educational level, intelligence and VJT scores. Age-, education- and gender differences were also assessed carrying out non parametric tests. Results showed that age and education positively affected performance in the subtests of Differences, Proverbs and Classifications, which are mostly based on previous knowledge, experience, and crystallized intelligence, but did not affect performance in the Absurdities subtest, which encompasses to some extent fluid intelligence. In addition, males showed higher scores than females in the subtests of Differences and Proverbs and in the total VJT, probably reflecting higher knowledge acquisition. Implications for future research are briefly discussed.

Overcoming navigational challenges: A novel approach to the study and assessment of topographical orientation.

Several studies investigating environmental navigation require participants to navigate in virtual environments, in which the proprioceptive and vestibular components present during real environmental navigation are lost. Here, we aimed to provide a novel computerized ecological navigational battery, investigating whether the absence of proprioceptive and vestibular inputs yields a representation of the navigational space comparable to that acquired ecologically. In Study 1, 38 participants underwent two sets of tasks, one performed in a laboratory-based setting (LBS) and the other in an ecological environment (EE), with both including evaluation of route, landmark, and survey knowledge and a landmark ordering task. All tasks, except the route task, significantly correlated between EE and LBS. In LBS, performance in the landmark ordering task was predicted by that in the survey task, but not by those in the route and landmark tasks. Results of Study 1 were replicated in Study 2, in which 44 participants completed a modified and shorter online version of LBS tests. Reliability of the online LBS tests was also tested and showed a moderate-to-high internal consistency. Overall, results show that the conditions in which tasks are performed affect the acquisition of route knowledge, likely due to the lack of proprioceptive and vestibular information in LBS. However, LBS tasks presented here provide a standard battery of tests that can overcome the replicability problems encountered by ecological navigation tests, while taking into consideration all the complexities of navigational processes in terms of the use of landmark, route, and survey strategies.

Commonalities and specificities between environmental navigation and autobiographical memory: A synthesis and a theoretical perspective.

It has been proposed that declarative memory evolved from spatial navigation, with episodic memory having its roots in mechanisms of egocentric navigation and semantic memory in those of allocentric navigation; however, whether these brain networks actually overlap is still unclear. Using Activation Likelihood Estimation, we assessed the correspondence between brain correlates of spatial navigation (SN) and autobiographical memory (AM), further testing whether neural substrates of episodic memory (EAM) and egocentric navigation, and those of semantic memory (SAM) and map-like navigation, coincide. SN and AM commonly activated the parahippocampal gyrus and middle hippocampus, posterior cingulate cortex and right angular gyrus, but also involved distinct brain regions. Similarly, EAM and egocentric navigation, besides sharing a network involving the right angular gyrus, bilateral posterior cingulate and parahippocampal gyrus, activated distinct brain regions; no region was commonly activated by SAM and allocentric navigation. We discuss findings in the light of theories on the relation between navigation and memory, and propose a new theoretical perspective, which takes into account the dynamic nature of navigational processes.

Mental representation of autobiographical memories along the sagittal mental timeline: Evidence from spatiotemporal interference.

Time is usually conceived of in terms of space: many natural languages refer to time according to a back-to-front axis. Indeed, whereas the past is usually conceived to be "behind us", the future is considered to be "in front of us." Despite temporal coding is pivotal for the development of autonoetic consciousness, little is known about the organization of autobiographical memories along this axis. Here we developed a spatial compatibility task (SCT) to test the organization of autobiographical memories along the sagittal plane, using spatiotemporal interference. Twenty-one participants were asked to recall both episodic and semantic autobiographical memories (EAM and SAM, respectively) to be used in the SCT. Then, during the SCT, they were asked to decide whether each event occurred before or after the event presented right before, using a response code that could be compatible with the back-to-front axis (future in front) or not (future at back). We found that performance was significantly worse during the non-compatible condition, especially for EAM. The results are discussed in light of the evidence for spatiotemporal encoding of episodic autobiographical memories, taking into account possible mechanisms explaining compatibility effects.

Duration reproduction in regular and irregular contexts after unilateral brain damage: Evidence from voxel-based lesion-symptom mapping and atlas-based hodological analysis.

It has been proposed that not completely overlapping brain networks support interval timing depending on whether or not an external, predictable temporal cue is provided during the task, aiding time estimation. Here we tested this hypothesis in a neuropsychological study, using both a topological approach - through voxel-based lesion-symptom mapping (VLSM), that assesses the relation between continuous behavioral scores and lesion information on a voxel-by-voxel basis - and a hodological approach, using an atlas-based tractography. A group of patients with unilateral focal brain lesions and their matched controls performed a duration reproduction task assessing time processing in two conditions, namely with regularly spaced stimuli during encoding and reproduction (Regular condition), and with irregularly spaced stimuli during the same task (Irregular condition). VLSM analyses showed that scores in the two conditions were associated with lesions involving partly separable clusters of voxels, with lower performance only in the Irregular condition being related to lesions involving the right insular cortex. Performance in both conditions correlated with the probability of disconnection of the right frontal superior longitudinal tract, and of the superior and middle branches of the right superior longitudinal fasciculus. These findings suggest that the dissociation between timing in regular and irregular contexts is not complete, since performance in both conditions relies on the integrity of a common suprasecond timing network. Furthermore, they are consistent with the hypothesis that tracking time without the aid of external cues selectively relies on the integration of psychophysiological changes in the right insula.

Inter-individual differences in resting-state functional connectivity are linked to interval timing in irregular contexts.

Behavioral evidence suggests that different mechanisms mediate duration perception depending on whether regular or irregular cues for time estimation are provided, and that individual differences in interoceptive processing may affect duration perception only in the latter case. However, no study has addressed brain correlates of this proposed distinction. Here participants performed a duration reproduction task in two conditions: with unevenly spaced stimuli during time estimation/reproduction (irregular), with regularly spaced stimuli provided during the same task (regular). They also underwent resting-state fMRI to assess regional functional connectivity, in order to link individual differences in behavioral performance to variations in patterns of intrinsic brain oscillations. Resting-state functional connectivity of the right precentral gyrus with the ipsilateral insula and putamen was predicted by duration reproduction performance selectively in the irregular condition. The connectivity of the right posterior insula, within a network modulated by participants' degree of interoceptive awareness, correlated positively with performance in the irregular condition only. Findings support the distinction between brain networks involved in duration processing with or without regular cues, and the hypothesis that the multimodal integration of interoceptive and exteroceptive cues is specifically involved in the latter.

Interoceptive awareness selectively predicts timing accuracy in irregular contexts.

Awareness of psychophysiological changes has been proposed to play a role in duration perception; however, evidence on whether interoceptive awareness affects timing is mixed, and it is not clear which task features favor the reliance on bodily changes to track time. Here we tested the hypothesis that interoceptive awareness is selectively involved in timing when the context does not provide reliable cues on elapsed time. We developed a novel paradigm assessing interval reproduction in two conditions: 1) with regularly spaced stimuli during the encoding/reproduction phase (regular condition), 2) with irregularly spaced stimuli during the encoding/reproduction phase (irregular condition). Interoceptive awareness was assessed using the "Self-Awareness Questionnaire", investigating the frequency of common bodily sensations. Interoceptive awareness predicted timing accuracy in the irregular, but not in the regular condition; also, the contribution was specifically due to awareness of visceral sensations rather than somatosensory sensations. Overall, results suggest that individual differences in interoception differently affect timing according to contextual features, consistently with evidence that different mechanisms mediate timing in different conditions.