Mental time travel and functional daily life activities in neglect patients: Recovery effects of rehabilitation by prism adaptation.

Recent neuropsychological evidence put forward impaired ability in processing particular aspects of time, such as Mental Time Travel (MTT), in brain damaged patients exhibiting a deficit of spatial attention (i.e., neglect) and the possibility to recover this MTT deficit through a manipulation of spatial attention by prism adaptation (PA). The aim of the present study was twofold. First, we explored whether the neglect patients' impairment in MTT is linked with an impairment in functional competences, such as processing temporal duration of everyday activities, motor abilities and independence in daily living. Second, we focused on rehabilitation, investigating the long-term duration of the benefits induced by a PA treatment on both mental time travel and the above-mentioned functional abilities. To these aims, neglect patients were submitted to a MTT task, as well as to a battery of tests assessing spatial attention, estimation of time duration, motor competence and independence in activities of daily living. All tests were performed before, at the end, and one week after 10 daily sessions of PA treatment inducing a leftward shift of spatial attention. Results suggest that neglect patients' impairment in MTT ability correlates with spatial attention deficit and with difficulties in producing reasonable temporal estimation of daily life activities. Crucially, the PA treatment induces a long-lasting and stable amelioration of MTT, spatial attention and functional competences.

Effects of spatial attention on mental time travel in patients with neglect.

Numerous studies agree that time is represented in spatial terms in the brain. Here we investigate how a deficit in orienting attention in space influences the ability to mentally travel in time, that is to recall the past and anticipate the future. Right brain-damaged patients, with (RBD-N+) and without neglect (RBD-N-), and healthy controls (HC) were subjected to a Mental Time Travel (MTT) task. Participants were asked to project themselves in time to past, present or future (i.e., self-projection) and, for each self-projection, to judge whether events were located relatively in the past or the future (i.e., self-reference). The MTT-task was performed before and after a manipulation, through prismatic adaptation (PA), inducing a leftward shift of spatial attention. Before PA, RBD-N+ were slower for future than for past events, whereas RBD-N- and HC responded similarly to past and future events. A leftward shift of spatial attention by PA reduced the difference in past/future processing in RBD-N+ and fastened RBD-N- and HC's response to past events. Assuming that time concepts, such as past/future, are coded with a left-to-right order on a mental time line (MTL), a recursive search of future-events can explain neglect patients' performance. Improvement of the spatial deficit following PA reduces the recursive search of future events on the rightmost part of the MTL, facilitating exploration of past events on the leftmost part of the MTL, finally favoring the correct location of past and future events. In addition, the study of the anatomical correlates of the temporal deficit in mental time travel through voxel-based lesion-symptom mapping showed a correlation with a lesion located in the insula and in the thalamus. These findings provide new insights about the inter-relations of space and time, and can pave the way to a procedure to rehabilitate a deficit in these cognitive domains.

Assessment of the Incremental Diagnostic Value of Florbetapir F 18 Imaging in Patients With Cognitive Impairment: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study.

IMPORTANCE: Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. OBJECTIVE: To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES: Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. RESULTS: Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9% in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P < .001). CONCLUSIONS AND RELEVANCE: Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.

Implicit and Explicit Routes to Recognize the Own Body: Evidence from Brain Damaged Patients.

Much research suggested that recognizing our own body-parts and attributing a body-part to our physical self-likely involve distinct processes. Accordingly, facilitation for self-body-parts was found when an implicit, but not an explicit, self-recognition was required. Here, we assess whether implicit and explicit bodily self-recognition is mediated by different cerebral networks and can be selectively impaired after brain lesion. To this aim, right- (RBD) and left- (LBD) brain damaged patients and age-matched controls were presented with rotated pictures of either self- or other-people hands. In the Implicit task participants were submitted to hand laterality judgments. In the Explicit task they had to judge whether the hand belonged, or not, to them. In the Implicit task, controls and LBD patients, but not RBD patients, showed an advantage for self-body stimuli. In the Explicit task a disadvantage emerged for self-compared to others' body stimuli in controls as well as in patients. Moreover, when we directly compared the performance of patients and controls, we found RBD, but not LBD, patients to be impaired in both the implicit and explicit recognition of self-body-part stimuli. Conversely, no differences were found for others' body-part stimuli. Crucially, 40% RBD patients showed a selective deficit for implicit processing of self-body-part stimuli, whereas 27% of them showed a selective deficit in the explicit recognition of their own body. Additionally, we provide anatomical evidence revealing the neural basis of this dissociation. Based on both behavioral and anatomical data, we suggest that different areas of the right hemisphere underpin implicit and explicit self-body knowledge.

Prismatic adaptation effects on spatial representation of time in neglect patients.

Processing of temporal information may require the use of spatial attention to represent time along a mental time line. We used prismatic adaptation (PA) to explore the contribution of spatial attention to the spatial representation of time in right brain damaged patients with and without neglect of left space and in age-matched healthy controls. Right brain damaged patients presented time underestimation deficits, that were significantly greater in patients with neglect than in patients without neglect. PA inducing leftward attentional deviation reduced time underestimation deficit in patients with neglect. The results support the hypothesis that a right hemispheric network has a role, per se, in time perception. Moreover, they suggest that right hemisphere is important in time perception for its control of spatial attention, engaged in spatial representation of time. Procedures that ameliorate left spatial deficits could also be useful for modulating temporal deficits in right brain damaged patients with neglect.

EEG and granular osmiophilic elements in early-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) is a rare genetic disorder mainly attributable to a mutation in the presenilin 1 (PSEN1) gene. Clinical profile and instrumental findings share common features with adult neuronal ceroid lipofuscinosis. We documented the clinical course in EOAD patients bearing mutations in PSEN1. Genetic screening for dementia, EEG acquisition and determination of granular osmiophilic elements (GRODs) from skin biopsy were performed in a patient suffering from a severe cognitive decline and visual hallucinations. The pathogenic M146I mutation in PSEN1, and instrumental findings common to adult neuronal ceroid lipofuscinosis were found in the same patient. Posterior low pseudoperiodic sequences at EEG and GRODS elements at skin biopsy might constitute a signature in EOAD.

Selective impairment of self body-parts processing in right brain-damaged patients.

To investigate whether the processing of the visual appearance of one's own body, that is the corporeal self is a unified or modular function we submitted eight right brain-damaged (RBD) patients and a group of fourteen age-matched neurologically healthy subjects, to a visual matching-to-sample task testing for corporeal self processing. If corporeal self processing is a unique function (i.e., body- and face-parts are processed by the same network), patients impaired in self body-parts (i.e., showing no self-advantage) should be impaired also in self face-parts; alternatively, if corporeal self processing is a modular function (i.e., body- and face-parts are processed by different networks), patients impaired in self body-parts should be unimpaired in self face-parts, unless the face-module is also damaged by the lesion. Results showed that healthy participants were more accurate in processing pictures representing their own as compared to other people's body- and face-parts, showing the so-called self-advantage. The patients' findings revealed a simple dissociation, in that patients who were impaired in the processing of self-related body-parts showed a preserved self-advantage when processing self-related face-parts, thus providing initial evidence of a modular representation of the corporeal self.

Visual processing of moving and static self body-parts.

Humans' ability to recognize static images of self body-parts can be lost following a lesion of the right hemisphere [Frassinetti, F., Maini, M., Romualdi, S., Galante, E., & Avanzi, S. (2008). Is it mine? Hemispheric asymmetries in corporeal self-recognition. Journal of Cognitive Neuroscience, 20, 1507-1516]. Here we investigated whether the visual information provided by the movement of self body-parts may be separately processed by right brain-damaged (RBD) patients and constitute a valuable cue to reduce their deficit in self body-parts processing. To pursue these aims, neurological healthy subjects and RBD patients were submitted to a matching-task of a pair of subsequent visual stimuli, in two conditions. In the dynamic condition, participants were shown movies of moving body-parts (hand, foot, arm and leg); in the static condition, participants were shown still images of the same body-parts. In each condition, on half of the trials at least one stimulus in the pair was from the participant's own body ('Self' condition), whereas on the remaining half of the trials both stimuli were from another person ('Other' condition). Results showed that in healthy participants the self-advantage was present when processing both static and dynamic body-parts, but it was more important in the latter condition. In RBD patients, however, the self-advantage was absent in the static, but present in the dynamic body-parts condition. These findings suggest that visual information from self body-parts in motion may be processed independently in patients with impaired static self-processing, thus pointing to a modular organization of the mechanisms responsible for the self/other distinction.

Is it mine? Hemispheric asymmetries in corporeal self-recognition.

The aim of this study was to investigate whether the recognition of "self body parts" is independent from the recognition of other people's body parts. If this is the case, the ability to recognize "self body parts" should be selectively impaired after lesion involving specific brain areas. To verify this hypothesis, patients with lesion of the right (right brain-damaged [RBD]) or left (left brain-damaged [LBD]) hemisphere and healthy subjects were submitted to a visual matching-to-sample task in two experiments. In the first experiment, stimuli depicted their own body parts or other people's body parts. In the second experiment, stimuli depicted parts of three categories: objects, bodies, and faces. In both experiments, participants were required to decide which of two vertically aligned images (the upper or the lower one) matched the central target stimulus. The results showed that the task indirectly tapped into bodily self-processing mechanisms, in that both LBD patients and normal subjects performed the task better when they visually matched their own, as compared to others', body parts. In contrast, RBD patients did not show such an advantage for self body parts. Moreover, they were more impaired than LBD patients and normal subjects when visually matching their own body parts, whereas this difference was not evident in performing the task with other people's body parts. RBD patients' performance for the other stimulus categories (face, body, object), although worse than LBD patients' and normal subjects' performance, was comparable across categories. These findings suggest that the right hemisphere may be involved in the recognition of self body parts, through a fronto-parietal network.

Long-lasting amelioration of visuospatial neglect by prism adaptation.

It has been shown that unilateral left neglect can be significantly improved for a short time after a short period of adaptation to a prismatic shift of the visual field to the right. In neuropsychological studies, however, there is no evidence demonstrating long-lasting effects following treatment by prism adaptation (PA). The first aim of the present study was to find out whether the short-term amelioration found after prismatic adaptation could be converted into long-term therapeutic improvement. Secondly, we investigated whether the improvement of neglect in standard tests could be generalized to ecological visuospatial tests. Thirdly, the effects of prism adaptation on different spatial domains (far, near and personal space) were evaluated. Fourthly, the influence of PA on high-order visuospatial functions, such as spatial representation, and on a low-order factor, i.e. sensory--motor bias, was investigated. Finally, we investigated the possible correlation between neglect amelioration, the adaptation effect and the visuomotor after-effect, as assessed by a pointing task during and after PA. Seven patients with right hemisphere lesion and left visuospatial neglect were treated with prismatic lenses in twice-daily sessions over a period of 2 weeks. In each training session, patients were required to perform a pointing task wearing base-left wedge prisms inducing a shift of the visual field to the right by 10. The presence of visual neglect and the duration of the amelioration achieved were assessed before the treatment and 2 days, 1 week and 5 weeks after treatment by using a standardized battery that included a series of behavioural and ecological visuospatial tests. Six control, untreated patients, matched to the experimental group for gravity and duration of illness, were submitted to the same tests at the same intervals as the experimental patients. The results showed an improvement in the experimental patients' performance after PA, which was maintained during the 5-week period after treatment. The amelioration of neglect was found in standard as well as in behavioural tests and in all spatial domains. In contrast, control patients did not show any improvement in neglect. The amelioration of neglect occurred only in patients who showed the adaptation effect and the after-effect in the pointing task. Neglect amelioration did not occur in one patient who did not show the adaptation effect and had an unstable after-effect. In conclusion, these findings show that prism adaptation is a productive way of achieving long-lasting improvements in neglect treatment.