Federico Nemmi

Segregation of neural circuits involved in spatial learning in reaching and navigational space.

Recent behavioral and neuropsychological studies suggest that visuo-spatial memory for reaching and navigational space is dissociated. In the present fMRI study, we investigated the hypothesis that learning spatial sequences in reaching and navigational space is processed by partially segregated neural systems. To this aim, we adapted the Corsi block tapping test (CBT) and the walking Corsi test (WalCT); the latter is a modification of the CBT in which subjects observe and reproduce spatial sequences by walking in a room instead of tapping wooden blocks on a table. Subjects were scanned while learning supra-span sequences of spatial locations through observation of video clips in which an actor tapped the blocks within reaching space (CBT) or walked on tiles placed on a carpet (WalCT). A large cerebral network spanning from visual occipital to parietal to frontal areas was activated during learning of both the CBT and the WalCT sequences. Within this network right lingual gyrus, calcarine sulcus and dorsolateral prefrontal cortex were specifically associated with learning in navigational space, whereas left inferior temporal gyrus, lingual and fusiform gyrus and middle occipital gyrus were associated with learning sequences in reaching space. These results support the idea of a partial segregation between neural circuits for reaching and navigational space not only in the domain of perception and action planning but also in spatial learning and long-term memory.

Parkinson's disease and local atrophy in subcortical nuclei: insight from shape analysis

Parkinsons disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta, inducing dopaminergic depletion in the striatum. Recently, subcortical nuclei shape analysis based on T1 imaging has been used in PD pathology. The present study aimed to test the hypothesis that changes in local volume detectable with T1-weighted imaging are concomitant with PD and may be used as biomarkers. We compared 21 PD patients and 20 control subjects using gray matter density and subcortical nuclei volume and shape. We also tested correlations between these parameters and clinical scales. A linear discriminant analyses was carried out using global volume and local atrophy. The differences revealed between the 2 groups were volume differences in the putamen and shape differences in the putamen and the caudate nucleus. A correlation was found between shape and motor symptoms. The discriminant analysis performed using local atrophy values led to the best classification. Our results show that shape analysis contributes valuable information to investigations concerning PD patients and helps to discriminate these patients from control subjects.

Cortical florbetapir-PET amyloid load in prodromal Alzheimer’s disease patients

BackgroundFlorbetapir (AV-45) has been shown to be a reliable tool to assess amyloid load in patients with Alzheimers disease (AD) at demential stages. Longitudinal studies also suggest that AV-45 has the ability to bind amyloid in the early stages of AD. In this study, we investigated AV-45 binding and its relation with cognitive performance in a group of patients at the prodromal stage of Alzheimers disease, recruited according to strict inclusion criteria.MethodsWe recruited patients at the prodromal stage of AD and matched control subjects. AV-45 binding was assessed using an innovative extraction method allowing quantifying uptake in the cortex only. AV-45 uptake was compared between groups in the precuneus, posterior cingulate, anterior cingulate, and orbito-frontal regions. Correlations between AV-45 uptake and cognitive performance were assessed.ResultsTwenty-two patients and 17 matched control subjects were included in the study. We report a significant increase of cortical AV-45 uptake in the patients compared to the control subjects in all regions of interest. Specific correlations were found within the patient group between mean global amyloid cortical load and cognitive performance in three different memory tests.ConclusionsThese findings suggest that at the prodromal stage of AD, memory decline is linked to an increase of cortical β-amyloid load.

Looking for the compass in a case of developmental topographical disorientation: A behavioral and neuroimaging study

Developmental topographical disorientation (DTD) is the presence of navigational deficits in the context of normal intellectual ability and in the absence of any perinatal, neurological, or psychiatric disorder. As only three cases of DTD have been fully described thus far, we are still unable to draw definitive conclusions about its nature and relationship with other visuospatial competencies, such as mental rotation. The case of Mr. L.A., a 38-year-old man with no history of neurological or psychiatric disorders, sheds some light on these open questions. A neuropsychological assessment including IQ, memory, visuospatial, visuoconstructive, and navigational tests showed that Mr. L.A. has pure navigational deficits affecting both route knowledge and cognitive map processing. Unlike previously described cases of DTD, Mr. L.A. was not affected by any other visuospatial or visuoconstructive deficits. In a functional magnetic resonance imaging (fMRI) task involving the recall of route knowledge, Mr. L.A. showed activation in the occipital areas, involved in low-level perceptual analysis of the stimuli, and showed no activation in the areas activated in controls with regard to route knowledge. The present case suggests that different types of DTD exist, which are characterized by different navigational difficulties and anomalous/lacking functional brain activities in specific navigational networks.

Multimodal MRI assessment of nigro‐striatal pathway in multiple system atrophy and Parkinson disease

Parkinsons disease (PD) and multiple system atrophy (MSA) are two neurodegenerative alpha‐synucleinopathies characterized by severe impairment of the nigro‐striatal pathway. Based on T1‐, T2*‐, and diffusion‐weighted magnetic resonance imaging (MRI), macro‐structural and micro‐structural abnormalities in these diseases can be detected.

A penny for your thoughts! patterns of fMRI activity reveal the content and the spatial topography of visual mental images

Visual mental imagery is a complex process that may be influenced by the content of mental images. Neuropsychological evidence from patients with hemineglect suggests that in the imagery domain environments and objects may be represented separately and may be selectively affected by brain lesions. In the present study, we used functional magnetic resonance imaging (fMRI) to assess the possibility of neural segregation among mental images depicting parts of an object, of an environment (imagined from a first‐person perspective), and of a geographical map, using both a mass univariate and a multivariate approach. Data show that different brain areas are involved in different types of mental images. Imagining an environment relies mainly on regions known to be involved in navigational skills, such as the retrosplenial complex and parahippocampal gyrus, whereas imagining a geographical map mainly requires activation of the left angular gyrus, known to be involved in the representation of categorical relations. Imagining a familiar object mainly requires activation of parietal areas involved in visual space analysis in both the imagery and the perceptual domain. We also found that the pattern of activity in most of these areas specifically codes for the spatial arrangement of the parts of the mental image. Our results clearly demonstrate a functional neural segregation for different contents of mental images and suggest that visuospatial information is coded by different patterns of activity in brain areas involved in visual mental imagery. Hum Brain Mapp 36:945–958, 2015.

Landmark sequencing and route knowledge: an fMRI study.

INTRODUCTION The ability to navigate in a familiar environment mainly relies on route knowledge, that is, a mental representation of relevant locations along a way, sequenced according to a navigational goal. Despite the clear ecological validity of this issue, route navigation and route knowledge have been scarcely investigated and little is known about the neural and cognitive bases of this navigational strategy. Using functional magnetic resonance imaging (fMRI) we tested the validity of the predictions based on the main cognitive models of spatial knowledge acquisition about route-based navigation. METHODS An order judgment task was used with two conditions (route and activity). Subjects were required to detect potential mismatches between a current sensory input and expectations deriving from route and activity knowledge. RESULTS A medial occipto-temporal (e.g., lingual gyrus, calcarine cortex, fusiform gyrus, parahippocampal cortex) network was found activated during the route task, whereas a temporo-parietal (temporo-parietal junction) and frontal (e.g., Brocas area) network was related to the activity task. CONCLUSIONS Functional data are congruent with cognitive models of route-based navigation. The route task activated areas related to both landmark identity and landmark order. Data are discussed in view of route-based navigation models.

Finding my own way: an fMRI single case study of a subject with developmental topographical disorientation

Developmental topographical disorientation (DTD) causes impaired spatial orientation and navigation from early childhood with no evidence of cerebral damage. Using fMRI and a landmark sequencing task, we investigated the hypothesis that Dr Wai’s abnormal cerebral activation pattern was related to his peculiar behavioral profile. Although Dr Wai was able to correctly perform landmark sequencing, he showed a lack of activity in regions activated in all control subjects and activity in areas that were not activated in any control subject. These results are discussed in light of cognitive and functional model of navigation, with relevant implications for DTD physiology.

Insight on AV-45 binding in white and grey matter from histogram analysis: a study on early Alzheimer’s disease patients and healthy subjects

PurposeAV-45 amyloid biomarker is known to show uptake in white matter in patients with Alzheimer’s disease (AD), but also in the healthy population. This binding, thought to be of a non-specific lipophilic nature, has not yet been investigated. The aim of this study was to determine the differential pattern of AV-45 binding in white matter in healthy and pathological populations.MethodsWe recruited 24 patients presenting with AD at an early stage and 17 matched, healthy subjects. We used an optimized positron emission tomography-magnetic resonance imaging (PET-MRI) registration method and an approach based on an intensity histogram using several indices. We compared the results of the intensity histogram analyses with a more canonical approach based on target-to-cerebellum Standard Uptake Value (SUVr) in white and grey matter using MANOVA and discriminant analyses. A cluster analysis on white and grey matter histograms was also performed.ResultsWhite matter histogram analysis revealed significant differences between AD and healthy subjects, which were not revealed by SUVr analysis. However, white matter histograms were not decisive to discriminate groups, and indices based on grey matter only showed better discriminative power than SUVr. The cluster analysis divided our sample into two clusters, showing different uptakes in grey, but also in white matter.ConclusionThese results demonstrate that AV-45 binding in white matter conveys subtle information not detectable using the SUVr approach. Although it is not more efficient than standard SUVr in discriminating AD patients from healthy subjects, this information could reveal white matter modifications.

Direct and indirect parieto-medial temporal pathways for spatial navigation in humans: evidence from resting-state functional connectivity

Anatomical and functional findings in primates suggest the existence of a dedicated parieto-medial temporal pathway for spatial navigation, consisting of both direct and indirect projections from the caudal inferior parietal lobe (cIPL) to the hippocampus and the parahippocampal cortex, with indirect projections relaying through the posterior cingulate and retrosplenial cortex. This neural network is largely unexplored in humans. This study aimed at testing the existence of a parieto-medial temporal pathway for spatial navigation in humans. We explored the cortical connectivity patterns of the parahippocampal place area (PPA), the retrosplenial cortex (RSC), and the hippocampus (HC) using resting-state functional connectivity MRI. Our results demonstrate the existence of connections between the medial temporal lobe structures, i.e., PPA and HC, and the angular gyrus (AG), the human homologue of cIPL, as well as between RSC and AG. These connectivity patterns seem to reflect the direct and the indirect projections found in primates from cIPL to the medial temporal lobe. Such a result deserves feasible considerations to better understand the brain networks underpinning human spatial navigation.