Atrophy of hippocampal subfields and amygdala nuclei in subjects with mild cognitive impairment progressing to Alzheimer's disease.

The hippocampus and amygdala are the first brain regions to show early signs of Alzheimer's Disease (AD) pathology. AD is preceded by a prodromal stage known as Mild Cognitive Impairment (MCI), a crucial crossroad in the clinical progression of the disease. The topographical development of AD has been the subject of extended investigation. However, it is still largely unknown how the transition from MCI to AD affects specific hippocampal and amygdala subregions. The present study is set to answer that question. We analyzed data from 223 subjects: 75 healthy controls, 52 individuals with MCI, and 96 AD patients obtained from the ADNI. The MCI group was further divided into two subgroups depending on whether individuals in the 48 months following the diagnosis either remained stable (N = 21) or progressed to AD (N = 31). A MANCOVA test evaluated group differences in the volume of distinct amygdala and hippocampal subregions obtained from magnetic resonance images. Subsequently, a stepwise linear discriminant analysis (LDA) determined which combination of magnetic resonance imaging parameters was most effective in predicting the conversion from MCI to AD. The predictive performance was assessed through a Receiver Operating Characteristic analysis. AD patients displayed widespread subregional atrophy. MCI individuals who progressed to AD showed selective atrophy of the hippocampal subiculum and tail compared to stable MCI individuals, who were undistinguishable from healthy controls. Converter MCI showed atrophy of the amygdala's accessory basal, central, and cortical nuclei. The LDA identified the hippocampal subiculum and the amygdala's lateral and accessory basal nuclei as significant predictors of MCI conversion to AD. The analysis returned a sensitivity value of 0.78 and a specificity value of 0.62. These findings highlight the importance of targeted assessments of distinct amygdala and hippocampus subregions to help dissect the clinical and pathophysiological development of the MCI to AD transition.

Atrophy of specific amygdala subfields in subjects converting to mild cognitive impairment.

Introduction: Accumulating evidence indicates that the amygdala exhibits early signs of Alzheimer's disease (AD) pathology. However, it is still unknown whether the atrophy of distinct subfields of the amygdala also participates in the transition from healthy cognition to mild cognitive impairment (MCI). Methods: Our sample was derived from the AD Neuroimaging Initiative 3 and consisted of 97 cognitively healthy (HC) individuals, sorted into two groups based on their clinical follow-up: 75 who remained stable (s-HC) and 22 who converted to MCI within 48 months (c-HC). Anatomical magnetic resonance (MR) images were analyzed using a semi-automatic approach that combines probabilistic methods and a priori information from ex vivo MR images and histology to segment and obtain quantitative structural metrics for different amygdala subfields in each participant. Spearman's correlations were performed between MR measures and baseline and longitudinal neuropsychological measures. We also included anatomical measurements of the whole amygdala, the hippocampus, a key target of AD-related pathology, and the whole cortical thickness as a test of spatial specificity. Results: Compared with s-HC individuals, c-HC subjects showed a reduced right amygdala volume, whereas no significant difference was observed for hippocampal volumes or changes in cortical thickness. In the amygdala subfields, we observed selected atrophy patterns in the basolateral nuclear complex, anterior amygdala area, and transitional area. Macro-structural alterations in these subfields correlated with variations of global indices of cognitive performance (measured at baseline and the 48-month follow-up), suggesting that amygdala changes shape the cognitive progression to MCI. Discussion: Our results provide anatomical evidence for the early involvement of the amygdala in the preclinical stages of AD. Highlights: Amygdala's atrophy marks elderly progression to mild cognitive impairment (MCI).Amygdala's was observed within the basolateral and amygdaloid complexes.Macro-structural alterations were associated with cognitive decline.No atrophy was found in the hippocampus and cortex.

LSD-induced changes in the functional connectivity of distinct thalamic nuclei.

The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging studies. However, a detailed analysis of LSD effects on nuclei-resolved thalamocortical connectivity is still missing. Here, in a group of healthy volunteers, we evaluated whether LSD intake alters the thalamocortical coupling in a nucleus-specific manner. Structural and resting-state functional Magnetic Resonance Imaging (MRI) data were acquired in a placebo-controlled study on subjects exposed to acute LSD administration. Structural MRI was used to parcel the thalamus into its constituent nuclei based on individual anatomy. Nucleus-specific changes of resting-state functional MRI (rs-fMRI) connectivity were mapped using a seed-based approach. LSD intake selectively increased the thalamocortical functional connectivity (FC) of the ventral complex, pulvinar, and non-specific nuclei. Functional coupling was increased between these nuclei and sensory cortices that include the somatosensory and auditory networks. The ventral and pulvinar nuclei also exhibited increased FC with parts of the associative cortex that are dense in serotonin type 2A receptors. These areas are hyperactive and hyper-connected upon LSD intake. At subcortical levels, LSD increased the functional coupling among the thalamus's ventral, pulvinar, and non-specific nuclei, but decreased the striatal-thalamic connectivity. These findings unravel some LSD effects on the modulation of subcortical-cortical circuits and associated behavioral outputs.

Sex differences in trigeminal neuralgia: a focus on radiological and clinical characteristics.

BACKGROUND: It is well established that trigeminal neuralgia is more prevalent in females than in males. Neurovascular compression with morphological changes of the trigeminal root represents the most recognized etiological factor. However, other factors may play a role in the framework of a multi-hit model. The primary aim of this study was to investigate sex differences in radiological and clinical characteristics of trigeminal neuralgia to better understand the multifactorial origin of this peculiar neuropathic pain condition. METHODS: In this cross-sectional study patients with a definite diagnosis of primary trigeminal neuralgia were consecutively enrolled. Each patient underwent 3T MRI with sequences dedicated to the study of neurovascular compression. Major morphological changes of the trigeminal root were quantitatively assessed. Clinical characteristics were systematically collected through a dedicated questionnaire. A logistic regression model was implemented to predict radiological and clinical characteristics based on sex. RESULTS: A total of 114 patients with classical (87) or idiopathic trigeminal neuralgia (27) were enrolled. Female sex was predictive for idiopathic trigeminal neuralgia. Male sex was predictive, among the comorbidities and clinical characteristics, for hypertension, the involvement of the left side and the second trigeminal division, alone or with the ophthalmic division. DISCUSSION: The preponderance of TN in the female sex and the association between idiopathic TN and the female sex suggest the role of additional etiological factors in the framework of a multi-hit model. The identification of clinical variables predicted by sex suggests the possibility that distinct phenotypes, with peculiar pathophysiological and therapeutic aspects, may occur in females and males.

The Spectrum of Neurological and Sensory Abnormalities in Gaucher Disease Patients: A Multidisciplinary Study (SENOPRO).

Gaucher disease (GD) has been increasingly recognized as a continuum of phenotypes with variable neurological and sensory involvement. No study has yet specifically explored the spectrum of neuropsychiatric and sensory abnormalities in GD patients through a multidisciplinary approach. Abnormalities involving the nervous system, including sensory abnormalities, cognitive disturbances, and psychiatric comorbidities, have been identified in GD1 and GD3 patients. In this prospective study, named SENOPRO, we performed neurological, neuroradiological, neuropsychological, ophthalmological, and hearing assessments in 22 GD patients: 19 GD1 and 3 GD3. First, we highlighted a high rate of parkinsonian motor and non-motor symptoms (including high rates of excessive daytime sleepiness), especially in GD1 patients harboring severe glucocerebrosidase variants. Secondly, neuropsychological evaluations revealed a high prevalence of cognitive impairment and psychiatric disturbances, both in patients initially classified as GD1 and GD3. Thirdly, hippocampal brain volume reduction was associated with impaired short- and long-term performance in an episodic memory test. Fourthly, audiometric assessment showed an impaired speech perception in noise in the majority of patients, indicative of an impaired central processing of hearing, associated with high rates of slight hearing loss both in GD1 and GD3 patients. Finally, relevant structural and functional abnormalities along the visual system were found both in GD1 and GD3 patients by means of visual evoked potentials and optical coherence tomography. Overall, our findings support the concept of GD as a spectrum of disease subtypes, and support the importance of in-depth periodic monitoring of cognitive and motor performances, mood, sleep patterns, and sensory abnormalities in all patients with GD, independently from the patient's initial classification.

Preferential signal pathways during the perception and imagery of familiar scenes: An effective connectivity study.

The perception and imagery of landmarks activate similar content-dependent brain areas, including occipital and temporo-medial brain regions. However, how these areas interact during visual perception and imagery of scenes, especially when recollecting their spatial location, remains unknown. Here, we combined functional magnetic resonance imaging (fMRI), resting-state functional connectivity (rs-fc), and effective connectivity to assess spontaneous fluctuations and task-induced modulation of signals among regions entailing scene-processing, the primary visual area and the hippocampus (HC), responsible for the retrieval of stored information. First, we functionally defined the scene-selective regions, that is, the occipital place area (OPA), the retrosplenial complex (RSC) and the parahippocampal place area (PPA), by using the face/scene localizer, observing that two portions of the PPA-anterior and posterior PPA-were consistently activated in all subjects. Second, the rs-fc analysis (n = 77) revealed a connectivity pathway similar to the one described in macaques, showing separate connectivity routes linking the anterior PPA with RSC and HC, and the posterior PPA with OPA. Third, we used dynamic causal modelling to evaluate whether the dynamic couplings among these regions differ between perception and imagery of familiar landmarks during a fMRI task (n = 16). We found a positive effect of HC on RSC during the retrieval of imagined places and an effect of occipital regions on both RSC and pPPA during the perception of scenes. Overall, we propose that under similar functional architecture at rest, different neural interactions take place between regions in the occipito-temporal higher-level visual cortex and the HC, subserving scene perception and imagery.

Whole brain surface-based morphometry and tract-based spatial statistics in migraine with aura patients: difference between pure visual and complex auras.

Background: The migrainous aura has different clinical phenotypes. While the various clinical differences are well-described, little is known about their neurophysiological underpinnings. To elucidate the latter, we compared white matter fiber bundles and gray matter cortical thickness between healthy controls (HC), patients with pure visual auras (MA) and patients with complex neurological auras (MA+). Methods: 3T MRI data were collected between attacks from 20 patients with MA and 15 with MA+, and compared with those from 19 HCs. We analyzed white matter fiber bundles using tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) and cortical thickness with surface-based morphometry of structural MRI data. Results: Tract-based spatial statistics showed no significant difference in diffusivity maps between the three subject groups. As compared to HCs, both MA and MA+ patients had significant cortical thinning in temporal, frontal, insular, postcentral, primary and associative visual areas. In the MA group, the right high-level visual-information-processing areas, including lingual gyrus, and the Rolandic operculum were thicker than in HCs, while in the MA+ group they were thinner. Discussion: These findings show that migraine with aura is associated with cortical thinning in multiple cortical areas and that the clinical heterogeneity of the aura is reflected by opposite thickness changes in high-level visual-information-processing, sensorimotor and language areas.

Interhemispheric interplay between the left and right premotor cortex during grasping as assessed by dynamic causal modelling.

Research on the contribution of the ipsilateral hemisphere to unilateral movements, and how it is mediated by transcallosal connections, has so far provided contradictory findings. By using dynamic causal modelling (DCM) and Parametric Empirical Bayes analyses applied to fMRI data, we sought to describe effective connectivity during pantomimed and imagined right-hand grasping within the grasping network, namely the anterior intraparietal sulcus, ventral and dorsal (PMd) premotor cortex, supplementary motor area and primary motor cortex (M1). The two-fold aim of the present work was to explore a) whether right and left parieto-frontal areas show similar connectivity couplings, and b) the interhemispheric dynamics between these regions across the two hemispheres. We detected a network architecture comparable across hemispheres during executed but not imagined grasping movements. Furthermore, during pantomimed grasping the interhemispheric crosstalk was mainly driven by premotor areas: we found an inhibitory influence from the right PMd toward the left premotor and motor areas and excitatory couplings between homologous ventral premotor and supplementary motor regions. Overall, our results support the view that dissociable components of unilateral grasping execution are encoded by a non-lateralized set of brain areas complexly intertwined by interhemispheric dynamics, whereas motor imagery obeys different principles.

Effect of optic flow on spatial updating: insight from an immersive virtual reality study.

Self-motion information is required to keep track of where we are with respect to our environment (spatial updating). Visual signals such as optic flow are relevant to provide information about self-motion, especially in the absence of vestibular and/or proprioceptive cues generated by physical movement. However, the role of optic flow on spatial updating is still debated. A virtual reality system based on a head-mounted display was used to allow participants to experience a self-motion sensation within a naturalistic environment in the absence of physical movement. We asked participants to keep track of spatial positions of a target during simulated self-motion while manipulating the availability of optic flow coming from the lower part of the environment (ground plane). In each trial, the ground could be a green lawn (optic flow ON) or covered in snow (optic flow OFF). We observed that the lack of optic flow on the ground had a detrimental effect on spatial updating. Furthermore, we explored the interaction between the optic flow availability and different characteristics of self-motion: we observed that increasing self-motion speed had a detrimental effect on spatial updating, especially in the absence of optic flow, while self-motion direction (leftward, forward, rightward) and path (translational and curvilinear) had no statically significant effect. Overall, we demonstrated that, in the absence of some idiothetic cues, the optic flow provided by the ground has a dominant role for the self-motion estimation and, hence, for the ability to update the spatial relationships between one's position and the position of the surrounding objects.

Effector-selective modulation of the effective connectivity within frontoparietal circuits during visuomotor tasks.

Despite extensive research, the functional architecture of the subregions of the dorsal posterior parietal cortex (PPC) involved in sensorimotor processing is far from clear. Here, we draw a thorough picture of the large-scale functional organization of the PPC to disentangle the fronto-parietal networks mediating visuomotor functions. To this aim, we reanalyzed available human functional magnetic resonance imaging data collected during the execution of saccades, hand, and foot pointing, and we combined individual surface-based activation, resting-state functional connectivity, and effective connectivity analyses. We described a functional distinction between a more lateral region in the posterior intraparietal sulcus (lpIPS), preferring saccades over pointing and coupled with the frontal eye fields (FEF) at rest, and a more medial portion (mpIPS) intrinsically correlated to the dorsal premotor cortex (PMd). Dynamic causal modeling revealed feedforward-feedback loops linking lpIPS with FEF during saccades and mpIPS with PMd during pointing, with substantial differences between hand and foot. Despite an intrinsic specialization of the action-specific fronto-parietal networks, our study reveals that their functioning is finely regulated according to the effector to be used, being the dynamic interactions within those networks differently modulated when carrying out a similar movement (i.e. pointing) but with distinct effectors (i.e. hand and foot).

Individual differences in mental imagery modulate effective connectivity of scene-selective regions during resting state.

Successful navigation relies on the ability to identify, perceive, and correctly process the spatial structure of a scene. It is well known that visual mental imagery plays a crucial role in navigation. Indeed, cortical regions encoding navigationally relevant information are also active during mental imagery of navigational scenes. However, it remains unknown whether their intrinsic activity and connectivity reflect the individuals' ability to imagine a scene. Here, we primarily investigated the intrinsic causal interactions among scene-selective brain regions such as Parahipoccampal Place Area (PPA), Retrosplenial Complex, and Occipital Place Area (OPA) using Dynamic Causal Modelling for resting-state functional magnetic resonance data. Second, we tested whether resting-state effective connectivity parameters among scene-selective regions could reflect individual differences in mental imagery in our sample, as assessed by the self-reported Vividness of Visual Imagery Questionnaire. We found an inhibitory influence of occipito-medial on temporal regions, and an excitatory influence of more anterior on more medial and posterior brain regions. Moreover, we found that a key role in imagery is played by the connection strength from OPA to PPA, especially in the left hemisphere, since the influence of the signal between these scene-selective regions positively correlated with good mental imagery ability. Our investigation contributes to the understanding of the complexity of the causal interaction among brain regions involved in navigation and provides new insight in understanding how an essential ability, such as mental imagery, can be explained by the intrinsic fluctuation of brain signal.

Assessing the effective connectivity of premotor areas during real vs imagined grasping: a DCM-PEB approach.

The parieto-frontal circuit underlying grasping, which requires the serial involvement of the anterior intraparietal area (aIPs) and the ventral premotor cortex (PMv), has been recently extended enlightening the role of the dorsal premotor cortex (PMd). The supplementary motor area (SMA) has been also suggested to encode grip force for grasping actions; furthermore, both PMd and SMA are known to play a crucial role in motor imagery. Here, we aimed at assessing the dynamic couplings between left aIPs, PMv, PMd, SMA and primary motor cortex (M1) by comparing executed and imagined right-hand grasping, using Dynamic Causal Modelling (DCM) and Parametrical Empirical Bayes (PEB) analyses. 24 subjects underwent an fMRI exam (3T) during which they were asked to perform or imagine a grasping movement visually cued by photographs of commonly used objects. We tested whether the two conditions a) exert a modulatory effect on both forward and feedback couplings among our areas of interest, and b) differ in terms of strength and sign of these parameters. Results of the real condition confirmed the serial involvement of aIPs, PMv and M1. PMv also exerted a positive influence on PMd and SMA, but received an inhibitory feedback only from PMd. Our results suggest that a general motor program for grasping is planned by the aIPs-PMv circuit; then, PMd and SMA encode high-level features of the movement. During imagery, the connection strength from aIPs to PMv was weaker and the information flow stopped in PMv; thus, a less complex motor program was planned. Moreover, results suggest that SMA and PMd cooperate to prevent motor execution. In conclusion, the comparison between execution and imagery reveals that during grasping premotor areas dynamically interplay in different ways, depending on task demands.