Associations between cortical ß-amyloid burden, fornix microstructure and cognitive processing of faces, places, bodies and other visual objects in early Alzheimer's disease.

Using two imaging modalities, that is, Pittsburgh compound B (PiB) positron emission tomography (PET) and diffusion tensor imaging (DTI) the present study tested associations between cortical amyloid-beta (Aß) burden and fornix microstructural changes with cognitive deficits in early Alzheimer's disease (AD), namely deficits in working memory (1-back) processing of visual object categories (faces, places, objects, bodies and verbal material). Second, we examined cortical Aß associations with fornix microstructure. Seventeen early AD patients and 17 healthy-matched controls were included. Constrained spherical deconvolution-based tractography was used to segment the fornix and a control tract the central branch of the superior longitudinal fasciculus (CB-SLF) previously implicated in working memory processes. Standard uptake value ratios (SUVR) of Aß were extracted from 45 cortical/subcortical regions from the AAL atlas and subject to principal component analysis for data reduction. Patients exhibited (i) impairments in cognitive performance (ii) reductions in fornix fractional anisotropy (FA) and (iii) increases in a component that loaded highly on cortical Aß. There were no group differences in CB-SLF FA and in a component loading highly on subcortical Aß. Partial correlation analysis in the patient group showed (i) positive associations between fornix FA and performance for all the visual object categories and (ii) a negative association between the cortical Aß component and performance for the object categories but not for the remaining classes of visual stimuli. A subsequent analysis showed a positive association between overall cognition (performance across distinct 1-back task conditions) with fornix FA but no association with cortical Aß burden, in keeping with influential accounts on early onset AD. This indicates that the fornix degenerates early in AD and contributes to deficits in working memory processing of visual object categories; though it is also important to acknowledge the importance of prospective longitudinal studies with larger samples. Overall, the effect sizes of fornical degeneration on visual working memory appeared stronger than the ones related to amyloid burden.

The longitudinal impact of type 2 diabetes on brain gyrification.

Type 2 diabetes has an effect on brain structure, including cortical gyrification. The significance of these changes is better understood if assessed over time. However, there is a lack of studies assessing longitudinally the effect of this disease with complex aethology in gyrification. While changes in this feature have been associated mainly with genetic legacy, our study allowed to shed light on the effect of the variation of glycaemic profile over time in gyrification in this metabolic disease. In this longitudinal study, we analysed brain anatomical magnetic resonance images of 15 participants with type 2 diabetes and 13 healthy control participants to investigate the impact of this metabolic disease on the gyrification index over a 7-year period. We observed a significant interaction between time and group in six regions, four of which (left precentral gyrus, left gyrus rectus, left subcentral gyrus and sulci and right inferior temporal gyrus) showed an increase in gyrification in type 2 diabetes and a decrease in the control group and the two others (left pericallosal sulcus and right inferior frontal sulcus) the opposite pattern. The variation of the gyrification was correlated with the variation of the glycaemic profile. Following the interaction, the simple main effect of time in each group separately has shown that in the group with diabetes, there were more regions susceptible to alterations of gyrification. In sum, our results raise credit for the possibility that glycaemic control also might influence gyrification in type 2 diabetes.

The Retinal Inner Plexiform Synaptic Layer Mirrors Grey Matter Thickness of Primary Visual Cortex with Increased Amyloid ß Load in Early Alzheimer's Disease.

The retina may serve as putative window into neuropathology of synaptic loss in Alzheimer's disease (AD). Here, we investigated synapse-rich layers versus layers composed by nuclei/cell bodies in an early stage of AD. In addition, we examined the associations between retinal changes and molecular and structural markers of cortical damage. We recruited 20 AD patients and 17 healthy controls (HC). Combining optical coherence tomography (OCT), magnetic resonance (MR), and positron emission tomography (PET) imaging, we measured retinal and primary visual cortex (V1) thicknesses, along with V1 amyloid ß (Aß) retention ([11C]-PiB PET tracer) and neuroinflammation ([11C]-PK11195 PET tracer). We found that V1 showed increased amyloid-binding potential, in the absence of neuroinflammation. Although thickness changes were still absent, we identified a positive association between the synapse-rich inner plexiform layer (IPL) and V1 in AD. This retinocortical interplay might reflect changes in synaptic function resulting from Aß deposition, contributing to early visual loss.

Processing of performance-matched visual object categories: faces and places are related to lower processing load in the frontoparietal executive network than other objects.

This study aimed to explore the differential role of the frontoparietal network in processing different visual object categories, matched for difficulty level, during a 1-back paradigm. To achieve this goal, we first mapped the effort-related frontoparietal saliency network, by contrasting activation elicited by face, object, place, body and verbal stimulus categories, which were matched for performance level, and speed of processing, with difficult scrambled stimuli. We then computed the weight of object predictors on that specific network, using an independent orthogonal analysis. Overall, our results demonstrated that face (and to some extent also places) stimuli were associated with lower processing load in regions of the frontoparietal network comparing to other visual categories, suggesting that face/place processing does require to a much smaller extent the recruitment of the frontoparietal control network than any other object categories. Thus, face detection and place detection seem to be routed in specific neuronal systems that readily encode the holistic nature of this type of objects. We conclude that the more limited recruitment of frontoparietal networks reflects the automaticity of face and place processing and their smaller dependence on general capacity limits.

Apathy Profile in Parkinson's and Huntington's Disease: A Comparative Cross-Sectional Study.

BACKGROUND/AIMS: Apathy is one of the most frequent, disabling and difficult-to-treat symptoms that show up in many neurodegenerative disorders. The aim of this study was to assess and compare apathy profile in Parkinson's and Huntington's patients using the same comprehensive instruments to measure apathy, cognition and depressive symptoms. MATERIALS AND METHODS: We consecutively assessed Parkinson's disease (PD) and Huntington's disease (HD) patients recruited from a Movement Disorders Unit. In all patients, information related to demographics, clinical data, motor score (Movement Disorders Society-Unified Parkinson Disease Rating Scale; Unified Huntington Disease Rating Scale), cognition (Montreal Cognitive Assessment scale), depressive symptoms (Beck Depression Inventory II) and apathy (Apathy Evaluation Scale - clinical version) was collected. Patients with dementia or major depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised criteria were excluded from the study. RESULTS: Seventy-five patients were enrolled, 45 with PD and 30 with HD. Apathy was present in 42.5% of PD patients and 51.7% of HD patients. In PD patients, apathy was associated with motor score, shorter duration of disease, lower dose of levodopa equivalent daily dose and depressive symptomatology, whereas in HD patients, apathy was related to disease duration, motor score and cognitive impairment. CONCLUSIONS: We found a similar prevalence of apathy in PD and HD patients but with different clinical correlations and different apathy domains involved, and this may warrant the development of different therapeutic approaches.

Irreversible atrophy in memory brain regions over 7 years is predicted by glycemic control in type 2 diabetes without mild cognitive impairment.

Memory-related impairments in type 2 diabetes may be mediated by insulin resistance and hyperglycemia. Previous cross-sectional studies have controversially suggested a relationship between metabolic control and a decrease in hippocampal volumes, but only longitudinal studies can test this hypothesis directly. We performed a longitudinal morphometric study to provide a direct test of a possible role of higher levels of glycated hemoglobin with long term brain structural integrity in key regions of the memory system - hippocampus, parahippocampal gyrus and fusiform gyrus. Grey matter volume was measured at two different times - baseline and after ~7 years. We found an association between higher initial levels of HbA1C and grey matter volume loss in all three core memory regions, even in the absence of mild cognitive impairment. Importantly, these neural effects persisted in spite of the fact that patients had significantly improved their glycemic control. This suggests that early high levels of HbA1c might be irreversibly associated with subsequent long-term atrophy in the medial temporal cortex and that early intensive management is critical.

Functional reorganization of memory processing in the hippocampus is associated with neuroprotector GLP-1 levels in type 2 diabetes.

Type 2 diabetes (T2D) often impairs memory functions, suggesting specific vulnerability of the hippocampus. In vivo neuroimaging studies relating encoding and retrieval of memory information with endogenous neuroprotection are lacking. The neuroprotector glucagon-like peptide (GLP-1) has a high receptor density in anterior/ventral hippocampus, as shown by animal models. Using an innovative event-related fMRI design in 34 participants we investigated patterns of hippocampal activity in T2D (n = 17) without mild cognitive impairment (MCI) versus healthy controls (n = 17) during an episodic memory task. We directly measured neurovascular coupling by estimating the hemodynamic response function using event-related analysis related to encoding and retrieval of episodic information in the hippocampus. We applied a mixed-effects general linear model analysis and a two-factor ANOVA to test for group differences. Significant between-group differences were found for memory encoding, showing evidence for functional reorganization: T2D patients showed an augmented activation in the posterior hippocampus while anterior activation was reduced. The latter was negatively correlated with both GLP-1 pre- and post-breakfast levels, in the absence of grey matter changes. These results suggest that patients with T2D without MCI have pre-symptomatic functional reorganization in brain regions underlying episodic memory, as a function of the concentration of the neuroprotective neuropeptide GLP-1.

Hemispheric Patterns of Recruitment of Object Processing Regions in Early Alzheimer's Disease: A Study Along the Entire Ventral Stream.

BACKGROUND: Investigation of neural response patterns along the entire network of functionally defined object recognition ventral stream regions in Alzheimer's disease (AD) is surprisingly lacking. OBJECTIVE: We aimed to investigate putative functional reorganization along a wide-ranging network of known regions in the ventral visual stream in mild AD. METHODS: Overall we investigated 6 regions of interest (5 of which were not investigated before), in 19 AD patients and 19 controls, in both hemispheres along the ventral visual stream: Fusiform Face Area, Fusiform Body Area, Extrastriate Body Area, Lateral Occipital Cortex, Parahippocampal Place Area, and Visual Word Form Area, while assessing object recognition performance. RESULTS: We found group differences in dprime measures for all object categories, corroborating generalized deficits in object recognition. Concerning neural responses, we found region dependent group differences respecting a priori expected Hemispheric asymmetries. Patients showed significantly decreased BOLD responses in the right hemisphere-biased Fusiform Body Area, and lower left hemisphere responses in the Visual Word Form Area (with a priori known left hemispheric bias), consistent with deficits in body shape and word/pseudoword processing deficits. This hemispheric dominance related effects were preserved when controlling for performance differences. Whole brain analysis during the recognition task showed enhanced activity in AD group of left dorsolateral prefrontal cortex, left cingulate gyrus, and in the posterior cingulate cortex- a hotspot of amyloid-ß accumulation. CONCLUSION: These findings demonstrate region dependent respecting hemispheric dominance patterns activation changes in independently localized selective regions in mild AD, accompanied by putative compensatory activity of frontal and cingular networks.

Textural properties of microglial activation in Alzheimer's disease as measured by (R)-[11C]PK11195 PET.

Alzheimer's disease is the most common form of dementia worldwide, accounting for 60-70% of diagnosed cases. According to the current understanding of molecular pathogenesis, the main hallmarks of this disease are the abnormal accumulation of amyloid plaques and neurofibrillary tangles. Therefore, biomarkers reflecting these underlying biological mechanisms are recognized as valid tools for an early diagnosis of Alzheimer's disease. Inflammatory mechanisms, such as microglial activation, are known to be involved in Alzheimer's disease onset and progression. This activated state of the microglia is associated with increased expression of the translocator protein 18 kDa. On that account, PET tracers capable of measuring this signature, such as (R)-[11C]PK11195, might be instrumental in assessing the state and evolution of Alzheimer's disease. This study aims to investigate the potential of Gray Level Co-occurrence Matrix-based textural parameters as an alternative to conventional quantification using kinetic models in (R)-[11C]PK11195 PET images. To achieve this goal, kinetic and textural parameters were computed on (R)-[11C]PK11195 PET images of 19 patients with an early diagnosis of Alzheimer's disease and 21 healthy controls and submitted separately to classification using a linear support vector machine. The classifier built using the textural parameters showed no inferior performance compared to the classical kinetic approach, yielding a slightly larger classification accuracy (accuracy of 0.7000, sensitivity of 0.6957, specificity of 0.7059 and balanced accuracy of 0.6967). In conclusion, our results support the notion that textural parameters may be an alternative to conventional quantification using kinetic models in (R)-[11C]PK11195 PET images. The proposed quantification method makes it possible to use simpler scanning procedures, which increase patient comfort and convenience. We further speculate that textural parameters may also provide an alternative to kinetic analysis in (R)-[11C]PK11195 PET neuroimaging studies involving other neurodegenerative disorders. Finally, we recognize that the potential role of this tracer is not in diagnosis but rather in the assessment and progression of the diffuse and dynamic distribution of inflammatory cell density in this disorder as a promising therapeutic target.

Dual PET-fMRI reveals a link between neuroinflammation, amyloid binding and compensatory task-related brain activity in Alzheimer's disease.

The interplay among neuropathological mechanisms underlying Alzheimer's disease (AD), as neuroinflammation and amyloid-beta (Aß), as well their impact on neuronal function remains elusive. A major gap in knowledge is the functional impact of neuroinflammation. The posterior cingulate cortex (PCC), as the most prominent site of amyloid pathology in AD, is a pivotal region to investigate the concomitant presence of pathophysiological mechanisms such as microglia activation, indexing neuroinflammation, and changes in task related activity. Here we used a dual PET approach to simultaneously study Aß load and neuroinflammation (TSPO uptake marker), using 11C-PiB and 11C-PK11195 radiotracers, respectively and fMRI to study task related neural activation in an AD sample (n = 19) and matched controls (n = 19). Here we show significantly increased Aß deposition, neuroinflammation and brain activity related to a visual object working memory task in this key region. Microglia activation was associated with increased brain activity specifically in patients, independently of amyloid binding, raising the possibility that abnormal brain activity might be restored in clinical trials aimed at reducing microglia activation.

Structural impairments in hippocampal and occipitotemporal networks specifically contribute to decline in place and face category processing but not to other visual object categories in healthy aging.

BACKGROUND: Functional neuroimaging studies have identified a set of nodes in the occipital-temporal cortex that preferentially respond to faces in comparison with other visual objects. By contrast, the processing of places seems to rely on parahippocampal cortex and structures heavily implicated in memory (e.g., the hippocampus). It has been suggested that human aging leads to decreased neural specialization of core face and place processing areas and impairments in face and place perception. METHODS: Using mediation analysis, we tested the potential contribution of micro- and macrostructure within the hippocampal and occipitotemporal systems to age-associated effects in face and place category processing (as measured by 1-back working memory tasks) in 55 healthy adults (age range 23-79 years). To test for specific contributions of the studied structures to face/place processing, we also studied a distinct tract (i.e., the anterior thalamic radiation [ATR]) and cognitive performance for other visual object categories (objects, bodies, and verbal material). Constrained spherical deconvolution-based tractography was used to reconstruct the fornix, the inferior longitudinal fasciculus (ILF), and the ATR. Hippocampal volumetric measures were segmented from FSL-FIRST toolbox. RESULTS: It was found that age associates with (a) decreases in fractional anisotropy (FA) in the fornix, in right ILF (but not left ILF), and in the ATR (b) reduced volume in the right and left hippocampus and (c) decline in visual object category processing. Importantly, mediation analysis showed that micro- and macrostructural impairments in the fornix and right hippocampus, respectively, associated with age-dependent decline in place processing. Alternatively, microstructural impairments in right hemispheric ILF associated with age-dependent decline in face processing. There were no other mediator effects of micro- and macrostructural variables on age-cognition relationships. CONCLUSION: Together, the findings support specific contributions of the fornix and right hippocampus in visuospatial scene processing and of the long-range right hemispheric occipitotemporal network in face category processing.

Frontoparietal microstructural damage mediates age-dependent working memory decline in face and body information processing: Evidence for dichotomic hemispheric bias mechanisms.

Age-associated damage in the microstructure of frontally-based connections (e.g. genu of the corpus callosum and superior longitudinal fasciculus) is believed to lead to impairments in processing speed and executive function. Using mediation analysis, we tested the potential contribution of callosal and frontoparietal association tracts to age-dependent effects on cognition/executive function as measured with 1-back working memory tasks for visual stimulus categories (i.e. faces and non-emotional bodies) in a group of 55 healthy adults (age range 23-79 years). Constrained spherical deconvolution-based tractography was employed to reconstruct the genu/prefrontal section of the corpus callosum (GCC) and the central/second branch of the superior longitudinal fasciculus (CB-SLF). Age was associated with (i) reductions in fractional anisotropy (FA) in the GCC and in the right and left CB-SLF and (iii) decline in visual object category processing. Mediation analysis revealed that microstructural damage in right hemispheric CB-SLF is associated with age-dependent decline in face processing likely reflecting the stimulus-specific/holistic nature of face processing within dedicated/specialized frontoparietal routes. By contrast, microstructural damage in left hemispheric CB-SLF associated with age-dependent decline in non-emotional body processing, consistent with the more abstract nature of non-emotional body categories. In sum, our findings suggest that frontoparietal microstructural damage mediates age-dependent decline in face and body information processing in a manner that reflects the hemispheric bias of holistic vs. abstract nature of face and non-emotional body category processing.

Investigating the Spatial Associations Between Amyloid-ß Deposition, Grey Matter Volume, and Neuroinflammation in Alzheimer's Disease.

BACKGROUND: It has been proposed that amyloid-ß (Aß) plays a causal role in Alzheimer's disease (AD) by triggering a series of pathologic events-possibly including neuroinflammation-which culminate in progressive brain atrophy. However, the interplay between the two pathological molecular events and how both are associated with neurodegeneration is still unclear. OBJECTIVE: We aimed to estimate the spatial inter-relationship between neurodegeneration, neuroinflammation and Aß deposition in a cohort of 20 mild AD patients and 17 healthy controls (HC). METHODS: We resorted to magnetic resonance imaging to measure cortical atrophy, using the radiotracer 11C-PK11195 PET to measure neuroinflammation levels and 11C-PiB PET to assess Aß levels. Between-group comparisons were computed to explore AD-related changes in the three types of markers. To examine the effects of each one of the molecular pathologic mechanisms on neurodegeneration we computed: 1) ANCOVAs with the anatomic data, controlling for radiotracer uptake differences between groups and 2) voxel-based multiple regression analysis between-modalities. In addition, associations in anatomically defined regions of interests were also investigated. RESULTS: We found significant differences between AD and controls in the levels of atrophy, neuroinflammation, and Aß deposition. Associations between Aß aggregation and brain atrophy were detected in AD in a widely distributed pattern, whereas associations between microglia activation and structural measures of neurodegeneration were restricted to few anatomically regions. CONCLUSION: In summary, Aß deposition, as opposed to neuroinflammation, was more associated with cortical atrophy, suggesting a prominent role of Aß in neurodegeneration at a mild stage of the AD.

Simultaneous changes in visual acuity, cortical population receptive field size, visual field map size, and retinal thickness in healthy human aging.

Healthy human aging is associated with a deterioration of visual acuity, retinal thinning, visual field map shrinkage and increasing population receptive field sizes. Here we ask how these changes are related to each other in a cross-sectional sample of fifty healthy adults aged 20-80 years. We hypothesized that age-related loss of macular retinal ganglion cells may lead to decreased visual field map sizes, and both may lead to increased pRF sizes in the cortical central visual field representation. We measured our participants' perceptual corrected visual acuity using standard ophthalmological letter charts. We then measured their early visual field map (V1, V2 and V3) functional population receptive field (pRF) sizes and structural surface areas using fMRI, and their retinal structure using high-definition optical coherence tomography. With increasing age visual acuity decreased, pRF sizes increased, visual field maps surface areas (but not whole-brain surface areas) decreased, and retinal thickness decreased. Among these measures, only functional pRF sizes predicted perceptual visual acuity, and Bayesian statistics support a null relationship between visual acuity and cortical or retinal structure. However, pRF sizes were in turn predicted by cortical structure only (visual field map surface areas), which were only predicted by retinal structure (thickness). These results suggest that simultaneous disruptions of neural structure and function throughout the early visual system may underlie the deterioration of perceptual visual acuity in healthy aging.

Distinct mechanisms drive hemispheric lateralization of object recognition in the visual word form and fusiform face areas.

The Visual Word Form Area (VWFA) and the Fusiform Face Area (FFA) represent classical examples of functional lateralization. The known hypothesis that lateralization of the VWFA and FFA are related remains controversial. We hypothesized that lateralization is independent and might be associated with lateralized high-level top-down mechanisms. For the VWFA this could emerge from left-lateralized language regions. This driving force might modulate local reorganization/recycling of function. Using an fMRI recognition paradigm, we quantified lateralization and investigated effective connectivity to examine mechanisms associated with lateralization in these regions (n = 58). Laterality patterns were more pronounced for VWFA than for FFA. Granger Causality Analysis found top-down effects only for the VWFA (left-lateralized, stemming from Broca's area). FFA exerted top-down effects on low-level visual areas. These findings suggest that distinct mechanisms are associated with hemispheric lateralization in object recognition: left lateralized top-down for VWFA and only early visual top-down effects concerning the FFA.

Is the Retina a Mirror of the Aging Brain? Aging of Neural Retina Layers and Primary Visual Cortex Across the Lifespan.

How aging concomitantly modulates the structural integrity of the brain and retina in healthy individuals remains an outstanding question. Given the strong bottom-up retinocortical connectivity, it is important to study how these structures co-evolve during healthy aging in order to unravel mechanisms that may affect the physiological integrity of both structures. For the 56 participants in the study, primary visual cortex (BA17), as well as frontal, parietal and temporal regions thicknesses were measured in T1-weighted magnetic resonance imaging (MRI), and retinal macular thickness (10 neuroretinal layers) was measured by optical coherence tomography (OCT) imaging. We investigated the statistical association of these measures and their age dependence. We found an age-related decay of primary visual cortical thickness that was significantly correlated with a decrease in global and multiple layer retinal thicknesses. The atrophy of both structures might jointly account for the decline of various visual capacities that accompany the aging process. Furthermore, associations with other cortical regions suggest that retinal status may index cortical integrity in general.

Impulsivity across reactive, proactive and cognitive domains in Parkinson's disease on dopaminergic medication: Evidence for multiple domain impairment.

Impulse control disorders (ICD) may occur in Parkinson's disease (PD) although it remains to be understood if such deficits may occur even in the absence of a formal ICD diagnosis. Moreover, studies addressing simultaneously distinct neurobehavioral domains, such as cognitive, proactive and reactive motor impulsivity, are still lacking. Here, we aimed to investigate if reactive, proactive and cognitive impulsivity involving risk taking are concomitantly affected in medicated PD patients, and whether deficits were dependent on response strategies, such as speed accuracy tradeoffs, or the proportion of omission vs. commission errors. We assessed three different impulsivity domains in a sample of 21 PD patients and 13 matched controls. We found impaired impulsivity in both reactive (p = 0.042) and cognitive domains (p = 0.015) for the PD patients, irrespective of response strategy. For the latter, effect sizes were larger for the actions related with reward processing (p = 0.017, dCohen = 0.9). In the proactive impulsivity task, PD patients showed significantly increased number of omissions (p = 0.041), a response strategy which was associated with preserved number of commission errors. Moreover, the number of premature and proactive response errors were correlated with disease stage. Our findings suggest that PD ON medication is characterized compared to healthy controls by impairment across several impulsivity domains, which is moderated in the proactive domain by the response strategy.

Interplay Between Macular Retinal Changes and White Matter Integrity in Early Alzheimer's Disease.

This study aims to investigate the relationship between structural changes in the retina and white matter in the brain, in early Alzheimer's disease (AD). Twenty-three healthy controls (mean age = 63.4±7.5 years) and seventeen AD patients (mean age = 66.5±6.6 years) were recruited for this study. By combining two imaging techniques-optical coherence tomography and diffusion tensor imaging (DTI)-the association between changes in the thickness of individual retinal layers and white matter dysfunction in early AD was assessed. Retinal layers were segmented, and thickness measurements were obtained for each layer. DTI images were analyzed with a quantitative data-driven approach to evaluating whole-brain diffusion metrics, using tract-based spatial statistics. Diffusion metrics, such as fractional anisotropy, are markers for white matter integrity. Multivariate and partial correlation analyses evaluating the association between individual retinal layers thickness and diffusion metrics were performed. We found that axial diffusivity, indexing axonal integrity, was significantly reduced in AD (p = 0.016, Cohen's d = 1.004) while in the retina, only a marginal trend for significance was found for the outer plexiform layer (p = 0.084, Cohen's d = 0.688). Furthermore, a positive association was found in the AD group between fractional anisotropy and the inner nuclear layer thickness (p < 0.05, r = 0.419, corrected for multiple comparisons by controlling family-wise error rate). Our findings suggest that axonal damage in the brain dominates early on in this condition and shows an association with retinal structural integrity already at initial stages of AD. These findings are consistent with an early axonal degeneration mechanism in AD.

Unisensory and multisensory Self-referential stimulation of the lower limb: An exploratory fMRI study on healthy subjects.

BACKGROUND: The holistic view of the person is the essence of the physiotherapy. Knowledge of approaches that develop the whole person promotes better patient outcomes. Multisensory Self-referential stimulation, more than a unisensory one, seems to produce a holistic experience of the Self ("Core-Self"). OBJECTIVES: (1) To analyze the somatotopic brain activation during unisensory and multisensorial Self-referential stimulus; and (2) to understand if the areas activated by multisensorial Self-referential stimulation are the ones responsible for the "Core-Self." METHODS: An exploratory functional magnetic resonance imaging (fMRI) study was performed with 10 healthy subjects, under the stimulation of the lower limbs with three Self-referential stimuli: unisensory auditory-verbal, unisensory tactile-manual, and multisensory, applying the unisensory stimuli simultaneously. RESULTS: Unisensory stimulation elicits bilateral activations of the temporoparietal junction (TPJ), of the primary somatosensory cortex (S1), of the primary motor cortex (BA4), of the premotor cortex (BA6) and of BA44; multisensory stimulation also elicits activity in TPJ, BA4, and BA6, and when compared with unisensory stimuli, activations were found in: (1) Cortical and subcortical midline structures-BA7 (precuneus), BA9 (medial prefrontal cortex), BA30 (posterior cingulated), superior colliculum and posterior cerebellum; and (2) Posterior lateral cortex-TPJ, posterior BA13 (insula), BA19, and BA37. Bilateral TPJ is the one that showed the biggest activation volume. CONCLUSION: This specific multisensory stimulation produces a brain activation map in regions that are responsible for multisensory Self-processing and may represent the Core-Self. We recommend the use of this specific multisensory stimulation as a physiotherapy intervention strategy that might promote the Self-reorganization.

Distinct preference for spatial frequency content in ventral stream regions underlying the recognition of scenes, faces, bodies and other objects.

The ventral visual pathway receives both inputs from parvocellular and magnocellular pathways, and combines information from distinct high and low spatial frequency channels (HSF and LSF). Using a random effects region of interest general linear model approach (n=21), we aimed to compare the selectivity to different spatial frequency channels in eight key areas involved in visual object recognition: FFA, OFA, and STS, for face processing; FBA, and EBA as body selective regions; (dorsal and ventral) LOC for object perception; PPA for processing information of places and VWFA as a region which responds to written verbal material. We found that face and body selective regions had significantly higher response to LSF, suggesting an important contribution of holistic processing favoring LSF channels, while other object responsive regions had a higher response to HSF, suggesting a more important role for detailed component processing. Both FBA and VWFA failed to reveal a preference to SF content. These findings apply in general to the preferred category, with the notable exception of PPA, which revealed a higher response to HSF for all categories of stimuli. Our results suggest that areas along the ventral stream have distinct spatial frequency preferences that seem to reflect both the nature of visual objects being processed, their position in the visual hierarchy, task demands and the relevance of holistic versus detailed processing.