Functional alterations in resting-state networks for Theory of Mind in Parkinson's disease.

In Parkinson's disease (PD), impairment of Theory of Mind (ToM) has recently attracted an increasing number of neuroscientific investigations. If and how functional connectivity of the ToM network is altered in PD is still an open question. First, we explored whether ToM network connectivity shows potential PD-specific functional alterations when compared to healthy controls (HC). Second, we tested the role of the duration of PD in the evolution of functional alterations in the ToM network. Between-group connectivity alterations were computed adopting resting-state functional magnetic resonance imaging (rs-fMRI) data of four groups: PD patients with short disease duration (PD-1, n = 72); PD patients with long disease duration (PD-2, n = 22); healthy controls for PD-1 (HC-1, n = 69); healthy controls for PD-2 (HC-2, n = 22). We explored connectivity differences in the ToM network within and between its three subnetworks: Affective, Cognitive and Core. PD-1 presented a global pattern of decreased functional connectivity within the ToM network, compared to HC-1. The alterations mainly involved the Cognitive and Affective ToM subnetworks and their reciprocal connections. PD-2-those with longer disease duration-showed an increased connectivity spanning the entire ToM network, albeit less consistently in the Core ToM network, compared to both the PD-1 and the HC-2 groups. Functional connectivity within the ToM network is altered in PD. The alterations follow a graded pattern, with decreased connectivity at short disease duration, which broadens to a generalized increase with longer disease duration. The alterations involve both the Cognitive and Affective subnetworks of ToM.

Connectome-based fingerprint of motor impairment is stable along the course of Parkinson's disease.

Functional alterations in brain connectivity have previously been described in Parkinson's disease, but it is not clear whether individual differences in connectivity profiles might be also linked to severity of motor-symptom manifestation. Here we investigated the relevance of individual functional connectivity patterns measured with resting-state fMRI with respect to motor-symptom severity in Parkinson's disease, through a whole-brain, data-driven approach (connectome-based predictive modeling). Neuroimaging and clinical data of Parkinson's disease patients from the Parkinson's Progression Markers Initiative were derived at baseline (session 1, n = 81) and at follow-up (session 2, n = 53). Connectome-based predictive modeling protocol was implemented to predict levels of motor impairment from individual connectivity profiles. The resulting predictive model comprised a network mainly involving functional connections between regions located in the cerebellum, and in the motor and frontoparietal networks. The predictive power of the model was stable along disease progression, as the connectivity within the same network could predict levels of motor impairment, even at a later stage of the disease. Finally, connectivity profiles within this network could be identified at the individual level, suggesting the presence of individual fingerprints within resting-state fMRI connectivity associated with motor manifestations in Parkinson's disease.

Deficits in Emotion Recognition and Theory of Mind in Parkinson's Disease Patients With and Without Cognitive Impairments.

Background: Emotion recognition and social deficits have been previously reported in Parkinson's disease (PD). However, the extent of these impairments is still unclear and social cognition is excluded from the cognitive domains considered in the current criteria for PD mild cognitive impairment (MCI). This study aims to analyze emotion recognition, affective and cognitive theory of mind in early PD patients classified according to Level II MCI criteria, and to evaluate the prevalence of socio-cognitive deficits in this sample. Methods: We enrolled 45 participants with PD, classified as cognitively unimpaired (CU; n = 32) or MCI (n = 13) based on a standard neuropsychological assessment. Social cognitive skills were evaluated through validated tests for emotion recognition (i.e., Ekman 60-faces test, Ek60 Test) and mental states attribution (Story-based Empathy Task, SET) and compared to a group of 45 healthy controls (HC). Between-group differences in social tasks were performed, as well as correlation analyses to assess the relationship between social, cognitive, and clinical variables. Finally, the number of patients with social cognitive impairments in both MCI and CU subgroups was computed based on Italian normative data. Results: Statistical comparison revealed significant differences among groups in the Ek60 test, with MCI obtaining significantly lower scores than HC and CU, especially for negative emotions. Significant differences were detected also in the SET, with lower performance in emotion and intention attribution for both PD groups compared to HC. A significant correlation emerged between the Ek60 test and emotion attribution. Nine patients showed poor performance at social tasks, five of them being classified as PD-CU. Discussion: Parkinson's disease cognitive profile was characterized by emotion recognition and attribution deficits. These results, as well as the detection of CU patients with isolated socio-cognitive impairments, underline the importance of assessing social cognition in PD as a possible early marker of cognitive decline.

Subcortical grey matter changes associated with motor symptoms evaluated by the Unified Parkinson's disease Rating Scale (part III): A longitudinal study in Parkinson's disease.

Parkinson disease (PD) is characterized by motor deficits related to structural changes in the basal ganglia-thalamocortical circuits. However, it is still unclear the exact nature of the association between grey matter alterations and motor symptoms. Therefore, the aim of our investigation was to identify the subcortical modifications associated with motor symptoms of PD over time - adopting voxel-based morphometry (VBM) and automated volumetry methods. We selected fifty subjects with PD from the Parkinson's Progression Markers Initiative (PPMI) database, who performed an MRI session at two time points: at baseline (i.e. at maximum 2 years after clinical diagnosis of PD) and after 48 months. Motor symptoms were assessed using the part III of the Unified Parkinson's Disease Rating Scale at the two time points. Our VBM and volumetric analyses showed a general atrophy in all subcortical regions when comparing baseline with 48 months. These findings confirmed previous observations indicating a subcortical alteration over time in PD. Furthermore, our findings supported the idea that a reduced volume in the thalamus and an increased volume in pallidum may be related to the decline in motor skills. These structural modifications are in accordance with the functional model of the basal ganglia-thalamocortical circuits controlling movements. Moreover, VBM and volumetry provided partially overlapping results, suggesting that these methods might capture complementary aspects of brain degeneration in PD.

Neural encoding and functional interactions underlying pantomimed movements.

Pantomimes are a unique movement category which can convey complex information about our intentions in the absence of any interaction with real objects. Indeed, we can pretend to use the same tool to perform different actions or to achieve the same goal adopting different tools. Nevertheless, how our brain implements pantomimed movements is still poorly understood. In our study, we explored the neural encoding and functional interactions underlying pantomimes adopting multivariate pattern analysis (MVPA) and connectivity analysis of fMRI data. Participants performed pantomimed movements, either grasp-to-move or grasp-to-use, as if they were interacting with two different tools (scissors or axe). These tools share the possibility to achieve the same goal. We adopted MVPA to investigate two levels of representation during the planning and execution of pantomimes: (1) distinguishing different actions performed with the same tool, (2) representing the same final goal irrespective of the adopted tool. We described widespread encoding of action information within regions of the so-called "tool" network. Several nodes of the network-comprising regions within the ventral and the dorsal stream-also represented goal information. The spatial distribution of goal information changed from planning-comprising posterior regions (i.e. parietal and temporal)-to execution-including also anterior regions (i.e. premotor cortex). Moreover, connectivity analysis provided evidence for task-specific bidirectional coupling between the ventral stream and parieto-frontal motor networks. Overall, we showed that pantomimes were characterized by specific patterns of action and goal encoding and by task-dependent cortical interactions.

Lockdown effects on Parkinson's disease during COVID-19 pandemic: a pilot study.

The coronavirus-disease 2019 (COVID-19) outbreak precipitated prolonged lock-down measures. The subsequent social distancing, isolation, and reduction in mobility increased psychological stress, which may worsen Parkinson's disease (PD). Therefore, telemedicine has been proposed to provide care to PD patients. To evaluate the effects of lock-down on motor and nonmotor symptoms in PD patients during the COVID-19 pandemic and the feasibility of telemedicine. Motor and nonmotor aspects were longitudinally assessed using structured questionnaires at baseline (in-person, February 2020) and at follow-up (remote web-based video, lock-down) evaluation. Of the seventeen PD patients evaluated at baseline, fourteen agreed to participate in, and completed follow-up evaluations. There was an impairment of nonmotor aspects measured with the MDS-UPDRS part I (p < 0.001) during lock-down. Nine patients participated independently in the telemedicine evaluation while five needed help from relatives. Our preliminary findings suggest an impairment of nonmotor symptoms in PD patients and support the feasibility and need for telemedicine in monitoring PD patients during the COVID-19 pandemic, to guarantee optimal assistance with reducing the burden of infection. Our findings also suggest that movement disorder clinics should be carefully considering socio-demographics and clinical features when developing telemedicine programs.

Decoding category and familiarity information during visual imagery.

Visual imagery relies on a widespread network of brain regions, partly engaged during the perception of external stimuli. Beyond the recruitment of category-selective areas (FFA, PPA), perception of familiar faces and places has been reported to engage brain areas associated with semantic information, comprising the precuneus, temporo-parietal junction (TPJ), medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC). Here we used multivariate pattern analyzes (MVPA) to examine to which degree areas of the visual imagery network, category-selective and semantic areas contain information regarding the category and familiarity of imagined stimuli. Participants were instructed via auditory cues to imagine personally familiar and unfamiliar stimuli (i.e. faces and places). Using region-of-interest (ROI)-based MVPA, we were able to distinguish between imagined faces and places within nodes of the visual imagery network (V1, SPL, aIPS), within category-selective inferotemporal regions (FFA, PPA) and across all brain regions of the extended semantic network (i.e. precuneus, mPFC, IFG and TPJ). Moreover, we were able to decode familiarity of imagined stimuli in the SPL and aIPS, and in some regions of the extended semantic network (in particular, right precuneus, right TPJ), but not in V1. Our results suggest that posterior visual areas - including V1 - host categorical representations about imagined stimuli, and that stimulus familiarity might be an additional aspect that is shared between perception and visual imagery.

The Role of Social Cognition Abilities in Parkinson's Disease in the Era of COVID-19 Emergency.

Introduction: Parkinson's Disease (PD) is characterized by motor and non-motor symptoms, among which deficits in social cognition might affect ~20% of patients. This study aims to evaluate the role of social cognitive abilities in the perceived impact of COVID-19 emergency, and the effects of lockdown measures on patients' social network and caregivers' burden. Methods: Fourteen PD patients performed a neuropsychological battery including sociocognitive tasks before the introduction of COVID-19 restrictive measures (i.e., social distancing and isolation). A structured interview through an online platform was performed in the last 2 weeks of the first lockdown phase to assess patients' health status, perception of COVID-19 emergency, changes in caregivers' burden, and patients' social isolation. Non-parametric analyses were performed to evaluate the association between social skills and patients' COVID-19 perception, as well as the effects of restrictive measures. Results: At baseline evaluation, half of the PD patients showed sociocognitive dysfunctions, mainly on mentalizing abilities. Patients with impaired social cognition skills showed a significantly lower concern on the possible effects of COVID-19 on their health. Caregiver burden and patients' social network remained stable during the lockdown. Conclusion: These preliminary results underline that PD sociocognitive dysfunctions might affect patients' abilities to estimate the effects of COVID-19 infection. However, the lack of a significant increase in caregivers' burden and social isolation suggests, in our sample, a good coping to COVID-19 emergency. Since COVID-19 pandemic can have direct and indirect severe consequences in patients with PD, the development of educational and preventive programs is recommended.

Decoding motor imagery and action planning in the early visual cortex: Overlapping but distinct neural mechanisms.

Recent evidence points to a role of the primary visual cortex that goes beyond visual processing into high-level cognitive and motor-related functions, including action planning, even in absence of feedforward visual information. It has been proposed that, at the neural level, motor imagery is a simulation based on motor representations, and neuroimaging studies have shown overlapping and shared activity patterns for motor imagery and action execution in frontal and parietal cortices. Yet, the role of the early visual cortex in motor imagery remains unclear. Here we used multivoxel pattern analyses on functional magnetic resonance imaging (fMRI) data to examine whether the content of motor imagery and action intention can be reliably decoded from the activity patterns in the retinotopic location of the target object in the early visual cortex. Further, we investigated whether the discrimination between specific actions generalizes across imagined and intended movements. Eighteen right-handed human participants (11 females) imagined or performed delayed hand actions towards a centrally located object composed of a small shape attached on a large shape. Actions consisted of grasping the large or small shape, and reaching to the center of the object. We found that despite comparable fMRI signal amplitude for different planned and imagined movements, activity patterns in the early visual cortex, as well as dorsal premotor and anterior intraparietal cortex, accurately represented action plans and action imagery. However, movement content is similar irrespective of whether actions are actively planned or covertly imagined in parietal but not early visual or premotor cortex, suggesting a generalized motor representation only in regions that are highly specialized in object directed grasping actions and movement goals. In sum, action planning and imagery have overlapping but non identical neural mechanisms in the cortical action network.

Hierarchical Action Encoding Within the Human Brain.

Humans are able to interact with objects with extreme flexibility. To achieve this ability, the brain does not only control specific muscular patterns, but it also needs to represent the abstract goal of an action, irrespective of its implementation. It is debated, however, how abstract action goals are implemented in the brain. To address this question, we used multivariate pattern analysis of functional magnetic resonance imaging data. Human participants performed grasping actions (precision grip, whole hand grip) with two different wrist orientations (canonical, rotated), using either the left or right hand. This design permitted to investigate a hierarchical organization consisting of three levels of abstraction: 1) "concrete action" encoding; 2) "effector-dependent goal" encoding (invariant to wrist orientation); and 3) "effector-independent goal" encoding (invariant to effector and wrist orientation). We found that motor cortices hosted joint encoding of concrete actions and of effector-dependent goals, while the parietal lobe housed a convergence of all three representations, comprising action goals within and across effectors. The left lateral occipito-temporal cortex showed effector-independent goal encoding, but no convergence across the three levels of representation. Our results support a hierarchical organization of action encoding, shedding light on the neural substrates supporting the extraordinary flexibility of human hand behavior.

Predictive coding of action intentions in dorsal and ventral visual stream is based on visual anticipations, memory-based information and motor preparation.

Predictions of upcoming movements are based on several types of neural signals that span the visual, somatosensory, motor and cognitive system. Thus far, pre-movement signals have been investigated while participants viewed the object to be acted upon. Here, we studied the contribution of information other than vision to the classification of preparatory signals for action, even in the absence of online visual information. We used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA) to test whether the neural signals evoked by visual, memory-based and somato-motor information can be reliably used to predict upcoming actions in areas of the dorsal and ventral visual stream during the preparatory phase preceding the action, while participants were lying still. Nineteen human participants (nine women) performed one of two actions towards an object with their eyes open or closed. Despite the well-known role of ventral stream areas in visual recognition tasks and the specialization of dorsal stream areas in somato-motor processes, we decoded action intention in areas of both streams based on visual, memory-based and somato-motor signals. Interestingly, we could reliably decode action intention in absence of visual information based on neural activity evoked when visual information was available and vice versa. Our results show a similar visual, memory and somato-motor representation of action planning in dorsal and ventral visual stream areas that allows predicting action intention across domains, regardless of the availability of visual information.

Parsing rooms: the role of the PPA and RSC in perceiving object relations and spatial layout.

The perception of a scene involves grasping the global space of the scene, usually called the spatial layout, as well as the objects in the scene and the relations between them. The main brain areas involved in scene perception, the parahippocampal place area (PPA) and retrosplenial cortex (RSC), are supposed to mostly support the processing of spatial layout. Here we manipulated the objects and their relations either by arranging objects within rooms in a common way or by scattering them randomly. The rooms were then varied for spatial layout by keeping or removing the walls of the room, a typical layout manipulation. We then combined a visual search paradigm, where participants actively search for an object within the room, with multivariate pattern analysis (MVPA). Both left and right PPA were sensitive to the layout properties, but the right PPA was also sensitive to the object relations even when the information about objects and their relations is used in the cross-categorization procedure on novel stimuli. The left and right RSC were sensitive to both spatial layout and object relations, but could only use the information about object relations for cross-categorization to novel stimuli. These effects were restricted to the PPA and RSC, as other control brain areas did not display the same pattern of results. Our results underline the importance of employing paradigms that require participants to explicitly retrieve domain-specific processes and indicate that objects and their relations are processed in the scene areas to a larger extent than previously assumed.

Common spatiotemporal processing of visual features shapes object representation.

Biological vision relies on representations of the physical world at different levels of complexity. Relevant features span from simple low-level properties, as contrast and spatial frequencies, to object-based attributes, as shape and category. However, how these features are integrated into coherent percepts is still debated. Moreover, these dimensions often share common biases: for instance, stimuli from the same category (e.g., tools) may have similar shapes. Here, using magnetoencephalography, we revealed the temporal dynamics of feature processing in human subjects attending to objects from six semantic categories. By employing Relative Weights Analysis, we mitigated collinearity between model-based descriptions of stimuli and showed that low-level properties (contrast and spatial frequencies), shape (medial-axis) and category are represented within the same spatial locations early in time: 100-150 ms after stimulus onset. This fast and overlapping processing may result from independent parallel computations, with categorical representation emerging later than the onset of low-level feature processing, yet before shape coding. Categorical information is represented both before and after shape, suggesting a role for this feature in the refinement of categorical matching.

Sex Differences in Affective Facial Reactions Are Present in Childhood.

Adults exposed to affective facial displays produce specific rapid facial reactions (RFRs) which are of lower intensity in males compared to females. We investigated such sex difference in a population of 60 primary school children (30 F; 30 M), aged 7-10 years. We recorded the surface electromyographic (EMG) signal from the corrugator supercilii and the zygomatici muscles, while children watched affective facial displays. Results showed the expected smiling RFR to smiling faces and the expected frowning RFR to sad faces. A systematic difference between male and female participants was observed, with boys showing less ample EMG responses than age-matched girls. We demonstrate that sex differences in the somatic component of affective motor patterns are present also in childhood.

Quantitative Diffusion Tensor Imaging Analysis of Low-Grade Gliomas: From Preclinical Application to Patient Care.

BACKGROUND: Preoperative diffusion tensor tractography (DTT) has recently been used to aid in the mapping of functional pathways to limit damage associated with resection of low-grade gliomas (LGGs). OBJECTIVE: To assess the predictive capacity of DTT as a biomarker of postoperative motor outcomes in patients with LGGs involving the corticospinal tract (CST). CST parameters obtained using a quantitative fiber tracking approach were used to investigate the reliability of the DTT biomarker by comparing their values in the tumoral (Tcst) and healthy (Hcst) hemispheres. METHODS: Thirty-seven patients with LGGs involving the CST were enrolled. Quantification of structural differences between the Tcst and Hcst were analyzed according to the novel biomarker (NF index), defined as follows: (Hcst NF - Tcst NF)/Hcst NF, where NF represents the number of fibers in each region. Logistic regression analysis was used to examine associations among clinical postoperative outcomes and NF index values, tumoral patterns, and premotor/motor evoked potentials. RESULTS: NF values significantly differed between the Tcst and Hcst. Analysis of the NF index showed that patients with a preoperative NF index <0.22 had a significantly lower risk of developing transient postoperative deficits (area under the curve, 0.92; 95% binomial confidence interval, 0.834-1). Patients with less pronounced differences in NF between the Tcst and Hcst also experienced better clinical outcomes. CONCLUSIONS: The NF index may be a useful biomarker for predicting clinical outcomes in patients with LGGs. Furthermore, the NF index may provide a preoperative estimate of the patient's potential for recovery from possible postsurgical neurologic deficits.

Independent Component Decomposition of Human Somatosensory Evoked Potentials Recorded by Micro-Electrocorticography.

High-density surface microelectrodes for electrocorticography (ECoG) have become more common in recent years for recording electrical signals from the cortex. With an acceptable invasiveness/signal fidelity trade-off and high spatial resolution, micro-ECoG is a promising tool to resolve fine task-related spatial-temporal dynamics. However, volume conduction - not a negligible phenomenon - is likely to frustrate efforts to obtain reliable and resolved signals from a sub-millimeter electrode array. To address this issue, we performed an independent component analysis (ICA) on micro-ECoG recordings of somatosensory-evoked potentials (SEPs) elicited by median nerve stimulation in three human patients undergoing brain surgery for tumor resection. Using well-described cortical responses in SEPs, we were able to validate our results showing that the array could segregate different functional units possessing unique, highly localized spatial distributions. The representation of signals through the root-mean-square (rms) maps and the signal-to-noise ratio (SNR) analysis emphasizes the advantages of adopting a source analysis approach on micro-ECoG recordings in order to obtain a clear picture of cortical activity. The implications are twofold: while on one side ICA may be used as a spatial-temporal filter extracting micro-signal components relevant to tasks for brain-computer interface (BCI) applications, it could also be adopted to accurately identify the sites of nonfunctional regions for clinical purposes.

Beta band modulations underlie action representations for movement planning.

To be able to interact with our environment, we need to transform incoming sensory information into goal-directed motor outputs. Whereas our ability to plan an appropriate movement based on sensory information appears effortless and simple, the underlying brain dynamics are still largely unknown. Here we used magnetoencephalography (MEG) to investigate this issue by recording brain activity during the planning of non-visually guided reaching and grasping actions, performed with either the left or right hand. Adopting a combination of univariate and multivariate analyses, we revealed specific patterns of beta power modulations underlying varying levels of neural representations during movement planning. (1) Effector-specific modulations were evident as a decrease in power in the beta band. Within both hemispheres, this decrease was stronger while planning a movement with the contralateral hand. (2) The comparison of planned grasping and reaching led to a relative increase in power in the beta band. These power changes were localized within temporal, premotor and posterior parietal cortices. Action-related modulations overlapped with effector-related beta power changes within widespread frontal and parietal regions, suggesting the possible integration of these two types of neural representations. (3) Multivariate analyses of action-specific power changes revealed that part of this broadband beta modulation also contributed to the encoding of an effector-independent neural representation of a planned action within fronto-parietal and temporal regions. Our results suggest that beta band power modulations play a central role in movement planning, within both the dorsal and ventral stream, by coding and integrating different levels of neural representations, ranging from the simple representation of the to-be-moved effector up to an abstract, effector-independent representation of the upcoming action.

MEG Multivariate Analysis Reveals Early Abstract Action Representations in the Lateral Occipitotemporal Cortex.

Understanding other people's actions is a fundamental prerequisite for social interactions. Whether action understanding relies on simulating the actions of others in the observers' motor system or on the access to conceptual knowledge stored in nonmotor areas is strongly debated. It has been argued previously that areas that play a crucial role in action understanding should (1) distinguish between different actions, (2) generalize across the ways in which actions are performed (Dinstein et al., 2008; Oosterhof et al., 2013; Caramazza et al., 2014), and (3) have access to action information around the time of action recognition (Hauk et al., 2008). Whereas previous studies focused on the first two criteria, little is known about the dynamics underlying action understanding. We examined which human brain regions are able to distinguish between pointing and grasping, regardless of reach direction (left or right) and effector (left or right hand), using multivariate pattern analysis of magnetoencephalography data. We show that the lateral occipitotemporal cortex (LOTC) has the earliest access to abstract action representations, which coincides with the time point from which there was enough information to allow discriminating between the two actions. By contrast, precentral regions, though recruited early, have access to such abstract representations substantially later. Our results demonstrate that in contrast to the LOTC, the early recruitment of precentral regions does not contain the detailed information that is required to recognize an action. We discuss previous theoretical claims of motor theories and how they are incompatible with our data. SIGNIFICANCE STATEMENT: It is debated whether our ability to understand other people's actions relies on the simulation of actions in the observers' motor system, or is based on access to conceptual knowledge stored in nonmotor areas. Here, using magnetoencephalography in combination with machine learning, we examined where in the brain and at which point in time it is possible to distinguish between pointing and grasping actions regardless of the way in which they are performed (effector, reach direction). We show that, in contrast to the predictions of motor theories of action understanding, the lateral occipitotemporal cortex has access to abstract action representations substantially earlier than precentral regions.

Second Surgery in Insular Low-Grade Gliomas.

BACKGROUND: Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR) are poorly documented. OBJECTIVE: The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs) that subsequently underwent second surgery. METHODS: A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR. RESULTS: At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs). Univariate analysis showed that TR is influenced by the following: extent of resection (EOR) (P < 0.002), ΔVT2T1 value (P < 0.001), histological diagnosis of oligodendroglioma (P = 0.017), and mutation of IDH1 (P = 0.022). The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P < 0.001). CONCLUSIONS: In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery.