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.

Recruitment of Control and Representational Components of the Semantic System during Successful and Unsuccessful Access to Complex Factual Knowledge.

Our ability to effectively retrieve complex semantic knowledge meaningfully impacts our daily lives, yet the neural processes that underly successful access and transient failures in access remain only partially understood. In this fMRI study, we contrast activation during successful semantic access, unsuccessful semantic access because of transient access failures (i.e., "tip-of-the-tongue," "feeling-of-knowing"), and trials where the semantic knowledge was not possessed. Twenty-four human participants (14 female) were presented 240 trivia-based questions relating to person, place, object, or scholastic knowledge domains. Analyses of the recall event indicated a relatively greater role of a dorsomedial section of the prefrontal cortex in unsuccessful semantic access and relatively greater recruitment of the pars orbitalis of the inferior frontal gyrus in successful access. Successful access was also associated with increased activation in knowledge domain-selective areas. Generally, knowledge domain-selective areas showed increased responses for both preferred and nonpreferred stimulus classes. The exception was place-selective regions (parahippocampal gyrus, transverse occipital sulcus, retrosplenial complex), which were recruited during unsuccessful access attempts for all stimulus domains. Collectively, these results suggest that prefrontal semantic control systems and classical spatial knowledge-selective regions work together to locate relevant information and that access to complex knowledge results in a broad activation of semantic representation extending to regions selective for other knowledge domains.SIGNIFICANCE STATEMENT The ability to access the deep factual knowledge we possess has a meaningful influence on our scholastic, professional, and social lives. In this fMRI study, we investigate the neural processes associated with successful access to this knowledge as well as transient failures in semantic access (tip-of-the-tongue/feeling-of-knowing). Participants attempted to answer trivia-style general knowledge questions drawn from four different knowledge domains. Results suggest that prefrontal semantic control systems and classical spatial knowledge-selective regions work to locate relevant information and that access to complex knowledge results in a broad activation of semantic representation extending to regions selective for other knowledge domains.

Can visual capture of sound separate auditory streams?

In noisy contexts, sound discrimination improves when the auditory sources are separated in space. This phenomenon, named Spatial Release from Masking (SRM), arises from the interaction between the auditory information reaching the ear and spatial attention resources. To examine the relative contribution of these two factors, we exploited an audio-visual illusion in a hearing-in-noise task to create conditions in which the initial stimulation to the ears is held constant, while the perceived separation between speech and masker is changed illusorily (visual capture of sound). In two experiments, we asked participants to identify a string of five digits pronounced by a female voice, embedded in either energetic (Experiment 1) or informational (Experiment 2) noise, before reporting the perceived location of the heard digits. Critically, the distance between target digits and masking noise was manipulated both physically (from 22.5 to 75.0 degrees) and illusorily, by pairing target sounds with visual stimuli either at same (audio-visual congruent) or different positions (15 degrees offset, leftward or rightward: audio-visual incongruent). The proportion of correctly reported digits increased with the physical separation between the target and masker, as expected from SRM. However, despite effective visual capture of sounds, performance was not modulated by illusory changes of target sound position. Our results are compatible with a limited role of central factors in the SRM phenomenon, at least in our experimental setting. Moreover, they add to the controversial literature on the limited effects of audio-visual capture in auditory stream separation.

Visual motion processing recruits regions selective for auditory motion in early deaf individuals.

In early deaf individuals, the auditory deprived temporal brain regions become engaged in visual processing. In our study we tested further the hypothesis that intrinsic functional specialization guides the expression of cross-modal responses in the deprived auditory cortex. We used functional MRI to characterize the brain response to horizontal, radial and stochastic visual motion in early deaf and hearing individuals matched for the use of oral or sign language. Visual motion showed enhanced response in the 'deaf' mid-lateral planum temporale, a region selective to auditory motion as demonstrated by a separate auditory motion localizer in hearing people. Moreover, multivariate pattern analysis revealed that this reorganized temporal region showed enhanced decoding of motion categories in the deaf group, while visual motion-selective region hMT+/V5 showed reduced decoding when compared to hearing people. Dynamic Causal Modelling revealed that the 'deaf' motion-selective temporal region shows a specific increase of its functional interactions with hMT+/V5 and is now part of a large-scale visual motion selective network. In addition, we observed preferential responses to radial, compared to horizontal, visual motion in the 'deaf' right superior temporal cortex region that also show preferential response to approaching/receding sounds in the hearing brain. Overall, our results suggest that the early experience of auditory deprivation interacts with intrinsic constraints and triggers a large-scale reallocation of computational load between auditory and visual brain regions that typically support the multisensory processing of motion information.

Certain, but incorrect: on the relation between subjective certainty and accuracy in sound localisation.

When asked to identify the position of a sound, listeners can report its perceived location as well as their subjective certainty about this spatial judgement. Yet, research to date focused primarily on measures of perceived location (e.g., accuracy and precision of pointing responses), neglecting instead the phenomenological experience of subjective spatial certainty. The present study aimed to investigate: (1) changes in subjective certainty about sound position induced by listening with one ear plugged (simulated monaural listening), compared to typical binaural listening and (2) the relation between subjective certainty about sound position and localisation accuracy. In two experiments (N = 20 each), participants localised single sounds delivered from one of 60 speakers hidden from view in front space. In each trial, they also provided a subjective rating of their spatial certainty about sound position. No feedback on response was provided. Overall, participants were mostly accurate and certain about sound position in binaural listening, whereas their accuracy and subjective certainty decreased in monaural listening. Interestingly, accuracy and certainty dissociated within single trials during monaural listening: in some trials participants were certain but incorrect, in others they were uncertain but correct. Furthermore, unlike accuracy, subjective certainty rapidly increased as a function of time during the monaural listening block. Finally, subjective certainty changed as a function of perceived location of the sound source. These novel findings reveal that listeners quickly update their subjective confidence on sound position, when they experience an altered listening condition, even in the absence of feedback. Furthermore, they document a dissociation between accuracy and subjective certainty when mapping auditory input to space.

Functional selectivity for face processing in the temporal voice area of early deaf individuals.

Brain systems supporting face and voice processing both contribute to the extraction of important information for social interaction (e.g., person identity). How does the brain reorganize when one of these channels is absent? Here, we explore this question by combining behavioral and multimodal neuroimaging measures (magneto-encephalography and functional imaging) in a group of early deaf humans. We show enhanced selective neural response for faces and for individual face coding in a specific region of the auditory cortex that is typically specialized for voice perception in hearing individuals. In this region, selectivity to face signals emerges early in the visual processing hierarchy, shortly after typical face-selective responses in the ventral visual pathway. Functional and effective connectivity analyses suggest reorganization in long-range connections from early visual areas to the face-selective temporal area in individuals with early and profound deafness. Altogether, these observations demonstrate that regions that typically specialize for voice processing in the hearing brain preferentially reorganize for face processing in born-deaf people. Our results support the idea that cross-modal plasticity in the case of early sensory deprivation relates to the original functional specialization of the reorganized brain regions.

White matter connectivity between occipital and temporal regions involved in face and voice processing in hearing and early deaf individuals.

Neuroplasticity following sensory deprivation has long inspired neuroscience research in the quest of understanding how sensory experience and genetics interact in developing the brain functional and structural architecture. Many studies have shown that sensory deprivation can lead to cross-modal functional recruitment of sensory deprived cortices. Little is known however about how structural reorganization may support these functional changes. In this study, we examined early deaf, hearing signer and hearing non-signer individuals using diffusion MRI to evaluate the potential structural connectivity linked to the functional recruitment of the temporal voice area by face stimuli in deaf individuals. More specifically, we characterized the structural connectivity between occipital, fusiform and temporal regions typically supporting voice- and face-selective processing. Despite the extensive functional reorganization for face processing in the temporal cortex of the deaf, macroscopic properties of these connections did not differ across groups. However, both occipito- and fusiform-temporal connections showed significant microstructural changes between groups (fractional anisotropy reduction, radial diffusivity increase). We propose that the reorganization of temporal regions after early auditory deprivation builds on intrinsic and mainly preserved anatomical connectivity between functionally specific temporal and occipital regions.

Tango and physiotherapy interventions in Parkinson's disease: a pilot study on efficacy outcomes on motor and cognitive skills.

Pharmacological treatments in Parkinson's disease (PD), albeit effective in alleviating many motor symptoms, have limited effects in non-motor signatures as cognitive impairment, as well as in other aspects included postural instability. Consequently, complementary interventions are nowadays a prerogative of clinical practice managing PD symptomatology. In this pilot longitudinal study, we recruited twenty-four PD patients participating in one of two interventions: adapted Argentine Tango or group-based physiotherapy. Participants underwent a motor and neuropsychological evaluation before and after four months of activities, carried out twice a week. We found a general stabilization of motor and cognitive abilities, with significant improvements in several motor skills, mainly pertaining to static and dynamic balance, similarly in both groups. At cognitive level, we measured a significant improvement in both groups in the Action Naming task. Interestingly, only PD patients in the Tango group improved their performance in the test measuring facial emotion recognition. These findings highlight the crucial role that physical activities have in the stabilization and slowdown of disease's progression in PD. They further highlight the beneficial effects of a group-based physical intervention, which, especially in the case of Tango, could lead to behavioral ameliorations in domains other than the motor, such as emotion recognition.

Task-based activation and resting-state connectivity predict individual differences in semantic capacity for complex semantic knowledge.

Our ability to know and access complex factual information has far reaching effects, influencing our scholastic, professional and social lives. Here we employ functional MRI to assess the relationship between individual differences in semantic aptitude in the task-based activation and resting-state functional connectivity. Using psychometric and behavioural measures, we quantified the semantic and executive aptitude of individuals and had them perform a general-knowledge semantic-retrieval task (N = 41) and recorded resting-state data (N = 43). During the semantic-retrieval task, participants accessed general-knowledge facts drawn from four different knowledge-domains (people, places, objects and 'scholastic'). Individuals with greater executive capacity more strongly recruit anterior sections of prefrontal cortex (PFC) and the precuneus, and individuals with lower semantic capacity more strongly activate a posterior section of the dorsomedial PFC (dmPFC). The role of these regions in semantic processing was validated by analysis of independent resting-state data, where increased connectivity between a left anterior PFC and the precuneus predict higher semantic aptitude, and increased connectivity between left anterior PFC and posterior dmPFC predict lower semantic aptitude. Results suggest that coordination between core semantic regions in the precuneus and anterior prefrontal regions associated with executive processes support greater semantic aptitude.

Combining concepts across categorical domains: a linking role of the precuneus.

The human capacity for semantic knowledge entails not only the representation of single concepts but the capacity to combine these concepts into the increasingly complex ideas that underlie human thought. This process involves not only the combination of concepts from within the same semantic category but frequently the conceptual combination across semantic domains. In this fMRI study (N=24) we investigate the cortical mechanisms underlying our ability to combine concepts across different semantic domains. Using five different semantic domains (People, Places, Food, Objects and Animals), we present sentences depicting concepts drawn from a single semantic domain as well as sentences that combine concepts from two of these domains. Contrasting single-category and combined-category sentences reveals that the precuneus is more active when concepts from different domains have to be combined. At the same time, we observe that distributed category selectivity representations persist when higher-order meaning involves the combination of categories and that this category-selective response is captured by the combination of the single categories composing the sentence. Collectively, these results suggest that the combination of concepts across different semantic domains is mediated by the precuneus, which functions to link together category-selective representations distributed across the cortex.

Orienting Auditory Attention through Vision: the Impact of Monaural Listening.

The understanding of linguistic messages can be made extremely complex by the simultaneous presence of interfering sounds, especially when they are also linguistic in nature. In two experiments, we tested if visual cues directing attention to spatial or temporal components of speech in noise can improve its identification. The hearing-in-noise task required identification of a five-digit sequence (target) embedded in a stream of time-reversed speech. Using a custom-built device located in front of the participant, we delivered visual cues to orient attention to the location of target sounds and/or their temporal window. In Exp. 1 ( n = 14), we validated this visual-to-auditory cueing method in normal-hearing listeners, tested under typical binaural listening conditions. In Exp. 2 ( n = 13), we assessed the efficacy of the same visual cues in normal-hearing listeners wearing a monaural ear plug, to study the effects of simulated monaural and conductive hearing loss on visual-to-auditory attention orienting. While Exp. 1 revealed a benefit of both spatial and temporal visual cues for hearing in noise, Exp. 2 showed that only the temporal visual cues remained effective during monaural listening. These findings indicate that when the acoustic experience is altered, visual-to-auditory attention orienting is more robust for temporal compared to spatial attributes of the auditory stimuli. These findings have implications for the relation between spatial and temporal attributes of sound objects, and when planning devices to orient audiovisual attention for subjects suffering from hearing loss.

Updating spatial hearing abilities through multisensory and motor cues.

Spatial hearing relies on a series of mechanisms for associating auditory cues with positions in space. When auditory cues are altered, humans, as well as other animals, can update the way they exploit auditory cues and partially compensate for their spatial hearing difficulties. In two experiments, we simulated monaural listening in hearing adults by temporarily plugging and muffing one ear, to assess the effects of active or passive training conditions. During active training, participants moved an audio-bracelet attached to their wrist, while continuously attending to the position of the sounds it produced. During passive training, participants received identical acoustic stimulation and performed exactly the same task, but the audio-bracelet was moved by the experimenter. Before and after training, we measured adaptation to monaural listening in three auditory tasks: single sound localization, minimum audible angle (MAA), spatial and temporal bisection. We also performed the tests twice in an untrained group, which completed the same auditory tasks but received no training. Results showed that participants significantly improved in single sound localization, across 3 consecutive days, but more in the active compared to the passive training group. This reveals that benefits of kinesthetic cues are additive with respect to those of paying attention to the position of sounds and/or seeing their positions when updating spatial hearing. The observed adaptation did not generalize to other auditory spatial tasks (space bisection and MAA), suggesting that partial updating of sound-space correspondences does not extend to all aspects of spatial hearing.

Interactions between egocentric and allocentric spatial coding of sounds revealed by a multisensory learning paradigm.

Although sound position is initially head-centred (egocentric coordinates), our brain can also represent sounds relative to one another (allocentric coordinates). Whether reference frames for spatial hearing are independent or interact remained largely unexplored. Here we developed a new allocentric spatial-hearing training and tested whether it can improve egocentric sound-localisation performance in normal-hearing adults listening with one ear plugged. Two groups of participants (N = 15 each) performed an egocentric sound-localisation task (point to a syllable), in monaural listening, before and after 4-days of multisensory training on triplets of white-noise bursts paired with occasional visual feedback. Critically, one group performed an allocentric task (auditory bisection task), whereas the other processed the same stimuli to perform an egocentric task (pointing to a designated sound of the triplet). Unlike most previous works, we tested also a no training group (N = 15). Egocentric sound-localisation abilities in the horizontal plane improved for all groups in the space ipsilateral to the ear-plug. This unexpected finding highlights the importance of including a no training group when studying sound localisation re-learning. Yet, performance changes were qualitatively different in trained compared to untrained participants, providing initial evidence that allocentric and multisensory procedures may prove useful when aiming to promote sound localisation re-learning.