Neural substrates of interoceptive sensibility: An integrated study in normal and pathological functioning.

In early studies interoception strictly referred to the awareness of visceral sensations, but recent theories have expanded this concept to denote the ongoing status of the body, including somatosensory feelings. Here, we integrated data from normal and pathological functioning to disclose neural underpinnings of interoceptive sensibility, taking into account the crucial distinction between visceral and somatosensory feelings. Twenty-seven healthy young individuals underwent structural MRI (including T1w images and DTI). Voxel-wise analyses of the gyrification index (GI) and fractional anisotropy (FA) data were performed to assess the relation between interoceptive sensibility and surface morphometry and anatomical connectivity. Thirty-three unilateral brain-damaged patients took part in this study for Voxel-Based Lesion-Symptom Mapping (VLSM) and track-wise hodological lesion-deficit analysis (TWH). All participants completed the Self-Awareness Questionnaire (SAQ), a self-report tool assessing interoceptive sensibility of visceral (F1) and somatosensory feelings (F2). Tract-Based Spatial Statistics showed that F2 was positively associated with FA in the bilateral anterior thalamic radiation, corticospinal tract, cingulum, forceps, inferior longitudinal, fronto-occipital, superior longitudinal, and uncinate fasciculi; no significant association was detected for F1. However, F1 was positively associated with GI in the left anterior cingulate cortex. VLSM showed that F1 mainly relies on the right posterior insula, whereas F2 is related mostly to subcortical nuclei and surrounding white matter in the right hemisphere. Accordingly, patients with disconnection of the anterior thalamic projection, corticospinal tract, inferior fronto-occipital, inferior longitudinal, uncinate and superior longitudinal fasciculus III showed lower scores on F2. Overall, results support the dissociation between interoceptive sensibility of visceral and somatosensory feelings.

Body Representation Alterations in Patients with Unilateral Brain Damage.

OBJECTIVE: Systematic studies about the impact of unilateral brain damage on the different body representations (body schema, body structural representation, and body semantics) are still rare. Aim of this study was to evaluate body representation deficits in a relatively large sample of patients with unilateral brain damage and to investigate the impact of right or left brain damage on body representations (BRs), independently from deficits in other cognitive processes. METHOD: Sixty-four patients with unilateral stroke (22 with left brain damage, LBD; 31 with right brain damage without neglect, RBD-N; 11 with right brain damage with neglect, RBD+N) and 41 healthy individuals underwent a specific battery including BR as well as control tasks. RESULTS: In more than a third of the sample, selective (37.5%) and pure (31%) deficits of BR were presented and equally distributed among the different BRs (˜10% for each representation), with selective (27.2%) and pure (22.7%) body schema deficit mainly presented after left brain damage. As a group, patients with unilateral brain damage, independently of the side of lesion (LBD, RBD-N, RBD+N), had significantly worse performance on body structural representation with respect to healthy individuals, whereas LBD had numerically worse performance on body schema with respect to healthy individuals and RBD-N. No significant differences among groups were found on body semantics. CONCLUSION: BR deficits are not a rare consequence of unilateral brain damage and are independent of a more general cognitive dysfunction. Accordingly, the need for an accurate assessment and specific neuropsychological training in clinical settings is discussed.

Identifying a Common Functional Framework for Apathy Large-Scale Brain Network.

Apathy is a neuropsychiatric condition characterized by reduced motivation, initiative, and interest in daily life activities, and it is commonly reported in several neurodegenerative disorders. The study aims to investigate large-scale brain networks involved in apathy syndrome in patients with frontotemporal dementia (FTD) and Parkinson's disease (PD) compared to a group of healthy controls (HC). The study sample includes a total of 60 subjects: 20 apathetic FTD and PD patients, 20 non apathetic FTD and PD patients, and 20 HC matched for age. Two disease-specific apathy-evaluation scales were used to measure the presence of apathy in FTD and PD patients; in the same day, a 3T brain magnetic resonance imaging (MRI) with structural and resting-state functional (fMRI) sequences was acquired. Differences in functional connectivity (FC) were assessed between apathetic and non-apathetic patients with and without primary clinical diagnosis revealed, using a whole-brain, seed-to-seed approach. A significant hypoconnectivity between apathetic patients (both FTD and PD) and HC was detected between left planum polare and both right pre- or post-central gyrus. Finally, to investigate whether such neural alterations were due to the underlying neurodegenerative pathology, we replicated the analysis by considering two independent patients' samples (i.e., non-apathetic PD and FTD). In these groups, functional differences were no longer detected. These alterations may subtend the involvement of neural pathways implicated in a specific reduction of information/elaboration processing and motor outcome in apathetic patients.

The Body across the Lifespan: On the Relation between Interoceptive Sensibility and High-Order Body Representations.

BACKGROUND: Interoceptive information plays a pivotal role in building higher-order cognitive body representations (BR) that neuropsychological and neuroimaging evidence classifies as action-oriented (i.e., body schema) or non-action-oriented (i.e., visuo-spatial body map). This study aimed to explore the development of BR, considering the association with the interoceptive sensibility throughout the lifespan. METHODS: Two hundred thirty-nine healthy participants divided into five age groups (7 to 8 years; 9 to 10 years; 18 to 40 years; 41 to 60 years; over 60 years) completed a self-report measure of interoceptive sensibility (the Self-Awareness Questionnaire; SAQ) and were given tasks assessing the two BR (action-oriented: hand laterality task; non-action-oriented: frontal body evocation task). RESULTS: Both children (7-8 and 9-10 years) and older adults (over 60 years) performed worse than young (18-40 years) and middle-aged adults (41-60 years) in action- and non-action-oriented BR tasks. Moderation analyses showed that the SAQ score significantly moderated the relationship between age and action-oriented BR. CONCLUSIONS: The current results are consistent with inverted U-shaped developmental curves for action- and non-action-oriented BR. As an innovative aspect, the ability to mentally represent one's own body parts in diverse states could be negatively affected by higher interoceptive sensibility levels in childhood and late adulthood.

Brain hemodynamic response in Examiner-Examinee dyads during spatial short-term memory task: an fNIRS study.

The Corsi Block-Tapping test (CBT) is a measure of spatial working memory (WM) in clinical practice, requiring an examinee to reproduce sequences of cubes tapped by an examiner. CBT implies complementary behaviors in the examiners and the examinees, as they have to attend a precise turn taking. Previous studies demonstrated that the Prefrontal Cortex (PFC) is activated during CBT, but scarce evidence is available on the neural correlates of CBT in the real setting. We assessed PFC activity in dyads of examiner-examinee participants while completing the real version of CBT, during conditions of increasing and exceeding workload. This procedure allowed to investigate whether brain activity in the dyads is coordinated. Results in the examinees showed that PFC activity was higher when the workload approached or reached participants' spatial WM span, and lower during workload conditions that were largely below or above their span. Interestingly, findings in the examiners paralleled the ones in the examinees, as examiners' brain activity increased and decreased in a similar way as the examinees' one. In the examiners, higher left-hemisphere activity was observed suggesting the likely activation of non-spatial WM processes. Data support a bell-shaped relationship between cognitive load and brain activity, and provide original insights on the cognitive processes activated in the examiner during CBT.

The Body Across Adulthood: On the Relation Between Interoception and Body Representations.

Interoceptive information plays a pivotal role in building body representations (BR), but the association between interoception and the different types of BR in healthy individuals has never been systematically investigated. Thus, this study aimed to explore the association between BR and interoceptive sensibility (IS) throughout adulthood. One hundred thirty-seven healthy participants (50 aged from 18 to 40 years old; 50 aged from 41 to 60 years old; and 37 over 60 years old) were given a self-report tool for assessing IS (the Self-Awareness Questionnaire; SAQ), and a specific battery including tasks evaluating three different BR (i.e., the body schema, using the Hand Laterality Task; the body structural representation, using the Frontal Body Evocation task, FBE; and body semantics, using the Object-Body Part Association Task) as well as control tasks (i.e., tasks with non-body stimuli). The older age group (aged over 60 years old) showed lower performances on the tasks probing the body schema and body structural representation than younger groups (aged 18 to 40 and 41 to 60 years old). More interestingly, worse performances on a task assessing the body schema were significantly associated with higher IS with older age, suggesting that higher awareness of one's inner body sensations would decrease the plasticity of this BR. These findings are interpreted according to the neuropsychological model of BR development and the effects of aging on the brain.

Clinical Utility of Two- and Three-Dimensional Visuoconstructional Tasks in Mild Cognitive Impairment and Early Alzheimer's Disease.

OBJECTIVE: The aim of this study was to investigate whether different types of visuoconstructional abilities are useful to distinguish individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from healthy controls (HCs). METHOD: We selected 20 patients with MCI and 14 with AD diagnosis based on standard criteria. The neuropsychological performance of MCI and AD groups were compared with that of a group of 11 HCs using a standard neuropsychological battery and visuoconstructional tasks that differed difficulty and type of implicated skills (graphomotor vs. non-graphomotor): two-dimensional (Clock Drawing Test, CDT; Block Design, BD; and Visual Puzzles, VP) and three-dimensional Block Construction (TBC). RESULTS: AD group scored significantly lower than HCs in BD, VP and TBC tasks, but no significant differences were found between HCs and MCI. CDT (copy condition) scores did not differ significantly among the groups. The receiver operating characteristic analysis showed that BD [sensitivity (se) = .85, specificity (sp) = .90, Youden index (J) = .76], VP (se = .78 and sp = .72, J = .51) and TBC (se = .71, sp = 100, J = .71) were accurate tasks to discriminate between AD and HCs. Moreover, BD tasks (se = .85, sp = .70, J = .55) and TBC (se = .71, sp = .80, J = .51) showed fair accuracy to differentiate between MCI and AD groups. CONCLUSIONS: These findings indicate that non-graphomotor visuoconstructional tasks are already impaired in the early stages of AD, but are preserved in MCI individuals when compared with HCs.

The development of body representations in school-aged children.

Following the triadic taxonomy, three different body representations do exist, namely the body semantics, the body structural representation and the body schema. The development of these body representations has been widely investigated in toddlers, but several issues remain to be addressed in school age. To assess age- and gender-related changes in different body representations and to investigate the presence of different patterns of interplay between these representations of the body, 90 children (age range: 7-10) and 37 young adults (age range: 18-35) were given tasks assessing the body semantics, the body structural representation and the body schema as well as control tasks. The present results suggested that the body schema, evaluated by means of hand laterality judgments, was still not completely developed in school-aged children, whereas the body structural representation reached an adult-like pattern by the age of 9-10 years. Finally, body semantics was fully developed in school-aged children. These findings were discussed in terms of their theoretical implications, for a better understanding of body representation development; also, implications for clinical assessment of body representation disorders were discussed.

Topological and hodological aspects of body representation in right brain damaged patients.

The triadic taxonomy posits that three distinct types of body representations do exist, namely the body schema (BS), which corresponds to the representation derived from multiple sensory and motor inputs, the body structural representation (BSR), which corresponds to the structural description of spatial relations among the body parts, and the body semantics (SEM), which corresponds to the lexical-semantic representation of the body. Although several studies have assessed neural correlates of these representations, no study has compared them in brain-damaged patients, controlling for deficits in other cognitive domains. Also, little is known about the contribution of the right hemisphere to different body representations. Here we used a computerized battery to test these three body representations in twenty-six right brain damaged patients, controlling for other cognitive deficits by means of tests tapping similar spatial and lexical processes on non-body related stimuli. Residual scores corresponding to the BS, the BSR and the SEM were used to test neural correlates, which were assessed by integrating topological and hodological approaches to lesion-deficit analyses. We found that the BSR was associated with lesion of the superior temporal gyrus, the insula, the supramarginal gyrus and the temporo-parietal junction, extending also to the Rolandic operculum and the inferior frontal gyrus. Also, it was associated with the disconnection probability of the posterior arcuate segment. The BS was associated with a small cluster of voxels in the precentral and postcentral gyri, whereas the SEM was associated with white matter lesion at the boundary between the parietal and temporal lobes. Overall, these results provide strong support to the regional and connectional contribution of the right hemisphere to body representation, and more specifically to the BSR.

Microstructural Changes in Motor Functional Conversion Disorder: Multimodal Imaging Approach on a Case.

BACKGROUND: Functional motor conversion disorders are characterized by neurological symptoms unrelated to brain structural lesions. The present study was conducted on a woman presenting motor symptoms causing motor dysfunction, using advanced multimodal neuroimaging techniques, electrophysiological and neuropsychological assessment. METHODS: The patient underwent fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) and functional magnetic resonance imaging (fMRI) with both task and resting-state paradigms and was compared with 11 healthy matched controls. To test differences in structural parameters, Bayesian comparison was performed. To test differences in functional parameters, a first- and second-level analysis was performed in task fMRI, while a seed-to-seed analysis to evaluate the connections between brain regions and identify intersubject variations was performed in resting-state fMRI. RESULTS: FDG-PET showed two patterns of brain metabolism, involving the cortical and subcortical structures. Regarding the diffusion data, microstructural parameters were altered for U-shape fibers for the hand and feet regions. Resting-state analysis showed hypoconnectivity between the parahippocampal and superior temporal gyrus. Neurophysiological assessment showed no alterations. Finally, an initial cognitive impairment was observed, paralleled by an anxiety and mild depressive state. CONCLUSIONS: While we confirmed no structural alterations sustaining this functional motor disorder, we report microstructural changes in sensory-motor integration for both the hand and feet regions that could functionally support clinical manifestations.

Left inferior parietal and posterior temporal cortices mediate the effect of action observation on semantic processing of objects: evidence from rTMS.

Previous studies showed that motor information related to tool use (i.e., functional actions) could affect processing of objects semantic properties, whereas motor information related to grasping or moving tool (i.e., structural actions) cannot. However, little is known about the neural correlates mediating such interaction between motor and semantic information. Here, healthy participants performed a semantic judgment task requiring identification of semantic relations among objects, after observing a functional, a structural or a pointing action prime. In a within-subject design, during prime presentation the participants underwent repetitive transcranial magnetic stimulation (rTMS) over the left supramarginal gyrus (SMG), the left posterior middle temporal gyrus (pMTG) or received sham stimulation. Results showed that in the sham condition observing functional actions (vs. structural and pointing actions) favoured processing of semantic relations based on function similarity (i.e., taxonomic relations), but not of relations based on co-occurrence within an event schema (i.e., thematic relations). Moreover, stimulation of both left SMG and pMTG abolished the effect of functional action primes worsening subsequent judgment about taxonomic relations, and this effect was greater after pMTG stimulation. rTMS did not affect processing of thematic semantic relations. We suggest that action observation triggers activation of functional motor information within left inferior parietal cortex, and that integration between functional motor and conceptual information in left temporal cortex could impact high-level semantic processing of tools.

Interoceptive awareness in focal brain-damaged patients.

BACKGROUND: Interoception is the basic process enabling evaluation of one's own internal state of body, but its alteration in brain-damaged patients has not been adequately investigated. Our study aimed to investigate awareness of visceral and somatosensorial sensations in brain-damaged patients with unilateral stroke. METHODS: Sixty patients (22 with left brain damage, LP; 25 with right brain damage without neglect, RPN-; and 13 with right brain-damage and extrapersonal and/or personal neglect, RPN+) and 45 healthy controls (HC) completed the Self-Awareness Questionnaire (SAQ), a self-report tool for assessing interoceptive awareness with two domains related to visceral (VD) and somatosensory feelings (SD), respectively. RESULTS: Comparing the SAQ subdomains scores between three groups of patients (LP, RPN-, and RPN+) and HC, we found that RPN+ had significantly lower scores on VD than HC and LP, whereas no significant difference was found on scores of SD between groups. CONCLUSION: Our results support the hypothesis of a right-hemispheric dominance for "interoceptive neural network" suggesting that processing of visceral sensations would be located mainly in the right hemisphere. Therefore, a careful assessment of interoceptive awareness in clinical practice would be useful to improve rehabilitation and to engage patients with deficit of interoceptive awareness in developing greater accuracy of body signals.

The closing-in phenomenon in constructional tasks in dementia and mild cognitive impairment.

OBJECTIVE: Closing-in (CI) consists in copying drawings near to (near-CI) or superimposed on (adherent-CI) the model and often occurs in dementia and mild cognitive impairment (MCI). We assessed whether a visuo-constructional task not requiring a grapho-motor response is sensitive to identify CI in Alzheimer's disease (AD), fronto-temporal dementia (FTD), vascular dementia (VD), and MCI. METHOD: We enrolled a sample of 162 patients with dementia (AD, FTD, or VD), 66 individuals with MCI, and 20 healthy adults (HAs) who completed a neuropsychological assessment and the Stick Design test that requires arranging matches for reproducing geometrical figures. RESULTS: CI in the Stick test was slightly (but not significantly) more frequent than that observed in the copying drawing task. CI frequency on both tests was high and similar in AD and FTD and lower in VD and MCI. On both tests, near-CI was the most common error in VD and MCI, whereas adherent-CI prevailed in patients with AD; a similar percentage of near-CI and adherent-CI was observed in FTD. Last, in the participants with dementia and MCI, the number of CIs was significantly correlated with an index of control and executive functions but not with spatial short-term memory. CONCLUSIONS: CI occurs with the same frequency in AD, VD, and FTD, but the prevalent type of CI varies across syndromes. The Stick Design test is a useful task to assess CI and its specific forms in dementia and MCI. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

A Multimodal Imaging Study in a Case of Bilateral Thalamic Damage With Multidomain Cognitive Impairment.

Severe thalamic injury can determine a particular type of vascular dementia affecting multiple network dysfunctions, considered the central role of thalamus as a hub for afferent and efferent stimuli. A 67-year-old male patient with bilateral thalamic stroke was studied with positron emission tomography, magnetic resonance imaging, and cognitive assessment, performed at baseline and at two follow-up evaluations. A pattern primarily involving thalamo-frontal connections was observed by both PET and tractography analyses. All significant differences between the patient and controls involved the anterior thalamic radiation, one of the major fiber tracts in the fronto-thalamic circuitry. In particular, altered tractography indices of higher radial diffusivity and apparent diffusion coefficient and reduced fractional anisotropy values for the anterior thalamic radiation were reported. In accordance with imaging findings, neuropsychological evaluation demonstrated a multidomain impairment including memory, executive functions, and attention. Additionally, the patients displayed behavioral symptoms, in absence of mood alterations. Multimodal imaging assessment, revealing the metabolic and microstructural alterations that attend to multidomain neuropsychological impairment, demonstrated multiple levels of adaptations to bilateral vascular thalamic injury.

Enactment effect in patients with Alzheimer's disease.

Introduction: Subjects can improve their performance on memory for action phrases if, during the encoding condition, they self-perform actions associated with verbs (subject-performed condition), or if they perceive the actions carried out by experimenter (experimenter-performed condition), with respect to a verbal task condition in which they only read or listen to the stimuli. This facilitation is labeled "Enactment effect" (EE), and is thought to be associated with episodic integration processes binding actions and nouns together in a coherent representation. Only recently, studies addressed EE in AD individuals reporting significant improvements on memory tasks in the subject-performed encoding condition. However, no studies tried to explore the cognitive mechanisms supporting EE in AD individuals. Method: Performance on recognition and cued recall tasks for action phrases were assessed in a sample of 32 mild-to-moderate AD individuals and 30 healthy adults, in verbal, subject-performed and experimenter-performed encoding conditions. Moreover, a cognitive assessment was completed to explore the possible correlates of EE in our participants. Results: Results showed that both subject-performed and experimenter-performed encoding conditions produced similar advantages over the verbal condition, in both memory tasks in both groups. Moreover, these memory advantages were strongly associated to executive processes, in both AD and healthy adults. Conclusions: The present study confirmed that EE is spared in mild to moderate AD. Our findings supported the role of episodic integration processes and suggested a contribution of executive processes in EE.

Neural correlates of apathy in patients with neurodegenerative disorders: an activation likelihood estimation (ALE) meta-analysis.

Apathy is commonly reported in Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD) and Parkinson's Disease (PD). In our meta-analysis we analysed a total of 41 studies to identify brain patterns associated with apathy. For these purposes we used activation likelihood estimation meta-analyses. Our main overall analysis showed that apathy is associated to hypometabolism and a decreased gray matter volume in the left inferior frontal gyrus (BA 45, 46). Disorder-specific analyses, not performed by means of meta-analysis, because of the small number of studies, but by means a label-based review, revealed an altered brain perfusion and decreased gray matter volume in anterior cingulate cortex (BA 24, 32) in AD patients and a decreased gray matter volume in inferior frontal gyrus (BA 44, 45) and parietal cortex (BA 40) in FTD patients. These findings suggest that apathy is mainly associated with a cortical dysfunction of areas involved in executive-cognitive processing (i.e. action planning) and emotional regulation (auto-activation and reward processing). Knowledge about the neural underpinnings of apathy is crucial for understanding its clinical characteristics in neurodegenerative diseases and for developing novel strategies of treatment in clinical practice.

Modulating interoception by insula stimulation: A double-blinded tDCS study.

Interoception consists in the perception and processing of internal body signals, such as heartbeat. Previous neuroimaging studies revealed that attention to heartbeat activated bilateral insula and premotor regions. In the present double-blind study, we aimed at testing the role of insula in interoception by means of transcranial direct current stimulation (tDCS) interfering with its activity. Sixteen healthy participants responded to a questionnaire to evaluate the tendency to be internally focused and performed a heartbeat counting task before and after tDCS in three sessions (left insula stimulation, right insula stimulation, sham stimulation). Real and reported heartbeat were recorded and used to calculate the accuracy scores. A significant interaction between stimulation condition and time (pre- and post-stimulation) was found due to a significant improvement of the interoceptive accuracy in the sham condition only. Our results demonstrated that stimulation over the insula reduced the possibility to improve the precision with which individuals detect internal signals.

Bi-cephalic parietal and cerebellar direct current stimulation interferes with early error correction in prism adaptation: Toward a complex view of the neural mechanisms underlying visuomotor control.

Prism Adaptation (PA) represents a valid tool to assess short-term visuomotor plasticity. Two adaptive processes are involved during PA: recalibration, contributing to early error compensation, and spatial realignment, contributing to after-effect development. Classical models on PA posit that adaptive mechanisms underlying PA rely on segregated regions in the brain. Indeed, they ascribe recalibration to the activity of the Posterior Parietal Cortex (PPC) and spatial realignment to the activity of the Cerebellum. The present experiment challenges the idea of a clear-cut separation of the role of the brain areas involved in PA, proposing an interpretation in terms of interrelated brain regions. To this purpose we interfered with the activity of the PPC and the Cerebellum by means of complementary protocols of stimulation. Bi-cephalic transcranial Direct Current Stimulation was delivered simultaneously on the PPC and the Cerebellum during PA in two groups of participants receiving real stimulation with opposite polarities (anode on PPC and cathode on Cerebellum or vice-versa) and in a control group (Sham stimulation). Differences in mean errors between groups were analyzed. Results show that the two groups of real stimulation exhibited larger displacements in early error compensation compared to the Sham Group, but they did not differ from each other. No group difference was found in late error compensation and after-effect. In conclusion, the present findings provide the first direct evidence that a brain circuit connecting the PPC and the Cerebellum is involved in early stages of visuomotor adaptation, and pave the way for updating classical models of PA.

Integrated Cognitive and Neuromotor Rehabilitation in Multiple Sclerosis: A Pragmatic Study.

Background: Few studies examined the effects of combined motor and cognitive rehabilitation in patients with multiple sclerosis (MS). The present prospective, multicenter, observational study aimed to determine the efficacy of an integrated cognitive and neuromotor rehabilitation program versus a traditional neuromotor training on walking, balance, cognition and emotional functioning in MS patients. Methods: Sixty three MS patients were selected and assigned either to the Integrated Treatment Group (ITG; n = 32), receiving neuropsychological treatment (performed by ERICA software and paper-pencil tasks) complemented by conventional neuromotor rehabilitation, or to the Motor Treatment Group (n = 31) receiving neuromotor rehabilitation only. The intervention included two 60-min sessions per week for 24 weeks. At baseline and at end of the training all patients underwent a wide-range neuropsychological, psychological/emotional, and motor assessment. Results: At baseline the two groups did not differ for demographic, neuropsychological, psychological/emotional, and motor features significantly. After rehabilitation, only ITG group significantly (p-corrected for False Discovery Rate) improved on test tapping spatial memory, attention and cognitive flexibility, as well as on scales assessing depression and motor performance (balance and gait). A regression analysis showed that neuropsychological and motor improvement was not related to improvements in fatigue and depression. Conclusion: The present study demonstrated positive effects in emotional, motor, and cognitive aspects in MS patients who received an integrated cognitive and neuromotor training. Overall, results are supportive of interventions combining motor and cognitive training for MS.

Fronto-Temporal Circuits in Musical Hallucinations: A PET-MR Case Study.

The aim of the study is to investigate morphofunctional circuits underlying musical hallucinations (MH) in a 72-years old female that underwent a simultaneous 18fluoredeoxyglucose positron emission tomography (PET) and advanced magnetic resonance (MR) exam. This represents a particular case of MH occurred in an healthy subject, not displaying neurological or psychopathological disorders, and studied simultaneously with a multimodal approach. For the resting-state fMRI analysis a seed to seed approach was chosen. For the task-based fMRI, 4 different auditory stimuli were presented. Imaging findings were compared with data obtained by ten healthy controls matched for age and sex. Neuropsychological evaluation and questionnaires investigating depression and anxiety were also administered. PET findings showed hypermetabolism of: superior temporal gyri, anterior cingulate, left orbital frontal, and medial temporal cortices. Structural MRI did not show macroscopical lesions except for gliotic spots along the uncinate fascicle pathways with an increased cortical thickness for the right orbitofrontal cortex (p = 0.003). DTI showed increased fractional anisotropy values in the left uncinate fascicle, when compared to controls (p = 0.04). Resting-state fMRI showed increased functional connectivity between the left inferior frontal gyrus and the left temporal fusiform cortex (p = 0.01). Task-based fMRI confirmed PET findings showing an increased activation of the superior temporal gyrus in all the auditory tasks except for the monotone stimulus, with a significant activation of the left orbital frontal cortex only during the song in foreign language, object of MH. Results on cognitive test did not show cognitive impairment, excepting for the performance on Frontal Assessment Battery where the patient fails in the cognitive domains of conceptualization, sensitive to interference, and inhibitory control. The subject did not show depressive or anxiety symptoms. Summarizing, multimodal imaging analyses in the MH case showed a microstructural alteration of the left uncinate fascicle paralleled by an increased metabolism and functional connectivity of cortical regions that receive left uncinate projections (orbital frontal cortex, and medial temporal cortex). This alteration of fronto-hyppocampal circuits could be responsible of retrieval of known songs even in the absence of real stimuli.