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.

Cerebral microstructural abnormalities in impulsivity: a magnetic resonance study.

Studies that investigated neurobiological parameters subtended to impulsivity trait found their relationship with structural and functional brain alterations. No studies investigated the white matter microstructural attributes of impulsivity in a large sample of healthy subjects. In the present study 1007 subjects from Human Connectome Project public dataset were divided in two groups, impulsive and not impulsive, basing on Delay Discounting task score. For both groups brain morphometric and microstructural characteristics were investigated. A t-test (correct for multiple comparisons) was performed for each brain parcel and impulsivity measure. Magnetic resonance diffusion images were pre-processed and selected to perform a voxelwise analysis on the fractional anisotropy (FA) maps between impulsive and not impulsive groups. Group analysis showed significant differences in morphometric brain data mainly for temporal and frontal lobes. The impulsive group presented higher FA values in four regions: bilateral medial lemniscus and midbrain reticular formation, right superior longitudinal fasciculus, left forceps major, right corticospinal tract. Not impulsive group showed higher FA values in two significant regions: right and left anterior thalamus radiation. Concluding, macroscopic and microstructural brain alterations were assessed, identifying new neuroanatomical substrates for multidimensional impulsivity construct in a large sample of healthy subjects.

Multimodal neuroimaging in anorexia nervosa.

Anorexia nervosa (AN) is a severe and complex psychiatric disorder characterized by intense fear about weight gain and finalized to food-related control behaviors. Growing interest has been demonstrated about neurobiological processes subtend to AN physiopathology. The present review aimed to collect neurostructural and neurofunctional available data from 2010 to 2019. Results have been organized according to the neuroimaging technique employed, also including a specific section on electroencephalographic results, mostly neglected in previous reviews. Diffuse cerebral vulnerability has been demonstrated and the contribution of several structures has been identified. Insula, cingulate cortex, parietal and frontal areas are primarily involved both by structural and functional perspectives. Moreover, consistent alterations in white matter integrity and brain electrical activity have been reported. Neuroimaging findings give a substantial contribution to AN pathophysiological description, also in order to understand altered but reversible processes in the passage from acute illness phase to disorder's remission, useful also for defining therapy.

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.

Neuroimaging of Narcolepsy and Primary Hypersomnias.

Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis of neurological disorders, including sleep disorders. At present, the diagnosis of narcolepsy and primary hypersomnias is largely limited to subjective assessments and objective measurements of behavior and sleep physiology. In this review, we focus on recent neuroimaging findings that provide insight into the neural basis of narcolepsy and the primary hypersomnias Kleine-Levin syndrome and idiopathic hypersomnia. We describe the role of neuroimaging in confirming previous genetic, neurochemical, and neurophysiological findings and highlight studies that permit a greater understanding of the symptoms of these sleep disorders. We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps, and the potential role for neuroimaging in understanding the pathogenesis and clinical features of narcolepsy and primary hypersomnias.

Gender Brain Structural Differences and Interoception.

Interoception, the ability to perceive inner body sensations, has been demonstrated to be different among genders, with a stronger female attention toward interoceptive information. No study correlated this capability with brain differences between males and females. This study aims to detect behavioral variances and structural neuroimaging interoception correlates in a sample of healthy volunteers matched for age. Seventy-three participants (37 females, mean age 43.5; 36 males, mean age 37.4) completed the Self-Awareness Questionnaire (SAQ) for interoceptive sensibility and underwent a structural MRI session. A t test corrected for Bonferroni multiple comparisons was performed to compare brain morphological parameters (cortical thickness and parcel volume) in both groups. A multivariate analysis of variance was performed to assess the effect of gender on scores obtained on the SAQ. A moderation model through multiple linear regression analysis was performed between gray matter volumes or parcels, cortical thickness, and the interoception score. Group analysis showed significant differences in morphometric brain data between males and females, both for cortical and subcortical volumes, but not for cortical thickness analyses. MANOVA underlined a significant difference in SAQ scores between males and females with higher values for the second ones. Moreover, a significant correlation between the interoception scores and gray matter volumes of the two groups has been detected, with a sharp prevalence for the female gender in the left insula with F1, F2, and SAQ interoception scores (R 2 = 0.41, p < 0.001). Our results demonstrated that in the female group, a stronger predisposition was found toward interoceptive sensations, and that multiple brain areas were correlated with interoceptive measure. These data sustain a female advantage in the attention toward this process and support the idea that interoception in females is a process more shared across several regions that participate in creating the sense of self.

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.

Validation of an electronic version of the Self-Awareness Questionnaire in English and Italian healthy samples.

OBJECTIVES: Interoception is a general sensitivity to bodily sensations that informs motivational processes and behaviours. Interoceptive abilities seem to be impaired in several clinical conditions, and the development of new pragmatic instruments to assess subjective components of interoception are crucially needed. An easy to use paper and pencil questionnaire measuring sensitivity to bodily sensations was validated in an Italian sample (Self-Awareness Questionnaire; SAQ). METHODS: In the present study, we created and evaluated an electronic version of the SAQ in Italian and English language. RESULTS: Psychometric properties of both electronic versions of the SAQ were validated in an Italian (n = 206) and an English (n = 275) sample, using factorial analyses. Differences in factorial structures observed between the two samples were discussed in terms of cultural impact on emotional regulation and bodily sensations processing. CONCLUSIONS: The electronic version of SAQ in English and Italian provides a pragmatic and validated tool to evaluate bodily signal sensitivity in clinical settings, informing the development of a new therapy targeting interoceptive processes, in a wide range of psychopathological conditions.

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.

The influence of interoceptive awareness on functional connectivity in patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity likely related to altered processing of sensory stimuli along the brain-gut axis. Previous neuroimaging studies demonstrated structural and functional alteration of several brain areas involved in bodily representation, e.g. the insula, in patients with IBS. By means of resting-state functional magnetic resonance imaging (rs-fMRI) we searched for alteration of functional connectivity within the network involved in self-bodily consciousness. We found significant inverse correlation between hypochondriasis assessed through a clinical questionnaire and connectivity between posterior cingulate cortex and left supramarginal gyrus, extending into the adjacent superior temporal gyrus. Moreover, we observed a significant and positive correlation between a clinical questionnaire assessing interoception and connectivity between left anterior ventral insula and two clusters located in supramarginal gyrus bilaterally.Our findings highlight an "abnormal network synchrony" reflecting functional alteration, in the absence of structural and micro-structural changes, which might represent a possible therapeutic target for Irritable Bowel Syndrome.

Altered functional connectivity of interoception in illness anxiety disorder.

Interoception collects all information coming from the body and is sustained by several brain areas such as insula and cingulate cortex. Here, we used resting-state functional magnetic resonance imaging to investigate functional connectivity (FC) of networks implied in interoception in patients with Illness anxiety disorders (IADs). We observed significantly reduced FC between the left extrastriate body area (EBA) and the paracentral lobule compared to healthy controls. Moreover, the correlation analysis between behavioural questionnaires and ROI to ROI FC showed that higher levels of illness anxiety were related to hyper-connectivity between EBA and amygdala and hippocampus. Scores on a questionnaire for interoceptive awareness were significantly correlated with higher FC between right hippocampus and nucleus accumbens bilaterally, and with higher connectivity between left anterior cingulate cortex (ACC) and left orbitofrontal cortex (OFC). Last, patients showed increased interoceptive awareness, measured by Self-Awareness Questionnaire (SAQ), and reduced capability in recognizing emotions, indicating inverse correlation between interoception and emotional awareness. Taken together our results suggested that, in absence of structural and micro-structural changes, patients with IADs show functional alteration in the neural network involved in the self-body representation; such functional alteration might be the target of possible treatments.

The relationships between interoception and alexithymic trait. The Self-Awareness Questionnaire in healthy subjects.

Interoception is the basic process enabling evaluation of one's own bodily states. Several previous studies suggested that altered interoception might be related to disorders in the ability to perceive and express emotions, i.e., alexithymia, and to defects in perceiving and describing one's own health status, i.e., hypochondriasis. The main aim of the present study was to investigate the relationships between alexithymic trait and interoceptive abilities evaluated by the "Self-Awareness Questionnaire" (SAQ), a novel self-report tool for assessing interoceptive awareness. Two hundred and fifty healthy subjects completed the SAQ, the Toronto Alexithymia Scale-20 items (TAS-20), and a questionnaire to assess hypochondriasis, the Illness Attitude Scale (IAS). The SAQ showed a two-factor structure, with good internal consistency (Cronbach's alpha = 0.88). We observed significant direct correlations between SAQ, TAS-20 and two of its subscales, and the IAS. Regression analysis confirmed that the difficulty in identifying and expressing emotions is significantly related with awareness for one's own interoceptive feelings and with a tendency to misinterpret and amplify bodily sensations. From a clinical point of view, the assessment of interoceptive awareness by the SAQ could be pivotal in evaluating several psychopathological conditions, such as the somatoform disorders.

Dopamine treatment and cognitive functioning in individuals with Parkinson's disease: the "cognitive flexibility" hypothesis seems to work.

BACKGROUND: Previous data suggest that (i) dopamine modulates the ability to implement nonroutine schemata and update operations (flexibility processes) and that (ii) dopamine-related improvement may be related to baseline dopamine levels in target pathways (inverted U-shaped hypothesis). OBJECTIVE: To investigate above hypotheses in individuals with Parkinson's disease (PD). METHODS: Twenty PD patients were administered tasks varying as to flexibility load in two treatment conditions: (i) "off" condition, about 18 hours after dopamine dose and (ii) "on" condition, after dopamine administration. PD patients were separated into two groups: low performers (i.e., performance on Digit Span Backward below the sample mean) and high performers (i.e., performance above the mean). Twenty healthy individuals performed the tasks in two sessions without taking drugs. RESULTS: Passing from the "off" to the "on" state, only low performer PD patients significantly improved their performance on high-flexibility measures (interference condition of the Stroop test; P < 0.05); no significant effect was found on low-flexibility tasks. CONCLUSIONS: These findings document that high-flexibility processes are sensitive to dopamine neuromodulation in the early phases of PD. This is in line with the hypothesis that striatal dopamine pathways, affected early by PD, are precociously implicated in the expression of cognitive disorders in these individuals.