Federico D’Agata

Shared “Core” Areas between the Pain and Other Task-Related Networks

The idea of a ‘pain matrix’ specifically devoted to the processing of nociceptive inputs has been challenged. Alternative views now propose that the activity of the primary and secondary somatosensory cortices (SI, SII), the insula and cingulate cortex may be related to a basic defensive system through which significant potentially dangerous events for the bodys integrity are detected. By reviewing the role of the SI, SII, the cingulate and the insular cortices in the perception of nociceptive and tactile stimuli, in attentional, emotional and reward tasks, and in interoception and memory, we found that all these task-related networks overlap in the dorsal anterior cingulate cortex, the anterior insula and the dorsal medial thalamus. A thorough analysis revealed that the ‘pain-related’ network shares important functional similarities with both somatomotor-somatosensory networks and emotional-interoceptive ones. We suggest that these shared areas constitute the central part of an adaptive control system involved in the processing and integration of salient information coming both from external and internal sources. These areas are activated in almost all fMRI tasks and have been indicated to play a pivotal role in switching between externally directed and internally directed brain networks.

The Recognition of Facial Emotions in Spinocerebellar Ataxia Patients

Patients with cerebellar lesions present some affective and cognitive disorders, defining a peculiar pattern of cognitive impairment, so-called cerebellar cognitive affective syndrome. This pattern has been confirmed in many genotypes of spinocerebellar ataxias (SCA), a group of genetically defined pathologies characterized by the degeneration of the cerebellum and its connections. Recently, in SCA patients, some authors focused the interest on social cognition evidencing an impairment of theory of mind and basic emotion recognition by verbal material. The recognition of emotions in faces is an essential component of social cognition; therefore, we assessed this ability in SCA patients, expanding the study from the basic verbal emotions to the basic and social visual emotion recognition. We assessed facial emotion recognition using two basic and social emotion tasks in a group of SCA patients together with a complete clinical and neuropsychological evaluation. We compared results with the performance of a control group. We demonstrated a significant difference between patients and controls both in basic and social emotion recognition, although we found a specific impairment only for social emotions. The deficit was not correlated to clinical and demographic features. The cognitive and psychological profile did not explain the impairment in emotion recognition. This result supports the hypothesis that the impairment in social emotion recognition could be specifically related to a defect in the corticocerebellar network.

Consensus Paper: Cerebellum and Emotion

Over the past three decades, insights into the role of the cerebellum in emotional processing have substantially increased. Indeed, methodological refinements in cerebellar lesion studies and major technological advancements in the field of neuroscience are in particular responsible to an exponential growth of knowledge on the topic. It is timely to review the available data and to critically evaluate the current status of the role of the cerebellum in emotion and related domains. The main aim of this article is to present an overview of current facts and ongoing debates relating to clinical, neuroimaging, and neurophysiological findings on the role of the cerebellum in key aspects of emotion. Experts in the field of cerebellar research discuss the range of cerebellar contributions to emotion in nine topics. Topics include the role of the cerebellum in perception and recognition, forwarding and encoding of emotional information, and the experience and regulation of emotional states in relation to motor, cognitive, and social behaviors. In addition, perspectives including cerebellar involvement in emotional learning, pain, emotional aspects of speech, and neuropsychiatric aspects of the cerebellum in mood disorders are briefly discussed. Results of this consensus paper illustrate how theory and empirical research have converged to produce a composite picture of brain topography, physiology, and function that establishes the role of the cerebellum in many aspects of emotional processing.

Video game play changes spatial and verbal memory: rehabilitation of a single case with traumatic brain injury

IntroductionTraumatic brain injury (TBI) occurs when mechanicalforce causes damage to brain tissue resulting in the dis-ruption of brain functioning. Cognition is frequentlydamaged after TBI; although the effects of TBI can bevariable, the domains of memory, attention, and executivefunctioning are consistently impaired. Memory deficit isone of the most (if not the most) common and disablingimpairments caused by TBI (Vakil 2005).Theuseof3D video games inbraindamagerehabilitationis a very little explored resource at the present time. 3Dvideo games are based on virtual reality technology. Theadvantage of using VR in cognitive rehabilitation is tosimulate many real life situations, thereby providing theopportunity for more ecologically valid and dynamicassessment and training (Rose et al. 2005). The utility of thismethod has been established through some spatial memorystudies (see Rose et al. 2005). It has been shown that navi-gation ofavirtualenvironmentallowsparticipantstoencodethe spatial layout of the virtual environment and activate anetwork of areas as the Hippocampus involved in memoryprocessing(Maguireetal.1998).Someauthorsassumedthathippocampal activations are more likely to be observedwhen the knowledge acquired concerns a complex anddetailed large-scale spatial layout (Woollett et al. 2008).The aim of this exploratory study was to assess themodifications occurring in cognitive functions, in particularspatial and verbal memory, and a potential fMRI increaseof signal in hippocampal and extrahippocampal brainregions in a TBI patient after a 3D video game rehabili-tation training.MethodsThe present study describes the rehabilitation of a 24-year-old, right-handed man, with 8 years of education. Hismedical history was unremarkable till when he wasinvolved in a motor vehicle crash and sustained a TBI ofmoderate severity. His Glasgow Coma Scale score was 5.He was diagnosed with trauma cranial injury. The patientwas tested 7 months after the event and was not in the post-traumatic amnesia (PTA) stage.Neuropsychological assessment indicated the presenceof a severe anterograde (recall and recognition) and retro-grade amnesia and deficits in spatial learning (supra-spanon Corsi’s test).Thetraining consistedofaseries of1.5 hsessions thriceaweek(totallengthofintervention:5 weeks).Thevideogamewas a driving simulator. During the training the participantwas requested to explore a complex virtual town from aground-levelperspective.Ineachtrainingsessionthesubjectinterchanged 20 min of navigation with 7 min of break.The patient was evaluated before and after training bymeans of a fMRI and a standardized neuropsychologicalassessment. He was then re-tested 1 and 2 months after thelast memory training session for two follow-up testingsessions.

Supratentorial gliomas in eloquent areas: which parameters can predict functional outcome and extent of resection?

Background To date, few parameters have been found that can aid in patient selection and surgical strategy for eloquent area gliomas. Aims The aim of the study was to analyze preoperative and intraoperative factors that can predict functional outcome and extent of resection in eloquent area tumors. Patients and Methods A retrospective analysis was conducted on 60 patients harboring supratentorial gliomas in eloquent areas undergoing awake surgery. The analysis considered clinical, neuroradiologic (morphologic), intraoperative, and postoperative factors. End-points were extent of resection (EOR) as well as functional short- and long-term outcome. Postoperatively, MRI objectively established the EOR. χ2 analyses were used to evaluate parameters that could be predictive. Multivariate logistic regression analyses were used to evaluate the best combination to predict binary positive outcomes. Results In 90% of the cases, subcortical stimulation was positive in the margins of the surgical cavity. Postoperatively, 51% of the patients deteriorated but 90% of the patients regained their preoperative neurological score. Factors negatively affecting EOR were volume, degree of subcortical infiltration, and presence of paresis (P<0.01). Sharp margins and cystic components were more amenable to gross total resection (P<0.01). Contrast enhancement (P<0.02), higher grade (P<0.01), paresis (P<0.01), and residual tumor in the cortex (P<0.02) negatively affected long-term functional outcomes, whereas postoperative deterioration could not be predicted for any factor other than paresis. Subcortical stimulation did not correlate with deterioration, both postoperatively (P<0.08) and at follow-up (P<0.042). Conclusions Biological and morphological factors such as type of margins, volume, preoperative neurological status, cystic components, histology and the type of infiltration into the white matter must be considered when planning intraoperative mapping.

Neurofunctional signature of hyperfamiliarity for unknown faces

Hyperfamiliarity for unknown faces is a rare selective disorder that consists of the disturbing and abnormal feeling of familiarity for unknown faces, while recognition of known faces is normal. In one such patient we investigated with a multimodal neuroimaging design the hitherto undescribed neural signature associated with hyperfamiliarity feelings. Behaviorally, signal detection methods revealed that the patient’s discrimination sensitivity between familiar and unfamiliar faces was significantly lower than that of matched controls, and her response criterion for familiarity decisions was significantly more liberal. At the neural level, while morphometric analysis and single-photon emission CT (SPECT) showed the atrophy and hypofunctioning of the left temporal regions, functional magnetic resonance imaging (fMRI) revealed that hyperfamiliarity feelings were selectively associated to enhanced activity in the right medial and inferior temporal cortices. We therefore characterize the neurofunctional signature of hyperfamiliarity for unknown faces as related to the loss of coordinated activity between the complementary face processing functions of the left and right temporal lobes.

The relationship between cortical thickness and body mass index differs between women with anorexia nervosa and healthy controls.

Anorexia nervosa (AN) is a severe psychiatric disorder characterized by extreme underweight. Studies conducted with structural MRI found reductions in brain volumes in several areas, but results are mixed. Cortical thickness has shown in other samples specific correlations with BMI in different BMI ranges. In this study, we applied a well validated procedure implemented in Freesurfer software toolkit to investigate cortical thickness in a sample of 21 patients with AN and 18 healthy controls, focusing on group differences and on the relationship between BMI and cortical thickness. Cortical thickness was reduced in patients with AN, but group differences did not survive correction for multiple comparisons. The relationship between BMI and cortical thickness was significantly different in patients with AN compared to controls in the left superior parietal/occipital cortex and left post central cortex. These findings suggest that the relationship between cortical thickness and BMI in patients with AN with less than two years of illness duration significantly differs from that in controls and possible biological mechanisms that may explain this relationship are discussed.

Selective Vulnerability of Cortical Border Zone to Microembolic Infarct

Background and Purpose— Endovascular procedures, including atrial fibrillation transcatheter ablation, may cause microembolization of brain arteries. Microemboli often cause small sized and clinically silent cerebral ischemias (SCI). These lesions are clearly visible on early postoperative magnetic resonance diffusion-weighted images. We analyzed SCI distribution in a population of patients submitted to atrial fibrillation transcatheter ablation. Methods— Seventy-eight of 927 consecutive patients submitted to atrial fibrillation transcatheter ablation were found positive for acute SCI on a postoperative magnetic resonance. SCI were identified and marked, and their coordinates were transformed from native space into the International Consortium for Brain Mapping/Montreal Neurological Institute space. We then computed the voxel-wise probability distribution map of the SCI using the activation likelihood estimation approach. Results— SCI were more commonly found in the cortex. In supratentorial regions, SCI selectively involved cortical border zone between anterior, middle, and posterior cerebral arteries; in infratentorial regions, distal territory of posteroinferior cerebellar artery. Possible explanations include selective embolization, linked to the vascular anatomy of pial arteries supplying those territories, reduced clearance of emboli in a relatively hypoperfused zone, or a combination of both. This particular distribution of lesions has been reported in both animal models and in patients with microemboli of different sources. Conclusions— A selective vulnerability of cortical border zone to microemboli occurring during atrial fibrillation transcatheter ablation was observed. We hypothesize that such selectivity may apply to microemboli of different sources.

Anxiety-dependent modulation of motor responses to pain expectancy

Abstract The relationship between pain expectancy and motor system plays a crucial role in the human defensive system. Here, we took advantage of the inhibitory modulation of the motor pathway to the muscle of the hand receiving painful stimuli, by recording motor-evoked potentials (MEPs) to Transcranial Magnetic Stimulation (TMS). We employed a classical conditioning paradigm in which neutral (visual and auditory) stimuli were conditioned by pairing either painful or not-painful stimuli (electric shocks) in separated groups. Only the Pain Group showed clear motor responses: i.e. a significant decrease in MEPs amplitude, with respect to the neutral condition, not only in conditioning stimuli, when actual shocks were paired with neutral stimuli, but also in conditioned stimuli, when shocks were only expected. Significant differences between the two groups suggest that the MEPs decrease is specific for pain expectancy and does not pertain to anticipation in general. Furthermore, in the Pain Group, a significant negative correlation between physiological responses to conditioned stimuli and the participants’ anxiety traits was found: the lower the MEPs amplitude, the higher the participants’ anxiety scores. The present findings suggest that, in order for defensive motor responses to occur, actual pain is not necessary; rather, anxiety-dependent pain expectancy can be sufficient.

Neuroimaging Correlates of Frontotemporal Dementia Associated with SQSTM1 Mutations

BACKGROUND Frontotemporal lobar degeneration (FTLD) is a progressive dementia characterized by focal atrophy of frontal and/or temporal lobes caused by mutations in the gene coding for sequestosome 1 (SQSTM1), among other genes. Rare SQSTM1 gene mutations have been associated with Pagets disease of bone, amyotrophic lateral sclerosis, and, more recently, frontotemporal lobar degeneration (FTLD). OBJECTIVE The aim of the study was to determine whether a characteristic pattern of grey and white matter loss is associated with SQSTM1 dysfunction. METHODS We performed a voxel-based morphometry (VBM) study in FTD subjects carrying SQSTM1 pathogenic variants (FTD/SQSTM1 mutation carriers; n = 10), compared with FTD subjects not carrying SQSTM1 mutations (Sporadic FTD; n = 20) and healthy controls with no SQSTM1 mutations (HC/SQSTM1 noncarriers; n = 20). The groups were matched according to current age, disease duration, and gender. RESULTS After comparing FTD/SQSTM1 carriers with Sporadic FTD, a predominantly right cortical atrophy pattern was localized in the inferior frontal, medial orbitofrontal, precentral gyri, and the anterior insula. White matter atrophy was found in both medial and inferior frontal gyri, pallidum, and putamen. FTD/SQSTM1 carriers compared with HC/SQSTM1 noncarriers showed atrophy at frontal, temporal, and parietal lobes of both hemispheres whereas the MRI pattern found in Sporadic FTD compared with controls was frontal and left temporal lobe atrophy, extending toward parietal and occipital lobes of both hemispheres. CONCLUSIONS These results suggest that fronto-orbito-insular regions including corticospinal projections as described in ALS are probably more susceptible to the damaging effect of SQSTM1 mutations delineatinga specific gene-linked atrophy pattern.