Elisabetta Geda

Grey matter abnormality in autism spectrum disorder: an activation likelihood estimation meta-analysis study

Background Autism spectrum disorder (ASD) is defined on a clinical basis by impairments in social interaction, verbal and non-verbal communication, and repetitive or stereotyped behaviours. Voxel based morphometry (VBM), a technique that gives a probabilistic measure of local grey matter (GM) and white matter concentration, has been used to study ASD patients: modifications in GM volume have been found in various brain regions, such as the corpus callosum, brainstem, amygdala, hippocampus and cerebellum. However, the findings are inconsistent with respect to the specific localisation and direction of GM modifications, and no paper has attempted to statistically summarise the results available in the literature. Methods The present study is a quantitative meta-analysis of the current VBM findings aimed at delineating the cortical regions with consistently increased or reduced GM concentrations. The activation likelihood estimation (ALE) was used, which is a quantitative voxel based meta-analysis method which can be used to estimate consistent activations across different imaging studies. Co-occurrence statistics of a PubMed query were generated, employing ‘autism spectrum disorder’ as the neuroanatomical lexicon. Results Significant ALE values related to GM increases were observed bilaterally in the cerebellum, in the middle temporal gyrus, in the right anterior cingulate cortex, caudate head, insula, fusiform gyrus, precuneus and posterior cingulate cortex, and in the left lingual gyrus. GM decreases were observed bilaterally in the cerebellar tonsil and inferior parietal lobule, in the right amygdala, insula, middle temporal gyrus, caudate tail and precuneus and in the left precentral gyrus.

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.

Functional anatomy of cortical areas characterized by Von Economo neurons.

Von Economo’s neurons (VENs) are large, bipolar or corkscrew-shaped neurons located in layers III and V of the frontoinsular and the anterior cingulate cortices. VENs are reported to be altered in pathologies such as frontotemporal dementia and autism, in which the individual’s self control is seriously compromised. To investigate the role of VENs in the active human brain, we have explored the functional connectivity of brain areas containing VENs by analyzing resting state functional connectivity (rsFC) in 20 healthy volunteers. Our results show that cortical areas containing VENs form a network of frontoparietal functional connectivity. With the use of fuzzy clustering techniques, we find that this network comprises four sub-networks: the first network cluster resembles a “saliency detection” attentional network, which includes superior frontal cortex (Brodmann’s Area, BA 10), inferior parietal lobe, anterior insula, and dorsal anterior cingulate cortex; the second cluster, part of a “sensory-motor network”, comprises the superior temporal, precentral and postcentral areas; the third cluster consists of frontal ventromedial and ventrodorsal areas constituted by parts of the “anterior default mode network”; and the fourth cluster encompasses dorsal anterior cingulate cortex, dorsomedial prefrontal, and superior frontal (BA 10) areas, resembling the anterior part of the “dorsal attentional network”. Thus, the network that emerges from analyzing functional connectivity among areas that are known to contain VENs is primarily involved in functions of saliency detection and self-regulation. In addition, parts of this network constitute sub-networks that partially overlap with the default mode, the sensory-motor and the dorsal attentional networks.

Linking coordinative and executive dysfunctions to atrophy in spinocerebellar ataxia 2 patients

Spinocerebellar ataxias type 2 (SCA2) is a rare genetic disorder characterised by the degeneration of the Cerebellum, its connections and many Brainstem areas. A voxel-based morphometry (VBM) analysis was performed on 12 genetically determined SCA2 patients and 31 controls, normalising the brains with two different atlases: one was created in-house with DARTEL (a diffeomorphic registration method) and the other was SUIT (an exclusive Cerebellum atlas). We administered two versions of a popular executive/planning functions test: the Tower of London, in the traditional and in a computerised version that does not require the use of hands, to correlate the regional atrophy with the tests’ performances and to discover the different associations of Cerebellum’s areas to cognitive dysfunctions. SCA2 showed a diffuse infratentorial atrophy with the whole Cerebellum and Brainstem affected, the overall patterns were highly overlapping between atlases with some minor differences. The DARTEL VBM also allowed detecting two sovratentorial clusters of atrophy, one in the left Inferior Parietal Lobule and the other in the Corticospinal Tracts. Additional analyses revealed a partial involvement of many White Matter tracts and of the Thalamus in the pathology. The classical Tower of London version correlated maximally with the right Lobule IV–V, when the computerised version correlated with the right Crus 1. The correlations of different versions of the test suggested a dissociation between the dysfunctions in SCA2: the Posterior Cerebellum was linked to the executive dysfunction while the Anterior Cerebellum was linked to the coordinative dysfunction.

Cerebellar clustering and functional connectivity during pain processing

The cerebellum has been traditionally considered a sensory-motor structure, but more recently has been related to other cognitive and affective functions. Previous research and meta-analytic studies suggested that it could be involved in pain processing. Our aim was to distinguish the functional networks subserved by the cerebellum during pain processing. We used functional magnetic resonance imaging (fMRI) on 12 subjects undergoing mechanical pain stimulation and resting state acquisition. For the analysis of data, we used fuzzy c-mean to cluster cerebellar activity of each participant during nociception. The mean time courses of the clusters were used as regressors in a general linear model (GLM) analysis to explore brain functional connectivity (FC) of the cerebellar clusters. We compared our results with the resting state FC of the same cluster and explored with meta-analysis the behavior profile of the FC networks. We identified three significant clusters: cluster V, involving the culmen and quadrangular lobules (vermis IV-V, hemispheres IV-V-VI); cluster VI, involving the posterior quadrangular lobule and superior semilunar lobule (hemisphere VI, crus 1, crus 2), and cluster VII, involving the inferior semilunar lobule (VIIb, crus1, crus 2). Cluster V was more connected during pain with sensory-motor areas, cluster VI with cognitive areas, and cluster VII with emotional areas. Our results indicate that during the application of mechanical punctate stimuli, the cerebellum is not only involved in sensory functions but also with areas typically associated with cognitive and affective functions. Cerebellum seems to be involved in various aspects of nociception, reflecting the multidimensionality of pain perception.

Concomitant use of transcranial direct current stimulation and computer-assisted training for the rehabilitation of attention in traumatic brain injured patients: Behavioral and neuroimaging results

Divided attention (DA), the ability to distribute cognitive resources among two or more simultaneous tasks, may be severely compromised after traumatic brain injury (TBI), resulting in problems with numerous activities involved with daily living. So far, no research has investigated whether the use of non-invasive brain stimulation associated with neuropsychological rehabilitation might contribute to the recovery of such cognitive function. The main purpose of this study was to assess the effectiveness of 10 transcranial direct current stimulation (tDCS) sessions combined with computer-assisted training; it also intended to explore the neural modifications induced by the treatment. Thirty-two patients with severe TBI participated in the study: 16 were part of the experimental group, and 16 part of the control group. The treatment included 20’ of tDCS, administered twice a day for 5 days. The electrodes were placed on the dorso-lateral prefrontal cortex. Their location varied across patients and it depended on each participant’s specific area of damage. The control group received sham tDCS. After each tDCS session, the patient received computer-assisted cognitive training on DA for 40’. The results showed that the experimental group significantly improved in DA performance between pre- and post-treatment, showing faster reaction times (RTs), and fewer omissions. No improvement was detected between the baseline assessment (i.e., 1 month before treatment) and the pre-training assessment, or within the control group. Functional magnetic resonance imaging (fMRI) data, obtained on the experimental group during a DA task, showed post-treatment lower cerebral activations in the right superior temporal gyrus (BA 42), right and left middle frontal gyrus (BA 6), right postcentral gyrus (BA 3) and left inferior frontal gyrus (BA 9). We interpreted such neural changes as normalization of previously abnormal hyperactivations.

Rehabilitation of Communicative Abilities in Patients with a History of TBI: Behavioral Improvements and Cerebral Changes in Resting-State Activity

A targeted training program for the rehabilitation of communicative abilities—Cognitive Pragmatic Treatment (CPT)—has been developed and previously tested on a sample of patients with traumatic brain injury (TBI), whose performance was found to have improved. Since cortical plasticity has been recognized as the main mechanism of functional recovery, we investigated whether and how behavioral improvements following the training program are accompanied by brain modifications. Eight TBI patients took part in the training program and were behaviorally assessed pre- and post-treatment; six of these patients were also evaluated with pre- and post-treatment resting state (rs) functional magnetic resonance imaging (fMRI). At the end of the rehabilitation program patients showed improvement in overall communicative performance, in both comprehension and production tasks. A follow-up retest revealed the stability of these results 3 months after completing the training program. At the brain level, we found significant increases in the amplitude of low frequency fluctuation (ALFF) index in the bilateral precentral gyrus, in the right middle and superior temporal gyri, in the right cingulate gyrus, and in the left inferior parietal lobule. We discuss these differences of brain activity in terms of their possible contribution to promoting recovery.

Cognitive Pragmatic Rehabilitation Program in Schizophrenia: A Single Case fMRI Study

Introduction. The present study was intended to evaluate the effects of a rehabilitative training, the Cognitive Pragmatic Treatment (CPT), aimed at improving communicative-pragmatic abilities and the related cognitive components, on the cerebral modifications of a single case patient diagnosed with schizophrenia. Methods. The patient underwent two functional magnetic resonance imaging (fMRI) sessions, before and after the treatment. In order to assess brain changes, we calculated the Amplitude of Low Frequency Fluctuation (ALFF) index of the resting-state fMRI signal, which is interpreted as reflecting the intensity of the spontaneous regional activity of the brain. Behavioural measures of the patients communicative performance were also gathered before and after training and at follow-up. Results. The patient improved his communicative performance in almost all tests. Posttraining stronger ALFF signal emerged in the superior, inferior, and medial frontal gyri, as well as the superior temporal gyri. Conclusions. Even if based on a single case study, these preliminary results show functional changes at the cerebral level that seem to support the patients behavioural improvements.

Bra.Di.P.O. and P.I.G.R.O.: Innovative Devices for Motor Learning Programs

Two mechatronics prototypes, useful for robotic neurotreatments and new clinical trainings, are here presented. P.I.G.R.O. (pneumatic interactive gait rehabilitation orthosis) is an active exoskeleton with an electropneumatic control. It imposes movements on lower limbs in order to produce in the patient’s brain proper motor cortex activation. Bra.Di.P.O. (brain discovery pneumatic orthosis) is an MR-compatible device, designed to improve fMRI (functional magnetic resonance imaging) analysis. The two devices are presented together because both are involved in the study of new robotic treatments of patients affected by ictus or brain stroke or in some motor learning experimental investigations carried out on healthy subjects.

P.I.G.R.O.: an active exoskeleton for robotic neurorehabilitation training driven by an electropneumatic control

This paper presents the structure and the main innovations of P.I.G.R.O. (Pneumatic Interactive Gait Rehabilitation Orthosis). It is an active exoskeleton electro-pneumatically controlled with 6 DoF (Degree of Freedom) in the sagittal plane. Robotic neurorehabilitation trainings are its main field of application. Some preliminary tests are carrying on with brain stroke and ictus patients.