Inefficient white matter activity in Schizophrenia evoked during intra and inter-hemispheric communication

Intensive cognitive tasks induce inefficient regional and network responses in schizophrenia (SCZ). fMRI-based studies have naturally focused on gray matter, but appropriately titrated visuo-motor integration tasks reliably activate inter- and intra-hemispheric white matter pathways. Such tasks can assess network inefficiency without demanding intensive cognitive effort. Here, we provide the first application of this framework to the study of white matter functional responses in SCZ. Event-related fMRI data were acquired from 28 patients (nine females, mean age 43.3, ±11.7) and 28 age- and gender-comparable controls (nine females, mean age 42.1 ± 10.1), using the Poffenberger paradigm, a rapid visual detection task used to induce intra- (ipsi-lateral visual and motor cortex) or inter-hemispheric (contra-lateral visual and motor cortex) transfer. fMRI data were pre- and post-processed to reliably isolate activations in white matter, using probabilistic tractography-based white matter tracts. For intra- and inter-hemispheric transfer conditions, SCZ evinced hyper-activations in longitudinal and transverse white matter tracts, with hyper-activation in sub-regions of the corpus callosum primarily observed during inter-hemispheric transfer. Evidence for the functional inefficiency of white matter was observed in conjunction with small (~50 ms) but significant increases in response times. Functional inefficiencies in SCZ are (1) observable in white matter, with the degree of inefficiency contextually related to task-conditions, and (2) are evoked by simple detection tasks without intense cognitive processing. These cumulative results while expanding our understanding of this dys-connection syndrome, also extend the search of biomarkers beyond the traditional realm of fMRI studies of gray matter

Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness

Because the visual cortices are contra-laterally organized, inter-hemispheric transfer tasks have been used to behaviorally probe how information briefly presented to one hemisphere of the visual cortex is integrated with responses resulting from the ipsi- or contra-lateral motor cortex. By forcing rapid information exchange across diverse regions, these tasks robustly activate not only gray matter regions, but also white matter tracts. It is likely that the response hand itself (dominant or non-dominant) modulates gray and white matter activations during within and inter-hemispheric transfer. Yet the role of uni-manual responses and/or right hand dominance in modulating brain activations during such basic tasks is unclear. Here we investigated how uni-manual responses with either hand modulated activations during a basic visuo-motor task (the established Poffenberger paradigm) alternating between inter- and within-hemispheric transfer conditions. In a large sample of strongly right-handed adults (n = 49), we used a factorial combination of transfer condition [Inter vs. Within] and response hand [Dominant(Right) vs. Non-Dominant (Left)] to discover fMRI-based activations in gray matter, and in narrowly defined white matter tracts. These tracts were identified using a priori probabilistic white matter atlases. Uni-manual responses with the right hand strongly modulated activations in gray matter, and notably in white matter. Furthermore, when responding with the left hand, activations during inter-hemispheric transfer were strongly predicted by the degree of right-hand dominance, with increased right-handedness predicting decreased fMRI activation. Finally, increasing age within the middle-aged sample was associated with a decrease in activations. These results provide novel evidence of complex relationships between uni-manual responses in right-handed subjects, and activations during within- and inter-hemispheric transfer suggest that the organization of the motor system exerts sophisticated functional effects. Moreover, our evidence of activation in white matter tracts is consistent with prior studies, confirming fMRI-detectable white matter activations which are systematically modulated by experimental condition

Effects of robot-assisted training for the unaffected arm in patients with hemiparetic cerebral palsy: a proof-of-concept pilot study

On a voluntary basis, 10 adolescents with hemiparesis due to cerebral palsy and 11 neurologically healthy control subjects participated in this proof-of-concept pilot study. The aim was to examine the effects of robot-assisted training for the unaffected arm in patients with hemiparetic cerebral palsy. Baseline comparison between the unaffected arm of the hemiparetic patients with cerebral palsy and the dominant arm of healthy control subjects showed significant differences on the Jebsen-Taylor Hand Function test and action planning ability tests. Within-group comparison after ten 30-minute sessions (five days a week for two consecutive weeks) of robot-assisted training for the unaffected arm showed significant improvements in patients with cerebral palsy on the Jebsen-Taylor Hand Function test (performed at both hands) and action planning ability test (evaluated at the unaffected arm). Our findings are in line with previous evidences of action planning deficits at the unaffected arm in patients with hemiparetic cerebral palsy and support the hypothesis that robot-assisted training for the unaffected arm may be useful to improve manual dexterity and action planning in patients with hemiparesis due to cerebral palsy

Effects of Robot-Assisted Training for the Unaffected Arm in Patients with Hemiparetic Cerebral Palsy: A Proof-of-Concept Pilot Study

On a voluntary basis, 10 adolescents with hemiparesis due to cerebral palsy and 11 neurologically healthy control subjects participated in this proof-of-concept pilot study. The aim was to examine the effects of robot-assisted training for the unaffected arm in patients with hemiparetic cerebral palsy. Baseline comparison between the unaffected arm of the hemiparetic patients with cerebral palsy and the dominant arm of healthy control subjects showed significant differences on the Jebsen-Taylor Hand Function test and action planning ability tests. Within-group comparison after ten 30-minute sessions (five days a week for two consecutive weeks) of robot-assisted training for the unaffected arm showed significant improvements in patients with cerebral palsy on the Jebsen-Taylor Hand Function test (performed at both hands) and action planning ability test (evaluated at the unaffected arm). Our findings are in line with previous evidences of action planning deficits at the unaffected arm in patients with hemiparetic cerebral palsy and support the hypothesis that robot-assisted training for the unaffected arm may be useful to improve manual dexterity and action planning in patients with hemiparesis due to cerebral palsy

Controllo esecutivo e lateralizzazione emisferica: studi di neuroimaging con paradigma di Stroop

Tutte le attività della vita quotidiana richiedono di prestare attenzione a certi aspetti dell’ambiente, ignorando quelli che sono irrilevanti o addirittura distraenti per l’attività che si sta svolgendo. Questa capacità di isolare gli elementi salienti dal flusso di informazioni che continuamente raggiunge il cervello è definita “attenzione selettiva”, e fa parte delle abilità cognitive di ordine superiore essenziali all’adattamento dell’uomo all’ambiente e quindi alla sua stessa sopravvivenza. Le funzioni esecutive, di cui l’attenzione selettiva rappresenta una componente, rendono l’elaborazione degli stimoli rilevanti prioritaria rispetto a quella degli stimoli irrilevanti, determinando un’adeguata risposta comportamentale. I meccanismi neurali alla base di queste funzioni sono già stati studiati, soprattutto in ambito visivo, con metodiche neuropsicologiche, e recentemente con tecniche elettrofisiologiche e di brain imaging (Corbetta et al., 1993; De Simone 1998; Banich et al., 2000; Pessoa et al., 2002). Si ritiene che per identificare un preciso stimolo visivo, vengano inizialmente innescati processi attenzionali automatici, ai quali seguono processi di attenzione selettiva da cui dipende l’identificazione dello stimolo stesso. Studi sull’uomo e sulla scimmia (Chelazzi et al., 1993; Luck e Hillyard 1994; Kastener et al., 1998; Smith et al., 2000; Hopf et al., 2002), dimostrano che l’attenzione selettiva agisce attraverso meccanismi inibitori che sopprimono l’informazione non rilevante riducendo l’interferenza. L’attenzione selettiva può essere misurata in condizioni sperimentali attraverso stimoli che introducono una condizione di interferenza tra l’elemento saliente e il distrattore. La più nota di queste procedure è il Test di Stroop, utilizzato anche nel nostro lavoro in una versione modificata. Gli stimoli variano per due dimensioni ed il soggetto deve ignorarne una per fornire la risposta corretta al test. La rapidità della risposta stima l’efficienza dell’attenzione selettiva. Scopo di questo lavoro è valutare con Risonanza Magnetica funzionale (fMRI) ad alto campo (3 Tesla) il ruolo delle funzioni esecutive, attraverso l’elaborazione di un paradigma sperimentale di Stroop che permetta di localizzare le aree cerebrali coinvolte nel processamento degli aspetti d’incongruenza della funzione attentiva. La Risonanza Magnetica funzionale è un metodo di indagine che permette di esplorare l’anatomia funzionale del cervello in maniera non invasiva. Per questi motivi la tecnica ha incontrato un notevole successo e negli ultimi anni sono stati pubblicati numerosi studi basati sull’applicazione della stessa. L’innovazione del nostro lavoro, rispetto agli studi precedenti, è rappresentata dall’utilizzo di un paradigma di Stroop strutturato con stimoli non verbali (frecce), confrontato con un paradigma di Stroop tradizionale (colorword). Dati preliminari raccolti in bambini normali e dislessici dicono che l’effetto Stroop si realizza anche in compiti che utilizzano stimoli non verbali. Nei dislessici, tuttavia, solo i compiti che utilizzano stimoli verbali danno un effetto d’incongruenza maggiore che nei controlli, suggerendo meccanismi diversi per i due tipi di compito (Faccioli, 2006; Faccioli et al., in stampa). In questo studio, abbiamo voluto verificarli in un gruppo di adulti normali, raccogliendo assieme ai dati comportamentali (tempi di reazione) quelli di fMRI. Questo ci ha permesso di provare che effetti d’interferenza simili corrispondono all’attivazione di aree cerebrali distinte nell’ambito di quelle coinvolte nel controllo esecutivo.Non disponibil

Permanenza di alterazioni cerebrali dopo assunzione di droghe anche dopo un periodo di cessazione dell’uso: il contributo del neuroimaging

Revisione della letteratura scientifica che ha l’obiettivo principale di definire un più corretto paradigma relativo alla guida sotto l’effetto di sostanze stupefacenti

Awake surgery between art and science. Part I: clinical and operative settings

Awake surgery requires coordinated teamwork and communication between the surgeon and the anesthesiologist, as he monitors the patient, the neuroradiologist as he interprets the images for intraoperative confirmation, and the neuropsychologist and neurophysiologist as they evaluate in real-time the patient’s responses to commands and questions. To improve comparison across published studies on clinical assessment and operative settings in awake surgery, we reviewed the literature, focusing on methodological differences and aims. In complex, interdisciplinary medical care, such differences can affect the outcome and the cost-benefit ratio of the treatment. Standardization of intraoperative mapping and related controversies will be discussed in Part II

Diffuse alterations in grey and white matter associated with cognitive impairment in Shwachman–Diamond syndrome: Evidence from a multimodal approach

Shwachman–Diamond syndrome is a rare recessive genetic disease caused by mutations in SBDS gene, at chromosome 7q11. Phenotypically, the syndrome is characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal dysplasia and variable cognitive impairments. Structural brain abnormalities (smaller head circumference and decreased brain volume) have also been reported. No correlation studies between brain abnormalities and neuropsychological features have yet been performed. In this study we investigate neuroanatomical findings, neurofunctional pathways and cognitive functioning of Shwachman–Diamond syndrome subjects compared with healthy controls. To be eligible for inclusion, participants were required to have known SBDS mutations on both alleles, no history of cranial trauma or any standard contraindication to magnetic resonance imaging. Appropriate tests were used to assess cognitive functions. The static images were acquired on a 3 × 0 T magnetic resonance scanner and blood oxygen level-dependent functional magnetic resonance imaging data were collected both during the execution of the Stroop task and at rest. Diffusion tensor imaging was used to assess brain white matter. The Tract-based Spatial Statistics package and probabilistic tractography were used to characterize white matter pathways. Nine participants (5 males), half of all the subjects aged 9–19 years included in the Italian Shwachman–Diamond Syndrome Registry, were evaluated and compared with nine healthy subjects, matched for sex and age. The patients performed less well than norms and controls on cognitive tasks (p = 0.0002). Overall, cortical thickness was greater in the patients, both in the left (+10%) and in the right (+15%) hemisphere, significantly differently increased in the temporal (left and right, p = 0.04), and right parietal (p = 0.03) lobes and in Brodmann area 44 (p = 0.04) of the right frontal lobe. The greatest increases were observed in the left limbic-anterior cingulate cortex (≥43%, p < 0.0004). Only in Broca's area in the left hemisphere did the patients show a thinner cortical thickness than that of controls (p = 0.01). Diffusion tensor imaging showed large, significant difference increases in both fractional anisotropy (+37%, p < 0.0001) and mean diffusivity (+35%, p < 0.005); the Tract-based Spatial Statistics analysis identified six abnormal clusters of white matter fibres in the fronto-callosal, right fronto-external capsulae, left fronto-parietal, right pontine, temporo-mesial and left anterior–medial–temporal regions. Brain areas activated during the Stroop task and those active during the resting state, are different, fewer and smaller in patients and correlate with worse performance (p = 0.002). Cognitive impairment in Shwachman–Diamond syndrome subjects is associated with diffuse brain anomalies in the grey matter (verbal skills with BA44 and BA20 in the right hemisphere; perceptual skills with BA5, 37, 20, 21, 42 in the left hemisphere) and white matter connectivity (verbal skills with alterations in the fronto-occipital fasciculus and with the inferior-longitudinal fasciculus; perceptual skills with the arcuate fasciculus, limbic and ponto-cerebellar fasciculus; memory skills with the arcuate fasciculus; executive functions with the anterior cingulated and arcuate fasciculus)

Early MRI changes in glioblastoma in the period between surgery and adjuvant therapy.

To investigate the increase in MRI contrast enhancement (CE) occurring in glioblastoma during the period between surgery and initiation of chemo-radiotherapy, thirty-seven patients with newly diagnosed glioblastoma were analyzed by early post-operative magnetic resonance (EPMR) imaging within three days of surgery and by pre-adjuvant magnetic resonance (PAMR) examination before adjuvant therapy. Areas of new CE were investigated by use of EPMR diffusion-weighted imaging and PAMR perfusion imaging (by arterial spin-labeling). PAMR was acquired, on average, 29.9 days later than EPMR (range 20-37 days). During this period an increased area of CE was observed for 17/37 patients. For 3/17 patients these regions were confined to areas of reduced EPMR diffusion, suggesting postsurgical infarct. For the other 14/17 patients, these areas suggested progression. For 11/17 patients the co-occurrence of hyperperfusion in PAMR perfusion suggested progression. PAMR perfusion and EPMR diffusion did not give consistent results for 3/17 patients for whom small new areas of CE were observed, presumably because of the poor spatial resolution of perfusion imaging. Before initiation of adjuvant therapy, areas of new CE of resected glioblastomas are frequently observed. Most of these suggest tumor progression, according to EPMR diffusion and PAMR perfusion criteria