86,603 research outputs found
Studio della plasticità maladattativa del tinnito cronico attraverso metodiche psicofisiologiche
No full textIl tinnito rappresenta una delle possibili condizioni cliniche correlate a fenomeni di plasticità maladattativa che si realizzano non solo nelle aree del pathway uditivo primario, ma anche nel contesto di aree cerebrali associative. La deprivazione sensoriale è considerata alla base della patogenesi del tinnito. Si ritiene che nel tentativo di preservare l’efficienza di codifica degli stimoli acustici in presenza di uno stato anche transitorio di ipoacusia si attivino dei meccanismi di compenso (“cental gain” compensatorio o di adattamento) (Norena e Farley, 2013) espressione di una plasticità neuronale che modifica la sensibilità dei neuroni centrali rendendoli iperattivi e quindi responsivi anche a stimoli di bassa intensità (Norena, 2011; Turrigiano, 2011). E’ stato dimostrato, inoltre, che la deprivazione sensoriale può modificare il livello di espressione dei recettori serotoninergici modificando la responsività neuronale di differenti aree cerebrali.
La tesi di dottorato si articola in due esperimenti che, attraverso metodiche psicofisiologiche (potenziali evocati uditivi sia stimolo che evento-correlati ossia gli Event Related Potentials-ERPs), hanno confermato la presenza di alterazioni sia in pathway neurotrasmettitoriali specifici che nella funzionalità di selettive aree corticali in corso di tinnito cronico.
Nel primo lavoro la valutazione dei parametri ABR e dell’indice elettrofisiologico derivato IDAP (Intensity Dependance of Auditory Evoked Potential) e N1 ASF slope hanno dimostrato la presenza di una disfunzione del tono serotoninergico centrale in presenza di sintomi uditivi fantasma. In particolare, il prolungamento della latenza dell’onda V e dell’interpicco III-V riscontrato nei nostri pazienti è da correlare con l’incrementata attività nel CI associabile ad uno squilibrio tra l’attività dei recettori 5-HT1A e 5-HT1B. Inoltre, la maggiore dipendenza dall’intensità dello stimolo dei potenziali evocati corticali e la compromissione dei processi di abituazione corticale (come mostrato dai valori IDAP) è da imputare alla disfunzione serotoninergica (in particolare ad una riduzione del tono serotoninergico) nell’ambito della corteccia uditiva primaria nei soggetti con tinnito. Tale disfunzione serotoninergica cioè, non solo rallenta il processamento dello stimolo nelle fasi più precoci (aumentate latenze del picco V e interpicco III-V) ma sembra rallentarne anche l’adeguato immagazzinamento corticale automatico (maggiori valori IDAP nei soggetti con tinnito rispetto ai controlli).
D’altro canto le modificazioni plastiche maladattative che in corso di tinnito si determinano anche a carico delle aree cerebrali associative possono accompagnarsi a disfunzioni cognitive più o meno complesse. In effetti, nel secondo lavoro lo studio del processamento attentivo dello stimolo acustico attraverso gli ERPs ha permesso di rilevare delle selettive disfunzioni attentive in corso di tinnito cronico. Oltre a confermare un globale rallentamento nelle fasi precoci della percezione dello stimolo si osserva come il tinnito non comprometta la capacità di discriminazione e memorizzazione conscia. La presenza di sintomi uditivi phantom sembra essere invece selettivamente associata a una specifica difficoltà nello switching attentivo verso eventi inattesi durante una risposta di orientamento. La difficoltà a shiftare l’attenzione è verosimilmente dovuta alla minore disponibilità di risorse attentive che si determina in presenza di tinnito. Tale stimolo endogeno, infatti, compete con le risorse attentive disponibili furtandole e impedendo che vengano adeguatamente impiegate per il riconoscimento di stimoli esterni salienti e significanti. Il nostro approccio psicofisiologico ha consentito di obbiettivare e misurare la presenza di tale deficit attentivo selettivo fornendo ipotesi circa le sue basi fisiopatologiche. Tale difficoltà a shiftare l’attenzione è infatti probabilmente legata ad una alterazione funzionale a carico di regioni cortico-sottocorticali (cortecce prefrontali, ACC, cervelletto) che intervengono nella definizione del network attentivo ventrale tipicamente coinvolto nei processi di orientamento allo stimolo (Corbetta e Shulman, 2002; Corbetta et al., 2008)
Ulteriori studi sono necessari per confermare i dati relativi sia alla disfunzione serotoninergica centrale che per indagare gli effetti dei cambiamenti plastici maladattativi sulle funzioni cognitive in corso di tinnito cronico. Tuttavia, da un punto di vista clinico, i nostri dati forniscono delle utili prospettive terapeutiche sia farmacologiche che riabilitative. La presenza di una disfunzione serotoninergica potrebbe verosimilmente giovarsi dell’uso di farmaci modulatori (agonisti/antagonisti) della 5-HT. Allo stesso modo, il riscontro di deficit attentivi selettivi consente di programmare interventi di riabilitazione cognitiva più appropriati nel tinnito focalizzandoli sull’abilità a orientare correttamente l’attenzione verso stimoli salienti durante un task cognitivo. Inoltre, le nostre ipotesi relative alla fisiopatologia dei disturbi attentivi nel tinnito potrebbero contribuire all’identificazione di nuove aree neurali target per il trattamento delle disfunzioni cognitive attraverso tecniche di neuro modulazione (ripetitive transcranial magnetic stimulation - rTMS; transcranial direct current stimulation - tDCS) nei soggetti con tinnito cronico
Age-related changes of protein SUMOylation balance in the AβPP Tg2576 mouse model of Alzheimer's disease
No full textAlzheimer's disease (AD) is a complex disorder that affects the central nervous system causing a severe neurodegeneration. This pathology affects an increasing number of people worldwide due to the overall aging of the human population. In recent years SUMO protein modification has emerged as a possible cellular mechanism involved in AD. Some of the proteins engaged in the physiopathological process of AD, like BACE1, GSK3-β tau, AβPP, and JNK, are in fact subject to protein SUMO modifications or interactions. Here, we have investigated the SUMO/deSUMOylation balance and SUMO-related proteins during the onset and progression of the pathology in the Tg2576 mouse model of AD. We examined four age-stages (1.5, 3, 6, 17 months old) and observed shows an increase in SUMO-1 protein conjugation at 3 and 6 months in transgenic mice with respect to WT in both cortex and hippocampus. Interestingly this is paralleled by increased expression levels of Ubc9 and SENP1 in both brain regions. At 6 months of age also the SUMO-1 mRNA resulted augmented. SUMO-2-ylation was surprisingly decreased in old transgenic mice and was unaltered in the other time windows. The fact that alterations in SUMO/deSUMOylation equilibrium occur from the early phases of AD suggests that global posttranslational modifications may play an important role in the mechanisms underlying disease pathogenesis, thus providing potential targets for pharmacological interventions. © 2014 Nisticò, Ferraina, Marconi, Blandini, Negri, Egebjerg and Feligioni
Frequency-dependent habituation deficit of the nociceptive blink reflex in aura with migraine headache. Can migraine aura play a modulating role?
No full textObjective
To study the influence of the migraine aura on the trigeminal nociception, we investigated the habituation of the nociceptive blink reflex (nBR) R2 responses in aura with migraine headache (AwMH) and comparatively in migraine without aura (MWoA) and healthy (HS) subjects.
Methods
Seventeen AwMH, 29 MWoA and 30 HS were studied. We delivered a series of 26 electrical stimuli, at different stimulation frequencies (SF) (0.05, 0.1, 0.2, 0.3, 0.5, 1Hz), subsequently subdivided in five blocks of five responses for each SF. Habituation was measured as the percentage decrease of the R2 area across the blocks.
Results
A significant frequency-dependent habituation deficit of the nBR R2 responses was found from 1 to 0.2 Hz SF in both MWoA and AwMH when compared to HS. AwMH did not shown habituation deficit at the higher 1 Hz SF and showed a less consistent deficit at 0.5 and 0.3 Hz SF.
Conclusions
We demonstrated in AwMH a deficit of habituation, although less pronounced than that observed in MWoA of comparable clinical severity.
Significance
We hypothesize that AwMH and MWoA share some pathogenetic aspects and that migraine aura physiopathology may play a modulating role on the excitability of the nociceptive trigeminal pathways
REPRESENTING SPATIAL INFORMATION FOR LIMB MOVEMENT - ROLE OF AREA 5 IN THE MONKEY
No full textHow is spatial information for limb movement encoded in the brain? Computational and psychophysical studies suggest that beginning hand position, via-points, and target are specified relative to the body to afford a comparison between the sensory (e.g., kinesthetic) reafferences and the commands that generate limb movement. Here we propose that the superior parietal lobule (Brodmann area 5) might represent a substrate for a body-centered positional code. Monkeys made arm movements in different parts of 3D space in a reaction-time task. We found that the activity of area 5 neurons can be related to either the starting point, dr the final point, or combinations of the two. Neural activity is monotonically tuned in a body-centered frame of reference, whose coordinates define the azimuth, elevation, and distance of the hand. Each spatial coordinate tends to be encoded in a different sub population of neurons. This parcellation could be a neural correlate of the psychophysical observation that these spatial parameters are processed in parallel and largely independent of each other in man
Reply to: Hannah et al. (2021) Commentary: ‘Does action-stopping involve separate pause and cancel processes? A view from premotor cortex’: Action-stopping models must consider the role of the dorsal premotor cortex
No full textEvidence of EEG Correlates of Memory-Based Decision-Making During A Transitive Inference Task
No full textMaking decisions based on previously acquired knowledge is fundamental for optimizing interactions
with a complex environment. The transitive inference task is an experimental paradigm developed for
studying the cognitive and behavioral correlates of this ability. It first requires learning the reciprocal
hierarchy between the adjacent items of a rank-ordered set, like the series A>B>C>D>E>F, and then
indicating, in a test phase, the ordinal relationship between all possible pair combinations (e.g.,C?F).
When performing this task, the accuracy in determining whether a given item is higher or lower in
rank than another depends on their rank differences. In fact, it is easier to compare items with a larger
rank difference than smaller ones. This phenomenon highlights a symbolic distance effect (SDE),
which is thought to reflect a spatial-like mental representation of the item's rank, arranged linearly in
working memory. Monkey neurophysiology studies have found a correlation between SDE and the
activity of neurons in both the parietal and prefrontal areas. Using EEG with human participants, we
found modulation of ERP components involved in visual attention from corresponding brain areas,
providing a functional link, from microscopic to macroscopic scales, emphasizing the role of these
brain regions in this cognitive function
Neuronal dynamics of signal selective motor plan cancellation in macaque dorsal premotor cortex
No full text
To close, not to close, or to act bigger? Managing the defect of large direct inguinal hernia to reduce the risk of recurrence during laparoscopic TAPP repair: a retrospective cohort study
No full textHernia recurrence is a common complication after inguinal hernia repair. Recent studies suggest that laparoscopic mesh repair with closure of direct hernia defects can reduce recurrence rates. Our study examines the effectiveness of this approach. A retrospective, multi-center cohort study was conducted on cases performed from January 2013 to April 2021. Patients with direct inguinal hernias (M3 according to EHS classification) undergoing TAPP were included. Three groups were present: closed-defect group, non-closed placing a standard-sized mesh group or non-closed placing an XL-sized mesh group. A 2-year follow-up was recorded. A total of 158 direct M3 inguinal hernias in 110 patients who underwent surgery were present. After propensity score matching at a 1:1 ratio, 22 patients for each group were analyzed. The mean age of patients was 62 years (41–84); with the majority being male (84.8%). 22 patients (40 hernias) underwent closure of the defect; 22 patients (39 hernias) did not undergo closure and used a standard-sized mesh; 22 patients (27 hernias) did not undergo closure and used an XL-sized mesh. There were 5 recurrences at 1 year post-operatively: all in the non-closure group with standard-sized mesh. This difference was statistically significant (p = 0.044). There were 7 recurrences (6.6%) at 2 years post-operatively: 6 in the non-closure group with standard-sized mesh and 1 in the non-closure group with XL-sized mesh (p = 0.007). Closing large direct inguinal hernia defects has shown promise in reducing early recurrence rates. However, conducting larger RCTs in the future could provide more conclusive evidence that might impact the way we approach laparoscopic inguinal hernia repair
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