Language impairment in Huntington's disease

Language alterations in Huntington's disease (HD) are reported, but their nature and correlation with other cognitive impairments are still under investigation. This study aimed to characterize the language disturbances in HD and to correlate them to motor and cognitive aspects of the disease. We studied 23 HD patients and 23 controls, matched for age and schooling, using the Boston Diagnostic Aphasia Examination, Boston Naming Test, the Token Test, Animal fluency, Action fluency, FAS-COWA, the Symbol Digit Modalities Test, the Stroop Test and the Hooper Visual Organization Test (HVOT). HD patients performed poorer in verbal fluency (p<0.0001), oral comprehension (p<0.0001), repetition (p<0.0001), oral agility (p<0.0001), reading comprehension (p=0.034) and narrative writing (p<0.0001). There was a moderate correlation between the Expressive Component and Language Competency Indexes and the HVOT (r=0.519, p=0.011 and r=0.450, p=0.031, respectively). Language alterations in HD seem to reflect a derangement in both frontostriatal and frontotemporal regions.

Longitudinal brain volumetric changes during one year in non-elderly healthy adults: a voxel-based morphometry study

Previous cross-sectional magnetic resonance imaging (MRI) studies of healthy aging in young adults have indicated the presence of significant inverse correlations between age and gray matter volumes, although not homogeneously across all brain regions. However, such cross-sectional studies have important limitations and there is a scarcity of detailed longitudinal MRI studies with repeated measures obtained in the same individuals in order to investigate regional gray matter changes during short periods of time in non-elderly healthy adults. In the present study, 52 healthy young adults aged 18 to 50 years (27 males and 25 females) were followed with repeated MRI acquisitions over approximately 15 months. Gray matter volumes were compared between the two times using voxel-based morphometry, with the prediction that volume changes would be detectable in the frontal lobe, temporal neocortex and hippocampus. Voxel-wise analyses showed significant (P < 0.05, family-wise error corrected) relative volume reductions of gray matter in two small foci located in the right orbitofrontal cortex and left hippocampus. Separate comparisons for males and females showed bilateral gray matter relative reductions in the orbitofrontal cortex over time only in males. We conclude that, in non-elderly healthy adults, subtle gray matter volume alterations are detectable after short periods of time. This underscores the dynamic nature of gray matter changes in the brain during adult life, with regional volume reductions being detectable in brain regions that are relevant to cognitive and emotional processes.

Monitoramento in vivo por imagem por ressonância magnética de células C6 de glioma marcadas com nanopartículas superparamagnéticas de óxido de ferro

OBJECTIVE: The aim of the current study was to monitor the migration of superparamagnetic iron oxide nanoparticle (SPION)-labeled C6 cells, which were used to induce glioblastoma tumor growth in an animal model, over time using magnetic resonance imaging (MRI), with the goal of aiding in tumor prognosis and therapy. METHODS: Two groups of male Wistar rats were used for the tumor induction model. In the first group (n=3), the tumors were induced via the injection of SPION-labeled C6 cells. In the second group (n=3), the tumors were induced via the injection of unlabeled C6 cells. Prussian Blue staining was performed to analyze the SPION distribution within the C6 cells in vitro. Tumor-inducing C6 cells were injected into the right frontal cortex, and subsequent tumor monitoring and SPION detection were performed using T2- and T2*-weighted MRI at a 2T field strength. In addition, cancerous tissue was histologically analyzed after performing the MRI studies. RESULTS: The in vitro qualitative evaluation demonstrated adequate distribution and satisfactory cell labeling of the SPIONs. At 14 or 21 days after C6 injection, a SPION-induced T2- and T2*-weighted MRI signal reduction was observed within the lesion located in the left frontal lobe on parasagittal topography. Moreover, histological staining of the tumor tissue with Prussian Blue revealed a broad distribution of SPIONs within the C6 cells. CONCLUSION: MRI analyses exhibit potential for monitoring the tumor growth of C6 cells efficiently labeled with SPIONs.

Seizure prediction and control in epilepsy

The first part of my thesis presents an overview of the different approaches used in the past two decades in the attempt to forecast epileptic seizure on the basis of intracranial and scalp EEG. Past research could reveal some value of linear and nonlinear algorithms to detect EEG features changing over different phases of the epileptic cycle. However, their exact value for seizure prediction, in terms of sensitivity and specificity, is still discussed and has to be evaluated. In particular, the monitored EEG features may fluctuate with the vigilance state and lead to false alarms. Recently, such a dependency on vigilance states has been reported for some seizure prediction methods, suggesting a reduced reliability. An additional factor limiting application and validation of most seizure-prediction techniques is their computational load. For the first time, the reliability of permutation entropy [PE] was verified in seizure prediction on scalp EEG data, contemporarily controlling for its dependency on different vigilance states. PE was recently introduced as an extremely fast and robust complexity measure for chaotic time series and thus suitable for online application even in portable systems. The capability of PE to distinguish between preictal and interictal state has been demonstrated using Receiver Operating Characteristics (ROC) analysis. Correlation analysis was used to assess dependency of PE on vigilance states. Scalp EEG-Data from two right temporal epileptic lobe (RTLE) patients and from one patient with right frontal lobe epilepsy were analysed. The last patient was included only in the correlation analysis, since no datasets including seizures have been available for him. The ROC analysis showed a good separability of interictal and preictal phases for both RTLE patients, suggesting that PE could be sensitive to EEG modifications, not visible on visual inspection, that might occur well in advance respect to the EEG and clinical onset of seizures. However, the simultaneous assessment of the changes in vigilance showed that: a) all seizures occurred in association with the transition of vigilance states; b) PE was sensitive in detecting different vigilance states, independently of seizure occurrences. Due to the limitations of the datasets, these results cannot rule out the capability of PE to detect preictal states. However, the good separability between pre- and interictal phases might depend exclusively on the coincidence of epileptic seizure onset with a transition from a state of low vigilance to a state of increased vigilance. The finding of a dependency of PE on vigilance state is an original finding, not reported in literature, and suggesting the possibility to classify vigilance states by means of PE in an authomatic and objectic way. The second part of my thesis provides the description of a novel behavioral task based on motor imagery skills, firstly introduced (Bruzzo et al. 2007), in order to study mental simulation of biological and non-biological movement in paranoid schizophrenics (PS). Immediately after the presentation of a real movement, participants had to imagine or re-enact the very same movement. By key release and key press respectively, participants had to indicate when they started and ended the mental simulation or the re-enactment, making it feasible to measure the duration of the simulated or re-enacted movements. The proportional error between duration of the re-enacted/simulated movement and the template movement were compared between different conditions, as well as between PS and healthy subjects. Results revealed a double dissociation between the mechanisms of mental simulation involved in biological and non-biologial movement simulation. While for PS were found large errors for simulation of biological movements, while being more acurate than healthy subjects during simulation of non-biological movements. Healthy subjects showed the opposite relationship, making errors during simulation of non-biological movements, but being most accurate during simulation of non-biological movements. However, the good timing precision during re-enactment of the movements in all conditions and in both groups of participants suggests that perception, memory and attention, as well as motor control processes were not affected. Based upon a long history of literature reporting the existence of psychotic episodes in epileptic patients, a longitudinal study, using a slightly modified behavioral paradigm, was carried out with two RTLE patients, one patient with idiopathic generalized epilepsy and one patient with extratemporal lobe epilepsy. Results provide strong evidence for a possibility to predict upcoming seizures in RTLE patients behaviorally. In the last part of the thesis it has been validated a behavioural strategy based on neurobiofeedback training, to voluntarily control seizures and to reduce there frequency. Three epileptic patients were included in this study. The biofeedback was based on monitoring of slow cortical potentials (SCPs) extracted online from scalp EEG. Patients were trained to produce positive shifts of SCPs. After a training phase patients were monitored for 6 months in order to validate the ability of the learned strategy to reduce seizure frequency. Two of the three refractory epileptic patients recruited for this study showed improvements in self-management and reduction of ictal episodes, even six months after the last training session.

Sonno e funzioni cognitive: ruolo della microstruttura del sonno NREM

STUDY OBJECTIVE: Cyclic Alternating Pattern (CAP) is a fluctuation of the arousal level during NREM sleep and consists of the alternation between two phases: phase A (divided into three subtypes A1, A2, and A3) and phase B. A1 is thought to be generated by the frontal cortex and is characterized by the presence of K complexes or delta bursts; additionally, CAP A1 seems to have a role in the involvement of sleep slow wave activity in cognitive processing. Our hypothesis was that an overall CAP rate would have a negative influence on cognitive performance due to excessive fluctuation of the arousal level during NREM sleep. However, we also predicted that CAP A1 would be positively correlated with cognitive functions, especially those related to frontal lobe functioning. For this reason, the objective of our study was to correlate objective sleep parameters with cognitive behavioral measures in normal healthy adults. METHODS: 8 subjects (4 males; 4 females; mean age 27.75 years, range 2334) were recruited for this study. Two nocturnal polysomnography (night 2 and 3 = N2 and N3) were carried out after a night of adaptation. A series of neuropsychological tests were performed by the subjects in the morning and afternoon of the second day (D2am; D2pm) and in the morning of the third day (D3am). Raw scores from the neuropsychological tests were used as dependent variables in the statistical analysis of the results. RESULTS: We computed a series of partial correlations between sleep microstructure parameters (CAP, A1, A2 and A3 rate) and a number of indices of cognitive functioning. CAP rate was positively correlated with visuospatial working memory (Corsi block test), Trial Making Test Part A (planning and motor sequencing) and the retention of words from the Hopkins Verbal Learning Test (HVLT). Conversely, CAP was negatively correlated with visuospatial fluency (Ruff Figure Fluency Test). CAP A1 were correlated with many of the tests of neuropsychological functioning, such as verbal fluency (as measured by the COWAT), working memory (as measured by the Digit Span – Backward test), and both delay recall and retention of the words from the HVLT. The same parameters were found to be negatively correlated with CAP A2 subtypes. CAP 3 were negatively correlated with the Trial Making Test Parts A and B. DISCUSSION: To our knowledge this is the first study indicating a role of CAP A1 and A2 on behavioral cognitive performance of healthy adults. The results suggest that high rate of CAP A1 might be related to an improvement whereas high rate of CAP A2 to a decline of cognitive functions. Further studies need to be done to better determine the role of the overall CAP rate and CAP A3 on cognitive behavioral performances.

Cognitive and affective processes in social actions and decisions

The question of how we make, and how we should make judgments and decisions has occupied thinkers for many centuries. This thesis has the aim to add new evidences to clarify the brain’s mechanisms for decisions. The cognitive and the emotional processes of social actions and decisions are investigated with the aim to understand which brain areas are mostly involved. Four experimental studies are presented. A specific kind of population is involved in the first study (as well as in study III) concerning patients with lesion of ventromedial prefrontal cortex (vmPFC). This region is collocated in the ventral surface of frontal lobe, and it seems have an important role in social and moral decision in forecasting the negative emotional consequences of choice. In study I, it is examined whether emotions, specifically social emotions subserved by the vmPFC, affect people’s willingness to trust others. In study II is observed how incidental emotions could encourage trusting behaviour, especially when individuals are not aware of emotive stimulation. Study III has the aim to gather a direct psychophysiological evidence, both in healthy and neurologically impaired individuals, that emotions are crucially involved in shaping moral judgment, by preventing moral violations. Study IV explores how the moral meaning of a decision and its subsequent action can modulate the basic component of action such as sense of agency.

Resa diagnostica di anamnesi, EEG intercritico ed home-made video negli episodi parossistici notturni: confronto con la VEPSG

Poiché la diagnosi differenziale degli episodi parossistici notturni è affidata alla VEPSG, tenendo conto dei limiti di tale metodica, il progetto attuale ha lo scopo di definire la resa diagnostica di strumenti alternativi alla VEPSG: anamnesi, home-made video ed EEG intercritico. Sono stati reclutati consecutivamente 13 pazienti, afferiti al nostro Dipartimento per episodi parossistici notturni. Ciascun paziente è stato sottoposto ad un protocollo diagnostico standardizzato. A 5 Medici Esperti in Epilessia e Medicina del Sonno è stato chiesto di formulare un orientamento diagnostico sulla base di anamnesi, EEG intercritico, home-made video e VEPSG. Attraverso l’elaborazione degli orientamenti diagnostici è stata calcolata la resa diagnostica delle procedure esaminate, a confronto con la VEPSG, attraverso il concetto di “accuratezza diagnostica”. Per 6 pazienti è stato possibile porre una diagnosi di Epilessia Frontale Notturna, per 2 di parasonnia, in 5 la diagnosi è rimasta dubbia. L’accuratezza diagnostica di ciascuna procedura è risultata moderata, con lievi differenze tra le diverse procedure (61.5% anamnesi; 66% home-made video; 69,2 % EEG intercritico). E’ essenziale migliorare ulteriormente l’accuratezza diagnostica di anamnesi, EEG intercritico ed home-made video, che possono risultare cruciali nei casi in cui la diagnosi non è certa o quando la VEPSG non è disponibile.

Studio neuroradiologico (morfologico e funzionale) nei pazienti con Epilessia Frontale Notturna

L'epilessia frontale notturna (EFN) è caratterizzata da crisi motorie che insorgono durante il sonno. Scopo del progetto è studiare le cause fisiopatologiche e morfo-funzionali che sottendono ai fenomeni motori nei pazienti con EFN e identificare alterazioni strutturali e/o metaboliche mediante tecniche avanzate di Risonanza Magnetica (RM). Abbiamo raccolto una casistica di pazienti con EFN afferenti al Centro Epilessia e dei Disturbi del Sonno del Dipartimento di Scienze Neurologiche, Università di Bologna. Ad ogni paziente è stato associato un controllo sano di età (± 5 anni) e sesso corrispondente. Tutti sono stati studiati mediante tecniche avanzate di RM comprendenti Spettroscopia del protone (1H-MRS), Tensore di diffusione ed imaging 3D ad alta risoluzione per analisi morfometriche. In particolare, la 1H-MRS è stata effettuata su due volumi di interesse localizzati nei talami e nel giro del cingolo anteriore. Sono stati inclusi nell’analisi finale 19 pazienti (7 M), età media 34 anni (range 19-50) e 14 controlli (6 M) età media 30 anni (range 19-40). A livello del cingolo anteriore il rapporto della concentrazione di N-Acetil-Aspartato rispetto alla Creatina (NAA/Cr) è risultato significativamente ridotto nei pazienti rispetto ai controlli (p=0,021). Relativamente all’analisi di correlazione, l'analisi tramite modelli di regressione multipla ha evidenziato che il rapporto NAA/Cr nel cingolo anteriore nei pazienti correlava con la frequenza delle crisi (p=0,048), essendo minore nei pazienti con crisi plurisettimanali/plurigiornaliere. Per interpretare il dato ottenuto è possibile solo fare delle ipotesi. L’NAA è un marker di integrità, densità e funzionalità neuronale. E’ possibile che alla base della EFN ci siano alterazioni metaboliche tessutali in precise strutture come il giro del cingolo anteriore. Questo apre nuove possibilità sull’utilizzo di strumenti di indagine basati sull’analisi di biosegnali, per caratterizzare aree coinvolte nella genesi della EFN ancora largamente sconosciute e chiarire ulteriormente l’eziologia di questo tipo di epilessia.

When that tune runs through your head: A PET investigation of auditory imagery for familiar melodies

The present study used positron emission tomography (PET) to examine the cerebral activity pattern associated with auditory imagery forfamiliar tunes. Subjects either imagined the continuation of nonverbaltunes cued by their first few notes, listened to a short sequence of notesas a control task, or listened and then reimagined that short sequence. Subtraction of the activation in the control task from that in the real-tune imagery task revealed primarily right-sided activation in frontal and superior temporal regions, plus supplementary motor area(SMA). Isolating retrieval of the real tunes by subtracting activation in the reimagine task from that in the real-tune imagery task revealedactivation primarily in right frontal areas and right superior temporal gyrus. Subtraction of activation in the control condition from that in the reimagine condition, intended to capture imagery of unfamiliarsequences, revealed activation in SMA, plus some left frontal regions. We conclude that areas of right auditory association cortex, together with right and left frontal cortices, are implicated in imagery for familiartunes, in accord with previous behavioral, lesion and PET data. Retrieval from musical semantic memory is mediated by structures in the right frontal lobe, in contrast to results from previous studies implicating left frontal areas for all semantic retrieval. The SMA seems to be involved specifically in image generation, implicating a motor code in this process.

When that tune runs through your head: a PET investigation of auditory imagery for familiar melodies

The present study used positron emission tomography (PET) to examine the cerebral activity pattern associated with auditory imagery for familiar tunes. Subjects either imagined the continuation of nonverbal tunes cued by their first few notes, listened to a short sequence of notes as a control task, or listened and then reimagined that short sequence. Subtraction of the activation in the control task from that in the real-tune imagery task revealed primarily right-sided activation in frontal and superior temporal regions, plus supplementary motor area (SMA). Isolating retrieval of the real tunes by subtracting activation in the reimagine task from that in the real-tune imagery task revealed activation primarily in right frontal areas and right superior temporal gyrus. Subtraction of activation in the control condition from that in the reimagine condition, intended to capture imagery of unfamiliar sequences, revealed activation in SMA, plus some left frontal regions. We conclude that areas of right auditory association cortex, together with right and left frontal cortices, are implicated in imagery for familiar tunes, in accord with previous behavioral, lesion and PET data. Retrieval from musical semantic memory is mediated by structures in the right frontal lobe, in contrast to results from previous studies implicating left frontal areas for all semantic retrieval. The SMA seems to be involved specifically in image generation, implicating a motor code in this process.

Outer skull landmark-based coordinates for measurement of cerebral blood flow and intracranial pressure in rabbits

Despite the increased use of intracranial neuromonitoring during experimental subarachnoid hemorrhage (SAH), coordinates for probe placement in rabbits are lacking. This study evaluates the safety and reliability of using outer skull landmarks to identify locations for placement of cerebral blood flow (CBF) and intraparenchymal intracranial pressure (ICP) probes. Experimental SAH was performed in 17 rabbits using an extracranial-intracranial shunt model. ICP probes were placed in the frontal lobe and compared to measurements recorded from the olfactory bulb. CBF probes were placed in various locations in the frontal cortex anterior to the coronary suture. Insertion depth, relation to the ventricular system, and ideal placement location were determined by post-mortem examination. ICP recordings at the time of SAH from the frontal lobe did not differ significantly from those obtained from the right olfactory bulb. Ideal coordinates for intraparenchymal CBF probes in the left and right frontal lobe were found to be located 4.6±0.9 and 4.5±1.2 anterior to the bregma, 4.7±0.7mm and 4.7±0.5mm parasagittal, and at depths of 4±0.5mm and 3.9±0.5mm, respectively. The results demonstrate that the presented coordinates based on skull landmarks allow reliable placement of intraparenchymal ICP and CBF probes in rabbit brains without the use of a stereotactic frame.

Stimulus-induced, sleep-bound, focal seizures: a case report

In nocturnal frontal lobe epilepsy (NFLE), seizures occur almost exclusively during NREM sleep. Why precisely these seizures are sleep-bound remains unknown. Studies of patients with nonlesional familial forms of NFLE have suggested the arousal system may play a major role in their pathogenesis. We report the case of a patient with pharmaco-resistant, probably cryptogenic form of non-familial NFLE and strictly sleep-bound seizures that could be elicited by alerting stimuli and were associated with ictal bilateral thalamic and right orbital-insular hyperperfusion on SPECT imaging.

Epileptogenic developmental venous anomaly: insights from simultaneous EEG/fMRI

Developmental venous anomalies (DVAs) are associated with epileptic seizures; however, the role of DVA in the epileptogenesis is still not established. Simultaneous interictal electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) recordings provide supplementary information to electroclinical data about the epileptic generators, and thus aid in the differentiation of clinically equivocal epilepsy syndromes. The main objective of our study was to characterize the epileptic network in a patient with DVA and epilepsy by simultaneous EEG/fMRI recordings. A 17-year-old woman with recently emerging generalized tonic-clonic seizures, and atypical generalized discharges, was investigated using simultaneous EEG/fMRI at the university hospital. Previous high-resolution MRI showed no structural abnormalities, except a DVA in the right frontal operculum. Interictal EEG recordings showed atypical generalized discharges, corresponding to positive focal blood oxygen level dependent (BOLD) correlates in the right frontal operculum, a region drained by the DVA. Additionally, widespread cortical bilateral negative BOLD correlates in the frontal and parietal lobes were delineated, resembling a generalized epileptic network. The EEG/fMRI recordings support a right frontal lobe epilepsy, originating in the vicinity of the DVA, propagating rapidly to both frontal and parietal lobes, as expressed on the scalp EEG by secondary bilateral synchrony. The DVA may be causative of focal epilepsies in cases where no concomitant epileptogenic lesions can be detected. Advanced imaging techniques, such as simultaneous EEG/fMRI, may thus aid in the differentiation of clinically equivocal epilepsy syndromes.

Nontraumatic intracranial epidural hematoma: a case report

An outwardly mummified and inwardly badly decomposed body was found in a garage. At autopsy, no injuries were detected. Apart from coronary heart disease, with an old myocardial scar and a hepatic steatosis, the most striking finding was a large intracranial epidural hemorrhage situated at the left frontal lobe. As a relevant traumatic genesis could be ruled out, we deemed this a nontraumatic epidural hematoma. This finding is extremely rare. Several underlying disorders have been discussed as causes of spontaneous epidural hematomas. In this presented case, the authors discuss possible etiological factors.

Focal laminar cortical infarcts following aneurysmal subarachnoid haemorrhage

INTRODUCTION: The aim of this prospective study was to analyse small band-like cortical infarcts after subarachnoid haemorrhage (SAH) using magnetic resonance imaging (MRI) with reference to additional digital subtraction angiography (DSA). METHODS: In a 5-year period between January 2002 and January 2007 10 out of 188 patients with aneurysmal SAH were evaluated (one patient Hunt and Hess grade I, one patient grade II, four patients grade III, two patients grade IV, and two patients grade V). The imaging protocol included serially performed MRI with diffusion- and perfusion-weighted images (DWI/PWI) at three time points after aneurysm treatment, and cerebral vasospasm (CVS) was analysed on follow-up DSA on day 7+/-3 after SAH. RESULTS: The lesions were located in the frontal lobe (n=10), in the insular cortex (n=3) and in the parietal lobe (n=1). The band-like infarcts occurred after a mean time interval of 5.8 days (range 3-10 days) and showed unexceptional adjacent thick sulcal clots. Seven out of ten patients with cortical infarcts had no or mild CVS, and in the remaining three patients DSA disclosed moderate (n=2) or severe (n=1) CVS. CONCLUSION: The infarct pattern after aneurysmal SAH includes cortical band-like lesions. In contrast to territorial infarcts or lacunar infarcts in the white matter which develop as a result of moderate or severe proximal and/or distal vasospasm visible on angiography, the cortical band-like lesions adjacent to sulcal clots may also develop without evidence of macroscopic vasospasm, implying a vasospastic reaction of the most distal superficial and intraparenchymal vessels.