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1.  Studying Memory Encoding to Promote Reliable Engagement of the Medial Temporal Lobe at the Single-Subject Level 
PLoS ONE  2015;10(3):e0119159.
The medial temporal lobe (MTL)—comprising hippocampus and the surrounding neocortical regions—is a targeted brain area sensitive to several neurological diseases. Although functional magnetic resonance imaging (fMRI) has been widely used to assess brain functional abnormalities, detecting MTL activation has been technically challenging. The aim of our study was to provide an fMRI paradigm that reliably activates MTL regions at the individual level, thus providing a useful tool for future research in clinical memory-related studies. Twenty young healthy adults underwent an event-related fMRI study consisting of three encoding conditions: word-pairs, face-name associations and complex visual scenes. A region-of-interest analysis at the individual level comparing novel and repeated stimuli independently for each task was performed. The results of this analysis yielded activations in the hippocampal and parahippocampal regions in most of the participants. Specifically, 95% and 100% of participants showed significant activations in the left hippocampus during the face-name encoding and in the right parahippocampus, respectively, during scene encoding. Additionally, a whole brain analysis, also comparing novel versus repeated stimuli at the group level, showed mainly left frontal activation during the word task. In this group analysis, the face-name association engaged the HP and fusiform gyri bilaterally, along with the left inferior frontal gyrus, and the complex visual scenes activated mainly the parahippocampus and hippocampus bilaterally. In sum, our task design represents a rapid and reliable manner to study and explore MTL activity at the individual level, thus providing a useful tool for future research in clinical memory-related fMRI studies.
PMCID: PMC4372361  PMID: 25803273
2.  Atypical language organization in temporal lobe epilepsy revealed by a passive semantic paradigm 
BMC Neurology  2014;14:98.
Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adults and can be successfully cured by surgery. One of the main complications of this surgery however is a decline in language abilities. The magnitude of this decline is related to the degree of language lateralization to the left hemisphere. Most fMRI paradigms used to determine language dominance in epileptic populations have used active language tasks. Sometimes, these paradigms are too complex and may result in patient underperformance. Only a few studies have used purely passive tasks, such as listening to standard speech.
In the present study we characterized language lateralization in patients with MTLE using a rapid and passive semantic language task. We used functional magnetic resonance imaging (fMRI) to study 23 patients [12 with Left (LMTLE), 11 with Right mesial temporal lobe epilepsy (RMTLE)] and 19 healthy right-handed controls using a 6 minute long semantic task in which subjects passively listened to groups of sentences (SEN) and pseudo sentences (PSEN). A lateralization index (LI) was computed using a priori regions of interest of the temporal lobe.
The LI for the significant contrasts produced activations for all participants in both temporal lobes. 81.8% of RMTLE patients and 79% of healthy individuals had a bilateral language representation for this particular task. However, 50% of LMTLE patients presented an atypical right hemispheric dominance in the LI. More importantly, the degree of right lateralization in LMTLE patients was correlated with the age of epilepsy onset.
The simple, rapid, non-collaboration dependent, passive task described in this study, produces a robust activation in the temporal lobe in both patients and controls and is capable of illustrating a pattern of atypical language organization for LMTLE patients. Furthermore, we observed that the atypical right-lateralization patterns in LMTLE patients was associated to earlier age at epilepsy onset. These results are in line with the idea that early onset of epileptic activity is associated to larger neuroplastic changes.
PMCID: PMC4017227  PMID: 24885511
Hippocampal sclerosis; Epilepsy surgery; Functional neuroimaging; Plasticity; Aphasia
3.  Linking motor-related brain potentials and velocity profiles in multi-joint arm reaching movements 
The study of the movement related brain potentials (MRPBs) needs accurate technical approaches to disentangle the specific patterns of bran activity during the preparation and execution of movements. During the last forty years, synchronizing the electromyographic activation (EMG) of the muscle with electrophysiological recordings (EEG) has been commonly ussed for these purposes. However, new clinical approaches in the study of motor diseases and rehabilitation suggest the demand of new paradigms that might go further into the study of the brain activity associated with the kinematics of movements. As a response to this call, we have used a 3-D hand-tracking system with the aim to record continuously the position of an ultrasonic sender attached to the hand during the performance of multi-joint self-paced movements. We synchronized time-series of position and velocity of the sender with the EEG recordings, obtaining specific patterns of brain activity as a function of the fluctuations of the kinematics during natural movement performance. Additionally, the distribution of the brain activity during the preparation and execution phases of movements was similar that reported previously using the EMG, suggesting the validity of our technique. We claim that this paradigm could be usable in patients because of its simplicity and the potential knowledge that can be extracted from clinical protocols.
PMCID: PMC4010756  PMID: 24808853
motor related brain potentials; 3-D movement analyser; time-series analysis; kinematics; self-paced movement; motor activity
4.  Structural Changes Induced by Daily Music Listening in the Recovering Brain after Middle Cerebral Artery Stroke: A Voxel-Based Morphometry Study 
Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve cognitive recovery and improve mood after an acute middle cerebral artery stroke. Extending this study, a voxel-based morphometry (VBM) analysis utilizing cost function masking was performed on the acute and 6-month post-stroke stage structural magnetic resonance imaging data of the patients (n = 49) who either listened to their favorite music [music group (MG), n = 16] or verbal material [audio book group (ABG), n = 18] or did not receive any listening material [control group (CG), n = 15] during the 6-month recovery period. Although all groups showed significant gray matter volume (GMV) increases from the acute to the 6-month stage, there was a specific network of frontal areas [left and right superior frontal gyrus (SFG), right medial SFG] and limbic areas [left ventral/subgenual anterior cingulate cortex (SACC) and right ventral striatum (VS)] in patients with left hemisphere damage in which the GMV increases were larger in the MG than in the ABG and in the CG. Moreover, the GM reorganization in the frontal areas correlated with enhanced recovery of verbal memory, focused attention, and language skills, whereas the GM reorganization in the SACC correlated with reduced negative mood. This study adds on previous results, showing that music listening after stroke not only enhances behavioral recovery, but also induces fine-grained neuroanatomical changes in the recovering brain.
PMCID: PMC4029020  PMID: 24860466
music; speech; stroke; magnetic resonance imaging; voxel-based morphometry; environmental enrichment; neuroplasticity; rehabilitation
5.  Sensorimotor Plasticity after Music-Supported Therapy in Chronic Stroke Patients Revealed by Transcranial Magnetic Stimulation 
PLoS ONE  2013;8(4):e61883.
Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention.
Methods and Results
In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance.
Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.
PMCID: PMC3629163  PMID: 23613966
6.  Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study 
Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician's brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy.
PMCID: PMC3759754  PMID: 24027507
stroke; music-supported therapy; music; plasticity; transcranial magnetic stimulation
7.  Prognostic value of cortically induced motor evoked activity by TMS in chronic stroke: Caveats from a revealing single clinical case 
BMC Neurology  2012;12:35.
We report the case of a chronic stroke patient (62 months after injury) showing total absence of motor activity evoked by transcranial magnetic stimulation (TMS) of spared regions of the left motor cortex, but near-to-complete recovery of motor abilities in the affected hand.
Case presentation
Multimodal investigations included detailed TMS based motor mapping, motor evoked potentials (MEP), and Cortical Silent period (CSP) as well as functional magnetic resonance imaging (fMRI) of motor activity, MRI based lesion analysis and Diffusion Tensor Imaging (DTI) Tractography of corticospinal tract (CST). Anatomical analysis revealed a left hemisphere subinsular lesion interrupting the descending left CST at the level of the internal capsule. The absence of MEPs after intense TMS pulses to the ipsilesional M1, and the reversible suppression of ongoing electromyographic (EMG) activity (indexed by CSP) demonstrate a weak modulation of subcortical systems by the ipsilesional left frontal cortex, but an inability to induce efficient descending volleys from those cortical locations to right hand and forearm muscles. Functional MRI recordings under grasping and finger tapping patterns involving the affected hand showed slight signs of subcortical recruitment, as compared to the unaffected hand and hemisphere, as well as the expected cortical activations.
The potential sources of motor voluntary activity for the affected hand in absence of MEPs are discussed. We conclude that multimodal analysis may contribute to a more accurate prognosis of stroke patients.
PMCID: PMC3411427  PMID: 22682434
8.  Neurophysiological mechanisms involved in language learning in adults 
Little is known about the brain mechanisms involved in word learning during infancy and in second language acquisition and about the way these new words become stable representations that sustain language processing. In several studies we have adopted the human simulation perspective, studying the effects of brain-lesions and combining different neuroimaging techniques such as event-related potentials and functional magnetic resonance imaging in order to examine the language learning (LL) process. In the present article, we review this evidence focusing on how different brain signatures relate to (i) the extraction of words from speech, (ii) the discovery of their embedded grammatical structure, and (iii) how meaning derived from verbal contexts can inform us about the cognitive mechanisms underlying the learning process. We compile these findings and frame them into an integrative neurophysiological model that tries to delineate the major neural networks that might be involved in the initial stages of LL. Finally, we propose that LL simulations can help us to understand natural language processing and how the recovery from language disorders in infants and adults can be accomplished.
PMCID: PMC2846313  PMID: 19933142
language learning; speech segmentation; contextual learning; functional connectivity; ERPs; fMRI
9.  Beneficial effects of word final stress in segmenting a new language: evidence from ERPs 
BMC Neuroscience  2008;9:23.
How do listeners manage to recognize words in an unfamiliar language? The physical continuity of the signal, in which real silent pauses between words are lacking, makes it a difficult task. However, there are multiple cues that can be exploited to localize word boundaries and to segment the acoustic signal. In the present study, word-stress was manipulated with statistical information and placed in different syllables within trisyllabic nonsense words to explore the result of the combination of the cues in an online word segmentation task.
The behavioral results showed that words were segmented better when stress was placed on the final syllables than when it was placed on the middle or first syllable. The electrophysiological results showed an increase in the amplitude of the P2 component, which seemed to be sensitive to word-stress and its location within words.
The results demonstrated that listeners can integrate specific prosodic and distributional cues when segmenting speech. An ERP component related to word-stress cues was identified: stressed syllables elicited larger amplitudes in the P2 component than unstressed ones.
PMCID: PMC2263048  PMID: 18282274

Results 1-9 (9)