Characterization of antiseizure medications effects on the EEG neurodynamic by fractal dimension.

Objectives: An important challenge in epilepsy is to define biomarkers of response to treatment. Many electroencephalography (EEG) methods and indices have been developed mainly using linear methods, e.g., spectral power and individual alpha frequency peak (IAF). However, brain activity is complex and non-linear, hence there is a need to explore EEG neurodynamics using nonlinear approaches. Here, we use the Fractal Dimension (FD), a measure of whole brain signal complexity, to measure the response to anti-seizure therapy in patients with Focal Epilepsy (FE) and compare it with linear methods. Materials: Twenty-five drug-responder (DR) patients with focal epilepsy were studied before (t1, named DR-t1) and after (t2, named DR-t2) the introduction of the anti-seizure medications (ASMs). DR-t1 and DR-t2 EEG results were compared against 40 age-matched healthy controls (HC). Methods: EEG data were investigated from two different angles: frequency domain-spectral properties in δ, θ, α, ß, and γ bands and the IAF peak, and time-domain-FD as a signature of the nonlinear complexity of the EEG signals. Those features were compared among the three groups. Results: The δ power differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p < 0.01 and DR-t2 vs. HC, p < 0.01). The θ power differed between DR-t1 and DR-t2 (p = 0.015) and between DR-t1 and HC (p = 0.01). The α power, similar to the δ, differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p < 0.01 and DR-t2 vs. HC, p < 0.01). The IAF value was lower for DR-t1 than DR-t2 (p = 0.048) and HC (p = 0.042). The FD value was lower in DR-t1 than in DR-t2 (p = 0.015) and HC (p = 0.011). Finally, Bayes Factor analysis showed that FD was 195 times more likely to separate DR-t1 from DR-t2 than IAF and 231 times than θ. Discussion: FD measured in baseline EEG signals is a non-linear brain measure of complexity more sensitive than EEG power or IAF in detecting a response to ASMs. This likely reflects the non-oscillatory nature of neural activity, which FD better describes. Conclusion: Our work suggests that FD is a promising measure to monitor the response to ASMs in FE.

Deep brain stimulation of globus pallidus internus and subthalamic nucleus in Parkinson's disease: a multicenter, retrospective study of efficacy and safety.

BACKGROUND: Deep brain stimulation (DBS) is an established therapeutic option in advanced Parkinson's disease (PD). Literature data and recent guidelines remain inconclusive about the best choice as a target between the subthalamic nucleus (STN) and the globus pallidus internus (GPi). MATERIALS AND METHODS: We retrospectively reviewed the clinical efficacy outcomes of 48 DBS-implanted patients (33 STN-DBS and 15 GPi-DBS) at a short- (<1 year from the surgery) and long-term (2-5 years) follow-up. Also, clinical safety outcomes, including postoperative surgical complications and severe side effects, were collected. RESULTS: We found no difference between STN-DBS and GPi-DBS in improving motor symptoms at short-term evaluation. However, STN-DBS achieved a more prominent reduction in oral therapy (L-DOPA equivalent daily dose, P = .02). By contrast, GPi-DBS was superior in ameliorating motor fluctuations and dyskinesia (MDS-UPDRS IV, P < .001) as well as motor experiences of daily living (MDS-UPDRS II, P = .03). The greater efficacy of GPi-DBS on motor fluctuations and experiences of daily living was also present at the long-term follow-up. We observed five serious adverse events, including two suicides, all among STN-DBS patients. CONCLUSION: Both STN-DBS and GPi-DBS are effective in improving motor symptoms severity and complications, but GPi-DBS has a greater impact on motor fluctuations and motor experiences of daily living. These results suggest that the two targets should be considered equivalent in motor efficacy, with GPi-DBS as a valuable option in patients with prominent motor complications. The occurrence of suicides in STN-treated patients claims further attention in target selection.

Poor reactivity of posterior electroencephalographic alpha rhythms during the eyes open condition in patients with dementia due to Parkinson's disease.

Here, we hypothesized that the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms during the transition from eyes-closed to -open condition might be lower in patients with Parkinson's disease dementia (PDD) than in patients with Alzheimer's disease dementia (ADD). A Eurasian database provided clinical-demographic-rsEEG datasets in 73 PDD patients, 35 ADD patients, and 25 matched cognitively unimpaired (Healthy) persons. The eLORETA freeware was used to estimate cortical rsEEG sources. Results showed substantial (greater than -10%) reduction (reactivity) in the posterior alpha source activities from the eyes-closed to the eyes-open condition in 88% of the Healthy seniors, 57% of the ADD patients, and only 35% of the PDD patients. In these alpha-reactive participants, there was lower reactivity in the parietal alpha source activities in the PDD group than in the healthy control seniors and the ADD patients. These results suggest that PDD patients show poor reactivity of mechanisms desynchronizing posterior rsEEG alpha rhythms in response to visual inputs. That neurophysiological biomarker may provide an endpoint for (non) pharmacological interventions for improving vigilance regulation in those patients.

Cortical thickness is inversely associated with transcranial magnetic stimulation-evoked N45 potential among young adults whose heavy drinking began in adolescence.

BACKGROUND: Adolescence is a particularly vulnerable stage of development in terms of the deleterious effects of alcohol. Both lower gray matter (GM) volume and greater GABAergic activity have been associated with chronic alcohol consumption during adolescence. However, the association between these measures has not been investigated. METHODS: In this exploratory study, we compared 26 young adults with a 10year history of heavy alcohol consumption with 21 controls who used little or no alcohol. Simultaneous transcranial magnetic stimulation and electroencephalography were used to assess transcranial magnetic stimulation-evoked N45 potentials, reflecting a balance between GABAergic inhibition and N-methyl-D-aspartate (NMDA) receptor-mediated glutaminergic excitation in the brain. GM thickness was measured from magnetic resonance images and GM and N45 potentials were then correlated. RESULTS: Cortical thickness was significantly lower in several brain regions in the heavy-drinking group than the light-drinking group. The N45 amplitude was significantly larger frontally in the heavy-drinking group. Among heavy drinkers, there were several statistically significant correlations between thinner GM and larger frontal N45 amplitudes that were not detectable in the light-drinking group. The strongest correlations were detected in the frontal and parietal lobes, especially in the left superior frontal gyrus and the left supramarginal gyrus, and in both hemispheres in the superior parietal lobes. CONCLUSIONS: These findings show that a thinner cortex and greater inhibitory neurotransmission are correlated in certain brain regions among young, long-term heavy alcohol users. Studies are needed to explore the possible causal mechanisms underlying these effects.

Objective measurement versus clinician-based assessment for Parkinson's disease.

INTRODUCTION: Although clinician-based assessment through standardized clinical rating scales is currently the gold standard for quantifying motor impairment in Parkinson's disease (PD), it is not without limitations, including intra- and inter-rater variability and a degree of approximation. There is increasing evidence supporting the use of objective motion analyses to complement clinician-based assessment. Objective measurement tools hold significant potential for improving the accuracy of clinical and research-based evaluations of patients. AREAS COVERED: The authors provide several examples from the literature demonstrating how different motion measurement tools, including optoelectronics, contactless and wearable systems allow for both the objective quantification and monitoring of key motor symptoms (such as bradykinesia, rigidity, tremor, and gait disturbances), and the identification of motor fluctuations in PD patients. Furthermore, they discuss how, from a clinician's perspective, objective measurements can help in various stages of PD management. EXPERT OPINION: In our opinion, sufficient evidence supports the assertion that objective monitoring systems enable accurate evaluation of motor symptoms and complications in PD. A range of devices can be utilized not only to support diagnosis but also to monitor motor symptom during the disease progression and can become relevant in the therapeutic decision-making process.

Reduced connectivity of primary auditory and motor cortices during exposure to auditory white noise.

Auditory white noise (WN) is widely used in daily life for inducing sleep, and in neuroscience to mask unwanted environmental noise and cues. However, WN was recently reported to influence corticospinal excitability and behavioral performance. Here, we expand previous preliminary findings on the influence of WN exposure on cortical functioning, and we hypothesize that it may modulate cortical connectivity. We tested our hypothesis by performing magnetoencephalography in 20 healthy subjects. WN reduces cortical connectivity of the primary auditory and motor regions with very distant cortical areas, showing a right lateralized connectivity reduction for primary motor cortex. The present results, together with previous finding concerning WN impact on corticospinal excitability and behavioral performance, further support the role of WN as a modulator of cortical function. This suggest avoiding its unrestricted use as a masking tool, while purposely designed and controlled WN application could be exploited to harness brain function and to treat neuropsychiatric conditions.

Navigated Transcranial Magnetic Stimulation Motor Mapping and Diffusion Tensor Imaging Tractography for Diencephalic Tumor in Pediatric Patients.

Background. In deep-seated brain tumors, adequate preoperative planning is mandatory to assess the best surgical corridor to obtain maximal safe resection. Functional diffusor tensor imaging (DTI) tractography based on navigated transcranial magnetic stimulation (nTMS) motor mapping has proven to be a valid preoperative examination method in adults. The aim of this paper is to present the application of nTMS and functional DTI tractography in a series of pediatric diencephalic tumors. Material and methods. Three patients affected by thalamic (one) and thalamopeduncular tumor (two) were successfully examined with nTMS motor mapping and DTI tractography between October 2020 and October 2021 (F:M 3:0, mean age 12 years ± 0.8). Cortical representation of leg, hand and mouth were determined in the affected hemisphere and the positive stimulation spots were set as seeds point for tractography. Results. Mapping of the motor cortex and tracts reconstruction for leg and hand were successful in all patients, while facial function was properly mapped in one patient only. In all cases, the procedure was well tolerated and no adverse events were recorded. Spatial relationships between tumor and functional tissue guided the surgical planning. Extent of the resection varied from 96.1% to 100% with a postoperative new motor deficit in one patient. Conclusions. nTMS and DTI fiber tracking is a feasible, effective and well-tolerated method to identify motor pathway in deep-seated lesion in pediatric population.

Selective Stimulus Intensity during Hotspot Search Ensures Faster and More Accurate Preoperative Motor Mapping with nTMS.

INTRODUCTION: Navigated transcranial magnetic stimulation (nTMS) has emerged as one of the most innovative techniques in neurosurgical practice. However, nTMS motor mapping involves rigorous steps, and the importance of an accurate execution method has not been emphasized enough. In particular, despite strict adherence to procedural protocols, we have observed high variability in map activation according to the choice of stimulation intensity (SI) right from the early stage of hotspot localization. We present a retrospective analysis of motor mappings performed between March 2020 and July 2022, where the SI was only chosen with rigorous care in the most recent ones, under the guide of an expert neurophysiologist. MATERIALS AND METHODS: In order to test the ability to reduce inaccurate responses and time expenditure using selective SI, data were collected from 16 patients who underwent mapping with the random method (group A) and 15 patients who underwent mapping with the proposed method (group B). The parameters considered were resting motor threshold (%), number of stimuli, number of valid motor evoked potentials (MEPs), number of valid MEPs considered true positives (TPs), number of valid MEPs considered false positives (FPs), ratio of true-positive MEPs to total stimuli, ratio of true-positive MEPs to valid MEPs, minimum amplitude, maximum amplitude and mapping time for each patient. RESULTS: The analysis showed statistically significant reductions in total stimulus demand, procedural time and number of false-positive MEPs. Significant increases were observed in the number of true-positive MEPs, the ratio of true-positive MEPs to total stimuli and the ratio of true-positive MEPs to valid MEPs. In the subgroups analyzed, there were similar trends, in particular, an increase in true positives and a decrease in false-positive responses. CONCLUSIONS: The precise selection of SI during hotspot search in nTMS motor mapping could provide reliable cortical maps in short time and with low employment of resources. This method seems to ensure that a MEP really represents a functionally eloquent cortical point, making mapping more intuitive even in less experienced centers.

Combining Transcranial Magnetic Stimulation and Deep Brain Stimulation: Current Knowledge, Relevance and Future Perspectives.

Deep brain stimulation (DBS) has emerged as an invasive neuromodulation technique for the treatment of several neurological disorders, but the mechanisms underlying its effects remain partially elusive. In this context, the application of Transcranial Magnetic Stimulation (TMS) in patients treated with DBS represents an intriguing approach to investigate the neurophysiology of cortico-basal networks. Experimental studies combining TMS and DBS that have been performed so far have mainly aimed to evaluate the effects of DBS on the cerebral cortex and thus to provide insights into DBS's mechanisms of action. The modulation of cortical excitability and plasticity by DBS is emerging as a potential contributor to its therapeutic effects. Moreover, pairing DBS and TMS stimuli could represent a method to induce cortical synaptic plasticity, the therapeutic potential of which is still unexplored. Furthermore, the advent of new DBS technologies and novel treatment targets will present new research opportunities and prospects to investigate brain networks. However, the application of the combined TMS-DBS approach is currently limited by safety concerns. In this review, we sought to present an overview of studies performed by combining TMS and DBS in neurological disorders, as well as available evidence and recommendations on the safety of their combination. Additionally, we outline perspectives for future research by highlighting knowledge gaps and possible novel applications of this approach.

Clinical, cognitive, and morphometric profiles of progressive supranuclear palsy phenotypes.

The International Parkinson's and Movement Disorder Society (MDS) criteria for progressive supranuclear palsy (PSP) have broadened the clinical spectrum of the disease and established phenotypic characterization according to the predominant manifestation at onset. The objective of this study is to describe clinical/cognitive and imaging features of a monocentric cohort of PSP patients, highlighting different patterns of functional disability according to the assigned phenotype. We retrospectively reviewed clinical/imaging data of 53 PSP patients diagnosed with probable PSP according to the MDS criteria and 40 age/sex-matched healthy controls (HCs). Neurological/neuropsychological assessments were performed using standardized scales, as well as comprehensive magnetic resonance imaging (MRI) morphometric measurements. In our cohort, there were 24/53 PSP-RS (Richardson's syndrome), 13/53 PSP-P (Parkinsonism), 7/53 PSP-PGF (Progressive gait freezing), and 9/53 PSP-Cog (Cognitive impairment). PSP-Cog presented the worst motor profiles, the highest percentages of dementia and impaired functional autonomy; 4/9 PSP-Cog and 2/7 PSP-PGF died. PSP-P had the lowest motor/cognitive burden. All MRI parameters had good discriminative efficacy vs. HCs, with P/M 2.0 discriminating PSP-PGF from PSP-RS and PSP-Cog. We highlighted discrete clinical and imaging patterns that best characterize different PSP phenotypes. PSP-Cog and PSP-PGF/RS manifest greater incidence of dementia and motor disability, respectively, while PSP-P has a more benign course. The identification of different phenotypes may be the expression of different progression patterns requiring tailored approaches in terms of follow-up and treatment. These findings support the concept of discrete patterns of Tau pathology within the PSP spectrum and encourage research for phenotype-specific outcome measures.

Assessing the interaction between L-dopa and γ-transcranial alternating current stimulation effects on primary motor cortex plasticity in Parkinson's disease.

L-dopa variably influences transcranial magnetic stimulation (TMS) parameters of motor cortex (M1) excitability and plasticity in Parkinson's disease (PD). In patients OFF dopaminergic medication, impaired M1 plasticity and defective GABA-A-ergic inhibition can be restored by boosting gamma (γ) oscillations via transcranial alternating current stimulation (tACS) during intermittent theta-burst stimulation (iTBS). However, it is unknown whether L-dopa modifies the beneficial effects of iTBS-γ-tACS on M1 in PD. In this study, a PD patients group underwent combined iTBS-γ-tACS and iTBS-sham-tACS, each performed both OFF and ON dopaminergic therapy (four sessions in total). Motor evoked potentials (MEPs) elicited by single TMS pulses and short-interval intracortical inhibition (SICI) were assessed before and after iTBS-tACS. We also evaluated possible SICI changes during γ-tACS delivered alone in OFF and ON conditions. The amplitude of MEP elicited by single TMS pulses and the degree of SICI inhibition significantly increased after iTBS-γ-tACS. The amount of change produced by iTBS-γ-tACS was similar in patients OFF and ON therapy. Finally, γ-tACS (delivered alone) modulated SICI during stimulation and this effect did not depend on the dopaminergic condition of patients. In conclusion, boosting cortical γ oscillatory activity via tACS during iTBS improved M1 plasticity and enhanced GABA-A-ergic transmission in PD patients to the same extent regardless of dopaminergic state. These results suggest a lack of interaction between L-dopa and γ-tACS effects at the M1 level. The possible neural substrate underlying iTBS-γ tACS effects, that is, γ-resonant GABA-A-ergic interneurons activity, may explain our findings.

Electroencephalographic hallmarks of Alzheimer's disease.

In the human brain, physiological aging is characterized by progressive neuronal loss, leading to disruption of synapses and to a degree of failure in neurotransmission and information flow. However, there is increasing evidence to support the notion that the aged brain has a remarkable level of resilience (i.s. ability to reorganize itself), with the aim of preserving its physiological activity. It is therefore of paramount interest to develop objective markers able to characterize the biological processes underlying brain aging in the intact human, and to distinguish them from brain degeneration associated to age-related neurological progressive diseases like Alzheimer's disease. EEG, alone and combined with transcranial magnetic stimulation (TMS-EEG), is particularly suited to this aim, due to the functional nature of the information provided, and thanks to the ease with which it can be integrated in ecological scenarios including behavioral tasks. In this review, we aimed to provide the reader with updated information about the role of modern methods of EEG and TMS-EEG analysis in the investigation of physiological brain aging and Alzheimer's disease. In particular, we focused on data about cortical connectivity obtained by using readouts such graph theory network brain organization and architecture, and transcranial evoked potentials (TEPs) during TMS-EEG. Overall, findings in the literature support an important potential contribution of such neurophysiological techniques to the understanding of the mechanisms underlying normal brain aging and the early (prodromal/pre-symptomatic) stages of dementia.

Non-invasive brain stimulation and neuroenhancement.

Attempts to enhance human memory and learning ability have a long tradition in science. This topic has recently gained substantial attention because of the increasing percentage of older individuals worldwide and the predicted rise of age-associated cognitive decline in brain functions. Transcranial brain stimulation methods, such as transcranial magnetic (TMS) and transcranial electric (tES) stimulation, have been extensively used in an effort to improve cognitive functions in humans. Here we summarize the available data on low-intensity tES for this purpose, in comparison to repetitive TMS and some pharmacological agents, such as caffeine and nicotine. There is no single area in the brain stimulation field in which only positive outcomes have been reported. For self-directed tES devices, how to restrict variability with regard to efficacy is an essential aspect of device design and function. As with any technique, reproducible outcomes depend on the equipment and how well this is matched to the experience and skill of the operator. For self-administered non-invasive brain stimulation, this requires device designs that rigorously incorporate human operator factors. The wide parameter space of non-invasive brain stimulation, including dose (e.g., duration, intensity (current density), number of repetitions), inclusion/exclusion (e.g., subject's age), and homeostatic effects, administration of tasks before and during stimulation, and, most importantly, placebo or nocebo effects, have to be taken into account. The outcomes of stimulation are expected to depend on these parameters and should be strictly controlled. The consensus among experts is that low-intensity tES is safe as long as tested and accepted protocols (including, for example, dose, inclusion/exclusion) are followed and devices are used which follow established engineering risk-management procedures. Devices and protocols that allow stimulation outside these parameters cannot claim to be "safe" where they are applying stimulation beyond that examined in published studies that also investigated potential side effects. Brain stimulation devices marketed for consumer use are distinct from medical devices because they do not make medical claims and are therefore not necessarily subject to the same level of regulation as medical devices (i.e., by government agencies tasked with regulating medical devices). Manufacturers must follow ethical and best practices in marketing tES stimulators, including not misleading users by referencing effects from human trials using devices and protocols not similar to theirs.

Action Selection and Motor Decision Making: Insights from Transcranial Magnetic Stimulation.

In everyday life, goal-oriented motor behaviour relies on the estimation of the rewards/costs associated with alternative actions and on the appropriate selection of movements. Motor decision making is defined as the process by which a motor plan is chosen among a set of competing actions based on the expected value. In the present literature review we discuss evidence from transcranial magnetic stimulation (TMS) studies of motor control. We focus primarily on studies of action selection for instructed movements and motor decision making. In the first section, we delve into the usefulness of various TMS paradigms to characterise the contribution of motor areas and distributed brain networks to cued action selection. Then, we address the influence of motivational information (e.g., reward and biomechanical cost) in guiding action choices based on TMS findings. Finally, we conclude that TMS represents a powerful tool for elucidating the neurophysiological mechanisms underlying action choices in humans.

Auditory driven gamma synchrony is associated with cortical thickness in widespread cortical areas.

OBJECTIVE: Gamma synchrony is a fundamental functional property of the cerebral cortex, impaired in multiple neuropsychiatric conditions (i.e. schizophrenia, Alzheimer's disease, stroke etc.). Auditory stimulation in the gamma range allows to drive gamma synchrony of the entire cortical mantle and to estimate the efficiency of the mechanisms sustaining it. As gamma synchrony depends strongly on the interplay between parvalbumin-positive interneurons and pyramidal neurons, we hypothesize an association between cortical thickness and gamma synchrony. To test this hypothesis, we employed a combined magnetoencephalography (MEG) - Magnetic Resonance Imaging (MRI) study. METHODS: Cortical thickness was estimated from anatomical MRI scans. MEG measurements related to exposure of 40 Hz amplitude modulated tones were projected onto the cortical surface. Two measures of cortical synchrony were considered: (a) inter-trial phase consistency at 40 Hz, providing a vertex-wise estimation of gamma synchronization, and (b) phase-locking values between primary auditory cortices and whole cortical mantle, providing a measure of long-range cortical synchrony. A correlation between cortical thickness and synchronization measures was then calculated for 72 MRI-MEG scans. RESULTS: Both inter-trial phase consistency and phase locking values showed a significant positive correlation with cortical thickness. For inter-trial phase consistency, clusters of strong associations were found in the temporal and frontal lobes, especially in the bilateral auditory and pre-motor cortices. Higher phase-locking values corresponded to higher cortical thickness in the frontal, temporal, occipital and parietal lobes. DISCUSSION AND CONCLUSIONS: In healthy subjects, a thicker cortex corresponds to higher gamma synchrony and connectivity in the primary auditory cortex and beyond, likely reflecting underlying cell density involved in gamma circuitries. This result hints towards an involvement of gamma synchrony together with underlying brain structure in brain areas for higher order cognitive functions. This study contributes to the understanding of inherent cortical functional and structural brain properties, which might in turn constitute the basis for the definition of useful biomarkers in patients showing aberrant gamma synchronization.

Brain Connectivity and Graph Theory Analysis in Alzheimer's and Parkinson's Disease: The Contribution of Electrophysiological Techniques.

In recent years, applications of the network science to electrophysiological data have increased as electrophysiological techniques are not only relatively low cost, largely available on the territory and non-invasive, but also potential tools for large population screening. One of the emergent methods for the study of functional connectivity in electrophysiological recordings is graph theory: it allows to describe the brain through a mathematic model, the graph, and provides a simple representation of a complex system. As Alzheimer's and Parkinson's disease are associated with synaptic disruptions and changes in the strength of functional connectivity, they can be well described by functional connectivity analysis computed via graph theory. The aim of the present review is to provide an overview of the most recent applications of the graph theory to electrophysiological data in the two by far most frequent neurodegenerative disorders, Alzheimer's and Parkinson's diseases.

TMS-EEG responses across the lifespan: Measurement, methods for characterisation and identified responses.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows probing of the neurophysiology of any neocortical brain area in vivo with millisecond accuracy. TMS-EEG is particularly unique compared with other available neurophysiological methods, as it can measure the state and dynamics of excitatory and inhibitory systems separately. Because of these capabilities, TMS-EEG responses are sensitive to the brain state, and the responses are influenced by brain maturation and ageing, making TMS-EEG a suitable method to study age-specific pathophysiology. In this review, we outline the TMS-EEG measurement procedure, the existing methods used for characterising TMS-EEG responses and the challenges associated with identifying the responses. We also summarise the findings thus far on how TMS-EEG responses change across the lifespan and the TMS-EEG features that separate typical and atypical brain maturation and ageing. Finally, we give an overview of the gaps in current knowledge to provide directions for future studies.

TMS-EEG Biomarkers of Amnestic Mild Cognitive Impairment Due to Alzheimer's Disease: A Proof-of-Concept Six Years Prospective Study.

Background: Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer's disease (AD) is a major scientific challenge. Objective: To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level. Methods: We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (npAD-MCI)]. Results: Patients with aMCI showed reduced motor cortex (M1) excitability and disrupted EEG synchronization [decreased intertrial coherence (ITC)] in alpha, beta and gamma frequency bands compared to the control subjects. The degree of alteration in M1 excitability and alpha ITC was comparable between pAD-MCI and npAD-MCI. Importantly, beta and gamma ITC impairment in the stimulated M1 was greater in pAD-MCI than npAD-MCI. Furthermore, an additional parameter related to the waveform shape of scalp signals, reflecting time-specific alterations in global TMS-induced activity [stability of the dipolar activity (sDA)], discriminated npAD-MCI from MCI who will convert to AD. Discussion: The above mentioned specific cortical changes, reflecting deficit of synchronization within the cortico-basal ganglia-thalamo-cortical loop in aMCI, may reflect the pathological processes underlying AD. These changes could be tested in larger cohorts as neurophysiological biomarkers of AD.

Preoperative Repetitive Navigated TMS and Functional White Matter Tractography in a Bilingual Patient with a Brain Tumor in Wernike Area.

Awake surgery and intraoperative neuromonitoring represent the gold standard for surgery of lesion located in language-eloquent areas of the dominant hemisphere, enabling the maximal safe resection while preserving language function. Nevertheless, this functional mapping is invasive; it can be executed only during surgery and in selected patients. Moreover, the number of neuro-oncological bilingual patients is constantly growing, and performing awake surgery in this group of patients can be difficult. In this scenario, the application of accurate, repeatable and non-invasive preoperative mapping procedures is needed, in order to define the anatomical distribution of both languages. Repetitive navigated transcranial magnetic stimulation (rnTMS) associated with functional subcortical fiber tracking (nTMS-based DTI-FT) represents a promising and comprehensive mapping tool to display language pathway and function reorganization in neurosurgical patients. Herein we report a case of a bilingual patient affected by brain tumor in the left temporal lobe, who underwent rnTMS mapping for both languages (Romanian and Italian), disclosing the true eloquence of the anterior part of the lesion in both tests. After surgery, language abilities were intact at follow-up in both languages. This case represents a preliminary application of nTMS-based DTI-FT in neurosurgery for brain tumor in eloquent areas in a bilingual patient.