The influence of corticospinal activity on TMS-evoked activity and connectivity in healthy subjects: A TMS-EEG study.

Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) can be used to analyze cortical reactivity and connectivity. However, the effects of corticospinal and peripheral muscle activity on TMS-evoked potentials (TEPs) are not well understood. The aim of this paper is to evaluate the relationship between cortico-spinal activity, in the form of peripheral motor-evoked potentials (MEPs), and the TEPs from motor areas, along with the connectivity among activated brain areas. TMS was applied to left and right motor cortex (M1), separately, at motor threshold while multi-channel EEG responses were recorded in 17 healthy human subjects. Cortical excitability and source imaging analysis were performed for all trials at each stimulation location, as well as comparing trials resulting in MEPs to those without. Connectivity analysis was also performed comparing trials resulting in MEPs to those without. Cortical excitability results significantly differed between the MEP and no-MEP conditions for left M1 TMS at 60 ms (CP1, CP3, C1) and for right M1 TMS at 54 ms (CP6, C6). Connectivity analysis revealed higher outflow and inflow between M1 and somatosensory cortex bi-directionally for trials with MEPs than those without for both left M1 TMS (at 60, 100, 164 ms) and right M1 TMS (at 54, 100, and 164 ms). Both TEP amplitudes and connectivity measures related to motor and somatosensory areas ipsilateral to the stimulation were shown to correspond with peripheral MEP amplitudes. This suggests that cortico-spinal activation, along with the resulting somatosensory feedback, affects the cortical activity and dynamics within motor areas reflected in the TEPs. The findings suggest that TMS-EEG, along with adaptive connectivity estimators, can be used to evaluate the cortical dynamics associated with sensorimotor integration and proprioceptive manipulation along with the influence of peripheral muscle feedback.

Predicting genitourinary toxicity in three-dimensional conformal radiotherapy for localized prostate cancer: A dose-volume parameters analysis of the bladder.

PURPOSE: In prostate cancer radiotherapy, the relationship between genitourinary (GU) toxicity and clinical-dosimetric parameters is debated. We report our analysis of the parameters associated with GU toxicity. MATERIALS AND METHODS: Eighty-six consecutive patients treated with conformal radiotherapy for localized prostate cancer were retrospectively analyzed; the bladder was delineated both as "whole bladder" (WB: Defined in its entirety as a solid organ) and "inferior bladder" (IB: Corresponding to the distal part of the bladder). GU toxicity and dose-volume parameters were correlated using the point biserial correlation coefficient. The normal tissue complication probability (NTCP) cut-off volume model was fitted to toxicity data; univariate analysis between GU toxicity and clinical parameters was done. RESULTS: Acute GU toxicity was correlated to doses higher than 80 Gy (P < 0.05) while late GU was correlated to doses higher than 77 Gy for WB and from 77.5 Gy for IB. The NTCP cut-off volume model identified for both WB and IB a bladder volume of 6 cc receiving a dose ≥77 Gy corresponding to a 50% probability of GU toxicity. At univariate analysis, acute GU toxicity was correlated with smoke (P < 0.001). CONCLUSION: Bladder maximal doses quantified as hotspots show a correlation to GU toxicity.

Sensorimotor cortex excitability and connectivity in Alzheimer's disease: A TMS-EEG Co-registration study.

Several studies have shown that, in spite of the fact that motor symptoms manifest late in the course of Alzheimer's disease (AD), neuropathological progression in the motor cortex parallels that in other brain areas generally considered more specific targets of the neurodegenerative process. It has been suggested that motor cortex excitability is enhanced in AD from the early stages, and that this is related to disease's severity and progression. To investigate the neurophysiological hallmarks of motor cortex functionality in early AD we combined transcranial magnetic stimulation (TMS) with electroencephalography (EEG). We demonstrated that in mild AD the sensorimotor system is hyperexcitable, despite the lack of clinically evident motor manifestations. This phenomenon causes a stronger response to stimulation in a specific time window, possibly due to locally acting reinforcing circuits, while network activity and connectivity is reduced. These changes could be interpreted as a compensatory mechanism allowing for the preservation of sensorimotor programming and execution over a long period of time, regardless of the disease's progression. Hum Brain Mapp 37:2083-2096, 2016. © 2016 Wiley Periodicals, Inc.

Optimal weighted averaging of event related activity from acquisitions with artifacts.

In several biomedical applications that require the signal processing of biological data, the starting procedure for noise reduction is the ensemble averaging of multiple repeated acquisitions (trials). This method is based on the assumption that each trial is composed of two additive components: (i) a time-locked activity related to some sensitive/stimulation phenomenon (ERA, Event Related Activity in the following) and (ii) a sum of several other non time-locked background activities. The averaging aims at estimating the ERA activity under very low Signal to Noise and Interference Ratio (SNIR). Although averaging is a well established tool, its performance can be improved in the presence of high-power disturbances (artifacts) by a trials classification and removal stage. In this paper we propose, model and evaluate a new approach that avoids trials removal, managing trials classified as artifact-free and artifact-prone with two different weights. Based on the model, a weights tuning is possible and through modeling and simulations we show that, when optimally configured, the proposed solution outperforms classical approaches.

Neurophysiological features of motor cortex excitability and plasticity in Subcortical Ischemic Vascular Dementia: a TMS mapping study.

OBJECTIVE: To evaluate neurophysiological features of M1 excitability and plasticity in Subcortical Ischemic Vascular Dementia (SIVD), by means of a TMS mapping study. METHODS: Seven SIVD and nine AD patients, along with nine control subjects were tested. The M1 excitability was studied by resting thresholds, area and volume of active cortical sites for forearm and hand's examined muscles. For M1 plasticity, coordinates of the hot-spot and the center of gravity (CoG) were evaluated. The correlation between the degree of hyperexcitability and the amount of M1 plastic rearrangement was also calculated. RESULTS: Multivariate analysis of excitability measures demonstrated similarly enhanced cortical excitability in AD and SIVD patients with respect to controls. SIVD patients showed a medial and frontal shift of CoG from the hot-spot, not statistically different from that observed in AD. A significant direct correlation was seen between parameters related to cortical excitability and those related to cortical plasticity. CONCLUSIONS: The results suggest the existence of common compensatory mechanisms in different kind of dementing diseases supporting the idea that cortical hyperexcitability can promote cortical plasticity. SIGNIFICANCE: This study characterizes neurophysiological features of motor cortex excitability and plasticity in SIVD, providing new insights on the correlation between cortical excitability and plasticity.

Unilateral cortical hyperexcitability in congenital hydrocephalus: a TMS study.

INTRODUCTION: Changes in cortical excitability are considered to play an important role in promoting brain plasticity both in healthy people and in neurological diseases. Hydrocephalus is a brain development disorder related to an excessive accumulation of cerebrospinal fluid (CSF) in the ventricular system. The functional relevance of cortical structural changes described in this disease is largely unexplored in human. We investigated cortical excitability using multimodal transcranial magnetic stimulation (TMS) in a case of congenital hydrocephalus with almost no neurological signs. METHODS: A caucasian 40 years old, ambidextrous and multilingual woman affected by occult spina bifida and congenital symmetrical hydrocephalous underwent a TMS study. The intracortical and interhemispheric paired pulse paradigms were used, together with the mapping technique. RESULTS: No significant differences were found in the resting motor thresholds between the two hemispheres. Instead, the intracortical excitability curves were statistically different between the two hemispheres (with short intracortical inhibition (SICI) being strongly reduced and intracortical facilitation (ICF) enhanced in the right one), and the interhemispheric curves showed a general hyper-excitability on the right hemisphere (when conditioned by the left one) and a general hypo-excitability in the left hemisphere (when conditioned by the right one). It is noteworthy that an asymmetric right hemisphere (RH) change of excitability was observed by means of mapping technique. CONCLUSION: We hypothesize that in this ambidextrous subject, the observed RH hyper-excitability could represent a mechanism of plasticity to preserve functionality of specific brain areas possibly devoted to some special skills, such as multilingualism.