[show abstract][hide abstract] ABSTRACT: measurement of plastic brain changes induced by a novel rehabilitative approach is a key requirement for validating its biological rationale linking the potential therapeutic gains to the changes in brain physiology. Objective. Based on an emerging notion linking cortical plastic changes to EEG sleep slow-wave activity (SWA) regulation, we aimed to assess the acute plastic changes induced by an imitation-based speech therapy in individuals with aphasia by comparing sleep SWA changes before and after therapy.
. A total of 13 left-hemispheric stroke patients underwent language assessment with the Western Aphasia Battery (WAB) before and after 2 consecutive high-density (hd) EEG sleep recordings interleaved by a daytime session of imitation-based speech therapy (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects [IMITATE]). This protocol is thought to stimulate bilateral connections between the inferior parietal lobule and the ventral premotor areas.
. A single exposure to IMITATE resulted in increases in local EEG SWA during subsequent sleep over the same regions predicted by the therapeutic rationale, particularly over the right hemisphere (unaffected by the lesion). Furthermore, changes in SWA over the left-precentral areas predicted changes in WAB repetition scores in our group, supporting the role of perilesional areas in predicting positive functional responses.
. Our results suggest that SWA changes occurring in brain areas activated during imitation-based aphasia therapy may reflect the acute plastic changes induced by this intervention. Further testing will be needed to evaluate SWA as a non-invasive assessment of changes induced by the therapy and as a predictor of positive long-term clinical outcome.
Neurorehabilitation and neural repair 08/2013; · 4.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: Our aim was to study long-term plasticity in the organization of cortical muscle representations due to extensive motor training for different skills. We were especially interested in whether skill-specific demands on independent hand muscle movements and synchronous leg muscle movements are reflected differently in the reorganization of muscle representations. We used navigated transcranial magnetic stimulation to estimate the size of cortical representations of opponens pollicis, abductor digiti minimi, and tibialis anterior muscles in five string instrument players, five figure skaters, and five controls. The extent of the representation area was presented as an amplitude-area curve showing the spatial distribution of motor evoked potentials. The size of representation areas was compared between the dominant and nondominant hemispheres and between the groups. The representation area of the left abductor digiti minimi (critical for reaching right tones) in the right, nondominant hemisphere was smaller in string players and the representation area of the tibialis anterior in the dominant hemisphere (critical for jumps) was larger in figure skaters when compared with controls. Reorganization in the motor cortex may differ depending upon the skill and an individual muscle's role in the skill. A smaller representation area of the independently used hand muscle in masters of fine motor skills may reflect long-term plasticity toward more focused representation, which may be beneficial in accurate and discrete cortical control of the muscle. Larger cortical representations are related to skill demanding coactivation of proximal and distal lower limb muscles.
[show abstract][hide abstract] ABSTRACT: When linking in time electrical stimulation of the peripheral nerve with transcranial magnetic stimulation (TMS), the excitability of the motor cortex can be modulated to evoke clear inhibition, as reflected by the amplitude decrement in the motor-evoked potentials (MEPs). This specific property, designated short-latency afferent inhibition (SAI), occurs when the nerve-TMS interstimulus interval (ISI) is approximately 25 ms and is considered to be a corticothalamic phenomenon. The aim of the present study was to use the electroencephalographic (EEG) responses to navigated-TMS coregistration to better characterize the neuronal circuits underlying SAI. The present experimental set included magnetic resonance imaging (MRI)-navigated TMS and 60-channel TMS-compatible EEG devices. TMS-evoked EEG responses and MEPs were analyzed in eight healthy volunteers; ISIs between median nerve and cortical stimulation were determined relative to the latency of the individual N20 component of the somatosensory-evoked potential (SEP) obtained after stimulation of the median nerve. ISIs from the latency of the N20 plus 3 ms and N20 plus 10 ms were investigated. In all experimental conditions, TMS-evoked EEG responses were characterized by a sequence of negative deflections peaking at approximately 7, 44, and 100 ms alternating with positive peaks at approximately 30, 60, and 180 ms post-TMS. Moreover, ISI N20+3 ms modulated both EEG-evoked activity and MEPs. In particular, it inhibited MEP amplitudes, attenuated cortical P60 and N100 responses, and induced motor cortex beta rhythm selective decrement of phase locking. The findings of the present experiment suggest the cortical origin of SAI that could result from the cortico-cortical activation of GABAergic-mediated inhibition onto the corticospinal neurons modulated by cholinergic activation able to reducing intralaminar inhibition and promoting intracolumnar inhibition.
Journal of Neurophysiology 03/2012; 108(1):314-23. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: The frontal cortex undergoes macrostructural and microstructural changes across the lifespan. These changes can be entirely physiological, such as the ones occurring in elderly individuals who are cognitively intact, or pathological, such as the ones occurring in patients with Alzheimer's disease. Here, we use simultaneous electroencephalography (EEG) and transcranial magnetic stimulation (TMS) to study how the excitability of the frontal cortex changes during healthy and pathological aging. Hence, we compared the TMS-evoked EEG potentials collected in healthy elderly individuals with the ones collected in healthy young individuals, and in patients with Alzheimer's disease. We have shown that the EEG response to TMS of the left superior frontal cortex is not affected by physiological aging but is markedly altered by cognitive impairment.
[show abstract][hide abstract] ABSTRACT: Patients with Unverricht-Lundborg disease, also referred to as progressive myoclonus epilepsy type 1, exhibit widespread motor symptoms and signs in addition to epileptic seizures, which suggest abnormal excitability of the primary motor pathways. To explore the plasticity of the sensory-motor cortex, we employed a modern neurophysiological method, the paired associative stimulation protocol, which resembles the concept of long-term potentiation of experimental studies. Seven patients with genetically verified Unverricht-Lundborg disease and 13 healthy control subjects were enrolled in the study to characterize cortical sensory-motor plasticity. In the study protocol, peripheral electric median nerve stimulation preceded navigated transcranial magnetic stimulation targeted to the representation area of thenar musculature on the contralateral primary motor cortex. The protocol consisted of 132 transcranial magnetic stimulation trials at 0.2 Hz, preceded by peripheral sensory stimulation at 25 ms. Motor-evoked potential amplitudes were analyzed at baseline and after the paired associative stimulation protocol at an intensity of 130% of the individual motor threshold. The patients with Unverricht-Lundborg disease exhibited an average decrease of 15% in motor-evoked potential amplitudes 30 minutes after paired associative stimulation, whereas in the control subjects, a significant increase (101%) was observed (P < .05), as expected. The results indicate a lack of normal cortical plasticity in Unverricht-Lundborg disease, which stresses the role of abnormal motor cortical functions or sensorimotor integration as possible pathophysiological contributors to the motor symptoms. The impaired cortical plasticity may be associated with the previously reported structural and physiological abnormalities of the primary motor cortex.
Movement Disorders 06/2011; 26(11):2095-100. · 4.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: Event-related potentials (ERPs) are important clinical and research instruments in neuropsychiatry, particularly due to their strategic role for the investigation of brain function. These techniques are often underutilized in the evaluation of neurological and psychiatric disorders, but ERPs are noninvasive instruments that directly reflect cortical neuronal activity. Previous studies using the P300, P3a, and MMN components of the ERP to study dementing illness are reviewed. The results suggest that particularly the P300 brain potential is sensitive to Alzheimer's disease processes during its early stages, and that easily performed stimulus discrimination tasks are the clinically most useful. Finally, these data suggest that the P300 ERP can aid in the diagnosis of dementia and may help in the assessment of early Alzheimer's disease.
International journal of Alzheimer's disease. 01/2011; 2011:653173.
[show abstract][hide abstract] ABSTRACT: Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas.
To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness.
In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD.
PLoS ONE 01/2011; 6(10):e26113. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intracortical inhibition (SICI) and facilitation (ICF) in the human motor cortex can be measured using a paired pulse transcranial magnetic stimulation (ppTMS) protocol. Recently, a technical device has been introduced, which allows recording electroencephalographic (EEG) responses to TMS of a given scalp site. The latency, amplitude and scalp topography of such responses are considered a reflection of cortico-cortical connectivity and functional state. The aim of the present study is to better characterize the neuronal circuits underlying motor cortex connectivity as well as the mechanisms regulating its balance between inhibition and facilitation by means of EEG navigated-ppTMS coregistration.
Sub-threshold and supra-threshold single and ppTMS of the left primary motor cortex were carried out during a multi-channel EEG recording on 8 healthy volunteers; the between-pulse intervals used in the paired pulse trials were 3 (for SICI) and 11 ms (for ICF). Motor evoked potentials (MEPs) from the opposite hand were simultaneously recorded.
Single and ppTMS induced EEG responses characterized by a sequence of negative deflections peaking at approximately 7, 18, 44, 100 and 280 ms alternated with positive peaks at approximately 13, 30, 60 and 190 ms post-TMS. Moreover, ppTMS modulated both EEG evoked activity and MEPs. Amplitude variability of EEG responses was correlated with - and therefore might partially explain - amplitude variability of MEPs.
EEG-ppTMS is a promising tool to better characterize the neuronal circuits underlying cortical effective connectivity as well as the mechanisms regulating the balance between inhibition and facilitation within the human cortices and the corticospinal pathway.
[show abstract][hide abstract] ABSTRACT: Transient cognitive and behavioral stabilization of patients with Alzheimer's disease (AD) is the main goal of acetylcholinesterase inhibitor (AChEI) therapy. Response to treatment is variable and it is usually assessed clinically via neuropsychological scales. Functional neuroimaging could ideally permit the objective evaluation of the topographic correlates of therapy on brain functioning, but is expensive and little available on a large scale. On the other hand, neurophysiological methods such as transcranial magnetic stimulation (TMS) could offer an alternative, low-cost and risk free tool of assessing response to treatment in AD. Previous TMS studies have demonstrated hyperexcitability and asymptomatic motor cortex reorganization in the early stages of AD in patients with normal motor function. The aim of this study was to compare motor cortex functionality in 10 AD patients before and after long-term AchEIs therapy in order to monitor potential drug-related changes in cortical excitability and organization. Examined parameters of motor cortex physiology were found to be unchanged in patients with stabilized cognitive performance during the therapy. TMS, along with clinical, neuropsychological, and neuroimaging data, could be an inexpensive measure of biological progression in AD and it might supplement traditional methods to assess the effects of therapy.
[show abstract][hide abstract] ABSTRACT: Navigated transcranial magnetic stimulation (nTMS) is a non-invasive method to localize the primary motor cortex (M1).
To assess the safety and feasibility of nTMS as a non-invasive preoperative mode of functional localization of M1 in epilepsy surgery candidates with intractable focal epilepsy due to lesions in the vicinity of M1.
We mapped the muscle representation areas of M1 with nTMS in 10 patients (age 2 to 55 years) with intractable epilepsy. The lesions were focal cortical dysplasia (n=6), ganglioglioma (n=2) polymicrogyria (n=1) or dysembryoblastic neuroepithelial tumour (n=1). The optimal stimulation sites and motor threshold (MT) of the distal hand or leg muscles were determined in both hemispheres. Cortical areas were mapped with stimulation intensities 100-120% of the MT to localize functional M1. Patients were on their stabile antiepileptic medication, and EEG was continuously monitored. The clinical benefit obtained with the preoperative nTMS mapping in the surgical decision making was scored as (1) essential, (2) beneficial, or (3) not beneficial, depending mainly on the difference between the functional and the presumed anatomic M1.
The M1 was successfully assessed in all but the 2 youngest patients (aged 2 and 5 years), in whom nTMS was unable to elicit motor responses. nTMS was regarded as essential or beneficial in the localization of M1 in relation to the lesions in 6 out of 10 cases. The optimal motor representation areas were mainly located symmetrically on the precentral gyrus, and corresponded to the presumed location of M1 in MRI. No clinical or EEG evidence of acute epileptogenic adverse effects were observed during the localization procedure. None of the operated patients developed post-operative motor deficits.
nTMS is a safe and feasible clinical tool for the non-invasive preoperative localization of motor cortex in patients with intractable epilepsy due to focal lesions adjacent or within the presumed M1 in MRI.
Epilepsy research 12/2010; 92(2-3):134-44. · 2.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transcranial magnetic stimulation (TMS) of the superior frontal gyrus in the non-primary motor area (NPMA) can evoke motor-evoked potentials (MEPs) at 20 ms latency range in contralateral distal hand muscles similar to stimulation of M1 and indicating monosynaptic corticospinal tracts. We compared the intracortical inhibitory and excitatory balance in primary motor cortex (M1) and in NPMA by navigated single- and paired-pulse TMS (ppTMS). We also evaluated the spatial stability of muscle representations in M1 and NPMA by remapping 11 healthy subjects one year after the initial mapping. Resting motor threshold (rMT) was higher in NPMA than in M1 as were the MEP amplitudes evoked by 120% rMT stimulation intensity of the local MT. Short-interval intracortical inhibition (SICI) was significantly weaker in NPMA than in M1 at ISI of 2 ms and conditioning stimulus (CS) 80% rMT. Our findings suggest that the cortical hand representations in NPMA 1) are connected to lower motoneurons monosynaptically, 2) are less strictly organized, i.e. motoneuron population representing a discrete hand muscle is sparser and less dense than in M1 and 3) have the capacity to generate powerful, rapid muscle contraction if sufficient number of motoneurones are activated. In NPMA, local intracortical inhibitory and excitatory activity is mainly similar to that in M1. The lower SICI in NPMA at an ISI of 2 ms may reflect less strict topographic organization and readiness to reorganization of neural circuits during motor learning or after motor deficits.
Human Brain Mapping 09/2010; 32(10):1692-703. · 6.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: The consolidation of memories in a variety of learning processes benefits from post-training sleep, and recent work has suggested a role for sleep slow wave activity (SWA). Previous studies using a visuomotor learning task showed a local increase in sleep SWA in right parietal cortex, which was correlated with post-sleep performance enhancement. In these as in most similar studies, learning took place in the evening, shortly before sleep. Thus, it is currently unknown whether learning a task in the morning, followed by the usual daily activities, would also result in a local increase in sleep SWA during the night, and in a correlated enhancement in performance the next day. To answer this question, a group of subjects performed a visuomotor learning task in the morning and was retested the following morning. Whole night sleep was recorded with high-density EEG. We found an increase of SWA over the right posterior parietal areas that was most evident during the second sleep cycle. Performance improved significantly the following morning, and the improvement was positively correlated with the SWA increase in the second sleep cycle. These results suggest that training-induced changes in sleep SWA and post-sleep improvements do not depend upon the time interval between original training and sleep.
Brain research bulletin 04/2010; 82(1-2):118-23. · 2.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: Our aim was to assess the potential of navigated transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) responses in studying neuronal reactivity and cortical connectivity in Alzheimer's disease (AD) and in mild cognitive impairment (MCI). We studied 14 right-handed subjects: five patients with AD, five patients with MCI and four healthy controls. Fifty TMS-pulses at an intensity of 110% of individually determined motor threshold were delivered to the hand area of primary motor cortex (M1) with navigated brain stimulation (NBS). Spreading of primary NBS-evoked neuronal activity was monitored with a compatible 60-channel EEG, and analyzed in time, frequency and spatial-domains. We found significantly reduced TMS-evoked P30 (time-locked response 30 ms after the magnetic stimulation) in the AD subjects. This reduction was seen in the temporo-parietal area ipsilateral to stimulation side as well as in the contralateral fronto-central cortex corresponding to the sensorimotor network, which is anatomically interconnected with the stimulated M1. In addition, there was a significant decrease in the N100 amplitude in the MCI subjects when compared with the control subjects. Thus, the combination of NBS and EEG revealed prominent changes in functional cortical connectivity and reactivity in the AD subjects. This pilot study suggests that the method may provide a novel tool for examining the degree and progression of dementia.
Journal of Neuroscience Methods 08/2008; 172(2):270-6. · 2.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sleep slow-wave activity (SWA) is thought to reflect sleep need, increasing in proportion to the previous time awake and decreasing during sleep, although the underlying mechanisms are unclear. Recent studies have shown that procedures presumably leading to local plastic changes in the cerebral cortex can lead to local changes in SWA during subsequent sleep. To further investigate the connection between cortical plasticity and sleep SWA, in this study we used a paired associative stimulation (PAS) protocol, in which median nerve stimuli were followed at different intervals (25 or 10 ms) by transcranial magnetic stimulation (TMS) pulses to the contralateral cortical hand area. As expected, such a protocol led to a sustained increase (long-term potentiation-like) or decrease (long-term depression-like) of cortical excitability as measured by motor evoked potentials. By using a TMS-compatible high-density electroencephalographic (EEG) system, we also found that, in individual subjects, TMS-evoked cortical responses over sensorimotor cortex changed with different interstimulus intervals. Moreover, during subsequent sleep, SWA increased locally in subjects whose TMS-evoked cortical responses had increased after PAS, and decreased in subjects whose cortical responses had decreased. Changes in TMS-evoked cortical EEG response and change in sleep SWA were localized to similar cortical regions and were positively correlated. Together, these results suggest that changes in cortical excitability in opposite directions lead to corresponding changes in local sleep regulation, as reflected by SWA, providing evidence for a tight relationship between cortical plasticity and sleep intensity.
Journal of Neuroscience 08/2008; 28(31):7911-8. · 6.91 Impact Factor