Sara Määttä

Factors influencing cortical silent period: Optimized stimulus location, intensity and muscle contraction

Inhibitory silent period (SP) is a transient suppression of voluntary muscle activity after depolarization of representative motor neuronal populations following transcranial magnetic stimulation (TMS). Our aim was to evaluate and present an optimal protocol for the measurement of SP by (1) determining the impact of muscle activation level and stimulus intensity (SI) on the duration of SP, and, (2) studying the relationship between motor evoked potential (MEP) and SP, using targeted stimulus delivery. Single magnetic pulses were focused on the optimal representation area of the thenar musculature on primary motor cortex. We utilized real-time 3D-positioning of TMS-evoked electric field on anatomical structures derived from individual MR-images. The SI varied from 80% to 120% of individual resting motor threshold (MT). Muscle activation levels varied from 20% to 80% of the maximal voluntary contraction (MVC). Contralateral SP lengthened significantly with increasing SI independent of target muscle activation. The peak amplitude of the MEP was affected by SI and force. Latency and duration of the MEP were practically unaffected by SI or force. Focal stimulation at 110-120% MT and approximately 50% MVC (with only negligible need for control) provides most stable and informative SP. MEP should be included in SP as the error from marking the onset diminishes. This study provides a guideline for the consistent measurement of SP, which is applicable when using navigated or traditional TMS.

Impaired Lumbar Movement Perception in Association With Postural Stability and Motor- and Somatosensory-Evoked Potentials in Lumbar Spinal Stenosis

Study Design. A descriptive study of the associations between different neurophysiologic findings in patients with lumbar spinal stenosis. Objectives. To evaluate the ability to sense a change in lumbar position and the associations between lumbar movement perception, postural stability, and motor-evoked potentials and somatosensory-evoked potentials. Summary of Background Data. Patients with low back pain have impaired postural control and impaired lumbar proprioception. Altered motor-evoked potentials and somatosensory-evoked potentials have been often observed in lumbar spinal stenosis. Methods. The study included 26 patients with clinically and radiologically diagnosed lumbar spinal stenosis. Their ability to sense lumbar rotation was assessed in a previously validated motorized trunk rotation unit in the seated position. The abilities to indicate the movement direction and the movement magnitude were used as indexes of the ability to sense the lumbar rotatory movement. The postural stability was measured with a vertical force platform. The motor-evoked potentials were elicited by transcranial and lumbar stimulation and recorded from anterior tibialis muscles. The somatosensory-evoked potentials were elicited by transcutaneous electrical stimulation of the tibial nerve at the ankle. Results. Twenty patients (76.9%;P = 0.006) reported the wrong movement direction. Furthermore, the patients consistently localized the movement sensation in their shoulders instead of the lumbar region. The altered motor-evoked potentials and somatosensory-evoked potentials were observed in 11 and 16 patients, respectively. Abnormal motor-evoked potentials had inconsistent associations with impaired movement perception and postural stability and abnormal somatosensory-evoked potentials had no associations with other findings. Conclusions. Many patients with lumbar spinal stenosis have difficulties in sensing the lumbar rotational movement, which may indicate impaired proprioceptive abilities. Abnormal motor-evoked potentials and somatosensory-evoked potentials are also frequent in lumbar spinal stenosis but do not necessarily occur in the same patients as the abnormal ability to sense trunk movement. These new findings add to our understanding of the pathophysiology of lumbar spinal stenosis.

Navigated TMS combined with EEG in mild cognitive impairment and Alzheimer's disease: a pilot study.

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 Alzheimers 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.

Human brain cortical correlates of short-latency afferent inhibition: a combined EEG-TMS study

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.

Non-primary motor areas in the human frontal lobe are connected directly to hand muscles

Structural studies in primates have shown that, in addition to the primary motor cortex (M1), premotor areas are a source of corticospinal tracts. The function of these putative corticospinal neuronal tracts in humans is still unclear. We found frontal non-primary motor areas (NPMAs), which react to targeted non-invasive magnetic pulses and activate peripheral muscles as fast as or even faster than those in M1. Hand muscle movements were observed in all our subjects about 20 ms after transcranial stimulation of the superior frontal gyrus (Brodmann areas 6 and 8). Stimulation of NPMA could activate both proximal and distal upper limb muscles with the same delay as a stimulation of the M1, indicating converging motor representations with direct functional connections to the hand. We suggest that these non-primary cortical motor representations provide additional capacity for the fast execution of movements. Such a capacity may play a role in motor learning and in recovery from motor deficits.

Spatial Span in Very Prematurely Born Adolescents

The working memory functions and processing speed of 35 adolescents born preterm (≤ 32 weeks of gestation) and those of 31 control adolescents were assessed at the age of 16 years. All study participants were free from major disabilities. There were no statistically significant differences in verbal IQ between the study groups. Adolescents born preterm performed less well in complex spatial span compared to their peers born full term, even when verbal IQ and processing speed were allowed to covary. Both groups performed equally well in other working memory tasks and processing speed. Gestational age was the primary contributor to spatial span performance. These results indicate a minor spatial working memory deficit in preterm born adolescents without major disability and with normal cognitive capacity. Our results are encouraging and indicate only minor neuropsychological consequences due to very preterm birth.

Selective attention event-related potential effects from auditory novel stimuli in children and adults

OBJECTIVE We investigated differences between children and adults in selective attention. METHODS Event-related potentials of 9 year-old children and adults were studied. Subjects performed an active dichotic novelty oddball task. We examined age-related differences in early selection by comparing non-target tones and late selection by comparing target tones in the attended and unattended channels. RESULTS In children, an attention effect was seen on the N1 response to standard tones. For the targets, both children and adults displayed enhanced P3b amplitudes on the attended side, and in adults, an attention effect was also seen on the N2 response. In children, novelty-elicited N2 responses were larger to left ear stimuli irrespective of the direction of attention. Adults displayed enhanced novelty-elicited N2 amplitudes on the attended side. CONCLUSIONS Developmental changes occur both in early attentional selection and target detection. Children employed efficiently the mechanisms of early selection when processing standard stimuli, whereas their processes in relation to novel stimuli were attention-independent and even varied with ear. Adults were able to maintain their attentional focus in the presence of unexpected stimuli. SIGNIFICANCE The results of this study contribute to elucidation of the development of selective attention.

New insights into Alzheimer's disease progression: A combined TMS and structural MRI study

Background: 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. Methodology and Principal Findings: 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 Alzheimers 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. Conclusions: 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.

Motor cortex excitability in Alzheimer's disease: a transcranial magnetic stimulation follow-up study

Transient cognitive and behavioral stabilization of patients with Alzheimers 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.

Plastic Changes Following Imitation-Based Speech and Language Therapy for Aphasia: A High-Density Sleep EEG Study

Background. Objective 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. Methods. 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. Results. 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. Conclusions. 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.