Cortical correlates of neuromotor development in healthy children.

OBJECTIVE: To examine the relationship between acquisition of fine motor skills in childhood and development of the motor cortex. METHODS: We measured finger tapping speed and mirror movements in 43 healthy right-handed subjects (6-26 years of age). While recording surface electromyographic activity from right and left first dorsal interosseus, we delivered focal transcranial magnetic stimulation (TMS) over the hand areas of each motor cortex. We measured motor evoked potential (MEP) threshold, and ipsilateral (iSP) and contralateral (CSP) silent periods. RESULTS: As children got older, finger speeds got faster, MEP threshold decreased, iSP duration increased and latency decreased. Finger tapping speed got faster as motor thresholds and iSP latency decreased, but was unrelated to CSP duration. In all subjects right hemisphere MEP thresholds were higher than those on the left and duration of right hemisphere CSP was longer than that on the left. Children under 10 years of age had higher left hand mirror movement scores, and fewer left hemisphere iSPs which were of longer duration. CONCLUSIONS: Maturation of finger tapping skills is closely related to developmental changes in the motor threshold and iSP latency. Studies are warranted to explore the relationship between these measures and other neuromotor skills in children with motor disorders. SIGNIFICANCE: TMS can provide important insights into certain functional aspects of neurodevelopment in children.     

Neuromagnetic correlates of sensorimotor synchronization

Sensorimotor synchronization tasks, in which subjects have to tap their finger in synchrony with an isochronous auditory click, typically reveal a synchronization error with the tap preceding the click by about 20 to 50 msec. Although extensive behavioral studies and a number of different explanatory accounts have located the cause of this so-called "negative asynchrony" on different levels of processing, the underlying mechanisms are still not completely understood. Almost nothing is known about the central processes, in particular, which sensory or motor events are synchronized by subjects. The present study examined central-level processing in synchronization tasks with magnetoencephalography (MEG). Eight subjects synchronized taps with their right index finger to an isochronous binaural pacing signal presented at an interstimulus interval of 800 msec. To gain information on central temporal coupling between "tap" and "click," evoked responses were averaged time-locked to the auditory signal and the tap onset. Tap-related responses could be explained with a three dipole model: One source, peaking at approximately 77 msec before tap onset, was localized in contralateral primary motor cortex (MI); the two other sources, peaking approximately at tap onset and 75 msec after tap onset, in contralateral primary somatosensory cortex (SI). Temporal coupling of these sources was compared in relation to different trigger points. The second SI source was equally well time-locked to the tap and to the auditory click. Furthermore, analysis of the time locking of this source activity as a function of the temporal order of tap and click showed that the second event - irrespective whether tap or click - was decisive in triggering the second SI source. This suggests that subjects use mainly sensory feedback in judging and evaluating whether they are "keeping time."     

Neuromagnetic recordings in temporal lobe epilepsy.

The introduction of whole-head magnetoencephalography (MEG) systems facilitating simultaneous recording from the entire brain surface has established MEG as a clinically feasible method for the evaluation of patients with temporal lobe epilepsy (TLE). In mesial TLE, two types of MEG spike dipoles could be identified: an anterior vertical and an anterior horizontal dipole. Dipole orientations can be used to attribute spike activity to temporal lobe subcompartments. Whereas the anterior vertical dipole is compatible with epileptic activity in the mediobasal temporal lobe, the anterior horizontal dipole can be explained by epileptic activity of the temporal tip cortex. In nonlesional TLE, medial and lateral vertical dipoles were found which could distinguish between medial and lateral temporal seizure onset zones as evidenced from invasive recordings. In lesional TLE, MEG could clarify the spatial relationship of the structural lesion to the irritative zone. Evaluation of patients with persistent seizures after epilepsy surgery may represent another clinical important application of MEG because magnetic fields are less influenced than electric fields by the prior operation. Simultaneous MEG and invasive EEG recordings indicate that epileptic activity restricted to mesial temporal structures cannot reliably be detected on MEG and that an extended cortical area of at least 6 to 8 cm2 involving also the basal temporal lobe is necessary to produce a reproducible MEG signal. In lateral neocortical TLE MEG seems to be more sensitive than scalp-EEG which further underlines the potential role of MEG for the study of nonlesional TLE. Whole-head MEG therefore can be regarded as a valuable and clinically relevant noninvasive method for the evaluation of patients with TLE.     

Impaired visuocortical discrimination learning of socially conditioned stimuli in social anxiety

In search of causative factors of social anxiety disorder (SAD), classical conditioning has been discussed as a potential trigger mechanism for many years. Recent findings suggest that the social relevance of the unconditioned stimulus (US) might play a major role in learning theories of SAD. Thus, this study applied a social conditioning paradigm with disorder-relevant US to examine the electrocortical correlates of affective learning. Twenty-four high socially anxious (HSA) and 23 age- and gender-matched low socially anxious (LSA) subjects were conditioned to 3 different faces flickering at a frequency of 15 Hz which were paired with auditory insults, compliments or neutral comments (US). The face-evoked electrocortical response was measured via steady-state visually evoked potentials and subjective measures of valence and arousal were obtained. Results revealed a significant interaction of social anxiety and conditioning, with LSA showing highest cortical activity to faces paired with insults and lowest activity to faces paired with compliments, while HSA did not differentiate between faces. No group differences were discovered in the affective ratings. The findings indicate a potentially impaired ability of HSA to discriminate between relevant and irrelevant social stimuli, which may constitute a perpetuating factor of SAD.     

Short-term groups with children: The yellow brick road to healthy development

This article will examine the diagnostic and treatment contributions of short-term groups with children and adolescents. The content will be based on a twelve week model, meeting weekly for one and a half hours. The creation of such groups will be explored, focusing on the importance of careful preparation in order to insure a successful group experience for both the children and the leader. A theory of development for short-term groups with children will be proposed. This theory is derived from the existing literature on long and short-term adult group development, as well as the developmental theory on long-term children's groups. A chart will focus on group dynamics, observable behaviors and the leader's role in the four stages of short-term group development.The Wizard of Oz is used to illustrate the theory supporting these stages of short-term group development. This paper was presented at the Children's Group Therapy Conference (Boston, MA) on May 1, 1993.     

Neuromagnetic correlates of visual motion coherence

In order to characterize cortical responses to coherent motion we use magnetoencephalography (MEG) to measure human brain activity that is modulated by the degree of global coherence in a visual motion stimulus. Five subjects passively viewed two-phase motion sequences of sparse random dot fields. In the first (incoherent) phase the dots moved in random directions; in the second (coherent) phase a variable percentage of dots moved uniformly in one direction while the others moved randomly. We show that: (i) visual-motion-evoked magnetic fields, measured with a whole-scalp neuromagnetometer, reveal two transient events, within which we identify two significant peaks--the 'ON-M220' peak approximately 220 ms after the onset of incoherent motion and the 'TR-M230' peak, approximately 230 ms after the transition from incoherent to coherent motion; (ii) in lateral occipital channels, the TR-M230 peak amplitude varies with the percentage of motion coherence; (iii) two main sources are active in response to the transition from incoherent to coherent motion, the human medial temporal area complex/V3 accessory area (hMT+/V3A) and the superior temporal sulcus (STS), and (iv) these distinct areas show a similar, significant dependence of response strength and latency on motion coherence.     

Neuromagnetic topography of photoconvulsive response in man.

The neuromagnetic method was applied to the study of photoconvulsive responses. The identification of specific magnetic field distributions over the scalp was achieved by; (a) a stimulation paradigm consisting of series of trains of flicker stimuli randomly presented to the epileptic patient, after eye closure, to get epileptic responses while avoiding seizures; (b) a novel procedure for data analysis, to select consistent responses. These patterns, when sufficiently stable in time and dipolar in shape, were used for source localization in the usual biomagnetic framework of the equivalent current dipole source representation. The results of this approach suggest that different specific cortical areas are repeatedly and randomly activated, involving mainly the frontal, occipital and temporal areas, often with a hemispheric prevalence.     

Neuromagnetic beta and gamma oscillations in the somatosensory cortex after music training in healthy older adults and a chronic stroke patient

ObjectiveExtensive rehabilitation training can lead to functional improvement even years after a stroke. Although neuronal plasticity is considered as a main origin of such ameliorations, specific subtending mechanisms need further investigation. Our aim was to obtain objective neuromagnetic measures sensitive to brain reorganizations induced by a music-supported training.MethodsWe applied 20-Hz vibrotactile stimuli to the index finger and the ring finger, recorded somatosensory steady-state responses with magnetoencephalography, and analyzed the cortical sources displaying oscillations synchronized with the external stimuli in two groups of healthy older adults before and after musical training or without training. In addition, we applied the same analysis for an anecdotic report of a single chronic stroke patient with hemiparetic arm and hand problems, who received music-supported therapy (MST).ResultsHealthy older adults showed significant finger separation within the primary somatotopic map. Beta dipole sources were more anterior located compared to gamma sources. An anterior shift of sources and increases in synchrony between the stimuli and beta and gamma oscillations were observed selectively after music training. In the stroke patient a normalization of somatotopic organization was observed after MST, with digit separation recovered after training and stimulus induced gamma synchrony increased.ConclusionsThe proposed stimulation paradigm captures the integrity of primary somatosensory hand representation. Source position and synchronization between the stimuli and gamma activity are indices, sensitive to music-supported training. Responsiveness was also observed in a chronic stroke patient, encouraging for the music-supported therapy. Notably, changes in somatosensory responses were observed, even though the therapy did not involve specific sensory discrimination training.SignificanceThe proposed protocol can be used for monitoring changes in neuronal organization during training and will improve the understanding of the brain mechanisms underlying rehabilitation.     

Somatosensory mismatch negativity in healthy children

Aim  Event-related potentials (ERPs) obtained when focused attention is kept away from the stimulus (unnoticed stimulation) are possibly linked to automatic mismatch-detection mechanisms, and could be a useful tool to investigate sensory discrimination ability. By considering the high impact of impaired somatosensory integration on many neurological disturbances in children, we aimed to verify whether mismatch-related responses to somatosensory stimulation could be obtained in healthy children.
Method  Eleven healthy participants (age range 6–11y, mean 8y 2mo, SD 1y 7mo; seven males, four females) underwent 'oddball' electrical stimulation of the right hand (80% frequent stimuli delivered to the thumb, 20% deviant stimuli delivered to the fifth finger). Data were compared with those obtained when the frequent stimuli to the thumb were omitted ('standard-omitted' protocol). ERPs were recorded at frontal, central, and parietal scalp locations. Children's overt attention was engaged by a demanding video game.
Results  In the oddball protocol, deviant stimulation elicited a left central negativity at about 160ms latency, followed by a left frontal negative response at about 220ms latency. Standard-omitted traces showed only a left parietal negative response spreading to right parietal regions.
Interpretation  Mismatch-related somatosensory responses can be reliably obtained in children, providing that appropriate technical contrivances are used. In clinical use, the frontal components, which are present only during the oddball protocol, could be a reliable and unequivocal neurophysiological marker of the automatic mismatch-detection mechanism.     

Neuromagnetic responses in silence after musical chord sequences

Neuromagnetic responses in silence after chord sequences ending in three kinds of musical cadences were investigated. The magnetoencephalographic signals of musically trained participants showed clear peaks around the bilateral temporal areas during the period of silence when the cadences were musically premature. Maximum global moment during the silent period was estimated in the auditory cortices. The time course of the source activities revealed two components, first around 80 ms and second around 150 or 200 ms, the latency of which differed depending on the cadence. These auditory cortical activities, particularly the second components, are suggested to reflect the participants' internal generation of a sound image associated with temporal or temporal-spectral expectations induced as a function of musical cadence.     

Comparison of urinary oxidative biomarkers in Iranian children with autism

Autism is a complex neurodevelopmental disorder usually presents in early childhood and thought to be influenced by genetic and environmental factors. Individuals with autism vary widely in abilities, intelligence, and behaviors. It is common for children with autism to exhibit eating disorders and some have preferences for soft and sweetened food making them susceptible to caries. Furthermore, a wide spectrum of medical and behavioral symptoms exhibited by children with autism makes routine dental care very difficult. Intellectual disability is evident in approximately 70% of individuals with autism and most psychiatric disorders, including autism, are associated with increased oxidative stress. 29 subjects diagnosed with autism, in the age group of 6 to 12 years, were a part of the study. Furturemore, 24 normal healthy siblings of same age group were taken as the control group.The present study aimed to evaluate oxidative stress biomarkers such as urinary total antioxidant concentration (TAC), catalase activity (CAT) and total thiol molecules (TTM). The results showed the autism group have significantly higher CAT activity and concomitant lower TAC and TTM concentration in comparison with control group. The results are discussed in relation to an increased vulnerability to oxidative damage, which may contribute to the development and clinical manifestation of symptoms of autism.     

Functional influences of the visuocortical projection on superior colliculus neurons in the rabbit

The effects of electrical stimulation of the visual cortex on superior colliculus neurons were investigated in adult Dutch-belted rabbits. Single units were recorded in the superior colliculus and classified as to receptive field type. Stimulation of the ipsilateral visual cortex activated 29% of the recorded superior colliculus units. No units were driven by stimulation of the contralateral visual cortex. Comparison of the relative proportional distributions of cortically driven and not driven cells having various receptive field types revealed an over-representation of driven motion type cells. The excitatory influence of the visuocortical projection to the superior colliculus in the rabbit shows a preference for neurons responsive to moving visual stimuli.     

Neuromagnetic evidence for early semantic access in word recognition

Magnetic brain responses recorded in the human magnetoencephalogram (MEG) distinguished between words with different semantics but carefully matched for frequency and length. Multiple recordings from a single subject showed that 100 ms following stimulus onset, significantly stronger neuromagnetic responses were elicited by words with strong multimodal semantic associations than by other word material. At this early processing step, there was a highly significant correlation (0.80) between the magnitude of brain responses to individual words recorded over parieto-occipital areas and their semantic association strengths. Subsequent to this early difference related to word meaning, additional differences in MEG responses emerged for words from different grammatical categories. Together, these results suggest that word meaning can be reflected by early neuromagnetic brain responses and before the grammatical information about the word is encoded.     

Epidermal innervation in healthy children and adolescents

Introduction: Epidermal nerve fiber (ENF) density, morphology, and epidermal innervation patterns were examined in children using 2 different techniques, punch biopsy and suction blister. Methods: Healthy children without symptoms or history of peripheral neuropathy and normal by neurologic examination were studied. Punch biopsy and suction blister specimens were collected from the lateral thigh and distal leg. ENFs were traced from confocal images of immunohistochemically stained samples. Statistical methods included repeated‐measures analysis of covariance. Results: Blister and biopsy nerve counts were associated. ENF density in children was dense, lower for older children (P < 0.01) and with no difference between boys and girls (P = 0.92). Many ENFs appeared multibranched and elongated. Conclusions: Epidermal innervation in the pediatric population is dense and age‐dependent. Blister specimens are less invasive and may provide an alternative to punch biopsy for determining ENF density in children at risk for neuropathy. Muscle Nerve 51 : 378–384, 2015     

Neuromagnetic responses from the second somatosensory cortex in man

Cerebral magnetic fields elicited by electric stimulation of peripheral nerves were studied in man. Responses were found over the Sylvian fissure at latencies of 95-125 ms for both contra- and ipsilateral stimuli. The field distribution indicated that the responses are generated in the second somatosensory cortex SII at the upper bank of the Sylvian fissure. These responses seem to provide the first non-invasive tool to study the function of SII in man.     

帕金森病患者和健康对照者的纵向CSF生物标志物对比研究

目的 探讨帕金森病(Parkinson's disease,PD)患者脑脊液(CSF)生物标志物的水平变化及其临床意义。方法 选取本院2018年3月-2019年3月收治的70例PD患者,并根据改良PD综合评分量表(UPDRS量表)及Hoehn-Yahr评分标准将患者分为轻度组(n=38)、中度组(n=18)和重度组(n=14)。另选择同期于本院接受体检健康人员70例作为对照组,检测并比较4组研究对象CSF生物标志物蛋白α-突触核蛋白(α-syn)、磷酸化Tau蛋白(P-Tau)及总Tau蛋白(T-Tau),微小RNA133 b(miR-133b)及C反应蛋白(CRP)、白细胞介素-8(IL-8)水平。结果 各组性别、年龄比较无明显差异(P>0.05); 不同病情严重程度PD患者UPDRS评分比较有明显差异,且均显著高于对照组(P<0.05); PD患者轻度组、中度组及重度组H-Y评分比较有明显差异(P<0.05)。各组α-syn、P-Tau、T-Tau、miR-133b、CRP及IL-8水平比较有明显差异(P<0.05),且随着PD患者病情严重程度加重,α-syn水平显著降低,P-Tau、T-Tau、miR-133b、CRP及IL-8水平显著升高(P<0.05)。Pearson相关分析显示,α-syn与UPDRS评分呈显著正相关,P-Tau、T-Tau、miR-133b、CRP及IL-8与UPDRS呈显著负相关(P<0.05)。受试者工作曲线(ROC)显示α-syn、P-Tau、T-Tau、miR-133b、CRP及IL-8水平诊断PD的曲线下面积(AUC)分别为0.755、0.785、0.742、0.746、0.779、0.755,联合诊断的AUC为0.905。结论 脑脊液生物标志物的水平变化是PD发生与发展的重要参考指标,其对于PD的诊断和病情严重程度判断具有重要价值     

Neuromagnetic imaging of cortical oscillations accompanying tactile stimulation

We applied a new method of imaging frequency-specific changes in brain activity in humans during a finger brushing task in order to measure changes in cortical rhythms during tactile stimulation. Neuromagnetic recordings were conducted in five subjects using a whole-head MEG system during tactile stimulation of the right index finger, with or without visual feedback, and while viewing another individual's index finger being stimulated. Volumetric images of changes in source power relative to pre-stimulus baseline levels were computed with 2 mm resolution over the entire brain using a minimum-variance beamforming algorithm (synthetic aperture magnetometry). Onset of tactile stimulation produced a brief (200-300 ms) suppression of mu band (8-15 Hz) and beta band (15-30 Hz) cortical activity in the primary somatosensory and primary motor cortex, respectively, followed by a bilateral increase in beta band activity ('beta rebound') in motor cortex. This pattern of suppression/rebound was absent when subjects observed finger brushing or brushing motions without receiving stimulation. In contrast, these conditions resulted in bilateral increases in beta band activity in sensorimotor areas and decreased power in the alpha (8-12 Hz) band in primary visual areas. These results show that spatially filtered MEG provides a useful method for directly imaging the temporal sequence of changes in cortical rhythms during transient tactile stimulation, and provide evidence that observation of tactile input to another individual's hand, or object motion itself, can influence independent rhythmic activity in visual and sensorimotor cortex.