EMG Rectification Is Detrimental for Identifying Abnormalities in Corticomuscular and Intermuscular Coherence in Spinocerebellar Ataxia Type 2.

Corticomuscular and intermuscular coherence (CMC, IMC) reflect connectivity between neuronal activity in the motor cortex measured by electroencephalography (EEG) and muscular activity measured by electromyography (EMG), or between activity in different muscles, respectively. There is an ongoing debate on the appropriateness of EMG rectification prior to coherence estimation. This work examines the effects of EMG rectification in CMC and IMC estimation in 20 spinocerebellar ataxia type 2 (SCA2) patients, 16 prodromal SCA2 gene mutation carriers, and 26 healthy controls during a repetitive upper or lower limb motor task. Coherence estimations were performed using the non-rectified raw EMG signal vs. the rectified EMG signal. EMG rectification decreases the level of significance of lower beta-frequency band CMC and IMC values in SCA2 patients and prodromal SCA2 mutation carriers vs. healthy controls, and also results in overall lower coherence values. EMG rectification is detrimental for beta-frequency band CMC and IMC estimation. One likely reason for this effect is distortion of coherence estimation in high-frequency signals, where the level of amplitude cancelation is high.

Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis.

OBJECTIVE: In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. METHODS: Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [11C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [11C]-PBR28 uptake. RESULTS: In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [11C]-PBR28 binding in the left motor cortex was correlated with FA (r = -0.68, p < 0.05) and cortical thickness (r = -0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = -0.77, p < 0.05), and cortical thickness (r = -0.75, p < 0.05) in the motor cortex. CONCLUSIONS: Increased uptake of the glial marker [11C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS.

Electro- and magneto-encephalographic spike source localization of small focal cortical dysplasia in the dorsal peri-rolandic region.

OBJECTIVE: Small focal cortical dysplasia (FCD) may be ambiguous or overlooked on magnetic resonance (MR) imaging. Source localization of EEG and magnetoencephalography (MEG) spikes was evaluated to confirm the diagnosis of small FCD. METHODS: This study included 6 epilepsy patients with a single small lesion on MR imaging suggesting FCD within a single gyrus among 181 consecutive epilepsy patients admitted to our epilepsy monitoring unit over 27 months. Stereotypical interictal spikes were detected on simultaneous EEG and MEG recordings and the onset-related source of averaged spikes was estimated. RESULTS: All 6 patients had unique clinical characteristics as follows: leg sensori-motor seizures in 5 patients and eye version in 1 patient; a small MR imaging lesion suggesting FCD in the dorsal peri-rolandic region, which had been overlooked until our evaluation; and both EEG and MEG dipoles were estimated adjacent to the MR imaging lesion. CONCLUSIONS: Source localization of EEG and MEG spikes can confirm the diagnosis of FCD based on a single small MR imaging lesion, which was overlooked by previous examination of MR images. SIGNIFICANCE: Examination of MR images should be based on spike source localization as well as seizure semiology to identify subtle MR imaging abnormalities.

Abnormal motor cortex excitability is associated with reduced cortical thickness in X monosomy.

Turner syndrome (TS) is a noninherited genetic disorder caused by the absence of one or part of one X chromosome. It is characterized by physical and cognitive phenotypes that include motor deficits that may be related to neuroanatomical abnormalities of sensorimotor pathways. Here, we used transcranial magnetic stimulation (TMS) and cortical thickness analysis to assess motor cortex excitability and cortical morphology in 17 individuals with TS (45, X) and 17 healthy controls. Exploratory analysis was performed to detect the effect of parental origin of the X chromosome (X(mat), X(pat)) on both measures. Results showed that long-interval intracortical inhibition was reduced and motor threshold (MT) was increased in TS relative to controls. Areas of reduced thickness were observed in the precentral gyrus of individuals with TS that correlated with MT. A significant difference between X(mat) (n = 11) and X(pat) (n = 6) individuals was found on the measure of long-interval intracortical inhibition. These findings demonstrate the presence of converging anatomical and neurophysiological abnormalities of the motor system in X monosomy.

RAD51 haploinsufficiency causes congenital mirror movements in humans.

Congenital mirror movements (CMM) are characterized by involuntary movements of one side of the body that mirror intentional movements on the opposite side. CMM reflect dysfunctions and structural abnormalities of the motor network and are mainly inherited in an autosomal-dominant fashion. Recently, heterozygous mutations in DCC, the gene encoding the receptor for netrin 1 and involved in the guidance of developing axons toward the midline, have been identified but CMM are genetically heterogeneous. By combining genome-wide linkage analysis and exome sequencing, we identified heterozygous mutations introducing premature termination codons in RAD51 in two families with CMM. RAD51 mRNA was significantly downregulated in individuals with CMM resulting from the degradation of the mutated mRNA by nonsense-mediated decay. RAD51 was specifically present in the developing mouse cortex and, more particularly, in a subpopulation of corticospinal axons at the pyramidal decussation. The identification of mutations in RAD51, known for its key role in the repair of DNA double-strand breaks through homologous recombination, in individuals with CMM reveals a totally unexpected role of RAD51 in neurodevelopment. These findings open a new field of investigation for researchers attempting to unravel the molecular pathways underlying bimanual motor control in humans.

Concurrent bilateral projection and activation of motor cortices in a patient with congenital mirror movements: a TMS study.

OBJECTIVES: Mirror movements (MMs) are unintended and unnecessary movements accompanying voluntary activity in homologous muscles on the opposite side of the body, particularly in distal arm muscles. Congenital MMs may be sporadic or familial. Several mechanisms have been proposed to explain persistent congenital MMs. Hypothesis 1 assumes the existence of an ipsilateral corticospinal pathway, and Hypothesis 2 the activation of both motor cortices. We report a new case of congenital mirror movements in a healthy woman. METHODS: Electromyographic recordings and focal transcranial magnetic stimulation (TMS) were used for neurophysiological evaluation. RESULTS: Voluntary contraction of either abductor pollicis brevis (APB) elicited mirror activation of the other APB. Focal TMS of either M1 elicited motor evoked potential (MEP) of normal latency and amplitude in both resting APB. TMS of the left cortex upon maximal contraction of the right APB and mirror contraction of the left APB produced interhemispheric inhibition (IHI) in the former and silent period (SP) in the later. CONCLUSIONS: The electrophysiological evaluation using transcranial magnetic stimulation provides evidence of the concurrent action of both mechanisms in this patient. SIGNIFICANCE: The combination of more than one hypothesis could be more appropriate for understanding the underlying mechanism in some MM cases.

Agenesis of the arcuate fasciculi in congenital bilateral perisylvian syndrome: a diffusion tensor imaging and tractography study.

OBJECTIVE: To describe the absence of the arcuate fasciculi in 2 cases of congenital bilateral perisylvian syndrome (CBPS). DESIGN: Case series. SETTING: Pediatric referral hospital-based study. PATIENTS: Two patients with CBPS, referred to our institution as candidates for surgical treatment of epilepsy. Intervention Diffusion tensor imaging (1.5-T scanner; 15 encoding directions; b = 800 s/mm(2)) and deterministic tractography of the main projection and association tracts. MAIN OUTCOME MEASURES: Neuropsychology evaluation; fractional anisotropy, apparent diffusion coefficients, and anatomical aspect of the tracts. RESULTS: Absence of the arcuate fasciculus was observed in both subjects. Ancillary findings were complete absence of the superior longitudinal fasciculi in 1 case and underdevelopment in the other. Low fractional anisotropy of the left inferior occipitofrontal fasciculus was found in both cases. The same tract was maloriented in 1 of the cases. CONCLUSION: Agenesis of the arcuate fasciculus may accompany CBPS.

Reduced cortical folding in mental retardation.

BACKGROUND AND PURPOSE: MR is a developmental disorder associated with impaired cognitive functioning and deficits in adaptive behavior. With a 2D region of interest-based GI, a preliminary study reported significantly reduced gyrification in the prefrontal lobe in MR. The purpose of this study was to further investigate the abnormalities of cortical gyrification in MR and to explore the possible causes of these abnormalities. MATERIALS AND METHODS: Thirteen patients with MR and 26 demographically matched healthy controls were included in this study. A 3D surface-based lGI was calculated as a measure to quantify gyrification. Then vertex-by-vertex contrasts of lGI were performed between patients with MR and healthy controls. RESULTS: Statistical analysis showed that patients with MR had significantly reduced lGI in multiple brain regions compared with healthy controls. These regions include the lateral and medial prefrontal cortices, the right superior temporal gyrus, the left superior parietal lobe, the bilateral insular and adjacent cortices, and the visual and motor cortices. CONCLUSIONS: The observed abnormal pattern of cortical gyrification revealed by significant reduction of lGI in multiple brain regions might reflect the developmental disturbance in intracortical organization and cortical connectivities in MR.

Reorganization of sensorimotor function after functional hemispherectomy studied using near-infrared spectroscopy.

Hemimegalencephaly is a rare congenital disease that occurs with intractable epilepsy and is a childhood developmental disorder. A functional hemispherectomy is indicated for the treatment of hemimegalencephaly with intractable epilepsy. We present a case of hemimegalencephaly in a 6-month-old male. After hemispherectomy, his seizures disappeared completely and postoperative neurological examination showed right hemiplegia. His right arm and limb function were recovered gradually by rehabilitation with passive movement. We investigated cortical activation using near-infrared spectroscopy (NIRS). Serial NIRS showed right cortical activation by passive movement of his right arm. We suggest that NIRS showed the ipsilateral reorganization process as an effect of neurorehabilitation for disconnection of the brain.

Diffusion tensor tractography can predict hemiparesis in infants with high risk factors.

Diffusion tensor tractography (DTT) is known to be useful in detecting white matter lesions. In the current study, we report on two hemiparetic patients with risk factors who showed abnormalities of the corticospinal tract (CST) on diffusion tensor tractography (DTT) prior to the manifestation of hemiparesis. Two hemiparetic patients with risk factors (preterm, low birth weight) and six age-matched normal control subjects were enrolled to this study. Diffusion tensor imaging (DTI) was performed at the age of 43 weeks (patient 1) and 33 weeks (patient 2) using 1.5-T with a Synergy-L Sensitivity Encoding (SENSE) head coil. We measured fractional anisotropy (FA), apparent diffusion coefficients (ADCs), and fiber counts of the CST. There were no definite asymmetric findings on physical examination and conventional brain MRI. By contrast, DTT showed a unilateral CST disruption at the periventricular white matter, low FA values, and low CST fiber counts compared with those of the unaffected CST and controls. These patients were diagnosed with hemiparetic cerebral palsy when we re-evaluated these patients at the age of 6 years (patient 1) and 3 years of age (patient 2), respectively. In these two patients, DTT revealed abnormalities of the CST prior to the manifestation of hemiparesis. Therefore, it seems that DTT would be a useful modality in detecting CST abnormalities in advance of clinical manifestation in infants with high risk factors.

Epilepsia partialis continua with dystonic hand movement in a patient with a malformation of cortical development.

Malformations of cortical development (MCD) with polymicrogyria and schizencephaly are due to abnormal cortical organization and usually manifest by intractable epilepsy and mental retardation. Epileptical activity is often hard to register and focal dystonia associated with such MCD has previously been described but without any metabolic imaging. We report here a 46-year-old man presenting with late-onset atypical abnormal movements of his left hand associated with right central region MCD. To demonstrate the involvement of an epileptical focus, we performed [(18)F]FDG-PET and fMRI both before and after a single dose of clobazam and diazepam, respectively. Characteristics of the abnormal hand movements, clinical response to the medication, and the result of the [(18)F]FDG-PET and fMRI investigations all favor the diagnosis of epilepsia partialis continua. We conclude that the dystonic movement is part of the partial seizure.

Presurgical and intraoperative mapping of the motor system in congenital truncation of the precentral gyrus.

A 43-year-old man presented with a grade II astrocytoma in the left postcentral gyrus and superior parietal lobule. Preoperative functional MR imaging and diffusion tensor imaging mapped distal upper-extremity primary motor cortex and white matter, respectively, adjacent to the tumor, within a congenitally truncated precentral gyrus. Because of the congenital anomaly, this region of primary motor cortex was inaccessible to direct visualization or intraoperative electrocortical stimulation. The integration of preoperative and intraoperative mapping data facilitated resection of the tumor while avoiding a postoperative motor deficit.

Coherent corticomuscular oscillations originate from primary motor cortex: evidence from patients with early brain lesions.

Coherent oscillations of neurons in the primary motor cortex (M1) have been shown to be involved in the corticospinal control of muscle activity. This interaction between M1 and muscle can be measured by the analysis of corticomuscular coherence in the beta-frequency range (beta-CMCoh; 14-30 Hz). Largely based on magnetoencephalographic (MEG) source-modeling data, it is widely assumed that beta-CMCoh reflects direct coupling between M1 and muscle. Deafferentation is capable of modulating beta-CMCoh, however, and therefore the influence of reafferent somatosensory signaling and corresponding neuronal activity in the somatosensory cortex (S1) has been unclear. We present transcranial magnetic stimulation (TMS) and MEG data from three adult patients suffering from congenital hemiparesis due to pre- and perinatally acquired lesions of the pyramidal tract. In these patients, interhemispheric reorganization had resulted in relocation of M1 to the contralesional hemisphere, ipsilateral to the paretic hand, whereas S1 had remained in the lesioned hemisphere. This topographic dichotomy allowed for an unequivocal topographic differentiation of M1 and S1 with MEG (which is not possible if M1 and S1 are directly adjacent within one hemisphere). In all patients, beta-CMCoh originated from the contralesional M1, in accordance with the TMS-evoked motor responses, and in contrast to the somatosensory evoked fields (SEFs) for which the sources (N20m) were localized in S1 of the lesioned hemisphere. These data provide direct evidence for the concept that beta-CMCoh reflects the motorcortical efferent drive from M1 to the spinal motoneuron pool and muscle. No evidence was found for a relevant contribution of neuronal activity in S1 to beta-CMCoh.

Sensorimotor organization in double cortex syndrome.

Subcortical band heterotopia is a diffuse malformation of cortical development related to pharmacologically intractable epilepsy. On magnetic resonance imaging (MRI), patients with "double cortex" syndrome (DCS) present with a band of heterotopic gray matter separated from the overlying cortex by a layer of white matter. The function and connectivity of the subcortical heterotopic band in humans is only partially understood. We studied six DCS patients with bilateral subcortical band heterotopias and six healthy controls using functional MRI (fMRI). In controls, simple motor task elicited contralateral activation of the primary motor cortex (M1) and ipsilateral activation of the cerebellum and left supplementary motor area (SMA). All DCS patients showed task-related contralateral activation of both M1 and the underlying heterotopic band. Ipsilateral motor activation was seen in 4/6 DCS patients. Furthermore, there were additional activations of nonprimary normotopic cortical areas. The sensory stimulus resulted in activation of the contralateral primary sensory cortex (SI) and the thalamus in all healthy subjects. The left sensory task also induced a contralateral activation of the insular cortex. Sensory activation of the contralateral SI was seen in all DCS patients and secondary somatosensory areas in 5/6. The heterotopic band beneath SI became activated in 3/6 DCS patients. Activations were also seen in subcortical structures for both paradigms. In DCS, motor and sensory tasks induce an activation of the subcortical heterotopic band. The recruitment of bilateral primary areas and higher-order association normotopic cortices indicates the need for a widespread network to perform simple tasks.

Spontaneous motor cortex encephalocele presenting with simple partial seizures and progressive hemiparesis. Case report and review of the literature.

Several cases of congenital or acquired temporal encephaloceles have been reported in the literature as the causative mechanism of simple and/or complex partial seizures. In this report the authors describe a rare case of spontaneous parietal encephalocele presenting with simple partial seizures and progressively increasing contralateral upper-extremity motor deficit. The unusual anatomical location of an encephalocele associated with seizures and the delayed seizure onset represent distinctive characteristics in this case. Preoperative imaging included surface electroencephalography, computerized tomography, and brain magnetic resonance imaging. Frameless neuronavigation and intraoperative cortical mapping were used to aid resection of the encephalocele, and the dural and bone defects were reconstructed. The surgical outcome in this case was excellent, and the patient has remained seizure free. The pertinent literature is reviewed in this report.

Lack of orientation due to a congenital brain malformation: a case study.

Topographical disorientation is usually described in patients who have lost the ability to orient themselves as a consequence of acquired focal brain damage. Here, we describe the case of a 20-year-old woman with a congenital brain malformation who has never been able to orient herself within the environment. We addressed in detail her ability to orient and navigate within the environment by administering a number of tasks in both ecological and experimental surroundings. The results indicate a complete inability to use any kind of strategy useful for orientation.

Structural and functional aberrations in the cerebral cortex of tenascin-C deficient mice.

The extracellular matrix glycoprotein tenascin-C (TNC) has been implicated in neural development and plasticity but many of its functions in vivo remain obscure. Here we addressed the question as to whether the constitutive absence of TNC in mice affects cortical physiology and structure. Defined major cell populations (neurons and inhibitory neuronal subpopulations, astrocytes, oligodendrocytes and microglia) were quantified in the somatosensory and motor cortices of adult TNC deficient (TNC-/-) and wild-type (TNC+/+) mice by immunofluorescence labelling and stereology. In both areas studied we found abnormally high neuronal density, astrogliosis, low density of parvalbumin-positive interneurons and reduced ratios of oligodendrocytes to neurons and of inhibitory to excitatory neurons in the TNC deficient as opposed to the non-deficient animals. Analysis of Golgi-impregnated layer V pyramidal neurons in TNC-/- animals showed aberrant dendrite tortuosity and redistribution of stubby spines within first- to third-order dendritic arbors. Significantly enhanced responses upon whisker stimulation were recorded epicranially over the barrel and the motor cortices of TNC-/- as compared to TNC+/+ animals, and this effect might be associated with the diminished inhibitory circuitry. These results indicate that TNC is essential for normal cortical development and function.

Subcortical nodular heterotopia: a functional MRI and somatosensory evoked potentials study.

Subcortical nodular heterotopia (SNH) associated with refractory epilepsy may be surgically treated, and a positive outcome can be expected following the complete excision of the malformed tissue. Recent functional neuroimaging studies have suggested the possible functional relevance of cerebral malformations, and may make it possible to improve presurgical planning, thus allowing extended resections and minimising post-operative deficits. We here report the case of a 19-year-old man with epilepsy and a giant SNH associated with diffused abnormal gyrations of the right temporal-parietal regions. Cortical functional organisation was investigated by means of functional magnetic resonance imaging (MRI) during sensory and motor tasks, and somatosensory evoked potentials. The results revealed enlarged and displaced motor and sensory cortical areas with heterotopic tissue functional activation. The relevance of these findings is discussed in the light of the possible surgical treatment of drug-refractory epilepsy associated with cerebral malformations: surgical treatment based on conventional MRI studies alone, without taking the functional nature of dysplastic tissues into account, may lead to considerable side effects.

Ipsilateral motor pathway confirmed by diffusion tensor tractography in a patient with schizencephaly.

We evaluated the hand motor function of a right hemiparetic patient with schizencephaly using a combination of fMRI, transcranial magnetic stimulation, and diffusion tensor tractography (DTT). Only the unaffected (right) primary sensori-motor cortex was found to be activated during either affected (right) or unaffected hand movements. Evoked motor potentials with similar characteristics were obtained from both abductor pollicis brevis muscles simultaneously when stimulating the unaffected motor cortex. Moreover, a tract presumed to be a corticospinal tract was observed in the unaffected hemisphere by DTT, however, no tract was observed in the affected hemisphere. Our results indicate that the ipsilateral corticospinal tract extended from the unaffected (right) motor cortex to both hands. This finding may reflect functional reorganization of motor function in a patient with congenital brain disorder.