Reduced afferent-induced facilitation of primary motor cortex excitability in restless legs syndrome.

Restless legs syndrome (RLS) is characterized by the association of an urge to move, and vesperal or nocturnal sensory symptoms; it is frequently associated with periodic limb movements. Evidence from imaging and electrophysiological studies suggests that RLS is linked to changes in sensorimotor integration. Nevertheless, the underlying mechanisms have not been characterized, and the cortical origin has yet to be confirmed. The objective of the present study was to establish whether or not sensorimotor integration in RLS patients is impaired in the evening. The time-dependent modulation of motor cortex excitability following peripheral electric nerve stimulation was studied in 14 idiopathic RLS patients, and 14 paired healthy controls. Different inter-stimulus intervals were used to measure short-latency and long-latency afferent inhibition (SAI and LAI) and afferent-induced facilitation (AIF). Motor evoked potentials were recorded from the first dorsal interosseous muscle in two experimental sessions (one in the morning and one in the evening). With the exception of LAI (which was present in the morning but absent in the evening in both healthy controls and RLS patients), no circadian variations were observed in sensorimotor integration. Although SAI was present in patients with RLS, AIF was disrupted (relative to controls) - suggesting the presence of an indirect sensorimotor integration disorder affecting the long corticocortical pathways in patients with RLS. The lack of circadian modulation in sensorimotor integration suggests that clinical circadian variations have other causes.

Involvement of cortico-subcortical circuits in normoacousic chronic tinnitus: A source localization EEG study.

OBJECTIVE: To better characterize brain circuits dysfunctions in normoacousic tinnitus sufferers. METHODS: 17 normoacousic chronic, unilateral high-pitched tinnitus sufferers (6 females, 43.6 ± 9.8 y.o, disease duration 22 ± 35 months) underwent a 29-channel resting-state electroencephalography (EEG - 5 min opened-eyes, 5 min closed-eyes) and auditory oddball paradigm for event-related potentials analyses (ERPs - N1, P2 and P300). Cortical 3D distribution of current source density was computed with sLORETA. Results were compared with 17 controls (9 females, 45.7 ± 15.1 y.o). RESULTS: Eyes opened, tinnitus sufferers had lower alpha and beta sources in the left inferior parietal lobule. Eyes closed, tinnitus sufferers had decreased alpha sources in the left inferior temporal and post-central gyri, and low gamma sources in the left middle temporal gyrus. EEG data did not correlate with tinnitus sufferers' clinical features. Subjects with tinnitus had shorter N1 and P2 latencies. P300 did not differ between groups. sLORETA solutions showed decreased sources of these ERPs in the left inferior temporal gyrus in the tinnitus group. CONCLUSIONS: We showed cortico-thalamo-cortical involvements in normoacousic tinnitus with hyperexcitability of the left auditory cortex and inferior temporal gyrus. SIGNIFICANCE: This might reflect processes of maladaptive cortical plasticity and memory consolidation. Further validation is needed to establish the value of this tool in customizing therapeutic approach.

Striatal hand in Parkinson's disease: the re-evaluation of an old clinical sign.

Among postural abnormalities in Parkinson's disease (PD), striatal hand (SH) is a particularly underexplored phenomenon. It leads to extreme abnormalities of hand posture, causing altered dexterity, pain and disfigurement. In our study, three blinded investigators examined several pictures of the hands of individuals with PD (N = 40) and controls (N = 15). The investigators quantified postural alterations using the Striatal Hand Score. Demographic and clinical data were also collected. As no differences were detected among investigators agreement, a final Hand Score (HS, range 0-4) was obtained for each hand. The Striatal Hand Score in both the left and right hand was significantly different in PD compared to controls (p < 0.001 for both left and right hand). Striatal hand was significantly worse on the side of PD onset, and on the side with greater PD symptomatology. The finding of a striatal hand was 100 % specific for a diagnosis of PD. Nine PD subjects were evaluated both on and off medication, and dopaminergic treatment did not significantly change the Striatal Hand Score. Our findings suggest that in patients without any explanation for hand deformities other than PD, striatal hand occurs very often, and is highly specific for the side of worst PD involvement. We recommend including an evaluation for SH as part of routine practice. This study emphasizes the importance of a careful observation of the patient in order to improve diagnostic accuracy.

Excitatory deep repetitive transcranial magnetic stimulation with H-coil as add-on treatment of motor symptoms in Parkinson's disease: an open label, pilot study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a potential treatment for Parkinson's disease (PD). H-coils, inducing deeper and wider magnetic fields compared to traditional coils, may be potentially useful in PD, characterized by widespread, bilateral involvement of cortico-subcortical circuits. OBJECTIVE: To evaluate the safety of repetitive deep TMS (rDTMS) with H-coil as add-on treatment of motor symptoms in PD. METHODS: Twenty-seven PD patients (aged 60.1 ± 6.8 y; PD-duration: 6.3 ± 2.8 y; motor-UPDRS: 39.6 ± 10.1) underwent 12 rDTMS sessions over 4 weeks at excitatory (10 Hz) frequency over primary motor (M1) and bilateral prefrontal (PF) regions. Motor UPDRS off therapy was assessed before and after the last rDTMS session, together with safety records at each treatment session. RESULTS: No drop-outs or adverse events were recorded. Motor UPDRS significantly improved after rDTMS (10.8 points average reduction; P < 0.0001). CONCLUSIONS: High-frequency rDTMS might be a safe treatment for PD motor symptoms. Further placebo-controlled, randomized studies are warranted.

Action-related semantic content and negation polarity modulate motor areas during sentence reading: an event-related desynchronization study.

Our study evaluated motor cortex involvement during silent reading of sentences referring to hand actions. We aimed at defining whether sentential polarity (affirmative vs. negative) would modulate motor cortex activation using the event-related desynchronization (ERD) analysis of the mu rhythm. Eleven healthy volunteers performed a reading task involving 160 sentences (80 affirmative: 40 hand-related, 40 abstract; 80 negative: 40 hand-related, 40 abstract). After reading each sentence, subjects had to decide whether the verb was high or low frequency in Italian. Electroencephalographic (EEG) activity was recorded with 32 surface electrodes and mu ERD analyses were performed for each subject. Hand-action related sentences induced a greater mu ERD over the left premotor and motor hand areas compared to abstract sentences. Mu ERD was greater and temporally delayed when the hand-related verbs were presented in the negative versus affirmative form. As predicted by the "embodied semantic" theory of language understanding, motor areas were activated during sentences referring to hand actions. In addition, motor cortex activation was larger for negative than affirmative motor sentences, a finding compatible with the hypothesis that comprehension is more demanding in the specific case of motor content negation.

Movement preparation and cortical processing of afferent inputs in cortical tremor: an event-related (de)synchronization (ERD/ERS) study.

OBJECTIVE: We sought to characterize cortical activity related to motor control in patients presenting with isolated cortical tremor, in order to determine whether or not myoclonus-related impairments are a source of event-related desynchronization/synchronization (ERD/ERS) disruption. METHODS: Nine patients presenting with isolated cortical tremor were compared with controls. Mu and beta ERD/ERS were computed over the scalp and brain surfaces using 128-channel electroencephalographic (EEG) recording during voluntary and passive finger extensions. We recorded somatosensory-evoked potentials following median nerve stimulation and performed myoclonic jerk-locked back-averaging of EEG activity. RESULTS: Back-averaging revealed a cortical premyoclonic spike in all patients. Five of the nine patients had exaggerated SEPs. The amplitude of mu ERD was greater in patients. Beta ERD/ERS did not differ from that seen in controls. Localizations of mu and beta ERD/ERS did not differ from controls and were identified in pre- and post-central sensorimotor cortical areas. CONCLUSIONS: The present results suggest a hyperexcitability of the cortico-subcortical loops responsible for movement preparation and execution. Post-movement inhibition related to cortical processing of afferent input is unaffected in isolated cortical myoclonus. SIGNIFICANCE: Intracortical abnormalities can differ in patients suffering from cortical myoclonus, according to whether or not the individuals have associated epileptic symptoms.

Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease.

OBJECTIVE: To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). BACKGROUND: Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. METHODS: In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. RESULTS: We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. CONCLUSION: iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.

Afferent-induced facilitation of primary motor cortex excitability in the region controlling hand muscles in humans.

Sensory inputs from cutaneous and limb receptors are known to influence motor cortex network excitability. Although most recent studies have focused on the inhibitory influences of afferent inputs on arm motor responses evoked by transcranial magnetic stimulation (TMS), facilitatory effects are rarely considered. In the present work, we sought to establish how proprioceptive sensory inputs modulate the excitability of the primary motor cortex region controlling certain hand and wrist muscles. Suprathreshold TMS pulses were preceded either by median nerve stimulation (MNS) or index finger stimulation with interstimulus intervals (ISIs) ranging from 20 to 200 ms (with particular focus on 40-80 ms). Motor-evoked potentials recorded in the abductor pollicis brevis (APB), first dorsalis interosseus and extensor carpi radialis muscles were strongly facilitated (by up to 150%) by MNS with ISIs of around 60 ms, whereas digit stimulation had only a weak effect. When MNS was delivered at the interval that evoked the optimal facilitatory effect, the H-reflex amplitude remained unchanged and APB motor responses evoked with transcranial electric stimulation were not increased as compared with TMS. Afferent-induced facilitation and short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) mechanisms are likely to interact in cortical circuits, as suggested by the strong facilitation observed when MNS was delivered concurrently with ICF and the reduction of SICI following MNS. We conclude that afferent-induced facilitation is a mechanism which probably involves muscle spindle afferents and should be considered when studying sensorimotor integration mechanisms in healthy and disease situations.

Cortical involvement in the sensory and motor symptoms of primary restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is characterized by closely interrelated motor and sensory disorders. Two types of involuntary movement can be observed: periodic leg movements during wakefulness (PLMW) and periodic leg movements during sleep (PLMS). Basal ganglia dysfunction in primary RLS has often been suggested. However, clinical observations raise the hypothesis of sensorimotor cortical involvement in RLS symptoms. Here, we explored cortical function via movement-related beta and mu rhythm reactivity. METHODS: Twelve patients with idiopathic, primary RLS were investigated and compared with 10 healthy subjects. In the patient group, we analyzed event-related beta and mu (de)synchronization (ERD/S) for PLMS and PLMW during a suggested immobilization test (SIT). An ERD/S analysis was also performed in patients and controls during self-paced right ankle dorsal flexion at 8:30 PM (i.e., the symptomatic period for patients) and 8:30 AM (the asymptomatic period). RESULTS: Before PLMS, there was no ERD. Intense ERS was recorded after PLMS. As with voluntary movement, cortical ERD was always observed before PLMW. After PLMW, ERS had a diffuse scalp distribution. Furthermore, the ERS and ERD amplitudes and durations for voluntary movement were greater during the symptomatic period than during the asymptomatic period and in comparison with healthy controls, who presented an evening decrease in these parameters. Patients and controls had similar ERD and ERS patterns in the morning. CONCLUSION: On the basis of a rhythm reactivity study, we conclude that the symptoms of RLS are related to cortical sensorimotor dysfunction.

Deficient "sensory" beta synchronization in Parkinson's disease.

OBJECTIVE: Beta rhythm movement-related synchronization (beta synchronization) reflects motor cortex deactivation and sensory afference processing. In Parkinson's disease (PD), decreased beta synchronization after active movement reflects abnormal motor cortex idling and may be involved in the pathophysiology of akinesia. The objectives of the present study were to (i) compare event-related synchronization after active and passive movement and electrical nerve stimulation in PD patients and healthy, age-matched volunteers and (ii) evaluate the effect of levodopa. METHODS: Using a 128-electrode EEG system, we studied beta synchronization after active and passive index finger movement and electrical median nerve stimulation in 13 patients and 12 control subjects. Patients were recorded before and after 150% of their usual morning dose of levodopa. RESULTS: The peak beta synchronization magnitude in the contralateral primary sensorimotor (PSM) cortex was significantly lower in PD patients after active movement, passive movement and electrical median nerve stimulation, compared with controls. Levodopa partially reversed the drop in beta synchronization after active movement but not after passive movement or electrical median nerve stimulation. DISCUSSION: If one considers that beta synchronization reflects sensory processing, our results suggest that integration of somaesthetic afferences in the PSM cortex is abnormal in PD during active and passive movement execution and after simple electrical median nerve stimulation. SIGNIFICANCE: Better understanding of the mechanisms involved in the deficient beta synchronization observed here could prompt the development of new therapeutic approaches aimed at strengthening defective processes. The lack of full beta synchronization restoration by levodopa might be related to the involvement of non-dopaminergic pathways.

Post-movement beta synchronization in subjects presenting with sensory deafferentation.

OBJECTIVE: We studied the time course and location of post-movement beta synchronization (PMBS) in patients presenting with sensory deafferentation, in order to assess the hypothetical relationship between the PMBS and the cortical processing of movement-related somatosensory afferent inputs. METHODS: We used the event-related synchronization (ERS) method. EEG activity was recorded (via a 128-electrode system) during brisk, unilateral right and left index finger extension by 10 patients presenting with neuropathic pain related to sensory deafferentation. Intra- and post-movement changes in beta source power were calculated relative to pre-movement baseline activity. We compared the PMBS results for the painful and non-painful body sides. Furthermore, PMBS patterns in patients were compared with those in nine healthy volunteers. RESULTS: PMBS pattern related to the painful side had a spatial distribution, with an ipsilateral preponderance, significantly more restricted than PMBS pattern on the non-painful side and in the control group. There were no significant differences between patient PMBS patterns on the non-painful side and those in the control group. CONCLUSIONS: Sensory deafferentation disrupts normal PMBS patterns. SIGNIFICANCE: This work provides additional arguments to the hypothesis supporting that the PMBS is influenced by movement-related somatosensory input processing.

The effects of low- and high-frequency repetitive TMS on the input/output properties of the human corticospinal pathway.

The objective of this study was to characterize the effects of various parameters (notably the frequency and intensity) of repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor (M1) and premotor (PMC) cortices on the excitability of the first dorsalis interosseus (FDI) corticospinal pathway. To this end, we applied a comprehensive input-output analysis after fitting the experimental results to a sigmoidal function. Twenty-six healthy subjects participated in the experiments. Repetitive TMS was applied either over M1 or PMC at 1 Hz (LF) for 30 min (1,800 pulses) or at 20 Hz (HF) for 20 min (1,600 pulses). In the HF condition, the TMS intensity was set to 90% (HF(90)) of the FDI's resting motor threshold (RMT). In the LF condition, the TMS intensity was set to either 90% (LF(90)) or 115% (LF(115)) of the RMT. The FDI input/output (I/O) curve was measured on both sides of the body before rTMS (the Pre session) and then during two Post sessions. For each subject, the I/O curves (i.e., the integral of the FDI motor-evoked potential (MEP) vs. stimulus intensity) were fitted using a Boltzmann sigmoidal function. The graph's maximum slope, S (50) and plateau value were then compared between Pre and Post sessions. LF(115) over M1 increased the slope of the FDI I/O curve but did not change the S (50) and plateau value. This also suggested an increase in the RMT. HF(90) led to a more complex effect, with an increase in the slope and a decrease in the S (50) and plateau value. We did not see a cross effect on the homologous FDI corticospinal pathway, and only PMC LF(90) had an effect on ipsilateral corticospinal excitability. Our results suggest that rTMS may exert a more complex influence on cortical network excitability than is usually reported (i.e. simple inhibitory or facilitatory effects). Analysis of the fitted stimulus response curve indicates a dichotomous influence of both low- and high-frequency rTMS on M1 cortical excitability; this may reflect intermingled effects on excitatory and inhibitory cortical networks.

Motor representation areas in epileptic patients with focal motor seizures: a TMS study.

PURPOSE: This study used TMS mapping to investigate the motor representation of the abductor pollicis brevis (APB) muscles in a group of patients with focal epilepsy originating in central or pre-central region. METHODS: Eight epileptic patients and eight control subjects participated in the study. The coil was moved in 1.5-cm steps along a grid drawn on the subject's skull over the motor cortex of both hemispheres. At each site, six APB motor responses (evoked by TMS at 1.2 times the resting motor threshold) were recorded and averaged. The peak-to-peak amplitude was measured and plotted against the mediolateral and anteroposterior coil positions. The area of each APB muscle representation was measured and the position of the optimal point was calculated. RESULTS: The resting motor threshold was increased bilaterally in epileptic patients. The maps were distorted in most patients (but not in control subjects), as evidenced by an off-centre optimal point. Interhemispheric differences in APB map areas were greater in patients than in control subjects. However, whether these increases in map area were on the epileptic side or on healthy side depended on the given subject. CONCLUSIONS: The changes in APB representation observed in epileptic patients demonstrate that reorganization occurs within the motor cortex. The heterogeneity of the present results is probably related to different locations of the epileptogenic and/or lesional areas and to a variety of compensatory phenomena that may occur, notably with respect to the disease duration.

Low frequency repetitive transcranial magnetic stimulation over premotor cortex can improve cortical tremor.

OBJECTIVE: To examine the effects of a 30 min, 1 Hz subthreshold rTMS in a case of cortical tremor which is caused by hyperexcitability of sensorimotor cortex. METHODS: Stimulation was applied over primary and, in a second time, over premotor cortex (M1 and PMC, respectively). Tremor was monitored by accelerometers placed on the index fingers of hands outstretched, before and several times after rTMS. Each rTMS session consisted of 1800 pulses delivered at 1 Hz with an intensity of 90% of resting motor threshold. RESULTS: PMC but not M1 stimulation led to a decrease of the postural tremor (90% decrease of acceleration total spectral power). This functional benefit was associated to normalization of electrophysiologic parameters (short-interval intracortical inhibition and cortical silent period duration). Moreover, when stimulating PMC during two daily sessions, improvement of the tremor was longer than one day stimulation and this benefit was associated with functional improvement. CONCLUSIONS: This study shows that 1 Hz rTMS over premotor cortex can improve cortical tremor. SIGNIFICANCE: These results raise the interest of the motor cortical stimulation as a possible therapeutic target for treatment of action tremor.

The effect of repetitive transcranial magnetic stimulation on dystonia: a clinical and pathophysiological approach.

Dystonia is characterized by sustained muscle contraction, which frequently causes repetitive, twisting movements or abnormal posture. The precise pathophysiological mechanisms of dystonia are still unknown. Several studies did demonstrate that, although motor cortex hyperexcitability appears to be responsible for abnormal co-contraction and overflow to adjacent muscles, plasticity mechanisms and integrative sensorimotor processing are also likely to be involved in this condition. Current dystonia treatments are based on oral medication, injection of botulinum toxin and, in a low proportion of cases, bi-pallidal deep brain stimulation. However, treatment outcome is generally disappointing. A few researchers have reported the application of repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex or the premotor cortex, with the goal of decreasing motor cortex hyperexcitability. This article reviews all studies using this technique in dystonia and discusses rTMS therapeutic impact and its possible mechanisms of action in this indication. Currently, the premotor cortex seems to be the best target for rTMS in dystonia. Rather than merely reducing the hyperexcitability of the primary motor cortex, this technique's clinical benefit seems to result from modifications in plasticity and restoration of sensorimotor integration. The corollary technique for chronic rTMS is electrical cortical stimulation. Even though this new therapeutic tool may have therapeutic promise, more studies are required to confirm it. In particular, we need to broaden our knowledge of rTMS impact on the various forms of dystonia and to optimize target localization.

Predominance of the contralateral movement-related activity in the subthalamo-cortical loop.

OBJECTIVE: Abnormal low- and high-frequency oscillatory activities have been linked to abnormal movement control in Parkinson's disease. We aimed to study how low- and high-frequency oscillatory activities are modulated by movement in the contralateral and ipsilateral subcorticocortical loops. METHODS: We studied mu, beta and gamma rhythm event-related desynchronisation (ERD) and synchronisation (ERS) recorded from electrode contacts in the subthalamic nucleus (STN) areas and over the primary sensorimotor (PSM) cortex. RESULTS: Mu and beta ERD/ERS patterns were very similar when comparing PSM cortex and STN areas and very different when comparing contralateral and ipsilateral structures. Beta rhythm ERS was more predominant over contralateral structures than over ipsilateral ones. Gamma rhythm ERS was only recorded from the contralateral STN area (particularly following administration of L-Dopa). For all patients, the best bipolar derivations - as defined by the earliest mu and beta ERD and the strongest beta and gamma ERS - always included the STN electrode contacts that produced the best clinical results. CONCLUSIONS: Movement-related activity is involved in the movement preparation in the contralateral subthalamo-cortical loop and in the movement execution in the bilateral subthalamo-cortical loops. SIGNIFICANCE: Contralateral beta rhythm ERD seemed to be related to bradykinesia of the limb performing the movement.

Relationship between event-related beta synchronization and afferent inputs: analysis of finger movement and peripheral nerve stimulations.

OBJECTIVE: We compared beta synchronization associated with voluntary finger movement with beta synchronization produced by sensory stimulation, in order to better understand the relationship between event-related beta synchronization (ERS) and the different afferent inputs. METHODS: Twenty-four subjects performed an index finger extension. They also received three types of electrical stimulation (cutaneous stimulation of the index finger, single and repetitive stimulation of the median nerve). An EEG was recorded using 38 scalp electrodes. Beta ERS was analyzed with respect to movement offset and the stimulus (or the last stimulus in the series, for repetitive stimulation). RESULTS: Median nerve stimulation and finger extension induced more intense beta ERS than cutaneous stimulation. The magnitude of beta ERS induced by movement or by single median nerve stimulation were not different but post movement beta synchronization duration was longer than beta ERS induced by single median nerve stimulation and cutaneous stimulation. CONCLUSIONS: This study demonstrates that beta ERS depends on the type and quantity of the afferent input. SIGNIFICANCE: This work reinforces the hypothesis of a relationship between beta ERS and processing of afferent inputs.

Neurophysiology of myoclonus.

Myoclonus may be generated by any area in the central nervous system. Finding its generator is helpful in the diagnostic process. Although clinical features have to be carefully analyzed as they may give a first idea, neurophysiologic study of myoclonus provides the most important clues for the determination of the generator. Surface electromyography (EMG) allows analyzing the recruitment order in generalized myoclonus, thereby suggesting either a cortical, brainstem, or spinal origin. It also reveals whether myoclonus is positive (jerks that are caused by muscle activation) or negative (jerks that are caused by brief muscle inhibition). In non-generalized myoclonus the EMG burst duration gives an idea of the level of the generator. Repetitive peripheral nerve stimulation is required to record somatosensory evoked potentials (SEPs) as well as long latency reflexes (LLR), especially the C reflex. The presence of giant cortical SEPs is an indirect argument for cortical myoclonus. Similarly the existence of LLR at rest orientates towards cortical reflex (sensitive to sensory stimuli) myoclonus. Finally EEG-EMG polygraphy is the only test which is able to prove directly the cortical origin of myoclonus. This is the case when focal cortical events precede myoclonus with a fixed delay. These premyoclonic cortical potentials may either be seen directly on raw recordings or require the use of jerk-locked back averaging (JLBA). This technique allows the averaging of the EEG prior to myoclonus onset (as determined by EMG) in order to reveal a premyoclonic spike that otherwise would remain undetected in the global EEG.