Awake Recordings Research Articles

Blood pressure variability and multiple organ damage in primary hypertension

Organ damage (OD) is an indicator of increased cardiovascular risk. Blood pressure variability (BPV) is related to greater incidence of events, regardless of the severity of hypertension. We investigated the relationship between ambulatory blood pressure monitoring (ABPM)-derived indices of BPV and the presence of multiple OD in primary hypertension (PH). One hundred and sixty-nine untreated patients with PH were evaluated. Systolic (SBP) and diastolic blood pressure (DBP) variability were assessed as the crude and weighted (w.) standard deviation (s.d.), and average real variability (ARV) of the mean value of 24-h, awake and asleep ABPM recordings. Left ventricular mass index, intima-media thickness, estimated-glomerular filtration rate and urinary albumin excretion were assessed as indices of cardiac, vascular and renal damage, respectively. Risk profile progressively increased starting from patients without OD to patients with only one sign of OD, and then to those with multiple OD. In addition to greater severity of the organ involvement, the only variables that were found to significantly differ between subjects with multiple and single OD were office SBP (160 ± 14 vs 154 ± 11 mm Hg, P=0.0423) and DBP (101 ± 7 vs 97 ± 8 mm Hg, P=0.0291), ambulatory arterial stiffness index (AASI) (0.60 ± 0.10 vs 0.50 ± 0.17, P=0.0158) and indices of BPV (24-h SBP s.d., 23 ± 5 vs 20 ± 6 mm Hg, P=0.0300; awake SBP s.d., 22 ± 6 vs 19 ± 6 mm Hg, P=0.0366; 24-h SBP w.s.d., 20 ± 5 vs 17 ± 5 mm Hg, P=0.0385; and 24-h SBP ARV, 18 ± 4 vs 15 ± 5 mm Hg, P=0.0420). All the above mentioned BPV parameters turned out to be determinants of multiple OD, regardless of several confounding variables, including BP levels. Therefore, in hypertensive patients increased SBP variability is associated with multiple signs of OD, regardless of BP values.

Chronic Evaluation of a Clinical System for Deep Brain Stimulation and Recording of Neural Network Activity

Background/Aims: In conjunction with therapeutic stimulation, next-generation deep brain stimulation (DBS) devices may offer the ability to record and analyze neural signals, providing for unprecedented insight into DBS effects on neural networks. This work was conducted to evaluate an implantable, clinical-grade system that permits concurrent stimulation and recording using a large animal (ovine) model recently developed to study DBS for epilepsy. Methods: Following anesthesia and 1.5-tesla MRI acquisition, unilateral anterior thalamic and hippocampal DBS leads were implanted (n = 3) using a frameless stereotactic system. Chronic, awake recordings of evoked potentials (EPs) and local field potentials were collected with the implanted device and analyzed off-line. Results: Hippocampal EPs were stable over long-term (>1 year) recording and consistent in morphology and latency with prior acute results. Thalamic and hippocampal DBS produced both excitatory and inhibitory network effects that were stimulation site and parameter dependent. Free roaming recordings illustrated periods of highly correlated activity between these two structures within the circuit of Papez. Conclusions: These results provide further insight into mechanisms of DBS therapy for epilepsy and an encouraging demonstration of the capabilities of this new technology, which in the future, may afford unique opportunities to study human brain function and neuromodulation mechanism of action.

427 LATE MORNING HYPOTENSION

Objective: To identify potential excessive lowering of blood pressure (BP) in treated hypertensive subjects in the late morning hours, around the peak effect of many BP lowering agents consumed in the morning. Methods: Analysis of 24 ambulatory blood pressure monitoring (ABPM) of 556 consecutive referred hypertensive subjects. Hypotension was defined as systolic BP< 110 mmHg or ≥25% lower than the mean 3 first awake recordings provided that it was also < 85% of the mean 24 h systolic BP and occurred before 1200 h (to avoid the inclusion of lunch related post-prandial hypotension). Results: Late morning hypotension (LMH) was seen in only 6.4% (13/203) of untreated-, but in 17.85% (63/353) of treated hypertensive subjects. The mean number of hypotensive recordings was 2.07/patient, with a mean BP of 102/64, 101/61 and 99/58 mmHg on 3 consecutive measurements taken∼20 minutes apart. As compared with treated hypertensive patients free of hypotension, the drug-treated group with LMH was older (means: 64.78 yrs. +/− 2.2 vs. 56.5 +/−1.1 yrs; p < 0.01), included more females (67 % vs. 49%, p < 0.01), had lower achieved daytime BP (127/73 vs. 136/80 mmHg; p < 0.01) and received more morning antihypertensive agents (N = 1.7 vs 1.1; p < 0.0001). Conclusion: In an unselected cohort of subjects treated for hypertension, late morning systolic hypotension (∼100 mmHg) is surprisingly common (∼18%) and is sustained for ∼40 minutes. Hypotension is linked to older age, female gender and larger number of drugs consumed in the morning. The recognition of this phenomenon appears important for daily treatment of high blood pressure.

Prognostic significance of serial postoperative EEG in extratemporal lobe epilepsy surgery

ObjectiveTo assess the prognostic value of postoperative EEG in patients surgically treated for drug-resistant extra-temporal lobe (ET) epilepsy. MethodsWe studied 63 consecutive patients with ET epilepsy who underwent epilepsy surgery and were followed up for at least 2years (mean duration of follow-up 6.2±2.3years, range 2–12). Follow-up evaluations were performed 2, 12, and 24months after surgery, and included standard EEG (at 2months) and long-term video-EEG monitoring during both wakefulness and sleep (at 12 and 24months). Seizure outcome was determined at each follow-up evaluation, and then at yearly intervals. Patients who were in Engel Class I at the last contact were classified as having a good outcome. ResultsSeizure outcome was good in 39 patients (62%). The presence of interictal epileptiform discharges (IED) in postoperative EEG at each time point was found to be associated with poor outcome. The strength of this association was greater for awake plus sleep recording as compared with awake recording alone. In a multiple regression model including all pre- and post-operative factors identified as predictors of outcome in univariate analysis, the presence of early (2months after surgery) EEG epileptiform abnormalities was found to be independently associated with poor seizure outcome. ConclusionsPostoperative IED may predict long-term outcome in patients undergoing resective surgery for ET epilepsy. SignificanceThe increase in risk of unfavourable outcome associated with EEG epileptiform abnormalities detected as early as two months after surgery may have substantial practical importance. Serial postoperative EEGs including sleep recording may add further predictive power and help making decision about antiepileptic drug discontinuation.

Evidence for Neuronal Desynchrony in the Aged Suprachiasmatic Nucleus Clock

Aging is associated with a deterioration of daily (circadian) rhythms in physiology and behavior. Deficits in the function of the central circadian pacemaker in the suprachiasmatic nucleus (SCN) have been implicated, but the responsible mechanisms have not been clearly delineated. In this report, we characterize the progression of rhythm deterioration in mice to 900 d of age. Longitudinal behavioral and sleep-wake recordings in up to 30-month-old mice showed strong fragmentation of rhythms, starting at the age of 700 d. Patch-clamp recordings in this age group revealed deficits in membrane properties and GABAergic postsynaptic current amplitude. A selective loss of circadian modulation of fast delayed-rectifier and A-type K+ currents was observed. At the tissue level, phase synchrony of SCN neurons was grossly disturbed, with some subpopulations peaking in anti-phase and a reduction in amplitude of the overall multiunit activity rhythm. We propose that aberrant SCN rhythmicity in old animals--with electrophysiological arrhythmia at the single-cell level and phase desynchronization at the network level--can account for defective circadian function with aging.

Response to comment on: Exp Brain Res. 2011 May 5th. Transcranial magnetic stimulation of macaque frontal eye fields decreases saccadic reaction time. Pierre Pouget PhD, Nicolas Wattiez MSc and Antoni Valero-Cabre MDPhD

We welcome the chance to respond to the comments of Pouget and Valero-Cabre about our recent study (Gerits et al. 2011, Experimental Brain Research), which showed an impact of continuous theta burst (cTBS) transcranial magnetic stimulation (TMS) over monkey frontal eye Welds (FEF) on prosaccade latency. No such eVect was observed when applying TBS over M1 instead, at a site 10–11 mm away from the eVective FEF site. We note that Pouget and Valero-Cabre acknowledge “the utmost importance” of extending TBS and other TMS protocols to animal models, as done in Gerits et al. (2011). They also state that “there is little doubt that Gerits et al. demonstrate for the Wrst time the feasibility of applying cTBS patterns to the awake monkey brain and record saccade behaviour immediately thereafter”. We share their enthusiasm for extending this approach with other TMS protocols, and in other behavioural and cognitive paradigms. Like them, we anticipate that larger eVects are there to be found and that TBS/TMS work in non-human primates may ultimately go well beyond what is known from human studies. Pouget and Valero-Cabre comment several times on the small absolute size of the observed cTBS eVect in Gerits et al. (mean 7 ms speeding of prosaccades after FEF cTBS, but not after M1 cTBS). Although small, this eVect was highly reliable (p < .0001 within each monkey, p < .000001 when pooling over monkeys). Moreover, it was highly systematic, as it was found in 8/8 comparisons after FEF cTBS, but in 0/8 after M1 cTBS. Although 7ms is small in absolute terms, it should be recalled that prosaccading is a simple task performed very quickly, with a mean diVerence of 7 ms representing a »5% change. In Gerits et al. (2011), this change could be produced by just 40 s of FEF cTBS, yet the observed eVect was comparable in size to that found on memory-guided saccades after much more drastic and invasive interventions (e.g. muscimol injection into area LIP, see Liu et al. 2010; Fig 1b and 1c). Finally, Pouget and Valero-Cabre query the sampling rate of Gerit et al.’s eyetracker (120 Hz, one sample every 8.3 ms) relative to the highly signiWcant mean eVect of 7 ms that was found, corresponding approximately to (just below) one sample. But it is well known that with a large number of repeated samples, one can reliably measure a mean eVect at or even below the measurement unit, and in Gerits et al. (2011), we had sampled 44,465 saccades in total. Pouget and Valero-Cabre comment on our comparison of the eVective FEF TBS site with the control M1 site that Jon Driver: Deceased

A Corticothalamic Circuit Model for Sound Identification in Complex Scenes

The identification of the sound sources present in the environment is essential for the survival of many animals. However, these sounds are not presented in isolation, as natural scenes consist of a superposition of sounds originating from multiple sources. The identification of a source under these circumstances is a complex computational problem that is readily solved by most animals. We present a model of the thalamocortical circuit that performs level-invariant recognition of auditory objects in complex auditory scenes. The circuit identifies the objects present from a large dictionary of possible elements and operates reliably for real sound signals with multiple concurrently active sources. The key model assumption is that the activities of some cortical neurons encode the difference between the observed signal and an internal estimate. Reanalysis of awake auditory cortex recordings revealed neurons with patterns of activity corresponding to such an error signal.

A Synaptic Strategy for Consolidation of Convergent Visuotopic Maps

The mechanisms by which experience guides refinement of converging afferent pathways are poorly understood. We describe a vision-driven refinement of corticocollicular inputs that determines the consolidation of retinal and visual cortical (VC) synapses on individual neurons in the superficial superior colliculus (sSC). Highly refined corticocollicular terminals form 1-2 days after eye-opening (EO), accompanied by VC-dependent filopodia sprouting on proximal dendrites, and PSD-95 and VC-dependent quadrupling of functional synapses. Delayed EO eliminates synapses, corticocollicular terminals, and spines on VC-recipient dendrites. Awake recordings after EO show that VC and retina cooperate to activate sSC neurons, and VC light responses precede sSC responses within intervals promoting potentiation. Eyelid closure is associated with more protracted cortical visual responses, causing the majority of VC spikes to follow those of the colliculus. These data implicate spike-timing plasticity as a mechanism for cortical input survival, and support a cooperative strategy for retinal and cortical coinnervation of the sSC.

EEG abnormalities and epilepsy in autistic spectrum disorders: Clinical and familial correlates

Our aim was to examine the characteristics of EEG findings and epilepsy in autistic spectrum disorders (ASD) and the associated clinical and familial risk factors. Fifty-seven children (86% male) with ASD, mean age 82 ± 36.2 months, were included in the study. Thirty-nine (68.4%) children had the diagnosis of autism, 15 (26.3%) had Pervasive Developmental Disorder Not Otherwise Specified, and 3 (5.3%) had high-functioning autism. One hour of sleep and/or awake EEG recordings was obtained for each child. All patients were evaluated with respect to clinical and familial characteristics and with the Childhood Autism Rating Scale, the Autism Behavior Checklist, and the Aberrant Behavior Checklist. The frequency of interictal epileptiform EEG abnormalities (IIEAs) was 24.6% ( n = 14), and the frequency of epilepsy was 14.2% ( n = 8). IIEAs were associated with a diagnosis of epilepsy ( P = 0.0001), Childhood Autism Rating Scale Activity scores ( P = 0.047), and a history of asthma and allergy ( P = 0.044). Epilepsy was associated with a family history of epilepsy ( P = 0.049) and psychiatric problems in the mother during pregnancy ( P = 0.0026). Future studies with larger samples will help to clarify the possible associations of epilepsy/IIEAs with asthma/allergy, hyperactivity, and familial factors in ASD.

The complementary value of sleep-deprived EEG in childhood onset epilepsy

Although EEG is an important diagnostic tool in suspected childhood onset epilepsy, as many as 50% of wakefulness records remain normal. Sleep-deprived EEG has been reported in adults to serve as an activator of epileptic discharges but such effect is still not agreed upon in children reporting small series. Assess the complementary diagnostic value of sleep deprivation on the induction of epileptic discharges in childhood onset epilepsy having a normal awake record within a period of 5 years. EEG recording was performed during the awake, drowsiness and sleep states following sleep deprivation of 6h. BACKGROUND RESULTS: Fifty five children of whom the initial record failed to detect epileptiform discharges, were assessed at age 5-17 years (mean: 10+/-3.7), 27 boys and 28 girls. Sleep occurred in 51 (92.7%) after sleep deprivation and in only 1 (1.8%) during an awake record. Epileptic discharges were detected in 15 of 55 (27.2%) previous non-epileptic awake records during the sleep-deprived EEG either during wakefulness and more frequent during sleep. Eight abnormal records were detected in 18 (44%) children presenting with a focal seizure and 7 of 35 (20%) associated with generalized seizures. Epileptic discharges were recorded mainly and more frequent during sleep. Our data suggests that sleep deprivation imposes an apparent activating impact uncovering epileptic discharges children corroborating with overt clinical seizures even beyond the sampling effect of repeat records.

Analyzing Variability in Neural Responses to Complex Natural Sounds in the Awake Songbird

Studies of auditory processing in awake, behaving songbirds allow for the possibility of new classes of experiments, including those involving attention and plasticity. Detecting and determining the significance of plasticity, however, requires assessing the intrinsic variability in neural responses. Effects such as rapid plasticity have been investigated in the auditory system through the use of the spectrotemporal receptive field (STRF), a characterization of the properties of sounds to which a neuron best responds. Here we investigated neural response variability in awake recordings obtained from zebra finch field L, the analog of the primary auditory cortex. To quantify the level of variability in the neural recordings, we used three similarity measures: an STRF-based metric, a spike-train correlation-based metric, and a spike-train discrimination-based metric. We then extracted a number of parameters from these measures, quantifying how they fluctuated over time. Our results indicate that 1) awake responses are quite stable over time; 2) the different measures of response are complementary-specifically, the spike-train-based measures yield new information complementary to the STRF; and 3) different STRF parameters show distinct levels of variability. These results provide critical constraints for the design of robust decoding strategies and novel experiments on attention and plasticity in the awake songbird.

Increased bursting in layer 2/3 neurones of awake neocortex

Increased bursting in layer 2/3 neurones of awake neocortex

Continuous spikes and waves during slow sleep in an adult

Continuous spikes and waves during slow wave sleep (CSWS) is rare and is considered to be an age-related epileptic syndrome occurring only in children. We report the case of a 21-year-old patient diagnosed with this syndrome. The patient had a history of seizures since the age of 3 and was admitted for continuous video/EEG monitoring to evaluate seizure exacerbation and unprovoked outbursts of anger. During 3 days of monitoring, awake EEG recordings showed focal slow wave activity in the right temporal region. CSWS were observed. After a change in his antiepileptic drug regimen, subsequent EEG recordings showed resolution of CSWS. As shown in our patient, CSWS can be observed in adults. In addition, continuous video/EEG monitoring including sleep is important in the evaluation of patients with sudden deterioration of seizure control accompanied by behavioral changes.

Autosomal dominant nocturnal frontal lobe epilepsy with a mutation in the CHRNB2 gene

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE; MIM 600513) has been associated with mutations in the genes coding for the alfa-4 (CHRNA4), beta-2 (CHRNB2), and alpha-2 (CHRNA2) subunits of the neuronal nicotinic acetylcholine receptor (nAChR) and for the corticotropin-releasing hormone (CRH). A four-generation ADNFLE family with six affected members was identified. All affected members presented the clinical characteristics of ADNFLE. Interictal awake and sleep EEG recordings showed no epileptiform abnormalities. Ictal video-EEG recordings showed focal seizures with frontal lobe semiology. Mutation analysis of the CHRNB2 gene revealed a c.859G>A transition (Val287Met) within the second transmembrane domain, identical to that previously described in a Scottish ADNFLE family. To our knowledge, this is the third family reported presenting a mutation in CHRNB2. The clinical phenotype appears similar to that described with mutations in CHRNA4, suggesting that mutations in these two subunits lead to similar functional alterations of the nAChR.

Usefulness of a morning routine EEG recording in patients with juvenile myoclonic epilepsy

To evaluate if a standard awake EEG recording in the morning is superior to afternoon awake EEG session in detecting generalized epileptiform discharges (GEDs) in patients with juvenile myoclonic epilepsy (JME). The study group included 29 consecutive patients (23 women; mean age 22.3+/-6.3 years; age at onset of JME 15.4+/-3.4 years) with JME. Out of 29 patients 5 were untreated, 9 patients were treated with valproate, 8 with lamotrigine, 6 with levetiracetam and 1 patient with valproate plus phenobarbital. Two routine consecutive interictal EEG recordings were performed at 9a.m. and at 3p.m., respectively, while the subject was awake, on the same day after a a regular nocturnal sleep at own home. The morning EEG recording showed GEDs (i.e., generalized polispike and waves, photoparoxysmal response, or both). in 20/29 patients. In 15 of these 20 patients, the afternoon recording was normal and this difference was statistically significant (p < or = 0.001). Moreover, there was a striking reduction of GEDs in three of the remaining five patients. Nine/29 patients had both morning and afternoon EEG recording normal. The results of this study have illustrated a significant greater rate of detection of generalized epileptiform abnormalities by performing standard awake EEG in the morning in comparison with an afternoon session.

Awake Systolic Blood Pressure Variability Correlates With Target-Organ Damage in Hypertensive Subjects

Growing evidence associates blood pressure (BP) variability with cardiovascular events in hypertensive patients. Here we tested the existence of a relationship between awake BP variability and target-organ damage in subjects referred for suspected hypertension. Systolic and diastolic BP variability were assessed as the standard deviation of the mean out of 24-hour, awake and asleep BP recordings in 180 untreated subjects, referred for suspected hypertension. Measurements were done at 15-minute intervals during daytime and 30-minute intervals during nighttime. Left ventricular mass index (by echo), intima-media thickness (by carotid ultrasonography), and microalbuminuria were assessed as indices of cardiac, vascular and renal damage, respectively. Intima-media thickness and left ventricular mass index progressively increased across tertiles of awake systolic BP variability (P for trend=0.001 and 0.003, respectively). Conversely, microalbuminuria was similar in the 3 tertiles (P=NS). Multivariable analysis identified age (P=0.0001), awake systolic BP (P=0.001), awake systolic BP variability (P=0.015) and diastolic BP load (P=0.01) as independent predictors of intima-media thickness; age (P=0.0001), male sex (P=0.012), awake systolic (P=0.0001) and diastolic BP (P=0.035), and awake systolic BP variability (P=0.028) as independent predictors of left ventricular mass index; awake systolic BP variability (P=0.01) and diastolic BP load (P=0.01) as independent predictors of microalbuminuria. Therefore, awake systolic BP variability by non-invasive ambulatory BP monitoring correlates with sub-clinical target-organ damage, independent of mean BP levels. Such relationship, found in subjects referred for recently suspected hypertension, likely appears early in the natural history of hypertension.

Sleep–wake study in an animal model of acute and chronic heat stress

The study of the variations in different parameters of sleep–wake states following exposure to high environmental heat in three different age groups of freely moving rats have been presented in this paper. Each age group of rats was subdivided in three group (i) acute heat stress — subjected to a single exposure for 4 h in the BOD (Biological Oxygen Demand) incubator at 38 °C; (ii) chronic heat stress — exposed for 21 days daily for 1 h in the incubator at 38 °C, and (iii) handling control groups. The polygraphic, analog as well as digital sleep–wake recordings were performed just after the heat exposure from acute stressed rats and on 22nd day from chronic stressed rats. The results of this study revealed that acute exposure to high environmental heat increases sleep efficiency with significant increase in SWS (slow wave sleep) decrease in AWA (awake) time in all three age groups of rats. The increase in SWS and the sleep efficiency in these groups of rats at the cost of decreased time of AWA, indicates the involvement of the hypothalamus in thermoregulatory mechanism to conserve the energy of the body following sudden exposure to high heat. However, the reverse results were observed in the chronic stressed groups of rats, which have occurred mostly owing to the adaptations of the brain functions due to repetitive exposure to environmental heat. In consequence, the present study exhibits that the sleep is highly susceptible to the environmental heat and it is sensitive to the intensity, duration and the mode of exposure.

Evidence for a neurophysiologic auditory deficit in children with benign epilepsy with centro-temporal spikes

Benign focal epilepsy in childhood with centro-temporal spikes (BECTS) is one of the most common forms of epilepsy. Recent studies have questioned the benign nature of BECTS, as they have revealed neuropsychological deficits in many domains including language. The aim of this study was to investigate whether the epileptic discharges during the night have long-term effects on auditory processing, as reflected on electrophysiological measures, during the day, which could underline the language deficits. In order to address these questions we recorded base line electroencephalograms (EEG), sleep EEG and auditory event related potentials in 12 children with BECTS and in age- and gender-matched controls. In the children with BECTS, 5 had unilateral and 3 had bilateral spikes. In the 5 patients with unilateral spikes present during sleep, an asymmetry of the auditory event related component (P85-120) was observed contralateral to the side of epileptiform activity compared to the normal symmetrical vertex distribution that was noted in all controls and in 3 the children with bilateral spikes. In all patients the peak to peak amplitude of this event related potential component was statistically greater compared to the controls. Analysis of subtraction waveforms (deviant - standard) revealed no evidence of a mismatch negativity component in any of the children with BECTS. We propose that the abnormality of P85-120 and the absence of mismatch negativity during wake recordings in this group may arise in response to the long-term effects of spikes occurring during sleep, resulting in disruption of the evolution and maintenance of echoic memory traces. These results may indicate that patients with BECTS have abnormal processing of auditory information at a sensory level ipsilateral to the hemisphere evoking spikes during sleep.

442 Depletion of DNA methyltransferase (DNMT)1, and/or DNMT3b mediates growth arrest and apoptosis in lung and esophageal cancer cells

15q11-q13 region is an area of well-known susceptibility to genomic rearrangements, in which several breakpoints have been identified (BP1–BP5). Duplication of this region is observed in two instances: presence of a supernumerary marker chromosome (SMC) derived of chromosome 15, or interstitial tandem duplication. Duplications are clinically characterized by a variable phenotype that includes central hypotonia, developmental delay, speech delay, seizure, minor dysmorphic features and autism.Retrospective clinical and molecular study of 30 unrelated patients who were identified among the patients seen at the genetic clinics of Robert DEBRE hospital with microduplication of the 15q11-q13 region.Fifteen patients presented with a supernumerary marker derived from chromosome 15. In fourteen cases the SMC was of large size, encompassing the Prader–Willi/Angelman critical region. All but one was maternal in origin. One patient had a PWS-like phenotype in absence of maternal UPD. In one case, the marker had a smaller size and contained only the BP1–BP2 region. Fifteen patients presented with interstitial duplication. Four cases were inherited from phenotypically normal parents (3 maternal and 1 paternal). Phenotypic features were somewhat variable and 57% presented with autism. Twelve patients showed cerebral anomalies and 18 patients had an abnormal EEG with a typical, recognizable pattern of excessive diffuse rapid spikes in the waking record, similar to the pattern observed after benzodiazepine exposure. Duplication of paternally expressed genes MKRN3, MAGEL2 and NDN in two autistic patients without extra material of a neighboring region enhances their likelihood to be genes related to autism.

The acute effect of music on interictal epileptiform discharges

This study was a prospective, randomized, single-blinded, crossover, placebo-controlled, pilot clinical trial investigating the effect of Mozart’s Sonata for Two Pianos (K448) on the frequency of interictal epileptiform discharges (IEDs) from the EEGs of children with benign childhood epilepsy with centrotemporal spikes, or “rolandic” epilepsy. The goal was to demonstrate decreased frequency of IEDs with exposure to K448. Four subjects were recruited and 4-hour awake EEG recordings performed. IED frequency per minute was averaged over each of three epochs per hour. Mean IED count per epoch, standard deviations, and variance were calculated. Only complete waking epochs were analyzed. Two subjects demonstrated sufficient waking IEDs for statistical analysis, consisting of three epochs of K448-related effects. Significant decreases in IEDs per minute (33.7, 50.6, and 33.9%) were demonstrated comparing baseline with exposure to K448, but not to control music (Beethoven’s Fü r Elise).