Estimate of Patients With Missed Seizures Because of Delay in Conventional EEG.

PURPOSE: There is frequent delay between ordering and placement of conventional EEG. Here we estimate how many patients had seizures during this delay. METHODS: Two hundred fifty consecutive adult patients who underwent conventional EEG monitoring at the University of Wisconsin Hospital were retrospectively chart reviewed for demographics, time of EEG order, clinical and other EEG-related information. Patients were stratified by use of anti-seizure medications before EEG and into low-risk, medium-risk, and high-risk groups based on 2HELPS2B score (0, 1, or >1). Monte Carlo simulations (500 trials) were performed to estimate seizures during delay. RESULTS: The median delay from EEG order to performing EEG was 2.00 hours (range of 0.5-8.00 hours) in the total cohort. For EEGs ordered after-hours, it was 2.00 hours (range 0.5-8.00 hours), and during business hours, it was 2.00 hours (range 0.5-6.00 hours). The place of EEG, intensive care unit, emergency department, and general floor, did not show significant difference (P = 0.84). Anti-seizure medication did not affect time to first seizure in the low-risk (P = 0.37), medium-risk (P = 0.44), or high-risk (P = 0.12) groups. The estimated % of patients who had a seizure in the delay period for low-risk group (2HELPS2B = 0) was 0.8%, for the medium-risk group (2HELPS2B = 1) was 10.3%, and for the high-risk group (2HELPS2B > 1) was 17.6%, and overall risk was 7.2%. CONCLUSIONS: The University of Wisconsin Hospital with 24-hour in-house EEG technologists has a median delay of 2 hours from order to start of EEG, shorter than published reports from other centers. Nonetheless, seizures were likely missed in about 7.2% of patients.

Delirium is associated with loss of feedback cortical connectivity.

INTRODUCTION: Post-operative delirium (POD) is associated with increased morbidity and mortality but is bereft of treatments, largely due to our limited understanding of the underlying pathophysiology. We hypothesized that delirium reflects a disturbance in cortical connectivity that leads to altered predictions of the sensory environment. METHODS: High-density electroencephalogram recordings during an oddball auditory roving paradigm were collected from 131 patients. Dynamic causal modeling (DCM) analysis facilitated inference about the neuronal connectivity and inhibition-excitation dynamics underlying auditory-evoked responses. RESULTS: Mismatch negativity amplitudes were smaller in patients with POD. DCM showed that delirium was associated with decreased left-sided superior temporal gyrus (l-STG) to auditory cortex feedback connectivity. Feedback connectivity also negatively correlated with delirium severity and systemic inflammation. Increased inhibition of l-STG, with consequent decreases in feed-forward and feed-back connectivity, occurred for oddball tones during delirium. DISCUSSION: Delirium is associated with decreased feedback cortical connectivity, possibly resulting from increased intrinsic inhibitory tone. HIGHLIGHTS: Mismatch negativity amplitude was reduced in patients with delirium. Patients with postoperative delirium had increased feedforward connectivity before surgery. Feedback connectivity was diminished from left-side superior temporal gyrus to left primary auditory sensory area during delirium. Feedback connectivity inversely correlated with inflammation and delirium severity.

Prevalence and localization of nocturnal epileptiform discharges in mild cognitive impairment.

Recent evidence shows that identifying and treating epileptiform abnormalities in patients with Alzheimer's disease could represent a potential avenue to improve clinical outcome. Specifically, animal and human studies have revealed that in the early phase of Alzheimer's disease, there is an increased risk of seizures. It has also been demonstrated that the administration of anti-seizure medications can slow the functional progression of the disease only in patients with EEG signs of cortical hyperexcitability. In addition, although it is not known at what disease stage hyperexcitability emerges, there remains no consensus regarding the imaging and diagnostic methods best able to detect interictal events to further distinguish different phenotypes of Alzheimer's disease. In this exploratory work, we studied 13 subjects with amnestic mild cognitive impairment and 20 healthy controls using overnight high-density EEG with 256 channels. All participants also underwent MRI and neuropsychological assessment. Electronic source reconstruction was also used to better select and localize spikes. We found spikes in six of 13 (46%) amnestic mild cognitive impairment compared with two of 20 (10%) healthy control participants (P = 0.035), representing a spike prevalence similar to that detected in previous studies of patients with early-stage Alzheimer's disease. The interictal events were low-amplitude temporal spikes more prevalent during non-rapid eye movement sleep. No statistically significant differences were found in cognitive performance between amnestic mild cognitive impairment patients with and without spikes, but a trend in immediate and delayed memory was observed. Moreover, no imaging findings of cortical and subcortical atrophy were found between amnestic mild cognitive impairment participants with and without epileptiform spikes. In summary, our exploratory study shows that patients with amnestic mild cognitive impairment reveal EEG signs of hyperexcitability early in the disease course, while no other significant differences in neuropsychological or imaging features were observed among the subgroups. If confirmed with longitudinal data, these exploratory findings could represent one of the first signatures of a preclinical epileptiform phenotype of amnestic mild cognitive impairment and its progression.

Greater tau pathology is associated with altered predictive coding.

Altered predictive coding may underlie the reduced auditory mismatch negativity amplitude observed in patients with dementia. We hypothesized that accumulating dementia-associated pathologies, including amyloid and tau, lead to disturbed predictions of our sensory environment. This would manifest as increased reliance on 'observed' sensory information with an associated increase in feedforward, and decrease in feedback, signalling. To test this hypothesis, we studied a cross-sectional cohort of participants who underwent PET imaging and high-density EEG during an oddball paradigm, and used dynamic casual modelling and Bayesian statistics to make inferences about the neuronal architectures (generators) and mechanisms (effective connectivity) underlying the observed auditory-evoked responses. Amyloid-ß imaging with [C-11] Pittsburgh Compound-B PET was qualitatively rated using established criteria. Tau-positive PET scans, with [F-18]MK-6240, were defined by an MK-6240 standardized uptake value ratio positivity threshold at 2 standard deviations above the mean of the Amyloid(-) group in the entorhinal cortex (entorhinal MK-6240 standardized uptake value ratio > 1.27). The cross-sectional cohort included a total of 56 participants [9 and 13 participants in the Tau(+) and Amyloid(+) subgroups, respectively: age interquartile range of (73.50-75.34) and (70.5-75.34) years, 56 and 69% females, respectively; 46 and 43 participants in the Tau(-) and Amyloid(-) subgroups, respectively: age interquartile range of (62.72-72.5) and (62.64-72.48) years, 67 and 65% females, respectively]. Mismatch negativity amplitudes were significantly smaller in Tau+ subgroup than Tau- subgroup (cluster statistics corrected for multiple comparisons: P = 0.028). Dynamic causal modelling showed that tau pathology was associated with increased feedforward connectivity and decreased feedback connectivity, with increased excitability of superior temporal gyrus but not inferior frontal regions. This effect on superior temporal gyrus was consistent with the distribution of tau disease on PET in these participants, indicating that the observed differences in mismatch negativity reflect pathological changes evolving in preclinical dementia. Exclusion of participants with diagnosed mild cognitive impairment or dementia did not affect the results. These observational data provide proof of concept that abnormalities in predictive coding may be detected in the preclinical phase of Alzheimer's disease. This framework also provides a construct to understand how progressive impairments lead to loss of orientation to the sensory world in dementia. Based on our modelling results, plus animal models indicating that Alzheimer's disease pathologies produce hyperexcitability of higher cortical regions through local disinhibition, mismatch negativity might be a useful monitor to deploy as strategies that target interneuron dysfunction are developed.

BCI-FES With Multimodal Feedback for Motor Recovery Poststroke.

An increasing number of research teams are investigating the efficacy of brain-computer interface (BCI)-mediated interventions for promoting motor recovery following stroke. A growing body of evidence suggests that of the various BCI designs, most effective are those that deliver functional electrical stimulation (FES) of upper extremity (UE) muscles contingent on movement intent. More specifically, BCI-FES interventions utilize algorithms that isolate motor signals-user-generated intent-to-move neural activity recorded from cerebral cortical motor areas-to drive electrical stimulation of individual muscles or muscle synergies. BCI-FES interventions aim to recover sensorimotor function of an impaired extremity by facilitating and/or inducing long-term motor learning-related neuroplastic changes in appropriate control circuitry. We developed a non-invasive, electroencephalogram (EEG)-based BCI-FES system that delivers closed-loop neural activity-triggered electrical stimulation of targeted distal muscles while providing the user with multimodal sensory feedback. This BCI-FES system consists of three components: (1) EEG acquisition and signal processing to extract real-time volitional and task-dependent neural command signals from cerebral cortical motor areas, (2) FES of muscles of the impaired hand contingent on the motor cortical neural command signals, and (3) multimodal sensory feedback associated with performance of the behavioral task, including visual information, linked activation of somatosensory afferents through intact sensorimotor circuits, and electro-tactile stimulation of the tongue. In this report, we describe device parameters and intervention protocols of our BCI-FES system which, combined with standard physical rehabilitation approaches, has proven efficacious in treating UE motor impairment in stroke survivors, regardless of level of impairment and chronicity.

Association Between Lateralized Periodic Discharge Amplitude and Seizure on Continuous EEG Monitoring in Patients With Structural Brain Abnormality in Critical Illness.

Objective: To investigate the association between lateralized periodic discharge (LPD) amplitude and seizure risk on an individual level in patients with structural brain abnormality. Methods: Retrospective case-control study of patients with structural brain abnormality undergoing continuous EEG monitoring was performed. We included 10 patients with LPDs and seizures as cases and 10 controls, patients with LPDs without seizure. Analysis was performed with a mixed-effects model with primary outcome measure of number of seizures per 8-h EEG epoch with fixed effects being variables of interest and random effect being subject ID. Results: Epochs with seizures showed a higher absolute amplitude (corrected p = 0.04) and a higher relative amplitude (corrected p = 0.04) of LPDs. Additionally, the number of seizures was higher in epochs that had LPDs with plus features (uncorrected p = 0.002) and LPDs with higher relative amplitude (uncorrected p = 0.005). Conclusion: Higher LPD amplitude is associated with increased risk of seizures on an individual patient level. A decreasing amplitude is suggestive of decreasing seizure risk, and may in fact be suggestive of decreasing ictal character of LPDs.

Engineering nonlinear epileptic biomarkers using deep learning and Benford's law.

In this study, we designed two deep neural networks to encode 16 features for early seizure detection in intracranial EEG and compared them and their frequency responses to 16 widely used engineered metrics to interpret their properties: epileptogenicity index (EI), phase locked high gamma (PLHG), time and frequency domain Cho Gaines distance (TDCG, FDCG), relative band powers, and log absolute band powers (from alpha, beta, theta, delta, low gamma, and high gamma bands). The deep learning models were pretrained for seizure identification on the time and frequency domains of 1 s, single-channel clips of 127 seizures (from 25 different subjects) using "leave-one-out" (LOO) cross validation. Each neural network extracted unique feature spaces that were interpreted using spectral power modulations before being used to train a Random Forest Classifier (RFC) for seizure identification. The Gini Importance of each feature was calculated from the pretrained RFC, enabling the most significant features (MSFs) for each task to be identified. The MSFs were extracted to train another RFC for UPenn and Mayo Clinic's Seizure Detection Kaggle Challenge. They obtained an AUC score of 0.93, demonstrating a transferable method to identify and interpret biomarkers for seizure detection.

Ipsilesional Mu Rhythm Desynchronization Correlates With Improvements in Affected Hand Grip Strength and Functional Connectivity in Sensorimotor Cortices Following BCI-FES Intervention for Upper Extremity in Stroke Survivors.

Stroke is a leading cause of acquired long-term upper extremity motor disability. Current standard of care trajectories fail to deliver sufficient motor rehabilitation to stroke survivors. Recent research suggests that use of brain-computer interface (BCI) devices improves motor function in stroke survivors, regardless of stroke severity and chronicity, and may induce and/or facilitate neuroplastic changes associated with motor rehabilitation. The present sub analyses of ongoing crossover-controlled trial NCT02098265 examine first whether, during movements of the affected hand compared to rest, ipsilesional Mu rhythm desynchronization of cerebral cortical sensorimotor areas [Brodmann's areas (BA) 1-7] is localized and tracks with changes in grip force strength. Secondly, we test the hypothesis that BCI intervention results in changes in frequency-specific directional flow of information transmission (direct path functional connectivity) in BA 1-7 by measuring changes in isolated effective coherence (iCoh) between cerebral cortical sensorimotor areas thought to relate to electrophysiological signatures of motor actions and motor learning. A sample of 16 stroke survivors with right hemisphere lesions (left hand motor impairment), received a maximum of 18-30 h of BCI intervention. Electroencephalograms were recorded during intervention sessions while outcome measures of motor function and capacity were assessed at baseline and completion of intervention. Greater desynchronization of Mu rhythm, during movements of the impaired hand compared to rest, were primarily localized to ipsilesional sensorimotor cortices (BA 1-7). In addition, increased Mu desynchronization in the ipsilesional primary motor cortex, Post vs. Pre BCI intervention, correlated significantly with improvements in hand function as assessed by grip force measurements. Moreover, the results show a significant change in the direction of causal information flow, as measured by iCoh, toward the ipsilesional motor (BA 4) and ipsilesional premotor cortices (BA 6) during BCI intervention. Significant iCoh increases from ipsilesional BA 4 to ipsilesional BA 6 were observed in both Mu [8-12 Hz] and Beta [18-26 Hz] frequency ranges. In summary, the present results are indicative of improvements in motor capacity and behavior, and they are consistent with the view that BCI-FES intervention improves functional motor capacity of the ipsilesional hemisphere and the impaired hand.

Quantitative spatio-temporal characterization of epileptic spikes using high density EEG: Differences between NREM sleep and REM sleep.

In this study, we applied high-density EEG recordings (HD-EEG) to quantitatively characterize the fine-grained spatiotemporal distribution of inter-ictal epileptiform discharges (IEDs) across different sleep stages. We quantified differences in spatial extent and duration of IEDs at the scalp and cortical levels using HD-EEG source-localization, during non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep, in six medication-refractory focal epilepsy patients during epilepsy monitoring unit admission. Statistical analyses were performed at single subject level and group level across different sleep stages for duration and distribution of IEDs. Tests were corrected for multiple comparisons across all channels and time points. Compared to NREM sleep, IEDs during REM sleep were of significantly shorter duration and spatially more restricted. Compared to NREM sleep, IEDs location in REM sleep also showed a higher concordance with electrographic ictal onset zone from scalp EEG recording. This study supports the localizing value of REM IEDs over NREM IEDs and suggests that HD-EEG may be of clinical utility in epilepsy surgery work-up.

Deficit Versus Nondeficit Schizophrenia: An MEG-EEG Investigation of Resting State and Source Coherence-Preliminary Data.

This study investigated the magneto- and electroencephalography (MEG and EEG, respectively) resting state to identify the deviations closely associated with the deficit syndrome (DS) in schizophrenia patients. Ten subjects in each group (control, DS, and nondeficit schizophrenia [NDS]) were included. Subjects underwent MEG-EEG recordings during a resting state condition. MEG coherence source imaging (CSI) in source space and spectral analysis in sensor space were performed. Significant differences were found between the 2 patient groups: (1) MEG and EEG spectral analysis showed significantly higher power at low frequencies (delta band) at sensor space in DS compared with NDS patients; (2) source analysis revealed larger power in the DS compared with NDS group at low frequencies in the frontal region; (3) NDS patients showed significantly higher MEG signal relative power in beta bands in sensor space compared with DS patients; (4) both DS and NDS patients showed higher EEG absolute power at higher beta band compared to controls; and (5) patients with DS were found to have a significantly higher MEG CSI than controls in the beta frequency band. These data support the observation of increased power in the low-frequency EEG/MEG rhythms associated with the DS. Increased power in the beta rhythms was more associated with the NDS.

Ipsilesional Mu Rhythm Desynchronization and Changes in Motor Behavior Following Post Stroke BCI Intervention for Motor Rehabilitation.

Loss of motor function is a common deficit following stroke insult and often manifests as persistent upper extremity (UE) disability which can affect a survivor's ability to participate in activities of daily living. Recent research suggests the use of brain-computer interface (BCI) devices might improve UE function in stroke survivors at various times since stroke. This randomized crossover-controlled trial examines whether intervention with this BCI device design attenuates the effects of hemiparesis, encourages reorganization of motor related brain signals (EEG measured sensorimotor rhythm desynchronization), and improves movement, as measured by the Action Research Arm Test (ARAT). A sample of 21 stroke survivors, presenting with varied times since stroke and levels of UE impairment, received a maximum of 18-30 h of intervention with a novel electroencephalogram-based BCI-driven functional electrical stimulator (EEG-BCI-FES) device. Driven by spectral power recordings from contralateral EEG electrodes during cued attempted grasping of the hand, the user's input to the EEG-BCI-FES device modulates horizontal movement of a virtual cursor and also facilitates concurrent stimulation of the impaired UE. Outcome measures of function and capacity were assessed at baseline, mid-therapy, and at completion of therapy while EEG was recorded only during intervention sessions. A significant increase in r-squared values [reflecting Mu rhythm (8-12 Hz) desynchronization as the result of attempted movements of the impaired hand] presented post-therapy compared to baseline. These findings suggest that intervention corresponds with greater desynchronization of Mu rhythm in the ipsilesional hemisphere during attempted movements of the impaired hand and this change is related to changes in behavior as a result of the intervention. BCI intervention may be an effective way of addressing the recovery of a stroke impaired UE and studying neuromechanical coupling with motor outputs. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02098265.

Evoked Potentials Investigations of Deficit Versus Nondeficit Schizophrenia: EEG-MEG Preliminary Data.

Heterogeneity of schizophrenia is a major obstacle toward understanding the disorder. One likely subtype is the deficit syndrome (DS) where patients suffer from predominantly negative symptoms. This study investigated the evoked responses and the evoked magnetic fields to identify the neurophysiological deviations associated with the DS. Ten subjects were recruited for each group (Control, DS, and Nondeficit schizophrenia [NDS]). Subjects underwent magnetoencephalography (MEG) and electroencephalography (EEG) testing while listening to an oddball paradigm to generate the P300 as well as a paired click paradigm to generate the mid-latency auditory-evoked responses (MLAER) in a sensory gating paradigm. MEG-coherence source imaging (CSI) during P300 task revealed a significantly higher average coherence value in DS than NDS subjects in the gamma band (30-80 Hz), when listening to standard stimuli but only NDS subjects had a higher average coherence level in the gamma band than controls when listening to the novel sounds. P50, N100, and P3a ERP amplitudes (EEG analysis) were significantly decreased in NDS compared with DS subjects. The data suggest that the deviations in the 2 patient groups are qualitatively different. Deviances in NDS patients suggest difficulty in both early (as in the gating paradigm), as well as later top-down processes (P300 paradigm). The main deviation in the DS group was an exaggerated responsiveness to ongoing irrelevant stimuli detected by EEG whereas NDS subjects had an exaggerated response to novelty.

Behavioral Outcomes Following Brain-Computer Interface Intervention for Upper Extremity Rehabilitation in Stroke: A Randomized Controlled Trial.

Stroke is a leading cause of persistent upper extremity (UE) motor disability in adults. Brain-computer interface (BCI) intervention has demonstrated potential as a motor rehabilitation strategy for stroke survivors. This sub-analysis of ongoing clinical trial (NCT02098265) examines rehabilitative efficacy of this BCI design and seeks to identify stroke participant characteristics associated with behavioral improvement. Stroke participants (n = 21) with UE impairment were assessed using Action Research Arm Test (ARAT) and measures of function. Nine participants completed three assessments during the experimental BCI intervention period and at 1-month follow-up. Twelve other participants first completed three assessments over a parallel time-matched control period and then crossed over into the BCI intervention condition 1-month later. Participants who realized positive change (≥1 point) in total ARAT performance of the stroke affected UE between the first and third assessments of the intervention period were dichotomized as "responders" (<1 = "non-responders") and similarly analyzed. Of the 14 participants with room for ARAT improvement, 64% (9/14) showed some positive change at completion and approximately 43% (6/14) of the participants had changes of minimal detectable change (MDC = 3 pts) or minimally clinical important difference (MCID = 5.7 points). Participants with room for improvement in the primary outcome measure made significant mean gains in ARATtotal score at completion (ΔARATtotal = 2, p = 0.028) and 1-month follow-up (ΔARATtotal = 3.4, p = 0.0010), controlling for severity, gender, chronicity, and concordance. Secondary outcome measures, SISmobility, SISadl, SISstrength, and 9HPTaffected, also showed significant improvement over time during intervention. Participants in intervention through follow-up showed a significantly increased improvement rate in SISstrength compared to controls (p = 0.0117), controlling for severity, chronicity, gender, as well as the individual effects of time and intervention type. Participants who best responded to BCI intervention, as evaluated by ARAT score improvement, showed significantly increased outcome values through completion and follow-up for SISmobility (p = 0.0002, p = 0.002) and SISstrength (p = 0.04995, p = 0.0483). These findings may suggest possible secondary outcome measure patterns indicative of increased improvement resulting from this BCI intervention regimen as well as demonstrating primary efficacy of this BCI design for treatment of UE impairment in stroke survivors. Clinical Trial Registration: ClinicalTrials.gov, NCT02098265.

Comparing EEG Nonlinearity in Deficit and Nondeficit Schizophrenia Patients: Preliminary Data.

Electroencephalogram (EEG) contains valuable information obtained noninvasively that can be used for assessment of brain's processing capacity of patients with psychiatric disorders. The purpose of the present work was to evaluate possible differences in EEG complexity between deficit (DS) and nondeficit (NDS) subtypes of schizophrenia as a reflection of the cognitive processing capacities in these groups. A particular nonlinear metric known as Lempel-Ziv complexity (LZC) was used as a computational tool in order to determine the randomness in EEG alpha band time series from 3 groups (deficit schizophrenia [n = 9], nondeficit schizophrenia [n = 10], and healthy controls [n = 10]) according to time series randomness. There was a significant difference in frontal EEG complexity between the DS and NDS subgroups ( p = .013), with DS group showing less complexity. A significant positive correlation was found between LZC values and Positive and Negative Syndrome Scale (PANSS) general psychopathology scores (ie, larger frontal EEG complexity correlated with more severe psychopathology), explained partially by the emotional component subscore of the PANSS. These findings suggest that cognitive processing occurring in the frontal networks in DS is less complex compared to NDS patients as reflected by EEG complexity measures. The data also suggest that there may be a relationship between the degree of emotionality and the complexity of the frontal EEG signal.

In vivo measurements of limbic glutamate and GABA concentrations in epileptic patients during affective and cognitive tasks: A microdialysis study.

Limbic system structures such as the amygdala (AMG) and the hippocampus (HIPP) are involved in affective and cognitive processing. However, because of the limitations in noninvasive technology, absolute concentrations of the neurotransmitters underlying limbic system engagement are not known. Here, we report changes in the concentrations of the neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) in the HIPP and the AMG of patients with nonlesional temporal lobe epilepsy undergoing surgery for intracranial subdural and depth electrode implantation. We utilized an in-vivo microdialysis technique while subjects were engaged in cognitive tasks with or without emotional content. The performance of an emotion learning task (EmoLearn) was associated with a significant increase in the concentration of glutamate in the HIPP when images with high valence content were processed, as compared to its concentration while processing images with low valence. In addition, significantly decreased levels of glutamate were found in the AMG when images with predominantly low valence content were processed, as compared to its concentration at baseline. The processing of face stimuli with anger/fear content (FaceMatch task) was accompanied with significantly decreased concentrations of GABA in the AMG and HIPP compared to its levels at the baseline. The processing of shapes on the other hand was accompanied with a significantly decreased concentration of the glutamate in the AMG as well as in the HIPP compared to the baseline. Finally, the performance of a nondeclarative memory task (weather prediction task-WPT) was associated with relatively large and opposite changes in the GABA levels compared to the baseline in the AMG (decrease) and the HIPP (increase). These data are relevant for showing an involvement of the amygdala and the hippocampus in emotional processing and provide additional neurochemical clues towards a more refined model of the functional circuitry of the human limbic system.

Glutamate and GABA concentration changes in the globus pallidus internus of Parkinson's patients during performance of implicit and declarative memory tasks: a report of two subjects.

The basal ganglia, typically associated with motor function, are involved in human cognitive processes, as demonstrated in behavioral, lesion, and noninvasive functional neuroimaging studies. Here we report task-contingent changes in concentrations of the neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) in the globus pallidus internus (GPi) of two patients with Parkinson's disease undergoing deep brain stimulation surgery by utilizing in-vivo microdialysis measurements during performance of implicit and declarative memory tasks. Performance of an implicit memory task (weather prediction task-WPT) was associated with increased levels of glutamate and GABA in the GPi compared to their concentrations at baseline. On the other hand, performance of a declarative memory task (verbal learning task-VLT) was associated with decreased levels of glutamate and GABA in GPi compared to baseline during the encoding and immediate recall phase with less conclusive results during the delayed recall phase. These results are in line with hypothesized changes in these neurotransmitter levels: an increase of excitatory (Glu) input from subthalamic nucleus (STN) to GPi during implicit memory task performance and a decrease of inhibitory inputs (GABA) from globus pallidus externus (GPe) and striatum to GPi during declarative memory performance. Consistent with our previous report on in-vivo neurotransmitter changes during tasks in STN, these data provide corroborative evidence for the direct involvement of basal ganglia in cognitive functions and complements our model of the functional circuitry of basal ganglia in the healthy and Parkinson's disease affected brain.

Motor cortex stimulation for neuropathic pain syndromes: a case series experience.

Neuropathic pain is a chronic condition lacking effective management and responding poorly to standard treatment protocols. Motor cortex stimulation has emerged as a new and promising therapeutic tool with outcomes potentially affected by the specific causes and location. In this study we report a series of eight cases in the neurosurgery practice of one of the authors (R.J.B.), including neuropathic pain syndromes of trigeminal or thalamic origin with or without anesthesia dolorosa. Pain relief was evaluated on the basis of comparison of Visual Analog scores at baseline and at 3 months after surgery. In addition, we assessed differences in pain relief outcomes between cases with trigeminal neuralgia and thalamic stroke, as well as cases with or without anesthesia dolorosa (i.e. pain with numbness of the affected area). Visual Analog Scale scores showed a statistically significant decrease of 4.19 (P=0.002) at 3 months follow-up compared with baseline. Pain relief levels in four of five patients in the subgroup with facial pain were higher than 50%, and none of the patients in the subgroup with thalamic and phantom limb pain showed such a good outcome. Furthermore, we found larger pain relief levels in facial pain conditions with versus without anesthesia dolorosa. These results point to utility of motor cortex stimulation in relieving neuropathic pain, as well as better outcomes for patients with facial pain and anesthesia dolorosa. Future studies should incorporate methods to noninvasively trial those patients who may benefit from surgical implantation to predict the outcomes and maximize their negative predictive value.

Relationships of behavioral measures of frontal lobe dysfunction with underlying electrophysiology in cocaine-dependent patients.

BACKGROUND AND OBJECTIVES: Despite evidence that frontal lobe functioning is impaired in cocaine-dependent individuals, relationships between behavioral measures of frontal dysfunction and electrophysiological measures of inhibition in cocaine use have not been explored. METHODS: Using the Frontal Systems Behavior Scale (FrSBe), frontal dysfunction was assessed in a group of abstinent cocaine-dependent subjects (N = 49) and healthy controls (N = 32). Using transcranial magnetic stimulation (TMS) and evoked potential (EP)-based electrophysiological measures of inhibition, we assessed associations between these measures and FrSBe estimates of frontal dysfunction. RESULTS: Patients had significantly higher FrSBe scores for executive dysfunction, disinhibition, and apathy than controls. Lower TMS-based resting motor thresholds (ie, hyperexcitability) were significantly associated with higher executive dysfunction scores in the patients. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Relationships between FrSBe scores and TMS-based measures highlight neurophysiological aberrations underlying frontal lobe dysfunction in cocaine abusers. TMS and EP measures may be useful probes of the intermediary steps between frontal lobe dysfunction and addictive behavior.

A statistical methodology to improve accuracy in differentiating schizophrenia patients from healthy controls.

We present a methodology to statistically discriminate among univariate and multivariate indices to improve accuracy in differentiating schizophrenia patients from healthy controls. Electroencephalogram data from 71 subjects (37 controls/34 patients) were analyzed. Data included P300 event-related response amplitudes and latencies as well as amplitudes and sensory gating indices derived from the P50, N100, and P200 auditory-evoked responses resulting in 20 indices analyzed. Receiver operator characteristic (ROC) curve analyses identified significant univariate indices; these underwent principal component analysis (PCA). Logistic regression of PCA components created a multivariate composite used in the final ROC. Eleven univariate ROCs were significant with area under the curve (AUC) >0.50. PCA of these indices resulted in a three-factor solution accounting for 76.96% of the variance. The first factor was defined primarily by P200 and P300 amplitudes, the second by P50 ratio and difference scores, and the third by P300 latency. ROC analysis using the logistic regression composite resulted in an AUC of 0.793 (0.06), p<0.001 (CI=0.685-0.901). A composite score of 0.456 had a sensitivity of 0.829 (correctly identifying schizophrenia patients) and a specificity of 0.703 (correctly identifying healthy controls). Results demonstrated the usefulness of combined statistical techniques in creating a multivariate composite that improves diagnostic accuracy.

The association between psychosis proneness and sensory gating in cocaine-dependent patients and healthy controls.

This was a naturalistic study of 23 abstinent cocaine-dependent patients and 38 controls who were studied using a paired-stimulus paradigm to elicit three mid-latency auditory evoked responses (MLAERs), namely, the P50, N100, and P200. Sensory gating was defined as the ratio of the S2 amplitude to the S1 amplitude. Psychosis-proneness was assessed using four Chapman psychosis proneness scales measuring perceptual aberration, magical ideation, social anhedonia, and physical anhedonia. Omnibus correlations based upon the entire sample revealed significant and differential relationships between the MLAER components and psychosis-proneness. Social Anhedonia scale scores accounted for the largest proportion of variance in the P50 gating ratio, while Perceptual Aberration scores accounted for the largest proportion of variance in P200 gating. Psychosis proneness and sensory gating appear to be associated. In particular, poorer P50 gating is related to higher scores on the Social Anhedonia scale in healthy controls and across mixed samples of cocainede-pendent patients and controls. These findings hold significance for the further understanding of the relationship between deficient sensory gating ability and the propensity to developing psychotic symptoms in a vulnerable population like cocaine-dependent individuals.