Isolated epileptiform activity in children and adolescents: prevalence, relevance, and implications for treatment.

In the field of psychiatry diagnoses are primarily based on the report of symptoms from either the patient, parents, or both, and a psychiatrist's observations. A psychiatric diagnosis is currently the most widely used basis for medication selection and the brain is seldom investigated directly as a source of those symptoms. This study addresses the request from the National Institute of Mental Health (NIMH) Research Domain Criteria Project (RDoC) for scientific research into neurological abnormalities that can be linked to psychiatric symptoms for the purpose of predicting medication response. One such neurological abnormality that has been the focus of many studies over the last three decades is isolated epileptiform discharges (IEDs) in children and adolescents without seizures. We conducted a systematic review of the literature to determine prevalence rates of IEDs within diagnostic categories. We then compared the prevalence of IEDs in the selected literature to our IRB-approved data archive. Our study found a consistent high prevalence of IEDs specifically for ADHD (majority > 25%) and ASD (majority > 59%), and consistent low prevalence rates were found for Depression (3%). If children and adolescents have failed multiple medication attempts, and more than one-third of them have IEDs, then an EEG would be justified within the RDoC paradigm.

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.

Diagnostic Utility of Sodium Lactate Infusion and CO2-35% Inhalation for Panic Disorder.

Laboratory measures have played an integral role in diagnosing pathology; however, compared to traditional medicine, psychiatric medicine has lagged behind in using such measures. A growing body of literature has begun to examine the viability and development of different laboratory measures in order to diagnose psychopathologies. The present review examines the current state of development of both sodium lactate infusion and CO2-35% inhalation as potential ancillary measures to diagnose panic disorder (PD). A previously established 3-step approach to identifying laboratory-based diagnostic tests was applied to available literature assessing the ability of both sodium lactate infusion or CO2-35% inhalation to induce panic attacks in PD patients, healthy controls, and individuals with other psychiatric conditions. Results suggest that across the literature reviewed, individuals with PD were more likely to exhibit panic attacks following administration of sodium lactate or CO2-35% compared to control participants. The majority of the studies examined only compared individuals with PD to healthy controls, suggesting that these ancillary measures are underdeveloped. In order to further determine the utility of these ancillary measures, research is needed to determine if panic attacks following administration of these chemical agents are unique to PD, or if individuals with related pathologies also respond, which may be indicative of transdiagnostic characteristics found across disorders.

Electroencephalogram (EEG) for children with autism spectrum disorder: evidential considerations for routine screening.

Routine electroencephalograms (EEG) are not recommended as a screen for epileptic discharges (EDs) in current practice guidelines for children with autism spectrum disorder (ASD). However, a review of the research from the last three decades suggests that this practice should be reevaluated. The significant comorbidity between epilepsy and ASD, its shared biological pathways, risk for developmental regression, and cognitive challenges demand increased clinical investigation requiring a proactive approach. This review highlights and explains the need for screening EEGs for children with ASD. EEG would assist in differentiating EDs from core features of ASD and could be included in a comprehensive assessment. EEG also meets the demand for evidence-based precision medicine and focused care for the individual, especially when overlapping processes of development are present.

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.

A cyclical path to recovery: Calling into question the wisdom of incarceration after restoration.

Around 20-25% of the current offenders in Cook County Jail of Chicago Illinois are mentally ill. Each one of these offenders had to be named competent to stand trial when they were first being tried in court. The majority of these offenders that were considered incompetent to stand trial (IST) had to go through the competency restoration process where they were housed in a state hospital and received treatment until the court could deem them to be competent to stand trial. Many defendants with minor offenses that were eventually deemed competent to stand trial, stood trial and were found guilty and sent to jail. Given the quality of psychiatric care and the inherent stress of being incarcerated, our question was, "is it efficient to spend the time and tax dollars on providing necessary treatment to mentally ill with minor offenses so they can stand trial and be sent to jail verses placement in community-based treatment programs?" To answer this question we reviewed the US literature addressing the alternatives to incarceration (i.e., diversion programs), and the success rate of those programs to minimize re-arrests and future criminal behavior. The studies on the efficacy of diversion programs remain sparse. The limited available studies point to a higher success rate in the ability to treat mentally ill misdemeanor offenders as well as prevent future criminal behavior; however these programs must be utilized early. Our conclusions are that diversion programs have the potential to reduce recidivism for misdemeanor offendors but further research needs to be conducted to ascertain the specifics of best practices for implementation of such programs.

The forsaking of the clinical EEG by psychiatry: how justified?

Despite decades of publications attesting to the role of the clinical EEG in diagnosing and managing psychiatric disorders, the procedure remains highly underutilized in the practice of psychiatry. The visually inspected EEG (vEEG) can detect various forms of abnormalities, each with its own clinical significance. Abnormalities can be paroxysmal (i.e., suggestive of an epileptic-like process) or stationary. The most important unanswered question remains the value of detecting epileptiform activity in a nonepileptic psychiatric patient in predicting favorable responses to anticonvulsant treatment. Despite the many shortcomings of vEEG, the available evidence suggests that in the presence of paroxysmal activity in a nonepileptic psychiatric patient a trial of a psychotropic anticonvulsant may be warranted if standard treatment has failed. More research on the contribution of paroxysmal EEG abnormalities to the problem of episodic psychiatric symptoms (e.g., panic attacks, dissociative episodes, repeated violence) is sorely needed. It is postulated that at least some of these conditions may represent an epilepsy spectrum disorder. Similarly, the significance of the presence of a slow-wave activity (whether focal or generalized) also deserves further well-designed research to ascertain the exact clinical significance. Nonetheless, the available data suggest that further medical workup is necessary to ascertain the nature and degree of the pathology when present.

A magnetoencephalography investigation of coherence source imaging in panic disorder.

Limbic and frontal structures are largely implicated in panic disorder (PD). Decreased coherence imaging values, as determined by magnetoencephalography (MEG), are suggestive of decreased or inefficient communication among these structures. We have previously demonstrated that coherence source imaging (CSI) values could be similar or higher in some PD patients. The purpose of the current investigation was to replicate these finding in a larger sample. Nine strictly diagnosed PD patients and nine age-matched and sex-matched healthy controls were examined. The CSI-MEG values of 26 frontotemporal regions (FTRs) and 28 extra-frontotemporal regions (ex-FTR; Brodmann areas) were determined for each participant. MEG scans were acquired using a 151-channel whole-head biomagnetometer system. Despite the relatively small sample size, CSI values were significantly lower in a number of FTRs in PD patients. In none of the ex-FTRs (i.e. posterior regions) were there differences between panic and control groups. The above data add to the complexity of understanding the nature of the pathophysiology of PD. Our finding of decreased focal coherence imaging values may reflect decreased excitability in these areas. The preliminary finding could be interpreted as an inhibitory process guarding against the spread of activity in closer hyperexcitable areas as seen in epilepsy. The current data provide evidence for dysfunctional communication within the frontotemporal structures. The findings have implications for the understanding of the neural circuitry underlying PD.

Inhibitory deficits in prepulse inhibition, sensory gating, and antisaccade eye movement in schizotypy.

Schizotypy is a term that refers to a continuum of personality characteristics, emerging from mental states ranging from organized and normal to unorganized and disordered; with the latter tending to include individuals with high schizotypal scores as well as those diagnosed with schizotypal personality disorder. Evidence from psychophysiological studies has found a relative weakness in the inhibitory functioning, including prepulse inhibition (PPI), sensory gating (SG), and antisaccade eye movement (AEM) in schizotypy and schizophrenia. As schizotypy and schizophrenia are in the same spectrum, understanding the nature of sensory and motor inhibitory weakness associated with schizotypy will optimize the prevention and intervention for both schizotypy and schizophrenia populations. This review aims at examining the deficits of sensory gating, saccade control, and prepulse inhibition in schizotypy; examining the relationship between the three measures and schizotypal symptoms and traits; examining the effect of nicotine on the three measures; and examining the relevant brain regions to the three measures. We searched multiple databases (such as MEDLINE, Pubmed, PsychINFO, Google Scholar) using combinations of the keywords: schizotypy, schizotypal personality disorder, prepulse inhibition, sensory gating and antisaccade for articles published in English since 1980. We found that three measures (SG, PPI and AEM) are associated with major schizotypal symptoms, suggesting that three measures could be used to predict the disease etiology and prognosis. Secondly, the three measures are modulated by nicotine administration at a certain level, providing a potential tool to study the role of nicotine in the cognition and symptom improvement in schizotypy. Thirdly, brain-imaging studies have localized activity in brain regions associated with sensory gating, saccade control, and prepulse inhibition, narrowing the search for brain regions to target for the treatment and prevention of schizotypy. Overall, the three measures are suggested to be a valuable tool to study the inhibitory deficits in schizotypy, and maybe used as a tool for the prevention and treatment of schizotypy as well.

EEG Abnormalities Are Associated With Poorer Depressive Symptom Outcomes With Escitalopram and Venlafaxine-XR, but Not Sertraline: Results From the Multicenter Randomized iSPOT-D Study.

Rationale Limited research is available on electrophysiological abnormalities such as epileptiform EEG or EEG slowing in depression and its association with antidepressant treatment response. Objectives We investigated the association between EEG abnormalities and antidepressant treatment response in the international Study to Predict Optimized Treatment in Depression (iSPOT-D). Methods Of 1008 participants with major depressive disorder randomized to escitalopram, sertraline, or venlafaxine-XR, 622 completed 8 weeks of treatment per protocol. The study also recruited 336 healthy controls. Treatment response was established after 8 weeks using the 17-item Hamilton Rating Scale for Depression (HRSD17). The resting-state EEG was assessed at baseline with eyes closed. EEG abnormalities including epileptiform activity, EEG slowing, and alpha peak frequency (APF) were scored for all subjects, blind to treatment outcome. Results Patients and controls did not differ in the occurrence of EEG abnormalities. Furthermore, in the per protocol sample the occurrence of epileptiform EEG and EEG slowing (as a combined marker) were associated with a reduced likelihood of responding to escitalopram (P = .019; odds ratio [OR] = 3.56) and venlafaxine-XR (P = .043; OR = 2.76), but not sertraline (OR = 0.73). The response rates for this "any EEG abnormality" groups versus the "no-abnormality" group were 33% and 64% for escitalopram and 41% and 66% for venlafaxine-XR, respectively. A slow APF was associated with treatment response only in the sertraline group (P = .21; d = .027). Conclusions EEG abnormalities are associated with nonresponse to escitalopram and venlafaxine-XR, but not sertraline, whereas a slow APF is associated to response for sertraline only.

Epilepsy spectrum disorders: A concept in need of validation or refutation.

Episodic psychiatric symptoms are not uncommon and range from panic attacks to repeated violent acts. Some evidence has accumulated over the years that at least in a subset of patients exhibiting these symptoms there may be evidence for the presence of focal cortical/subcortical hyperexcitability. In these cases the condition could be conceptualized as an epilepsy spectrum disorder (ESD) with significant treatment implications. There is currently no clear demarcation of this category of symptoms, their prevalence, an understanding of how these symptoms occur, what is appropriate work up and possible treatments. In this article, we propose that milder degrees of increased neural excitability (i.e., a subthreshold excitation insufficient to cause seizures) may nonetheless be capable of causing observable phenotypic changes. The observable phenotypic changes depend on the degree of hyperexcitability and the location of the hyperexcitable neural tissue. The location of the abnormal neural tissue may dictate the initial manifestation of an attack resulting from activation of the hyperexcitable tissue, but the anatomical connectivity of the abnormal region will dictate the breadth of manifestations. We provide some evidence, derived mainly from either electroencephalography studies of these populations or clinical reports of response to anti-epilepsy treatment, for the assumption and propose methods to test the advanced hypothesis.

Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part I: Neurophysiology.

The neurophysiological components that have been proposed as biomarkers or as endophenotypes for schizophrenia can be measured through electroencephalography (EEG) and magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), polysomnography (PSG), registration of event-related potentials (ERPs), assessment of smooth pursuit eye movements (SPEM) and antisaccade paradigms. Most of them demonstrate deficits in schizophrenia, show at least moderate stability over time and do not depend on clinical status, which means that they fulfil the criteria as valid endophenotypes for genetic studies. Deficits in cortical inhibition and plasticity measured using non-invasive brain stimulation techniques seem promising markers of outcome and prognosis. However the utility of these markers as biomarkers for predicting conversion to psychosis, response to treatments, or for tracking disease progression needs to be further studied.

Physiological correlates of positive symptoms in schizophrenia.

Patients with schizophrenia have been hypothesized to have a functional impairment in filtering irrelevant sensory information, which may result in positive symptoms such as hallucinations or delusions. Many evidences suggest that abnormalities in the event-related brain potentials (ERPs), resting state electroencephalography (EEG) and synchronized oscillatory activity of neurons may reflect core pathophysiological mechanisms of schizophrenia. Abnormalities in amplitude and latency of the ERPs reflecting aberrations in gating and difficulties in the detection of changes in auditory stimuli, as well as defects in stimuli evaluation and integration of information are common in patients with schizophrenia. This chapter highlights the findings of electrophysiological studies in schizophrenia dealing with early sensory perception and attention, automatic sensory detection of stimuli changes and cognitive evaluation and integration of information, relevant to the pathophysiological mechanisms underpinning hallucinations and delusions. Results of electrophysiological studies investigating the neural correlates of positive symptoms suggest aberrant intrinsic organization of functional brain networks.

What does the electroencephalogram tell us about the mechanisms of action of ECT in major depressive disorders?

Electroconvulsive therapy (ECT) remains to be one of the most effective treatment options in treatment-resistant major depressive disorder (MDD). From the early days, researchers have embarked on extracting information from electroencephalography (EEG) recordings before, during, and after ECT to identify neurophysiological targets of ECT and discover EEG predictors of response to ECT in patients with MDD. In this article, we provide an overview of visually detected and quantitative EEG features that could help in furthering our understanding of the mechanisms of action of ECT in MDD. We further discuss the EEG findings in the context of postulated hypotheses of ECT therapeutic pathways. We introduce an alternative and unifying hypothesis suggesting that ECT may exert its therapeutic efficacy through resetting the aberrant functional connectivity and promoting the generation of new and healthy connections in brain regions implicated in MDD pathophysiology, a mechanism that may be in part mediated by the ECT-induced activation of inhibitory and neuroplasticity mechanisms. We further discuss the added value of EEG markers in the larger context of ECT research and as complementary to neuroimaging and genetic markers. We conclude by drawing attention to the need for longitudinal studies in large cohort of patients and the need for standardization and validation of EEG algorithms of functional connectivity across studies to facilitate the translation of EEG correlates of ECT response in routine clinical practice.

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.

Electrophysiological aberrations associated with negative symptoms in schizophrenia.

Clinical heterogeneity is a confound common to all of schizophrenia research. Deficit schizophrenia has been proposed as a homogeneous disease entity within the schizophrenia syndrome. The use of the Schedule for the Deficit Syndrome (SDS) has allowed the definition of a subgroup dominated by persistent and primary negative symptoms. While a number of studies have appeared over the years examining the electrophysiological correlates of the cluster of negative symptoms in schizophrenia, only a few studies have actually focused on the Deficit Syndrome (DS). In this chapter, electrophysiological investigations utilizing EEG, Evoked Potentials (EPs), polysomnography (PSG), or magnetoencephalography (MEG) to probe "negative symptoms," or "Deficit Syndrome" are reviewed. While this line of research is evidently in its infancy, two significant trends emerge. First, spectral EEG studies link increased slow wave activity during wakefulness to the prevalence of negative symptoms. Second, sleep studies point to an association between decrease in slow wave sleep and prevalence of negative symptoms. Several studies also indicate a relationship of negative symptoms with reduced alpha activity. A host of other abnormalities including sensory gating and P300 attenuation are less consistently reported. Three studies specifically addressed electrophysiology of the DS. Two of the three studies provided evidence suggesting that the DS may be a separate disease entity and not simply a severe form of schizophrenia.

Predictive value of isolated epileptiform discharges for a favorable therapeutic response to antiepileptic drugs in nonepileptic psychiatric patients.

The efficacy of antiepileptic drugs (AEDs) in treating behavioral symptoms in nonepileptic psychiatric patients with abnormal EEGs is currently unknown. Although isolated epileptiform discharges have been reported in many psychiatric conditions, they are most commonly observed in patients with aggression, panic, or autistic spectrum disorders. The literature search was guided by 3 criteria: (1) studies had patients who did not experience seizures, (2) patients had EEGs, and (3) an AED was administered. Most important finding is that the number of "controlled" studies was extremely small. Overall, most reports suggest that the use of an AED can be associated with clinical and, at times, improved EEG abnormalities. Additionally, six controlled studies were found for other psychiatric disorders, such as learning disabilities with similar results. Overall, the use of anticonvulsants to treat nonepileptic psychiatric patients needs further controlled studies to better define indications, adequate EEG work-up, best AED to be used, and optimal durations of treatment attempts.

Anticonvulsant medications for panic disorder: a review and synthesis of the evidence.

OBJECTIVES: Currently, there are no guidelines for when to use an antiepileptic drug (AED) in nonepileptic panic disorder (PD) patients. We conducted this review to ascertain what guidance available literature can provide as to when to consider AEDs for PD patients. METHODS: The primary data sources were PubMed and Google-Scholars. Search was limited to "English" and "Humans". Only papers addressing use of nonbenzodiazepine AEDs in PD were included. Data regarding study subjects, the AED utilized, and clinical responses were collected. EEG data were used to classify reports of patients with abnormal versus those with normal and/or no EEG work-up. RESULTS: Ten reports were identified for use of AEDs in PD patients with abnormal EEGs with a total of 20 patients (17 responders). None of the 10 reports were controlled studies. Eighteen reports were identified for use of AEDs in panic patients with either normal EEGs or unselected groups (no EEG work-up). Out of the 18 reports, three were controlled studies. Included in the 18 studies were 253 patients (137 responders). CONCLUSIONS: We preliminary concluded that EEG work-up could be useful in guiding the treatment in PD as an abnormal EEG may be indicative of a higher likelihood of a positive response to an AED.