Alpha event-related synchronization after eye closing differs in Alzheimer's disease and dementia with Lewy bodies: a magnetoencephalography study.

BACKGROUND: The electroencephalography (EEG) abnormalities found in patients with dementia with Lewy bodies (DLB) are conflicting. In this study, we used magnetoencephalography, which has higher spatial resolution than electroencephalography, to explore neurophysiological features of DLB that may aid in the differential diagnosis. METHODS: Six patients with DLB, 11 patients with Alzheimer's disease, and 11 age-matched normal subjects were recruited. We investigated alterations in the ratio of event-related synchronization (ERS) in the alpha band after eye-closing. RESULTS: Although the averaged ratio change of alpha ERS after eye-closing appeared predominantly in the posterior brain regions in all study groups, DLB patients had the weakest ratio change of alpha ERS. In particular, DLB patients exhibited a significantly reduced ratio change of alpha ERS in the bilateral inferior temporal gyrus, right occipital pole, and left parieto-occipital cortex compared to Alzheimer's disease patients or normal controls. CONCLUSION: Our findings indicated that a reduced ratio change of alpha ERS in the posterior brain regions elicited by eye-closing is a brain electromagnetic feature of DLB.

Induced oscillatory responses during the Sternberg's visual memory task in patients with Alzheimer's disease and mild cognitive impairment.

In this study we used magnetoencephalography during a modified version of the Sternberg's memory recognition task performed by patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI), and by age-matched healthy controls to identify differences in induced oscillatory responses. For analyses, we focused on the retention period of the working memory task. Multiple-source beamformer and Brain Voyager were used for localization of source-power changes across the cortex and for statistic group analyses, respectively. We found significant differences in oscillatory response during the task, specifically in beta and gamma frequency bands: patients with AD showed reduced beta event-related desynchronization (ERD) in the right central area compared to controls, and reduced gamma ERD in the left prefrontal and medial parietal cortex compared to patients with MCI. Our findings suggest that reduced oscillatory responses over certain brain regions in high frequency bands (i.e., beta, gamma), and especially in the beta band that was significantly different between AD patients and healthy subjects, may represent brain electromagnetic changes underlying visual-object working memory dysfunction in early AD, and a neurophysiological indicator of cognitive decline.

[Endophenotypes in schizophrenia: a review of electrophysiological studies].

Schizophrenia patients consistently show some deficiency in electrophysiological measures, such as PPI (Prepulse Inhibition), ERP (Event-Related Potential) components (mismatch negativity, P50, P300), EEG (Electroencephalography), and MEG (Magnetoencephalography). These components have been intensively studied as quantitative biological markers (i.e., endophenotypes) for psychiatric disorders. Recently brain oscillations, especially gamma (30-80 Hz) band activity (GBA), are being increasingly investigated as new candidate endophenotypes. In this review, we summarize the current status, perspective, and limitations of representative paradigms for investigating abnormal electrophysiological components of schizophrenia, along with relevant genetic polymorphism.

Psychopathology and working memory-induced activation of the prefrontal cortex in schizophrenia-like psychosis of epilepsy: Evidence from magnetoencephalography.

AIM: The aim of this study was to investigate whether magnetoencephalographic oscillations underlying working memory dysfunction in the dorsolateral prefrontal cortex (DLPFC) are related to psychopathological disturbance in patients with schizophrenia-like psychosis of epilepsy (SLPE). METHODS: Twelve patients with SLPE and 14 non-psychotic epilepsy controls participated in this study. Magnetoencephalography was recorded while patients performed a visual working memory (WM) task. Psychopathology was assessed using a four-factor structure of the Brief Psychiatric Rating Scale, and regression analyses were carried out to examine the relative impact of severity of psychopathology on WM-induced activation of the DLPFC. RESULTS: We found that activation of the WM-compromising DLPFC, as indicated by increased alpha desynchronization in patients with SLPE compared with their non-psychotic counterparts, showed a positive linear correlation with disorganization symptom scores. This association remained significant after controlling for confounding factors, including age, task performance, IQ, and duration of psychosis. CONCLUSION: Our results indicate that abnormal activation in prefrontal areas engaged during working memory may be critical to domains of psychopathology, in particular disorganized thought-processing in patients with SLPE.

Working memory abnormalities in chronic interictal epileptic psychosis and schizophrenia revealed by magnetoencephalography.

Working memory (WM) deficits are considered a core cognitive dysfunction in schizophrenia. To determine cognitive abnormalities in chronic interictal psychosis (CIP), and to assess whether these abnormalities are distinguishable from those seen in schizophrenia in terms of WM deficits, we used magnetoencephalography during a WM task performed by patients with CIP, nonpsychotic epilepsy, and schizophrenia and by healthy subjects. Multiple Source Beamformer and Brain-Voyager were used for analysis. In both patients with CIP and those with schizophrenia, we found dorsolateral prefrontal hyperactivation and left inferior temporal hypoactivation, as indicated by alpha event-related desynchronization and synchronization, respectively. Patients with schizophrenia also showed alpha2 event-related desynchronization in the mid-prefrontal cortex relative to healthy controls. Direct comparison of patients with CIP and schizophrenia rendered no difference in source-power changes. Our findings indicate similar functional cognitive abnormalities in CIP and schizophrenia in the prefrontal and left temporal cortex, which supports the possibility that these disorders share common underlying pathophysiological mechanisms.

Frontal shift of posterior alpha activity is correlated with cognitive impairment in early Alzheimer's disease: a magnetoencephalography-beamformer study.

BACKGROUND: Induced-oscillatory activity is considered a key factor for understanding functional processes in the brain. Magnetoencephalography (MEG) can measure oscillatory activity non-invasively with higher spatial resolution than electroencephalography (EEG). However, MEG has rarely been used to explore functional abnormalities that may represent state markers in patients with Alzheimer's disease (AD). METHODS: Thirteen patients with early AD and 14 age-matched normal controls participated in the present study. Magnetoencephalography activity was acquired during eyes-open and eyes-closed states. Alpha event-related synchronization (ERS) after eye closing was calculated and its cortical sources superimposed on each individual's magnetic resonance imaging (MRI) scan. The resulting functional image was converted into a Talairach-transformed anatomical brain image and group comparisons were made. We also assessed correlations between cortical ERS sources showing significant between-group differences in alpha activity and external clinical parameters, especially measures of cognitive function. RESULTS: The averaged alpha ERS after eye closing appeared dominantly in posterior brain regions in both patients with AD and healthy controls. However, there was a significant increase in alpha ERS in frontal regions, maximal over the prefrontal cortex, in patients with AD relative to controls, indicating a frontal shift of the posterior dominant MEG alpha rhythm in AD patients. This frontal ERS source in the alpha band was negatively correlated with Mini-Mental State Examination scores in the AD patient group. CONCLUSIONS: The findings indicate that a frontal shift of alpha ERS elicited by an eyes-open/eyes-closed paradigm may be an early brain electromagnetic change in patients with AD, probably representing a physiological state marker of the disease. Furthermore, the results confirm that the beamformer with group comparison analysis is a useful tool with which to explore functional processes in the brain, as indicated by oscillatory activity changes.

Impaired regional hemodynamic response in schizophrenia during multiple prefrontal activation tasks: a two-channel near-infrared spectroscopy study.

In schizophrenia, dysfunction of the prefrontal cortex (PFC), regarded as a core feature of the disease, has been investigated by different neuroimaging methods. Near infrared spectroscopy (NIRS), a novel neurophysiological method, is being increasingly used in the investigation of frontal dysfunction in schizophrenia. However, NIRS measurements during multiple frontal activation tasks have been rarely reported. The purpose of this study was to compare hemodynamic changes in the PFC between patients with schizophrenia and healthy controls during four different types of frontal lobe tasks using a 2-channel NIRS system. Thirty patients with schizophrenia and thirty age- and gender-matched healthy controls were enrolled in this study. In both groups, changes in oxygenated hemoglobin concentration (Delta[oxyHb]) at the bilateral forehead were measured during Verbal fluency test letter version (VFT-letter), VFT category version, Tower of Hanoi (TOH), the Sternberg and Stroop tasks. Regarding Delta[oxyHb] in PFC, a diagnosis group effect was found for VFT-letter and TOH. Significant negative correlation was found between left Delta[oxyHb] during TOH and negative and cognitive symptom scores in schizophrenia patients. Right Delta[oxyHb] during TOH also showed significant negative correlation with cognitive symptoms scores. No significant correlation between Delta[oxyHb] and clinical characteristics were observed during VFT-letter. These findings suggest that among a battery of frontal lobe tasks administered to schizophrenia patients, VFT-letter and TOH are more sensitive to detect PFC activation, as indicated by Delta[oxyHb] using a 2-channel NIRS. Taken together, these findings and those of previous neuroimaging studies suggest that VFT-letter and TOH might represent possible candidate physiological markers of prefrontal dysfunction in schizophrenia, though extensive testing in clinical settings will be necessary.

Association study of the G72 gene with schizophrenia in a Japanese population: a multicenter study.

G72 is one of the most widely tested genes for association with schizophrenia. As G72 activates the D-amino acid oxidase (DAO), G72 is termed D-amino acid oxidase activator (DAOA). The aim of this study is to investigate the association between G72 and schizophrenia in a Japanese population, using the largest sample size to date (1774 patients with schizophrenia and 2092 healthy controls). We examined eight single nucleotide polymorphisms (SNPs), which had been associated with schizophrenia in previous studies. We found nominal evidence for association of alleles, M22/rs778293, M23/rs3918342 and M24/rs1421292, and the genotype of M22/rs778293 with schizophrenia, although there was no association of allele or genotype in the other five SNPs. We also found nominal haplotypic association, including M15/rs2391191 and M19/rs778294 with schizophrenia. However, these associations were no longer positive after correction for multiple testing. We conclude that G72 might not play a major role in the risk for schizophrenia in the Japanese population.

Impaired prepulse inhibition and habituation of acoustic startle response in Japanese patients with schizophrenia.

Prepulse inhibition (PPI) and habituation of the acoustic startle reflex (ASR) are considered to be candidate endophenotypes of schizophrenia. However, to our knowledge, only one group has investigated these startle measures in Asian patients with schizophrenia. In the present study, we evaluated these startle measures in 51 Japanese patients with schizophrenia and compared them with those of 55 healthy age- and sex-matched Japanese controls. A human startle response monitoring system was used to deliver acoustic startle stimuli, and record and score the electromyographic activity of the orbicularis oculi muscle. The startle measures examined were mean magnitude of ASR to pulse alone trials in initial block (SR), habituation of ASR during the session (HAB), and PPI at prepulse intensities of 82 dB (PPI82), 86 dB (PPI86), and 90 dB (PPI90) sound pressure level. SR was not significantly different between the patients and controls. Patients displayed significantly reduced HAB and PPI for all prepulse intensities compared to controls. The greatest statistical difference in PPI between patients and controls was found with PPI86. This did not correlate with any clinical variable in each group. Our results indicate that PPI and habituation of ASR are impaired in Asian patients with schizophrenia.

Event-related synchronization of alpha activity in early Alzheimer's disease and mild cognitive impairment: an MEG study combining beamformer and group comparison.

In patients with Alzheimer's disease (AD), it is sometimes challenging to identify typical findings in electroencephalography (EEG) or magnetoencephalography (MEG) such as a slowing of the posterior dominant activity or an increase in slow activity. In this MEG study, we evaluated the event-related synchronization (ERS) of alpha activity after eye closing in patients with early AD and mild cognitive impairment (MCI) who presented no slow MEG pattern. Thirteen patients with probable AD and thirteen patients with MCI, who met NINCDS-ADRDA and Petersen's diagnostic criteria, respectively, were enrolled. We also selected fourteen age-matched normal control subjects. MEG activity was acquired during eye-open and eye-closed states. The ERS after eye closing within 8-15Hz frequency band was calculated and its cortical source was superimposed on the individual's MRI by using the beamformer implemented in Brain Electrical Source Analysis (BESA). The Source image was converted into a standardized image, and group comparisons across patients with AD, MCI and controls were performed using BrainVoyager QX. The averaged ERS was observed dominantly in posterior regions in all three groups. Significant difference in ERS was observed only for the comparison between AD patients and controls, with AD patients showing increased ERS in frontal regions. Frontal shift of posterior alpha activity was observed clearly in AD patients using the combination of beamformer and group comparison.

Frontal activity during the digit symbol substitution test determined by multichannel near-infrared spectroscopy.

BACKGROUND: The digit symbol substitution test (DSST) is a clinically useful and widely accepted tool for the detection of various psychiatric disorders. Investigating neural activity during the DSST is useful when considering the relationship between the poor performance on the DSST and neurocognitive deficits. However, obtaining reliable functional imaging of the neural mechanisms associated with this test is challenging due to motion artifacts. AIMS: To circumvent this problem, we examined frontal lobe activity during the DSST using multichannel near-infrared spectroscopy, a noninvasive functional imaging technique that does not interfere with the DSST procedure. METHODS: Twenty-five healthy volunteers were enrolled in this study. Changes in the concentration of oxygenated hemoglobin (oxyHb) during the DSST were determined bilaterally in 52 measurement points (channels) on the frontal area. RESULTS: We found significant increases in oxyHb in more than 70% of the channels, with the intensity of the increase being more pronounced in the left hemisphere. Several channels showed significant positive correlations between changes in oxyHb and DSST performance. Some of the channels with a significant increase in oxyHb during the DSST did not show a correlation with the DSST performance. CONCLUSIONS: Our findings indicate that the DSST could prove useful as a frontal lobe stimulating task. Further examinations of DSST/near-infrared spectroscopy analyses of neural mechanisms in patients with psychiatric and neurological diseases are necessary to assess its effectiveness in clinical practice for the evaluation of neuropsychopathology.

Cephalic auras of supplementary motor area origin: an ictal MEG and SAM(g2) study.

Although a nonspecific cephalic sensation, the so-called "cephalic aura," is a common sensory aura, particularly in frontal lobe seizures, but is rarely is the entire sensory seizure event. The unusual presentation of cephalic sensations in isolation representing supplementary motor area (SMA) seizures, which are commonly unaccompanied by ictal electroencephalography (EEG) changes, can easily lead to misdiagnosis of nonepileptic psychogenic seizures. We illustrate the case of a 36-year-old male patient with frontal lobe epilepsy who presented with isolated cephalic auras described as a nonvertiginous sense of head movement without observable clinical signs after his habitual partial motor seizures were controlled with pharmacotherapy. Video/EEG recordings showed no recognizable epileptic discharges time-locked to the onset of the isolated cephalic auras. Ictal magnetoencephalography (MEG) with synthetic aperture magnetometry-kurtosis (SAM(g(2))) analysis demonstrated the SMA onset of the cephalic auras; thus, MEG was essential in differentiating these isolated auras from nonepileptic psychogenic events.

Tuberous sclerosis: localizing the epileptogenic tuber with synthetic aperture magnetometry with excess kurtosis analysis.

The hallmark of tuberous sclerosis is the presence of multiple cortical tubers. Identifying the epileptogenic tubers is difficult and often requires invasive intracranial electroencephalograph (EEG) monitoring. We report on a patient with tuberous sclerosis upon whom the novel magnetoencephalography (MEG) technique of synthetic aperture magnetometry (SAM) with excess kurtosis (g2) analysis was performed for localization of the epileptogenic tuber. Simultaneous electroencephalography (EEG) was also performed. MEG data, as analyzed by SAM(g2), were superimposed on the patient's MRIs. In the fluid attenuated inversion recovery MRIs, several tubers and subependymal nodules could be identified, with the largest tubers being located in the right frontal and left anteriotemporal regions. Despite multiple cortical lesions existing, the SAM(g2) images showed a single large tuber and surrounding epileptogenic tissue in the left temporal cortex. We suggest that MEG with SAM(g2) analysis may be clinically useful for the accurate identification of epileptogenic tubers in patients with tuberous sclerosis.

Resting-state EEG source localization and functional connectivity in schizophrenia-like psychosis of epilepsy.

BACKGROUND: It is unclear whether, like in schizophrenia, psychosis-related disruption in connectivity between certain regions, as an index of intrinsic functional disintegration, occurs in schizophrenia-like psychosis of epilepsy (SLPE). In this study, we sought to determine abnormal patterns of resting-state EEG oscillations and functional connectivity in patients with SLPE, compared with nonpsychotic epilepsy patients, and to assess correlations with psychopathological deficits. METHODOLOGY/PRINCIPAL FINDINGS: Resting EEG was recorded in 21 patients with focal epilepsy and SLPE and in 21 clinically-matched non-psychotic epilepsy controls. Source current density and functional connectivity were determined using eLORETA software. For connectivity analysis, a novel nonlinear connectivity measure called "lagged phase synchronization" was used. We found increased theta oscillations in regions involved in the default mode network (DMN), namely the medial and lateral parietal cortex bilaterally in the psychotic patients relative to their nonpsychotic counterparts. In addition, patients with psychosis had increased beta temporo-prefrontal connectivity in the hemisphere with predominant seizure focus. This functional connectivity in temporo-prefrontal circuits correlated with positive symptoms. Additionally, there was increased interhemispheric phase synchronization between the auditory cortex of the affected temporal lobe and the Broca's area correlating with auditory hallucination scores. CONCLUSIONS/SIGNIFICANCE: In addition to dysfunction of parietal regions that are part of the DMN, resting-state disrupted connectivity of the medial temporal cortex with prefrontal areas that are either involved in the DMN or implicated in psychopathological dysfunction may be critical to schizophrenia-like psychosis, especially in individuals with temporal lobe epilepsy. This suggests that DMN deficits might be a core neurobiological feature of the disorder, and that abnormalities in theta oscillations and beta phase synchronization represent the underlying neural activity.

Decreased α event-related synchronization in the left posterior temporal cortex in schizophrenia: a magnetoencephalography-beamformer study.

Alpha rhythm is one of the most prominent electromagnetic changes in the brain, and electroencephalography (EEG) alpha reactivity disturbance may sometimes represent an early sign of cerebral dysfunction. Although magnetoencephalography (MEG) has a better spatial resolution than EEG, it has not extensively been used to explore alpha-power change deficits in schizophrenia as a possible neurophysiological marker of the disease. The purpose of this study was to use MEG to identify abnormalities in alpha synchronization induced by eye-closing in schizophrenia patients compared to healthy controls, and to investigate whether alpha reactivity deficits correlate with clinical features of the disorder. MEG data were recorded in 22 schizophrenia patients and 20 age- and gender-matched controls during eyes-open/eyes-closed resting states. Cortical sources of event-related synchronization (ERS) were estimated using multiple source beamformer, and BrainVoyager was used for statistic group analysis. A significant decrease in ERS in the upper alpha band (10-13 Hz) was found in the left posterior temporal region in schizophrenia patients relative to controls, and this activity showed correlation with visual memory scores. This upper alpha ERS deficit may indicate left temporal dysfunction and visual-information processing impairment in schizophrenia, and upon further confirmation it might represent a neurophysiological state marker of the disorder.

Frontal cortex activation associated with speeded processing of visuospatial working memory revealed by multichannel near-infrared spectroscopy during Advanced Trail Making Test performance.

Although visuospatial working memory (VSWM) is commonly used during speeded and unconscious memory processing in daily life, most neuroimaging studies on VSWM use tasks that impose motor restrictions onto the examinees to avoid movement-related artifacts. Multichannel near-infrared spectroscopy (NIRS), however, can measure cortical activation during cognitive processing without interfering with task procedure. The purpose of this study is to determine whether multichannel NIRS can detect VSWM-induced frontal cortex activation similar to that seen in VSWM performance in daily-life activity. Using NIRS, we measured relative changes in the concentration of oxygenated hemoglobin as an index of frontal activation in 52 measurement points (channels) on the frontal area during the Advanced Trail Making Test (ATMT), a tool used to assess VSWM. The ATMT consists of two tasks, R and F, with the former assessing motor factors and the latter relating to both motor and cognitive factors involved in speeded and unconscious VSWM operations. Twenty-six healthy volunteers were enrolled in this study. Channel activation during Task F performance was observed bilaterally over the dorsolateral and ventrolateral prefrontal cortex. This distribution may reflect central executive function of working memory. Channel activation during Task R was circumscribed to part of the left ventrolateral prefrontal cortex partially overlapping with areas active during Task F performance, likely representing task-related motor factor activation. Our findings suggest that multichannel NIRS during ATMT performance is an appropriate means of measuring cortical activation induced by VSWM operations during daily activity.

Post-movement beta rebound abnormality as indicator of mirror neuron system dysfunction in autistic spectrum disorder: an MEG study.

The mu rhythm is regarded as a physiological indicator of the human mirror neuron system (MNS). The dysfunctional MNS hypothesis in patients with autistic spectrum disorder (ASD) has often been tested using EEG and MEG, targeting mu rhythm suppression during action observation/execution, although with controversial results. We explored neural activity related to the MNS in patients with ASD, focusing on power increase in the beta frequency band after observation and execution of movements, known as post-movement beta rebound (PMBR). Multiple source beamformer (MSBF) and BrainVoyager QX were used for MEG source imaging and statistical group analysis, respectively. Seven patients with ASD and ten normal subjects participated in this study. During the MEG recordings, the subjects were asked to observe and later execute object-related hand actions performed by an experimenter. We found that both groups exhibited pronounced PMBR exceeding 20% when observing and executing actions with a similar topographic distribution of maximal activity. However, significantly reduced PMBR was found only during the observation condition in the patients relative to controls in cortical regions within the MNS, namely the sensorimotor area, premotor cortex and superior temporal gyrus. Reduced PMBR during the observation condition was also found in the medial prefrontal cortex. These results support the notion of a dysfunctional execution/observation matching system related to MNS impairment in patients with ASD, and the feasibility of using MEG to detect neural activity, in particular PMBR abnormalities, as an index of MNS dysfunction during performance of motor or cognitive tasks.

Discriminant analysis in schizophrenia and healthy subjects using prefrontal activation during frontal lobe tasks: a near-infrared spectroscopy.

While psychiatric disorders such as schizophrenia are largely diagnosed on symptomatology, several studies have attempted to determine which biomarkers can discriminate schizophrenia patients from non-patients with schizophrenia. The objective of this study is to assess whether near-infrared spectroscopy (NIRS) measurement can distinguish schizophrenia patients from healthy subjects. Sixty patients with schizophrenia and sixty age- and gender-matched healthy controls were divided into two sequential groups. The concentration change in oxygenated hemoglobin (Delta[oxy-Hb]) was measured in the bilateral prefrontal areas (Fp1-F7 and Fp2-F8) during the Verbal Fluency Test (VFT) letter version and category version, Tower of Hanoi (TOH), Sternberg's (SBT) and Stroop Tasks. In the first group, schizophrenia patients showed poorer task performance on all tasks and less prefrontal cortex activation during all but the Stroop Task compared to healthy subjects. In the second group, schizophrenia patients showed poorer task performance and less prefrontal cortex activation during VFTs and TOH tasks than healthy subjects. We then performed discriminant analysis by a stepwise method using Delta[oxy-Hb] and task performance measures as independent variables. The discriminant analysis in the first group included task performance of TOH, VFT letter and VFT category and Delta[oxy-Hb] of VFT letter. As a result, 88.3% of the participants were correctly classified as being schizophrenic or healthy subjects in the first analysis. The discriminant function derived from the first group correctly assigned 75% of the subjects in the second group. Our findings suggest that NIRS measurement could be applied to differentiate patients with schizophrenia from healthy subjects.

Relationship between prepulse inhibition of acoustic startle response and schizotypy in healthy Japanese subjects.

Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) is the most common psychophysiological index of sensorimotor gating. Several studies have investigated the relationship of PPI of ASR to schizotypy in Caucasians. However, little has been reported on this relationship in Asians. We investigated a possible relationship between PPI of ASR and schizotypy in 79 healthy Japanese subjects. Schizotypy was assessed by the Schizotypal personality Questionnaire (SPQ). PPI was evaluated at signal-to-noise ratios (SnRs: difference between background noise intensity and prepulse intensity) of +12, +16, and +20 dB. The total SPQ score, cognitive/perceptual score, and interpersonal score correlated negatively with PPI at SnR of +16 and +20 dB. We conclude that PPI is associated with the trait of schizotypy in healthy Asian subjects.

Factors associated with impaired quality of life in younger and older adults with epilepsy.

The purpose of this study is to weigh psychological state, patients' demographics, seizure-related factors, and medical comorbidity in older adults with epilepsy against the same parameters in younger adults in an attempt to identify best quality of life (QoL) predictors. The Quality of Life in Epilepsy Inventory for Adults (QOLIE-31) and the Beck Depression Inventory-II (BDI-II) were completed by 146 patients with localization-related epilepsy. There was no statistical difference in the QOLIE-31 total score between younger and older adults. Best QoL predictors were BDI-II and seizure frequency, with BDI-II providing more than 3 times the impact of seizure frequency. BDI-II also substantively predicted most QOLIE-31 domains. Additionally, epilepsy duration positively correlated with overall QoL only among older adults. In summary, in younger as well as older adult epilepsy patients, depressive symptoms emerge as the strongest predictor of QoL. However, older adults appear to adapt better to their chronic health problem.