Supplements to Clinical neurophysiology最新文献

Background: Gray matter atrophy is regarded as a valid marker of neurodegeneration in Alzheimer's disease (AD), but few studies have investigated in detail the topographic changes associated with normal aging. In addition, few studies have compared the changes in the earliest clinical stage of AD (prodromal AD (pAD)) with those of healthy aging. Here we aimed to investigate the topographical distribution of age-related cortical atrophy and to compare it with that associated with prodromal and estabilished AD.

Methods: Structural T1-weighted high-resolution brain magnetic resonance imaging scans were acquired from 60 healthy volunteers (20 young adults, YA: age 32.7 +/- 4.5 years; 40 elderly subjects, HE: age 71.3 +/- 6.2 years), 16 mild cognitive impairment subjects who converted to AD within 2 years (prodromal AD, pAD: age 72.8 +/- 5.4), and 20 mild to moderate AD patients (mAD, age 72.5 +/- 10.3). Cortical gray matter differences were investigated using a surface-based anatomical mesh modeling technique (cortical pattern matching) and region-of-interest (ROI) analyses based on hypothesized brain networks taught to have a functional and a structural link to each other. Differences in cortical atrophy were assessed between groups, as well as the effect of age within groups.

Results: HE compared to YA showed a 10-30% deficit in cortical gray matter in widespread frontal, temporal, and parietal regions (p = 0.0001 by permutation testing), 6-13% loss in the visual and sensorimotor cortices (p < 0.01) and up to 13% loss in the direct hippocampal pathway ROIs (p < 0.001). pAD patients showed on average 8-9% cortical loss compared to HE (p < 0.0001), mainly in the left (up to 6% loss, p = 0.06) and right polysynaptic hippocampal pathway ROIs (up to 8% loss, p = 0.01), and in the left and right olfactory/orbitofrontal cortex (up to 12-15% loss, p < 0.001). The pattern of cortical atrophy in mAD versus HE was similar to that in pAD, but was more severe in the direct hippocampal pathway ROIs and sensorimotor, visual and temporal cortices (13-15% loss compared with HE, p < 0.0001).

Conclusion: Gray matter loss occurs during aging with rates of atrophy even more severe than that observed during the course of AD. These changes may be caused by normal mechanisms. In pAD, cortical atrophy due to disease is milder than that due to aging, maybe resulting from a slowed down velocity of cell loss, but affects specific brain areas. These findings are consistent with the view that AD is not merely accelerated aging.

Objective: Most of the work on disturbed oscillatory activity during auditory tasks in schizophrenia has focused on reduced gamma oscillations at fronto-central sites. Recent studies of our group, however, indicate a more general disturbance affecting the spatial distribution of oscillatory brain activity of gamma as well as slow frequencies, such as alpha oscillations.

Methods: During a passive auditory listening task, electroencephalography was recorded from healthy controls and patients with schizophrenia. Stimulus-locked alpha activity within the first 250 ms after stimulus onset was analyzed from midline electrodes.

Results: Healthy controls showed the common fronto-central maximum of the early alpha response, while patients with schizophrenia showed lower fronto-central and larger parieto-occipital alpha activity than controls, leading to a more similar amplitude distribution across the midline electrode sites.

Conclusions: The present results indicate malfunctioning long-range inhibition of task-irrelevant cortical areas in schizophrenia, which may disturb functional integration of perception and attention. We emphasize the importance of the whole-brain network theory for the understanding of schizophrenia since it proposes that integrative brain function is based on the coexistence and cooperative action of many interwoven and interacting sub-mechanisms.

Significance: Neuropsychiatric illnesses such as schizophrenia are marked by communication and coordination failures between different brain regions and different frequency bands.

Our perspective on resting-state electroencephalogram (EEG) is that it provides a window into the substrate of cognitive and perceptual processing, reflecting the dynamic potential of the brain's current functional state. In an extended research program into the electrophysiology of attention deficit/hyperactivity disorder (AD/HD), we have examined resting-state EEG power and coherence, and event-related potentials (ERPs), in children, adolescents, and adults with the disorder. We sought initially to identify consistent AD/HD anomalies in these measures, relative to normal control subjects, and then to understand how these differences related to existing models of AD/HD. An emergent strand in this program has been to clarify the EEG correlates of "arousal" and to understand the role of arousal dysfunction as a core anomaly in AD/HD. To date, findings in this strand serve to rule out a commonly held dictum in the AD/HD field: that elevated theta/beta ratio is an indicator of hypo-arousal. In turn, this requires further work to elucidate the ratio's functional significance in the disorder. Our brain dynamics studies relating prestimulus EEG amplitude and phase states to ERP outcomes are expected to help in this regard, but we are still at a relatively early stage, currently examining these relationships in control children, in order to better understand normal aspects of brain dynamics before turning to children with AD/HD. This range of studies provides a framework for our recent work relating resting-state EEG anomalies, in individuals with AD/HD, to their symptom profile. This has had promising results, indicating links between increased inattention scores and reduced resting EEG gamma power. With resting-state EEG coherence, reduced left lateralized coherences across several bands have correlated negatively with inattention scores, while reduced frontal interhemispheric coherence has been correlated negatively with hyperactivity/impulsivity scores. Such linkages appear to provide encouraging leads for future EEG research in AD/HD.

Background: Gamma-band oscillations and their synchronization have been implicated in the coordination of activity between distributed neuronal assemblies in the service of sensory registration of stimuli and perceptual binding of their features. Prior electroencephalographic (EEG) studies of chronic schizophrenia patients have documented deficits in the magnitude and/or phase synchrony of stimulus-evoked gamma oscillations, findings that have been linked to neurotransmission abnormalities involving GABA and NMDA-glutamate receptors. However, it remains unclear whether these abnormalities are present at the onset of the illness, or indeed, whether they are present during the prodromal period preceding illness onset. Accordingly, we examined the magnitude and phase synchrony of the transient gamma-band response (GBR) elicited by an auditory stimulus in young patients with schizophrenia and in patients at clinical high risk for psychosis based on their manifestation of putatively prodromal symptoms.

Methods: EEG was recorded during an auditory oddball target detection task in three groups: young schizophrenia patients early in their illness (YSZ; n = 19), patients at clinical high risk for psychosis (CHR; n = 55), and healthy controls (HC; n = 42). Single-trial EEG epochs and the average event-related potential time-locked to standard tones from the oddball task were subjected to time-frequency decomposition using Morlet wavelet transformations. The GBR between 50 and 100 ms following the tone onset was quantified in terms of evoked power, total power, and the phase-locking factor (PLF) reflecting cross-trial phase synchrony.

Results: GBR evoked power was significantly reduced in YSZ (p < 0.01) and CHR (p < 0.05) patients, relative to HC. Similarly, GBR PLF was significantly reduced in YSZ (p < 0.01) and showed a marginal reduction in CHR patients (p = 0.057), relative to HC. GBR total power was not reduced in CHR patients (p = 0.68) and showed only a trend level reduction in YSZ (p = 0.072). Within the CHR group. there were no significant GBR differences between the patients who converted to a psychotic disorder and those who did not convert to psychosis during a 12-month follow-up period.

Conclusion: Reductions in the transient auditory GBR, as reflected by evoked power and phase synchrony, are evident in the early stages of schizophrenia and appear to precede psychosis onset. However, the absence of total power GBR abnormalities in CHR patients, with only a trend toward reduction in YSZ patients, suggests that the magnitude of the GBR is intact early in the course

Brain oscillations have gained tremendous importance in neuroscience during recent decades as functional building blocks of sensory-cognitive processes. Research also shows that event-related oscillations (EROs) in "alpha," "beta," "gamma," "delta," and "theta" frequency windows are highly modified in pathological brains, especially in patients with cognitive impairment. The strategies and methods applied in the present report reflect the innate organization of the brain: "the whole brain work." The present paper is an account of methods such as evoked/event-related spectra, evoked/ERDs, coherence analysis, and phase-locking. The report does not aim to cover all strategies related to the systems theory applied in brain research literature. However, the essential methods and concepts are applied in several examples from Alzheimer's disease (AD), schizophrenia, and bipolar disorder (BD), and such examples lead to fundamental statements in the search for neurophysiological biomarkers in cognitive impairment. An overview of the results clearly demonstrates that it is obligatory to apply the method of oscillations in multiple electroencephalogram frequency windows in search of functional biomarkers and to detect the effects of drug applications. Again, according to the summary of results in AD patients and BD patients, multiple oscillations and selectively distributed recordings must be analyzed and should include multiple locations. Selective connectivity between selectively distributed neural networks has to be computed by means of spatial coherence. Therefore, by designing a strategy for diagnostics, the differential diagnostics, and application of (preventive) drugs, neurophysiological information should be analyzed within a framework including multiple methods and multiple frequency bands. The application of drugs/neurotransmitters gains a new impact with the analysis of oscillations and coherences. A more clear and differentiated analysis of drug effects can be attained in comparison to the application of the conventional wide-band evoked potential and event-related potential applications.

Alzheimer's disease (AD) is a devastating neurodegenerative dementing illness. Early diagnosis at the prodromal stage is an important topic of current research. Significant advances were recently made in the validation process of several biomarkers, including structural/amyloid imaging, cerebrospinal fluid measurements, and glucose positron emission tomography. Nevertheless, there remains a need to develop an efficient, low cost, potentially portable, noninvasive biomarker in the diagnosis, course, or treatment of AD. There is also a great need for a biomarker that would reflect functional brain dynamic changes within a very short time period, such as milliseconds, to provide information about cognitive deficits. Electrophysiological methods have the highest time resolution for reflecting brain dynamics in cognitive impairments. There are several strategies available for measuring cognitive changes, including spontaneous electroencephalography (EEG), sensory-evoked oscillations (SEOs), and event-related oscillations (EROs). The term "sensory-evoked" (SE) implies responses elicited upon simple sensory stimulation, whereas "event-related" (ER) indicates responses elicited upon a cognitive task, generally an oddball paradigm. Further selective connectivity deficit in sensory or cognitive networks is reflected by coherence measurements. When simple sensory stimulus is used, a sensory network becomes activated, whereas an oddball task initiates an activation in a sensory network and additionally in a related cognitive network. In AD, spontaneous activity reveals a topographically changed pattern of oscillations. In addition, the most common finding in spontaneous EEG of AD is decrease of fast and increase of slow frequencies. The hyperexcitability of motor and sensory cortices in AD has been demonstrated in many studies. The motor cortex hyperexcitability has been shown by transcranial magnetic stimulation studies. Also, the SEOs reflecting sensory network indicate a visual sensory cortex hyperexcitability in AD, as demonstrated by increased responses over posterior regions of the hemispheres. On the other hand, ERO studies reflecting activation of a cognitive network imply decreased responses in fronto-central regions of the brain in delta and theta frequencies. Coherence studies show the connectivity between different parts of the brain. Studies of SE coherence in mild AD subjects imply almost intact connectivity in all frequency ranges, whereas ER coherence is decreased in wide connections in alpha, theta, and delta frequency ranges. Moreover, alpha ER coherence seems to be sensitive to cholinergic treatment in AD. In further research in a search of AD biomarkers, multimodal methods should be introduced to electrophysiology in order to validate these methods. Standardization and harmonization of user-friendly acquisition and analysis protocols in larger cohort populations are also needed in order to incorporate electrophysiology as a part of

Background: In electroencephalogram (EEG) studies of auditory steady-state responses (ASSRs), patients with schizophrenia show a deficit in power and/or phase-locking, particularly at the 40 Hz frequency where these responses resonate. In addition, studies of the transient gamma-band response (GBR) elicited by single tones have revealed deficits in gamma power and phase-locking in schizophrenia. We examined the degree to which the 40 Hz ASSR and the transient GBR to single tones are correlated and whether they assess overlapping or distinct gamma-band abnormalities in schizophrenia.

Methods: EEG was recorded during 40 Hz ASSR and auditory oddball paradigms from 28 patients with schizophrenia or schizoaffective disorder (SZ) and 25 age- and gender-matched healthy controls (HC). The ASSR was elicited by 500 ms click trains, and the transient GBR was elicited by the standard tones from the oddball paradigm. Gamma phase and magnitude values, calculated using Morlet wavelet transformations, were used to derive total power and phase-locking measures.

Results: Relative to HC, SZ patients had significant deficits in total gamma power and phase-locking for both ASSR- and GBR-based measures. Within both groups, the 40 Hz ASSR and GBR phase-locking measures were significantly correlated, with a similar trend evident for the total power measures. Moreover, co-varying for GBR substantially reduced 40 Hz ASSR power and phase-locking differences between the groups.

Conclusions: 40 Hz ASSR and transient GBR measures provide very similar information about auditory gamma abnormalities in schizophrenia, despite the overall enhancement of 40 Hz ASSR total power and phase-locking values relative to the corresponding GBR values.

Objective: The value of spontaneous electroencephalography (EEG) oscillations in distinguishing patients in vegetative state (VS) and minimally conscious states (MCS) was studied.

Methods: We quantified dynamic repertoire of EEG oscillations in resting condition with closed eyes in patients in VS and MCS. The exact composition of EEG oscillations was assessed by the probability-classification analysis of short-term EEG spectral patterns.

Results: The probability of delta, theta, and slow-alpha oscillations occurrence was smaller for patients in MCS than for VS. Additionally, only patients in MCS demonstrated fast-alpha oscillation occurrence. Depending on the type and composition of EEG oscillations, the probability of their occurrence was either etiology dependent or independent. The probability of EEG oscillations occurrence differentiated brain injuries with different etiologies.

Conclusions: Spontaneous EEG oscillations have a potential value in distinguishing patients in VS and MCS.

Significance: This work may have implications for clinical care, rehabilitative programs, and medical-legal decisions in patients with impaired consciousness states following coma due to acute brain injuries.

Highlights: The probability of delta, theta, and slow-alpha oscillations occurrence was smaller and the probability of fast-alpha oscillations occurrence was higher for patients in MCS than for patients in VS. The probability of EEG oscillations occurrence differentiated brain injuries with different etiologies. Spontaneous EEG has a potential value in distinguishing patients in VS and MCS.

This survey covers the potential use of neurophysiological changes as a biomarker in four neuropsychiatric diseases (attention deficit hyperactivity disorder (ADHD), Alzheimer's disease (AD), bipolar disorder (BD), and schizophrenia (SZ)). Great developments have been made in the search of biomarkers in these disorders, especially in AD. Nevertheless, there is a tremendous need to develop an efficient, low-cost, potentially portable, non-invasive biomarker in the diagnosis, course, or treatment of the above-mentioned disorders. Electrophysiological methods would provide a tool that would reflect functional brain dynamic changes within milliseconds and also may be used as an ensemble of biomarkers that is greatly needed in the evaluation of cognitive changes seen in these disorders. The strategies for measuring cognitive changes include spontaneous electroencephalography (EEG), sensory evoked oscillation (SEO), and event-related oscillations (ERO). Further selective connectivity deficit in sensory or cognitive networks is reflected by coherence measurements. Possible candidate biomarkers discussed in an interactive panel can be summarized as follows: for ADHD: (a) elevation of delta and theta, (b) diminished alpha and beta responses in spontaneous EEG; for SZ: (a) decrease of ERO gamma responses, (b) decreased ERO in all other frequency ranges, (c) invariant ERO gamma response in relation to working memory demand; for euthymic BD: (a) decreased event-related gamma coherence, (b) decreased alpha in ERO and in spontaneous EEG; for manic BD: (a) lower alpha and higher beta in ERO, (b) decreased event-related gamma coherence, (c) lower alpha and beta in ERO after valproate; and for AD: (a) decreased alpha and beta, and increased theta and delta in spontaneous EEG, (b) hyperexcitability of motor cortices as shown by transcortical magnetic stimulation, (c) hyperexcitability of visual sensory cortex as indicated by increased SEO theta responses, (d) lower delta ERO, (e) lower delta, theta, and alpha event-related coherence, (f) higher theta synchrony and higher alpha event-related coherence in cholinergically treated AD subjects. In further research in the search for biomarkers, multimodal methods should be introduced to electrophysiology for validation purposes. Also, providing the protocols for standardization and harmonization of user-friendly acquisition or analysis methods that would be applied in larger cohort populations should be used to incorporate these electrophysiologic methods into the clinical criteria. In an extension to conventional anatomical, biochemical and brain imaging biomarkers, the use of neurophysiologic markers may lead to new applications for functional interpretrations and also the possibility to monitor treatments tailored for individuals.

Background: Abnormalities in coherent cortical circuit functioning, reflected in gamma band activity (to approximately 40 Hz), may be a core deficit in schizophrenia. The early auditory gamma band response (EAGBR) is a neurophysiologically simple probe of circuit functioning in primary auditory cortex. We examined the EAGBR in first hospitalized schizophrenia to assess whether it was reduced at first hospitalization.

Method: Wavelet evoked power and intertrial phase locking of the EAGBR at Fz to standard tones during an oddball target detection task were examined in 28 first hospitalized schizophrenia patients (10 female) and 44 control subjects (17 female).

Results: At first hospitalization EAGBR trial-to-trial phase locking and evoked power were significantly reduced in patients. Although reduced overall in patients, greater total symptoms were significantly associated with greater gamma phase locking and power. Additionally, greater EAGBR power was marginally associated with greater positive factor scores, hallucinations, and thinking disturbance.

Conclusions: Abnormalities of gamma band functioning in local auditory sensory circuits are present in schizophrenia at first hospitalization further evidence that basic sensory processes are impaired in schizophrenia. It remains to be determined whether the EAGBR becomes permanently impaired with disease progression, and if its reduction is specific to schizophrenia.