Elif Tülay

Auditory delta event-related oscillatory responses are decreased in Alzheimer's disease.

Background: Visual delta event-related (ERO) and evoked oscillations (EO) of Alzheimer patients (AD) are different than healthy. In the present study, the analysis is extented to include auditory ERO and EO in AD. The rationale is to reveal whether the auditory ERO delta responses are also reduced, and whether this is a general phenomenon in Alzheimer patients upon applying stimuli with cognitive load. Methods: Thirty-four mild AD subjects (17 de-novo and 17 medicated (cholinergic)) and seventeen healthy controls were included. Auditory oddball paradigm and sensory auditory stimuli were applied to the subjects. Oscillatory responses were analyzed by measuring maximum amplitudes in delta frequency range (0.5–3.5 Hz). Results: Auditory delta ERO (0.5–3.5 Hz) responses of healthy controls were higher than either de-novo AD or medicated AD group, without a difference between two AD subgroups. Furthermore, the auditory EO after presentation of tone bursts yielded no group difference. Conclusion: Our findings imply that delta ERO is highly unstable in AD patients in comparison to age-matched healthy controls only during the cognitive paradigm. Our results favor the hypothesis that neural delta networks are activated during cognitive tasks and that the reduced delta response is a general phenomenon in AD, due to cognitive impairment.

A comparative analysis of sensory visual evoked oscillations with visual cognitive event related oscillations in Alzheimer's disease.

We compared visual evoked oscillatory responses of subjects with Alzheimers disease (AD) (n=22) to healthy elderly controls (n=19) elicited by simple light stimuli. The visual evoked oscillatory responses in AD subjects without cholinergic treatment (n=11) show significant differences (df=2.38, F=4.957, P=0.012) from the controls and the AD subjects treated with a cholinesterase inhibitor (n=11). Higher theta oscillatory responses in untreated AD subjects are seen on the electrode locations over bi-parietal and right occipital regions after simple light stimuli with less, if any, cognitive load. These changes were restricted to the theta frequency range only and are related to location, frequency bands and drug effects. In our previous work we observed that visual event related oscillations elicited after the visual stimuli with a higher cognitive load, i.e. an oddball target, display lower amplitudes: between controls and AD subjects in delta frequency band without a drug effect, over the left and mid-central region. These differences between the visual evoked oscillations and the visual event related oscillations imply that there are at least two different cognitive circuits that are activated upon visual stimuli in AD patients.

Decrease of event-related delta oscillations in euthymic patients with bipolar disorder

Decreased delta oscillation upon cognitive load is common in patients with Alzheimer׳s disease, mild cognitive impairment, and schizophrenia. However, there is no previous study analyzing the delta responses in euthymic medication-free patients with bipolar disorder. Participants comprised of 22 euthymic medication-free patients with DSM-IV diagnoses of bipolar disorder and 21 healthy controls who were matched to the patients for sex, age, and education. Electroencephalographic activity was recorded at 30 electrode sites using an application of an auditory oddball paradigm. The maximum peak-to-peak amplitudes for each subject׳s averaged delta response (0.5-3.5Hz) were measured. There was a significant inter-group difference in evoked and event-related delta (0.5-3.5Hz) responses. Post-hoc comparisons revealed that the event-related delta oscillatory responses of the bipolar patient group were significantly lower than those of the healthy control group over the temporo-parietal and occipital electrode sites. Euthymic bipolar patients showed reduced event-related delta oscillatory responses in comparison to healthy subjects under cognitive load. The decrease of delta oscillations may be a common phenomenon that can be observed in different neuropsychiatric disorders with cognitive dysfunction.

Multiple gamma oscillations in the brain: a new strategy to differentiate functional correlates and P300 dynamics.

Brain oscillations in the gamma frequency band, - i.e. oscillations greater than 25 Hz - have attracted increasing attention over the last few decades in the research of sensory-cognitive processes. In the neuroscience research literature, a great number of reports aim to describe the functional correlates of oscillatory responses in the gamma frequency window. However, analysis using a broadband frequency window often leads to divergent functional interpretations and controversies. In order to provide a more exact approach, we have used a strategy by defining multiple frequency and multiple time windows according to the combined analysis of conventional power spectral windows, frequency adaptive multiple filters, and inter-trial coherence. The analysis in frequency windows of 25-30 Hz, 30-35 Hz, and 40-48 Hz enables the investigator to provide a distinction of cognitive and/or sensory responses. Moreover, according to topological differentiation and the consideration of neuroanatomic pathways, more reliable interpretations of gamma responses are reached.

Event related beta and gamma oscillatory responses during perception of affective pictures

Several studies reveal that unpleasant pictures elicit higher beta and gamma responses than pleasant and/or neutral pictures; however, the effect of stimulation design (block or random) has not been studied before. The aim of the study is to analyze the common and distinct parameters of affective picture perception in block and random designs by means of analysis of high frequency oscillatory dynamics (beta and gamma). EEG of 22 healthy subjects was recorded at 32 locations. The participants passively viewed 120 emotional pictures (10 × 4 unpleasant, 10 × 4 pleasant, 10 × 4 neutral) in block and random designs. The phase-locking and power of event related beta (14-28 Hz) and gamma (29-48 Hz) oscillations were analyzed for two different time windows (0-200 ms/200-400 ms). Statistical analysis showed that in the 0-200 ms time window, during the block design, unpleasant stimulation elicited higher beta phase-locking and beta power than the pleasant and neutral stimulation (p<0.05). In the 200-400 ms time window, during the block design, over occipital electrodes unpleasant stimulation elicited higher gamma response power than the pleasant stimulation and neutral stimulation (p<0.05). Unpleasant stimulation did not elicit higher beta or gamma responses in the random design. The present study showed that experimental design highly influences the perception of IAPS pictures. Unpleasant stimulation elicited higher event related beta and gamma phase-locking and power only in block design but not in random design. It seems that longer blocks of aversive pictures affect the brain more than the rapid observation of these pictures.

Best method for analysis of brain oscillations in healthy subjects and neuropsychiatric diseases

The research related to brain oscillations and their connectivity is in a new take-off trend including the applications in neuropsychiatric diseases. What is the best strategy to learn about functional correlation of oscillations? In this report, we emphasize combined application of several analytical methods as power spectra, adaptive filtering of Event Related Potentials, inter-trial coherence and spatial coherence. These combined analysis procedure gives the most profound approach to understanding of EEG responses. Examples from healthy subjects, Alzheimers Diseases, schizophrenia, and Bipolar Disorder are described.

Increased Beta Frequency (15-30 Hz) Oscillatory Responses in Euthymic Bipolar Patients Under Lithium Monotherapy

The effect of lithium on neurocognition is not still fully explored. Brain oscillatory activity is altered in bipolar disorder. We aimed to assess the oscillatory responses of euthymic bipolar patients and how they are affected by lithium monotherapy. Event-related oscillations in response to visual target stimulus during an oddball paradigm in 16 euthymic drug-free and 13 euthymic lithium-treated bipolar patients were compared with 16 healthy controls. The maximum peak-to-peak amplitudes were measured for each subject’s averaged beta (15-30 Hz) responses in the 0- to 300-ms time window over frontal (F3, Fz, F4), central (C3, Cz, C4), temporal (T7, T8), temporo-parietal (TP7, TP8), parietal (P3, Pz, P4), and occipital (O1, Oz, O2) areas. Patients under lithium monotherapy had significantly higher beta responses to visual target stimuli than healthy controls (P = .017) and drug-free patients (P = .015). The increase in beta response was observed at all electrode locations, however, the difference was statistically significant for the left (T7; P = .016) and right (T8; P = .031) temporal beta responses. Increased beta responses in drug-free patients and further significant increase in lithium-treated patients may be indicative of a core pathophysiological process of bipolar disorder and how it is affected by lithium. Whether the finding corresponds to lithium’s corrective effect on the underlying pathology or to its neurocognitive side effect remains to be further explored. In either case, the finding is a sign that the oscillatory activity may be useful in tracking medication effect in bipolar disorder.