Theta oscillation during auditory change detection: An MEG study

To study the phase and power characteristics of brain oscillations during the preattentive detection of auditory deviance, we recorded magnetoencephalographic responses in 10 healthy subjects with an oddball paradigm. As the subject was watching a silent movie, standard tones (1000-Hz frequency, 100-ms duration) and their duration deviants (50-ms duration, probability of 15%) were randomly delivered binaurally. In addition to localizing the magnetic counterpart of mismatch negativity (MMNm) with equivalent current dipole modeling, we also measured the phase-locking value (PLV) and power change of the oscillatory responses to standard and deviant stimuli by employing the Morlet wavelet-based analysis. The MMNm signals peaking at 150-200 ms after the onset of deviant were localized in bilateral temporal regions with larger amplitudes in the right hemisphere. Then 50 ms after the onset of either standard or deviant stimuli, we observed an increase of PLV and power of theta and alpha oscillations in bilateral temporal regions. PLVs of theta and alpha activities to deviant stimuli were significantly larger in the right than left hemisphere (P < 0.001). Compared with standard stimuli, deviants elicited a larger theta PLV (P < 0.001) at 150-300 ms and a larger theta power change (P < 0.05) at 50-300 ms for the responses in the right temporal region. In addition, a prominent theta phase-locking of deviant-elicited responses was found in the right frontal area at 110-250 ms (P < 0.01). Our current data suggest that a pronounced phase and power modulation on sound-elicited theta oscillations might characterize the change detection processing in the temporo-frontal network as reflected by the mismatch negativity.     

40-Hz steady state response in Alzheimer's disease and mild cognitive impairment

The 40-Hz steady state response (SSR) reflects early sensory processing and can be measured with electroencephalography (EEG). The current study compared the 40-Hz SSR in groups consisting of mild Alzheimer's disease patients (AD) (n = 15), subjects with mild cognitive impairment (MCI) (n = 20) and healthy elderly control subjects (n = 20). All participants were naïve for psychoactive drugs. Auditory click trains at a frequency of 40-Hz evoked the 40-Hz SSR. To evaluate test-retest reliability (TRR), subjects underwent a similar assessment 1 week after the first. The results showed a high TRR and a significant increase of 40-Hz SSR power in the AD group compared to MCI and controls. Furthermore a moderate correlation between 40-Hz SSR power and cognitive performance as measured by ADAS-cog was shown.The results suggest that 40-Hz SSR might be an interesting candidate marker of disease progression.     

How much does phase resetting contribute to event-related EEG abnormalities in schizophrenia?

Objective: Patients suffering from schizophrenia demonstrate impaired low frequency electrophysiological responses to stimuli, but it remains unclear whether these abnormalities arise from phase resetting of ongoing oscillations, new phase-locked (evoked) activity or non-phase-locked (induced) activity. Our goal is to clarify the contribution of each of these three processes to the impairment of neural activity during information processing in schizophrenia, by using statistics that do not confound increases in the mean post-stimulus signal with phase resetting. Methods: Thirty-four male schizophrenia patients and 34 healthy matched controls performed an auditory oddball task. We applied the analysis procedure developed by Martinez-Montes et al. [18] based on complex-valued wavelet transform to event-related signal elicited by target stimuli. Results: The largest abnormalities were found for phase-locked delta (1–4 Hz) and non-phase-locked theta (4–8 Hz). Delta phase resetting was moderately impaired and related to symptoms of disorganization. It also predicted evoked theta signal. Conclusion: The substantial reduction of both evoked and induced oscillatory activity in schizophrenia indicates diminished recruitment of brain circuits engaged not only in stimulus-locked perceptual processing but also in more extensive processing less tightly time locked to the stimulus. Although reduced phase resetting makes a lesser contribution, it indicates a deficit in the ability to harness ongoing electrical activity.     

Linkage and linkage disequilibrium of evoked EEG oscillations with CHRM2 receptor gene polymorphisms: implications for human brain dynamics and cognition.

Event-related oscillations (ERO) offer an alternative theoretical and methodological approach to the analysis of event-related EEG responses. The P300 event-related potential (ERP) is elicited through the superposition of the delta (1-3 Hz) and theta (3-7 Hz) band oscillatory responses. The cholinergic neurotransmitter system has a key function in modulating excitatory post-synaptic potentials caused by glutamate, and therefore influences P300 generation and the underlying oscillatory responses. Here we report significant linkage and linkage disequilibrium between target case frontal theta band, visual evoked brain oscillations and a single nucleotide polymorphism (SNP) from the cholinergic muscarinic receptor gene (CHRM2) on chromosome 7. We also demonstrate significant linkage disequilibrium between CHRM2 SNPs and target case parietal delta band visual evoked oscillations (LD P<0.001). These findings were not observed for the equivalent non-target case data, suggesting a role for the CHRM2 gene in higher cognitive processing in humans.     

Increased frontal phase-locking of event-related theta oscillations in Alzheimer patients treated with cholinesterase inhibitors.

This is a pilot study describing event-related oscillations in patients with Alzheimer-type dementia (AD). Theta responses of 22 mild probable AD subjects according to NINCDS-ADRDA criteria (11 non-treated, 11 treated by cholinesterase inhibitors), and 20 healthy elderly controls were analyzed by using the conventional visual oddball paradigm. We aimed to compare theta responses of the three groups in a range between 4-7 Hz at the frontal electrodes. At F(3) location, theta responses of healthy subjects were phase locked to stimulation and theta oscillatory responses of non-treated Alzheimer patients showed weaker phase-locking, i.e. average of Z-transformed means of correlation coefficients between single trials was closer to zero. In treated AD patients, phase-locking following target stimulation was two times higher in comparison to the responses of non-treated patients. The results indicate that the phase-locking of theta oscillations at F(3) in the treated patients is as strong as the control subjects. The F(4) theta responses were not statistically significant between the groups. Our findings imply that the theta responses at F(3) location are highly unstable in comparison to F(4) in non-treated mild AD patients and cholinergic agents may modulate event-related theta oscillatory activities in the frontal regions.     

Event-related beta oscillations are affected by emotional eliciting stimuli

According to previous results, negative emotional facial expressions elicit oscillatory beta responses. The present study analyzes event-related beta oscillations upon presentation of International Affective Picture System (IAPS) and aims to show whether behavior of beta in response to negative IAPS pictures also have similar dynamics. IAPS pictures (unpleasant, pleasant, and neutral) were presented as a block and random passive viewing to 14 healthy subjects (8 male). Only with pictures with similar luminance level were selected as stimuli. Event-Related Potentials (ERPs) were recorded from 30 different scalp locations, and adaptive digital filtering was used for analysis in different frequency windows. The maximum peak-to-peak amplitudes were measured for each subject's averaged beta responses (15–30 Hz) in the 0 and 300 ms time window. Beta responses were significantly higher for unpleasant pictures than for pleasant and neutral pictures (average 50%). Beta responses were significantly higher for unpleasant than for pleasant pictures over frontal, central and parietal electrode sides (p < 0.05). Furthermore, beta responses were significantly higher for unpleasant than for neutral pictures over parietal and occipital electrodes (p < 0.04). In addition, the pleasant pictures elicited higher beta responses than neutral pictures over occipital electrode sites (p < 0.04). The results of the present study indicate that negative emotions are related to increased beta responses in humans, independent of stimulus types (facial expression or IAPS pictures). Accordingly, beta responses to negative emotions are possibly a common phenomenon. The standardization of luminance in pictures may reduce divergences between results from different laboratories.     

MCI patients’ EEGs show group differences between those who progress and those who do not progress to AD

The theta/gamma and alpha3/alpha2 ratio were investigated as early markers for prognosticating of progression to dementia. 76 subjects with mild cognitive impairment (MCI) underwent EEG recording, MRI scans and neuropsychological (NPS) tests. After 3 years of follow-up, three subgroups were characterized as converters to Alzheimer's disease (AD, N = 18), converters to non-AD dementia (N = 14) and non-converters (N = 44). The theta/gamma and alpha3/alpha2 ratio, performance on cognitive tests and hippocampal volume, as evaluated at the time of initial MCI diagnosis, were studied in the three groups. As expected, MCI to AD converters had the smallest mean hippocampal volume and poorest performance on verbal learning tests, whereas MCI to non-AD converters had poorest cognitive performance in non-verbal learning tests, abstract thinking, and letter fluency. Increased theta/gamma ratio was associated with conversion to both AD and non-AD dementia; increased alpha3/alpha2 ratio was only associated with conversion to AD.Theta/gamma and alpha3/alpha2 ratio could be promising prognostic markers in MCI patients. In particular, the increase of high alpha frequency seems to be associated with conversion in AD. EEG markers allow a mean correct percentage of correct classification up to 88.3%. Future prospective studies are needed to evaluate the sensitivity and specificity of these measures for predicting an AD outcome.     

N-methyl-d-aspartic acid receptor antagonist–induced frequency oscillations in mice recreate pattern of electrophysiological deficits in schizophrenia

Introduction: Electrophysiological responses to auditory stimuli have provided a useful means of elucidating mechanisms and evaluating treatments in psychiatric disorders. Deficits in gating during paired-click tasks and lack of mismatch negativity following deviant stimuli have been well characterized in patients with schizophrenia. Recently, analyses of basal, induced, and evoked frequency oscillations have gained support as additional measures of cognitive processing in patients and animal models. The purpose of this study is to examine frequency oscillations in mice across the theta (4–7.5 Hz) and gamma (31–61 Hz) bands in the context of N-methyl-d-aspartic acid receptor (NMDAR) hypofunction and dopaminergic hyperactivity, both of which are thought to serve as pharmacological models of schizophrenia.     

Brain oscillatory 4–35 Hz EEG responses during an n-back task with complex visual stimuli

Brain oscillatory responses of 4–35 Hz EEG frequencies elicited during performance of a visual n-back task with complex visual stimuli were assessed in 20 adult volunteers. Spectral power changes were assessed separately for target and non-target stimuli in four different memory load conditions (0, 1, 2, and 3-back). The presentation of both target and non-target stimuli elicited long-lasting ∼4–8 Hz power increases, which were more prominent at the beginning of stimulus onset during presentation of target stimuli, as compared to non-target stimuli, in the 0-back memory load condition. ∼8–25 Hz power decreases appeared at stimulus onset. These power decreases were more prominent during the presentation of target stimuli, as compared to non-target stimuli, and their duration increased as a function of memory load between the 0-, 1-, and 2-back, but not the 3-back, memory load conditions. The current results provide further evidence in support of the notion of a complex interplay between both ∼4–8 Hz power increases and ∼8–25 Hz power decreases during cognitive memory task performance.     

Study of thyroid hormone receptor alpha gene polymorphisms on Alzheimer's disease

Because the action of thyroid hormone (T3) is involved in adult cognitive functions, we wanted to assess the association between THRA gene polymorphisms, which encodes the T3 nuclear receptor TRα1, and Alzheimer's disease (AD) risk.We analysed 5 single nucleotide polymorphisms (SNPs) of THRA, covering the known common genetic variability of the gene, in the Lille AD case-control study (710 cases/597 controls). We observed that subjects bearing the rs939348 TT genotype had a tendency to have a higher risk of developing AD (adjusted OR [95%CI] = 1.71 [0.99-2.95] p = 0.06). We extended our finding to three other independent AD case-control studies and observed similar trends. When combining the 4 studies (1749 cases/1339 controls), we observed an overall significant higher risk of AD in TT subjects (adjusted OR [95%CI] = 1.42 [1.03-1.96], p = 0.03) compared with C allele bearers. However, when combining our data with the available data coming from 2 American genome wide association studies on AD, we observed a weak and not significant association (OR = 1.19 [0.97-1.45], p = 0.10).The relationship between the genetic variability of the THRA gene and AD risk remains uncertain but cannot be entirely excluded.     

Beta (~16 Hz) frequency neural oscillations mediate auditory sensory gating in humans

The brain's oscillatory activities in response to sensory input are likely signals representing different stages of sensory information processing. To understand these signals, it is critical to establish the specificity of the timing and frequency of oscillations associated with sensory and sensory-related cognitive processing. We used a simple paired auditory stimulus paradigm for sensory gating and sought to identify time- and frequency-specific oscillatory components contributing to sensory gating. Using a discrete wavelet decomposition technique we separated single-trial time-frequency components of evoked potentials elicited by the first of two stimuli. Regression analyses were then used to identify the components most relevant to the suppression of the second evoked potential response. The results suggested that beta oscillation indexed a neural process associated with the strength of sensory gating.     

Polymorphism C in the serotonin transporter gene (SLC6A4) in questionable dementia and Alzheimer's disease

The promoter region of the serotonin transporter gene (SLC6A4) shows a 22-bp tandem repeat polymorphism, indicated as polymorphism C, that has been associated to depression, obsessive-compulsive disorder, memory impairment, and anxiety. Less clear are data regarding its association with Alzheimer's disease (AD). No data were reported regarding its association with questionable dementia (QD). In this study we investigate for polymorphism C in the SLC6A4 gene 302 elderly subjects with a clinical diagnosis of AD (n = 105), QD (n = 88) and no cognitive impairment (n = 114) attending a geriatric ward. A community-dwelling sample of 390 healthy subjects was also included in the analysis. A significant higher prevalence of the C16/C16 genotype in AD than in QD was observed (37.14% vs. 3%; p = 0.041, OR 2.001, 95%CI 1.018–4.024), while no differences in the C16/C14 and C14/C14 genotypes as well as in the estimated allele frequencies were found. No further differences among the three groups of subjects were found, also when they were compared with the community-dwelling sample. These findings suggest that SLC6A4 gene variation may have only a minor role, if any, in AD or QD.     

Glutamate receptor blockade in the rostral ventromedial medulla reduces the force of multisegmental motor responses to supramaximal noxious stimuli

The rostral ventromedial medulla (RVM) has been established as part of a descending pain-modulatory pathway. While the RVM has been shown to modulate homosegmental nociceptive reflexes such as tail flick or hindpaw withdrawal, it is not known what role the RVM plays in modulating the magnitude of multisegmental, organized motor responses elicited by noxious stimuli. Using local blockade of glutamate receptors with the non-specific glutamate receptor antagonist kynurenate (known to selectively block nociceptive facilitatory ON-cells), we tested the hypothesis that the RVM facilitates the magnitude of multi-limb movements elicited by intense noxious stimuli. In male Sprague–Dawley rats, we determined the minimum alveolar concentration (MAC) of isoflurane necessary to block multi-limb motor responses to noxious tail clamp. MAC was determined so that all animals were anesthetized at an equipotent isoflurane concentration (0.7 MAC). Supramaximal mechanical stimulation of the hindpaw or electrical stimulation of the tail elicited synchronous, repetitive movements in all four limbs that ceased upon, or shortly after (<5 s) termination of the stimulus. Kynurenate microinjection (2 nmol) into the RVM significantly attenuated, by 40–60%, the peak and integrated limb forces elicited by noxious mechanical stimulation of the hindpaw (p < 0.001; two-way ANOVA; n = 8) or electrical stimulation of the tail (peak force: p < 0.011, two-way ANOVA; n = 8), with significant recovery 40–60 min following injection. The results suggest that glutamatergic excitation of RVM neurons, presumably ON-cells, facilitates organized, multi-limb escape responses to intense noxious stimuli.     

Delta and theta oscillations as risk markers in adolescent offspring of alcoholics.

BACKGROUND: Visual P300 is consistently lower in alcohol-dependent individuals, their offspring and subjects at risk. Delta and theta event-related oscillations (ERO) are the major contributors to the P300 signal. The total and evoked power in delta and theta bands in the 300 to 700 ms post-stimulus window (corresponding to the zone of P300 maxima) was compared between adolescent offspring of alcoholics (high-risk) and age-matched normal controls (low-risk), to assess the utility of the risk markers. METHODS: EEG was recorded during the performance of a visual oddball task. The S-transform algorithm decomposed the EEG signals into different frequency bands and the group differences in total and evoked power in the oscillatory responses during the P300 time window (300 to 700 ms) were analyzed using a multivariate design. Similar analysis was performed on P300 peak amplitude for the target. RESULTS: The high-risk group showed significantly lower parietal post-stimulus evoked and total power in the delta band for targets. A decrease in total power was seen centrally and parietally in the theta band. The P300 peak amplitude in the parietal electrodes was also significantly lower in the high-risk group. CONCLUSIONS: The decreased total theta power and total and evoked delta power for visual targets in high risk individuals may serve as an endophenotypic marker in the development of alcoholism and other disinhibitory disorders. The differences seen between the offspring of alcoholics and controls may have a cholinergic basis. The ERO measures appear to be more robust than the P300 amplitude in differentiating the groups.     

Theta rhythmicities following expected visual and auditory targets.

Evoked (EPs) as well as event-related potentials (ERPs) were recorded from two groups of 10 healthy, voluntary subjects in auditory and visual modalities. For ERP recordings 'the omitted stimulus paradigm' was employed, in which the subjects were expected to mark mentally the onset time (time prediction task) of the omitted stimulus (target). The standard auditory (AEP) and visual (VEP) evoked potentials and auditory and visual ERPs to the preceding stimuli of the omitted ones were analyzed in time and frequency domains. In the time domain the time prediction task induced increases of the amplitudes of waves existing in standard EPs; however, an additional wave or component could not be detected. Analysis of amplitude frequency characteristics (AFCs) revealed, however, selective, significant increases of the theta (3-6 Hz) frequency components of the responses concerned. These theta increases were especially evident in the frontal and parietal recording sites. Our findings suggest an association between the theta frequency components of transient evoked responses, the association areas of the brain and cognitive performance. The neurophysiological basis of scalp recorded ERPs are discussed in relation to the findings of animal studies with EEG and single unit recordings from cortical and subcortical structures.     

Visual contrast sensitivity in Alzheimer’s disease,mild cognitive impairment,and older adults with cognitive complaints

Deficits in contrast sensitivity (CS) have been reported in Alzheimer’s disease (AD). However, the extent of these deficits in prodromal AD stages, including mild cognitive impairment (MCI) or even earlier, has not been investigated. In this study, CS was assessed using frequency doubling technology in older adults with AD (n = 10), amnestic MCI (n = 28), cognitive complaints without performance deficits (CC; n = 20), and healthy controls (HC; n = 29). The association between CS and cognition was also evaluated. Finally, the accuracy of CS measures for classifying MCI versus HC was evaluated. CS deficits were found in AD and MCI, while CC showed intermediate performance between MCI and HC. Upper right visual field CS showed the most significant difference among groups. CS was also associated with cognitive performance. Finally, CS measures accurately classified MCI versus HC. The CS deficits in AD and MCI, and intermediate performance in CC, indicate that these measures are sensitive to early AD-associated changes. Therefore, frequency doubling technology-based measures of CS may have promise as a novel AD biomarker.     

Differential brain response to alcohol cue distractors across stages of alcohol dependence

Altered attention to alcohol-related cues is implicated in the craving and relapse cycle characteristic of alcohol dependence (ALC). Prior cue reactivity studies typically invoke explicit attention to alcohol cues, so the neural response underlying incidental cue exposure remains unclear. Here, we embed infrequent, task-irrelevant alcohol and non-alcohol cues in an attention-demanding task, enabling evaluation of brain responses to distracting alcohol cues. Alcohol dependent individuals, across illness phase (n = 44), and controls (n = 20) performed a cue-reactivity fMRI target detection task. Significant Group-by-Distractor effects were observed in dorsal anterior cingulate cortex (ACC), inferior parietal lobule, and amygdala. Controls and long-term abstainers increased recruitment of attention and cognitive control regions, while recent and long-term abstainers decreased limbic recruitment to alcohol distractors. Across phases of ALC, self-reported craving positively correlated with cue-related activations in ventral ACC, medial prefrontal cortex, and cerebellum. Results indicate that brain responses elicited by incidental alcohol cues differentiate phases of ALC.     

Occipital cortex activation studied with simultaneous recordings of functional transcranial Doppler ultrasound (fTCD) and visual evoked potential (VEP) in cognitively normal human subjects: Effect of healthy aging

We evaluated effect of aging, gender and eye (sighting) dominance on relationship between visual evoked flow response (VEFR) and visual evoked potential (VEP), which refers to neurovascular coupling. The VEFR was defined as a percentage increase of the ratio of mean blood flow velocity in the contralateral (according to the side of dominant eye processing) posterior cerebral artery P2 segment to those in ipsilateral middle cerebral artery from the baseline during half-field stimulation. Vasoneural coupling index (CI) was defined as “100 × VEFR/VEP P100 amplitude”. Compared to the healthy elderly subjects (n: 19; female/male: 6/13, mean age: 69.7 ± 7), younger participants (n: 28; female/male: 16/12; mean age: 31.1 ± 4.7) had significantly higher VEFR for both sides: 18.9 ± 6.7% versus 11.2 ± 6.7%, p < 0.001 and 17.3 ± 7.7% versus 11.8 ± 5.5%, p: 0.007, for the hemisphere contralateral to dominant and nondominant eye (D and ND side), respectively. Albeit absence of any correlation between their latencies, VEP and VEFR amplitudes were well correlated. However, this was significant only for younger subjects and more evident in D side. The CI was higher in young subjects compared to those in old ones (6.49 ± 2.79 versus 4.75 ± 2.35, respectively, p = 0.007). But, this age-related trend remained as borderline when sides were analyzed individually: In the young subjects CI was 5.99 ± 2.21 and 6.96 ± 3.22 for D and ND sides, while those were 4.27 ± 2.60 and 5.19 ± 2.07 in old ones. This study confirmed diminished visual evoked flow in relation with advancing age, and suggested that “weakened” neurovascular coupling (as evidenced by a decreased VEP and VEFR correlation along with decreased CI) as one of the underlying mechanisms.     

20 Hz membrane potential oscillations are driven by synaptic inputs in collision-detecting neurons in the frog optic tectum

Although the firing patterns of collision-detecting neurons have been described in detail in several species, the mechanisms generating responses in these neurons to visual objects on a collision course remain largely unknown. This is partly due to the limited number of intracellular recordings from such neurons, particularly in vertebrate species. By employing patch recordings in a novel integrated frog eye-tectum preparation we tested the hypothesis that OFF retinal ganglion cells were driving the responses to visual objects on a collision course in the frog optic tectum neurons. We found that the majority (22/26) of neurons in layer 6 responding to visual stimuli fitted the definition of η class collision-detectors: they readily responded to a looming stimulus imitating collision but not a receding stimulus (spike count difference ∼10 times) and the spike firing rate peaked after the stimulus visual angle reached a threshold value of ∼20–45°. In the majority of these neurons (15/22) a slow frequency oscillation (f = ∼20 Hz) of the neuronal membrane potential could be detected in the responses to a simulated collision stimulus, as well as to turning off the lights. Since OFF retinal ganglion cells could produce such oscillations, our observations are in agreement with the hypothesis that ‘collision’ responses in the frog optic tectum neurons are driven by synaptic inputs from OFF retinal ganglion cells.     

Low-frequency oscillations arising from competitive interactions between visual stimuli in macaque inferotemporal cortex

Some neurons in the inferotemporal cortex (IT) of the macaque monkey respond to visual stimuli by firing action potentials in a series of sharply defined bursts at a frequency of about 5 Hz. The aim of the present study was to test the hypothesis that the oscillatory responses of these neurons depend on competitive interactions with other neurons selective for different stimuli. To test this hypothesis, we monitored responses to probe images displayed in the presence of other already visible backdrop images. Two stimuli were used in testing each neuron: a foveal image that, when displayed alone, elicited an excitatory response (the "object") and a peripheral image that, when displayed alone, elicited little or no activity (the "flanker"). We assessed the results of presenting these images separately and together in monkeys trained to maintain central fixation. Two novel phenomena emerged. First, displaying the object in the presence of the flanker enhanced the strength of the oscillatory component of the response to the object. This effect varied in strength across task contexts and may have depended on the monkey's allocating attention to the flanker. Second, displaying the flanker in the presence of the object gave rise to sometimes strong oscillations in which the initial phase was negative. This was all the more striking because the flanker by itself elicited little or no response. This effect was robust and invariant across task contexts. These results can be accounted for by competition between two neuronal populations, one selective for the object and the other for the flanker, if it is assumed that the visual responses of each population are subject to fatigue.