Frontally mediated inhibitory processing and white matter microstructure: age and alcoholism effects

RationaleThe NOGO P3 event-related potential is a sensitive marker of alcoholism, relates to EEG oscillation in the δ and θ frequency ranges, and reflects activation of an inhibitory processing network. Degradation of white matter tracts related to age or alcoholism should negatively affect the oscillatory activity within the network.ObjectiveThis study aims to evaluate the effect of alcoholism and age on δ and θ oscillations and the relationship between these oscillations and measures of white matter microstructural integrity.MethodsData from ten long-term alcoholics to 25 nonalcoholic controls were used to derive P3 from Fz, Cz, and Pz using a visual GO/NOGO protocol. Total power and across trial phase synchrony measures were calculated for δ and θ frequencies. DTI, 1.5 T, data formed the basis of quantitative fiber tracking in the left and right cingulate bundles and the genu and splenium of the corpus callosum. Fractional anisotropy and diffusivity (λL and λT) measures were calculated from each tract.ResultsNOGO P3 amplitude and δ power at Cz were smaller in alcoholics than controls. Lower δ total power was related to higher λT in the left and right cingulate bundles. GO P3 amplitude was lower and GO P3 latency was longer with advancing age, but none of the time-frequency analysis measures displayed significant age or diagnosis effects.ConclusionsThe relation of δ total power at CZ with λT in the cingulate bundles provides correlational evidence for a functional role of fronto-parietal white matter tracts in inhibitory processing

Deficient event-related theta oscillations in individuals at risk for alcoholism: A study of reward processing and impulsivity features

Individuals at high risk to develop alcoholism often manifest neurocognitive deficits as well as increased impulsivity. Event-related oscillations (EROs) have been used to effectively measure brain (dys)function during cognitive tasks in individuals with alcoholism and related disorders and in those at risk to develop these disorders. The current study examines ERO theta power during reward processing as well as impulsivity in adolescent and young adult subjects at high risk for alcoholism.EROs were recorded during a monetary gambling task (MGT) in 12-25 years old participants (N = 1821; males = 48%) from high risk alcoholic families (HR, N = 1534) and comparison low risk community families (LR, N = 287) from the Collaborative Study on the Genetics of Alcoholism (COGA). Impulsivity scores and prevalence of externalizing diagnoses were also compared between LR and HR groups.HR offspring showed lower theta power and decreased current source density (CSD) activity than LR offspring during loss and gain conditions. Younger males had higher theta power than younger females in both groups, while the older HR females showed more theta power than older HR males. Younger subjects showed higher theta power than older subjects in each comparison. Differences in topography (i.e., frontalization) between groups were also observed. Further, HR subjects across gender had higher impulsivity scores and increased prevalence of externalizing disorders compared to LR subjects.As theta power during reward processing is found to be lower not only in alcoholics, but also in HR subjects, it is proposed that reduced reward-related theta power, in addition to impulsivity and externalizing features, may be related in a predisposition to develop alcoholism and related disorders

The utility of latency and spectral analysis methods in evoked potential recordings from patients with hepatic encephalopathy

Evoked potentials (EPs) are small phasic potentials that are elicited in conjunction with sensory, motor and cognitive events. EP variables have been assessed in patients with cirrhosis but in general, methods were inadequately standardized and study populations incompletely characterized, leading to some studies questioning the validity of EP’s in diagnosing and monitoring hepatic encephalopathy, while other studies indicated that there is only a low positive yield with these investigations. Few studies have attempted tri-modal sensory and cognitive recordings. Recorded waveforms may demonstrate altered morphology while possessing broadly normal latencies. Since EP analysis is usually performed solely in the time domain, latency measurements do not therefore highlight morphological changes to the waveform and so abnormalities may go unreported. The aim of this study was twofold (i) to measure sensory and cognitive EPs in patients with cirrhosis in relation to their neuropsychiatric status and (ii) to address frequency content in relation to neuropsychiatric status by examining EPs with two spectral techniques, the Fourier Transform (FT) and the Power Spectral Density Estimate (PSD). Seventy patients with biopsy–proven cirrhosis were classified using clinical, psychometric and EEG criteria as unimpaired or as having minimal or overt hepatic encephalopathy (HE). Forty-eight healthy individuals served as controls. Visual (VEPs), brainstem auditory (BAEPs) somatosensory (SSEPs) and cognitive auditory (P300) EPs were recorded under standardized conditions. Significant latency differences were observed in sensory EPs between patients and controls with patient subgroups differences being less significant. The cognitive auditory P300 however, distinguished the patient subpopulations from one another. Frequency shifts are observed in all EP modalities with significant differences also occurring between patient groups. The sensitivity and specificity of the frequency-domain is comparable to that of the time-domain. Paired EP investigations analysed by latency indicate BAEP and P300 best discriminate any degree of encephalopathy; in the frequency domain it is the VEP combined with SEP and in the time-frequency domain it is the SEP. These findings suggest that EPs, when performed as a bank of multimodal tests and with spectral analysis, could provide a sensitive and specific method for the diagnosis and monitoring of hepatic encephalopathy

Event-Related Theta Power during Lexical-Semantic Retrieval and Decision Conflict is Modulated by Alcohol Intoxication: Anatomically Constrained MEG

Language processing is commonly characterized by an event-related increase in theta power (4–7 Hz) in scalp EEG. Oscillatory brain dynamics underlying alcohol’s effects on language are poorly understood despite impairments on verbal tasks. To investigate how moderate alcohol intoxication modulates event-related theta activity during visual word processing, healthy social drinkers (N = 22, 11 females) participated in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. They performed a double-duty lexical decision task as they detected real words among non-words. An additional requirement to respond to all real words that also referred to animals induced response conflict. High density whole-head MEG signals and midline scalp EEG data were decomposed for each trial with Morlet wavelets. Each person’s reconstructed cortical surface was used to constrain noise-normalized distributed minimum norm inverse solutions for theta frequencies. Alcohol intoxication increased reaction time and marginally affected accuracy. The overall spatio-temporal pattern is consistent with the left-lateralized fronto-temporal activation observed in language studies applying time-domain analysis. Event-related theta power was sensitive to the two functions manipulated by the task. First, theta estimated to the left-lateralized fronto-temporal areas reflected lexical-semantic retrieval, indicating that this measure is well suited for investigating the neural basis of language functions. While alcohol attenuated theta power overall, it was particularly deleterious to semantic retrieval since it reduced theta to real words but not pseudowords. Second, a highly overlapping prefrontal network comprising lateral prefrontal and anterior cingulate cortex was sensitive to decision conflict and was also affected by intoxication, in agreement with previous studies indicating that executive functions are especially vulnerable to alcohol intoxication

An EEG investigation of learning and decision making in smokers

To improve the efficacy of addiction treatments it is important to understand the learning and behavioural processes involved. The experimental work presented here aims to further our understanding of the behaviour and related brain activity of smokers, using a range of experimental paradigms and Electroencephalographic (EEG) techniques. A range of behavioural tasks adapted from the animal literature for use with humans, were utilised to explore the choices made by smokers and the effect of smoking-related cues on drug-seeking behaviour. Tasks included concurrent choice and variations of the Pavlovian to Instrumental Transfer (PIT) task. EEG data was recorded during these experiments, and analysed using Event Related Potential (ERP) and frequency measures, to identify a neural component related to these effects. Resting EEG data was also collected and analysed to investigate the relationship between EEG frequency measures and individual difference measures. Behavioural results broadly replicated those found in both animal and human research; smoking related cues enhanced responding for smoking- related outcomes showing Pavlovian control of Instrumental behaviour. Extinction of the Pavlovian cues did not reduce instrumental responses in the transfer stage of a PIT task. However no ERP or frequency components were found that consistently correlated with these behavioural effects. The resting EEG data showed higher beta levels (less desynchronisation) in those with longer histories of smoking (four years and over) suggestive of either sensitisation or the loss of inhibitory neural control in long term smokers. In summary, the behavioural data adds support to a growing body of literature regarding the effects of cues on the behaviour of addicted individuals. More work and perhaps other techniques need to be utilised in order to explore the neural correlates of these behavioural effects and the resting data suggests a promising route for further research

Induced brain activity as indicator of cognitive processes: experimental-methodical analyses and algorithms for online-applications

Die Signalverarbeitung von elektroenzephalographischen (EEG) Signalen ist ein entscheidendes Werkzeug, um die kognitiven Prozessen verstehen zu können. Beispielweise wird induzierte Hirnaktivität in mehreren Untersuchungen mit kognitiver Leistung assoziiert. Deshalb ist die Gewinnung von elektrophysiologischen Parametern grundlegend für die Charakterisierung von kognitiven Prozessen sowie von kognitiven Dysfunktionen in neurologischen Erkrankungen. Besonders bei Epilepsie treten häufig Störungen wie Gedächtnis-, oder Aufmerksamkeitsprobleme auf, zusätzlich zu Anfällen. Neurofeedback (bzw. EEG-Biofeedback) ist eine Therapiemethode, die zusätzlich zu medikamentösen- und chirurgischen Therapien bei der Behandlung vieler neurologischer Krankheiten, einschließlich Epilepsie, erfolgreich praktiziert wird. Neurofeedback wird jedoch meist dafür angewendet, eine Anfallsreduzierung zu erzielen. Dagegen wird eine Verbesserung kognitiver Fähigkeiten auf der Basis elektrophysiologischer Änderungen selten vorgesehen. Darüber hinaus sind die aktuellen Neurofeedbackstrategien für diesen Zweck ungeeignet. Der Grund dafür sind unter anderem nicht adäquate Verfahren für die Gewinnung und Quantifizierung induzierter Hirnaktivität. Unter Berücksichtigung der oben genannten Punkten wurden die kognitiven Leistungen von einer Patientengruppe (Epilepsie) und einer Probandengruppe anhand der ereignisbezogenen De-/Synchronisation (ERD/ERS) Methode untersucht. Signifikante Unterschiede wurden im Theta bzw. Alpha Band festgestellt. Diese Ergebnisse unterstützen die Verwertung von auf ERD/ERS basierten kognitiven Parametern bei Epilepsie. Anhand einer methodischen Untersuchung von dynamischen Eigenschaften wurde ein onlinefähiger ERD/ERS Algorithmus für zukünftige Neurofeedback Applikationen ausgewählt. Basierend auf dem ausgewählten Parameter wurde eine Methodik für die online Gewinnung und Quantifizierung von kognitionsbezogener induzierter Hirnaktivität entwickelt. Die dazugehörigen Prozeduren sind in Module organisiert, um die Prozessapplikabilität zu erhöhen. Mehrere Bestandteile der Methodik, einschließlich der Rolle von Elektrodenmontagen sowie die Eliminierung bzw. Reduktion der evozierten Aktivität, wurden anhand kognitiver Aufgaben evaluiert und optimiert. Die Entwicklung einer geeigneten Neurofeedback Strategie sowie die Bestätigung der psychophysiologischen Hypothese anhand einer Pilotstudie sollen Gegenstand der zukünftigen Arbeitschritte sein.Processing of electroencephalographic (EEG) signals is a key step towards understanding cognitive brain processes. Particularly, there is growing evidence that the analysis of induced brain oscillations is a powerful tool to analyze cognitive performance. Thus, the extraction of electrophysiological features characterizing not only cognitive processes but also cognitive dysfunctions by neurological diseases is fundamental. Especially in the case of epilepsy, cognitive dysfunctions such as memory or attentional problems are often present additionally to seizures. Neurofeedback (or EEG-biofeedback) is a psychological technique that, as a supplement to medication and surgical therapies, has been demonstrated to provide further improvement in many neurological diseases, including epilepsy. However, most efforts of neurofeedback have traditionally been dedicated to the reduction of seizure frequency, and little attention has been paid for improving cognitive deficits by means of specific electrophysiological changes. Furthermore, current neurofeedback approaches are not suitable for these purposes because the parameters used do not take into consideration the relationship between memory performance and event-induced brain activity. Considering all these aspects, the cognitive performance of a group of epilepsy patients and a group of healthy controls was analyzed based on the event-related de /synchronization (ERD/ERS) method. Significant differences between both populations in the theta and upper alpha bands were observed. These findings support the possible exploitation of cognitive quantitative parameters in epilepsy based on ERD/ERS. An algorithm for the online ERD/ERS calculation was selected for future neurofeedback applications, as the result of a comparative dynamic study. Subsequently, a methodology for the online extraction and quantification of cognitive-induced brain activity was developed based on the selected algorithm. The procedure is functionally organized in blocks of algorithms in order to increase applicability. Several aspects, including the role of electrode montages and the reduction or minimization of the evoked activity, were examined based on cognitive studies as part of the optimization process. Future steps should include the design of a special training paradigm as well as a pilot study for confirming the theoretical approach proposed in this work

Differences in visual attention processing: An event-related potential comparative analysis within psychotic disorders

>Magister Scientiae - MScINTRODUCTION: Sustained attention is known to be dysfunctional in psychotic disorders. Sustained attention is the ability to remain focused on a specific time-locked stimulus within a task. We aimed to determine whether there are specific group differences between CON and three psychotic disorders: SCZ, MPD and BPD, then to determine differences between these psychotic disorders. This included differences in behavioural performance and prominent electrophysiological event-related potential (ERP) wave components during cueing and target processing of a visual sustained attention task. Further we aimed to characterize ERP waveform component relationships across and within these groups for demographics, substance use, behavioural performance, and clinical variables, the last limited to the psychotic groups. Lastly, we investigated the effects of prescribed medications on ERP wave components within the psychotic groups. METHODOLOGY: 103 participants (29 schizophrenia (SCZ), 28 bipolar disorder with a history of psychosis (BPD), 21 methamphetamine-induced psychotic disorder (MPD), and 30 controls (CON)) underwent electroencephalography (EEG) record while completing a visual continuous performance task. Participants were presented with 60 trials with three consecutive S’s, the presentation of the third S required a behavioural response. Prominent ERP waveform components were extracted from cues and target stimulus. Group differences were determined by ANOVA with Bonferroni post-hoc correction or multivariate Kruskal-Wallis test dependent on data distribution. Relationships between ERP wave components were determined appropriate with Spearman’s Rank order correlation analyses. RESULTS: (1) MPD reported higher use of substances compared to CON, SCZ and BPD. SCZ behavioural performance was poorer compared to CON which was shown by their longer response times, reduced accuracy and increased errors of omission. Clinically, MPD was found to have a shorter duration of illness compared to SCZ. Then SCZ was found to have more positive symptoms compared to BPD whereas BPD had more negative symptoms compared to SCZ. For the first cue, wave component differences were found only over the left hemisphere, for P100 amplitude over the frontal cortex, P300 amplitude over the central cortex, and N170 amplitude over the parietal cortex. For the presentation of the second cue, differences noted for all groups were localised to the frontal and central brain regions, for P100 and N170 ERP waveforms. For the target stimulus wave component differences were found over the prefrontal, frontal and parietal brain regions, within CON, SCZ, BPD and MPD. (2) For the first cue, education positively correlated with the N170 left parietal amplitude in CON and P300 right parietal amplitude in MPD. During the second cue, the left parietal N170 latency in SCZ correlated positively with education and the left central P300 latency correlated negatively with education in MPD. The age on the day of testing correlated positively with the target left frontal P300 latency in MPD. For the first cue, substance use positively correlated with the left and right parietal P300 latency and negatively for the right parietal P100 amplitude in SCZ. In MPD, a negative correlation was noted across left and right prefrontal N170 and P300 amplitudes, and positive correlation for the left prefrontal P300 latency in MPD. For the target stimulus, correlations were evident for the left and right parietal N70, N170 amplitudes, P300 latency, the right parietal P100 amplitude and left central P300 latency in SCZ. For the first cue, in SCZ PANSS total score correlated positively with left and right central P300 amplitudes and the left parietal P300 amplitude. For the second cue; in MPD, the PANSS negative symptom score, positively correlated with the P100 and N170 left parietal amplitude, left and right parietal P150 amplitude, left central and right parietal P300 amplitude. For the target, the Hamilton depression rating scale correlated positively with the left and right frontal P300 amplitude in MPD and then negatively with the right parietal P300 amplitude in SCZ. Behavioural performance in CON, positively correlated with the left parietal N70, P100, P150 and N170 amplitude the number of correct responses, and left central N170 amplitude. While the number of impulsive responses correlated negatively with the left parietal N70, P100, P150 and N170 and the left central N170 amplitude of CON. For the second cue, behavioural performance was related to the fronto-parietal relationship across all groups. For the target stimulus, impulsive responses positively correlated with the left parietal N70 latency in SCZ. Overall response time negatively correlated with the right parietal P300 latency for SCZ. (3) Medication was found to affect ERP wave components during the sustained visual attention task. For the first cue FGA’s increased the left central P100 amplitude in both SCZ and BPD and decreased the left parietal P100 amplitude in SCZ only. The use of antipsychotics increased the right parietal N70 and left central P100 amplitudes in BPD, specifically the right prefrontal N170 amplitude was increased with the use of SGA’s. Then clozapine use increased the left frontal P100 amplitude in SCZ. For the second cue, SGA’s decreased the right parietal P150 amplitude in SCZ but in MPD the right parietal P150 amplitude was increased with haloperidol use, and FGA. SGA’s increased the left parietal P300 latency in BPD and sodium valproate decreased the left prefrontal P300 latency. For the target stimulus, SGA’s decreased the right parietal P100, P150 and left parietal P150 amplitudes and increased the left central P300 latency in BPD. CONCLUSION: (1) sustained attentional performance is poorer in SCZ. Our study adds to previous studies showing attention processing deficits in SCZ, are evident during cueing of a sustained attention tasks; (2) substance use was found to slow cognitive processing, education improved executive function and information processing, and symptom severity was associated with dysfunction of prefrontal and frontal cortices; (3) antipsychotic medication was related to improved processing of salient information. These data support the current literature and provide novel insights to the attentional processing deficits during cueing in the psychotic disorders

An EEG investigation of learning and decision making in smokers

To improve the efficacy of addiction treatments it is important to understand the learning and behavioural processes involved. The experimental work presented here aims to further our understanding of the behaviour and related brain activity of smokers, using a range of experimental paradigms and Electroencephalographic (EEG) techniques. A range of behavioural tasks adapted from the animal literature for use with humans, were utilised to explore the choices made by smokers and the effect of smoking-related cues on drug-seeking behaviour. Tasks included concurrent choice and variations of the Pavlovian to Instrumental Transfer (PIT) task. EEG data was recorded during these experiments, and analysed using Event Related Potential (ERP) and frequency measures, to identify a neural component related to these effects. Resting EEG data was also collected and analysed to investigate the relationship between EEG frequency measures and individual difference measures. Behavioural results broadly replicated those found in both animal and human research; smoking related cues enhanced responding for smoking- related outcomes showing Pavlovian control of Instrumental behaviour. Extinction of the Pavlovian cues did not reduce instrumental responses in the transfer stage of a PIT task. However no ERP or frequency components were found that consistently correlated with these behavioural effects. The resting EEG data showed higher beta levels (less desynchronisation) in those with longer histories of smoking (four years and over) suggestive of either sensitisation or the loss of inhibitory neural control in long term smokers. In summary, the behavioural data adds support to a growing body of literature regarding the effects of cues on the behaviour of addicted individuals. More work and perhaps other techniques need to be utilised in order to explore the neural correlates of these behavioural effects and the resting data suggests a promising route for further research