Oscillatory connectivity as a mechanism of auditory sensory gating and its disruption in schizophrenia.

Although innumerable studies using an auditory sensory gating paradigm have confirmed that individuals with schizophrenia (SZ) show less reduction in brain response to the second in a pair of clicks, this large literature has not yielded consensus on the circuit(s) responsible for gating nor for the gating difference in SZ. Clinically stable adult inpatients (N = 157) and matched community participants (N = 90) participated in a standard auditory sensory gating protocol. Responses to paired clicks were quantified as peak-to-peak amplitude from a response at approximately 50 ms to a response at approximately 100 ms in MEG-derived source waveforms. For bilateral sources in each of four regions near Heschl's gyrus, the gating ratio was computed as the response to the second stimulus divided by the response to the first stimulus. Spectrally resolved Granger causality quantified effective connectivity among regions manifested in alpha-band oscillatory coupling before and during stimulation. Poorer sensory gating localized to A1 in SZ than in controls confirmed previous results, here found in adjacent brain regions as well. Spontaneous, stimulus-independent effective connectivity within the hemisphere from angular gyrus to portions of the superior temporal gyrus was lower in SZ and correlated with gating ratio. Significant involvement of frontal and subcortical brain regions previously proposed as contributing to the auditory gating abnormality was not found. Findings point to endogenous connectivity evident in a sequence of activity from angular gyrus to portions of superior temporal gyrus as a mechanism contributing to normal and abnormal gating in SZ and potentially to sensory and cognitive symptoms.

Feedback-Related Brain Potentials Indicate the Influence of Craving on Decision-Making in Patients with Alcohol Use Disorder: An Experimental Study.

INTRODUCTION: Alcohol craving is a key symptom of alcohol use disorder (AUD) and a significant cause of poor treatment outcome and frequent relapse. Craving is supposed to impair executive functions by modulating reward salience and decision-making. OBJECTIVE: The present study sought to clarify this modulation by scrutinizing reward feedback processing in an experimental decision-making task, which was accomplished by AUD patients in 2 conditions, in the context of induced alcohol craving and in neutral context. METHODS: AUD inpatients (N = 40) accomplished the Balloon Analog Risk Task, while their EEG was monitored; counterbalanced across conditions, the tasks were preceded either by craving induction by means of imagery and olfactory alcohol cues, or by neutral cues. Decision choice and variability, and event-related potentials (ERPs) prior to (stimulus-preceding negativity [SPN]) and following (P2a) reward feedback upon decisions, and the outcome-related feedback-related negativity (FRN) were compared between conditions and between patients, who experienced high craving upon alcohol cues (N = 18) and those who did not (N = 22). RESULTS: Upon craving induction (vs. neutral condition), high-craving AUD patients showed less adjustment of decision choice to preceding reward experience and more variable decisions than low-craving AUD patients, together with accentuated reward-associated ERP (SPN and P2a), while outcome-related FRN was not modified by craving. CONCLUSIONS: Results support orientation to reward in AUD patients, particularly amplified upon experienced craving, which may interfere with (feedback-guided) decision-making even in alcohol-unrelated context. Craving-accentuated ERP indices suggest neuroadaptive changes of cognitive-motivational states upon chronic alcohol abuse. Together with altered reward-related expectancies, this has to be considered in intervention and relapse prevention.

Consistency of abnormal sensory gating in first-admission and chronic schizophrenia across quantification methods.

The auditory P50/M50 ERP/event-related field is subject to sensory gating, with partial suppression of the amplitude of the second of two (S1 and S2) clicks presented 500 ms apart. Schizophrenia patients have less gating, although quantification methods and associated effect sizes vary across studies using first-admission and/or using chronic patients. The present study evaluated the impact of several methods of quantifying gating in first-admission (FA) and chronic (CHR) schizophrenia patients and in healthy controls (HC). Magnetoencephalogram was measured in 35 FA, 58 CHR, and 28 HC during a paired-click protocol. Sensory gating was quantified on sensor and source levels as a ratio (S2/S1) and as a S1-minus-S2 difference, with M50 amplitude scored relative to baseline and relative to M100 and to M40. Independent of quantification method, patients showed less sensory gating than HC, with medium-to-large effect sizes, without differences between FA and CHR. Results indicate that the frequently reported sensory gating deficit in schizophrenia is robust to variations in quantification methods and stage of disorder.

Reduced mismatch negativity and increased variability of brain activity in schizophrenia.

OBJECTIVES: Schizophrenia patients commonly exhibit smaller amplitudes of mismatch negativity (MMN) than in controls. It remains unclear whether this results from deficient processes indexed by MMN or 'normally' though more variable processing. The present magnetoencephalographic study addressed this question by analyzing intra-individual trial-by-trial variability and MMN amplitude. METHODS: Twenty inpatients meeting ICD criteria for schizophrenia and 18 healthy controls participated in an auditory oddball experiment. The neuromagnetic mismatch field (MMNm) was defined as the difference waveform deviant minus standard tone response. Variability index (VI) in different frequency bands was quantified as trial-by-trial variation of stimulus-evoked responses and epoch-by-epoch variation of signal amplitude during a resting condition. RESULTS: Patients displayed a smaller MMNm amplitude and higher VI during the oddball experiment and during the resting condition than in controls. VI and MMNm amplitude were correlated in controls, but not in patients. CONCLUSION: Reduced MMN in schizophrenia cannot be explained by augmented variability of brain activity; deficient auditory sensory memory and stimulus related phase-locking may characterize the disorder. SIGNIFICANCE: Understanding the contribution of diminished temporal stability of neuronal network dynamics to schizophrenia is crucial in modeling the impact of such instability on performance and thus for understanding deviant attention and memory functions.

Evoked and induced oscillatory activity contributes to abnormal auditory sensory gating in schizophrenia.

The ratio of magnetoencephalogram-recorded brain responses occurring 50ms after paired clicks (S2-evoked M50/S1-evoked M50) serves as a measure of sensory gating. An abnormally large ratio is commonly found in schizophrenia. Whether this abnormality indicates impaired gating is debated. Using event-related oscillations the present study sought to elucidate processes contributing to the phenomenon of altered M50 gating ratio. Schizophrenia inpatients (n=50) showed the expected large M50 gating ratio relative to 48 healthy controls, which correlated with less induced frontally generated activity in the 10-15Hz frequency band starting 200ms before the onset of S2. Patients also produced smaller alpha (8-12Hz) and gamma (60-80Hz) responses to S1. Results suggest that the deviant gating ratio in schizophrenia is a consequence of a complex alteration in the processing of incoming information that cannot be attributed to impaired gating alone.

Medio-frontal and anterior temporal abnormalities in children with attention deficit hyperactivity disorder (ADHD) during an acoustic antisaccade task as revealed by electro-cortical source reconstruction.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent disorders in children and adolescence. Impulsivity is one of three core symptoms and likely associated with inhibition difficulties. To date the neural correlate of the antisaccade task, a test of response inhibition, has not been studied in children with (or without) ADHD. METHODS: Antisaccade responses to visual and acoustic cues were examined in nine unmedicated boys with ADHD (mean age 122.44 ± 20.81 months) and 14 healthy control children (mean age 115.64 ± 22.87 months, three girls) while an electroencephalogram (EEG) was recorded. Brain activity before saccade onset was reconstructed using a 23-source-montage. RESULTS: When cues were acoustic, children with ADHD had a higher source activity than control children in Medio-Frontal Cortex (MFC) between -230 and -120 ms and in the left-hemispheric Temporal Anterior Cortex (TAC) between -112 and 0 ms before saccade onset, despite both groups performing similarly behaviourally (antisaccades errors and saccade latency). When visual cues were used EEG-activity preceding antisaccades did not differ between groups. CONCLUSION: Children with ADHD exhibit altered functioning of the TAC and MFC during an antisaccade task elicited by acoustic cues. Children with ADHD need more source activation to reach the same behavioural level as control children.

Neural signatures of semantic and phonemic fluency in young and old adults.

As we age, our ability to select and to produce words changes, yet we know little about the underlying neural substrate of word-finding difficulties in old adults. This study was designed to elucidate changes in specific frontally mediated retrieval processes involved in word-finding difficulties associated with advanced age. We implemented two overt verbal (semantic and phonemic) fluency tasks during fMRI and compared brain activity patterns of old and young adults. Performance during the phonemic task was comparable for both age groups and mirrored by strongly left-lateralized (frontal) activity patterns. On the other hand, a significant drop of performance during the semantic task in the older group was accompanied by additional right (inferior and middle) frontal activity, which was negatively correlated with performance. Moreover, the younger group recruited different subportions of the left inferior frontal gyrus for both fluency tasks, whereas the older participants failed to show this distinction. Thus, functional integrity and efficient recruitment of left frontal language areas seems to be critical for successful word retrieval in old age.

The consumption of khat and other drugs in Somali combatants: a cross-sectional study.

BACKGROUND: For more than a decade, most parts of Somalia have not been under the control of any type of government. This "failure of state" is complete in the central and southern regions and most apparent in Mogadishu, which had been for a long period in the hands of warlords deploying their private militias in a battle for resources. In contrast, the northern part of Somalia has had relatively stable control under regional administrations, which are, however, not internationally recognized. The present study provides information about drug abuse among active security personnel and militia with an emphasis on regional differences in relation to the lack of central governmental control-to our knowledge the first account on this topic. METHODS AND FINDINGS: Trained local interviewers conducted a total of 8,723 interviews of armed personnel in seven convenience samples in different regions of Somalia; 587 (6.3%) respondents discontinued the interview and 12 (0.001%) were excluded for other reasons. We assessed basic sociodemographic information, self-reported khat use, and how respondents perceived the use of khat, cannabis (which includes both hashish and marijuana), psychoactive tablets (e.g., benzodiazepines), alcohol, solvents, and hemp seeds in their units. The cautious interpretation of our data suggest that sociodemographic characteristics and drug use among military personnel differ substantially between northern and southern/central Somalia. In total, 36.4% (99% confidence interval [CI] 19.3%-57.7%) of respondents reported khat use in the week before the interview, whereas in some regions of southern/central Somalia khat use, especially excessive use, was reported more frequently. Self-reported khat use differed substantially from the perceived use in units. According to the perception of respondents, the most frequent form of drug use is khat chewing (on average, 70.1% in previous week, 99% CI 63.6%-76.5%), followed by smoking cannabis (10.7%, 99% CI 0%-30.4%), ingesting psychoactive tablets (8.5%, 99% CI 0%-24.4%), drinking alcohol (5.3%, 99% CI 0%-13.8%), inhaling solvents (1.8%, 99% CI 0%-5.1%), and eating hemp seeds (0.6%, 99% CI 0%-2.0%). Perceived use of khat differs little between northern and southern Somalia, but perceived use of other drugs reaches alarmingly high levels in some regions of the south, especially related to smoking cannabis and using psychoactive tablets. CONCLUSIONS: Our data suggest that drug use has quantitatively and qualitatively changed over the course of conflicts in southern Somalia, as current patterns are in contrast to traditional use. Although future studies using random sampling methods need to confirm our results, we hypothesize that drug-related problems of armed staff and other vulnerable groups in southern Somalia has reached proportions formerly unknown to the country, especially as we believe that any biases in our data would lead to an underestimation of actual drug use. We recommend that future disarmament, demobilization, and reintegration (DDR) programs need to be prepared to deal with significant drug-related problems in Somalia.

Processing of emotional adjectives: Evidence from startle EMG and ERPs.

Affective startle modulation in the electromyographic (EMG), auditory startle evoked potentials, and visually evoked potentials (VEPs) were assessed while subjects evaluated pleasant, unpleasant, and neutral adjectives. Acoustic startle probes were presented at random time points 2.5-4.0 s after word onset. The visual P2 and P3 potentials were generally larger during processing of emotional than of neutral adjectives. In contrast, the late positive component was enhanced and was correlated with larger EMG startle responses and auditory startle evoked potential P3 amplitudes for pleasant words only. During internal cognitive activity, the startle reflex represents a measure of "processing interrupt." Thus the startle tone interrupted processing of particularly pleasant adjectives and caused re-alerting to environmental stimuli. Specific effects for pleasant material may arise from a "positivity offset," favoring responses to pleasant material at lower arousal levels.

Khat use as risk factor for psychotic disorders: a cross-sectional and case-control study in Somalia.

BACKGROUND: Little is known about the prevalence of khat-induced psychotic disorders in East African countries, where the chewing of khat leaves is common. Its main psycho-active component cathinone produces effects similar to those of amphetamine. We aimed to explore the prevalence of psychotic disorders among the general population and the association between khat use and psychotic symptoms. METHODS: In an epidemiological household assessment in the city of Hargeisa, North-West Somalia, trained local interviewers screened 4,854 randomly selected persons from among the general population for disability due to severe mental problems. The identified cases were interviewed based on a structured interview and compared to healthy matched controls. Psychotic symptoms were assessed using the items of the WHO Composite International Diagnostic Interview and quantified with the Positive and Negative Symptoms Scale. Statistical testing included Student's t-test and ANOVA. RESULTS: Local interviewers found that rates of severe disability due to mental disorders were 8.4% among males (above the age of 12) and differed according to war experiences (no war experience: 3.2%; civilian war survivors: 8.0%; ex-combatants: 15.9%). The clinical interview verified that in 83% of positive screening cases psychotic symptoms were the most prominent manifestations of psychiatric illness. On average, cases with psychotic symptoms had started to use khat earlier in life than matched controls and had been using khat 8.6 years before positive symptoms emerged. In most cases with psychotic symptoms, a pattern of binge use (> two 'bundles' per day) preceded the onset of psychotic symptoms, in contrast to controls of the same age. We found significant correlations between variables of khat consumption and clinical scales (0.35 to 0.50; p < 0.05), and between the age of onset of khat chewing and symptom onset (0.70; p <0.001). CONCLUSION: Evidence indicates a relationship between the consumption of khat and the onset of psychotic symptoms among the male population, whereby not the khat intake per se but rather early onset and excessive khat chewing seemed to be related to psychotic symptoms. The khat problem must be addressed by means other than prohibition, given the widespread use and its role in Somali culture.

Mapping the brain's orchestration during speech comprehension: task-specific facilitation of regional synchrony in neural networks.

BACKGROUND: How does the brain convert sounds and phonemes into comprehensible speech? In the present magnetoencephalographic study we examined the hypothesis that the coherence of electromagnetic oscillatory activity within and across brain areas indicates neurophysiological processes linked to speech comprehension. RESULTS: Amplitude-modulated (sinusoidal 41.5 Hz) auditory verbal and nonverbal stimuli served to drive steady-state oscillations in neural networks involved in speech comprehension. Stimuli were presented to 12 subjects in the following conditions (a) an incomprehensible string of words, (b) the same string of words after being introduced as a comprehensible sentence by proper articulation, and (c) nonverbal stimulations that included a 600-Hz tone, a scale, and a melody. Coherence, defined as correlated activation of magnetic steady state fields across brain areas and measured as simultaneous activation of current dipoles in source space (Minimum-Norm-Estimates), increased within left- temporal-posterior areas when the sound string was perceived as a comprehensible sentence. Intra-hemispheric coherence was larger within the left than the right hemisphere for the sentence (condition (b) relative to all other conditions), and tended to be larger within the right than the left hemisphere for nonverbal stimuli (condition (c), tone and melody relative to the other conditions), leading to a more pronounced hemispheric asymmetry for nonverbal than verbal material. CONCLUSIONS: We conclude that coherent neuronal network activity may index encoding of verbal information on the sentence level and can be used as a tool to investigate auditory speech comprehension.

Cerebral lateralization in schizophrenia and dyslexia: neuromagnetic responses to auditory stimuli.

Many studies have shown altered hemispheric asymmetry-particularly in perisylvian regions-in schizophrenia patients as well as in individuals with dyslexia. Here we explore the similarity of these findings comparing the localization of the magnetic auditory N100m to the German syllable [ba:] in schizophrenia patients, dyslexic adults, and healthy control subjects. Control subjects showed the typical finding of more anterior sources in the right than in the left perisylvian region. In contrast, both schizophrenia patients and dyslexic subjects displayed a symmetrical N100m source configuration. While in people with dyslexia the alteration appears to originate in the right hemisphere, left-hemispheric deviations might contribute to reduced asymmetry in schizophrenia patients. Our results indicate that an absence of lateralized auditory responses in the temporal lobes may reflect a common deviance present in dyslexia and schizophrenia. The nonspecific finding of reduced cerebral laterality may be accounted for by population-specific differences in the functional organization of perisylvian sites.

Source distribution of neuromagnetic slow-wave activity in schizophrenic patients--effects of activation.

When slow waves in the EEG delta and theta frequency range appear in the waking state, they may indicate pathological conditions including psychopathology. The generators of focal slow waves can be mapped using magnetic source imaging. The resulting brain maps may possibly characterize dysfunctional brain areas. The present study examined the stability of the density and distribution of MEG slow waves during three conditions-rest, mental arithmetic and imagery-in 30 schizophrenic patients and 17 healthy controls. Schizophrenic patients displayed a higher density of delta and theta generators primarily in temporal and parietal areas. The group difference was not affected by the particular conditions. The focal concentration of delta and theta slow waves did not differ between patients with and without neuroleptic medication, whereas the prominence of theta dipoles in the temporal area correlated with neuroleptic dosage. The relative amount of temporal slow waves was correlated with the negative symptoms score (PANSS-N) suggesting that temporal dysfunction may be related to negative symptomatology.Results suggest that the distribution of slow-wave activity, measured in a standardized setting, might add diagnostic information about brain abnormalities in schizophrenia.

Effective behavioral treatment of focal hand dystonia in musicians alters somatosensory cortical organization.

New perspectives in neurorehabilitation suggest that behavioral treatments of movement disorders may modify the functional organization of central somatosensory neural networks. On the basis of the assumption that use-dependent reorganization in these networks contributes to the fundamental abnormalities seen in focal dystonia, we treated 10 affected musicians and measured the concomitant somatosensory changes by using whole-head magnetoencephalography. We found that effective treatment, using the method of sensory motor retuning, leads to alterations in the functional organization of the somatosensory cortex. Specifically, before treatment, somatosensory relationships of the individual fingers differ between the affected and unaffected hands, whereas after treatment, finger representations contralateral to the dystonic side become more similar to the less-affected side. Further, somatosensory finger representations are ordered more according to homuncular principles after treatment. In addition, the observed physiologic changes correlated with behavioral data. These results confirm that plastic changes in parallel with emergent neurological dysfunction may be reversed by context-specific, intensive training-based remediation.

Expansion of the tonotopic area in the auditory cortex of the blind.

A part of the core area of the auditory cortex was examined in nine blind and 10 sighted individuals by magnetic source imaging and was found to be enlarged by a factor of 1.8 in the blind compared with the sighted humans. Moreover, the latency of the N1m component of the auditory-evoked magnetic response was significantly decreased in the blind. The development of use-dependent cortical reorganization may be a consequence of the absence of visual input in combination with enhanced auditory activity generated by the long-term concentration by blind individuals on nonvisual cues to interact appropriately with the environment. It is consistent with and well suited to mediate the demonstrated increased ability of the blind to accurately localize acoustic sources in peripheral auditory fields and to decode speech.