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Background MDD patients with abnormal EEG patterns seem more likely to be non-responsive to the antidepressants escitalopram and venlafaxine, but not sertraline, than patients without EEG abnormalities. This finding suggests that patients with both MDD and abnormal EEGs may differentially respond to antidepressant treatment. In the current study, we investigated whether depressed patients with an abnormal EEG show a normalization of the EEG related to antidepressant treatment and response and whether such effect is drug specific, and whether having had early life stress (ELS) increases the chance of abnormal activity. Methods Baseline and week 8 EEGs and depression symptoms were extracted from a large multicenter study (iSPOT-D, n = 1008) where depressed patients were randomized to escitalopram, sertraline, or venlafaxine-XR treatment. We calculated Odds Ratios of EEG normalization and depression response in patients with an abnormal EEG at baseline, comparing sertraline versus other antidepressants. Results Fifty seven patients with abnormal EEGs were included. EEGs did not normalize significantly more with sertraline compared to other antidepressants (OR = 1.9, p = .280). However, patients with a normalized EEG taking sertraline were 5.2 times more likely to respond than subjects taking other antidepressants (p = .019). ELS was not significantly related to abnormal activity. Limitations Neurophysiological recordings were limited in time (two times 2-minute EEGs) and statistical power (n = 57 abnormal EEGs). Conclusions Response rates in patients with normalized EEG taking sertraline were significantly larger than in subjects treated with escitalopram/venlafaxine. This adds to personalized medicine and suggests a possible drug repurposing for sertraline.

This was a naturalistic study of 23 abstinent cocaine-dependent patients and 38 controls who were studied using a paired-stimulus paradigm to elicit three mid-latency auditory evoked responses (MLAERs), namely, the P50, N100, and P200. Sensory gating was defined as the ratio of the S2 amplitude to the S1 amplitude. Psychosis-proneness was assessed using four Chapman psychosis proneness scales measuring perceptual aberration, magical ideation, social anhedonia, and physical anhedonia. Omnibus correlations based upon the entire sample revealed significant and differential relationships between the MLAER components and psychosis-proneness. Social Anhedonia scale scores accounted for the largest proportion of variance in the P50 gating ratio, while Perceptual Aberration scores accounted for the largest proportion of variance in P200 gating. Psychosis proneness and sensory gating appear to be associated. In particular, poorer P50 gating is related to higher scores on the Social Anhedonia scale in healthy controls and across mixed samples of cocainede-pendent patients and controls. These findings hold significance for the further understanding of the relationship between deficient sensory gating ability and the propensity to developing psychotic symptoms in a vulnerable population like cocaine-dependent individuals.

Objective The cerebral network subserving repetition suppression (RS) of the P50 auditory evoked response as observed using paired-identical-stimulus (S1–S2) paradigms is not well-described. Methods We analyzed S1–S2 data from electrodes placed on the cortices of 64 epilepsy patients. We identified regions with maximal amplitude responses to S1 (i.e., stimulus registration), regions with maximal suppression of responses to S2 relative to S1 (i.e., RS), and regions with no or minimal RS 30–80 ms post stimulation. Results Several temporal, parietal and cingulate area regions were shown to have significant initial registration activity (i.e., strong P50 response to S1). Moreover, prefrontal, cingulate, and parietal lobe regions not previously proposed to be part of the P50 habituation neural circuitry were found to exhibit significant RS. Conclusions The data suggest that the neural network underlying the initial phases of the RS process may include regions not previously thought to be involved like the parietal and cingulate cortexes. In addition, a significant role for the frontal lobe in mediating this function is supported. Significance A number of regions of interest are identified through invasive recording that will allow further probing of the RS function using less invasive technology.

Background Reduced amplitude of the P300 event-related potential in auditory oddball tasks may characterize schizophrenia (SZ) but is also reported in bipolar disorder. Similarity of auditory processing abnormalities between these diagnoses is uncertain, given the frequent combination of both psychotic and nonpsychotic patients in bipolar samples; abnormalities may be restricted to psychosis. In addition, typically only latency and amplitude of brain responses at selected sensors and singular time points are used to characterize neural responses. Comprehensive quantification of brain activations involving both spatiotemporal and time-frequency analyses could better identify unique auditory oddball responses among patients with different psychotic disorders. Methods Sixty SZ, 60 bipolar I with psychosis (BPP), and 60 healthy subjects (H) were compared on neural responses during an auditory oddball task using multisensor electroencephalography. Principal components analysis was used to reduce multisensor data before evaluating group differences on voltage and frequency of neural responses over time. Results Linear discriminant analysis revealed five variables that best differentiated groups: 1) late beta activity to standard stimuli; 2) late beta/gamma activity to targets discriminated BPP from other groups; 3) midlatency theta/alpha activity to standards; 4) target-related voltage at the late N2 response discriminated both psychosis groups from H; and 5) target-related voltage during early N2 discriminated BPP from H. Conclusions Although the P300 significantly differentiated psychotic groups from H, it did not uniquely discriminate groups beyond the above variables. No variable uniquely discriminated SZ, perhaps indicating utility of this task for studying psychosis-associated neurophysiology generally and BPP specifically.

In this study, we employed iterative independent component analysis of single-trial auditory evoked responses to identify features of the P50 and N100 components that provide maximum separation between normal controls and schizophrenia subjects and compared the results against classical ensemble averaging.We analyzed data from 13 schizophrenia and 20 normal control subjects. Responses were obtained in a paired-stimulus paradigm, in which an auditory stimulus S(1) is followed by an identical S(2). The amplitude and latency of the P50 and N100 components in response to the S(1) and S(2) stimuli were measured in each single trial and used as features to classify the responses into two groups. Several methods were used for classification, while their performance was quantified in a 10-fold stratified cross-validation approach.We found that normal controls tended to respond earlier and their individual responses had significantly higher amplitude (p0.01) and significantly less latency variability (p0.01) compared to schizophrenia patients. The S(1) latency was the most significant discriminatory feature (p0.01) followed by S(2) latency (p0.01). The S(2) amplitude, though relatively larger in normal subjects (p0.05), was the least discriminatory feature. Classification based on single-trial analysis yielded 100% accuracy, while the classical ensemble averaging yielded only a maximum of 76% accuracy.Our results demonstrate that single-trial analysis can accurately separate schizophrenia patients from normal controls and suggest that inter-trial variability plays a significant role in information processing in the human brain.The proposed technique may have a significant impact as a clinical tool in the quest for identifying physiological markers of schizophrenia.

Medically unexplained symptoms (MUS) are a major medical burden and our current understanding of the pathophysiological process leading to their development remains minimal. While research has strongly linked chronic stress to the development of MUS the exact mechanisms and the reason for the many variations in the resultant symptomatology remain unclear. In this paper we advance the hypothesis that an internal (visceral) sensory gating system must exist akin to the much better studied external sensory gating system. The hypothesis is based on the observations that under normal conditions sensations of internal organs do not reach consciousness (i.e., filtered or gated out on a subconscious or preattentive level). As visceral sensations are usually perceived only when there is a pathological process affecting the organ, then failure of this internal gating system leading to the sensations arriving to consciousness must be interpreted by the brain to indicate pathology in this organ. If the hypothesis proves to be true and such a system does exist, the implications are many and significant including developing methods for assessing the system and possibly correcting it.

Background Repetition suppression (RS) phenomena, such as those observed using paired-identical-stimulus (S1–S2) paradigms, likely reflect adaptive functions such as habituation and, more specifically, sensory gating. Methods To better characterize the neural networks underlying RS, we analyzed auditory S1–S2 data from electrodes placed on the cortices of 64 epilepsy patients who were being evaluated for surgical therapy. We identified regions with maximal amplitude responses to S1 (i.e., stimulus registration regions), regions with maximal suppression of responses to S2 relative to S1 (i.e., RS), and regions with no or minimal RS. Results Auditory perceptual regions, such as the superior temporal gyri, were shown to have significant initial registration activity (i.e., strong response to S1). Several prefrontal, cingulate, and parietal lobe regions were found to exhibit stronger RS than those recorded from the auditory perceptual areas. Conclusions The data strongly suggest that the neural network underlying repetition suppression may include regions not previously thought to be involved, such as the parietal and cingulate cortexes. In addition, the data also support the notion that the initial response to stimuli and the ability to suppress the stimuli if repeated are two separate, but likely related, functions.

After a brief introduction to the Arab region, six recent and influential papers that have appeared in one of the three leading psychiatry journals from the region are summarized. The first paper discusses the lifetime prevalence of mental disorders in Lebanon and assesses the influence of war. From a representative sample of 2857 individuals they showed that only a minority of individuals with a diagnosable mental disorder have received professional treatment. War exposure increased the risk of first onset of anxiety, mood, and impulse control disorders. The second paper examines the impact of ethnicity on psychiatric disorders in a sample of foreign workers living in Saudi Arabia. They concluded that ethnicity and level of employment influence both the diagnosis and the disposition from the ER (emergency room) with South East Asians more likely to be hospitalized. The next paper discusses the Inter-Rater Reliability of the Short Arabic Form of The Present State Examination (PSE-10) and provides evidence of good reliability and adequate levels of internal consistency. The next study provided evidence for the effectiveness of treatment by home visits from the community psychiatry services in reducing the number of admissions and the duration of hospital stays in chronic schizophrenia patients in the Kingdom of Bahrain. The fifth selected paper discusses the ethical and psychiatric implications of adolescent cosmetic surgery and provides data collected from 3300 Arab females from ten countries. The article concludes by a discussion by the leading Arab psychiatrist Ahmed Okasha on new perspectives on the "social brain".

Objective Although the fact that brain diseases can cause behavioral, cognitive and emotional changes is well-established, a field specifically addressing this area has been slow to develop. A proper nomenclature that places this field in a proper position within the larger field of psychiatry has also been difficult to arrive at. In this article the development of concepts and nomenclature related to disorders on the border between Neurology and Psychiatry is reviewed. Methods Both the evolution of the “organicity” concepts in the DSM system as well as the parallel development in the actual clinical field of Neuropsychiatry are examined. Results The author concludes that while the field of Psychiatry in general continues to struggle with the mind–body dualism problem, classification of neuropsychiatric disorders does not seem to be influenced by this issue. The subspecialty field of Neuropsychiatry continues to evolve rapidly with a subspecialty certification already in place. Conclusions and recommendations The author supports the use of the term “Neuropsychiatric” to refer to the subgroups of psychiatric disorders directly or indirectly resulting from manifest brain pathology.

For patients with schizophrenia, a deficient gating (or filtering) of sensory input has been described. One major approach to study this sensory gating is to measure event-related potentials (ERPs) in response to paired clicks. In these experiments, sensory gating is quantified as amplitude reduction of the ERP components P50 and N100 from the 1st to the 2nd stimulus. In ERP studies brain electrical signals are averaged over single trials. Alterations in phase locking might be one factor contributing to the observed deficits in sensory gating, but findings have been inconclusive as yet. In particular, the contribution of different frequency bands to the deficit required further investigation. We studied N100 gating by intracranial recordings in a sample of epilepsy patients and subdivided the group into good and poor gators of the intracranial ERP component N100. Data were evaluated by frequency specific wavelet-based phase and power analyses. Poor N100 gators had an increased phase locking in the frequency range from 6.0-15.1 Hz after the 2nd stimulus, as compared to good gators. Other group differences were apparent already before the 2nd stimulus. Poor gators had less phase locked beta band activity (20.2-30.0 Hz) than good gators 200-315 ms after the onset of the 1st stimulus. Within the group of poor gators, lower values of phase locking in this frequency range were also associated with lower gating ratios. The reduced beta band response in response to the 1st stimulus may reflect poorer memory encoding of the 1st stimulus in poor gators. This in turn might lead to increased demands to process the 2nd stimulus.

The role of a reduced N100 (or N1) component of the auditory event related potential as a potential trait marker of schizophrenia is critically discussed in this review. We suggest that the extent of the N100 amplitude reduction in schizophrenia depends on experimental and subject factors, as well as on clinical variables: N100 is more consistently reduced in studies using interstimulus intervals (ISIs) > 1 s than in studies using shorter ISIs. An increase of the N100 amplitude by allocation of attention is often lacking in schizophrenia patients. A reduction of the N100 amplitude is nevertheless also observed when such an allocation is not required, proposing that both endogenous and exogenous constituents of the N100 are affected by schizophrenia. N100 is more consistently reduced in medicated than unmedicated patients, but a reduction of the N100 amplitude as a consequence of antipsychotic medication was shown in only two of seven studies. In line with that, the association between the N100 reduction and degree of psychopathology of patients appears to be weak overall. A reduced N100 amplitude is found in first degree relatives of schizophrenia patients, but the risk of developing schizophrenia is not reflected in the N100 amplitude reduction.

Investigating the neurobiological basis of schizophrenia is a critical step toward establishing its diagnostic validity, predicting outcome, delineating causative mechanisms and identifying objective targets for treatment research. Over the past two decades, there have been several advances in this field, principally related to developments in neuroimaging, electrophysiological and neuropathological approaches. Several neurobiological alterations in domains of brain structure, physiology and neurochemistry have been documented that may reflect diverse pathophysiological pathways from the "genome to the phenome". While none of the observed abnormalities are likely to qualify as diagnostic markers at this time, many can serve as potential intermediate phenotypes for elucidating etiological factors including susceptibility genes, and as therapeutic targets for novel drug discovery. Despite several challenges including the substantial phenotypic, pathophysiologic and etiological heterogeneity of schizophrenia, technological limitations, and the less than ideal animal models, considerable progress has been made in characterizing the neurobiological substrate of schizophrenia. The accumulating fact-base on the neurobiology of schizophrenia calls for novel integrative model(s) that may generate new, testable predictions.

Auditory and somatosensory responses to paired stimuli were investigated for commonality of frontal activation that may be associated with gating using magnetoencephalography (MEG). A paired stimulus paradigm for each sensory evoked study tested right and left hemispheres independently in ten normal controls. MR-FOCUSS, a current density technique, imaged simultaneously active cortical sources. Each subject showed source localization, in the primary auditory or somatosensory cortex, for the respective stimuli following both the first (S1) and second (S2) impulses. Gating ratios for the auditory M50 response, equivalent to the P50 in EEG, were 0.54+/-0.24 and 0.63+/-0.52 for the right and left hemispheres. Somatosensory gating ratios were evaluated for early and late latencies as the pulse duration elicits extended response. Early gating ratios for right and left hemispheres were 0.69+/-0.21 and 0.69+/-0.41 while late ratios were 0.81+/-0.41 and 0.80+/-0.48. Regions of activation in the frontal cortex, beyond the primary auditory or somatosensory cortex, were mapped within 25 ms of peak S1 latencies in 9/10 subjects during auditory stimulus and in 10/10 subjects for somatosensory stimulus. Similar frontal activations were mapped within 25 ms of peak S2 latencies for 75% of auditory responses and for 100% of somatosensory responses. Comparison between modalities showed similar frontal region activations for 17/20 S1 responses and for 13/20 S2 responses. MEG offers a technique for evaluating cross modality gating. The results suggest similar frontal sources are simultaneously active during auditory and somatosensory habituation.

Although there are several reports of patients with cocaine dependence displaying cognitive deficits, the nature of their information processing deficits is not well characterized. In the present study, the attentional performance of cocaine-dependent patients (n = 14) was examined and compared with that of healthy control individuals (n = 15). Attention was assessed using an auditory oddball event-related task as well as the Continuous Performance Test (CPT; Identical Pairs version). The cocaine-dependent group displayed P300 amplitude reduction compared to controls. The group difference in P300 response latency did not reach significance. On the CPT, the cocaine-dependent patients displayed significantly poorer discriminability and greater errors of commission than the controls. There was a positive correlation between performance on the oddball event-related task and performance on the CPT. This investigation provides converging behavioral and electrophysiological evidence of attentional deficits in cocaine-dependent patients.

Objective The role of the hippocampus in sensory gating is unresolved as yet. The current study was conducted in order to examine the effects of hippocampal lesions on the function of auditory sensory gating. Methods Epilepsy patients with unilateral and bilateral hippocampal sclerosis (HS) were investigated. Auditory-evoked potentials (AEPs) were recorded by multichannel scalp EEG in a double-click experiment. Gating was defined as the response decrease of the AEP components from 1st to 2nd click. Results Diagnosis (left vs. right vs. bilateral HS) did not affect the amplitudes or gating of the P50, N100 or P200 components. However, diagnosis had an impact on the topography of the N100 component after its peak maximum: In right HS patients, the N100 was left-lateralized, while it was nearly symmetrically distributed in patients with left HS and right lateralized in patients with bilateral HS. Besides the N100, the topography of the P200 component was affected by diagnosis. Conclusions Findings suggest that auditory activity, as reflected in the N100 and P200 components, is modulated by the hippocampus, but not sensory gating in its classical definition. Significance Deficits in P50 gating in schizophrenia are unlikely to be explained by hippocampal deficits.

Early (P50) and late (P200) auditory sensory gating were assessed in low and high schizotypal personality groups using Raine's Schizotypal Personality Questionnaire. We also assessed the impact of smoking as it relates to low and high schizotypal personalities. Low and high schizoptypal personality groups were divided into subgroups of participants who either smoked or did not smoke tobacco cigarettes. Participants were 39 (18 men) right-handed undergraduates. Using a paired-tone paradigm (40 pairs, 70 dB, 1000 Hz), smokers were tested while abstaining from smoking, and 5 min after smoking. Non-smokers were tested similarly without smoking. Midline and hemispheric sites were evaluated at frontal (F3/Fz/F4), fronto-central (FC3/FCz/FC4), central (C3/Cz/C4), centro-parietal (CP3/CPz/CP4), and parietal (P3/Pz/P4) regions. P50 sensory gating was better at midline sites than left/right hemispheric sites, whereas there was no difference in activation with respect to location for P200 sensory gating. Cz had better P50 sensory gating than other midline regions, whereas Fz, FCz and Cz had better P200 sensory gating than CPz and Pz. Hemispheric comparisons were made. At the central region for non-smokers, high schizotypys showed poorer P50 sensory gating than low schizotypys. Among low schizotypys, smokers showed poorer P50 sensory gating than non-smokers at the fronto-central and central regions smokers showed better P200 sensory gating than non-smokers at the central region. Smoking had no acute impact on either early (P50) or late (P200) sensory gating. Our data support the notion that early sensory gating and late sensory gating represent different sensory gating mechanisms with respect to low and high schizotypy personalities. Individual differences in early and late sensory gating need further investigation.

Oscillatory activity in the gamma band range (30-50 Hz) and its functional relation to auditory evoked potentials (AEPs) is yet poorly understood. In the current study, we capitalized on the advantage of intracranial recordings and studied gamma band activity (GBA) in an auditory sensory gating experiment. Recordings were obtained from the lateral surface of the temporal lobe in 34 epileptic patients undergoing presurgical evaluation. Two kinds of activity were differentiated: evoked (phase locked) and induced (not phase locked) GBA. In 18 patients, an intracranial P50 was observed. At electrodes with maximal P50, evoked GBA occurred with a similar peak latency as the P50. However, the intensities of P50 and evoked GBA were only modestly correlated, suggesting that the intracranial P50 does not represent a subset of evoked GBA. The peak frequency of the intracranial evoked GBA was on average relatively low (approximately 25 Hz) and is, therefore, probably not equivalent to extracranially recorded GBA which has normally a peak frequency of approximately 40 Hz. Induced GBA was detected in 10 subjects, nearly exclusively in the region of the superior temporal lobe. The induced GBA was increased after stimulation for several hundred milliseconds and encompassed frequencies up to 200 Hz. Single-trial analysis revealed that induced GBA occurred in relatively short bursts (mostly <

Background Auditory hallucinations are often resistant to treatment and can produce significant distress and behavioral difficulties. A preliminary report based on 24 patients with schizophrenia or schizoaffective disorder indicated greater improvement in auditory hallucinations following 1-hertz left temporoparietal repetitive transcranial magnetic stimulation (rTMS) compared to sham stimulation. Data from the full 50-subject sample incorporating 26 new patients are now presented to more comprehensively assess safety/tolerability, efficacy and moderators of this intervention. Methods Right-handed patients experiencing auditory hallucinations at least 5 times per day were randomly allocated to receive either rTMS or sham stimulation. A total of 132 minutes of rTMS was administered over 9 days at 90% motor threshold using a double-masked, sham-controlled, parallel design. Results Hallucination Change Score was more improved for rTMS relative to sham stimulation ( p = .008) as was the Clinical Global Impressions Scale ( p = .0004). Hallucination frequency was significantly decreased during rTMS relative to sham stimulation ( p = .0014) and was a moderator of rTMS effects ( p = .008). There was no evidence of neurocognitive impairment associated with rTMS. Conclusions Left temporoparietal 1-hertz rTMS warrants further study as an intervention for auditory hallucinations. Data suggest that this intervention selectively alters neurobiological factors determining frequency of these hallucinations.