Serotonergic interhemispheric asymmetry: gender difference in the orbital cortex

The asymmetry of tritiated imipramine (IMI) binding sites (which are associated with serotonergic mechanisms) were investigated in the orbital frontal cortex in 6 women and men who died of natural causes, and who did not have a history of mental disorders. There was significant interhemispheric asymmetry in both sexes, higher Bmax on the right side compared with the left. The Bmax values of IMI binding in the right orbital cortex in women were significantly higher than in men. Our preliminary findings--gender difference of serotonergic mechanisms in some area of the human brain--are in accordance with the observed gender differences in a variety of serotonin-regulated behaviors (sexual behavior, aggression and impulse control), and serotonergic mental disorders (eating disorders, suicidal behavior, anxiety disorders and depression).     

Does 3H-imipramine binding asymmetry indicate psychiatric illness?

We have accepted that serotonin is essentially an inhibitory neurotransmitter in the human brain, so we propose that it is precisely this inhibiting effect that has weakened in psychiatric cases. We have investigated the asymmetry of tritiated imipramine binding sites (Bmax) in the frontal cortices of homicide victims (n = 6) and controls (n = 6) who died of natural causes. Of these homicide victims examined in our experiment, five proved to have been psychiatric cases and one case had no psychiatric record. The two groups were comparable in age, gender and postmortem delay. The number of imipramine binding sites (Bmax) in the frontal cortices of controls was significantly higher in the right hemisphere than in the left hemisphere. But the homicide victims who were psychiatric cases had significantly higher (Bmax) values in the left hemisphere. While we only found higher Bmax values in the left hemisphere of homicide victims with mental diseases, our data may serve to prove the direct role of the serotonergic mechanism in the development of psychiatric cases.     

Distinct neurophysiological mechanisms for manic and cycloid psychoses: evidence from a P300 study on manic patients

Pathologically asymmetrical P300 fields with right lateralized peaks were described in core schizophrenia as an expression of left-temporal functional deficits, while higher than normal amplitudes were found in cycloid psychosis. This latter finding appeared to be specific for cycloid psychosis and was explained by a generalized cerebral hyperarousal. Based on some psychopathological analogies with cycloid psychosis, and on the comparable pharmacological treatment of the acute episodes, a group of 19 manic patients was investigated immediately after remission and clinical stabilization of an episode. Patients with psychotic features were excluded to avoid overlaps with cycloid psychosis. Patients showed normal P300 amplitudes and no pathological asymmetries of the field, but more posterior positive areas compared to age- and sex-matched controls. This indicates that the neurophysiological changes underlying mania are different from both core schizophrenia and cycloid psychosis. Based on previous three-dimensional source location studies, this finding indicates that disinhibition due to reduced frontal lobe activity, and not hyperarousal, is the basic functional mechanism of manic disorders.     

Further evidence supporting the role of the serotonin system in suicidal behavior: a preliminary study of suicide attempters

The 3H-imipramine binding parameters (Bmax and Kd) were studied in platelets from female suicide attempters and from healthy volunteers. The Bmax was significantly lower among suicide attempters, with no modification of the Kd. These results provide support of the hypothesis that decreased serotonin function may play a role in suicidal behavior.     

正常成人处于气功态和催眠态脑诱发电位实验研究

目的　观察 4 9例正常成人处于“正常态”、“气功入静态”和“催眠状态”的脑诱发电位 ,分析气功发功和催眠诱导对大脑生理过程的不同效应。方法　观察视觉诱发电位 (VEP)、听觉诱发电位(AEP)、听觉脑干诱发电位 (ABR)、关联性负变 (CNV)和P3 0 0 的潜伏期和波幅。结果　催眠状态下P3 0 0(T P3 )波幅降低 ,与正常态相比有极显著差异 (P <0 .0 1) ;AEP(P2 ) ,CNV(M2 )波幅降低 ,与正常态和气功入静态相比均存在显著差异 (P <0 .0 5 ) ;VEP(P2 、P3 )波幅降低 ,与正常态或气功入静态相比分别存在显著差异 (P <0 .0 5 )。结论　催眠诱导对大脑生理过程的影响与气功发功存在差别。     

康复期男性海洛因依赖者注意力与听觉P300的研究

目的探讨处于康复期的海洛因依赖者注意力与听觉P300的特点以及二者的关系。方法以数字划销测验（NCT）评估38例康复期的男性海洛因依赖者（MPHD）和14例健康对照的注意力，同时以脑诱发电位仪检测康复期MPHD及健康对照前额区（Fz）、中央区（Cz）及项区（Pz）听觉P300。结果康复期MPHDNCTI阶段、Ⅱ阶段、Ⅲ阶段、V阶段净分及总净分均显著低于对照组（P〈0．05或P〈0．01）；Cz点AEP—P300波幅显著低于健康对照组（P〈0．05）。MPHDFz、Cz点AEP-P300波幅与净分V呈正相关（P〈0．01），在Pz点AEP—P300波幅与净分Ⅲ呈正相关（P〈0．05）；在Cz点AEP—P300潜伏期与净分工及净分Ⅲ呈正相关（P〈0．05）。结论康复期MPHD存在明显的注意力损害与皮质功能的紊乱，AEP—P300可在一定程度上反映海洛因依赖者注意力损害的程度。     

Cognition in epilepsy: a multichannel event related potential (P300) study

Auditory event-related potentials (AERP) were elicited in 68 epileptic patients and 30 age-matched controls. Epileptic patients had significantly prolonged N2 and P300 (P3) latencies compared with controls. Seven patients were above the range of 3 standard deviations from the control mean values. Amongst epileptics, patients with temporal lobe epilepsy had significantly prolonged P3 latencies compared to patients with idiopathic generalized epilepsy. Patients with abnormal EEGs had significantly prolonged P3 latencies compared to those with normal EEGs. Patients on anticonvulsant monotherapy had shorter P3 latencies, compared to patients taking a combination of two or more anticonvulsants. Patients on shorter duration of treatment had less prolonged P3 latencies compared to those on longer anticonvulsant treatment.     

Cognition in relapsing-remitting multiple sclerosis: a multichannel event-related potential (P300) study

Auditory event-related potentials (AERP) were elicited in 47 patients with relapsing-remitting (RR) multiple sclerosis (MS) and 24 age-matched controls. MS patients had significantly prolonged N2 and P3 latencies as well as low P3 amplitude compared with controls. Seven of them exceeded 3 standard deviations from the control mean values. The observed N2 and P3 alterations are associated with the patients' disability status as it is defined by the Kurtzke expanded disability status scale (EDSS), but are not related to the duration of the disease. A possible cognitive decline as reflected in the observed AERP components alterations in MS patients is subsequently discussed.     

Brainstem Raphe Alterations Depicted by Transcranial Sonography Do Not Result in Serotonergic Functional Impairment

In transcranial sonography (TCS), hypoechogenic signal of mesencephalic raphe structures has been described as a frequent finding in unipolar depression. It remains unclear if raphe hypoechogenicity represents a correlate for an altered serotonergic system. The loudness dependence of auditory evoked potentials (LDAEP) has been proposed as an indirect indicator of central serotonergic activity. Aim of this study was to evaluate TCS and LDAEP as independent variables of the human cerebral serotonergic system. Sonographic and electrophysiological investigations as well as psychometric assessment were performed blindly in 44 healthy subjects (28.7 ± 7.0 years; 24 females). Hypoechogenic raphe was detected in 6 subjects (13.6%). Three probands (6.8%) exhibit hyperechogenicity of Substantia nigra. LDAEP values ranged between ?2.80 and 8.40 mVeff/10dB (2.31 ± 2.44). No correlations between LDAEP and sonographic findings were found. There were no significant correlations with the psychometric assessments. At least in healthy subjects, our findings do not support the hypothesis that abnormal structural finding of hypoechogenic BR in TCS is accompanied by a functional impairment of serotonergic system as assessed by LDAEP. Further multimodal studies on patients with depressive disorders are needed to elucidate the impact of the hypoechogenic raphe signal in the pathophysiology of depression.     

Specific P300 features in patients with cycloid psychosis

In previous studies, low amplitudes and asymmetrical topography with right-sided peaks of the P300-evoked response have been repeatedly described in schizophrenic patients. A sample consisting of 18 patients with cycloid psychosis fulfilling the criteria of Perris and Brockington and 18 controls was investigated with a standard auditory odd-ball paradigm and multichannel evoked potential recordings. Patients had normal P300 topographies and latencies but significantly higher amplitudes than the controls. Higher than normal P300 amplitudes have not been described in any other psychiatric disorder until now, and indicate an enhanced level of arousal. Future studies are expected to shed light on the question of whether high P300 amplitudes are transitory sequelae of the acute psychotic episode or a trait of cycloid psychosis.     

Changes in auditory P300 event-related potentials and brainstem evoked potentials in diabetes mellitus

To investigate the influence of diabetes mellitus on higher cognitive functions electrophysiologically, we studied auditory P300 event-related potentials (P300) in 40 NIDDM patients, taking into account wave I-V latencies (I-V) in auditory brainstem evoked potentials, clinical parameters and head MRI findings. Compared with 20 controls, diabetics had significantly longer P300 and I-V latencies. P300 latencies in diabetics correlated with neither I-V. HbA₁, blood glucose levels, nor disease duration. Of the 13 diabetics investigated neuroradiologically, four had lacunar infarcts with prolonged electrophysiological values. The remaining nine had normal MRI scans, but their physiological parameters were still significantly longer than those of controls. These findings suggest that NIDDM can independently alter higher cognitive and the central auditory pathway functions. Our data also suggest that these alterations occur regardless of the recent metabolic derangement and disease duration. Cerebrovascular ischemia, if present, also appears to contribute in part to cognitive alterations.     

Serotonergic modulation of the P13 midlatency auditory evoked potential in the rat

The vertex-recorded, sleep state-dependent P13 midlatency auditory evoked potential in the rat may be generated, in part, by pedunculopontine nucleus (PPN) projections. Injections into the PPN of the 5-HT(1A) serotonin receptor agonist, 8-hydroxy-2-di-n-propylaminotetralin hydrobromide (DPAT), were found to reduce the amplitude of the P13 potential in a dose- and time-dependent manner. The suppressive effect of DPAT was blocked or reduced by pretreatment with the 5-HT(1A) serotonin receptor antagonist, Pindobind. These results show that the P13 potential can be modulated by known inhibitory serotonergic inputs to the PPN.     

Alterations in tonotopy and auditory cerebral asymmetry in schizophrenia.

BACKGROUND: Deficits in basic auditory perception have been described in schizophrenia. Previous electrophysiologic imaging research has documented a structure-function disassociation in the auditory system in schizophrenia. This study examines whether the most fundamental level of auditory cortical organization, tonotopy, is altered in schizophrenia. METHODS: The tonotopic organization for five tone frequencies in 19 patients with schizophrenia and 22 comparison subjects was evaluated using magnetoencephalography. Auditory evoked magnetic field dipole locations were examined for the N100m component for each frequency. RESULTS: The expected linear relationship between depth and frequency was found in the comparison subjects but not in the schizophrenia group (p <.004). In addition, normal anterior-posterior asymmetry of the N100m was found to be reduced at all five stimulation frequencies employed in the study (p <.04). No relationships between clinical symptom ratings and either tonotopy or asymmetry were observed. CONCLUSIONS: This finding suggests that the tonotopic organization of the auditory cortex in schizophrenia is disturbed and may help explain the relatively poor behavioral performance of schizophrenia patients on simple frequency discrimination tasks. Alterations in fundamental sensory organization may underlie or interact with higher order cognitive mechanisms to produce changes in cognitive task performance.     

Cognitive evoked potentials to anticipated oesophageal stimulus in humans: quantitative assessment of the cognitive aspects of visceral perception

Evoked potential studies provide an objective measure of the neural pathways involved with perception. The effects of cognitive factors, such as anticipation or awareness, on evoked potentials are not known. The aim was to compare the evoked potential response to oesophageal stimulation with the cortical activity associated with anticipation of the same stimulus. In 12 healthy men (23.5 +/- 4 years), oesophageal electrical stimulation (15 mA, 0.2 Hz, 0.2 msec) was applied, and the evoked potentials recorded using scalp electrodes. A computerized model of randomly skipped stimuli (4:1 ratio) was used to separately record the evoked potentials associated with stimulation and those associated with an anticipated stimulus. The electrical stimulus represented the nontarget stimulus and the skipped impulse the target (anticipatory) stimulus. This anticipatory evoked potential was also compared to auditory P300 evoked potentials. Reproducible evoked potentials and auditory P300 responses were elicited in all subjects. Anticipatory evoked potentials (peak latency 282.1 +/- 7.9 msec, amplitude 8.2 +/- 0.7 microV, P < 0.05 vs auditory P300 evoked potential) were obtained with the skipped stimulus. This anticipatory evoked potential was located frontocentrally, while the auditory P300 potential was located in the centro-parietal cortex. The anticipatory evoked potential associated with expectation of an oesophageal stimulus, although of similar latency to that of the auditory P300 evoked response, originates from a different cortical location. The recording of cognitive evoked potentials to an expected oesophageal stimulus depends on attention to, and awareness of, the actual stimulus. Anticipatory evoked potentials to GI stimuli may provide an objective electrophysiological tool for the assessment of the cognitive factors associated with visceral perception.     

EVENT-RELATED POTENTIALS DURING AUDITORY ODDBALL,AND COMBINED AUDITORY ODDBALL–VISUAL PARADIGMS

The purpose of the current study was to investigate the properties of a new modification of the classical auditory oddball paradigm (auditory oddball paradigm combined with passive visual stimulation, AERPs+VEPs) and compare the scalp topography obtained with the new paradigm and the classical auditory oddball paradigm (AERPs) in healthy humans. The responses to bimodal stimulation, and to the classical oddball paradigm were similar to those reported in other studies in terms of location, amplitudes, and latencies of P1, N1, P2, N2, and P300. The new modification of the oddball paradigm produced P300 at fronto-central locations in contrast to centro-parietal locations during the classical oddball paradigm. The amplitudes and latencies of P300 were also significantly larger during the new than the classical paradigm. Furthermore, the amplitudes of N1 and P2, but not N2 were significantly higher and differed in location during the new paradigm in response to both target and standard stimuli. The latencies of all three waves were significantly longer and the latency of P2 differed in location between the new and the classical paradigms in response to only the standard stimuli. The results of this study suggest that the new modification of the classical oddball paradigm produces different neural responses to the classical oddball paradigm. Therefore, this modification can be used to investigate dysfunctions in sensory and cognitive processing in clinical samples.     

Initial serotonin transport into viable platelets and imipramine binding to platelet membranes

Summary. Transport of serotonin into human platelets is a paradigm for neuronal reuptake to investigate putatively low neurotransmitter availability in certain psychiatric diseases. However, inconsistent results have been obtained on serotonin binding to platelet membranes at equilibrium and transport during initial phase into isolated platelets. In the present study we applied a rapid oil-centrifugation technique to study ¹⁴C-serotonin transport for 15 s into viable human platelets during the initial phase, compared to the binding of ³H-imipramine at equilibrium (60 min) to membranes isolated from platelets of the same individuals and to their blood serotonin levels. Platelets were viable for two h after the isolation procedure; concomitant with the decrease in viability transport also decreased. Initial transport into viable cells was observed for two min. Across 19 healthy individuals blood serotonin levels correlated with the halfmaximal saturation constants of binding, K_D, for imipramine but not with any other transport or binding parameters, such as V_max or B_max. Inhibition studies with psychoactive drugs showed good correlation between transport during the initial phase and binding at equilibrium (r = 0.83). It is speculated that changes in the V_max of transport reflect problems with isolation, pretreatment with drugs, the energy load of the cell, and polymorphism of the serotonin transporter. The latter shows a polymorphism in the 5′regulatory region with a 44-bp insertion (l, long form) or deletion (s, short form). Results by Greenberg et al. indicate that in platelets from healthy men the l-variant was associated with increased initial serotonin uptake. Thus for genotyping, we suggest to subdivide patient and control groups in addition to psychopathology also according to their peripheral biochemical lesions. Received December 3, 2001; accepted February 4, 2002     

精神分裂症患者事件相关电位P300与临床症状关系的研究

目的　探讨精神分裂症P3 0 0 主要指标尤峰间潜伏期的变化及其与临床症状的关系。方法　检测 4 0例精神分裂症患者 (患者组 )和 36名正常人 (对照组 )CZ、C3 、C4电极位置的P3 0 0 ,并用阳性和阴性症状量表 (PANSS)评定患者临床症状。结果　与正常对照组相比 ,在CZ、C3 、C4三点 ,患者组P3波幅低 (P <0 0 1) ,并与阴性症状分呈负相关 (r=- 0 4 0 3,- 0 4 30 ,- 0 35 7) ;N2 潜伏期长 (P <0 0 1) ;P2 N2 峰间潜伏期长 (P <0 0 5和P <0 0 1) ,并与PANSS量表总分、阳性症状、思维障碍、激活性等多种症状分呈负相关 (P <0 0 1～ 0 0 5 ) ;N2 P3 峰间潜伏期短 (P <0 0 1) ,在CZ 点与PANSS量表总分(r=- 0 36 3)和一般症状分 (r=- 0 392 )呈负相关。结论　精神分裂症患者的P3 波幅、N2 潜伏期、P2 N2 、N2 P3 峰间潜伏期有明显异常 ,其中P3 波幅、P2 N2 、N2 P3 峰间潜伏期与多种临床症状呈相关性     

Aggression, hyperactivity and platelet imipramine binding.

We measured platelet 3H-imipramine binding parameters in 16 subjects affected by different types of mental deficiency, all characterized by hyperactive and/or aggressive behaviour, and in 16 healthy controls. The patients had a lower maximum binding capacity than the controls, with no difference in Kd, irrespectively of the type of mental disorder. These findings suggest a link between 5-HT disturbances, reflected by reduced imipramine binding sites, and behavioural dyscontrol, expressed as hyperactivity and aggression.     

Evolutionary and mechanistic drivers of laterality: A review and new synthesis

Laterality, best understood as asymmetries of bilateral structures or biases in behaviour, has been demonstrated in species from all major vertebrate classes, and in many invertebrates, showing a large degree of evolutionary conservation across vertebrate groups. Despite the establishment of this phenomenon in so many species, however, the evolutionary and mechanistic study of laterality is uneven with numerous areas in this field requiring greater attention. Here, I present a partial review of how far the study of laterality has come, outlining previous pioneering work, I discuss the hypothesized costs and benefits of a lateralized brain and the suggested path of the evolution of laterality for populations and individuals. I propose an expansion of laterality research into areas that have been touched upon in the past but require stronger evidence from which the field will greatly benefit. Namely, I suggest a continuation of the phylogenetic approach to investigating laterality to better understand its evolutionary path; and a further focus on mechanistic drivers, with special attention to genetic and environmental effects. Putting together the puzzle of laterality using as many pieces as possible will provide a stronger understanding of this field, allowing us to continue to expand the field in novel ways.