Early CNV Research Articles

Acute mechanical stress in primary porcine RPE cells induces angiogenic factor expression and in vitro angiogenesis

BackgroundChoroidal neovascularization (CNV) is a major cause of blindness in patients with age-related macular degeneration. CNV is characterized by new blood vessel growth and subretinal fluid accumulation, which results in mechanical pressure on retinal pigment epithelial (RPE) cells. The overexpression of RPE-derived angiogenic factors plays an important role in inducing CNV. In this work, we investigated the effect of mechanical stress on the expression of angiogenic factors in porcine RPE cells and determined the impact of conditioned medium on in-vitro angiogenesis.ResultsThe goal of this study was to determine whether low levels of acute mechanical stress during early CNV can induce the expression of angiogenic factors in RPE cells and accelerate angiogenesis. Using a novel device, acute mechanical stress was applied to primary porcine RPE cells and the resulting changes in the expression of major angiogenic factors, VEGF, ANG2, HIF-1α, IL6, IL8 and TNF-α, were examined using immunocytochemistry, qRT-PCR, and ELISA. An in vitro tube formation assay was used to determine the effect of secreted angiogenic proteins due to mechanical stress on endothelial tube formation by human umbilical vein endothelial cells (HUVECs). Our results showed an increase in the expression of VEGF, ANG2, IL-6 and IL-8 in response to mechanical stress, resulting in increased in vitro angiogenesis. Abnormal epithelial-mesenchymal transition (EMT) in RPE cells is also associated with CNV and further retinal degeneration. Our qRT-PCR results verified an increase in the expression of EMT genes, CDH2, VIM and FN1, in RPE cells.ConclusionsIn conclusion, we showed that acute mechanical stress induces the expression of major angiogenic and EMT factors and promotes in vitro angiogenesis, suggesting that mechanical stress plays a role in promoting aberrant angiogenesis in AMD.

Negative emotional state slows down movement speed: behavioral and neural evidence.

BackgroundAthletic performance is affected by emotional state. Athletes may underperform in competition due to poor emotion regulation. Movement speed plays an important role in many competition events. Flexible control of movement speed is critical for effective athletic performance. Although behavioral evidence showed that negative emotion can influence movement speed, the nature of the relationship remains controversial. Thus, the present study investigated how negative emotion affects movement speed and the neural mechanism underlying the interaction between emotion processing and movement control.MethodsThe present study combined electroencephalography (EEG) technology with a cued-action task to investigate the effect of negative emotion on movement speed. In total, 21 undergraduate students were recruited for this study. Participants were asked to perform six consecutive action tasks after viewing an emotional picture. Pictures were presented in two blocks (one negative and one neutral). After the participants completed a set of tasks (neutral of negative), they were subjected to complete a 9-point self-assessment manikin scale. Participants underwent EEG while performing the tasks.ResultsAt the behavior level, there was a significant main effect of emotional valence on movement speed, with participants exhibiting significantly slower movements in the negative emotional condition than in the neutral condition. EEG data showed increased theta oscillation and larger P1 amplitude in response to negative than to neural images suggesting that more cognitive resources were required to process negative than neutral images. EEG data also showed a larger late CNV area in the neutral condition than in the negative condition, which suggested that there was a significant decrease in brain activation during action tasks in negative emotional condition than in the neural. While the early CNV did not reveal a significant main effect of emotional valence.ConclusionThe present results indicate that a negative emotion can slow movement, which is largely due to negative emotional processing consuming more resources than non-emotional processing and this interference effect mainly occurred in the late movement preparation phase.

Hypertensive disorders of pregnancy increase the risk of developing neovascular age-related macular degeneration in later life

ABSTRACTBackground: Hypertensive disorders of pregnancy (HDP) and short-term adverse outcomes have long been recognized; however, survivors remain at risk of long-term complications. We investigated whether HDP is associated with the development of choroidal neovascular age-related macular degeneration (CNV AMD).Methods: We identified 31,454 women who experienced HDP based on Utah birth certificates and 62,908 unexposed women matched 2:1 to the exposed. Risk of CNV AMD was estimated using Cox models.Findings: Women with HDP exhibited an 80% higher risk for early CNV AMD (age < 70 y; 95%CI 1.23–2.58).Conclusion: Our findings may have implications forearlier CNV AMD screening and detection.

Neurophysiological mechanisms of interval timing dissociate inattentive and combined ADHD subtypes

It is far from conclusive what distinguishes the inattentive (ADD) and the combined (ADHD-C) subtype of ADHD on the neuronal level. Theoretical considerations suggest that especially interval timing processes may dissociate these subtypes from each other. Combining high-density EEG recordings with source localization analyses, we examine whether there are ADHD-subtype specific modulations of neurophysiological processes subserving interval timing in matched groups of ADD (n = 16), ADHD-C (n = 16) and controls (n = 16). Patients with ADD and ADHD-C show deficits in interval timing, which was correlated with the degree of inattention in ADD patients. Compared to healthy controls, patients with ADHD-C display a somewhat weaker, yet consistent response preparation process (contingent negative variation, CNV). In patients with ADD, the early CNV is interrupted, indicating an oscillatory disruption of the interval timing process. This is associated with activations in the supplemental motor areas and the middle frontal gyrus. Patients with ADD display adequate feedback learning mechanisms (feedback-related negativity, FRN), which is not the case in patients with ADHD-C. The results suggest that altered pacemaker-accumulation processes in medial frontal structures distinguish the ADD from the ADHD-C subtype. Particularly in patients with ADD phasic interruptions of preparatory neurophysiological processes are evident, making this a possible diagnostic feature.

O175 High-density ERPS for working memory for faces, words, and figures in young and elder healthy volunteers

Objectives We aimed at studying brain electrical activity underlying the changes in working memory encoding for different kinds of visual stimuli, related to healthy aging. Methods The participants were young healthy adults (10 female and 12 male), aged 20–30 years and elder healthy adults (12 female and 12 male), aged 50–70 years. All participants performed three delayed match-to-sample visual tasks. The stimuli were monochrome photographs of unfamiliar faces, patterns composed of 8 cubes, and 5-letter Russian abstract nouns. Participants had to memorize the first stimulus in a pair and compare it to the second stimulus presented with 2000 ms delay. 128-channel EEG was recorded with 500 Hz digitization rate. We analyzed the visual response elicited by the first stimulus in a pair and the following slow potential (CNV). Results The task-specific age-related differences ( p 0.05 ) were found in N170 component. Its amplitude was reduced for geometric patterns, and enhanced for faces and words in Elder compared to Young group. The differences were task-specific in their topography in 450–900 ms time window (LPP) and in early CNV. The non-specific age-related amplitude reduction ( p 0.05 ) in elders was in P100 and P300 components, and the non-specific amplitude increase was in N280 and CNV in the central region. Discussion Brain activity during visual item encoding and maintenance showed task-specific and non-specific differences between elder and young healthy participants, depending on the latency of the recorded components of evoked activity. Conclusions The non-specific increased electrical brain activity recorded from the scalp surface in Elder group can be a manifestation of general compensatory processes taking place in the certain brain structures in healthy aging. Significance The results may have a prognostic value for healthy aging vs. age-related memory problems.

Striatal morphology correlates with frontostriatal electrophysiological motor processing in Huntington's disease: an IMAGE-HD study.

BackgroundHuntington's disease (HD) causes progressive atrophy to the striatum, a critical node in frontostriatal circuitry. Maintenance of motor function is dependent on functional connectivity of these premotor, motor, and dorsolateral frontostriatal circuits, and structural integrity of the striatum itself. We aimed to investigate whether size and shape of the striatum as a measure of frontostriatal circuit structural integrity was correlated with functional frontostriatal electrophysiological neural premotor processing (contingent negative variation, CNV), to better understand motoric structure–function relationships in early HD.MethodsMagnetic resonance imaging (MRI) scans and electrophysiological (EEG) measures of premotor processing were obtained from a combined HD group (12 presymptomatic, 7 symptomatic). Manual segmentation of caudate and putamen was conducted with subsequent shape analysis. Separate correlational analyses (volume and shape) included covariates of age, gender, intracranial volume, and time between EEG and MRI.ResultsRight caudate volume correlated with early CNV latency over frontocentral regions and late CNV frontally, whereas right caudate shape correlated with early CNV latency centrally. Left caudate volume correlated with early CNV latency over centroparietal regions and late CNV frontally. Right and left putamen volumes correlated with early CNV latency frontally, and right and left putamen shape/volume correlated with parietal CNV slope.ConclusionsTiming (latency) and pattern (slope) of frontostriatal circuit‐mediated premotor functional activation across scalp regions were correlated with abnormalities in structural integrity of the key frontostriatal circuit component, the striatum (size and shape). This was accompanied by normal reaction times, suggesting it may be undetected in regular tasks due to preserved motor “performance.” Such differences in functional activation may reflect atrophy‐based frontostriatal circuitry despecialization and/or compensatory recruitment of additional brain regions.

Abnormal Electrophysiological Motor Responses in Huntington's Disease: Evidence of Premanifest Compensation.

BackgroundHuntington's disease (HD) causes progressive motor dysfunction through characteristic atrophy. Changes to neural structure begin in premanifest stages yet individuals are able to maintain a high degree of function, suggesting involvement of supportive processing during motor performance. Electroencephalography (EEG) enables the investigation of subtle impairments at the neuronal level, and possible compensatory strategies, by examining differential activation patterns. We aimed to use EEG to investigate neural motor processing (via the Readiness Potential; RP), premotor processing and sensorimotor integration (Contingent Negative Variation; CNV) during simple motor performance in HD.MethodsWe assessed neural activity associated with motor preparation and processing in 20 premanifest (pre-HD), 14 symptomatic HD (symp-HD), and 17 healthy controls. Participants performed sequential tapping within two experimental paradigms (simple tapping; Go/No-Go). RP and CNV potentials were calculated separately for each group.ResultsMotor components and behavioural measures did not distinguish pre-HD from controls. Compared to controls and pre-HD, symp-HD demonstrated significantly reduced relative amplitude and latency of the RP, whereas controls and pre-HD did not differ. However, early CNV was found to significantly differ between control and pre-HD groups, due to enhanced early CNV in pre-HD.ConclusionsFor the first time, we provide evidence of atypical activation during preparatory processing in pre-HD. The increased activation during this early stage of the disease may reflect ancillary processing in the form of recruitment of additional neural resources for adequate motor preparation, despite atrophic disruption to structure and circuitry. We propose an early adaptive compensation mechanism in pre-HD during motor preparation.

The antisaccade task performance deficit and specific CNV abnormalities in patients with stereotyped paraphilia and schizophrenia.

Antisaccade task performance and mean amplitudes of slow cortical potentials (contingent negative variation--CNV) were investigated in 19 healthy volunteers, 16 schizophrenic patients (SP), and 12 patients with stereotyped form of paraphilia (PP). Compared with healthy subjects, schizophrenic and paraphilic patients committed significantly more erroneous saccades. The clear between-group CNV differences were observed during the early CNV stage that is associated with cognitive aspects of preparatory set. In SP, as compared to controls, the significant decline of CNV amplitude was found at frontal-central area. PP have demonstrated the lack of CNV over central and parietal regions, but their CNV amplitudes in frontal area did not differ from values of control group. Thus, two distinct types of CNV abnormalities have been found. The SP results have been interpreted as support for frontal dysfunction in schizophrenia. The disconnection between prefrontal cortex, sensorimotor cortex, and related subcortical structures is hypothesized in paraphilia group.

Transforming Growth Factor-Beta Inhibition Reduces Progression of Early Choroidal Neovascularization Lesions in Rats: P17 and P144 Peptides

The purpose of this study was to assess the effects of transforming growth factor beta (TGF-β) inhibitor peptides (P17 & P144) on early laser-induced choroidal neovascularization (LI-CNV) lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA) was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control), P17 (IV-17), and P144 (IV-144) groups, whereas intravitreal groups included P17 (IVT-17), P144 (IVT-144), and a mixture of both peptides (IVT-17+144) (with fellow eyes receiving vehicle alone). CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-β, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3rd week in IVT-17 and IVT-144 groups, and also from the 2nd week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-β inhibitor peptides (P17 & P144) decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising as a single therapy or adjuvant to anti-VEGF drugs.

Does the early CNV reflect the retrieval of time interval in the CNV paradigm?

Does the early CNV reflect the retrieval of time interval in the CNV paradigm?

Transforming Growth Factor-β Inhibition Decreases Diode Laser–Induced Choroidal Neovascularization Development in Rats: P17 and P144 Peptides

To assess the effect of transforming growth factor (TGF)-β inhibitor peptides (P17 and P144) on the development of laser-induced choroidal neovascularization (LI-CNV) in a rat model. Sixty-one Long-Evans rats underwent diode LI-CNV model. Forty-eight hours later, treatment was administered. The intravenous control group (IV-control) and intravenous P17 group (IV-17) received five doses (0.2 mg every 72 hours) of vehicle and P17, respectively. Four groups received intravitreal injections of P17 low-dose (LD-17; 1 mg/mL) and high-dose (HD-17; 20 mg/mL) and P144 low-dose (LD-144; 1 mg/mL) and high-dose (HD-144; 3 mg/mL), and fellow eyes received vehicle. CNV evolution was assessed weekly by fluorescein angiography (FA). After death, VEGF, TGF-β and PDGF protein levels were measured by ELISA in RPE and retina homogenates. Data were analyzed with commercially available statistical analysis software. The mean CNV area, measured in pixels, was significantly lower at the second and fourth weeks in IV-17 (P < 0.05) and from the second week in HD-17 (P < 0.05), whereas LD-144 and HD-144 showed significant differences at every time point (P < 0.05). LD-17 showed significantly lower protein levels of TGF-β in retina and PDGF in RPE (P < 0.05), whereas HD-17 showed lower levels of VEGF (RPE and retina; P < 0.05), TGF-β (RPE and retina; P < 0.05), and PDGF (RPE; P < 0.05). HD-144 showed lower VEGF levels in the retina (P < 0.05). TGF-β inhibition with these peptides represents a promising new therapeutic line for CNV targeting a different pathway than current therapies. More studies are needed to assess this effect on early CNV, alone or in combination with anti-VEGF.

Interferon γ–Inducible Protein-10 (IP-10) and Eotaxin as Biomarkers in Age-Related Macular Degeneration

To analyze serum cytokine levels in subjects with different stages of AMD and to study the expression of salient cytokines in postmortem eyes with AMD. A suspension array system was used to analyze sera (n = 18 to 20/group) from control subjects and those with early AMD (AREDS stage 1), intermediate dry AMD (AREDS stage 3), advanced AMD with geographic atrophy (GA), or neovascular AMD (CNV). Postmortem eyes with AMD or control eyes were examined immunohistochemically for expression of IP-10 and eotaxin (n = 4 to 8/group). Serum eotaxin and IP-10 levels were significantly elevated in all stages of AMD, except for eotaxin levels in neovascular AMD (P < 0.07). The peak of serum IP-10 concentration was at intermediate dry AMD. In donor eyes, IP-10 and eotaxin expressions were increased in the RPE of eyes with early AMD, GA, and CNV. Eotaxin accumulated within the layer of basal linear/laminar deposits in all stages of AMD, while IP-10 was mainly in eyes with GA and CNV. IP-10 was abundant in the connective tissue matrix associated with CNV, and eotaxin was usually present but more focally and with less intense staining. Both IP-10 and eotaxin were expressed by neovascular endothelial cells. Both IP-10 and eotaxin were expressed in the neurosensory retina, but there was no detectable difference in staining between eyes with or without AMD. IP-10 and eotaxin may be early biomarkers in AMD. The authors hypothesize that the relative balance between levels of IP-10 and eotaxin is critical in regulating the neovascular response.

P02-151 - The antisaccadic CNV in patients with schizophrenia and paraphilia

ObjectivesThe aim of the study was to assess the frontal cortex functioning in schizophrenics and patients with paraphilia using CNV analysis in antisaccade paradigm.Methods9 paranoid schizophrenics, 13 patients with stereotyped forms of paraphilia, and 10 healthy subjects performed horizontal antisaccades. All participants were right-handed males. EEG was recorded from 19 sites. Mean amplitudes of slow negative potentials time-locked to peripheral target (CNV) were analyzed over two intervals: 1000-800 ms (early CNV), and 200-0 ms (late CNV) before peripheral target. Fixation period was 1200-1400 ms.ResultsSignificant increase of errors was revealed in patients with schizophrenia (13,6±4,4%) and parafilia (12,4±2,8%) compared to controls (4,1±1,0%). The significant between-group differences were obtained for the amplitude of early CNV, related to cognitive aspects of preparatory set. Bilateral frontal-central-parietal distribution of early CNV with a maximal amplitude at the saggital sites (Fz, Cz) was observed in control subjects. Significant decline of the CNV amplitude most pronounced in the saggital frontal region (Fz) was found in schizophrenics compared to controls. In patients with paraphilia the negativity zone didn't include central and parietal regions, but CNV amplitude at frontal sites didn't differ from control values.ConclusionsThe obtained results demonstrate that poor antisaccade performance was associated with different neural mechanisms in patients with schizophrenia and paraphilia.The deficit of frontal activation was found in schizophrenic patients. Lack of the activation of central-parietal region in paraphilia group may reflect dysturbed interaction between cortical and subcortical systems involved in the executive regulation of behavior.

Arousal-state modulation in children with AD/HD

Objective To investigate the effect of arousal-state modulation, via manipulation of stimulus event-rate, on response inhibition in children with Attention-Deficit/Hyperactivity disorder (AD/HD) using behavioural and ERP measures. Methods Eighteen children with AD/HD, aged 7–14 years, and 18 age-and sex-matched controls performed a cued visual Go/Nogo task (70% Go) with stimuli presented at fast, medium and slow event-rates. Task performance and ERPs to Warning, Go and Nogo stimuli, as well as preparation between the S1–S2 interval, were examined for group differences. Results AD/HD subjects displayed poorer response inhibition during the fast condition, accompanied by a reduced Nogo P3. Group differences during the fast rate extended to Warning cues, with the AD/HD group showing ERP evidence of atypical orienting/preparation, as indexed by the early and late CNV, and early sensory/attentive processing prior to S2. Conclusions Although deficient response inhibition has been proposed as the core deficit in AD/HD, the results of the present study highlight the key role of energetic factors. Furthermore, group differences found to cues suggest that this effect extends to the processing of task-irrelevant stimuli. Significance This was the first ERP Go/Nogo task investigation using three event-rates, and the results support the theory that state factors may contribute to response inhibition deficits in AD/HD.

Developmental differences in behavioral and event-related brain responses associated with response preparation and inhibition in a go/nogo task.

The present study investigated developmental trends in response inhibition and preparation by studying behavior and event-related brain activity in a cued go/nogo task, administered to nine-year-old children and young adults. Hits, false alarms, inattention, and impulsivity scores and ERP measures of inhibition (fronto-central nogo-N2 and P3), target selection (parietal go-nogo P3 difference), and response preparation (contingent negative variation; CNV) were collected. Higher false alarm and impulsivity scores and the absence of the fronto-central nogo P3 all suggest a developmental lag in response inhibition in children. A developmental lag in sustained attention processes was suggested by worse target detection and larger parietal target/nontarget P3 effects in children. Cue orientation and response preparation processes were respectively measured by early and late CNV activity. Children displayed smaller early CNV amplitudes at fronto-central locations, but mature late CNV. The smaller early CNV activity might indicate inefficient cue-orientation processes caused by incomplete frontal lobe development.

Age differences in contingent negative variation activity of healthy young adults and presenile subjects

20 selected right-handed very healthy subjects (10 young adults and 10 presenile subjects mean age 28.3 and 59.6) were tested for CNV activity with a simple warned reaction time (RT) paradigm. EEG and CNV components (post-S1, N1, P2, P3; early CNV; N1200; late CNV; CNV resolution) were recorded from Fz, C3, Cz, C4, P3, Pz, and P4 referenced to linked mastoid electrodes. EOG, RT and stimuli were also recorded. The presenile group differed significantly from the younger group in the auditory post-S1 N1 and P3, and in the early (O-wave) and late (P-wave) CNV complex components. A progressive amplitude reduction only in frontal leads between O-wave and P-wave with the lowest point being reached in the P-wave was characteristic in the presenile group. Further, presenile subjects showed relatively flat CNV waveshapes of low amplitude and, as a whole, performed a little less well than young persons. This finding suggests that the statistically significant changes in post-S1 EPRs and CNV activity recorded in our presenile subjects, without appreciable deficits in behavioral and mental performance, could be alerting signs of early brain involutional processes related to minimal and subclinical decrement of orienting, attentiveness and response preparation capabilities. If such is the case and it could be confirmed in a larger sample of very healthy subjects, these age-related changes in the presenium could be of considerable practical importance for clinical and research applications.

Electrophysiological changes elicited by auditory stimuli given a positive or negative value: a study comparing anhedonic with hedonic subjects

The present experiment investigates in ‘normal’ subjects the relationship between personality characteristics (anhedonia versus hedonia) and the influence of the affective value of acoustic stimuli (positive, negative, neutral) on various electrophysiolgocical indices reflecting either tonic activation or phasic arousal (EEG power spectra, contingent negative variation: CNV, heart rate, skin potential responses: SPR) as well as on behavioural indices (reaction time: RT). Eighteen subjects were divided into two groups according to their scores at two self-rating questionnaires, the Chapman's Physical Anhedonia Scale (PAS) and the Beck-Weissman's Dysfunctional Attitude Scale (DAS) that quantifies cognitive distortions presumed to constitute high risk for depression: 9 with high scores at both scales formed the A group (Anhedonic-dysfunctional), 9 with low scores at both scales, the H group (Hedonic-adapted) The electrophysiological indices were recorded during 3 situations: the first one was a classical CNV paradigm with a motor reaction time task in which one of 3 tones of different pitch represented the warning stimulus S1; during the second, conditioning phase, two of these tones were associated with either a success (and reward) or a failure (and punishment) during a memory task in order to make them acquire either a positive or a negative affective value; the third situation consisted in the repeating of the first CNV paradigm in order to test the effect of the positive and the negative stimuli versus the neutral one on RTs and electrophysiological data. Significant between-group differences were found regarding tonic activation as well as phasic arousal indices from the very beginning of the experiment when all stimuli were neutral ones, the anhedonics exhibiting higher activation and arousal than the hedonics at the cortical (increased CNV amplitude, increased power in the beta frequency band), cardiovascular (higher heart rate habituating more slowly) and behavioural (faster RTs) levels. Significant between-group differences were also found concerning reactivity to affective stimuli during the third situation: both the orienting response (but only at the cortical level: early CNV) and the motor preparation processes (late CNV) were in the A group significantly less reactive to affective stimuli (especially to the positive one) than in the H group, in particular concerning the frontal (Fz) data.

Topographic and functional characteristics of early and late CNV components

Topographic and functional characteristics of early and late CNV components

CNV rebound and aging

Thirty-five young (ages 18–32 years), 38 older (ages 55–69 years), and 23 elderly (ages 70–85 years) individuals were tested in two CNV paradigms: (1) a constant-foreperiod reaction time task consisting of a light flash-tone-key press sequence (control trials); (2) a divided-attention (50%-letters) task in which two types of trials occurred randomly — no-letters trials (which were identical to control trials) and letters trials (which were similar to control trials except for the inclusion of visually presented letters within the flash-tone interval as part of a short-term memory task). In the divided attention task, all 3 groups showed significant decreases in frontal, central and parietal late CNV amplitudes during letters trials. In no-letters trials, young and older individuals showed significant elevations in late CNV amplitude (rebound effect); the oldest group did not. Early CNV amplitude was decreased in all groups when the short-term memory task was presented (letters trials). The oldest group also showed a paradoxical reduction in early CNV when the task was omitted (no-letters trials). This failure of elderly subjects to demonstrate frontal discrimination of early CNV between letters and no-letters trials suggests an age-related sluggishness in switching from a divided attention set (preparing for both letters and tone in letters trials) to an undivided attention set (preparing only for tone in the no-letters trials). The frontal brain areas appear to mediate, in part, this weakened capacity of the elderly to switch attention. Latency of P3 to S1 was longer and amplitude smaller in the two older groups compared to young subjects; these parameters did not differentiate older and oldest groups. Diminished amplitudes of central and parietal P3 found in both older groups appears to reflect impairment in attention functions. The robustness of frontal P3 amplitudes in both age groups suggests that orienting and/or dishabituation processes may hold up with aging.

Individual differences in the effect of smoking on frontal-central distribution of the CNV: Some observations on smokers' control of attentional behaviour

A previous investigation of individual differences in cortical activation during smoking reported differential development of vertex CNV ‘O’ and ‘E’ wave components in introverted and extraverted smokers. In the present paper the frontal CNV recorded from 12 extraverted and 12 introverted smokers was analysed under simple and choice foreperiod conditions during sham and real smoking. Smokers were matched for age, sex and neuroticism. Analysis of variance revealed significant group by smoking session effects for the later ‘E’ wave component but not for the early ‘O’ wave component. ‘O’ wave negativity though more prominent in frontal regions particularly in extraverts tended to be more affected by foreperiod conditions than smoking sessions. In general smoking produced an increase in central negativity in extraverts, and a decrease in parietal positivity in introverts. These results challenge the stimulus-related/response-related separation of smoking effects made previously to account for early and late CNV component differences. It is suggested that a distinction of CNV components in terms of input (sensory) and output (motor) aspects may anyway be inappropriate. An attempt is made to relate CNV negativity/positivity topography differences to a motor model of attentional strategies differentially deployed during smoking. Extraverted smoker strategies may aim to relieve boredom, enhance readiness to act and so increase central negativity. Introverts may smoke to inhibit distraction, maintain a complex attentional set, and so these affect parietal positivity. It is further suggested that the pharmacological effects of nicotine are those of a generalized mild stressor which supplement the motor aspects of smoking in inducing more motivated performance. Some further predictions concerning the effect of smoking on cortical activity are discussed.