Postimperative Negative Variation Research Articles

Contingent negative variation as an evaluation indicator of neurocognitive disorder after traumatic brain injury.

Neurocognitive disorders are commonly observed in patients suffering from traumatic brain injury (TBI). Methods to assess neurocognitive disorders have thus drawn the general attention of the public, especially electrophysiology parameter such as contingent negative variation (CNV), which has been given more emphasis as a neurophysiological marker in event-related potentials (ERPs) for diagnosing a neurocognitive disorder and assessing its severity. The present study focused on the correlations between CNV parameters and levels of daily living activities and social function to explore the potential of CNV as an objective assessment tool. Thirty-one patients with a diagnosis of neurocognitive disorder after a TBI according to ICD-10 were enrolled as the patient group, and 24 matched healthy volunteers were enrolled as the control group. The activity of daily living scale, functional activities questionnaire, social disability screening schedule, and scale of personality change following TBI were used to assess daily living activity and social function. The scale scores in patients were significantly higher than those in controls. Maximum amplitudes before S2 and during the post-imperative negative variation (PINV) period were also significantly higher in the patient group compared to the control group and were positively correlated with four scale scores. The duration of PINV at Fz and Cz was significantly shorter in the patient group than in the control group. The CNV return to baseline from a positive wave at electrode Fz and Cz occurred significantly earlier in the control group than in the patient group, while at Pz, the result showed the opposite. Lower amplitudes of CNV were associated with more severe neurocognitive disorder and greater impairments in daily life abilities and social function. The duration of PINV and the latency of returning to baseline from a positive wave were correlated with the neurocognitive disorder to some extent. CNV could be used as an objective, electrophysiology-based parameter for evaluating the severity of the neurocognitive disorder and personality changes after TBI.

Late N1 and postimperative negative variation analysis depending on the previous trial history in paradigms of increasing auditory complexity.

Predictive coding reflects the ability of the human brain to extract environmental patterns in order to reformulate previous expectations. The present report analyzes through the late N1 auditory component and the postimperative negative variation (PINV) the updating of predictions regarding the characteristics of a new trial, depending on the previous trial history, complexity, and type of trial (standard or deviant). Data were obtained from 31 healthy subjects recorded in a previous study based on two paradigms composed of stimulus sequences of decreasing or increasing frequencies intermingled with the sporadic appearance of unexpected tone endings. Our results showed a higher amplitude for the most complex condition and deviant trials for both the late N1 and PINV components. Additionally, the N1 and PINV presented a different amplitude response to the standard and deviant trials as a function of previous trial history, suggesting a continuous updating of trial categorization. The results suggest that the late N1 and PINV components are involved in the generation of an internal model about the rules of external auditory stimulation.NEW & NOTEWORTHY The present study showed a higher amplitude for the late N1 and the PINV with reference to both the prediction performed in auditory paradigms of higher abstraction and the unexpected breaking of the extracted rules. Additionally, both components were modulated depending on the local probability, which would suggest that they are continuously being updated by the previous stimulus history.

The controllability of aversive and neutral pictures: an event-related potential study

Control over physically aversive stimuli may reduce stress, arousal and physiological responses to these stimuli. Nonetheless, avoidance of emotionally aversive stimuli/excessive attempts to control negative emotion might alternatively increase the salience of these stimuli. Here, we used a novel paradigm to examine the effect of controllability on the processing of aversive and neutral pictures (using the late positive potential, LPP) and response uncertainty (using the post-imperative negative variation, PINV). Participants (n = 48) were told that they could press a button to terminate the presentation of an aversive or neutral picture, but this was only true during some blocks of the experiment and not others. Results showed that the LPP was larger for control compared to no control blocks and that this was driven by larger LPPs to aversive pictures during the first control block, but only for participants who had started the task in a no control block. Therefore, knowing that aversive stimuli might not always be controllable (i.e., a prior experience of uncontrollability) appears to increase the motivational salience of these stimuli once control becomes possible. In addition, uncontrollability increased both the early and late PINV, and the late PINV was larger for the second compared to the first control block. As such, the current study provides the first evidence that the PINV can be elicited using aversive and neutral pictures and suggests functional differentiation between the early and late portions of the PINV. Results support the utility of this novel paradigm for examining control over emotional stimuli.

Contingent negative variation in patients with deficit schizophrenia or bipolar I disorder with psychotic features: Measurement and correlation with clinical characteristics

Background: Schizophrenia is a highly heterogeneous disease. Event-related potentials have been regarded to establish intermediate phenotypes of schizophrenia. Our previous study found that patients with deficit schizophrenia (DS) are relatively homogeneous and show a significantly longer onset latency of contingent negative variation (CNV) expectancy wave. Aims: To further examine CNV in patients with first-episode and drug-naïve DS or bipolar I disorder (BP I) with psychotic features, and also investigate correlations between CNV and clinical characteristics in DS and BP I. Method: We elicited a CNV using an alarm (S1)-imperative (S2) paradigm in 30 DS patients or 33 BP I with psychotic features as well as 40 healthy controls. Results: CNV amplitude was significantly smaller and reaction time significantly longer in the DS and BP I groups than in healthy controls. Post-imperative negative variation (PINV) interval was significantly shorter in the DS group than in healthy controls. The onset latency of CNV expectancy wave was significantly longer and PINV area significantly smaller in the DS group than in the other groups. In the DS group, CNV amplitude and PINV interval correlated negatively with the subscale of negative symptoms on the Positive and Negative Syndrome Scale (PANSS); CNV amplitude also correlated negatively with disease duration. In the BP I group, CNV amplitude and reaction time showed no correlation with clinical features. Conclusions: CNV amplitude is a common trait marker for psychosis. The onset latency of CNV expectancy wave appears to be a specific trait marker and may be used to identify candidate genes for DS.

Time-dependent post-imperative negative variation indicates adaptation and problem solving in migraine patients

According to the Seligman theory of learned helplessness, depression is caused by a repetitive experience of loss of control resulting in internal, stable and global attributional styles for negative events. In depressed patients and healthy controls experiencing such events, an increased amplitude of the post-imperative negative variation (PINV) has been described. The aim of the study was to investigate a possible correlation between migraine, depression, learned helplessness and PINV. 24 patients suffering from migraine without aura and 24 healthy controls were exposed to a situation of loss of control whilst the contingent negative variation (CNV) from C3, C4 and Cz were recorded. Before conducting the experiment, the subjects were asked to answer the Beck Depression Inventory (BDI) and the German attributional style questionnaire (GASQ). Amplitudes of total CNV, early and late component and PINV were calculated in eight blocks of four recordings each. The results confirm findings of a pronounced PINV in situations of loss of control, though high amplitudes were not correlated with low values in the GASQ and therefore with learned helplessness. High PINV in migraine patients correlated with high scores in the BDI and the list of the complaints questionnaire. However, this was not the case in healthy controls. In this experimental situation, PINV in migraine patients can be interpreted as an expectancy potential in order to avoid failure and helplessness.

Dopamine Inactivation Efficacy Related to Functional DAT1 and COMT Variants Influences Motor Response Evaluation

BackgroundDopamine plays an important role in orienting, response anticipation and movement evaluation. Thus, we examined the influence of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of motor processing in a contingent negative variation (CNV) task.Methods64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as motor postimperative negative variation were assessed. Adolescents were genotyped for the COMT Val158Met and two DAT1 polymorphisms (variable number tandem repeats in the 3′-untranslated region and in intron 8).ResultsThe results revealed a significant interaction between COMT and DAT1, indicating that COMT exerted stronger effects on lateralized motor post-processing (centro-parietal motor postimperative negative variation) in homozygous carriers of a DAT1 haplotype increasing DAT1 expression. Source analysis showed that the time interval 500–1000 ms after the motor response was specifically affected in contrast to preceding movement anticipation and programming stages, which were not altered.ConclusionsMotor slow negative waves allow the genomic imaging of dopamine inactivation effects on cortical motor post-processing during response evaluation. This is the first report to point towards epistatic effects in the motor system during response evaluation, i.e. during the post-processing of an already executed movement rather than during movement programming.

Lateralized movement-related potential amplitudes differentiate between schizophrenia/schizoaffective disorder and major depression

ObjectiveTo examine whether deficits in focal lateralized motor system activation would differentiate between subjects with schizophrenia/schizoaffective disorder and subjects with a major depressive episode. Reductions of Bereitschaftspotential amplitude have been described for both diagnostic groups. MethodsWe analyzed multi-channel lateralized movement-related potentials (LMRP) during choice reaction movements in 16 schizophrenic/schizoaffective patients in partial remission with predominant negative symptoms, 18 patients with a non-psychotic major depression and two healthy control groups age-matched to the respective patient groups (20/23 subjects). ResultsA significant reduction of lateralized potentials over the (pre-)motor areas immediately preceding and around movement execution was found only in subjects with schizophrenia/schizoaffective disorder but not with a major depressive episode. Reduced LMRP amplitudes correlated with negative symptoms (SANS score). Other movement stages (preceding response-locked ‘contingent negative variation’ during response selection and post-movement evaluation during motor postimperative negative variation) were not affected in the same way. ConclusionsDeficits in focal motor cortex activation during movement execution may reflect rather schizophrenia-specific deficits in fronto-striatal circuits. A general lack of drive and depressed mood did not alter the degree of lateralization of motor activation during movement execution. SignificanceLateralization of movement-related potentials could differentiate psychotic from non-psychotic disorders on the group level.

Cortical post-movement and sensory processing disentangled by temporary deafferentation

Motor system calibration depends crucially on the adjustment to the consequences of a movement, which often occur when the movement itself is already completed. The mechanisms by which reafferent feedback information is compared to the programmed movement remain unclear. In the current study, the hypothesis of a short term memory trace in the motor cortex which outlasts quick movements and is generated independently from reafferent feedback was challenged by temporal deafferentation. Post-movement cortical potentials were recorded by high-resolution EEG during a reaction time task which required speeded unilateral right-hand or left-hand button presses. We analysed lateralized motor N700 (motor post-imperative negative variation), a post-movement component, under temporary deafferentation achieved through application of a blood pressure tourniquet in ten healthy adult subjects. Motor N700 persisted under deafferentation in the absence of reafferent tactile and proprioceptive feedback input into the sensorimotor cortex, which was abolished under deafferentation. Source analysis pointed towards continuing activation in the pre-/primary motor cortex. Thus, motor post-processing can be dissociated from reafferent sensory feedback. Motor cortex activation outlasts quick movements for about a second also in the absence of a reafferent signal. Continuing motor cortex activation could act as an internal motor model in motor learning and allow better adjustment of movements according to the evaluation of their consequences.

Increased performance uncertainty in children with ADHD? - Elevated post-imperative negative variation (PINV) over the ventrolateral prefrontal cortex

BackgroundWe aimed to investigate the influences of attention deficit/hyperactivity disorder (ADHD) on response evaluation, as reflected by the postimperative negative variation (PINV), a slow event-related potential.MethodsWe investigated PINV as an indicator of performance uncertainty in an audio-visual contingent negative variation (CNV) paradigm with an interstimulus interval of 3 seconds. A constant, unilateral, quick motor reaction with either the right or the left thumb was required after an auditory forewarned (S1) visual imperative stimulus (S2). We examined 18 ADHD patients (combined or hyperactive-impulsive subtype) aged between 8 and 14 years and an age-, sex and IQ-matched control group of 19 healthy subjects using 64-channel high-density EEG. A first run was recorded drug-free, a second one under methylphenidate (MPH) medication in the ADHD group.ResultsWe found a significantly increased negativity of the PINV-component over the ventrolateral prefrontal cortex in ADHD children compared to the healthy control group. PINV amplitude was influenced by movement side, most likely due to the slightly more difficult task when left hand responses were required. After the intake of MPH, PINV amplitudes of ADHD children normalized.ConclusionsWe conclude that children with ADHD are likely to be more uncertain about the correctness of their performance and interpret the increased PINV as a hint towards compensatory mechanisms for a deficit in the evaluation of contingencies. Further studies are needed to assess the exact extent to which remainders of eye-movement related potentials contribute to PINV amplitude despite the correction for eye-artifacts.

Research Letter: Reproducibility and predictive value of the post-imperative negative variation during aversive instrumental learning in depression

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Electrophysiological changes in late life depression and their relation to structural brain changes

Late life depression is often accompanied by slowed information processing during neuropsychological testing, and this has been related to underlying cerebrovascular disease. We investigated whether changes in electrophysiological markers of information processing might share the same pathological correlates. Differences in power spectra frequency, contingent negative variation (CNV), post-imperative negative variation (PINV), and auditory P300a amplitude and latency in 19 patients with DSM-IV major depression aged ≥ 60 years were compared with 25 recordings in age-matched healthy controls. Associations with total brain volume and degree of white matter hyperintensities (WMH) were examined in those who had undergone additional magnetic resonance imaging (MRI). Compared with healthy controls, patients had more slow-wave delta (group difference: p = 0.024) and theta activity (p = 0.015) as well as alpha activity (p = 0.005) but no decrease in beta band frequency (p = 0.077). None of these changes related differently to brain volume or WMH in patients or controls. Patients further showed prolonged P300a latencies (p = 0.027), which were associated with decreased total brain volume in patients but not controls (interaction by group: p = 0.004). While there were no overall differences in PINV between both groups, patients showed a decrease in PINV magnitude with increasing WMH, a relation that was not seen in controls (interaction by group: p = 0.024). Patients with late life depression show changes in several electrophysiological markers of cerebral arousal and information processing, some of which relate to brain atrophy and WMH on MRI.

Loss of control during instrumental learning: A source localization study

This study used multi-channel electroencephalography (EEG) to investigate cortical correlates of response-outcome contingency appraisal as indexed by the postimperative negative variation (PINV) during instrumental learning. PINV data were subjected to standardized low resolution brain electromagnetic tomography (sLORETA) for source localization. Forty-six healthy adult persons underwent a forewarned S1–S2 paradigm where response-outcome contingencies varied in three consecutive conditions. Initially subjects could control aversive stimulation by a correct behavioral response followed by loss of control and subsequent restitution of control. Throughout the experiment, reaction times, errors, ratings of controllability, arousal, emotional valence and helplessness were assessed. Topographical EEG analyses showed that in particular frontal PINV magnitudes covaried with the experimental manipulation. Loss of control induced extensive response-outcome uncertainty accompanied by a fronto-central PINV maximum. sLORETA functional analyses of the PINV revealed that dependent on the experimental conditions frontal, temporal and parietal areas seem to be related to PINV formation. In particular during loss of control, between-conditions sLORETA comparisons found Brodmann Area 24 in the anterior cingulate cortex (ACC) to be associated with PINV generation, which was confirmed by correlational analyses. These results provide further evidence for the role of the ACC in detecting response conflict and its involvement in the generation of the PINV.

Changes in Cortical Potential Associated With Modulation of Peripheral Sympathetic Activity in Patients With Epilepsy

To examine the immediate and sustained effects of volitional sympathetic modulation, using galvanic skin response (GSR) biofeedback training on cortical excitability in patients with drug-resistant epilepsy. Ten patients undertook 12 sessions of GSR biofeedback training over 1 month, during which they were trained to increase sympathetic arousal, using GSR biofeedback. Contingent negative variation (CNV) (a slow cortical potential reflecting cortical arousal and excitability) and the related post imperative negative variation (PINV) were quantified before and after biofeedback treatment. A significant reduction in CNV amplitude was observed in both the short-term (within the first session, after 10 minutes of GSR biofeedback) and long-term (sustained after 12 training sessions). Specifically, the change in baseline CNV amplitude after the 12 training sessions correlated with a percentage reduction in seizure frequency. Furthermore, changes in baseline amplitude of the PINV also correlated with seizure reduction. Our findings demonstrate that behavioral enhancement of peripheral sympathetic tone (GSR) is associated with modulation of indices of cortical excitability. Moreover, GSR biofeedback training over repeated sessions was associated with a chronic baseline reduction in slow cortical potentials and concurrent therapeutic improvement.

Exposure to uncontrollable stress and the postimperative negative variation (PINV): Prior control matters

The main goal of this study was to assess cortical functioning as indexed by the postimperative negative variation (PINV) induced by uncontrollable stress. Sixty-six persons were randomly assigned to three groups who underwent different sequences of stressor controllability. Within an S1–S2 paradigm, one group had initial control over aversive stimulation followed by loss of control and restitution of control. The other groups initially experienced either uncontrollability or controllability followed by a condition of control. Uncontrollable stress significantly enhanced PINV magnitudes independent of preceding control. However, control over aversive stimulation prior to loss of control normalized PINVs during restitution of control. Persons not experiencing prior control showed enhanced PINVs, longer reaction times, and more errors during restitution of control. We conclude that cortical activation changes are linked to the evaluation of instrumental contingencies. However, the exact determination of brain regions involved in the processing of uncontrollable stress needs further investigation.

Effects of stressor controllability on psychophysiological, cognitive and behavioural responses in patients with major depression and dysthymia

BackgroundThe experience of uncontrollability and helplessness in the face of stressful life events is regarded as an important determinant in the development and maintenance of depression. The inability to successfully deal with stressors might be linked to dysfunctional prefrontal functioning. We assessed cognitive, behavioural and physiological effects of stressor uncontrollability in depressed and healthy individuals. In addition, relationships between altered cortical processing and cognitive vulnerability traits of depression were analysed.MethodA total of 26 unmedicated depressed patients and 24 matched healthy controls were tested in an expanded forewarned reaction (S1–S2) paradigm. In a factorial design, stressor controllability varied across three consecutive conditions: (a) control, (b) loss of control and (c) restitution of control. Throughout the experiment, error rates, ratings of controllability, arousal, emotional valence and helplessness were assessed together with the post-imperative negative variation (PINV) of the electroencephalogram.ResultsDepressed participants showed an enhanced frontal PINV as an electrophysiological index of altered information processing during both loss of control and restitution of control. They also felt more helpless than controls. Furthermore, frontal PINV magnitudes were associated with habitual rumination in the depressed subsample.ConclusionsThese findings indicate that depressed patients are more susceptible to stressor uncontrollability than healthy subjects. Moreover, the experience of uncontrollability seems to bias subsequent information processing in a situation where control is objectively re-established. Alterations in prefrontal functioning appear to contribute to this vulnerability and are also linked to trait markers of depression.

Longitudinal Assessment of Response Preparation and Evaluation in Migraine Gives Evidence for Deviant Maturation

Evidence for deviant maturation of sensory processing in migraine has come recently from cross-sectional studies during childhood. Age-dependent development of response preparation and evaluation is characterized using a longitudinal design in school-aged migraine patients and controls in order to challenge the hypothesis of migraine as a maturation disorder. Forty-six children with migraine and 57 healthy controls aged 6-18 years were investigated and followed up 4 years later using a simple acoustic contingent negative variation (CNV) paradigm. Maturation in controls was characterized by increasing negativity of late and total CNV and stability of initial CNV (iCNV) and the motor postimperative negative variation (mPINV). Migraine patients showed a lack of development for late and total CNV and decreasing iCNV and mPINV negativity. This first longitudinal study confirms cross-sectional results of deviant CNV maturation in migraine. Altered maturation was not correlated with clinical improvement and may represent a vulnerability marker for migraine.

Anticipation of affect in dysthymia: Behavioral and neurophysiological indicators

Anticipation for future affective events and prediction uncertainty were examined in healthy controls and individuals with dysthymia (DYS) using behavioral responses and the contingent negative variation (CNV) and post-imperative negative variation (PINV) event-related potential (ERP) components. Warning stimuli forecasted the valence of subsequently presented adjectives (“+”, positive; “=”, neutral; “−”, negative), and participants indicated whether each adjective would describe them over the next two weeks. Controls expected fewer negative, and individuals with DYS expected fewer positive, adjectives to apply to them. CNV amplitudes were enhanced in controls prior to positive versus other adjectives. Response times and PINV amplitudes were greater following neutral compared to other adjectives, and PINV was larger overall in dysthymics compared to controls. In sum, healthy controls and individuals with DYS exhibit different behavioral and neurophysiological biases in anticipation for future affective events. These results are discussed in the context of cognitive theories of depression.

Central Mechanisms of Controlled-Release Metoprolol in Migraine: A Double-Blind, Placebo-Controlled Study

beta-Blockers are widely used in the prophylaxis of migraine and have been described as very effective drugs in many studies. Some investigators have demonstrated that the clinical improvement of migraine corresponds to the normalization of the contingent negative variation (CNV), a slow cortical potential measuring cortical information processing. However, most of these studies have contained a variety of methodological pitfalls, which we attempted to address in the current study. Twenty patients suffering from migraine without aura were randomly divided into two groups. The groups were treated either with controlled-release metoprolol or placebo for 3 months, using a double-blind design. Twice before and once after each month of the treatment the CNV was recorded. After 3 months, a significant reduction of migraine frequency, duration and intensity was demonstrated for the metoprolol compared with the placebo group. The CNV was characterized by a marked reduction of the amplitude of the total CNV and postimperative negative variation and normalization of the eartly CNV habituation following treatment. Therefore, metoprolol may exert its prophylactic effect in migraine through the influence on cortical information processing and excitability represented by the CNV.

Stereotyped topography of different elevated contingent negative variation components in children with migraine without aura points towards a subcortical dysfunction

Increased negativity during contingent negative variation (CNV) is thought to reflect abnormal neural activation in adult migraineurs’ attention related processing. Findings in childhood and adolescence have yielded less clear results. This study characterizes the age-dependent development of CNV topography in migraine during childhood in order to elucidate the origin and cerebral generators of described CNV elevations. A large sample of children with primary headache (migraine with/without aura, tension type headache) and healthy controls aged 6–18 years was examined in a CNV paradigm using 64-channel high resolution DC-EEG. Patients were tested for diagnose-related topographic group differences of initial CNV (iCNV), late CNV (lCNV) and postimperative negative variation (PINV). All three CNV components of 6–11-year-old migraineurs without aura showed elevated negativity over the supplementary motor area (SMA) and around the vertex. Migraine children lacked age-dependent development of late CNV around Cz as previously reported. However, they showed a normal development of late CNV over pre-/primary motor cortex (MI). There was no marked elevation of iCNV amplitude over frontal areas (orienting reaction) nor specific amplitude elevations over “motor” or “sensory” areas during sustained attention (late CNV). Additional “pre-mature” activation e.g., in the locus coeruleus (leading to diffuse cortical activation summing up to a maximum over the vertex) or the basal ganglia (interacting with SMA) explained the rather stereotyped CNV elevation around the vertex better than a specific implication of the cortical systems responsible for orienting, motor preparation or sensory attention.

Motor processing after movement execution as revealed by evoked and induced activity

Event-related synchronization (ERS) in the beta frequency band following movement execution has shown that motor processing is not completed yet when a movement ends. It is known that induced and evoked activities reflect different aspects of cortical processing which may result in different time courses. In the current study, we analyzed topography of postimperative negative variation (PINV) in 39 healthy right-handed adolescents in an acoustic forewarned reaction time (contingent negative variation, CNV) task using a 64-electrode high-density sensor array. We dissociated different PINV components in their time course from postmovement beta ERS in order to provide fundamental knowledge about evoked and induced EEG components after movement execution as a basis for further analysis of postmovement processing. A postmovement negativity occurred from about 500 to 1200 ms after the imperative stimulus (peaking about 600 ms after a right-hand button press) at central electrodes, contralateral to the response movement side. Current source density (CSD) analysis confirmed the current sinks over motor areas [contralateral primary motor/premotor and supplementary/cingulate motor area]. The described DC component (motor PINV, mPINV) differed in time course and localization from later “classical” PINV (cPINV) which is thought to reflect contingency reappraisal. mPINV could also be distinguished topographically from a mere delayed CNV resolution. When mPINV and ERS at the same left central electrode were compared, both parameters showed different time courses. Left central mPINV rather paralleled ERS at midcentral electrodes. Therefore, we suggest that the topography of mPINV provides first hints towards an involvement of contralateral primary motor cortex in postmovement processing beyond a mere idling state as reflected by later beta ERS. mPINV could be a useful tool to investigate the role of primary motor cortex in motor-learning processes. The combined analysis of induced and evoked activities seems to be able to elucidate different aspects of cortical connectivity and motor processes following movement.