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Selective microstimulation of central nervous system neurons.

The goal of this study was to identify stimulus parameters and electrode geometries that were effective in selectively stimulating targeted neuronal populations within the central nervous system (CNS). Cable models of neurons that included an axon, initial segment, soma, and branching dendritic tree, with geometries and membrane dynamics derived from mammalian motoneurons, were used to study excitation with extracellular electrodes. The models reproduced a wide range of experimentally documented excitation patterns including current-distance and strength-duration relationships. Evaluation of different stimulus paradigms was performed using populations of fifty cells and fifty fibers of passage randomly positioned about an extracellular electrode(s). Monophasic cathodic or anodic stimuli enabled selective stimulation of fibers over cells or cells over fibers, respectively. However, when a symmetrical charge-balancing stimulus phase was incorporated, selectivity was greatly diminished. An anodic first, cathodic second asymmetrical biphasic stimulus enabled selective stimulation of fibers, while a cathodic first, anodic second asymmetrical biphasic stimulus enabled selective stimulation of cells. These novel waveforms provided enhanced selectivity while preserving charge balancing as is required to minimize the risk of electrode corrosion and tissue injury. Furthermore, the models developed in this study can predict the effectiveness of electrode geometries and stimulus parameters for selective activation of specific neuronal populations, and in turn represent useful tools for the design of electrodes and stimulus waveforms for use in CNS neural prosthetic devices.

Animals↗

Regulation by Rab3A of an endogenous modulator of neurotransmitter release at mouse motor nerve endings.

Rab3A, a small GTP-binding protein attached to synaptic vesicles, has been implicated in several stages in the process of neurosecretion, including a late stage occurring just prior to the actual release of neurotransmitter. The inhibitory neuromodulator adenosine also targets a late step in the neurosecretory pathway. We thus compared neuromuscular junctions from adult Rab3A(-/-) mutant mice with those from wild-type mice with respect to: (a) the basic electrophysiological correlates of neurotransmitter release at different stimulation frequencies, and (b) the actions of exogenous and endogenous adenosine on neurotransmitter release in normal calcium solutions. Neither the spontaneous quantal release of acetylcholine (ACh) nor basal evoked ACh release (0.05 Hz) differed between the mutant and wild-type mice. At 50-100 Hz stimulation (10-19 stimuli), facilitation of release was observed in the mutant mice but not in wild-type, followed by a depression of ACh release in both strains. ACh release at the end of the stimulus train in the mutant mouse was approximately double that of the wild-type mouse. The threshold concentration for inhibition of ACh release by exogenous adenosine was over 20-fold lower in the mutant mouse than in the wild-type mouse. The adenosine A(1) receptor antagonist 8-cyclopentyltheophylline (CPT) increased ACh release (0.05-1 Hz stimulation) in the mutant mouse under conditions in which it had no effect in the wild-type mouse. CPT had no effect on the pattern of responses recorded during repetitive stimulation in either strain. The results suggest that Rab3A reduces the potency of adenosine as an endogenous mediator of neuromuscular depression.

Acetylcholine↗

Direct demonstration of the effects of repetitive transcranial magnetic stimulation on the excitability of the human motor cortex.

The effects of repetitive transcranial magnetic stimulation (rTMS; 20 stimuli at 5 Hz at 120% resting motor threshold intensity using a biphasic stimulus pulse) on the excitability of human motor cortex were investigated in two patients who had an electrode implanted into the cervical epidural space. The corticospinal D wave increased in amplitude with successive stimuli, and reached a maximum after three or five pulses. At this stage, the amplitude of the I waves was unchanged, but after a further 10 stimuli an additional I wave was recruited. Both effects were still evident 2 min after the end of the rTMS. The effects are compatible with a short-term increase in cortical excitability during suprathreshold rTMS.

Aged↗

What bilateral displays do.

Bilateral presentations of stimuli produce asymmetries larger than those of unilateral presentations, an effect that exists across modalities. In the case of visual field differences at least 13 hypotheses of the effect have been proposed, 6 of which suggest that some form of hemispheric interaction is responsible for the bilateral advantage. Previous research has eliminated all 7 noninteraction hypotheses, has supported the class of hemispheric interaction mechanisms, and has ruled out two specific instances of the latter. Here four experiments test the remaining hypotheses. The results support the homolog activation hypothesis, which states that bilateral stimulation by similar stimuli activates homologous areas of the two hemispheres, disrupting communication between the areas. The other hypotheses were eliminated.

Arousal↗

Biphasic cytokine expression by T cell clones from patients with atopic dermatitis with different incubation periods and strengths of stimuli.

It has been proposed that T helper (Th) 2 cells play a key role in the pathogenesis of atopic dermatitis (AD) because of clinical and experimental findings including hyper IgE, eosinophilia and Th2 type cytokine overexpression, etc. In contrast, several observations such as Th1 type cytokine detection in chronic lesions and histological features resembling allergic contact dermatitis suggest that Th1 rather than Th2 cells are important for the pathogenesis of skin lesions. In order to clarify this paradox, we investigated the function of T cell clones established from AD patients. Most T cell clones induced by house dust mite antigen and interleukin (IL)-2 from peripheral blood mononuclear cells of two AD patients exhibited CD4+/ CD8-, CD45RO+/ CD45RA-, and produced high levels of IL-4 and low levels of interferon-gamma (IFN-gamma) after phytohemagglutinin (PHA) (1 microg/ml) stimulation, suggesting a Th2 subtype. When stimulated with a high dose of concanavalin A (conA) (10 microg/ml), however, these clones produced high amounts of IFN-gamma. IL-4 production reached a peak 24 hours after conA (10 ,g/ml) stimulation, whereas IFN-gamma production was increased up to 48 hours after stimulation. The findings of T cell receptor (TCR) stimulation with immobilized anti-CD3 monoclonal antibody (mAb) showed that the suitable strength of TCR stimulation for IFN-y production was higher than for IL-4. Also, in the TCR stimulated condition, the peak of IFN-gamma production was later than that of IL-4. These results indicate that T cell clones which exhibited a Th2 profile under weak stimulation can produce IFN-y in the late phase of stimulation when strong stimuli are used. The results are consistent with the previous observation that IFN-gamma production prominently appears in the chronic and late phase lesions of AD.

Adolescent↗

Exercise-induced alterations in neutrophil degranulation and respiratory burst activity: possible mechanisms of action.

Neutrophils constitute 50-60% of all circulating leukocytes; they present the first line of microbicidal defense and are involved in inflammatory responses. To examine immunocompetence in athletes, numerous studies have investigated the effects of exercise on the number of circulating neutrophils and their response to stimulation by chemotactic stimuli and activating factors. Exercise causes a biphasic increase in the number of neutrophils in the blood, arising from increases in catecholamine and cortisol concentrations. Moderate intensity exercise may enhance neutrophil respiratory burst activity, possibly through increases in the concentrations of growth hormone and the inflammatory cytokine IL-6. In contrast, intense or long duration exercise may suppress neutrophil degranulation and the production of reactive oxidants via elevated circulating concentrations of epinephrine (adrenaline) and cortisol. There is evidence of neutrophil degranulation and activation of the respiratory burst following exercise-induced muscle damage. In principle, improved responsiveness of neutrophils to stimulation following exercise of moderate intensity could mean that individuals participating in moderate exercise may have improved resistance to infection. Conversely, competitive athletes undertaking regular intense exercise may be at greater risk of contracting illness. However, there are limited data to support this concept. To elucidate the cellular mechanisms involved in the neutrophil responses to exercise, researchers have examined changes in the expression of cell membrane receptors, the production and release of reactive oxidants and more recently, calcium signaling. The investigation of possible modifications of other signal transduction events following exercise has not been possible because of current methodological limitations. At present, variation in exercise-induced alterations in neutrophil function appears to be due to differences in exercise protocols, training status, sampling points and laboratory assay techniques.

Cell Degranulation↗

The effect of muscimol micro-injections into the fastigial nucleus on the optokinetic response and the vestibulo-ocular reflex in the alert monkey.

Eye movements of four macaque monkeys were investigated after unilateral micro-injections of the GABA agonist muscimol (1 microgram in 1 microliter NaCl) into the caudal fastigial nucleus, i.e. the fastigial oculomotor region. Spontaneous eye movements in the dark and in the light were tested, as well as those evoked by vestibular stimulation in the dark (sinusoidal: 0.1-0.2 Hz, +/- 40-100 deg/s, velocity trapezoid acceleration 40 deg/s2, constant velocity 120 deg/s), optokinetic stimulation (sinusoidal: 0.1-0.2 Hz, +/- 40-100 deg/s, constant velocity 60-100 deg/s), and visual-vestibular conflict stimulation. With these stimuli, smooth pursuit mechanisms (fast build-up of optokinetic slow phase velocity), the vestibulo-ocular reflex (VOR) and the velocity storage mechanism were investigated. Muscimol injections consistently led to specific eye movement changes which were maximal 30-60 min after the injection and lasted 4-6 h. The fast initial rise of OKN slow phase velocity to the contralateral side decreased by 45% (range 24%-82%) of its pre-injection value, while it was virtually unaltered on the ipsilateral side (average decrease of 1%, range from a decrease of 20% to an increase of 32%). For conflict ramp stimulation, the suppression of vestibular nystagmus was less (decrease of 50%, range 12-82%) towards the contralateral side while it remained unchanged on the ipsilateral side. The VOR in the dark and the velocity storage mechanism were not altered. For the latter, the slow build-up of optokinetic nystagmus velocity, the optokinetic afternystagmus (OKAN) and the time constant of decay for the vestibular nystagmus were evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of phospholipases A(2) in growth-dependent changes in prostaglandin release from 3T6 fibroblasts.

Previously, we reported a growth-dependent change in prostaglandin production as a consequence of a marked growth-dependent alteration in arachidonic acid (AA) mobilization from phospholipids. Our present results show that fetal calf serum (FCS) and 4 beta-phorbol-12-myristate acetate (PMA) caused an enhancement of phospholipase A(2) (PLA(2)) activity in the membrane fraction of non-confluent cells allowing PLA(2) access to its substrate and the release of AA. Western blot analysis has shown that FCS and PMA increased secreted PLA(2) (sPLA(2)) expression in non-confluent 3T6 fibroblast cultures. Moreover, FCS and PMA induced dithiothreitol-sensitive and bromoenol lactone-sensitive PLA(2) activities in cytosol and membrane fraction. However, these stimuli did not modify significantly the PLA(2) activity in both fractions when 3T6 fibroblasts reached a high cell density. This could be associated with the impairment of AA mobilization in these cell culture conditions. On the other hand, we observed that FCS and PMA induced the same prostaglandin H synthase-2 induction in non-confluent and confluent culture conditions. Moreover, the prostaglandin E(2) levels reached in cell culture supernatants were independent of the degree of confluence when AA was added exogenously. These results suggest that the changes of intracellular distribution of PLA(2) activity of sPLA(2) and iPLA(2) stimulated by exogenous stimuli may be controlled by cell density conditions which constitute an important mechanism in the regulation of prostaglandin release.

Animals↗

Blockade and recovery of cholinergic transmission in rats treated with hemicholinium 3.

Nerve-induced responses of parotid gland and gastrocnemius muscle were reduced by HC-3 (1 mg kg-1) in proportion to the number of stimuli. Contractions by somatic muscle at 100 Hz were abolished after 6.0 X 10(3) stimuli while 14 X 10(3) were applied at 20 Hz before secretion was blocked. As stimulus rate was decreased, blockade of secretion resulted from fewer stimuli but no difference in ACh content was found between stimulated and unstimulated glands. When stimuli were withheld for 1.5 h transmission recovered temporarily; initial secretory flow rate was only 50% of that in untreated controls when stimulation resumed. In both organs, the time during which responses were sustained, however, was much shorter than when the preparations were stimulated initially. After choline, recovery of transmission was dose-dependent: 150 mg kg-1 were required to restore responsiveness to the muscle and the gland comparable to that in HC-3-treated rats stimulated for the first time. Resting recovery, when stimuli are withheld, probably depends upon stored transmitter becoming mobilized rather than on de novo transmitter synthesis because the endogenous choline in plasma is only 1/1000 of that following exogenous choline.

Acetylcholine↗

Long-term potentiation induced by theta frequency stimulation is regulated by a protein phosphatase-1-operated gate.

Long-term potentiation (LTP) can be induced in the Schaffer collateral-->CA1 synapse of hippocampus by stimulation in the theta frequency range (5-12 Hz), an effect that depends on activation of the cAMP pathway. We investigated the mechanisms of the cAMP contribution to this form of LTP in the rat hippocampal slice preparation. theta pulse stimulation (TPS; 150 stimuli at 10 Hz) by itself did not induce LTP, but the addition of either the beta-adrenergic agonist isoproterenol or the cAMP analog 8-bromo-cAMP (8-Br-cAMP) enabled TPS-induced LTP. The isoproterenol effect was blocked by postsynaptic inhibition of cAMP-dependent protein kinase. Several lines of evidence indicated that cAMP enabled LTP by blocking postsynaptic protein phosphatase-1 (PP1). Activators of the cAMP pathway reduced PP1 activity in the CA1 region and increased the active form of inhibitor-1, an endogenous inhibitor of PP1. Postsynaptic injection of activated inhibitor-1 mimicked the LTP-enabling effect of cAMP pathway stimulation. TPS evoked complex spiking when isoproterenol was present. However, complex spiking was not sufficient to enable TPS-induced LTP, which additionally required the inhibition of postsynaptic PP1. PP1 inhibition seems to promote the activation of Ca(2+)/calmodulin-dependent protein kinase (CaMKII), because (1) a CaMKII inhibitor blocked the induction of LTP by TPS paired with either isoproterenol or activated inhibitor-1 and (2) CaMKII in area CA1 was activated by the combination of TPS and 8-Br-cAMP but not by either stimulus alone. These results indicate that the cAMP pathway enables TPS-induced LTP by inhibiting PP1, thereby enhancing Ca(2+)-independent CaMKII activity.

8-Bromo Cyclic Adenosine Monophosphate↗

An approach to probe some neural systems interaction by functional MRI at neural time scale down to milliseconds.

In this paper, we demonstrate an approach by which some evoked neuronal events can be probed by functional MRI (fMRI) signal with temporal resolution at the time scale of tens of milliseconds. The approach is based on the close relationship between neuronal electrical events and fMRI signal that is experimentally demonstrated in concurrent fMRI and electroencephalographic (EEG) studies conducted in a rat model with forepaw electrical stimulation. We observed a refractory period of neuronal origin in a two-stimuli paradigm: the first stimulation pulse suppressed the evoked activity in both EEG and fMRI signal responding to the subsequent stimulus for a period of several hundred milliseconds. When there was an apparent site-site interaction detected in the evoked EEG signal induced by two stimuli that were primarily targeted to activate two different sites in the brain, fMRI also displayed signal amplitude modulation because of the interactive event. With visual stimulation using two short pulses in the human brain, a similar refractory phenomenon was observed in activated fMRI signals in the primary visual cortex. In addition, for interstimulus intervals shorter than the known latency time of the evoked potential induced by the first stimulus ( approximately 100 ms) in the primary visual cortex of the human brain, the suppression was not present. Thus, by controlling the temporal relation of input tasks, it is possible to study temporal evolution of certain neural events at the time scale of their evoked electrical activity by noninvasive fMRI methodology.

Animals↗

Significance of ventricular arrhythmias initiated by programmed ventricular stimulation: the importance of the type of ventricular arrhythmia induced and the number of premature stimuli required.

An increasing number of premature ventricular stimuli are being used during programmed stimulation of the heart in the investigation of patients with documented or suspected ventricular arrhythmias. To analyze the significance of the different types of ventricular arrhythmias that are initiated, we evaluated in a prospective study the effect of from one to four ventricular premature stimuli in 52 patients without (non-VT group) and 50 patients with (prior-VT group) documented ventricular tachycardia or ventricular fibrillation. More than half of the patients in the prior-VT group had coronary heart disease. In the majority of patients of the non-VT group the heart was normal. In 44 of the 50 patients in the prior-VT group the clinically documented ventricular arrhythmia was initiated by programmed ventricular stimulation of the heart. In 88% of these 44 patients, one or two ventricular premature beats were required to initiate the clinical arrhythmia. A ventricular arrhythmia could be initiated in 31 of the 52 patients in the non-VT group. The ventricular arrhythmias included nonsustained monomorphic ventricular tachycardia (two patients), six to 25 complexes of sustained polymorphic ventricular tachycardia (24 patients), and ventricular fibrillation (five patients). In 70% of patients in the non-VT group three or four ventricular premature beats were required to initiate the ventricular arrhythmia. Our results indicate that not only the number of extrastimuli required to initiate ventricular arrhythmias but also the type of ventricular arrhythmia initiated differed between the two groups of patients. Nonsustained polymorphic ventricular tachycardia and ventricular fibrillation are nonspecific responses to aggressive stimulation protocols.

Adolescent↗

Osmotic inhibition of prolactin secretion in rats.

Chronic hyponatremia is known to cause inhibition of pituitary vasopressin (AVP) and oxytocin (OT) secretion in response to most physiological stimuli, as well as a marked inhibition of synthesis of these peptides. Because many studies have implicated neurohypophyseal peptides in the regulation of pituitary prolactin (PRL) secretion, we investigated the effects of chronic hyponatremia on basal and stimulus-induced PRL secretion in rats. Hyponatremia was induced by subcutaneous infusion of 1-deamino-[8-D-arginine]-vasopressin (dDAVP) (5 ng/h) to rats fed a nutritionally balanced liquid diet, and plasma [Na+] was maintained < or = 115 mmol/l for 10-12 days. After this period, hyponatremic rats and normonatremic controls fed the same diet without dDAVP were subjected to one of the following stimuli known to stimulate PRL release in rats: 3 min exposure to ether, hemorrhage (20 ml/kg), intravenous injection of 5-hydroxytryptophane (5-HTP, 10 mg/kg), or intravenous injection of estradiol (5 micrograms/kg). A baseline blood sample was collected before each stimulus, and 3-6 additional blood samples were collected at selected intervals after the stimulus. Baseline levels of plasma PRL were not different between normonatremic and hyponatremic rats. However, PRL responses induced by either or estradiol, but not those induced by hemorrhage or 5-HTP, were very significantly blunted in the chronically hyponatremic rats. Plasma AVP and OT responses were measured as an index of magnocellular secretion, but did not correlate with the PRL responses for any of the stimuli tested.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗

The induction of homo- vs. heterosynaptic LTD in area CA1 of hippocampal slices from adult rats.

The induction of long-term depression (LTD) was investigated in area CA1 of hippocampal slices from adult rats. To produce LTD, prolonged low-frequency stimulation (LFS, 900 stimuli at 1 Hz) was delivered to one of two independent Schaffer-collateral/commissural projections, while the second input served as a control to monitor heterosynaptic effects. The depression was calculated as percent decrease in the slope of the dendritic field EPSP relative to baseline values, and LTD was considered established if the response decrement was at least 15% in magnitude and stable for 30-60 min. By delivering LFS in conditions of different relative baseline response magnitudes, it was revealed that the intensity of afferent low-frequency activity has a significant impact on the induction frequency, magnitude and input-specificity of the depression: the rate of LTD occurrence and the effect of LFS on the absolute response decrement increased successively as the stimulation strength was raised, but the impact of LFS on the relative LTD magnitude decreased at higher stimulation intensities; the depression was specific to the stimulated input (homosynaptic LTD) when baseline responses were spike-free, but spread to the pathway which was silent during LFS (heterosynaptic LTD) in experiments conducted above spiking threshold. The results indicate that in the adult rat (i) the induction of input-specific LTD is dependent on the level of synaptic activation during LFS, and (ii) LTD can easily be obtained in strongly stimulated pathways but may be the result of a generalized decrease in the postsynaptic response.

Animals↗

Temporal facilitation of the flexor reflex induced by C-fiber activity: comparison between adult and aged rats.

We investigated the wind-up phenomenon of the flexor reflex in adult and aged rats. The sural nerve was stimulated at C-fiber strength and reflex activity was recorded from the semitendinosus muscle. The wind-up rate, the increment rate of the C-fiber response (i.e. activity from 100 to 600 ms after stimulation) by successive stimuli (five train pulses), was decreased exponentially with increasing stimulus intervals from 3 to 20 s. The time constant of the decay for the aged rats was 9.2+/-3.2 s (mean+/-SD), which was significantly longer than for the adult rats (6.4+/-2.9 s). The findings indicate that the effects of C-fiber activation on the spinal nociceptive pathways attenuate more slowly in aged rats as compared with adult rats.

Action Potentials↗

Neuromuscular and biomechanical coupling in human cycling: modulation of cutaneous reflex responses to sural nerve stimulation.

This study tested the hypothesis that the modulation of cutaneous reflexes during human cycling would be dependent on muscle biomechanical function and phase of leg movement. The coupling between neuromuscular (electromyographic, EMG), kinetic and kinematic responses to brief innocuous (75% of the pain threshold PnT) and noxious (125% PnT) sural nerve stimulation were studied. Stimuli were delivered pseudorandomly at eight equidistant (45 degrees) positions of the crank cycle. Peak ipsilateral middle latency EMG reflex responses were calculated between 70 and 130 ms post stimulus in Biceps Femoris (BF), Rectus Femoris (RF), Tibialis Anterior (TA) and Soleus (SOL). Peak torque, knee and ankle joint angle changes were calculated between 140 and 220 ms post stimulus to quantify net kinetic and kinematic reflex modulation. Reflex responses were predominately suppressive during early activation of all muscles and facilitatory during BF and TA muscle inactivation. EMG reflex responses in monoarticular lower leg muscles TA and SOL were well correlated with ankle angle in dorsi/plantaflexion, whereas the correlation between reflex modulation in biarticular upper leg muscles (BF and RF) and knee angle changes in flexion/extension was weaker. Stimulation provoked significant ankle eversion over the whole crank cycle for both stimulus intensities, which was correlated with TA and BF EMG reflex responses. Torque modulation followed EMG and kinematic changes in a movement phase-dependent manner. Reflex magnitude was stimulation intensity-dependent. Supplementary nociceptive activation may contribute for this increase. We conclude that sural nerve stimulation during human cycling evokes distinct reflex responses in muscles operating around the knee (BF and RF) and the ankle (TA and SOL). These reflexes are modulated in a phase-dependent manner depending on muscle biomechanical function to generate energy for limb and crank propulsion during a specific region in the cycle. This modulation contributed to a specific adaptation of joint motion and force production in order to maintain task performance.

Adult↗

Brain processing of visual sexual stimuli in healthy men: a functional magnetic resonance imaging study.

The brain plays a central role in sexual motivation. To identify cerebral areas whose activation was correlated with sexual desire, eight healthy male volunteers were studied with functional magnetic resonance imaging (fMRI). Visual stimuli were sexually stimulating photographs (S condition) and emotionally neutral photographs (N condition). Subjective responses pertaining to sexual desire were recorded after each condition. To image the entire brain, separate runs focused on the upper and the lower parts of the brain. Statistical Parametric Mapping was used for data analysis. Subjective ratings confirmed that sexual pictures effectively induced sexual arousal. In the S condition compared to the N condition, a group analysis conducted on the upper part of the brain demonstrated an increased signal in the parietal lobes (superior parietal lobules, left intraparietal sulcus, left inferior parietal lobule, and right postcentral gyrus), the right parietooccipital sulcus, the left superior occipital gyrus, and the precentral gyri. In addition, a decreased signal was recorded in the right posterior cingulate gyrus and the left precuneus. In individual analyses conducted on the lower part of the brain, an increased signal was found in the right and/or left middle occipital gyrus in seven subjects, and in the right and/or left fusiform gyrus in six subjects. In conclusion, fMRI allows to identify brain responses to visual sexual stimuli. Among activated regions in the S condition, parietal areas are known to be involved in attentional processes directed toward motivationally relevant stimuli, while frontal premotor areas have been implicated in motor preparation and motor imagery. Further work is needed to identify those specific features of the neural responses that distinguish sexual desire from other emotional and motivational states.

Adult↗

Responses to positive and negative smoking-related images: effects of current smoking status and degree of smoking addiction.

The literature indicates that stimulant users of various dependency levels endorse and react differently to stimuli that portray the stimulant either positively or negatively, however these studies have not been extended to smoking. Here pictures are used to depict either positive or negative connotations of smoking. The current study concentrated on smokers with different levels of dependency. Seventy-three digital images were rated on both a smoking and emotional content scale. The pictures were rank ordered, yielding the 10 most positive and negative smoking-related pictures. Emotional content scores for these pictures were also recorded. Data from 148 subjects [light- (n=28), heavy- (n=17), ex- (n=32) and never-smokers (n=71)] were analysed. Using a mixed factorial ANOVA light- and heavy-smokers were found to score positive pictures significantly more positive than the never-smokers, they did not vary on negative or emotional ratings. Thus positive pictures did not distinguish heavy and light levels of substance use as suggested by the literature and this was not influenced by emotional content.

Adult↗