Orienting responses and habituation among persons with traumatic brain injury: distinctive aspects of apathetic and disinhibited behaviours.

PURPOSE: This study focused on basic attentional impairments among persons with TBI who were behaviourally evaluated as suffering from either apathetic or disinhibition symptoms. METHODS: Differences in orienting responses (ORs) and habituation rates were examined between patients (n = 18) and controls (n = 18) and between two TBI sub-groups: Apathetic (n = 9) and disinhibited patients (n = 9). Skin conductance responses were used to measure ORs and habituation rates. RESULTS: The results revealed that the TBI patients did not differ from the control group in their ORs and habituation rate. However, marked differences emerged between the two TBI sub-groups. Apathetic patients presented attenuated ORs and more rapid habituation as compared to disinhibited patients. The findings indicate that when examining attentional impairments in the TBI population, different attentional patterns may counterbalance each other. CONCLUSION: As a result, the performance of the entire group may not adequately reflect the basic attentional impairments of its members. The study of attention deficits may benefit from consideration of systematic neuro-pathological differences within the TBI population.

Serum levels of sex hormones and corticosterone throughout 4- and 5-day estrous cycles in Fischer 344 rats and their simulation in ovariectomized females.

Among inbred strains of rats, the Fischer 344 (F344) is commonly used in immunological and behavioral studies. However, little is known about patterns of sex hormones and corticosterone (CORT) secretion throughout the estrous cycle in this strain, which is characterized by a marked CORT response to stress and variable length of cycles. In the current study, using radioimmunoassays, we assessed serum levels of progesterone, estradiol, LH, testosterone, prolactin and CORT, at 1-h intervals throughout the estrous cycle in F344 female rats with 4- and 5-day cycles, as well as in males. Vaginal smears were obtained from 268 females for 15 consecutive days to determine individual length of the estrous cycle and the exact estrous phase upon blood withdrawal, which was conducted once in each rat on the 12th day of smearing. The results indicated that both 4- and 5-day cyclers have two distinct and marked surges of progesterone, one on proestrus day and the other on diestrous-1 day. Testosterone levels in 5-day cyclers peaked on diestrus-3, one day earlier than in 4-day cyclers. Daily peak levels of CORT gradually increased from estrus day to proestrous day, whereas daily nadir levels of CORT remained unchanged. To simulate the natural kinetics of specific sex hormones in ovariectomized females, different doses of estradiol, progesterone, testosterone, prolactin or CORT were injected s.c. or i.p., or 90-day sustained release pellets containing different doses of estradiol or progesterone were implanted. The findings indicated dose- and time-dependent effects, suggesting regimens for modeling the estrous cycle or replacement therapy.

Diurnal changes in lung tumor clearance and their relation to NK cell cytotoxicity in the blood and spleen.

Natural killer cell cytotoxicity (NKCC) was reported to manifest a circadian rhythm, peaking during wakefulness in both human blood and rat spleen. Using F344 rats, we investigated whether such fluctuations (i) reflect changes in NK cell numbers or in cytotoxicity per cell; (ii) coincide in the blood and spleen; (iii) correspond with clearance of NK-sensitive tumor cells from the lungs and (iv) influence formation of lung metastases. Two rat groups were housed in opposite 12:12 hr lighting regimens. Two hours after the onset of light or dark, both groups were either sacrificed or intravenously inoculated with tumor cells to study the following indices: NKCC and NK cell numbers in the spleen (n = 29) and blood (n = 79), lung clearance of tumor cells (n = 142) and lung metastasis (n = 69). The tumor employed, MADB106, is an NK-sensitive mammary adenocarcinoma that metastasizes only to the lungs. The results indicated that, during the dark phase, splenic NKCC increased (37% higher lytic unit [LU](50)) mostly due to a 28.9% higher percentage of NK cells in the spleen. In contrast, blood NKCC decreased by 42.5% (LU(20)) and this decline was independent of circulating NK cell numbers, which remained constant. Lung tumor clearance increased in the dark (up to 42% lower retention 9 hr after inoculation), but no corresponding changes in the number of metastases were observed 3 weeks later. We conclude that diurnal changes in rats' NKCC are organ-specific, involve changes in both cell distribution and activity and may affect short-term in vivo indices of NK tumoricidal activity.

Attenuation of the tumor-promoting effect of surgery by spinal blockade in rats.

BACKGROUND: The perioperative period is characterized by a state of immunosuppression, which was shown in animal studies to underlie the promotion of tumor metastasis by surgery. As this immunosuppression is partly ascribed to the neuroendocrine stress response, the authors hypothesized that spinal blockade, known to attenuate this response, may reduce the tumor-promoting effect of surgery. METHODS: Fischer-344 rats were subjected to a laparotomy during general halothane anesthesia alone or combined with either systemic morphine (10 mg/kg) or spinal block using bupivacaine (50 microg) with morphine (10 microg). Control groups were either anesthetized or undisturbed. Blood was drawn 5 h after surgery to assess number and activity of natural killer cells, or rats were inoculated intravenously with MADB106 adenocarcinoma cells, which metastasize only to the lungs. Metastatic development was assessed by quantifying lung retention of tumor cells 24 h after inoculation or by counting pulmonary metastases 3 weeks later. RESULTS: Laparotomy conducted during general anesthesia alone increased lung tumor retention up to 17-fold. The addition of spinal block reduced this effect by 70%. The number of metastases increased from 16.7 +/- 10.5 (mean +/- SD) in the control group to 37.2 +/- 24.4 after surgery and was reduced to 10.5 +/- 4.7 during spinal block. Systemic morphine also reduced the effects of surgery, but to a lesser degree. Natural killer cell activity was suppressed to a similar extent by surgery and by anesthesia alone. CONCLUSIONS: The addition of spinal blockade to general halothane anesthesia markedly attenuates the promotion of metastasis by surgery.

Suppression of NK cell activity and of resistance to metastasis by stress: a role for adrenal catecholamines and beta-adrenoceptors.

Although acute stress has been reported to suppress natural killer cell activity (NKA) and host resistance to metastasis, it is unclear whether the sympathetic nervous system (SNS) has a role in these effects. The current study in Fischer 344 rats assessed the involvement of adrenal catecholamines and beta(1)- and beta(2)-adrenoceptors in mediating these deleterious effects of swim stress. In addition to assessing the number and activity of NK cells following swim stress, we used a tumor model based on the MADB106 mammary adenocarcinoma line: this syngeneic tumor metastasizes only to the lungs, and its lung tumor retention (LTR) and metastatic colonization are highly sensitive to NKA. The findings indicate that stress increased both LTR, assessed 24 h after inoculation, and the number of lung metastases, counted 3 weeks later. These effects were attenuated or completely abolished by the ganglionic blocker chlorisondamine (3 mg/kg i.p.), by adrenal demedullation, by a selective beta-adrenergic antagonist (nadolol, 0.4 mg/kg), and additively by a selective beta(1)- (atenolol, 1-6 mg/kg) and a selective beta(2)-antagonist (either butoxamine 4-32 mg/kg or ICI-118,551 0.3-8 mg/kg). Stress also suppressed NKA, and adrenal demedullation prevented this suppression. Administration of adrenaline (0.1-1 mg/kg) or of a beta-adrenergic agonist (metaproterenol, 0.8 mg/kg), in physiologically relevant doses, suppressed NKA in a dose-dependent manner, and increased LTR to levels characteristic of swim stress. Taken together, these findings suggest that acute stress, by releasing catecholamines from the adrenal glands and activating beta(1)- and beta(2)-adrenoceptors, suppresses NKA and consequently compromises resistance to NK-sensitive metastasis.

Timing within the menstrual cycle, sex, and the use of oral contraceptives determine adrenergic suppression of NK cell activity.

Physiological responses that involve adrenergic mechanisms, such as stress-induced changes in cardiovascular indices, were reported to fluctuate along the menstrual cycle. Metastatic development following surgery was also reported to vary according to the menstrual phase during which a primary breast tumour was removed. Natural killer (NK) cells are believed to play an important role in controlling metastases. Our recent studies in rats demonstrated that adrenergic suppression of NK activity and of resistance to metastasis is more profound during oestrous phases characterized by high levels of oestradiol. In the current study in humans, we examined the in vitro impact of a beta-adrenergic agonist, metaproterenol (MP), on NK activity, comparing blood drawn from (a) women tested at 3-4 different phases of their menstrual cycle (n = 10), (b) women using oral contraceptives (OC) (n = 10), and (c) men (n = 7). NK activity in each blood sample was assessed in the presence of 5 different concentrations of MP (10(-8)M to 10(-6)M), and in its absence (baseline). The results indicated marked group differences in the magnitude of NK suppression by MP: EC(50)was 2. 6-fold lower in the luteal phase compared to the follicular phase, and 1.8-fold lower in OC users compared to men, who were least susceptible to the effects of MP. No significant group differences or menstrual effects in baseline levels of NK activity were evident. These findings provide the first empirical evidence for menstrual regulation of adrenergic impact on cellular immune competence. Relevance of these findings to the relation between the timing of breast cancer excision within the menstrual cycle and survival rates is discussed.

Timing within the oestrous cycle modulates adrenergic suppression of NK activity and resistance to metastasis: possible clinical implications.

Clinical observations suggest that the rate of metastatic development and long-term mortality following surgery in breast cancer patients is influenced by the menstrual phase during which surgery is conducted. The menstrual cycle is known to modulate various physiological responses and medical conditions that involve adrenergic mechanisms (e.g., asthma). Natural killer activity (NKA), an immune function controlling metastasis, is suppressed following surgery, and in vitro by adrenaline. We therefore hypothesize that the clinical observation may be partly attributable to surgery-induced adrenergic suppression of NK-dependent resistance to metastasis, a suppression that depends on menstrual phase during surgery. To test this hypothesis in rats, 140 F344 females at different phases of their oestrous cycle were injected with a beta-adrenergic agonist, metaproterenol (MP) (0.4 or 0.8 mg kg(-1), s.c.), or with vehicle, before i.v. inoculation with MADB106 tumour cells. This syngeneic mammary adenocarcinoma line metastasizes only to the lungs, and is highly sensitive to NKA. In a second experiment, the suppression of NKA by MP was studied in vitro in blood drawn at different phases of the oestrous cycle (n = 36). Finally, the effects of stress on the number and activity of NK cells were assessed along the oestrous cycle (n = 71). The findings indicate that the suppressive effects of MP on resistance to metastasis and on NKA, are significantly greater during the oestrous phase characterized by high oestradiol levels (D3/proestrus/oestrus). Similarly, NKA per cell was suppressed by stress only during this phase. In untreated animals, in which inadvertent stress was minimized, no effects of the oestrous cycle on NKA or on resistance to metastasis were evident. These findings indicate that the oestrous cycle modulates adrenergic suppression of NKA and of resistance to metastasis. The relevance of these findings to the above clinical observation, as well as that of our related findings in women from a parallel study, is discussed.

Higher natural killer cell activity in schizophrenic patients: the impact of serum factors, medication, and smoking.

Schizophrenia has been associated with altered immunity and reduced occurrence of autoimmune diseases and malignancies. A few studies in schizophrenic patients have assessed natural killer cell activity (NKA), but no consistent findings have emerged. However, NKA was assessed using standard procedures and in the absence of autologous serum and the various cytokines that modulate NKA and appear to be abnormal in schizophrenic patients. In the current study, therefore, the number of NK cells and the activity of the individual NK cell were assessed in whole blood shortly after blood withdrawal, in both the presence and the absence of autologous serum. Twenty-nine schizophrenic patients (11 nonmedicated), 8 nonschizophrenic control patients (bipolar and personality disorders), and 31 age-matched healthy controls were studied. Schizophrenic patients showed higher NKA per NK cell than controls and nonschizophrenic patients. This difference remained significant even when the nonmedicated schizophrenics, who showed the highest levels of NKA, were excluded. However, the increase in NKA was more pronounced in the presence of serum and was reduced to an insignificant level when serum was removed from the same samples. In both schizophrenic patients and controls, smokers and women showed lower NKA. Numbers of NK cells did not differ among groups, although medication affected blood concentration of other leukocytes. These findings indicate that the effects of serum factors, psychiatric medication, gender, and smoking should be considered when assessing NKA in schizophrenic patients. The observed higher NKA may help explain the surprising reports of low incidence of lung cancer and other malignancies in schizophrenic patients, despite their higher rate of smoking.

Orienting response reinstatement and dishabituation: effects of substituting, adding, and deleting components of nonsignificant stimuli.

The prediction that orienting response (OR) reinstatement is negatively related to the measure of common features, shared by the stimulus input and representations of preceding events, and positively related to the measure of their distinctive features, was examined. A nonsignificant test stimulus (TS) was presented after nine repetitions of a standard stimulus (SS), followed by two additional repetitions of SS. TS was created by either substituting 0, 1, or 2 components of SS (Experiment 1), or by either adding or deleting 0, 1, or 2 components of SS (Experiment 2). Skin conductance changes to TS (OR reinstatement) and the subsequent SS (dishabituation) were used as dependent measures. The results of Experiment 1 supported the prediction that substituting components of neutral stimuli affects OR reinstatement, with a larger effect for between-categories than within-categories substitution. Experiment 2 demonstrated that adding and deleting components similarly affects OR reinstatement.

Psychophysiologic assessment of aversive conditioning in posttraumatic stress disorder.

BACKGROUND: The objective of this study was to evaluate the acquisition, generalization, and extinction of conditioned physiologic responses to aversive stimuli in posttraumatic stress disorder (PTSD). METHODS: Thirty-six PTSD patients, 20 individuals with past trauma and no current PTSD, and 30 mentally healthy individuals without exposure to major trauma underwent a differential aversive conditioning experiment. Bursts of 105 dB white noise were used as unconditioned stimuli (UCSs), and 35x24 mm slides of different colors served as either CS+ (paired) or CS- (unpaired) stimuli. Heart rate (HR) and nondominant palm skin conductance (SC) were measured at rest and between 1 and 4 sec following each CS presentation. RESULTS: The PTSD group showed higher levels of resting SC and resting HR, larger SC responses to the initial presentation of unpaired CSs, larger HR responses following paired CS+ stimuli, larger SC responses to unpaired CS- during acquisition and extinction, and larger SC and HR responses to CS+ during extinction. The group differences in responses to CS+ during extinction remained statistically significant after controlling for age, resting physiologic levels, and initial responsivity. CONCLUSIONS: PTSD is associated with elevated autonomic responses to both innocuous and aversive stimuli, with larger responses to unpaired cues and with reduced extinction of conditioned responses.

Hypothermia in barbiturate-anesthetized rats suppresses natural killer cell activity and compromises resistance to tumor metastasis: a role for adrenergic mechanisms.

BACKGROUND: Clinical studies have implicated surgery in promoting infections and compromising immune functions, including natural killer cell activity. Animal studies indicate that surgery-induced suppression of natural killer cell activity also promotes tumor metastasis. Hypothermia, a common surgical complication, has been suggested to underlie some of the deleterious consequences of surgery. This study evaluated the effect of hypothermia on the activity and number of blood natural killer cells and on host susceptibility to metastasis. The involvement of adrenergic mechanisms was also considered. METHODS: Fischer-344 rats remained awake in their cages (control group) or were anesthetized with 70 mg/kg thiopental and maintained for 2.5 h at core body temperatures of 30-32 degrees C (hypothermia group) or 38 degrees C (normothermia group). Thereafter, at several time points, blood was drawn so natural killer cell activity could be assessed, or rats were injected with syngeneic MADB106 tumor cells that metastasize only to the lungs. Lungs were removed 9 h later for assessment of lung tumor retention, or 4 weeks later for counting of metastases. RESULTS: Normothermic anesthesia reduced natural killer cell activity (lytic units at 30% specific killing, mean +/- SEM) to 39+/-6.2% of control levels and hypothermia further reduced it to 15+/-6.6%. These changes were not accompanied by alterations in the numbers of circulating natural killer cells. Hypothermia increased tumor retention to 250% of control levels, and the number of metastases increased from 1.1+/-0.4 to 4.7+/-1.2. Normothermia had no significant effects on this index. Nadolol (0.4 mg/kg), a beta-adrenergic antagonist, significantly attenuated the effect of hypothermia on tumor retention. CONCLUSIONS: Hypothermia under thiopental anesthesia suppresses natural killer cell activity and compromises host resistance to metastatic formation, possibly via adrenergic mechanisms. Such suppression may place patients with metastasizing tumors or dormant viral infections at greater risk for complications after intraoperative hypothermia.

Evidence that stress and surgical interventions promote tumor development by suppressing natural killer cell activity.

Stress and surgery have been suggested to compromise host resistance to infectious and malignant diseases in experimental and clinical settings. Because stress affects numerous physiological systems, the role of the immune system in mediating such effects is unclear. In the current study, we assessed the degree to which stress-induced alterations in natural killer (NK) cell activity underlie increased susceptibility to tumor development in F344 rats. Two stress paradigms were used: forced swim and abdominal surgery. Host resistance to tumor development was studied using 3 tumor models syngeneic to inbred F344 rats: CRNK-16 leukemia and the MADB106 mammary adenocarcinoma, both sensitive to NK activity, and the NK-insensitive C4047 colon cancer. Swim stress increased CRNK-16-associated mortality and metastatic development of MADB106 but not metastasis of C4047 cells. In both stress paradigms, stress suppressed NK activity (NKA) for a duration that paralleled its metastasis-enhancing effects on the MADB106 tumor. In vivo depletion of large granular lymphocyte/NK cells abolished the metastasis-enhancing effects of swim stress but not of surgical stress. Our findings indicate that stress-induced suppression of NKA is sufficient to cause enhanced tumor development. Under certain stressful conditions, suppression of NKA is the primary mediator of the tumor-enhancing effects of stress, while under other conditions, additional factors play a significant role. Clinical circumstances in which surgical stress may induce enhanced metastatic growth are discussed.

In vivo beta-adrenergic stimulation suppresses natural killer activity and compromises resistance to tumor metastasis in rats.

The sympathetic nervous system has been implicated in mediating stress-induced alterations in NK cell activity, particularly through stimulation of beta-adrenergic receptors. However, because catecholamines induce time-dependent alterations in the distribution of NK cells, the impact of beta-adrenergic stimulation on individual NK cell cytotoxicity is not clear, nor are its implications regarding host resistance to metastatic spread. To address these issues, we used the beta-adrenergic agonist, metaproterenol (MP), in F344 rats. The number of blood NK cells doubled within 10 min of MP administration and returned to baseline levels within 1 h. By this time, MP suppressed blood NK activity in a dose-dependent manner. Two beta-adrenergic antagonists, propranolol, which crosses the blood-brain barrier, and nadolol, which does not, blocked this suppression. Corresponding findings were obtained using an NK-sensitive tumor model, the MADB106. MP caused an up to 10 times increase in the number of tumor cells retained in the lungs 1 day after inoculation and a similar rise in the number of consequent lung metastases detected 3 wk later. These effects were dose dependent and nadolol reversible. NK cells appear to play a central role in mediating the tumor-enhancing effects of MP because their selective depletion nearly abolished this effect. Overall, our findings suggest that independent of the transitory increase in numbers of blood NK cells, in vivo beta-adrenergic stimulation suppresses NK activity in the rat. This suppression is induced peripherally and can compromise host resistance to NK-sensitive tumors. Homologies to studies in humans and clinical relevance are discussed.

Effects of item repetitions and variations on the efficiency of the guilty knowledge test.

Two mock-crime experiments were designed to examine the effects of question repetition and variation on the efficiency of the guilty knowledge test. In the first experiment, two factors (single vs. multiple questions, and high vs. low motivation) were manipulated and in the second experiment, which was an analog study conducted in a police laboratory using field equipment, only the first factor was examined. Similar detection efficiencies were obtained in both experiments when a single question was repeated 12 times, and when each of four different questions was repeated 3 times. The results also showed that accumulating information across repetitions and across physiological measures tended to increase detection efficiency and reduce false positive errors. The results of Experiment 1 suggest that motivation to avoid detection may be associated with better detection efficiency.

Increased susceptibility to metastasis during pro-oestrus/oestrus in rats: possible role of oestradiol and natural killer cells.

It has been suggested that tumour development and immunocompetence are affected by the menstrual and the oestrous cycle, and sex hormones have been shown to modulate lymphokine production, neuroendocrine activity and immunity. In this study, we assessed natural killer cell activity and host susceptibility to metastasis during the oestrous cycle in the Fischer 344 inbred rat strain. Females were inoculated intravenously with MADB106 tumour cells, a syngeneic mammary adenocarcinoma cell line that metastasises only to the lungs. The susceptibility to metastatic development of this tumour was found to be significantly higher during pro-oestrus and oestrus than during metoestrus and dioestrus. Two days of exposure to oestradiol benzoate caused similar effects in ovariectomised females, and a single administration of progesterone reduced this effect of oestradiol to a statistically non-significant level. The tumour was found to be negative for oestradiol receptors, and its in vitro proliferation rate was not affected by oestradiol or progesterone, suggesting that the effects of sex hormones on the metastatic process are not attributable to a direct effect on tumour cells. Because the metastatic process of MADB106 tumour cells is known, and confirmed here, to be highly controlled by large granular lymphocyte/natural killer (LGL/NK) cell activity, we assessed their role in mediating the effects of the oestrous cycle. The number and activity levels of circulating blood LG/NK cells (NKR-PI+ bright) were studied. Findings indicated oestrous-dependent alterations in the number of LGL/NK cells and suggested a diminished NK activity per LGL/NK cell during pro-oestrus/ oestrus, the same phases that were characterised by higher susceptibility to metastatic development. These findings provide the first empirical evidence for a causal relationship between a short-term exposure to elevated oestradiol/low progesterone levels and decreased resistance to tumour metastasis, and it is hypothesised that an alteration in LGL/NK cell activity underlies these effects. Homologies and relevance to clinical phenomena are discussed.

Stimulus novelty and significance in electrodermal orienting responses: the effects of adding versus deleting stimulus components.

Several aspects of a feature-matching theory formulated to account for the roles of stimulus novelty and significance in determining orienting responses (ORs) were examined. Stimulus significance and stimulus novelty were independently manipulated, and the electrodermal component of the OR was measured while sequences of compound pictorial or verbal stimuli were presented. Each sequence included a test stimulus, which was either significant or neutral, and was preceded by several standard control stimuli. Novelty was manipulated by either adding or deleting components from the standard stimuli, and significance was defined within the framework of the guilty knowledge paradigm. A change in the number of components of both verbal and pictorial test stimuli affected OR magnitude for significant but not for neutral test stimuli. Similar ORs were obtained regardless of the direction of stimulus change.

Is an apple a fruit? Semantic relatedness as reflected by psychophysiological responsivity.

In the present study, we investigated orienting response generalization across various types of semantically related stimuli. Four experiments, based on a modified version of the guilty knowledge technique, were designed to examine whether semantic relations based on abstract features are reflected by electrodermal responsivity. No generalization across coordinates was obtained, but a moderate degree of generalization was demonstrated between a word and its superordinate category (e.g., table-furniture) and between a word and its synonym. Complete generalization occurred from a verbal label of an object to its pictorial representation, and vice versa. These results are compatible with our proposal that partial identification of the test stimulus as relevant is a necessary condition for generalization in the guilty knowledge technique.

Psychophysiological detection through the guilty knowledge technique: effects of mental countermeasures.

The effects of mental countermeasures on the efficiency of psychophysiological detection with the Guilty Knowledge Technique were examined in a mock-crime experiment with 4 groups of participants: innocent participants who were not involved in the mock crime, guilty controls who committed the mock crime but received no countermeasure instructions, and guilty participants who received countermeasure instructions, and guilty participants who received countermeasure instructions and were allowed to practice the countermeasures. The countermeasure instructions encouraged participants to recall emotional situations from their past and imagine themselves in these situations during presentation of irrelevant questions. Results revealed a significant reduction in electrodermal detection efficiency under the 2 countermeasure conditions with no differences between them. No countermeasures effects were observed with the respiration line length measure.

A randomized controlled outcome and follow-up study of Mann's time-limited psychotherapy.

Thirty-three patients were assessed for suitability for time-limited psychotherapy (TLP). A battery of outcome measures was composed of patient self-report measurements and objective judgments by external ("masked") raters. Patients were randomly assigned to either the experimental group, which received TLP immediately, or the control group, whose TLP was delayed for 3 months. Patients were evaluated on outcome measures at TLP termination and again at 6 and 12 months after termination. Significant improvement was observed in the experimental group after TLP, but the control patients did not show any systemic changes after waiting. However, after TLP, the control patients improved significantly. The average effect size measured by the differences between gain scores of the experimental patients (before vs. after treatment) and those of the control patients (before vs. after waiting) was 0.986 SD. The gains achieved after therapy were stable in both groups after 6- and 12-month follow-ups.

Generalization of the orienting response to significant stimuli: the roles of common and distinctive stimulus components.

This study focused on the effects of common and distinctive stimulus components on the generalization of the orienting response (OR) to significant stimuli. Compound pictorial stimuli were used as the relevant items memorized by the subjects. Skin conductance responses were measured during the subsequent presentation of a stimulus sequence that included a test stimulus that shared some common components with the relevant one. The two types of stimulus components (common and distinctive) were independently manipulated. As predicted by the feature-matching theory, both types of features affected OR generalization, but the distinctive components effect was due mainly to a large decline in OR with the introduction of the first distinctive component. As hypothesized, no interaction was observed between the effects of common and distinctive components. Contrary to expectations, similar OR generalization was obtained regardless of whether the test stimulus was constructed by deleting stimulus components from the relevant stimulus or by adding components to that stimulus.