Evoked potential correlates of signal recognition between and within modalities.

Electrical responses evoked by clicks, flashes, changes in noise level, and changes in light level were recorded from the scalps of human subjects set to detect one of the stimuli. An early negative component of the evoked responses reflects selection between sensory modalities, whereas the later positive component reflects a more complex intramodal discrimination.

Effects on humans of 9 -tetrahydrocannabinol administered by smoking.

Twelve chronic marijuana users received triangle up(9)-tetrahydrocannabinol by smoking. The magnitude of their pulse increment was highly correlated with their subjective experiences. Three of the 12 subjects subsequently received triangle up(9)-tetrahydrocannabinol labeled with carbon-14; the time course of its concentration in plasma was highly correlated with the pulse increment. Subjective symptoms, however, appeared later and dissipated more slowly.

P3 in schizophrenia is affected by stimulus modality, response requirements, medication status, and negative symptoms.

Eighteen schizophrenics who were not taking medication, 13 schizophrenics who were taking medication, and 37 age-matched controls were tested with event-related potential paradigms designed to elicit P3 response automatically or effortfully (ie, with a choice reaction time task). Electroencephalograms were recorded from the 19 standard 10-20 electrode sites. Compared with controls, both groups of schizophrenics had reduced P3 amplitudes for both effortful and automatic paradigms. P3 latencies were delayed relative to controls for the medication-taking schizophrenics in the effortful paradigms. Negative symptoms derived from the Brief Psychiatric Rating Scale within 1 week of event-related potential testing correlated negatively with both auditory and visual P3 amplitude in the subjects who were not taking medication. There was no evidence that P3 is smaller over left temporal electrode sites in schizophrenics, as has been reported by others. P3 amplitude reduction in schizophrenia is a robust psychobiological phenomenon that is present regardless of medication status or task demands.

Psychophysiological correlates of the practice of Tantric Yoga meditation.

Autonomic and electroencephalographic (EEG) correlates of Tantric Yoga meditation were studied in three groups of subjects as they progressed from normal consciousness into meditation. Groups differed in their level of meditation proficiency. Measures of skin resistance, heart rate, respiration, autonomic orienting responses, resting EEG, EEG alpha and theta frequencies, sleep-scored EEG, averaged evoked responses, and subjective experience were employed. Unlike most previously reported meditation studies, proficient meditators demonstrated increased autonomic activation during meditation while unexperienced meditators demonstrated autonomic relaxation. During meditation, proficient meditators demonstrated increased alpha and theta power, minimal evidence of EEG-defined sleep, and decreased autonomic orienting to external stimulation. An episode of sudden autonomic activation was observed that was characterized by the meditator as an approach to the Yogic ecstatic state of intense concentration. These findings challenge the current "relaxation" model of meditative states.

Stress test reactivity in panic disorder.

The psychological and physiological reactivity of 52 patients with panic disorder to mental arithmetic, cold pressor, and 5% carbon dioxide inhalation tests was compared with that of 26 age- and sex-matched normal subjects. In general, patients with panic disorder were neither more physiologically reactive to these stressors than normal subjects nor slower to recover from them, but they were tonically more anxious and much more likely to ask to stop carbon dioxide inhalation or to report panic attacks during this test. Patients who reported panic attacks (46%) had manifested greater anticipatory anxiety before the gas was delivered, accompanied with increased beta-adrenergic cardiac tone. Thus, anticipatory anxiety can be an important factor in panic provocation. Physiological measures varied greatly in their sensitivity to phasic or tonic anxiety. Carbon dioxide stimulated large increases in respiratory minute volume, but these increases were no greater for patients than for normal subjects.

Auditory event-related potentials and electrodermal activity in medicated and unmedicated schizophrenics.

Event-related potentials (ERPs) and electrodermal activity were studied in 14 medicated schizophrenics, 17 unmedicated schizophrenics, and 23 age- and education-matched controls. Subjects were run in three auditory stimulus paradigms differing from the usual ERP paradigms in having interstimulus intervals greater than 12 sec to permit measurement of the longer latency skin conductance response (SCR). In every paradigm medicated but not unmedicated schizophrenics had smaller N120 amplitudes and fewer SCRs than controls. In addition, medicated schizophrenics showed reduced P200 amplitude and latency, longer P320 latency, and reduced skin conductance levels in certain paradigms. These effects cannot easily be attributed to different mental states of medicated and unmedicated patients, since their Brief Psychiatric Rating Scale scores were almost the same. It is more probable that antipsychotic and antiparkinsonian drugs reduced electrodermal activity through anticholinergic mechanisms and that the antipsychotic drugs attenuated N120 through other biological mechanisms.

Physiologic instability in panic disorder and generalized anxiety disorder.

BACKGROUND: Because panic attacks can be accompanied by surges in physiologic activation, we tested the hypothesis that panic disorder is characterized by fluctuations of physiologic variables in the absence of external triggers. METHODS: Sixteen patients with panic disorder, 15 with generalized anxiety disorder, and 19 normal control subjects were asked to sit quietly for 30 min. Electrodermal, cardiovascular, and respiratory measures were analyzed using complex demodulation to quantify variability in physiologic indices. RESULTS: Both patient groups reported equally more anxiety and cardiac symptoms than control subjects, but certain other somatic symptoms, including breathlessness, were elevated only in panic disorder patients. Mean end-tidal pCO(2) and respiratory rates were lower, and tidal volume and the number of sighs were higher in panic disorder patients than control subjects. Neither cardiovascular (heart rate, arterial pressure, cardiac output), nor electrodermal instability including sighs distinguished the groups; however, tidal volume instability was greater in panic disorder than generalized anxiety disorder patients or control subjects. Several other respiratory measures (pCO(2), respiratory rate, minute volume, duty cycle) showed greater instability in both patient groups than in control subjects. CONCLUSIONS: Respiration is particularly unstable in panic disorder, underlining the importance of respiratory physiology in understanding this disorder. Whether our findings represent state or trait characteristics is discussed.

Characteristics of sighing in panic disorder.

BACKGROUND: Sighs, breaths with larger tidal volumes than surrounding breaths, have been reported as being more frequent in patients with anxiety disorders. METHODS: Sixteen patients with panic disorder, 15 with generalized anxiety disorder, and 19 normal control subjects were asked to sit quietly for 30 min. Respiratory volumes and timing were recorded with inductive plethysmography and expired pCO(2), from nasal prongs. RESULTS: Panic disorder patients sighed more and had tonically lower end-tidal pCO(2)s than control subjects, whereas generalized anxiety disorder patients were intermediate. Sighs defined as >2.0 times the subject mean discriminated groups best. Sigh frequency was more predictive of individual pCO(2) levels than was minute volume. Ensemble averaging of respiratory variables for sequences of breaths surrounding sighs showed no evidence that sighs were triggered by increased pCO(2) or reduced tidal volume in any group. Sigh breaths were larger in panic disorder patients than in control subjects. After sighs, pCO(2) and tidal volume did not return to baseline levels as quickly in panic disorder patients as in control subjects. CONCLUSIONS: Hypocapnia in panic disorder patients is related to sigh frequency. In none of the groups was sighing a homeostatic response. Panic disorder patients show less peripheral chemoreflex gain than control subjects, which would maintain low pCO(2) levels after sighing.

Skin conductance habituation in panic disorder patients.

Skin conductance habituation was compared between 38 patients meeting DSM-III criteria for Panic Disorder and 29 normal controls. Approximately half of each group was randomly assigned to be given 100 dB SPL tones and the other half 75 dB tones. All indices pointed to slowed habituation in patients compared with normals: number of trials to response habituation, total number of responses, and slope of decline of skin conductance level. Patient-normal differences were not significantly larger for 100 dB than for 75 dB. In addition, patients compared with normals had more nonspecific fluctuations, higher skin conductance levels, and a shorter response latency to the first stimulus. Stepwise discriminant analyses classified patients and normals better in the 100 dB than in the 75 dB condition, and showed that the various skin conductancy variables were largely redundant at the higher intensity.

Auditory brain stem and cortical evoked potentials in schizophrenia.

Auditory brain stem and cortical evoked potentials were recorded from 15 schizophrenics and 15 controls. There were significant cortical evoked potential differences between the two groups. However, brain stem evoked potentials were almost identical, suggesting that the cortical evoked potential differences are not due to peripheral factors such as inability to match sensory thresholds or defects in auditory acuity.

Cortical responsiveness during talking and listening in schizophrenia: an event-related brain potential study.

BACKGROUND: Failures to recognize inner speech as self-generated may underlie positive symptoms of schizophrenia-like auditory hallucinations. This could result from a faulty comparison in auditory cortex between speech-related corollary discharge and reafferent discharges from thinking or speaking, with misattribution of internal thoughts to external sources. Although compelling, failures to monitor covert speech (thoughts) are not as amenable to investigation as failures to monitor overt speech (talking). METHODS: Effects of talking on auditory cortex responsiveness were assessed in 10 healthy adults and 12 patients with schizophrenia (DSM-IV) using N1 event-related potentials (ERPs) to acoustic and visual probes during talking aloud, listening to one's speech played back, and silent baseline. Trials contaminated by muscle artifact while talking were excluded. RESULTS: Talking and listening affected N1 to acoustic but not to visual probes, reflecting modality specificity of effects. Patterns of responses to acoustic probes differed between control subjects and patients. N1 to acoustic probes was reduced during talking compared with baseline in control subjects, but not in patients. Listening reduced N1 equivalently in both groups. CONCLUSIONS: Although the failure of N1 to be reduced during talking was not related to current hallucinations in patients, it may be related to the potential to hallucinate.

Imipramine and alprazolam effects on stress test reactivity in panic disorder.

The reactivity of 40 panic disorder patients on mental arithmetic, cold pressor, and 5% CO2 inhalation stressors was tested before and after 8 weeks of treatment with imipramine, alprazolam, or placebo. Mean levels of subjective and physiological stress measures were compared during a baseline before any stressors were given, and at anticipation, stressor, and recovery periods for each stressor. After treatment, imipramine patients differed from the other two treatment groups on the prestressor baseline in showing higher systolic blood pressure (mean difference about 10 mmHg), higher diastolic blood pressure (10 mm Hg), higher heart rate (15 bpm), less respiratory sinus arrhythmia, shorter pulse transit time, and lower T-wave amplitude. Respiratory measures, electrodermal measures, body movement, and self-reported anxiety and excitement did not distinguish the groups. Reactivity to the stress tests was unaffected by the medications, but tonic differences present in the baseline persisted.

Autonomic characteristics of agoraphobia with panic attacks.

We compared electrodermal and heart rate measures of autonomic activation between patients meeting DSM-III criteria for agoraphobia with panic attacks and controls in terms of tonic level, reactivity to various types of stimuli, recovery, habituation, and spontaneous variability. The most striking differences between groups in the laboratory were higher tonic levels of skin conductance and heart rate among patients. Patients' heart rates were also tonically elevated in a test situation outside the laboratory. Certain measures of habituation and spontaneous variability also differed between groups, but there were only weak and inconsistent differences in reactivity to, or recovery from, stimuli with diverse qualities of novelty, startlingness, intensity, or phobicity. The elevated activation levels may be signs of a chronic state or may be phobic responses to the testing situations. A minority of patients failed to show these elevated levels.

ERPs in schizophrenia: effects of antipsychotic medication.

Thirty unmedicated schizophrenics were compared to 29 age-matched controls on auditory and visual event-related brain potential (ERP) paradigms. Twenty-one of these patients were tested again after 1 week on placebo and after 4 weeks on antipsychotic medication. Before treatment, N1, N2, and P3 components of the auditory ERP were smaller in the schizophrenics than in the controls. Although visual N2 was smaller in schizophrenics, visual P3 was not. In spite of significant clinical improvement with antipsychotic treatment, amplitudes of auditory and visual N1, N2, and P3 were not significantly changed. Higher blood levels of antipsychotic medication were related to reductions in auditory P3 latency, however. In addition, higher levels of cerebrospinal fluid (CSF) MHPG (methoxyhydroxyphenylglycol) were associated with larger auditory N1s and larger auditory and visual P3s, suggesting an influence of arousal on these components in schizophrenics. In spite of this influence, reduction of the auditory P3 in schizophrenia is an enduring trait of the disease, which is not affected by antipsychotic medication or clinical improvement.

Automatic and effortful processing in aging and dementia: event-related brain potentials.

Automatic and effortful processes were investigated using event-related brain potentials (ERPs) recorded from moderately impaired subjects with probable Alzheimer's Disease (AD), normal elderly, and normal young controls. The effects of effortful attention on ERPs to loud noises and the effects of stimulus intrusiveness on effortfully elicited ERPs were studied. First, ERPs to task relevant and irrelevant startling noises were compared. Second, ERPs to startling noises and moderate tones were compared when both were targets. The effects of age (young vs. elderly controls) and effects of dementing disease (AD subjects vs. elderly controls) were also assessed. Effortful attention augmented noise-elicited P300 amplitude in elderly subjects, but not in young. Intrusiveness augmented task-relevant P300 amplitude in young subjects, but not in elderly. Neither variable affected P300 amplitude in AD subjects. Thus, effects of age and disease depended on how P300 was elicited: when effortfully elicited, P300 amplitude was affected by disease but not age; when automatically elicited, P300 amplitude was affected by age but not disease. N1 effects differed from P300 effects.

Plasma lipid levels in patients with panic disorder or agoraphobia.

Plasma lipids were measured in 102 subjects with panic disorder or agoraphobia. In women, but not men, a significantly higher than expected number of subjects had cholesterol values that exceeded the 75th percentile of national reference values for their sex and age.

Cortical responsiveness during inner speech in schizophrenia: an event-related potential study.

OBJECTIVE: The study assessed the effects of inner speech on auditory cortical responsiveness in schizophrenia. METHOD: Comparison subjects (N=15) and patients with schizophrenia (N=15) were presented with acoustic and visual stimuli during three conditions: while subjects were silent, when spontaneous inner speech might occur; during directed inner speech, while subjects repeated a statement silently to themselves; and while subjects listened to recorded speech. N1 event-related potentials were recorded during the three conditions. RESULTS: N1 event-related potentials elicited by acoustic stimuli, but not by visual stimuli, were lower during directed inner speech than during the silent baseline condition in the comparison subjects but not in the patients. CONCLUSIONS: Abnormal auditory cortical responsiveness to inner speech in patients with schizophrenia may be a sign of corollary discharge dysfunction, which may potentially cause misattribution of inner speech to external voices.

Neurophysiological evidence of corollary discharge dysfunction in schizophrenia.

OBJECTIVE: Speaking is hypothesized to generate a corollary discharge of motor speech commands transmitted to the auditory cortex, dampening its response to self-generated speech sounds. Event-related potentials were used to test whether failures of corollary discharge during speech contribute to the pathophysiology of schizophrenia. METHOD: The N1 component of the event-related potential elicited by vowels was recorded while the vowels were spoken by seven patients with schizophrenia and seven healthy comparison subjects and while the same vowels were played back. RESULTS: In the healthy subjects, the N1 elicited by spoken vowels was smaller than the N1 elicited by played-back vowels. This reduction in N1 elicited by spoken vowels was not observed in the patients with schizophrenia. CONCLUSIONS: These findings provide direct neurophysiological evidence for a corollary discharge that dampens sensory responses to self-generated, relative to externally presented, percepts in healthy comparison subjects and its failure in patients with schizophrenia.

Surreptitious drug use by patients in a panic disorder study.

In a double-blind, placebo-controlled trial comparing alprazolam and imipramine for panic disorder, serum analysis revealed that a substantial proportion of the patients took explicitly prohibited anxiolytic medication. Excluding these patients changed the results.

Ambulatory heart rate changes in patients with panic attacks.

Of 33 "panic" attacks reported by patients wearing an ambulatory solid-state heart rate/activity monitor for 6 days, 19 (58%) occurred at heart rates disproportionate to activity levels and different enough from surrounding heart rates to indicate a distinct physiologic state. Intense panic attacks with three or more symptoms were the most readily identified. ECG monitoring found the elevated heart rates to be sinus tachycardias. Heart rate elevation did not occur during anticipatory anxiety episodes. Ambulatory heart rate recordings confirm the presence of major physiologic changes during self-reported panic attacks.