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PubMed2000

Mapping auditory hallucinations in schizophrenia using functional magnetic resonance imaging.

BACKGROUND: Perceptions of speech in the absence of an auditory stimulus (auditory verbal hallucinations) are a cardinal feature of schizophrenia. Functional neuroimaging provides a powerful means of measuring neural activity during auditory hallucinations, but the results from previous studies have been inconsistent. This may reflect the acquisition of small numbers of images in each subject and the confounding effects of patients actively signaling when hallucinations occur. METHODS: We examined 6 patients with schizophrenia who were experiencing frequent auditory hallucinations, using a novel functional magnetic resonance imaging method that permitted the measurement of spontaneous neural activity without requiring subjects to signal when hallucinations occurred. Approximately 50 individual scans were acquired at unpredictable intervals in each subject while they were intermittently hallucinating. Immediately after each scan, subjects reported whether they had been hallucinating at that instant. Neural activity when patients were and were not experiencing hallucinations was compared in each subject and the group as a whole. RESULTS: Auditory hallucinations were associated with activation in the inferior frontal/insular, anterior cingulate, and temporal cortex bilaterally (with greater responses on the right), the right thalamus and inferior colliculus, and the left hippocampus and parahippocampal cortex (P<.0001). CONCLUSIONS: Auditory hallucinations may be mediated by a distributed network of cortical and subcortical areas. Previous neuroimaging studies of auditory hallucinations may have identified different components of this network.

Auditory Perception↗
PubMed2006

Age-related influences on the clinical characteristics of new-onset hallucinations in Parkinson's disease patients.

The objective of this study was to determine the demographic influences on the sensory characteristics (pure visual vs. nonvisual or mixed visual/nonvisual) of new-onset hallucinations in Parkinson's disease (PD). We utilized 6-year longitudinal interview data from 60 PD patients who had never hallucinated at baseline and reinterviewed them at 6, 18, 48, and 72 months to assess the presence and type of hallucination that developed as the first form of hallucination. We analyzed data by Generalized Estimating Equations methods and by nonparametric tests. Over 6 years, 37 of 60 patients developed hallucinations, and the first hallucinations were pure visual in 18, pure nonvisual in 9, and mixed visual/nonvisual in 10. At the time of first onset of hallucinations, patients whose hallucinations were nonvisual or mixed were significantly older than those with purely visual hallucinations (mean age, 69.8+/-8.3 vs. 61.9+/-10.6; P=0.031). PD duration in the two groups, however, was statistically comparable (9.6+/-4.4 vs. 12.9+/-8.6 years). Though classically described as visual, hallucinations in PD frequently involve other sensory modalities. Age-related disinhibition may facilitate wider cortical activation in PD and potentiate aberrant signaling that invokes other types of hallucinations besides the classic visual forms.

Age Factors↗
PubMed2006

Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease.

We aimed to determine prospectively whether rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, provided benefits in patients with and without visual hallucinations in a population with dementia associated with Parkinson's disease (PDD). This was a 24-week double-blind placebo-controlled study. Primary efficacy measures were the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary efficacy measures included activities of daily living, behavioral symptoms, and executive and attentional functions. Patients were stratified according to the presence of visual hallucinations at baseline. The study included 188 visual hallucinators (118 on rivastigmine, 70 on placebo) and 348 nonvisual hallucinators (239 on rivastigmine, 109 on placebo). Rivastigmine provided benefits in both visual hallucinators and nonvisual hallucinators. Absolute responses to rivastigmine on the ADAS-cog were comparable over 6 months, although rivastigmine-placebo differences tended to be larger in visual hallucinators (4.27; P = 0.002) than in nonhallucinators (2.09; P = 0.015). On the ADCS-CGIC, differences between rivastigmine and placebo were 0.5 in visual hallucinators (P = 0.030) and 0.3 in nonhallucinators (P = 0.111). Rivastigmine provided benefits on all secondary efficacy measures, and placebo declines and treatment differences were more marked in visual hallucinators. Adverse events were reported more frequently by rivastigmine-treated patients, although this difference was less marked in visual hallucinators. Visual hallucinations appear to predict more rapid decline and possibly greater therapeutic benefit from rivastigmine treatment in PDD.

Aged↗
PubMed2004

Antiparkinsonian medication is not a risk factor for the development of hallucinations in Parkinson's disease.

BACKGROUND: It was commonly assumed that psychotic phenomena in Parkinson's disease (PD) are mainly drug related. Accumulating evidence suggests the existence of other risk factors for psychosis in PD. Aims. To evaluate the contribution of the drug profile of patients with PD to emergence of hallucinations. METHODS: We compared patients with and without hallucinations, using Cox proportional hazards model, concerning drug profile at the time of hallucinations emergence. RESULTS: Of 422 consecutive patients, 113 had dementia, while 90 patients experienced hallucinations (46 had both dementia and hallucinations). The mean levodopa dose for the group of patients with hallucinations was 650 +/- 279 mg/day at the time of hallucinations onset, which was not significantly different from the levodopa dose at last visit for the group without hallucinations (621 +/- 326 mg/day). Supplementary treatment with amantadine, selegiline, dopamine agonists, entacapone and anticholinergics did not increase the risk for the development of hallucinations. CONCLUSIONS: We did not confirm drug treatment as a risk factor for hallucinations in PD. Our study suggests the existence of "endogenic" factors as substantial contributors in the genesis of PD hallucinations. The clinical implications may be earlier administration of antipsychotic treatment and not as traditionally accepted, dose reduction of antiparkinsonian drugs.

Adult↗
PubMed1983

Ocular motility testing in the evaluation of visual hallucinations.

Distinguishing organic visual hallucinations from those caused by hysteria or malingering is important but difficult. We found that ocular motility testing is helpful in making the distinction in some patients who allege that their hallucinations move. A 9-year-old girl thought to have organic hallucinations, possibly caused by an occipital lobe neoplasm, was unable to generate smooth pursuit movements when she attempted to follow the movements of the hallucinations. Instead, she executed a series of small downward saccades. Her hallucinations were presumably stress-induced. Conversely, a 62-year-old man with hypertension, arteriosclerotic heart disease, and depression, whose hallucinations were thought to be hysterical, was able to execute smooth pursuit movements when he attempted to follow the hallucinations. Detection of a previously unrecognized visual field defect helped to establish that the hallucinations were organic. Thus, patients with moving organic hallucinations may produce smooth pursuit movements when attempting to follow the hallucinations, but patients with feigned or hysterical hallucinations, who lack a fixation target, are likely to execute a series of saccades.

Brain Ischemia↗
PubMed1998

Cognitive processes in auditory hallucinations: attributional biases and metacognition.

BACKGROUND: Cognitive models suggest that auditory hallucinations are experienced when mental events are misattributed to an external source; therefore, this study was designed to examine attributional biases in patients experiencing auditory hallucinations. The study also examined the role of metacognitive beliefs in the experience of auditory hallucinations, as some theories have implicated metacognition in the development and maintenance of auditory hallucinations. METHODS: Fifteen participants with a diagnosis of schizophrenia experiencing auditory hallucinations were compared with 15 non-hallucinating schizophrenics and 15 non-psychiatric control subjects on several measures, including an immediate source monitoring task and a questionnaire assessing metacognitive beliefs. RESULTS: Results indicated that patients experiencing hallucinations exhibited the predicted bias towards misattributing internal events to an external source, as measured by ratings of internality of responses in a word association task. All groups had lower perceived levels of internality and control for emotionally salient words, which provides further evidence for the importance of emotional content in hallucinations. Patients experiencing hallucinations were found to score higher than the other two groups on metacognitive beliefs about uncontrollability and danger and positive beliefs about worry. In addition, a logistic regression analysis showed that beliefs about uncontrollability and danger were predictive of whether subjects experienced auditory hallucinations or not. CONCLUSIONS: These results offer considerable support to cognitive bias models of auditory hallucinations, particularly those that implicate metacognition.

Adult↗
PubMed2004

Individual differences in lateralisation of hallucinations associated with sleep paralysis.

Individual differences were investigated in the lateralisation of two general categories of hypnagogic and hypnopompic hallucinations associated with sleep paralysis: (1) Vestibular-motor (V-M) hallucinations; comprising sensations of floating, flying, illusory locomotion and postural adjustments, out-of-body experiences (OBE), and autoscopy; and (2) Intruder hallucinations; incorporating a sense of the presence, and visual and auditory hallucinations of external, alien agents. Left-right lateralisation of such hallucinations, as well as handedness and footedness, were assessed in a diverse, nonclinical sample of 201 subjects participating in a web-based survey of sleep paralysis experiences. V-M hallucinations, but not Intruder hallucinations were predicted, based on the hypothesised distinctive neural sources of the different hallucinations, to be positively associated with handedness and footedness. Specifically, the predictions were based on the hypothesis that the activation of components of a vestibular, motor, and kinaesthetic bodily-self neuromatrix underlies V-M hallucinations, whereas a threat-activated vigilance system is responsible for Intruder hallucinations. As predicted, limb preferences were consistently found to be significantly and positively associated with a side bias of V-M, but not Intruder, hallucinations.

Adolescent↗
PubMed2000

Hallucinations in Parkinson's disease: prevalence, phenomenology and risk factors.

Hallucinations, mainly of a visual nature, are considered to affect about one-quarter of patients with Parkinson's disease. They are commonly viewed as a side-effect of antiparkinsonian treatment, but other factors may be involved. The aim of this study was to determine the phenomenology, prevalence and risk factors of hallucinations in Parkinson's disease. Two-hundred and sixteen consecutive patients fulfilling clinical criteria for Parkinson's disease were studied. Demographic and clinical variables were recorded, including motor and cognitive status, depressive symptoms and sleep-wake disturbances. Patients with and without hallucinations were compared using non-parametric tests, and logistic regression was applied to significant data. Hallucinations had been present during the previous 3 months in 39.8% of the patients, and fell into three categories: minor forms, consisting of a sensation of a presence (person), a sideways passage (commonly of an animal) or illusions were present in 25.5% of the patients (an isolated occurrence in 14.3%), formed visual hallucinations were present in 22.2% (isolated in 9.3%) and auditory hallucinations were present in 9.7% (isolated in 2.3%). Patients with minor hallucinations had a higher depression score than non-hallucinators but did not differ in other respects. Logistic regression analysis identified three factors independently predictive of formed visual hallucinations: severe cognitive disorders, daytime somnolence and a long duration of Parkinson's disease. These findings indicate that, when minor hallucinations are included, the total prevalence is much higher than previously reported. A simple side-effect of dopaminergic treatment is not sufficient to explain the occurrence of all visual hallucinations. The main risk factor in treated patients is cognitive impairment, although sleep-wake cycle disturbances, and possibly other factors related to the duration of the disease, act as cofactors.

Aged↗
PubMed1989

Musical hallucinations. The sounds of silence?

Hallucinations may occur in any sensory modality. Auditory hallucinations, usually ascribed to psychiatric illness, take various forms including the perception of voices, cries, noises, or rarely, music. Formed musical hallucinations, (ie, the perception of either vocal or instrumental melodies), reported in the English literature to date have typically been associated with marked hearing loss, advanced age (average 67.8 years), female sex (71%), lack of response to treatment, and general lack of associated psychopathology. We have collected data on seven additional patients with musical hallucinations. The average age of these patients was 72.9 years; all were women. Six had significant hearing problems. All reported onset of musical hallucinations after the age of 60. Interestingly, all seven had major psychiatric illnesses. Four had major depression, two had late-onset schizophrenia, and one had multi-infarct dementia. Of the five who had CT scans, one was normal and the rest demonstrated varying degrees of brain pathology. Neuroleptics were used with varying results in three cases; antidepressants were used in two depressed patients and were temporally related to the onset of musical hallucinations in one patient. Electroconvulsive therapy (ECT) was very effective in treating depression and musical hallucinations in the three patients for whom it was used, usually providing relief from hallucinations after only two treatments. Our collection of cases demonstrates that musical hallucinations can occur in association with psychiatric illness, and perhaps unlike the hallucinations associated with isolated hearing loss, may respond to conventional treatments for the underlying psychiatric disorder. Hearing loss is neither a necessary nor sufficient condition for the occurrence of musical hallucinations.

Aged↗
PubMed1996

Qualitative changes in hallucinations.

OBJECTIVE: This study examined which characteristics of hallucinations are most likely to change after inpatient treatment. METHOD: Fifty hallucinating psychiatric inpatients were given semistructured interviews shortly after admission and again shortly before discharge to elicit detailed descriptions of 12 characteristics of hallucinations. RESULTS: Twenty-eight (56%) of the 50 patients continued to report hallucinations after inpatient treatment. Posttreatment hallucinations differed significantly from pretreatment hallucinations in that they were less frequent, less intense, and less likely to prompt overt behavioral responses. Other characteristics of hallucinations remained relatively stable. CONCLUSIONS: Even when treatment does not eliminate hallucinations, it may alter them significantly. Outcome criteria that consider only the presence or absence of hallucinations may miss important changes in the nature of the symptom. This demonstrates that there is no simple "on-off switch" for hallucinations and supports multifactorial theories of the etiology of hallucinations.

Adult↗
PubMed2004

Altered cortical visual processing in PD with hallucinations: an fMRI study.

OBJECTIVE: To compare fMRI activation during two visual stimulation paradigms in Parkinson disease (PD) subjects with chronic visual hallucinations vs PD patients who had never hallucinated. METHODS: Twelve pairs of PD subjects, matched for age, PD duration, and dopaminergic drug exposure duration, participated in this study. The authors examined group differences in activation during stroboscopic (flashing) vs no visual stimulation and kinematic (apparent motion) vs stationary visual stimulation. RESULTS: During stroboscopic stimulation, non-hallucinating PD subjects showed significantly greater activation in the parietal lobe and cingulate gyrus compared to hallucinating PD subjects. In contrast, the hallucinating subjects showed significantly greater activation in the inferior frontal gyrus and the caudate nucleus. During kinematic stimulation, non-hallucinating PD subjects showed significantly greater activation in area V5/MT, parietal lobe, and cingulate gyrus compared to hallucinating PD subjects. Hallucinating PD subjects showed significantly greater activation in the superior frontal gyrus. CONCLUSIONS: PD patients with chronic visual hallucinations respond to visual stimuli with greater frontal and subcortical activation and less visual cortical activation than non-hallucinating PD subjects. Shifting visual circuitry from posterior to anterior regions associated primarily with attention processes suggests altered network organization may play a role in the pathophysiology of visual hallucinations in PD.

Aged↗
PubMedDate not supplied

[Study of associated clinical variables and phenomenology of hallucinations in Parkinson's].

INTRODUCTION: Although hallucinations are considered to be a dopaminergic related phenomenon, the correlation between hallucinations with other features in Parkinson's disease (PD) still remains controversial. OBJECTIVES: To define the phenomenology and factors that contribute to hallucinations in patients with idiopathic PD, and to determine their correlation with the Parkinsonian motor state (on versus off ). METHOD: A consecutive series of patients with PD were examined using the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRSm), Hoehn and Yahr stage (HY), Mini-Mental State Examination (MMSE) and a questionnaire on hallucinations, motor state and sleep disorders. Patient's characteristics, treatment, motor status, and sleep disorders were correlated with the presence of hallucinations using parametric and non-parametric tests. RESULTS: Thirty eight patients (18 men, 20 women) with a mean age of 73.3 +/- 7 years, PD duration of 9 +/- 7 years, median HY stage of 2 (2-5), and a MMSE of 25 +/- 4 were included. Compared to non hallucinators (15 patients), hallucinators (23 patients) had a higher HY (p = 0.01), UPDRSm (p = 0.004), PD duration (p = 0.01), PD treatment duration (p = 0.03), presence of sleep disorders (p = 0.05) and were taking higher total daily doses of levodopa (p = 0.05). A multivariate analysis found that higher UPDRSm scores and total levodopa daily dose were the main clinical variables associated with hallucinations. Age, gender, MMSE scores, prior levodopa dose or dopaminergic agonists, and motor state did not influence the presence of hallucinations. CONCLUSIONS: In this study, hallucinations were not correlated with the Parkinsonian motor state. Although motor severity impairment and total levodopa daily dose were the main clinical variables associated with hallucinations, other clinical factors such as sleep disorders and treatment duration should be considered.

Aged↗
PubMed1995

Command hallucinations in outpatients with schizophrenia.

BACKGROUND: The presence of command hallucinations in individuals with schizophrenia may result in an increase in clinical monitoring to reduce the perceived risk of violent behavior. However, the issue of whether command hallucinations hold any clinical relevance in relatively stable outpatient samples has not been established. METHOD: The clinical and research records of individuals with schizophrenia who participated in outpatient research protocols at the University of California, San Diego were reviewed for the presence of command hallucinations. Information on clinical characteristics was collected in a detailed chart review from 106 patient records. RESULTS: Command hallucinations were reported by one half of all patients with auditory hallucinations, and these hallucinations often were violent in content. Yet, in over a third of the patients, these hallucinations had not been documented in their clinical charts, but instead were uncovered during a secondary source review. Patients with command hallucinations generally did not differ on prognostic or clinical course variables. However, the 2 patients who committed suicide during the study were patients with command hallucinations. CONCLUSION: Although command hallucinations may be more frequent than clinicians generally note, in most cases they have minimal influence on the outcome of schizophrenia. However, in outpatients with schizophrenia who have a history of suicide attempts, suicidal command hallucinations should be taken seriously.

Adult↗
PubMed1996

Functional neuroimaging of hallucinations in schizophrenia: toward an integration of bottom-up and top-down approaches.

Hallucinations in schizophrenia represent an important clinical problem, an interesting neuropsychological enigma, and a significant challenge for neuroscientific research. Functional neuroimaging techniques allow the in vivo, systems-level study of brain dysfunction underlying this debilitating symptom. Clinical and scientific vantage points that can inform the design and interpretation of functional neuroimaging studies of schizophrenic hallucinations are outlined. These include considerations of the phenomenology of hallucinations, the relationship of hallucinations to other symptoms of schizophrenia, and the neuropsychological functions that are thought to be disrupted in hallucinations. They also include the anatomical and chemical brain systems in which abnormalities are implicated in schizophrenia, the neurologic conditions in which hallucinations may occur, the neurochemical contexts that are associated with hallucinations, and the methodologic details of the functional neuroimaging techniques employed. Bottom-up and top-down functional neuroimaging strategies for the investigation of schizophrenic hallucinations with positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI) are reviewed. Bottom-up approaches start with or measure the biology associated with hallucinations. Top-down approaches start from the specific neuropsychological dysfunctions thought to be associated with hallucinations. The distributed brain regions, systems and functions implicated in schizophrenic hallucination formation are then discussed in the context of an integration of bottom-up and top-down approaches. Focus is placed upon abnormalities in the functions of, and interactions among, auditory-linguistic association cortices, caudal and rostral limbic/paralimbic systems, prefrontal cortices, ventral striatum and (non-specific projection and associative) thalamic nuclei, as well as upon the glutamatergic, GABAergic and ventral tegmental dopaminergic modulation of these systems.

Brain Mapping↗
PubMed2004

Pathways that make voices: white matter changes in auditory hallucinations.

BACKGROUND: The origin of auditory hallucinations, which are one of the core symptoms of schizophrenia, is still a matter of debate. It has been hypothesized that alterations in connectivity between frontal and parietotemporal speech-related areas might contribute to the pathogenesis of auditory hallucinations. These networks are assumed to become dysfunctional during the generation and monitoring of inner speech. Magnetic resonance diffusion tensor imaging is a relatively new in vivo method to investigate the directionality of cortical white matter tracts. OBJECTIVE: To investigate, using diffusion tensor imaging, whether previously described abnormal activation patterns observed during auditory hallucinations relate to changes in structural interconnections between the frontal and parietotemporal speech-related areas. METHODS: A 1.5 T magnetic resonance scanner was used to acquire twelve 5-mm slices covering the Sylvian fissure. Fractional anisotropy was assessed in 13 patients prone to auditory hallucinations, in 13 patients without auditory hallucinations, and in 13 healthy control subjects. Structural magnetic resonance imaging was conducted in the same session. Based on an analysis of variance, areas with significantly different fractional anisotropy values between groups were selected for a confirmatory region of interest analysis. Additionally, descriptive voxel-based t tests between the groups were computed. RESULTS: In patients with hallucinations, we found significantly higher white matter directionality in the lateral parts of the temporoparietal section of the arcuate fasciculus and in parts of the anterior corpus callosum compared with control subjects and patients without hallucinations. Comparing patients with hallucinations with patients without hallucinations, we found significant differences most pronounced in the left hemispheric fiber tracts, including the cingulate bundle. CONCLUSION: Our findings suggest that during inner speech, the alterations of white matter fiber tracts in patients with frequent hallucinations lead to abnormal coactivation in regions related to the acoustical processing of external stimuli. This abnormal activation may account for the patients' inability to distinguish self-generated thoughts from external stimulation.

Adult↗
PubMed2006

Does seasonal variation affect hallucinations in PD? A longitudinal study.

The objective of this study was to examine the chronobiology of visual hallucinations in Parkinson's disease (PD) patients to test whether hallucinations are more severe during darker months (winter) than summer months. We extracted longitudinal data on the UPDRS Thought Disorder (TD) score, taken as part of regular patient management on sequential visits through a 1-year cycle in hallucinating PD patients. To reduce the confounding effects of medication adjustments, analysis was restricted to patients with a baseline evaluation that did not involve a medication change. The primary outcome was the seasonal change in hallucination severity, defined as a change in TD score or neuroleptic use. Using Wilcoxon rank-sum tests, we compared the exacerbation of hallucination by season, focusing on winter (December through February) versus summer (June through August). A total of 51 hallucinating patients met entry criteria, and their longitudinal data were analyzed. There was no difference in hallucination severity with changing season; the level of wintertime exacerbation was no greater than summertime exacerbation (P = 0.42). Although hallucinations frequently develop in dimmed environments and evening hours, the darkness of wintertime does not exacerbate hallucinations in PD subjects on stable medications. Because we found no evidence of seasonal variations, we cannot recommend phototherapy or other strategies affecting chronobiological systems as research priorities to treat PD hallucinations. (c) 2006 Movement Disorder Society.

Darkness↗
PubMed2006

Hypoperfusion of the auditory and prefrontal cortices in Parkinsonian patients with verbal hallucinations.

We examined patients with and without auditory hallucinations, using n-isopropyl-p-[123I]iodoamphetamine single photon emission computed tomographic imaging. We assessed verbal hallucinations in the present study: patients with nonverbal auditory hallucinations were excluded. A total of 11 patients with verbal and visual hallucinations and 17 patients with visual hallucinations only were enrolled. Patients with both verbal and visual hallucinations revealed significant hypoperfusion in the bilateral prefrontal cortex and right superior temporal gyrus compared to patients with visual hallucinations only. There were no significant hyperperfusion in patients with verbal plus visual hallucinations. These results may support the release hallucination theory in verbal hallucinations of Parkinson's disease, although another explanations may be more appropriate and further studies are required.

Aged↗
PubMed2004

Aging and visual hallucinations in elderly psychiatric outpatients.

Estimates of the reported prevalence of visual hallucinations in the elderly vary from study to study. The aim of the present investigation was to re-evaluate the prevalence of visual hallucinations in elderly psychiatric outpatients and to examine pertinent risk factors. One hundred and twenty-two elderly (> or =60 years old) consecutive outpatients at our university hospital were investigated with a questionnaire regarding visual hallucinations and the Mini-Mental State Examination. Twelve of 122 (10%) patients suffered from visual hallucinations. Although advanced age, lower MMSE scores and dementia were significantly associated with the presence of visual hallucinations, logistic regression analysis revealed that only advanced age showed a tendency to predict the presence of visual hallucinations. In 53 patients with dementia examined separately, only advanced age was significantly associated with visual hallucinations. The present findings suggest that the prevalence of visual hallucinations in the elderly is about 10% and that aging is an important risk factor in the development of visual hallucinations in dementia. Further studies are required in order to investigate the contribution of age-related factors such as lowering visual acuity, bereavement and loneliness to the presence of visual hallucinations.

Aged↗