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The hodotopic framework is a recent revision of Geschwind's disconnection paradigm incorporating advances in functional and white matter imaging. Its intention is to help clinico-pathological correlations across a range of neurological and psychiatric conditions and generate novel research questions. Here I consider hallucinations within this framework. The paper is divided into three parts. The first reviews the auditory and visual hallucination literature from the dual perspectives of dysfunction localised to specific brain regions (topological) and dysfunction related to connections between brain regions (hodological), combining evidence from tractography, functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) studies. Patients prone to hallucinations have complex, task-specific hodological abnormalities that persist between hallucination episodes. During hallucinations, topological increases in activity are found whose location defines hallucination content and modality. Whether these activity increases are accompanied by transient hodological change is unclear. The second part of the paper addresses this issue in EEG and fMRI studies of a 200-year-old paradigm. Photic stimulation within a specific frequency and luminance range induces hallucinations of geometrical patterns, colours and motion in normal subjects. By comparing hallucination-inducing with control stimulation, topological activity increases were identified in visual areas whose specialisations matched the induced hallucination contents. During hallucinations, fMRI connectivity between LGN and cortex changed from a positive to negative relationship while EEG connectivity between occipital and other brain regions increased. The complex and dynamic topological and hodological changes during induced hallucinations are consistent with a shift in thalamocortical circuitry from tonic to burst mode and may have direct relevance to the Charles Bonnet Syndrome. The third part of the paper considers the relevance of the finding to other disorders, examines the strengths and limitations of our current imaging approaches to connectivity and looks to future developments in the field.
Musical hallucinations are relatively rare auditory percepts which, due to their intrusive nature and the accompanying fear of impending mental decline, tend to cause significant distress and impairment. Although their etiology and pathophysiology appear to be heterogeneous and no evidence-based treatment methods are available, case reports indicate that acetylcholinesterase inhibitors may yield positive results in patients with comorbid hearing loss. We present two female patients (aged 76 and 78 years) both of whom suffered from hearing impairment and practically incessant musical hallucinations. Both patients were successfully treated with the acetylcholinesterase inhibitor rivastigmine. Based on these two case descriptions and an overview of studies describing the use of acetylcholinesterase inhibitors in similar patients, we discuss possible mechanisms and propose further research on the use of acetylcholinesterase inhibitors for musical hallucinations experienced in concordance with hearing loss.
Musical hallucinations are poorly understood phenomena. Their relation with epilepsy was first described over a century ago, but never systematically explored. We, therefore, reviewed the literature, and assessed all descriptions of musical hallucinations attributed to epileptic activity. Our search yielded 191 articles, which together describe 983 unique patients, with 24 detailed descriptions of musical hallucinations related to epilepsy. We also describe six of our own patients. Based on the phenomenological descriptions and neurophysiological data, we distinguish four subgroups of epilepsy-related musical hallucination, comprising auras/ictal, inter-ictal and post-ictal phenomena, and phenomena related to brain stimulation. The case descriptions suggest that musical hallucinations in epilepsy can be conceptualised as lying on a continuum with other auditory hallucinations, including verbal auditory hallucinations, and-notably-tinnitus. To account for the underlying mechanism we propose a Bayesian model involving top-down and bottom-up prediction errors within the auditory network that incorporates findings from EEG and MEG studies. An analysis of phenomenological characteristics, pharmacological triggers, and treatment effects suggests wider ramifications for understanding musical hallucinations. We, therefore, conclude that musical hallucinations in epilepsy open a window to understanding these phenomena in a variety of conditions.
Hallucinations involve sensing things such as visions, sounds, or smells that seem real but are not. These things are created by the mind. However, little is known about the distribution of incident hallucinations in the community. This paper aims to examine manifestation and frequency of the hallucinatory experiences within the general Croatian population.
Hearing perception in individuals with auditory hallucinations has not been well studied. Auditory hallucinations have previously been shown to involve primary auditory cortex activation. This activation suggests that auditory hallucinations activate the terminal of the auditory pathway as if auditory signals are submitted from the cochlea, and that a hallucinatory event is therefore perceived as hearing. The primary auditory cortex is stimulated by some unknown source that is outside of the auditory pathway. The current study aimed to assess the outcomes of stimulating the primary auditory cortex through the auditory pathway in individuals who have experienced auditory hallucinations. Sixteen patients with schizophrenia underwent functional magnetic resonance imaging (fMRI) sessions, as well as hallucination assessments. During the fMRI session, auditory stimuli were presented in one-second intervals at times when scanner noise was absent. Participants listened to auditory stimuli of sine waves (SW) (4-5.5kHz), English words (EW), and acoustically reversed English words (arEW) in a block design fashion. The arEW were employed to deliver the sound of a human voice with minimal linguistic components. Patients' auditory hallucination severity was assessed by the auditory hallucination item of the Brief Psychiatric Rating Scale (BPRS). During perception of arEW when compared with perception of SW, bilateral activation of the globus pallidus correlated with severity of auditory hallucinations. EW when compared with arEW did not correlate with auditory hallucination severity. Our findings suggest that the sensitivity of the globus pallidus to the human voice is associated with the severity of auditory hallucination.
Previous reports suggest that adverse events during childhood could be related to an array of psychiatric problems. Here, we question the relationship between childhood traumatic experiences and the sensory complexity of hallucinations in a cohort of 75 children and adolescents. We evidence a positive link between the number of sensory modalities involved in hallucinations and history of childhood trauma, even after controlling for the co-occurrence of suicidal ideation or the number of ICD-10 diagnoses. These findings support initiatives in which a routine exploration of traumatic events in childhood is performed when multimodal hallucinations are present.
Although many structural and functional abnormalities have been related to schizophrenia, until now, no single biological marker has been of diagnostic clinical utility. One way to obtain more valid findings is to focus on the symptoms instead of the syndrome. Auditory hallucinations (AHs) are one of the most frequent and reliable symptoms of psychosis. We present a review of our main findings, using a multidisciplinary approach, on auditory hallucinations. Firstly, by applying a new auditory emotional paradigm specific for psychosis, we found an enhanced activation of limbic and frontal brain areas in response to emotional words in these patients. Secondly, in a voxel-based morphometric study, we obtained a significant decreased gray matter concentration in the insula (bilateral), superior temporal gyrus (bilateral), and amygdala (left) in patients compared to healthy subjects. This gray matter loss was directly related to the intensity of AH. Thirdly, using a new method for looking at areas of coincidence between gray matter loss and functional activation, large coinciding brain clusters were found in the left and right middle temporal and superior temporal gyri. Finally, we summarized our main findings from our studies of the molecular genetics of auditory hallucinations. Taking these data together, an integrative model to explain the neurobiological basis of this psychotic symptom is presented.
Recent findings have demonstrated that emotional prosody (EP) attracts attention involuntarily (Grandjean et al., 2008). The automat shift of attention toward emotionally salient stimuli can be overcome by attentional control (Hahn et al., 2010). Attentional control is impaired in schizophrenia, especially in schizophrenic patients with hallucinations because the "voices" capture attention increasing the processing load and competing for top-down resources. The present study investigates how involuntary attention is driven by implicit EP in schizophrenia with auditory verbal hallucinations (AVH) and without (NAVH). Fifteen AVH patients, 12 NAVH patients and 16 healthy controls (HC) completed a dual-task dichotic listening paradigm, in which an emotional vocal outburst was paired with a neutral vocalization spoken in male and female voices. Participants were asked to report the speaker's gender while attending to either the left or right ear. NAVH patients and HC revealed shorter response times for stimuli presented to the attended left ear than the attended right ear. This laterality effect was not present in AVH patients. In addition, NAVH patients and HC showed faster responses when the EP stimulus was presented to the unattended ear, probably because of less interference between the attention-controlled gender voice identification task and involuntary EP processing. AVH patients did not benefit from presenting emotional stimuli to the unattended ear. The findings suggest that similar to HC, NAVH patients show a right hemispheric bias for EP processing. AVH patients seem to be less lateralized for EP and therefore might be more susceptible to interfering involuntary EP processing; regardless which ear/hemisphere receives the bottom up input.
Throughout the lifespan, the cerebral cortex adapts its structure and function in response to changing sensory input [1, 2]. Whilst such changes are typically adaptive, they can be maladaptive when they follow damage to the peripheral nervous system, including phantom limb pain and tinnitus [3, 4]. An intriguing example occurs in individuals with acquired ocular pathologies-most commonly age-related macular degeneration (MD) [5]-who lose their foveal vision but retain intact acuity in the peripheral visual field. Up to 40% of ocular pathology patients develop long-term hallucinations involving flashes of light, shapes, or geometric patterns and/or complex hallucinations, including faces, animals, or entire scenes, a condition known as Charles Bonnet Syndrome (CBS) [6, 7, 8]. Though CBS was first described over 250 years ago [9, 10], the neural basis for the hallucinations remains unclear, with no satisfactory explanation as to why some individuals develop hallucinations, while many do not. An influential but untested hypothesis for the visual hallucinations in CBS is that retinal deafferentation causes hyperexcitability in early visual cortex. To assess this, we investigated electrophysiological responses to peripheral visual field stimulation in MD patients with and without hallucinations and in matched controls without ocular pathology. Participants performed a concurrent attention task within intact portions of their peripheral visual field, while ignoring flickering checkerboards that drove periodic electrophysiological responses. CBS individuals showed strikingly elevated visual cortical responses to peripheral field stimulation compared with patients without hallucinations and controls, providing direct support for the hypothesis of visual cortical hyperexcitability in CBS.
Auditory hallucinations, the perception of a sound without a corresponding source, are common in people with hearing impairment. Two forms can be distinguished: simple (i.e., tinnitus) and complex hallucinations (speech and music). Little is known about the precise mechanisms underlying these types of hallucinations. Here we tested the assumption that spontaneous activity in the auditory pathways, following deafferentation, underlies these hallucinations and is related to their phenomenology. By extracting (fractional) Amplitude of Low Frequency Fluctuation [(f)ALFF] scores from resting state fMRI of 18 hearing impaired patients with complex hallucinations (voices or music), 18 hearing impaired patients with simple hallucinations (tinnitus or murmuring), and 20 controls with normal hearing, we investigated differences in spontaneous brain activity between these groups. Spontaneous activity in the anterior and posterior cingulate cortex of hearing-impaired groups was significantly higher than in the controls. The group with complex hallucinations showed elevated activity in the bilateral temporal cortex including Wernicke's area, while spontaneous activity of the group with simple hallucinations was mainly located in the cerebellum. These results suggest a decrease in error monitoring in both hearing-impaired groups. Spontaneous activity of language-related areas only in complex hallucinations suggests that the manifestation of the spontaneous activity represents the phenomenology of the hallucination. The link between cerebellar activity and simple hallucinations, such as tinnitus, is new and may have consequences for treatment.
Olfactory dysfunctions and hallucinations are considered common nonmotor symptoms in Parkinson's disease (PD). Visual and auditory hallucinations are well-known; however, olfactory hallucinations (OHs) are not fully investigated. The aim of this study was to evaluate OHs in PD patients, and their correlation to motor impairment, cognitive abilities, visual and auditory hallucinations, and olfactory and gustatory function.
The pathophysiology of visual hallucinations in Parkinson's disease has yet to be characterized. Although stimulus-driven ("bottom-up") processes are known to be impaired, the role of "top-down" processes remains to be determined. Distinguishing between conscious and non-conscious detections (i.e. access to consciousness) may be a valuable way of monitoring top-down processes. Conscious access to visual inputs was investigated to identify the neural substrates underlying susceptibility to hallucinations in Parkinson's disease. Seventeen healthy controls, 18 Parkinson's disease patients with minor visual hallucinations and 16 without were enrolled in the study. During functional magnetic resonance imaging, the participants performed a visual detection task. The detection threshold was significantly higher in each patient group than in healthy controls while the two groups of patients did not differ significantly. Compared with hallucination-free patients, patients with minor hallucinations displayed hyperactivation of prefrontal and right occipital cortices, and hypoactivation of the left cingulate, temporal and occipital cortices. During conscious access to visual inputs, the functional network in patients with visual hallucinations differed from that seen in patients without visual hallucinations. This suggests that the supremacy of top-down processes in visual information processing may enhance susceptibility to hallucinations in Parkinson's disease.
This case report describes the progression of symptoms in a young deaf female. Her initial psychotic symptoms occur at the age of 16, but she did not come into contact with a psychiatric treatment facility before the age of 27, where she felt symptoms were distressing. The case report describes the difficulties in evaluating psychotic symptoms in a deaf patient, as well as the use of specialized scales in combination with the standard psychiatric evaluation. The current evidence, concerning the prevalence of psychotic symptoms, as well as the influence of deafness on the understanding of psychosis, is described.
Hallucinations are common in Parkinson's disease and can be distressing to patients and their families. They are associated with higher rates of nursing home placement and with increased mortality. Their underlying mechanisms have been elusive, but recent advances in network imaging provides some intriguing insights into possible underlying drivers. Treatment is complicated by risk of worsening Parkinson's motor symptoms and by higher rates of mortality with antipsychotics, but new therapeutic avenues are emerging that offer potential hope.
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