Disorders of Higher Brain Regions Associated with Hallucinations

Hallucinations are also associated with primary pathology at higher levels of the brain. Most prominent in this category are those that occur in migraine, epilepsy, and schizophrenia. Investigation of cerebral activity associated with hallucinations in these settings has been aided in recent years by the development of techniques such as electroencephalography (EEG), evoked potentials, single photon emission computed tomography (SPECT), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI). Combined with data from other avenues of investigation, studies employing these tools have implicated a number of higher brain regions in the generation of hallucinations, corresponding to their form, content, and setting.

1. Cortical Sensory Activity Associated with Hallucinations

Regardless of the mechanism by which they are generated (primary peripheral, midbrain/thalamic, or higher brain disturbances), hallucinations appear to be associated with activity in cortical sensory regions corresponding to their modality and complexity. The hallucinations described previously may be described as complex or formed. Noncomplex hallucinations are referred to interchangeably as simple, unformed, or crude. In the visual system, these are known as photopsias, and they occur frequently with migraines. In this setting, the most common forms are colorless glittering spots and black-and-white zigzag patterns known as fortification lines. They often occur unilaterally but may fill the entire visual field. Photopsias can also occur, briefly, at the onset of partial seizures and for the first few days following an infarction of the central visual system. In both settings they tend to be brightly colored and unilateral. In addition, disorders of visual input may give rise to photopsias. Simple hallucinations are believed to reflect activity in primary sensory or adjacent early unimodal association areas and to correspond in form to the area's functional specialization. For example, colored photopsias would be associated with activity in occipital subregions involved in color processing, as described previously.

Complex hallucinations are associated with activity in sensory association areas, with or without involvement of primary sensory cortex. As with simple hallucinations, their form and content correspond to the location of activity. We investigated neural activity associated with auditory/visual hallucinations in a 23-year-old man with schizophrenia. The subject underwent PET scanning while experiencing frequent hallucinations of colored, moving scenes containing disembodied, rolling heads that spoke to him in a derogatory fashion. Using techniques that allow for identification of activity simultaneous with hallucinatory events, we detected activations in occipital and temporal visual association cortex (higher order visual perception), temporal auditory-linguistic association cortex (speech perception), and temporoparietal and prefrontal heteromodal association cortex (intermodal processing) (Fig. 1). Activations were bilateral but more extensive on the left, perhaps reflecting the dominance of that hemisphere for language.

2. Limbic/Paralimbic Activity Associated with Hallucinations

The previously mentioned study included five other subjects, all of whom experienced frequent auditory/ verbal hallucinations in the setting of schizophrenia. Although each had a somewhat different pattern of sensory cortical activation, perhaps reflecting differences in the form and content of their hallucinations, group analysis revealed a highly significant pattern of common activations in thalamic, limbic, and

Primary motor and somatosensory Heteromoda! association cortex:

cortex: processes basic motor and tactile integrates complex percepts from multiple information (associated with pressing button sensory modalities with stored information, to report hallucinations) leading to object recognition

Primary motor and somatosensory Heteromoda! association cortex:

cortex: processes basic motor and tactile integrates complex percepts from multiple information (associated with pressing button sensory modalities with stored information, to report hallucinations) leading to object recognition

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