Based on recent insight into the thalamocortical system and its role in perception and conscious experience, a unified pathophysiological framework for hallucinations in neurological and psychiatric conditions is proposed, which integrates previously unrelated neurobiological and psychological findings. Gamma-frequency rhythms of discharge activity from thalamic and cortical neurons are facilitated by cholinergic arousal and resonate in networks of thalamocortical circuits, thereby transiently forming assemblies of coherent gamma oscillations under constraints of afferent sensory input and prefrontal attentional mechanisms. If perception is based on synchronisation of intrinsic gamma activity in the thalamocortical system, then sensory input to specific thalamic nuclei may merely play a constraining role. Hallucinations can be regarded as underconstrained perceptions that arise when the impact of sensory input on activation of thalamocortical circuits and synchronisation of thalamocortical gamma activity is reduced. In conditions that are accompanied by hallucinations, factors such as cortical hyperexcitability, cortical attentional mechanisms, hyperarousal, increased noise in specific thalamic nuclei, and random sensory input to specific thalamic nuclei may, to a varying degree, contribute to underconstrained activation of thalamocortical circuits. The reticular thalamic nucleus plays an important role in suppressing random activity of relay cells in specific thalamic nuclei, and its dysfunction may be implicated in the biological vulnerability to hallucinations in schizophrenia. Combined with general activation during cholinergic arousal, this leads to excessive disinhibition in specific thalamic nuclei, which may allow cortical attentional mechanisms to recruit thalamic relay cells into resonant assemblies of gamma oscillations, regardless of their actual sensory input, thereby producing an underconstrained perceptual experience.

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Background/Aims: Visuospatial impairments are known to occur in Alzheimer’s disease (AD). We hypothesised that functional magnetic resonance imaging (fMRI) response in task-related brain regions would be impaired in patients with AD during the task and that treatment with acetyl cholinesterase inhibitors would enhance activations in brain regions concerned with this visual perceptual processing. Method: Ten AD subjects were neuropsychologically assessed and underwent fMRI imaging whilst performing a series of visuospatial perception tasks, before and after treatment with acetyl cholinesterase inhibitors. Eleven healthy elderly comparison subjects were also scanned twice. Results: Regions of increased brain activation in AD included the left precuneus, left cuneus, left supramarginal gyrus, right parieto-temporal cortex and right inferior parietal lobule. Further, increased activation in the left precuneus was found to correlate significantly with improved functioning of activities of daily living. Conclusions: We believe this to be the first fMRI study that, after controlling for the confound of repeat scanning, demonstrates altered patterns of brain activation associated with visuospatial processing following treatment in patients with AD. The treatment-related improvement of visual perception in AD may rely on enhanced attentional mechanisms, thereby possibly supporting independent living through improvement on activities of daily living.