Visual Neuroscience
Hallucinations
On the neurobiology of hallucinations
Who wrote it
Patricia Boksa, a neuroscientist at the Douglas Mental Health University Institute and the Department of Psychiatry of McGill University in Montréal, writing an editorial for the Journal of Psychiatry & Neuroscience, the Canadian Medical Association’s journal of the field. It appeared in July 2009, in volume 34, number 4, on pages 260 to 262: three pages, twenty-seven references, open access, and no competing interests declared.
What it is
An editorial, not a study. It is a short tour of what neuroscience knows about hallucinations, asked as one question, how close are we to understanding the brain mechanisms behind the hallucinations of psychotic disorders like schizophrenia, and written around the review of the hallucinating brain that Allen and colleagues had published the year before. Their model of auditory hallucination is what this page draws on the scan and as a circuit. She offers the piece as a foray, hoping it will “provoke increased interest and thought on this fascinating and challenging subject”.
What she is saying
A hallucination is a perception with no stimulus behind it and a compelling sense that it is real. It is a diagnostic feature of schizophrenia, where sixty to seventy per cent of people have them, most often voices; but it is not a sign of illness alone. Between seven and thirty per cent of children and adolescents report them, a third to a half of bereaved spouses see or hear the person they have lost, culture shapes where imagination ends, and mild sensory deprivation, half a ping pong ball over each eye and the sound of a waterfall, can bring vivid imagery to some healthy people. Whether the same mechanism is at work in patients and in the well is, she warns, not known.
The first clue is where lesions fall: in people hallucinating after brain damage, the damage lies in the pathway of the sense that hallucinates. Imaging of patients with schizophrenia fills the picture in. The most consistent structural finding is less grey matter in the superior temporal gyrus, primary auditory cortex included, with one large study adding the dorsolateral prefrontal cortex; functional studies of people hallucinating in the scanner find the language areas and the primary auditory cortex more active; and studies of connectivity agree that the links among temporal, prefrontal and anterior cingulate regions are altered. Hallucination, in other words, lives in the circuitry of normal hearing, language and their control.
The idea that ties the findings together is that a hallucinating person misattributes their own inner speech to the outside world. Her windows onto that are the oddest and the best part of the editorial: you cannot tickle yourself because you anticipate the touch, but people with hallucinations or passivity symptoms feel self-tickling as keenly as another’s touch; hypnotised people hearing real speech and people told to hallucinate it both light up the right anterior cingulate cortex, though she is careful about what that proves; and on waking from REM dreams, women show the same lapse in telling self-made from external stimuli. Deficits in judging time may feed the same confusion.
Allen’s model gathers it into three parts, which the circuit on this page draws: overactivity in the primary and secondary auditory cortex, altered connectivity with the language areas of the inferior frontal cortex, and weakened control by the anterior cingulate, prefrontal, premotor and cerebellar cortices. How that altered activity arises she leaves open, pointing to Behrendt’s idea that perception rides on gamma rhythms in thalamocortical loops which, in schizophrenia, slip the hold of the senses and fall to attention instead, and to the parvalbumin interneurons that pace those rhythms. On treatment, slow rTMS over the right temporoparietal cortex damps resistant voices with a mean effect size of 0.76, larger, for comparison, than clozapine’s 0.48 against typical antipsychotics on a general rating scale.
She closes on the limits. In people, brain activity can only be shown to go with hallucinations, never to cause them; and the animals that would settle cause cannot tell us whether they hallucinate, since the behaviours taken for it are too unspecific. Useful insight has been gained, and there is a long way still to go.
Boksa P. On the neurobiology of hallucinations. Journal of Psychiatry & Neuroscience 2009;34(4):260–262. PMID 19568476
Pick a region in the list, or a box in the circuit, and what the imaging found there appears here, for the state showing.
What it does
Disease
Damage
When perception is intact
In hallucinating people
Allen's model is a claim about signal flow. Hearing is not what breaks — someone who hallucinates hears the world exactly as anyone else does. What breaks is the handling of the brain's own inner speech: the control regions normally send a copy of the command with it, marking it as self-generated, and when that copy fails to arrive the same inner speech is heard as a voice from somewhere else.
Hearing the world unchanged in both
Sound arrives from the world, is relayed by the thalamus and is worked up through the auditory cortices until it is heard. This pathway is the same either way: hallucination is not a failure of hearing, and someone who hallucinates hears the world as anyone else does.
The brain's own inner speech tagged as one's own
Boksa opens by unsettling the assumption that hallucinations belong to schizophrenia alone. She adds one crucial caveat: it is unknown at present whether hallucinations are generated by similar mechanisms in patients and in healthy people.
of people with schizophrenia experience hallucinations, auditory being the most common.
of children and adolescents report hallucinations, across six community surveys in various countries.
of bereaved spouses report hallucinations of the deceased.
halves of a ping pong ball over the eyes, plus a waterfall recording, can induce vivid dreamlike imagery in some healthy people.
Allen and colleagues reviewed structural, functional and connectivity studies of the hallucinating brain. Boksa's summary of their findings, and of the model they propose.
| Method | Finding |
|---|---|
| Structural | The most consistent result is reduced grey matter volume in the superior temporal gyrus, including primary auditory cortex. One fairly large study also found volume reduction in the DLPFC, suggesting faulty frontotemporal interactions may underlie the sense that hallucinations are involuntary. |
| Functional | Studies of actively hallucinating participants generally report increased activity in language areas and primary auditory cortex, strongly implicating superior and middle temporal gyri — though other nonsensory cortical and subcortical areas have been implicated too. |
| Connectivity | Diffusion tensor and functional imaging concur in showing altered connectivity among temporal, prefrontal and anterior cingulate regions. |
| Allen's model | Overactivity in primary and/or secondary auditory cortices, altered connectivity with inferior frontal language areas, and weakened control by anterior cingulate, prefrontal, premotor and cerebellar cortices. |
| Lesions | In psychologically normal individuals hallucinating after a lesion, the lesion was generally in the sensory pathway of the same modality as the hallucination. |
| Treatment | Slow rTMS over right temporoparietal cortex reduced treatment-resistant auditory hallucinations, mean effect size 0.76. Boksa offers a comparison: clozapine versus typical antipsychotics scored 0.48 on the Brief Psychiatric Rating Scale — though that meta-analysis did not target hallucinations specifically. |
Three approaches Boksa reports, each with the reservation she attaches to it.
| Approach | What it showed | Boksa's reservation |
|---|---|---|
| Self-tickling | A self-generated stimulus is attenuated because we anticipate its sensory consequences. Healthy controls found self-tickling less intense than an experimenter's touch; participants with auditory hallucinations or passivity phenomena did not discriminate between the two. | The underlying mechanisms for such misattribution are not yet understood. |
| Hypnosis | The right anterior cingulate activated in hypnotisable people both when hearing real speech and when instructed to hallucinate, but not when imagining speech — suggesting a role in attributing speech to an external source. | Controls should also have activated the ACC on hearing real speech, and did not. Altered ACC activation also appears in non-hallucinatory hypnotic suggestion, so it may reflect suggestibility itself. |
| REM sleep | Hallucinations and delusions are regular features of REM. On waking from REM dreams, women — but not men — showed a deficit in monitoring self-generated versus externally generated stimuli. | Offered as a potential insight rather than an established parallel. |
The editorial's closing argument, which is as much about the limits of the evidence as about the evidence.
In studies with human participants, neural processes can only be shown to correlate with hallucinations, not to definitively cause them. Every finding above is an association.
Animal models, which are normally where causal evidence comes from, do not resolve it. Monkeys and dogs can apparently tell their own vocalisations from another animal's, so one might expect them to misattribute under abnormal conditions — but assessing whether an animal is hallucinating is problematic. Monkeys given drugs known to produce psychosis in humans do show behavioural changes, yet what has been categorised as hallucinatory-like behaviour, such as responding to nonapparent stimuli or staring for extended periods, is too nonspecific for research into mechanism.
Boksa's own conclusion is that although useful insight has been gained, we still have a long way to go to fully understand what causes the voices and visions of schizophrenia.
Each region’s parcels as one surface in its colour, faded where the state showing has it fall back, with the brain’s surface for context.
Scan MNI152 template · AAL-116 parcellation
Regions the ten of Allen’s model, each drawn on the atlas parcels it occupies, approximate where the list says so.
Studies the papers the readings name, in full.
- Aleman A, Sommer IE, Kahn RS. Efficacy of slow repetitive transcranial magnetic stimulation in the treatment of resistant auditory hallucinations in schizophrenia: a meta-analysis. J Clin Psychiatry 2007;68(3):416–421. doi:10.4088/jcp.v68n0310
- Allen P, Larøi F, McGuire PK, Aleman A. The hallucinating brain: a review of structural and functional neuroimaging studies of hallucinations. Neurosci Biobehav Rev 2008;32(1):175–191. doi:10.1016/j.neubiorev.2007.07.012
- Behrendt RP. Dysregulation of thalamic sensory “transmission” in schizophrenia: neurochemical vulnerability to hallucinations. J Psychopharmacol 2006;20(3):356–372. doi:10.1177/0269881105057696
- Blakemore SJ, Frith CD, Wolpert DM. Spatio-temporal prediction modulates the perception of self-produced stimuli. J Cogn Neurosci 1999;11(5):551–559. doi:10.1162/089892999563607
- Blakemore SJ, Smith J, Steel R, Johnstone CE, Frith CD. The perception of self-produced sensory stimuli in patients with auditory hallucinations and passivity experiences: evidence for a breakdown in self-monitoring. Psychol Med 2000;30(5):1131–1139. doi:10.1017/s0033291799002676
- Ford JM, Mathalon DH. Corollary discharge dysfunction in schizophrenia: can it explain auditory hallucinations? Int J Psychophysiol 2005;58(2–3):179–189. doi:10.1016/j.ijpsycho.2005.01.014
- Lawrie SM, Buechel C, Whalley HC, Frith CD, Friston KJ, Johnstone EC. Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations. Biol Psychiatry 2002;51(12):1008–1011. doi:10.1016/s0006-3223(02)01316-1
- Lodge DJ, Behrens MM, Grace AA. A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia. J Neurosci 2009;29(8):2344–2354. doi:10.1523/JNEUROSCI.5419-08.2009
- Raz A, Fan J, Posner MI. Hypnotic suggestion reduces conflict in the human brain. Proc Natl Acad Sci USA 2005;102(28):9978–9983. doi:10.1073/pnas.0503064102
- Sohal VS, Zhang F, Yizhar O, Deisseroth K. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 2009;459(7247):698–702. doi:10.1038/nature07991
- Stephan KE, Friston KJ, Frith CD. Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull 2009;35(3):509–527. doi:10.1093/schbul/sbn176
- Szechtman H, Woody E, Bowers KS, Nahmias C. Where the imaginal appears real: a positron emission tomography study of auditory hallucinations. Proc Natl Acad Sci USA 1998;95(4):1956–1960. doi:10.1073/pnas.95.4.1956
- Waters F, Jablensky A. Time discrimination deficits in schizophrenia patients with first-rank (passivity) symptoms. Psychiatry Res 2009;167(1–2):12–20. doi:10.1016/j.psychres.2008.04.004
An educational visualization of Boksa P, “On the neurobiology of hallucinations,” Journal of Psychiatry & Neuroscience 2009;34(4):260–262 — open access at PMC2702442. Regions are drawn on the MNI152 template using the AAL-116 parcellation; each named region is matched to its nearest atlas parcel, and where that match is approximate the panel says so. The editorial concerns auditory hallucinations in schizophrenia almost throughout and does not address serotonergic, glutamatergic or default-mode accounts. It is now well over fifteen years old, and the field has moved. Not a diagnostic tool. About · Privacy & support · Terms of use.