Anushka Irodi, who is a third-year medical student at Pembroke College, University of Cambridge currently studying Neuroscience for her intercalation. She is Co-President of the Pembroke College Medical & Veterinary Society, Committee Member of the Cambridge University Students’ Clinical Research Society and has a keen interest in translational research and scientific entrepreneurship. Having undertaken several research placements in the past, she is looking forward to her upcoming 2023 summer internship investigating meningioma pathogenesis in the Bronner lab at Caltech, USA. Her future aspirations lie in the direction of clinical academia and scientific commercialisation.

The Phantom of the RetinaIt

 

It was at the end of 2016 that Eric Nieman first began to see the alphabet fog1. On one day, it would be a pale yet dazzling green and on the next, it would be a dense dark grey. The words written in the fog could sometimes echo new events, such as a recent phrase Eric had recently heard on the radio, but would often be from the past, such as the contents of old conversations with friends. For most people, the visions would have been bewildering at best, and utterly terrifying at worst. What conclusion could there be other than the observer having lost their mind?

 

Fortunately, as a doctor, Eric knew this was not the case. Forty years prior, he had been diagnosed with glaucoma, a disease that damages the optic nerve and leads to loss of vision. Though he had undergone treatment at the time, his vision had gradually deteriorated and by 2013, he was entirely blind in his right eye with extremely limited vision in the left. Three years later, he began to see the startling visions of coloured fog and was diagnosed with Charles Bonnet Syndrome (CBS).

 

CBS is a neurological condition characterised by the occurrence of vivid visual hallucinations in patients who have often previously suffered some damage to their visual pathway at the level of the eye or higher centres in the brain2. The syndrome was first documented in 1760 by the Swiss scientist, Charles Bonnet. He reported that his grandfather, who had undergone cataract surgery in both eyes eleven years prior, had begun to develop dynamic coloured visions of men, women, birds, buildings, carriages and tapestries3. Patients with CBS cannot hear, smell, taste or touch any of their hallucinatory visions and are in fact, usually aware that what they see is not real4. The hallucinations that appear can range from simple images such as the fog that appeared in front of Eric, to complex scenes such as the plethora of objects seen by Bonnet’s grandfather5.

 

Since 1760, many more cases of CBS have been reported. Indeed, it is a relatively common disorder, affecting 1 in 5 people with poor vision and close to 50 million people worldwide6. Despite this, awareness of the condition is low within the patient population and even amongst the treating physicians7. A likely reason for this is one alluded to earlier; many sufferers are afraid of revealing their hallucinations for fear of being labelled mentally unstable2.

 

What causes these people to hallucinate?

 

One promising theory posits the idea of a ‘release’ mechanism triggered by sensory deprivation8. According to this hypothesis, loss of visual input disinhibits higher visual association centres, resulting in inappropriate patterns of neural excitation that give rise to ‘phantom vision’. This was explained elegantly by the eminent neuroscientist, V.S. Ramachandran9, using the example of a cat.

 

When we see a cat, it is the physical attributes (shape, size, colour, texture) that are captured in the retina of our eye. This information is split into visual processing streams that reach the primary visual cortex (V1) in the brain. It is then combined and analysed in higher processing centres to allow us to identify and recall the cat. However, when we imagine a cat, it appears that this information flow is reversed. We use our memories of cats and all their associated attributes from higher visual processing centres to influence the activity of V1. It is the interaction and activation of these areas in a top-down approach that allow us to ‘see’ an imaginary cat in front of us.

 

Ramachandran suggests that the line between seeing and imagining becomes blurred in a CBS patient. In a typical person, imagining a cat does not equate to ‘seeing’ the cat. This is due to the visual input signal provided by the active retinal cells informing you that the cat is not actually there. Following visual pathway damage, a CBS patient’s brain ‘fills in’ the missing visual information in the world around them, drawing on memory and experience present in the higher visual centres. The inhibition normally provided by visual input on higher brain centres is lost and thus what would usually be ‘imagined’ is instead perceived as being ‘seen’.

 

Though this remains one of multiple theories at present, there is evidence to support it. In a study by Merabet and colleagues10, healthy individuals were fitted with blindfolds and monitored over five days. The sudden and complete visual deprivation induced visual hallucinations akin to those seen in CBS, in over ~70% of subjects. A similar phenomenon is also seen in phantom limb pain11, a syndrome in which recent amputees complain of pain in the amputated, missing limb. It is theorised here too, that the loss of sensory input produces hallucinatory sensation. However, the hallucinations are tactile, corresponding to the sensory domain lost in this case.

 

Interestingly, external social factors may also play a role in CBS pathogenesis. Jones and colleagues12 saw that CBS patients experienced an exacerbation of visual hallucinations during the recent COVID-19 pandemic and that this was linked significantly to increased social isolation and loneliness. It has been suggested that this social isolation contributes in some form to the sensory deprivation that triggers visions7.

 

The picture thus remains incomplete and the answer to the question: “What causes these people to hallucinate?” remains elusive. Due to our poor understanding of the pathophysiology of this syndrome, we lack effective therapies for managing it. Improving a patient’s vision with methods such as eyeglasses or laser eye surgery has been reported to alleviate the incidence of hallucinations13. However, where interventions to enhance remaining vision are unsuccessful, the only remaining route of treatment is pharmacological. Unfortunately this is largely inefficacious and can often elicit unwanted side effects13. In the meantime, patients like Eric continue to face deterioration of their condition.

 

Further research into this intriguing syndrome is urgently needed in order to develop better therapeutics. In this process, we may also move one step closer to understanding the mystery that is the human mind.

 

Bibliography

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Pang L. Hallucinations Experienced by Visually Impaired: Charles Bonnet Syndrome. Optom Vis Sci. 2016 Dec;93(12):1466–78.

 

Damas-Mora J, Skelton-Robinson M, Jenner FA. The Charles Bonnet Syndrome in perspective. Psychol Med. 1982 May;12(2):251–61.

 

Gold K, Rabins PV. Isolated visual hallucinations and the Charles Bonnet syndrome: A review of the literature and presentation of six cases. Compr Psychiatry. 1989 Jan 1;30(1):90–8.

 

Wilkinson F. Auras and other hallucinations: windows on the visual brain. In: Progress in Brain Research [Internet]. Elsevier; 2004 [cited 2023 May 1]. p. 305–20. (The roots of visual awareness: a festschrift in honour of Alan Cowey; vol. 144). Available from: https://www.sciencedirect.com/science/article/pii/S0079612303144214

 

Subhi Y, Nielsen MA, Scott DAR, Holm LM, Singh A. Prevalence of Charles Bonnet syndrome in low vision: a systematic review and meta-analysis. Ann Eye Sci. 2022 Jun 15;7(0):12–12.

 

Jones L, Ditzel-Finn L, Enoch J, Moosajee M. An overview of psychological and social factors in Charles Bonnet syndrome. Ther Adv Ophthalmol. 2021 Jan 1;13:25158414211034716.

 

Manford M, Andermann F. Complex visual hallucinations. Clinical and neurobiological insights. Brain. 1998 Oct 1;121(10):1819–40.

 

Ramachandran VS, Blakeslee S. Phantoms in the Brain: Human Nature and the Architecture of the Mind. Fourth Estate; 1999. 328 p.

 

Merabet LB, Maguire D, Warde A, Alterescu K, Stickgold R, Pascual-Leone A. Visual Hallucinations During Prolonged Blindfolding in Sighted Subjects. J Neuroophthalmol. 2004 Jun;24(2):109.

 

Guenther K. ‘It’s All Done With Mirrors’: V.S. Ramachandran and the Material Culture of Phantom Limb Research. Med Hist. 2016 Jul;60(3):342–58.

 

Jones L, Ditzel-Finn L, Potts J, Moosajee M. Exacerbation of visual hallucinations in Charles Bonnet syndrome due to the social implications of COVID-19. BMJ Open Ophthalmol. 2021 Feb 1;6(1):e000670.

 

Hartney KE, Catalano G, Catalano MC. Charles Bonnet Syndrome: Are Medications Necessary? J Psychiatr Pract. 2011 Mar;17(2):137.