Things That Go Bump in the Mind!

Hi everyone! I have talked about fossils, and then promised that I would discuss 'more lively topics'! I am both keeping and breaking my promise in this post, since I am delving into the more paranormal side of (neuro)biology.

Ghost /ɡəʊst/ (n.): an apparition, usually of a dead person, which is believed to appear or become manifest to the living, typically as a nebulous image.

Stories of ghosts involve an awake individual perceiving the presence of something or someone, often considered malevolent, that is not physically present. These perceptions range most commonly from hearing (such as in the story of Ukiko), seeing (as claimed in the photograph of the ghost of Lord Combermere) and mechanical or thermal sensing by the skin (shivers down the spine!).

Notwithstanding the existence of these paranormals, humans perceive things that are not physically there. Given below are examples of such GHOSTS IN (NEURO)BIOLOGY.

Phosphenes

These are images or visual hallucinations, produced due to the firing of the retinal cells, strangely in the absence of any light entering the eye. They can appear as flashes, streaks of light, spots of light, or other small light shapes (Fig 1A). Generally, phosphene images can be produced due to:

1. Mechanical stimulation, such as rubbing one’s eyes.

2. Electrical stimulation of the visual cortex by several sources such as exposure to high energy radiation, magnetic fields and certain pharmaceuticals or stress.

Functional magnetic resonance imaging (fMRI) has revealed the regions within the brain with neuronal activity that are responsible for the generation of phosphenes (Fig1B, Ashtari, M. et al. (2014)). Transcranial magnetic stimulation (TMS) has allowed more detailed mapping of regions within the visual cortex that are sensitive to this stimulation and produce phosphenes (Fig1C, Schaeffner, L.F. et al (2017)).

Using TMS on specific visual cortex regions produces light flashes in the retina of the blind, opening up the possibility of non-invasive visual prosthetics. (Wang, H.Z., Wong, Y.T. (2023)) Generation of phosphenes is used as a diagnostic for visual cortex function.

It has been discovered that in patients suffering from migraine, visual cortex excitability is increased with lower activation threshold (leading to phosphene generation). (Aurora, S.K. et al. (2003)) This provides a brain activity pathway to target for therapy.

Closed-eye visualisations (CEVs)

These are very rare occurrences when the afflicted person perceives images upon closure of the eyes which ceases upon opening the eyes even in a dark room. The images seen can be simple lines or flashes or as complex as an image of an aboriginal man in bright clothing walking in a detailed landscape (Huang, C.W. et al. (2016)). Importantly, the afflicted recognises that the hallucinations are not real.

CEVs are distinct from phosphenes, particularly in terms of image complexity and the transient nature of CEV episodes. A seemingly related visualisation is Charles Bonnet Syndrome. This is more common, brought on by loss or severe impairment of vision and presents in the open eye state. Varied conditions can precipitate CEV such as alcohol withdrawal (Desai, S. et al. (2021)), clarithromycin treatment (Young, M.J. et al. (2021)), hyponatrimia (Peck, T. et al (2018)), and subdural hematoma (Huang, C.W. et al. (2016)).

Mechanisms for CEV are not elucidated yet, given the paucity of reported cases. Based on similarities with visual hallucinations in Parkinson’s disease (Firbank, M.J. et al. (2018)) and the reduction of GABA levels in response to clarithromycin, it has been proposed that suppression of GABA-ergic signalling might lead to the generation of CEV.

Figure 2. SPECT (single-photon emission computed tomography) imaging of cerebral blood flow (CBF): increased CBF in left posterior parieto-occipital lobe (arrow) in CEV during eye closure (A), which is reduced upon eye opening (B) and absent when recovered from CEV (C) (Huang, C.W. et al. (2016)).

Phantom Limbs

This phenomenon was first described as “sensory ghost” in 1872 (Mitchell, S.W. (1872)). It is now clear that almost all patients who have had a limb amputated will feel the presence of the lost limb. Post-amputation, an area in the somatosensory cortex (S1) corresponding to the lost limb loses input from the limb and is reorganised, resulting in neuroplastic alterations of the boundaries of the S1 body map. This reorganisation is thought to be the cause of multiple manifestations including the surfacing of previously masked responses and phantom limb pain (PLP) affecting 50–80% of all amputees.

Non-invasive methodologies such as MEG (magnetoencephalography) (Fig. 3A, Ramachandran, V.S., Rogers-Ramachandran, D. (2000)) and fMRI (Fig. 3B, MacIver, K. (2008)) are used to map the normal brain-limb motor links and hence also the topographical reorganisation of the cortex in amputees. Crucially, this reorganisation demonstrates neuroplasticity in the adult brain. Most importantly, finding causal links between cortical reorganisation and pain has allowed surgical implants of electrodes in the epidural space to effect a motor cortex stimulation which recently demonstrated significant reduction of PLP (Fagundes, W. (2025)).

Figure 3. Brain imaging of the phantom limb phenomenon. A: MEG imaging shows that the hand area (green) is missing from the right hemisphere of a left hand amputee and is activated by sensory input from face (red) and upper arm (blue). B: fMRI imaging of brain showing increased cortical activity in patients when imagining clenching of amputated fist compared to imagined exercise of healthy controls.

Conclusion

Biological ghosts exist! They are phenomena created by incredible quirks of the wiring within our brains. So don't be expecting any Goosebumps-esque occurrences anytime soon. Please share your thoughts (and any bio-ghost stories!) in the comments below. C u soon!