How do the blind 'see'? The role of spontaneous brain activity in self-generated perception

Abstract

Spontaneous activity of the human brain has been well documented, but little is known about the functional role of this ubiquitous neural phenomenon. It has previously been hypothesized that spontaneous brain activity underlies unprompted (internally generated) behaviour. We tested whether spontaneous brain activity might underlie internally-generated vision by studying the cortical visual system of five blind/visually-impaired individuals who experience vivid visual hallucinations (Charles Bonnet syndrome). Neural populations in the visual system of these individuals are deprived of external input, which may lead to their hyper-sensitization to spontaneous activity fluctuations. To test whether these spontaneous fluctuations can subserve visual hallucinations, the functional MRI brain activity of participants with Charles Bonnet syndrome obtained while they reported their hallucinations (spontaneous internally-generated vision) was compared to the: (i) brain activity evoked by veridical vision (externally-triggered vision) in sighted controls who were presented with a visual simulation of the hallucinatory streams; and (ii) brain activity of non-hallucinating blind controls during visual imagery (cued internally-generated vision). All conditions showed activity spanning large portions of the visual system. However, only the hallucination condition in the Charles Bonnet syndrome participants demonstrated unique temporal dynamics, characterized by a slow build-up of neural activity prior to the reported onset of hallucinations. This build-up was most pronounced in early visual cortex and then decayed along the visual hierarchy. These results suggest that, in the absence of external visual input, a build-up of spontaneous fluctuations in early visual cortex may activate the visual hierarchy, thereby triggering the experience of vision.

Keywords: Charles Bonnet syndrome; functional MRI; spontaneous activity; spontaneous behaviour; visual hallucinations.

Figure 1

Schematic of experimental design and participants. (A) Top: Individuals with CBS were asked to verbally/manually report their visual hallucinations while in the MRI scanner. Inset: Schematic of blood oxygenation level-dependent (BOLD) signal in the visual system, vertical line represents the timing of hallucination report. The hypothesis for this condition is that activation in the visual system would ramp up prior to the perception of hallucinations. Bottom: Schematic of hallucination content of all CBS participants (Table 1). Top row depicts the hallucinatory content of the three CBS participants who were able to report their hallucinations; bottom row depicts the hallucinatory content of the two participants who were unable to report their hallucinations (see ‘Materials and methods’ section). (B) Verbal reports of hallucinations of the CBS participant were illustrated as movies, which were presented to sighted control participants. Inset: The experimental hypothesis of this condition is that activation in the visual system would ramp up only after visual stimuli are perceived. (C) All participants completed a visual imagery scan, in which they were asked to imagine faces, houses, objects and patterns. Inset: The hypothesis for this condition is that activation in the visual system would ramp up only after visual imagery has initiated. As depicted in this figure, visual hallucinations, like other visual experiences, were hypothesized to activate the entire visual hierarchy.

Figure 2

Hallucination compared to normal vision. Left column: Unthresholded maps; right column: The same maps with a statistical threshold, corrected for multiple comparisons. (A) CBS group maps in the hallucination condition (hallucination versus baseline), projected onto a representative flat cortical surface (the same map projected onto an inflated cortical surface is presented for reference). Wide red/blue contours depict significant areas of activation/deactivation, corrected for multiple comparisons. (B) Sighted control group maps in the simulated hallucination condition (simulated hallucinations versus baseline). Black contours depict significant areas of activation or deactivation, corrected for multiple comparisons. (C) The same group maps of the sighted controls in the simulated-hallucination condition, as presented in B, superimposed with the significant areas activated/deactivated during hallucinations in the CBS group (wide contours, as in A). White contours depict visual landmarks, based on a probabilistic atlas. FEF = frontal eye field; LH = left hemisphere; LO = lateral occipital complex; pIPS = posterior intraparietal sulcus; RH = right hemisphere. See Supplementary Figs 1 and 2.

Figure 3

Hallucination compared to visual imagery. Left column: Unthresholded maps; right column: the same maps with a statistical threshold, corrected for multiple comparisons. Group maps of the CBS group (A), blind control group (B), and sighted control group (C) during the visual imagery condition (imagery versus baseline). These maps are overlaid with the contours of areas activated/deactivated during hallucinations in the CBS group (as presented in Fig. 2, wide contours). Note the spatial overlap between hallucination and imagery activations in both the CBS and blind control groups in the left panel. FEF = frontal eye field; LH = left hemisphere; LO = lateral occipital complex; pIPS = posterior intraparietal sulcus; RH = right hemisphere. See also Supplementary Figs 4 and 5.

Figure 4

Hallucination, vision and visual imagery have different temporal dynamics. (A) Regions of interest V1–V4 (yellow contours), FFA (purple contours), lip areas (light blue contours). (B) Event-related averaging of group activations within each region of interest. Rows correspond with regions of interest (top row: V1–V4; middle row: FFA; and bottom row: lip region), and columns correspond with experimental conditions (hallucination in CBS participants and simulated hallucination in sighted controls in the left column, and visual imagery in the right column). Groups are represented by green, black and grey lines for CBS, sighted controls, and blind controls, respectively. Dashed lines depict hallucination onset (CBS), stimulus appearance in the visual condition (sighted controls) and onset of imagery instruction in the imagery condition. Note that visual (V1–V4, FFA) activations in the CBS group precede the onset of hallucinations, as marked with dark green arrows. This is unlike non-visual activations (lips region of interest) in the CBS group, simulated-hallucination activations in the sighted control group and imagery activations in all groups. See also Supplementary Figs 6–8.

Figure 5

Hallucination-related preceding signals decay along the visual hierarchy. The top and bottom plots present the data of the CBS group in the hallucination and imagery conditions, respectively. X-axes represent the hierarchical rank of visual regions of interest (Supplementary Table 1), grey labels depict one representative region of interest from each ranking category. Y-axes represent the optimal lag of the HRF relative to stimulus onset, as fitted to signals from these regions of interest. Dots depict group means for regions of interest and error bars depict standard deviations. IPS = intraparietal sulcus; SPL = superior parietal lobe.