Lingual gyrus

The lingual gyrus, located in the occipital lobe, plays a role in visual memory, facial recognition, and the perception of letters, shapes, colors, and motion. Studies have shown that individuals with VS/VSS often exhibit increased gray matter volume (GMV) and hypermetabolism of the lingual gyrus [ ]. Hypermetabolism of the right lingual gyrus has been demonstrated with PET imaging [ ], and increased GMV in the right lingual gyrus has been shown with voxel-based morphometry (VBM) [ ] These changes were most prominent in the lingual gyrus–fusiform gyrus junction [ ] and in the post-thalamic visual pathways from the right pulvinar to the right lingual gyrus [ ]. The magnitude of GMV was associated with disease duration but not severity. The researchers also found increased lactate and glutamate concentrations in the right lingual gyrus of VS patients, thus suggesting metabolic hyperactivation [ ].

These changes in GMV likely indicate a dynamic increase in synaptic strength and plasticity over time. This increase in synaptic activity may reflect chronicity. Given the role of the lingual gyrus in multisensory integration, alterations in connectivity and metabolism could explain the abnormalities beyond vision that individuals with VSS report, including auditory and tactile sensitivities.

Visual cortex

The visual cortex consists of multiple specialized areas that collaboratively form one’s conscious visual experience. Individuals with VSS exhibited morphologic changes in GMV of the left primary (V1) and secondary (V2) visual cortices, as well as the left visual motion area (V5), when compared with matched controls [ ]. White matter alterations also were evident with diffusion tensor imaging (DTI) in the visual cortex, as well as the frontal and temporal cortex, including the inferior fronto-occipital fascicle, sagittal stratum, and right superior longitudinal fasciculus [ ]. Electrophysical studies using VEP indicate possible dysfunction in the primary visual and visual association cortices as well, but the results were mixed [ ].

These areas comprise the visual motion network in the dorsal stream. It is plausible that hyperexcitation in these areas may result in the illusion of a moving, full-field, pixelated overlay. These anatomic changes were not associated with clinical features, such as duration or severity, perhaps indicating an inherent trait and not a consequence of VSS per se.

Thalamus

The thalamus plays a crucial role in relaying sensory information to the cortex. Dysregulation in thalamic processing has been proposed as a potential factor in VSS [ ].

In contrast to post-thalamic pathways to the lingual gyrus, there was reduced connectivity between the pulvinar and bilateral dorsal aspects of the caudate nuclei [ ]. This part of the visual cortico-striatal loop helps inhibit general visual noise through a feedforward mechanism. A bottom-up disruption may allow this error to reach higher processing areas, implying a disruption in filtering and integrating visual information versus internal generation.

When neuronal integration and synchronization of the thalamus is disrupted, thalamocortical dysrhythmia (TCD) may arise. TCD is thought to be a frequency imbalance due to dysregulated neural oscillations between the thalamus and cortex, thus contributing to a host of persistent sensory disturbances. With the Intuitive Colorimeter (IC), VS patients exhibited a yellow–blue color preference and disliked blue–violet wavelengths as compared with controls [ ]. This could implicate the koniocellular pathway, which includes cells that transmit short-wave (S-cone) signals related to blue–yellow color vision through the thalamocortical pathway. These findings further support the use of chromatic filters, which may promote thalamocortical synchrony.

Attentional and salience networks

These networks allocate cognitive resources to facilitate directed attention and awareness of relevant stimuli in the environment. Widespread disturbances were found in those with VSS in the integration of these networks with the ventral attention network (VAN) and dorsal attention network (DAN) using fMRI [ ]. Several parts of the VAN were less well integrated with the visual motion network, thus suggesting a reduced capacity to refocus visual attention to the environment.

Altered coupling also was noted between the default mode network (DMN) and DAN, and within the salience network itself. The DMN is active when an individual is at rest or engaged in internally focused thoughts. The anterior cingulate cortex (ACC) and anterior insula (AI) function as part of the salience network to assign significance to sensory and internal stimuli. Any aberrant connectivity between these networks implies a shift from the self-referential cognition of the default mode network (DFM) to the directed attention of the DAN. This dysfunctional salience and attentional modulation may misappropriate irrelevant internal stimuli as external perception.

Further support for an attentional interaction comes from eye movement studies. Patients with VSS had longer prosaccade latencies and more antisaccade errors, as well as a delayed onset of inhibition of return [ ]. The investigators suggest that disrupted attentional networks may increase saccade-related activity, as opposed to poor frontally mediated inhibitory control. These findings may provide an oculomotor profile to aid in the measurement of dysfunction and assist in the determination of a therapeutic intervention.

Other brain sites

Many other neurologic sites have been implicated including the frontal eye fields, right middle temporal (MT) gyrus, right parahippocampal gyrus, left superior temporal gyrus, bilateral cuneus, precuneus, supplementary motor cortex, premotor cortex, posterior cingulate cortex, left primary auditory cortex, left fusiform gyrus, and left cerebellum [ ]. This list is not exhaustive, and it is important to view this condition as a multidimensional sensorimotor network disorder , combining afferent, efferent, and central processing components. Clearly, more research in the area is needed to obtain a more accurate representation of the VS/VSS neural pathways.

It is worth noting that this condition is related to, but distinct from, migraine, thus displaying its own metabolic and structural profile on neuroimaging studies. In addition, neuro-ophthalmic evaluation has shown normal pupillary light reflex and contrast sensitivity in patients with VSS compared with migraineurs further supporting this distinction [ ].

Many possibilities have been proposed to be the neurophysiological-based etiology of VS, as discussed earlier. One that is frequently mentioned is hyperexcitability of the angular gyrus [ ]. However, more recently, another neural site was proposed, namely the extrastriate visual area of the MT region [ ]. It is well-known that MT is active in the generation and perception of visual motion and furthermore has poor overall retinotopic mapping. However, when its small clusters of cells are stimulated, they are directionally specific. But, when injured, for example, a mild traumatic brain injury (mTBI), a marked increase occurs in its cellular spontaneous activity, thus resulting in hyperexcitability of its cells. If sustained, current spread would take place, with the resultant simultaneous stimulation of all of the cells. This would give rise to multidirectional signals, that is, dynamic visual noise, that is, VS. Furthermore, because MT has a chromatic input, this could be responsible for the VS being chromatic in most cases. Hence, the use of a precision chromatic filter would reduce the overall luminance of the visual field and in turn decrease the cellular hyperexcitability, as well as its chromatic bias acting to filter out the blue–green end of the spectrum.