We assessed here the brain activity in response to emotionally laden visual stimuli in one schizophrenia patient with agCC and in a group of schizophrenia patients of similar age, but with no evident damage to the brain (CC group). The results showed that the visual cortex activation in response to visual stimuli, regardless of their emotional content, was comparable in agCC patient and CC group both in terms of localization and intensity of activation. The only difference in this respect was that in the CC group a larger area was recruited, which included, among others, subcortical and prefrontal regions. In contrast, when comparing the brain activation in response to the emotional charge of the visual stimulation we observed a very large, non-specific and non-lateralized cerebral activation in the agCC patient, in contrast with the CC group, which showed a more lateralized and spatially localized activation. The analysis of the BOLD signal change in each of the activated regions obtained in the CC group revealed that the agCC patient actually had an opposite activation pattern relative to most participants with no CC agenesis, indicating a dysfunctional response to these kind of stimuli, consistent with the clinical presentation of this particular patient.
The congenital absence of CC, agenesis, is the main “natural” pathology of this brain structure and it has recently been estimated to have a prevalence of 1:4000 (Paul et al., 2007
). While its etiology is yet unclear, there are studies linking this condition to genetic and environmental factors occurring prenatally, typically between the 3rd and 12th week of pregnancy when this structure develops. For instance, both in animal models, as well as in humans, the pioneer axons from cingulate cortex are the first to cross the midline during embryonic development, providing guidance, and support for the callosal axons which cross the midline later (Rash and Richards, 2001
; Ren et al., 2006
). It is interesting to note that the gene disrupted in schizophrenia 1 (DISC1) was found to be inactivated in all 129 strain mice (an animal model in which 70% present agCC) and was causally linked to the agCC (Clapcote and Roder, 2006
). This finding not only shows that a genetic mutation may cause the agCC, but that there may be a common
genetic mutation that is seen in both agCC and schizophrenia. In addition to the genetic factors, infectious, vascular, and toxic causes of agCC were also identified (Paul et al., 2007
Based on the topography of the agenesis in our case study, which encompassed the dorsal CC aspect, above the genu, and surrounding the midline, as well as the istmus and anterior half of the spelnium, there are a number of cortical areas that may be disconnected from their contralateral homotopic parts. Parts of dorsolateral prefrontal cortex (BA9/BA44/BA45), including Broca’s area, as well as the superior temporal cortex, including Wernicke’s area, are usually connected to parts of CC that are absent in our patient. Even though the patient did not show marked language problems, she had nevertheless difficulty in encoding and interpreting verbal material. Other cortical regions that could be disconnected in our clinical case are: anterior cingulate cortex (BA32), posterior parietal cortex (BA7), supplementary motor, and premotor areas (BA6). Taken together, these regions are part of mirror neuron system (Iacoboni and Mazziotta, 2007
) and the clinical evidence that they could be affected by the agCC in our patient is given by her difficulty in imitating the other’s gestures.
Our imaging results illustrate two main points. On the one hand, we showed that in both our agCC patient and in the group of patients with no apparent damage to the CC, there was similar brain activity during basic visual information processing. Corroborated with the neurological evaluation showing that the patient did not have difficulty integrating visual information from the two visual fields, this indicates that, contrary to cases of corpus callosotomy (Schulte and Muller-Oehring, 2011
), the developmental dysgenesis of this structure does not affect the visual pathways and the integration of information from both visual fields. This may be due to the fact that the posterior part of the splenium, which connects the occipital and inferior temporal cortices, was intact in our agCC patient. On the other hand, the CC group and agCC patient showed different patterns of brain activity when the emotional nature of visual information was taken into account. Corroborated with the presence of visual distortions and hallucinations, as well as with the increased suspicion and persecution beliefs in agCC patient, our findings suggest that the CC agenesis may be a compounding factor in exacerbating some of the positive symptoms in schizophrenia. Of course, further research is necessary to actually link the severity of the positive symptoms to structural damage of the CC, but in the future it may be an important indicator for clinicians to suspect callosal damage when positive symptoms are very prominent in the early onset of the disease.
There are two main limitations in our study. First, is that we have only one case with CC agenesis and schizophrenia; it would have been better to compare two groups instead of a case with a group. However, given the rarity of the agenesis (1:4000) in the general population, finding enough cases is very difficult. Another limitation in our study is the lack of a clinical case that presents CC agenesis, but does not have schizophrenia. Such a case would have been useful in illustrating the impact of the structural damage on the emotional information processing in the absence of schizophrenia. However, we believe that despite these limitation, our data can be useful in showing the compounding effect of a structural damage in schizophrenia on the brain functioning.