The link between healthy speech perception and pathological voice hearing - a pivotal role for Broca's region

The six neuroimaging studies presented in this dissertation investigate the mechanisms and brain networks underlying top-down processes in normal speech perception on the one hand and pathological speech perception by auditory verbal hallucinations (AVH, “voice hearing”) on the other hand. The first fMRI study shows that, physiologically, speech perception is influenced by prior expectations in such a manner that unintelligible degraded speech sounds can suddenly be decoded when prior lexical-semantic information is available. This perceptual effect is presumably based on lexical-semantic expectations provided by higher order areas such as the left angular gyrus which may affect the semantic processing in the left middle temporal gyrus and modulate expected auditory signals in the thalamus. Broca’s region (area 44/45) could contribute to this process by searching for meaningful content in impoverished speech-like sequences. However, as study 2 demonstrates, in area 44 of Broca’s region merely the anterior-ventral part seems to be devoted to this task as this region is functionally heterogeneous. In particular, meta-analytic parcellation based on the whole-brain co-activation pattern across a wide range of neuroimaging experiments revealed that left area 44 contains five subunits primarily involved in rhythmic sequencing (posterior-ventral cluster), phonological processes in speech articulation (posterior-dorsal-cluster), working memory (anterior-dorsal cluster), detection of meaning in language and social contexts (anterior-ventral cluster) and cognitive control (inferior frontal junction cluster), respectively. Furthermore, the fMRI resting state functional connectivity analysis reported in study 3 emphasizes the importance of Broca’s region in AVH in psychotic patients. In particular, the results of this analysis suggest that imbalances in the functional connectivity pattern of the speech-relevant part of Broca’s region might lead to the misattribution of self-produced verbal imagery to an external source. Specifically, the perception of alien voices in the absence of sensory stimulation might arise from a decoupling between Broca’s region and the verbal monitoring system in combination with increased interactions within the speech articulation network. In addition, study 3 also provides evidence for abnormal top-down influences on speech processing in AVH reflected in disturbed connectivity of the left middle temporal gyrus and the left angular gyrus with other regions involved in speech perception. Moreover, the fMRI resting state analysis presented in study 4 suggests that Broca’s right-sided homotope might equally contribute to the pathology of AVH. Furthermore, abnormal coupling with medial temporal lobe memory structures might reflect intrusions of verbal memory fragments that are subsequently perceived as alien voices. Evidence for disturbed connectivity between areas involved in language and memory processes was also found in non-psychotic individuals with AVH in study 5. Finally, study 6 demonstrates an important negative finding that strengthens the specificity of the aforementioned results on disturbed functional connectivity of Broca’s region in AVH. In particular, it could be shown that major depression is specifically associated with hyperconnectivity of regions involved in affective and introspective processes but not with any abnormal connectivity within the speech perception network from study 1. Therefore, abnormal connectivity between Broca’s region and other regions implicated in speech perception seems to be specific to the symptom of AVH, as they are found in psychotic and non-psychotic patients showing this clinical phenotype but not in patients with affective psychosis (i.e., major depression). Together, these studies thus demonstrate that Broca’s region is multifunctional and forms an important hub in top-down driven speech perception where degraded bottom-up speech signals are restored to meaningful sentences based on lexical-semantic expectations as well as in the pathology of AVH where speech is perceived in the absence of bottom-up sensory signals.