Longitudinal structural and functional brain changes associated with stuttering improvement by therapy or brain lesion
by Annika Primaßin
Date of Examination:2019-03-26
Date of issue:2019-06-11
Advisor:Prof. Dr. Martin Sommer
Referee:Prof. Dr. Martin Sommer
Referee:Prof. Dr. Annekathrin Schacht
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Abstract
English
Stuttering is a speech fluency disorder which is affecting motor speech production and communication in the daily life of persons who stutter (PWS). The involuntarily occurring core symptoms of stuttering are sound and syllable repetitions, sound prolongations and speech blocks (Bloodstein & Ratner, 2008). In addition to these core symptoms, secondary accompanying symptoms like movements of limbs, neck and head as well as facial grimaces can appear (Guitar & McCauley, 2010). PWS repeatedly experience high communicative pressure and psychological strain. Subsequently, they often develop social withdrawal to hide their stuttering. Therefore, a reduced quality of life is measured in some PWS (Carter, Breen, Yaruss, & Beilby, 2017; Kohmäscher, 2017; Natke & Alpermann, 2010). Stuttering therapies enhance speech fluency and support patients in their handling with adverse emotions and attitudes towards their stuttering (Neumann et al., 2016). Even though the effectiveness of different types of intense stuttering therapies has been evaluated on a behavioural level, there is a research gap regarding the long-term effects of intense stuttering therapies on brain structure and function. In fact, to our knowledge, changes of white matter integrity following the participation in an intense stuttering therapy have not been investigated yet. Therefore, the present thesis investigates the effects of therapy-induced long-term white matter plasticity changes as well as brain activation changes in adolescent and adult PWS. For this purpose, we recruited stuttering patients taking part in the “Kasseler Stottertherapie” (Euler, Gudenberg, A. W. v., Jung, & Neumann, 2009). This is an evidence-based fluency shaping therapy approach accomplished in a group setting and with a high intensity (Euler et al., 2009; Euler, Anders, Merkel, & von Gudenberg, A Wolff, 2016; Euler & Wolff v. Gudenberg, 2000; Neumann et al., 2016). In addition, a case report of a cessation of stuttering after a left cerebellar haemorrhage is presented in this thesis. In the first study of this dissertation, we used diffusion tensor imaging (DTI) to evaluate long-term therapy-induced changes of white matter integrity in stuttering patients. For this purpose, we added two control groups and compared the longitudinal structural changes of the intervention group with the structural changes of stuttering control participants not taking part in any therapy and healthy control participants. By using Tract-Based Spatial Statistics (Smith et al., 2006; Smith et al., 2007), we investigated changes in fibre integrity within whole-brain and region of interest analyses. Our results show that the effects of therapy in the intervention group were versatile: Referring to the behavioural level, a significant decline of stuttering severity as well as of the impact of stuttering on the quality of life were detected and attributed to the stuttering treatment. Regarding white matter integrity changes, we observed a significant increase of fractional anisotropy (FA) in the left superior longitudinal fasciculus. In contrast to the intervention group, a significant decrease of white matter integrity was found in stuttering and healthy control participants. This white matter decline could have been triggered through the process of ageing. The second purpose of this study was to replicate previous findings of a reduction of white matter integrity in PWS compared to healthy controls (Cykowski, Fox, Ingham, Ingham, & Robin, 2010; Neef, Anwander, & Friederici, 2015; Sommer, Koch, Paulus, Weiller, & Buchel, 2002). We were able to confirm this reduced white matter integrity in right hemispheric brain regions including parts of the inferior longitudinal fasciculus close to the callosal body, cingulum, inferior-fronto-occipital fasciculus and the corticospinal tract. With our study, we provided first evidence that an intense stuttering therapy has the potential to change white matter plasticity in stuttering patients. Future studies are necessary to replicate this result and to relate this outcome to the aetiology of stuttering. In the second study of this thesis, we evaluated long-term changes in brain activation induced by an intense stuttering therapy and its maintenance phase. We compared brain activation changes in the treatment group with the changes measured in both control groups (healthy participants and stuttering participants not currently taking part in any stuttering therapy). The research aim was to investigate therapy-induced activation changes and to discuss them with regard to the therapeutic principles of action. The following results were obtained: In comparison to healthy and stuttering control participants, stuttering patients showed an increase of activity in motor (e.g. left and right rolandic operculum) and in cognition and emotion processing areas (e.g. left amygdala, right supramarginal gyrus). The effect of therapy was also traceable on the behavioural level. Only stuttering patients of the intervention group showed a significant decline of stuttering severity and a significantly decreased impact of stuttering on the quality of life. Our results underline the importance of also considering non-motor brain regions meaningful for therapeutic achievements as well as for the aetiology of stuttering. The third part of this thesis consists of a case report about the cessaction of stuttering after a cerebellar haemorrhage. The 52 years old female patient stuttered since childhood and had taken part in a stuttering-related magnet resonance imaging (MRI) research study at the University Medical Center Göttingen. After taking part in the study, she developed a left acoustic neuroma which was subsequently surgically removed. Postoperatively, the patient presented with a cerebellar haemorrhage and, as a consequence, various neurological symptoms and impairments. After the rehabilitation period, the patient reported a cessation of her stuttering as a consequence of the cerebellar haemorrhage. We became conscious of her clinical course and invited her to a revisited measurement. The aim of this second measurement and the case report were to elucidate neurophysiological processes which are responsible for the cessation of stuttering. For the revisited measurement, we used the same behavioural measurements and functional and diffusion MRI protocols as in the previous study measurement. To compare the (functional) MRI data of the single patient with a reference group, we added a control group with healthy participants and another control group with stuttering participants to our analyses. The study outcomes were manifold: The conducted lesion analysis indicated a large cerebellar lesion, including approximately 1/5 of the left cerebellum. The tract-based spatial statistics analysis showed a primary white matter decrease caused by the haemorrhage in the lesioned parts of the cerebellum. A secondary white matter impairment was detected in the corpus callosum, right inferior fronto-occipital fasciculus, left anterior thalamic radiation, left cingulum and right posterior corona radiata. The whole-brain functional MRI (fMRI) analysis revealed a modality-related difference in brain activity from the first to the second measurement. During covert speaking, parietal and temporal areas showed an increase of activation. This increase of activation was not traceable during covert humming. Also in our region of interest (ROI) analysis in the left and right BA 44, the single case patient showed a hyperactivation during covert speaking at the second measurement when comparing her with the control groups. This hyperactivation was again modality-related and therefore only measureable during covert speaking. Our results were discussed in respect to the cerebello-thalamo-cortical pathway. The cerebellar disinhibition caused by the lesion might have led to an overactivity in thalamus and motor cortex, represented by the hyperactivation during covert speaking. Therefore, the cerebellar disinhibition and its triggered overactivation along the cerebello-thalamo-cortical pathway might have facilitated the cessation of stuttering. Taken together, the object of the current thesis was to evaluate the long-term longitudinal effects of an intense stuttering therapy or a brain lesion on brain structure and function in PWS. The results provide first evidence that the reduction of white matter integrity (often seen as the deficit in neural processing in PWS; see Packman, 2012) can be altered through an intense stuttering therapy. Furthermore, our research demonstrates that an intense stuttering therapy has the potential to enhance an increase of brain activation in areas that were hypoactivated before therapy. This enhancement even takes place in non-motor regions. And last, this thesis underlines the importance of the cerebello-thalamo-cortical pathway for the aetiology of stuttering.
Keywords: stuttering; therapy; MRI; longitudinal