Martin Domin

Current Smoking and Reduced Gray Matter Volume—a Voxel-Based Morphometry Study

Nicotine modulates prefrontal processing when tested with functional imaging. Previous studies on changes in regional brain volumes in small samples, reporting different life-time exposure to nicotine, identified reduced volume in smokers in prefrontal areas but reported controversial results for other areas. We investigated the association of cigarette smoking and regional gray and white matter volume by using voxel-based morphometry (VBM) for T1-weighted high-resolution magnetic resonance imaging in 315 current-smokers and 659 never-smokers from the representative Study of Health in Pomerania (SHIP). Our study showed that in current-smokers smoking is significantly associated with gray matter volume loss in the prefrontal cortex, the anterior cingulate cortex, the insula, and the olfactory gyrus. White matter volumes were not relevantly reduced in current-smokers. In current-smokers, we found associations of gray matter loss and smoking exposure (pack-years) in the prefrontal cortex, the anterior and middle cingulate cortex, and the superior temporal and angular gyrus, which however did not stand corrections for multiple testing. We confirmed associations between smoking and gray matter differences in the prefrontal cortex, the anterior cingulate cortex and the insula in the general population of Pomerania (Germany). For the first time, we identified differences in brain volumes in the olfactory gyrus. Other cerebral regions did not show significant differences when correcting for multiple comparisons within the whole brain. The regions of structural deficits might be involved in addictive behavior and withdrawal symptoms, whereas further investigations have to show if the observed atrophies were caused by smoking itself or are preexisting differences between smoking and non-smoking individuals.

Contralesional Motor Cortex Activation Depends on Ipsilesional Corticospinal Tract Integrity in Well-Recovered Subcortical Stroke Patients

Background. The relationship between structural and functional integrity of descending motor pathways can predict the potential for motor recovery after stroke. The authors examine the relationship between brain imaging biomarkers within contralesional and ipsilesional hemispheres and hand function in well-recovered patients after subcortical stroke at the level of the internal capsule. Objective. Measures of functional activation and integrity of the ipsilesional corticospinal tract might predict paretic hand function. Methods. A total of 14 patients in the chronic stable phase of motor recovery after subcortical stroke and 24 healthy age-matched individuals participated in the study. Functional MRI was used to examine BOLD contrast during passive wrist flexion–extension and paced or maximum-velocity active fist clenching. Functional integrity of the corticospinal pathway was assessed by transcranial magnetic stimulation to obtain motor-evoked potentials (MEPs) in the first dorsal interosseus muscle of the paretic and nonparetic hands. Fractional anisotropy and the proportion of traces between hemispheres in the posterior limb of both internal capsules were quantified using diffusion-weighted MRI. Results. Patients with smaller MEPs had a weaker paretic hand and more primary motor cortex activation in their affected hemisphere. Asymmetry between white matter tracts of either hemisphere was associated with reduced precision grip strength and increased BOLD activation within the contralesional dorsal premotor cortex for demanding hand tasks. Conclusion. There may be beneficial reorganization in contralesional secondary motor areas with increasing damage to the corticospinal tract after subcortical stroke. Associations between clinical, functional, and structural integrity measures in chronic stroke may lead to a better understanding of motor recovery processes.

Comparison of Parameter Threshold Combinations for Diffusion Tensor Tractography in Chronic Stroke Patients and Healthy Subjects

Background Although quantitative evaluation of diffusion tensor imaging (DTI) data seemed to be extremely important for clinical research its application is under debate. Besides fractional anisotropy (FA) the quantitative comparison between hemispheres of the number of fibers reconstructed by means of diffusion tensor tractography (DTT) is commonly used. However, the tractography-related parameters FA, minimum tract length (LENGTH) and the angle between two contiguous tracking steps (ANGLE) are inconsistently applied. Using 18 combinations we tested for the influence of parameter thresholds on the amount of reconstructed fibers for the posterior pyramidal tract in both hemispheres in order to obtain meaningful thresholds for DTT. Results In 14 chronic stroke patients with unilateral lesions of the pyramidal tract around the height of the internal capsule and considerable motor deficits a 3-way repeated-measures ANOVA showed a significant interaction between the effects of FA and ANGLE level on reconstructed fiber lateralization, F (2.9, 37.67) = 3.01, p = 0.044, and a significant main effect FA, F (1.4, 18.1) = 11.58, p = 0.001. Post-hoc pairwise comparisons showed that this interaction was completely driven by FA. In 22 right-handed healthy subjects no significant interactions or main effects could be found. Conclusion The parameter threshold combinations with highest FA showed highest effect. ANGLE and LENGTH insofar influenced the lateralization effect when selected as liberal as possible, short LENGTH and large ANGLE thresholds. The DTT approach should be used with great care since results are highly dependent on the thresholds applied.

The cerebral representation of temporomandibular joint occlusion and its alternation by occlusal splints

Occlusal splints are a common and effective therapy for temporomandibular joint disorder. Latest hypotheses on the impact of occlusal splints suggest an altered cerebral control on the occlusion movements after using a splint. However, the impact of using a splint during chewing on its cerebral representation is quite unknown. We used functional magnetic resonance imaging (fMRI) to investigate brain activities during occlusal function in centric occlusion on natural teeth or on occlusal splints in fifteen healthy subjects. Comparisons between conditions revealed an increased activation for the bilateral occlusion without a splint in bilateral primary and secondary sensorimotor areas, the putamen, inferior parietal and prefrontal cortex (left dorsal and bilateral orbital) and anterior insular. In contrast, using a splint increased activation in the bilateral prefrontal lobe (bilateral BA 10), bilateral temporo‐parietal (BA 39), occipital and cerebellar hemispheres. An additionally applied individually based evaluation of representation sites in regions of interest demonstrated that the somatotopic representation for both conditions in the pre‐ and postcentral gyri did not significantly differ. Furthermore, this analysis confirmed the decreasing effect of the splint on bilateral primary and secondary motor and somatosensory cortical activation. In contrast to the decreasing effect on sensorimotor areas, an increased level of activity in the fronto‐parieto‐occipital and cerebellar network might be associated with the therapeutic effect of occlusal splints. Hum Brain Mapp, 2012.

Structural alterations in white-matter tracts connecting (para-)limbic and prefrontal brain regions in borderline personality disorder.

BACKGROUND A dysfunctional network of prefrontal and (para-)limbic brain region has been suggested to underlie emotional dysregulation in borderline personality disorder (BPD). Abnormal activity in this network may be due to structural alterations in white-matter tracts connecting prefrontal and (para-)limbic brain regions. To test this hypothesis, we investigated the structural integrity of major white-matter tracts connecting these regions in BPD. METHOD Using diffusion tensor imaging, we investigated fractional anisotropy (FA), axonal anisotropy (AD) and radial diffusivity (RD) in the uncinate fasciculus, the major white-matter tract connecting (para-)limbic and prefrontal brain regions, in 26 healthy controls (HC) and 26 BPD participants. To clarify the specificity of possible white-matter alterations among HC and BPD participants, FA, AD and RD were also investigated in the cingulum. RESULTS We found distinct structural alterations in the uncinate fasciculus but not in the cingulum of BPD participants. Compared to HC participants, BPD participants showed lower FA and higher RD in the uncinate fasciculus. By contrast, AD did not differ in the uncinate fasciculus of HC and BPD participants. CONCLUSIONS Our finding of abnormal FA and RD in the uncinate fasciculus indicates distinct white-matter alterations in BPD, presumably due to stress-induced myelin degeneration in the aftermath of stressful life events. Although these alterations may account for abnormal activity in brain regions implicated in emotion dysregulation, such as the amygdala, anterior cingulate cortex and prefrontal cortex, it remains to be determined whether these alterations are specific for BPD.

Diffusion tensor imaging abnormalities in photosensitive juvenile myoclonic epilepsy

Multiple structural white matter abnormalities have been described in patients with juvenile myoclonic epilepsy (JME). In the present study, the question of whether microstructural variations exist between the two subgroups of JME, with and without photoparoxysmal responses (PPR positive and negative), was addressed using diffusion tensor imaging.

Telephone counseling and attendance in a national mammography-screening program a randomized controlled trial.

BACKGROUND In Germany, a mammography-screening program (MSP) was implemented on a national level. It complies with all criteria of the European guidelines for quality assurance in screening mammography; however, the attendance rate is 54%, falling short of the target attendance rate of 70%. The aim of this study was to investigate whether additional telephone counseling improves attendance among nonresponders and the level of satisfaction with telephone counseling. DESIGN In a prospective RCT, women identified as nonresponders in the MSP were randomized to a control group that received written reminders or to an intervention group that additionally received telephone counseling. In a follow-up, a subset of the intervention group was contacted by telephone regarding their satisfaction with telephone counseling. SETTING/PARTICIPANTS In 2008, a total of 5477 women aged 50-69 years who were eligible for the German MSP but had not participated up to 6 weeks after the first invitation were included in the study. INTERVENTIONS Individual telephone counseling consisted of scripted calls from a trained counselor who provided information on MSP and answered the womans questions. MAIN OUTCOME MEASURES Report of mammography use provided by the screening unit 3 months after the reminder was sent. RESULTS Analysis was conducted in 2009. Comparison of screening attendance revealed a significantly higher attendance rate in the intervention group compared with controls (29.7% vs 26.1%, p=0.0035). When only women for whom telephone numbers were available were analyzed, attendance was even better (35.5% vs 29.7%, p=0.0004). In the follow-up, 278 of 404 women were actually surveyed. Of those, 33% stated that telephone counseling had influenced their decision, 56% stated that they had undergone screening mammography, and 77% agreed that personal telephone counseling should be used routinely to encourage nonresponders to go for screening. CONCLUSIONS Individual telephone counseling for nonresponders to a national program for breast cancer screening was well accepted by participants and effective. TRIAL REGISTRATION This study is registered at the Australian New Zealand Clinical Trials Registry ACTRN12611000645954.

They Are Laughing at Me: Cerebral Mediation of Cognitive Biases in Social Anxiety

The fear of embarrassment and humiliation is the central element of social anxiety. This frequent condition is associated with cognitive biases indicating increased sensitivity to signals of social threat, which are assumed to play a causal role in the maintenance of social anxiety. Here, we employed laughter, a potent medium for the expression of acceptance and rejection, as an experimental stimulus in participants selected for varying degrees of social anxiety to identify cerebral mediators of cognitive biases in social anxiety using functional magnetic resonance imaging in combination with mediation analysis. We directly demonstrated that cerebral activation patterns within the dorsal attention network including the left dorsolateral and dorsomedial prefrontal cortex mediate the influence of social anxiety on laughter perception. This mediation proved to be specific for social anxiety after correction for measures of general state and trait anxiety and occurred most prominently under bimodal audiovisual laughter presentation when compared with monomodal auditory or visual laughter cues. Considering the possibility to modulate cognitive biases and cerebral activity by neuropsychological trainings, non-invasive electrophysiological stimulation and psychotherapy, this study represents a starting point for a whole line of translational research projects and identifies promising targets for electrophysiological interventions aiming to alleviate cognitive biases and symptom severity in social anxiety.

Changes in cortical activation in craniomandibular disorders during splint therapy – A single subject fMRI study

There is some controversial discussion within the therapy of craniomandibular disorders (CMDs) about the mode of action of occlusal splints. Here we present a case report on one CMD-patient measuring cerebral activation changes with functional magnetic resonance imaging (fMRI) before and after therapy with a stabilization splint. Wearing the Michigan splint for 11 nights and partially days resulted in substantial pain relief and changes in occlusal movement performance. Cerebral activation during occlusion was decreased after therapy (PRE-POST) in bilateral sensorimotor regions but also additional areas such as left posterior insula, right superior temporal cortex and bilateral occipital lobe. During the first usage of the splint in the scanner (PRE) increased activation in the left dorsolateral prefrontal lobe (BA 9) was observed. After splint training occlusion with the splint compared to without a splint increasingly involved the left superior parietal lobe (BA 7, POST). Whereas BA 9 might be associated with increasing working memory load due to the manipulation with an unusual object, the BA 7 activation in the POST session might document increased sensorimotor interaction after getting used to the splint. Our findings indicate that wearing an occlusion splint triggers activation in parietal sensorimotor integration areas, also observed after long periods of sensorimotor training. These additional recourses might improve coordination and physiological handling of the masticatory system.

Connectivity-Based Predictions of Hand Motor Outcome for Patients at the Subacute Stage After Stroke

Background: Connectivity-based predictions of hand motor outcome have been proposed to be useful in stroke patients. We intended to assess the prognostic value of different imaging methods on short-term (3 months) and long-term (6 months) motor outcome after stroke. Methods: We measured resting state functional connectivity (rsFC), diffusion weighted imaging (DWI) and grip strength in 19 stroke patients within the first days (5–9 days) after stroke. Outcome measurements for short-term (3 months) and long-term (6 months) motor function was assessed by the Motricity Index (MI) of the upper limb and the box and block test (BB). Patients were predominantly mildly affected since signed consent was necessary at inclusion. We performed a multiple stepwise regression analysis to compare the predictive value of rsFC, DWI and clinical measurements. Results: Patients showed relevant improvement in both motor outcome tests. As expected grip strength at inclusion was a predictor for short- and long-term motor outcome as assessed by MI. Diffusion-based tract volume (DTV) of the tracts between ipsilesional primary motor cortex and contralesional anterior cerebellar hemisphere showed a strong trend (p = 0.05) for a predictive power for long-term motor outcome as measured by MI. DTV of the interhemispheric tracts between both primary motor cortices was predictive for both short- and long-term motor outcome in BB. rsFC was not associated with motor outcome. Conclusions: Grip strength is a good predictor of hand motor outcome concerning strength-related measurements (MI) for mildly affected subacute patients. Therefore additional connectivity measurements seem to be redundant in this group. Using more complex movement recruiting bilateral motor areas as an outcome parameter, DTV and in particular interhemispheric pathways might enhance predictive value of hand motor outcome.