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Background and purpose
The insula has important functions in monitoring and integrating physiological responses to a personal experience of multimodal input. The experience of chills in response to auditory stimuli is an important example for a relevant arousing experience coupled with bodily response. A group study about altered chill experiences in patients with insula lesions is lacking.
Methods
Twenty-eight stroke patients with predominantly insula lesions in the chronic stage and 14 age-matched controls were investigated using chill stimuli of both valences (music, harsh sounds). Group differences were analyzed in subjective chill reports, associated bodily responses (skin conductance response), lesion mapping, diffusion-weighted imaging and functional magnetic resonance imaging. Other neuropsychological deficits were excluded by comprehensive testing. Diffusion-weighted imaging was quantified for four insula tracts using fractional anisotropy.
Results
The frequency of chill experiences was comparable between participant groups. However, bodily responses were decreased for the stroke group. Whereas there was no association of lesion location, a positive association was found for the skin conductance response during aversive sounds and the tract connecting anterior inferior insula and left temporal pole in the stroke group. Similarly, functional magnetic resonance imaging activation in areas hypothesized to compensate for damage was increased with bodily response.
Conclusions
A decoupling of felt arousal and bodily response after insula lesion was observed. Impaired bodily response was related to an impaired interaction of the left anterior insula and the temporal pole.
Neuroinflammatory mechanisms and maladaptive neuroplasticity underlie the progression of complex regional pain syndrome (CRPS), which is prototypical of central neuropathic pain conditions. While cortical maladaptive alterations are well described, little is known about the contribution of the brainstem to the pathophysiology. This study investigates the role of pain-modulatory brainstem pathways in CRPS using the nociceptive blink reflex (nBR), which not only provides a direct read-out of brainstem excitability and habituation to painful stimuli but may also be suitable for use as a diagnostic biomarker for CRPS. Thirteen patients with CRPS and thirteen healthy controls (HCs) participated in this prospective case-control study investigating the polysynaptic trigemino-cervical (R2) nBR response. The R2 area and its habituation were assessed following repeated supraorbital electrical stimulation. Between-group comparisons included evaluations of diagnostic characteristics as a potential biomarker for the disease. Patients with CRPS showed a substantial decrease in habituation on the stimulated (Cohen’s d: 1.3; p = 0.012) and the non-stimulated side (Cohen’s d: 1.1; p = 0.04). This is the first study to reveal altered nBR habituation as a pathophysiological mechanism and potential diagnostic biomarker in CRPS. We confirmed previous findings of altered nBR excitability, but the diagnostic accuracy was inferior. Future studies should investigate the nBR as a marker of progression to central mechanisms in CRPS and as a biomarker to predict treatment response or prognosis.
Changes in Interhemispheric Motor Connectivity Across the Lifespan: A Combined TMS and DTI Study
(2019)
Age-related decline in interhemispheric connectivity between motor areas has been reported with both transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) measurements. However, not all studies were able to confirm these findings, and previous studies did not apply structural (DTI) and functional (TMS) measurements within each individual appropriately. Here, we investigated age dependency of the ipsilateral silent period (ISP) and integrity of fibers in the corpus callosum as operationalized by fractional anisotrophy (FA), using TMS and DTI, respectively, in 20 participants between 19 and 72 years of age. We found age-dependent increase for ISP, and decrease of FA, both indicating a decrease in interhemispheric inhibition, with a negative association between FA and ISP for the dominant hemisphere (r = −0.39, p = 0.043). Our findings suggest that aging leads to decline of interhemispheric motor connectivity, as evidenced in both structural and functional parameters, which should be taken into account when interpreting disease- or medication-related changes.
Arm Ability Training (AAT) has been specifically designed to promote manual dexterity recovery for stroke patients who have mild to moderate arm paresis. The motor control problems that these patients suffer from relate to a lack of efficiency in terms of the sensorimotor integration needed for dexterity. Various sensorimotor arm and hand abilities such as speed of selective movements, the capacity to make precise goal-directed arm movements, coordinated visually guided movements, steadiness, and finger dexterity all contribute to our “dexterity” in daily life. All these abilities are deficient in stroke patients who have mild to moderate paresis causing focal disability. The AAT explicitly and repetitively trains all these sensorimotor abilities at the individual's performance limit with eight different tasks; it further implements various task difficulty levels and integrates augmented feedback in the form of intermittent knowledge of results. The evidence from two randomized controlled trials indicates the clinical effectiveness of the AAT with regard to the promotion of “dexterity” recovery and the reduction of focal disability in stroke patients with mild to moderate arm paresis. In addition, the effects have been shown to be superior to time-equivalent “best conventional therapy.” Further, studies in healthy subjects showed that the AAT induced substantial sensorimotor learning. The observed learning dynamics indicate that different underlying sensorimotor arm and hand abilities are trained. Capacities strengthened by the training can, in part, be used by both arms. Non-invasive brain stimulation experiments and functional magnetic resonance imaging data documented that at an early stage in the training cortical sensorimotor network areas are involved in learning induced by the AAT, yet differentially for the tasks trained. With prolonged training over 2 to 3 weeks, subcortical structures seem to take over. While behavioral similarities in training responses have been observed in healthy volunteers and patients, training-induced functional re-organization in survivors of a subcortical stroke uniquely involved the ipsilesional premotor cortex as an adaptive recruitment of this secondary motor area. Thus, training-induced plasticity in healthy and brain-damaged subjects are not necessarily the same.
Background
A bidirectional functional link between vestibular and fear-related disorders has been previously suggested.
Objective
To test a potential overlap of vestibular and fear systems with regard to their brain imaging representation maps.
Methods
By use of voxel-based mapping permutation of subject images, we conducted a meta-analysis of earlier functional magnetic resonance imaging (fMRI) studies applying vestibular stimulation and fear conditioning in healthy volunteers.
Results
Common clusters of concordance of vestibular stimulation and fear conditioning were found in the bilateral anterior insula cortex, ventrolateral prefrontal cortex and the right temporal pole, bilaterally in the adjacent ventrolateral prefrontal cortex, cingulate gyrus, secondary somatosensory cortex, superior temporal and intraparietal lobe, supplementary motor area and premotor cortex, as well as subcortical areas, such as the bilateral thalamus, mesencephalic brainstem including the collicular complex, pons, cerebellar vermis and bilateral cerebellar hemispheres. Peak areas of high concordance for activations during vestibular stimulation but deactivations during fear conditioning were centered on the posterior insula and S2.
Conclusions
The structural overlap of both networks allows the following functional interpretations: first, the amygdala, superior colliculi, and antero-medial thalamus might represent a release of preprogramed sensorimotor patterns of approach or avoidance. Second, the activation (vestibular system) and deactivation (fear system) of the bilateral posterior insula is compatible with the view that downregulation of the fear network by acute vestibular disorders or unfamiliar vestibular stimulation makes unpleasant perceived body accelerations less distressing. This also fits the clinical observation that patients with bilateral vestibular loss suffer from less vertigo-related anxiety.
Background
Chronic pain of different aetiologies and localization has been associated with less grey matter volume (GMV) in several cortical and subcortical brain areas. Recent meta-analyses reported low reproducibility of GMV alterations between studies and pain syndromes.
Methods
To investigate GMV in common chronic pain conditions defined by body location (chronic back pain, n = 174; migraine, n = 92; craniomandibular disorder, n = 39) compared to controls (n = 296), we conducted voxel-based morphometry and determined GMV from high-resolution cranial MRIs obtained in an epidemiologic survey. Mediation analyses were performed between the presence of chronic pain and GMV testing the mediators stress and mild depression. The predictability of chronic pain was investigated with binomial logistic regression.
Results
Whole-brain analyses yielded reduced GMV within the left anterior insula and the anterior cingulate cortex, for a ROI approach additionally the left posterior insula and left hippocampus showing less GMV across all patients with chronic pain. The relationship of pain with GMV in the left hippocampus was mediated by self-reported stressors in the last 12 months. Binomial logistic regression revealed a predictive effect for GMV in the left hippocampus and left anterior insula/temporal pole for the presence of chronic pain.
Conclusions
Chronic pain across three different pain conditions was characterized by less GMV in brain regions consistently described for different chronic pain conditions before. Less GMV in the left hippocampus mediated by experienced stress during the last year might be related to altered pain learning mechanisms in chronic pain patients.
Significance
Grey matter reorganization could serve as a diagnostic biomarker for chronic pain. In a large cohort, we here replicated findings of less grey matter volume across three pain conditions in the left anterior and posterior insula, anterior cingulate and left hippocampus. Less hippocampal grey matter was mediated by experienced stress.
Background: Biomarkers for gains of evidence based interventions for upper limb motor training in the subacute stage following stroke have rarely been described. Information about these parameters might help to identify patients who benefit from specific interventions and to determine individually expected behavioral gains for a certain period of therapy.
Objective: To evaluate predictors for hand motor outcome after arm ability training in the subacute stage after stroke selected from known potentially relevant parameters (initial motor strength, structural integrity of the pyramidal tract and functional motor cortex integrity).
Methods: We applied the arm ability training (AAT) over 3 weeks to a subpopulation of stroke patients with mild arm paresis, i.e., in 14 patients on average 4 weeks after stroke. The following biomarkers were measured before therapy onset: grip strength on the affected hand, transcranial magnetic stimulation recruitment curve steepness over the primary motor hand area [slope ratio between the ipsilesional hemisphere (IH) and contralesional hemisphere (CH)], and diffusion weighted MRI fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC; determined as a lateralization index between IH and CH). Outcome was assessed as the AATgain (percentage improvement over training). The “Test d'Evaluation des Membres Supérieurs de Personnes Âgées” (TEMPA) was assessed before and after training to test for possible associations of AAT with activity of daily living.
Results: A stepwise linear regression identified the lateralization index of PLIC FA as the only significant predictor for AAT-gain (R2 = 0.519; P = 0.029). AAT-gain was positively associated (r = 0.59; P = 0.028) with improvement in arm function during daily activities (TEMPA).
Conclusions: While all mildly affected patients achieved a clinically relevant therapeutic effect, pyramidal tract integrity nevertheless had a modifying role for clinical benefit.
Neural characteristics of verbal creativity as assessed by word generation tasks have been recently identified, but differences in resting-state functional connectivity (rFC) between experts and non-experts in creative writing have not been reported yet. Previous electroencephalography (EEG) coherence measures during rest demonstrated a decreased cooperation between brain areas in association with creative thinking ability. Here, we used resting-state functional magnetic resonance imaging to compare 20 experts in creative writing and 23 age-matched non-experts with respect to rFC strengths within a brain network previously found to be associated with creative writing. Decreased rFC for experts was found between areas 44 of both hemispheres. Increased rFC for experts was observed between right hemispheric caudate and intraparietal sulcus. Correlation analysis of verbal creativity indices (VCIs) with rFC values in the expert group revealed predominantly negative associations, particularly of rFC between left area 44 and left temporal pole. Overall, our data support previous findings of reduced connectivity between interhemispheric areas and increased right-hemispheric connectivity during rest in highly verbally creative individuals.
We, here, provide a personal review article on the development of a functional MRI in the radiology departments of two German university medicine units. Although the international community for human brain mapping has met since 1995, the researchers fascinated by human brain function are still young and innovative. However, the impact of functional magnetic resonance imaging (fMRI) on prognosis and treatment decisions is restricted, even though standardized methods have been developed. The tradeoff between the groundbreaking studies on brain function and the attempt to provide reliable biomarkers for clinical decisions is large. By describing some historical developments in the field of fMRI, from a personal view, the rise of this method in clinical neuroscience during the last 25 years might be understandable. We aim to provide some background for (a) the historical developments of fMRI, (b) the establishment of two research units for fMRI in the departments of radiology in Germany, and (c) a description of some contributions within the selected fields of systems neuroscience, clinical neurology, and behavioral psychology.