Katharina Rosengarth

Structural brain changes in tinnitus: Grey matter decrease in auditory and non-auditory brain areas

Tinnitus, the phantom perception of sound, is a frequent disorder that causes significant morbidity. The pathophysiological mechanisms involved in tinnitus generation are still under exploration. Electrophysiological and functional neuroimaging studies give increasing evidence for abnormal functioning both within the central auditory system and in non-auditory brain areas. However, observed changes show great variability, hence lacking a conclusive picture. Recently, structural alterations in the central nervous system have been detected in tinnitus patients by voxel-based morphometry (VBM). Here we aimed to replicate these findings in an independent study sample. We performed structural MRI scans in 28 tinnitus patients with normal audiometry and used VBM to compare results with a control group, matched for age, sex and hearing status. As major results we found significant grey matter decreases in the tinnitus group in the right inferior colliculus and in the left hippocampus. However, neither changes in the subcallosal area nor in the thalamus as described recently have been observed. Our results underscore that (1.) VBM allows to detect structural alterations in tinnitus patients, which seem to be related to tinnitus pathophysiology. (2.) Both, areas in the auditory and the limbic system are involved giving further evidence for the important role of the limbic system in the pathophysiology of tinnitus. (3.) Even groups with similar clinical characteristics might differ in the underlying neurobiological changes.

Distinct patterns of functional and structural neuroplasticity associated with learning Morse code.

Learning is based on neuroplasticity, i.e. on the capability of the brain to adapt to new experiences. Different mechanisms of neuroplasticity have been described, ranging from synaptic remodeling to changes in complex neural circuitry. To further study the relationship between changes in neural activity and changes in gray matter density associated with learning, we performed a combined longitudinal functional and morphometric magnetic resonance imaging (MRI) study on healthy volunteers who learned to decipher Morse code. We investigated 16 healthy subjects using functional MR imaging (fMRI) and voxel-based morphometry (VBM) before and after they had learned to decipher Morse code. The same set of Morse-code signals was presented to participants pre- and post-training. We found an increase in task-specific neural activity in brain regions known to be critically involved in language perception and memory, such as the inferior parietal cortex bilaterally and the medial parietal cortex during Morse code deciphering. Furthermore we found an increase in gray matter density in the left occipitotemporal region, extending into the fusiform gyrus. Anatomically neighboring sites of functional and structural neuroplasticity were revealed in the left occipitotemporal/inferior temporal cortex, but these regions only marginally overlapped. Implications of this morpho-functional dissociation for learning concepts are discussed.

Functional and structural brain modifications induced by oculomotor training in patients with age-related macular degeneration

Patients with age-related macular degeneration (AMD) are reliant on their peripheral visual field. Oculomotor training can help them to find the best area on intact peripheral retina and to efficiently stabilize eccentric fixation. In this study, nine patients with AMD were trained over a period of 6 months using oculomotor training protocols to improve fixation stability. They were followed over an additional period of 6 months, where they completed an auditory memory training as a sham training. In this cross-over design five patients started with the sham training and four with the oculomotor training. Seven healthy age-matched subjects, who did not take part in any training procedure, served as controls. During the 6 months of training the AMD subjects and the control group took part in three functional and structural magnetic resonance imaging (MRI) sessions to assess training-related changes in the brain function and structure. The sham-training phase was accompanied by two more fMRI measurements, resulting in five MRI sessions at intervals of 3 months for all participants. Despite substantial variability in the training effects, on average, AMD patients benefited from the training measurements as indexed by significant improvements in their fixation stability, visual acuity, and reading speed. The patients showed a significant positive correlation between brain activation changes and improvements in fixation stability in the visual cortex during training. These correlations were less pronounced on the long-term after training had ceased. We also found a significant increase in gray and white matter in the posterior cerebellum after training in the patient group. Our results show that functional and structural brain changes can be associated, at least on the short-term, with benefits of oculomotor and/or reading training in patients with central scotomata resulting from AMD.

Perceptual learning in patients with macular degeneration

Patients with age-related macular degeneration (AMD) or hereditary macular dystrophies (JMD) rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT) at their preferred retinal locus (PRL) used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later) took part in three functional magnetic resonance imaging (fMRI) sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p = 0.001) in the stimulus onset asynchrony (SOA) between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p = 0.014). The following trends were observed: (i) improvement in Vernier acuity for an eccentric line-bisection task; (ii) positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r = 0.531); (iii) positive correlation between the increase in task performance and initial fixation stability (r = 0.730). The first two trends were non-significant, whereas the third trend was significant at p = 0.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex.

The effect of feedback on performance and brain activation during perceptual learning.

We investigated the role of informative feedback on the neural correlates of perceptual learning in a coherent-motion detection paradigm. Stimulus displays consisted of four patches of moving dots briefly (500 ms) presented simultaneously, one patch in each visual quadrant. The coherence level was varied in the target patch from near threshold to high, while the other three patches contained only noise. The participants judged whether coherent motion was present or absent in the target patch. To guarantee central fixation, a secondary RSVP digit-detection task was performed at fixation. Over six training sessions subjects learned to detect coherent motion in a predefined quadrant (i.e., the learned location). Half of our subjects were randomly assigned to the feedback group, where they received informative feedback after each response during training, whereas the other group received non-informative feedback during training that a response button was pressed. We investigated whether the presence of informative feedback during training had an influence on the learning success and on the resulting BOLD response. Behavioral data of 24 subjects showed improved performance with increasing practice. Informative feedback promoted learning for motion displays with high coherence levels, whereas it had little effect on learning for displays with near-threshold coherence levels. Learning enhanced fMRI responses in early visual cortex and motion-sensitive area MT+ and these changes were most pronounced for high coherence levels. Activation in the insular and cingulate cortex was mainly influenced by coherence level and trained location. We conclude that feedback modulates behavioral performance and, to a lesser extent, brain activation in areas responsible for monitoring perceptual learning.

From perceptual to lexico-semantic analysis—cortical plasticity enabling new levels of processing

Certain kinds of stimuli can be processed on multiple levels. While the neural correlates of different levels of processing (LOPs) have been investigated to some extent, most of the studies involve skills and/or knowledge already present when performing the task. In this study we specifically sought to identify neural correlates of an evolving skill that allows the transition from perceptual to a lexico‐semantic stimulus analysis. Eighteen participants were trained to decode 12 letters of Morse code that were presented acoustically inside and outside of the scanner environment. Morse code was presented in trains of three letters while brain activity was assessed with fMRI. Participants either attended to the stimulus length (perceptual analysis), or evaluated its meaning distinguishing words from nonwords (lexico‐semantic analysis). Perceptual and lexico‐semantic analyses shared a mutual network comprising the left premotor cortex, the supplementary motor area (SMA) and the inferior parietal lobule (IPL). Perceptual analysis was associated with a strong brain activation in the SMA and the superior temporal gyrus bilaterally (STG), which remained unaltered from pre and post training. In the lexico‐semantic analysis post learning, study participants showed additional activation in the left inferior frontal cortex (IFC) and in the left occipitotemporal cortex (OTC), regions known to be critically involved in lexical processing. Our data provide evidence for cortical plasticity evolving with a learning process enabling the transition from perceptual to lexico‐semantic stimulus analysis. Importantly, the activation pattern remains task‐related LOP and is thus the result of a decision process as to which LOP to engage in. Hum Brain Mapp 36:4512–4528, 2015.

Assessing language dominance with functional MRI: The role of control tasks and statistical analysis

There is a discrepancy between the brain regions revealed by functional neuroimaging techniques and those brain regions where a loss of function, either by lesion or by electrocortical stimulation, induces language disorders. To differentiate between essential and non-essential language-related processes, we investigated the effects of linguistic control tasks and different analysis methods for functional MRI data. Twelve subjects solved two linguistic generation tasks: (1) a verb generation task and (2) an antonym generation task (each with a linguistic control task on the phonological level) as well as two decision tasks of semantic congruency (each with a cognitive high-level control task). Differential contrasts and conjunction analyses were carried out on the single-subject level and an individual lateralization index (LI) was computed. On the group level we determined the percent signal change in the left inferior frontal gyrus (IFG: BA 44 and BA 45). The conjunction analysis of multiple language tasks led to significantly greater absolute LIs than the LIs based on the single task versus fixation contrasts. A further significant increase of the magnitude of the LIs could be achieved by using the phonological control conditions. Although the decision tasks appear to be more robust to changes in the statistical threshold, the combined generation tasks had an advantage over the decision tasks both for assessing language dominance and locating Brocas area. These results underline the need for conjunction analysis based on several language tasks to suppress highly task-specific processes. They also point to the need for high-level cognitive control tasks to partial out general, language supporting but not language critical processes. Higher absolute LIs, which reflect unambiguously hemispheric language dominance, can be thus obtained.

The continuous awake craniotomy (CAC) protocol: a novel protocol for awake craniotomies

Abstract Objective: The generally used asleep-awake-asleep protocol makes reliable intra-operative testing difficult as patients are frequently disoriented when woken-up from sedation. Furthermore, this protocol carries potential risks for the patient, the most common among them being respiratory complications. In an effort to eliminate potential risks for the patient during awake craniotomies, and in order to improve reliability of intra-operative test results, we implemented a new protocol for awake craniotomies, the continuous awake craniotomy protocol, where the patient is not sedated during the entire procedure. We present first results of this new protocol. Methods: In a prospective study we analyzed awake craniotomies that were performed between September 2006 and June 2008. Data included OR-records, anesthesiological protocols, patient charts, and neuropsychological records. Results: Data of 12 consecutive primary brain tumor patients (six men/six women) with a mean age of 46 years who underwent 13 awake craniotomies were analyzed. A gross total resection was achieved in ten patients (83.3%), of which one patient (8.3%) suffered from a new neurological deficit postoperatively. One patient suffered a generalized seizure and one a focal seizure triggered by direct cortical stimulation. There were no anesthesiological or surgical complications in this study. Conclusion: This study shows that the continuous awake craniotomy protocol is safe, was tolerated well by all patients, and created a very controllable situation during all surgeries. Applying this method, sedation related complications, such as respiratory complications and hemodynamic dysregulation, can be avoided, as are potential risks during an intra-operative wake-up phase. Furthermore, intra-operative neuropsychological test results become more reliable.

Aversive faces activate pain responsive regions in the brain.

Recent evidence points to an overlap in the neural systems processing pain and social distress. In this functional MRI study we focus on the possible interplay between the processing of a psychosocial stressor and somatic pain within pain responsive brain regions, the latter being identified in an independent localizer experiment. A paradigm based on emotional induction (Hariri et al., 2000, Neuroreport 11(1):43–48) was combined with moderate heat pain to yield a factorial design with factor ‘pain’ as somatic stressor and factor ‘faces’ as nonpainful psychosocial stressor. Pain responsive regions of interest in the insula, SII cortex, and thalamus were activated by the factor ‘faces’ to a various extent. The hemodynamic response to both factors tends to aggregate in a compressive manner in these regions.

Fluorescence-guidance in non-Gadolinium enhancing, but FET-PET positive gliomas

OBJECTIVES We report on five patients with gadolinium-negative (non-enhancing magnetic resonance imaging-MRI) but 18F-fluoroethyl tyrosine positron-emission tomography (FET-PET) positive glioma (NEG) undergoing surgery under fluorescence-guidance with fluorescein sodium 10% (FL, Alkon, Germany) in combination with a dedicated light filter (YELLOW 560 nm, Carl Zeiss Meditec, Germany). PATIENTS AND METHOD Since 2017, five patients (3 female, 2 male; mean age 45.4 years) underwent fluorescence-guided surgery for supratentorial, intracerebral lesions which showed no contrast-enhancement in the preoperative MRI but were, however, strongly suspicious for gliomas. Accordingly, all patients received a preoperative FET-PET scan and detailed histopathological workup was performed. After giving written informed consent, all patients received 5 mg/kg of FL at the induction of anesthesia. Surgery was conducted under white light and under the YELLOW 560 nm filter. We reviewed the surgical protocols, navigational storage and the image databases of our surgical microscopes for evidence of intraoperative fluorescence that corresponded to the FET-PET positive area. RESULTS In all patients we found distinct accordances between the FET-PET positive areas and the fluorescing regions within the targeted lesions. Histopathological workup of the fluorescent tissue revealed anaplastic oligodendroglioma, IDH-mutant and 1p/19-codeleted (WHO grade III) (n = 2), anaplastic astrocytoma, IDH-mutant (WHO grade III) (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grade II) (n = 1) and pilocytic astrocytoma (WHO grade I) (n = 1). No adverse events were noted. DISCUSSION AND CONCLUSION Despite the lack of gadolinium-enhancement in the preoperative MRI, all patients intravenously received FL to guide resection. Irrespective of the final grading, FL was extremely helpful in detecting the lesions and in identifying their border zones. In selected patients with NEG, but strong metabolic activity according to the FET-PET, FL may significantly increase the accuracy of surgery.