Derek V. M. Ott

Do the Congenitally Blind Have a Stria of Gennari? First Intracortical Insights In Vivo

The primary visual cortex V1, when dissected, is characterized by an easily identifiable anatomical landmark: the stria of Gennari or Gennari stripe. However, the origin and function of the Gennari stripe is so far unknown. In order to shed some light on this question, we acquired 7-T magnetic resonance imaging (MRI) brain scans of congenitally blind (CB) people, who have never had visual experience. If the stria of Gennari requires visual input to develop or to maintain its homeostasis, such subjects should lack this structure. If it is reliably detectable in the CB, it must form and persist independently of visual sensation. This question has never previously been explored in living subjects. For the first time, the use of 7-T high-resolution MRI enables such investigations because of the excellent signal-to-noise ratio at this magnetic field strength. For comparison, we scanned sighted subjects using the same experimental parameters. We detected the stria of Gennari reliably in both sighted and blind subjects, showing that this anatomical feature is not a developmental result of visual input, and it does not degenerate in the absence of visual input.

Prosody meets syntax: the role of the corpus callosum

Contemporary neural models of auditory language comprehension proposed that the two hemispheres are differently specialized in the processing of segmental and suprasegmental features of language. While segmental processing of syntactic and lexical semantic information is predominantly assigned to the left hemisphere, the right hemisphere is thought to have a primacy for the processing of suprasegmental prosodic information such as accentuation and boundary marking. A dynamic interplay between the hemispheres is assumed to allow for the timely coordination of both information types. The present event-related potential study investigated whether the anterior and/or posterior portion of the corpus callosum provide the crucial brain basis for the online interaction of syntactic and prosodic information. Patients with lesions in the anterior two-thirds of the corpus callosum connecting orbital and frontal structures, or the posterior third of the corpus callosum connecting temporal, parietal and occipital areas, as well as matched healthy controls, were tested in a paradigm that crossed syntactic and prosodic manipulations. An anterior negativity elicited by a mismatch between syntactically predicted phrase structure and prosodic intonation was analysed as a marker for syntax-prosody interaction. Healthy controls and patients with lesions in the anterior corpus callosum showed this anterior negativity demonstrating an intact interplay between syntax and prosody. No such effect was found in patients with lesions in the posterior corpus callosum, although they exhibited intact, prosody-independent syntactic processing comparable with healthy controls and patients with lesions in the anterior corpus callosum. These data support the interplay between the speech processing streams in the left and right hemispheres via the posterior portion of the corpus callosum, building the brain basis for the coordination and integration of local syntactic and prosodic features during auditory speech comprehension.

Repetitive TMS Suggests a Role of the Human Dorsal Premotor Cortex in Action Prediction

Predicting the actions of other individuals is crucial for our daily interactions. Recent evidence suggests that the prediction of object-directed arm and full-body actions employs the dorsal premotor cortex (PMd). Thus, the neural substrate involved in action control may also be essential for action prediction. Here, we aimed to address this issue and hypothesized that disrupting the PMd impairs action prediction. Using fMRI-guided coil navigation, rTMS (five pulses, 10 Hz) was applied over the left PMd and over the vertex (control region) while participants observed everyday actions in video clips that were transiently occluded for 1 s. The participants detected manipulations in the time course of occluded actions, which required them to internally predict the actions during occlusion. To differentiate between functional roles that the PMd could play in prediction, rTMS was either delivered at occluder-onset (TMS-early), affecting the initiation of action prediction, or 300 ms later during occlusion (TMS-late), affecting the maintenance of an ongoing prediction. TMS-early over the left PMd produced more prediction errors than TMS-early over the vertex. TMS-late had no effect on prediction performance, suggesting that the left PMd might be involved particularly during the initiation of internally guided action prediction but may play a subordinate role in maintaining ongoing prediction. These findings open a new perspective on the role of the left PMd in action prediction which is in line with its functions in action control and in cognitive tasks. In the discussion, the relevance of the left PMd for integrating external action parameters with the observer’s motor repertoire is emphasized. Overall, the results are in line with the notion that premotor functions are employed in both action control and action observation.

Emotional speech perception unfolding in time: The role of the basal ganglia

The basal ganglia (BG) have repeatedly been linked to emotional speech processing in studies involving patients with neurodegenerative and structural changes of the BG. However, the majority of previous studies did not consider that (i) emotional speech processing entails multiple processing steps, and the possibility that (ii) the BG may engage in one rather than the other of these processing steps. In the present study we investigate three different stages of emotional speech processing (emotional salience detection, meaning-related processing, and identification) in the same patient group to verify whether lesions to the BG affect these stages in a qualitatively different manner. Specifically, we explore early implicit emotional speech processing (probe verification) in an ERP experiment followed by an explicit behavioral emotional recognition task. In both experiments, participants listened to emotional sentences expressing one of four emotions (anger, fear, disgust, happiness) or neutral sentences. In line with previous evidence patients and healthy controls show differentiation of emotional and neutral sentences in the P200 component (emotional salience detection) and a following negative-going brain wave (meaning-related processing). However, the behavioral recognition (identification stage) of emotional sentences was impaired in BG patients, but not in healthy controls. The current data provide further support that the BG are involved in late, explicit rather than early emotional speech processing stages.

Continuous theta-burst stimulation (cTBS) over the lateral prefrontal cortex alters reinforcement learning bias

The prefrontal cortex is known to play a key role in higher-order cognitive functions. Recently, we showed that this brain region is active in reinforcement learning, during which subjects constantly have to integrate trial outcomes in order to optimize performance. To further elucidate the role of the dorsolateral prefrontal cortex (DLPFC) in reinforcement learning, we applied continuous theta-burst stimulation (cTBS) either to the left or right DLPFC, or to the vertex as a control region, respectively, prior to the performance of a probabilistic learning task in an fMRI environment. While there was no influence of cTBS on learning performance per se, we observed a stimulation-dependent modulation of reward vs. punishment sensitivity: Left-hemispherical DLPFC stimulation led to a more reward-guided performance, while right-hemispherical cTBS induced a more avoidance-guided behavior. FMRI results showed enhanced prediction error coding in the ventral striatum in subjects stimulated over the left as compared to the right DLPFC. Both behavioral and imaging results are in line with recent findings that left, but not right-hemispherical stimulation can trigger a release of dopamine in the ventral striatum, which has been suggested to increase the relative impact of rewards rather than punishment on behavior.

Whole-brain mapping of venous vessel size in humans using the hypercapnia-induced BOLD effect.

Measuring the morphology of the cerebral microvasculature by vessel-size imaging (VSI) is a promising approach for clinical applications, such as the characterization of tumor angiogenesis and stroke. Despite the great potential of VSI, this method has not yet found widespread use in practice due to the lack of experience in testing it on healthy humans. Since this limitation derives mainly from the need for an invasive injection of a contrast agent, this work explores the possibility to employ instead the easily accessible blood oxygenation level dependent (BOLD) effect for VSI of the venous microstructure. It is demonstrated that BOLD-VSI in humans can be realized by a hypercapnic challenge using a fast gradient-echo (GE) and spin-echo (SE) sequence at 7T. Reproducible maps of the mean venous vessel radius, based on the BOLD-induced changes in GE and SE relaxation rates, could be obtained within a scan time of 10min. Moreover, the method yields maps of venous blood volume and vessel density. Owing to its non-invasive character, BOLD-VSI provides a low-risk method to analyze the venous microstructure, which will not only be useful in clinical applications, but also provide a better understanding of BOLD effect.

DEVELOPMENT OF MESIAL TEMPORAL LOBE EPILEPSY IN CHOREA-ACANTHOCYTOSIS

Chorea-acanthocytosis (ChAc) is a hereditary movement disorder that is caused by recessive mutations in the VPS13A gene on chromosome 9q21, encoding for chorein.1 Epilepsy is currently not considered a core clinical feature of ChAc, although approximately 40% of patients are affected by seizures. We report on 3 patients with mesial temporal lobe epilepsy as the first, predominant clinical indication, and in 2 of the patients so far the sole clinical symptom of the disease. For the first time in this context, a pathologic process in the medial temporal lobes, leading to hippocampal atrophy, is unequivocally documented. ### Case histories. Patient 1 was a 14-year-old boy when, after repeat epigastric sensations, a first seemingly generalized tonic-clonic seizure led to hospital admission. Several weeks prior, he had started to complain about repetitive deja vu. Repeat EEG studies most frequently showed normal 10/second alpha-, but also paroxysmal generalized theta-, right hemispheric delta-, and right temporo-occipital spike- and sharp-wave activity. Until the present, 4 years after the initial onset, 2 more tonic-clonic seizures have occurred, and, with variable frequencies, the patient continues to report rising epigastric sensations, deja vu, and amnesic auras. Medical treatment currently consists of the administration of topiramate (300 mg/day). Patient 2, the older brother of patient 1, had a first complex partial seizure at 23 years of age. His history was unremarkable; no febrile seizures had been reported. Lately, however, he has also reported repeat episodes of deja vu. EEG findings ranged from normal 9/second alpha- to intermittent and continuous spike- and sharp-wave activity over both frontotemporal regions. Apart from rare epigastric auras, the patient is presently (i.e., 8 months after his first epileptic seizure) seizure-free under levetiracetam (2,500 mg/day). Patient 3 is a 39-year-old man …

Transcranial Magnetic Stimulation Intensities in Cognitive Paradigms

Background Transcranial magnetic stimulation (TMS) has become an important experimental tool for exploring the brains functional anatomy. As TMS interferes with neural activity, the hypothetical function of the stimulated area can thus be tested. One unresolved methodological issue in TMS experiments is the question of how to adequately calibrate stimulation intensities. The motor threshold (MT) is often taken as a reference for individually adapted stimulation intensities in TMS experiments, even if they do not involve the motor system. The aim of the present study was to evaluate whether it is reasonable to adjust stimulation intensities in each subject to the individual MT if prefrontal regions are stimulated prior to the performance of a cognitive paradigm. Methods and Findings Repetitive TMS (rTMS) was applied prior to a working memory task, either at the ‘fixed’ intensity of 40% maximum stimulator output (MSO), or individually adapted at 90% of the subjects MT. Stimulation was applied to a target region in the left posterior middle frontal gyrus (pMFG), as indicated by a functional magnetic resonance imaging (fMRI) localizer acquired beforehand, or to a control site (vertex). Results show that MT predicted the effect size after stimulating subjects with the fixed intensity (i.e., subjects with a low MT showed a greater behavioral effect). Nevertheless, the individual adaptation of intensities did not lead to stable effects. Conclusion Therefore, we suggest assessing MT and account for it as a measure for general cortical TMS susceptibility, even if TMS is applied outside the motor domain.

Prediction processes during multiple object tracking (MOT): Involvement of dorsal and ventral premotor cortices

The multiple object tracking (MOT) paradigm is a cognitive task that requires parallel tracking of several identical, moving objects following nongoal‐directed, arbitrary motion trajectories.

Deficits in subprocesses of visual feature search after frontal, parietal, and temporal brain lesions-a modeling approach

Deficits in visuospatial attention are commonly observed after different kinds of brain lesions. However, the structure–function relationships are not well understood. We investigated whether our response time (RT) model, strategies of visual search (STRAVIS), combined with a linear model of brain lesions, enables us to relate specific impairments in cognitive processes to specific sites of focal brain lesions. In STRAVIS, RTs in overt visual feature search with graded target-distractor similarity are decomposed into the durations of successive search steps. Fitting the model to an observers RTs yields individual estimates of the parameters “attentional focus size,” “attentional dwell time,” and “movement time of attention or the eyes.” In 28 patients with various focal lesions to the frontal, parietal, and/or temporal cortex and 28 matched controls, we determined with the help of linear models which lesions were most predictive for each parameter. Predictions were validated with a second sample of 12 patients and 12 controls. Critical lesion areas for the STRAVIS focus size were the dorsolateral prefrontal cortex and the temporal lobe, with dorsolateral prefrontal cortex lesions reducing the focus and temporal lesions enlarging it. The STRAVIS dwell time was reduced in patients with lesions to the anterior insula and the superior parietal lobe. Lesions to the frontal eye fields, the superior parietal lobe, and the parieto-occipital cortex were most detrimental to the STRAVIS movement time. Applying linear models to a patient sample with heterogeneous lesions may be a promising new method for investigating how different brain areas interplay in a complex task.