Oxytocinergic modulation of speech production-a double-blind placebo-controlled fMRI study.

Many socio-affective behaviors, such as speech, are modulated by oxytocin. While oxytocin modulates speech perception, it is not known whether it also affects speech production. Here, we investigated effects of oxytocin administration and interactions with the functional rs53576 oxytocin receptor (OXTR) polymorphism on produced speech and its underlying brain activity. During functional magnetic resonance imaging, 52 healthy male participants read sentences out loud with either neutral or happy intonation, a covert reading condition served as a common baseline. Participants were studied once under the influence of intranasal oxytocin and in another session under placebo. Oxytocin administration increased the second formant of produced vowels. This acoustic feature has previously been associated with speech valence; however, the acoustic differences were not perceptually distinguishable in our experimental setting. When preparing to speak, oxytocin enhanced brain activity in sensorimotor cortices and regions of both dorsal and right ventral speech processing streams, as well as subcortical and cortical limbic and executive control regions. In some of these regions, the rs53576 OXTR polymorphism modulated oxytocin administration-related brain activity. Oxytocin also gated cortical-basal ganglia circuits involved in the generation of happy prosody. Our findings suggest that several neural processes underlying speech production are modulated by oxytocin, including control of not only affective intonation but also sensorimotor aspects during emotionally neutral speech.

How the conception of control influences our understanding of actions.

Wilful movement requires neural control. Commonly, neural computations are thought to generate motor commands that bring the musculoskeletal system - that is, the plant - from its current physical state into a desired physical state. The current state can be estimated from past motor commands and from sensory information. Modelling movement on the basis of this concept of plant control strives to explain behaviour by identifying the computational principles for control signals that can reproduce the observed features of movements. From an alternative perspective, movements emerge in a dynamically coupled agent-environment system from the pursuit of subjective perceptual goals. Modelling movement on the basis of this concept of perceptual control aims to identify the controlled percepts and their coupling rules that can give rise to the observed characteristics of behaviour. In this Perspective, we discuss a broad spectrum of approaches to modelling human motor control and their notions of control signals, internal models, handling of sensory feedback delays and learning. We focus on the influence that the plant control and the perceptual control perspective may have on decisions when modelling empirical data, which may in turn shape our understanding of actions.

Aberrant sensorimotor coupling and movement planning in complex regional pain syndrome.

ABSTRACT: Complex regional pain syndrome (CRPS) is characterized by inflammation and a failure of multimodal signal integration in the central nervous system (CNS). Central nervous system reorganization might account for sensory deficits, pain, and motor symptoms in CRPS, but it is not clear how motor control is affected by CNS mechanisms. The present study characterized the motor performance and related cortical activity of 16 CRPS patients and 16 control participants during the planning of visually guided unimanual grips, in patients with either the unaffected left or the affected right hand, and investigated resting-state sensorimotor coupling in MRI. Patients started isometric movements further in advance of the "go" cue and earlier than control participants. Even when accounting for this different timing, results showed side-independent overactivation in planning-related sensorimotor regions in CRPS during manual grips and increased functional coupling between those regions at rest. Fear of movement or individual pain scores contributed only marginally to the observed effects. The study suggests that changes in planning-related sensorimotor CNS regions may explain difficulties with force exertion and motor control in CRPS.Perspective : Functional changes in motor planning-related brain regions might indicate that feedback-enhanced functional motor training may be effective for CRPS rehabilitation.

Neurocognitive Outcome and Seizure Freedom After Awake Surgery of Gliomas.

Objectives: Gliomas are often diagnosed due to epileptic seizures as well as neurocognitive deficits. First treatment choice for patients with gliomas in speech-related areas is awake surgery, which aims at maximizing tumor resection while preserving or improving patient's neurological status. The present study aimed at evaluating neurocognitive functioning and occurrence of epileptic seizures in patients suffering from gliomas located in language-related areas before and after awake surgery as well as during their follow up course of disease. Materials and Methods: In this prospective study we included patients who underwent awake surgery for glioma in the inferior frontal gyrus, superior temporal gyrus, or anterior temporal lobe. Preoperatively, as well as in the short-term (median 4.1 months, IQR 2.1-6.0) and long-term (median 18.3 months, IQR 12.3-36.6) postoperative course, neurocognitive functioning, neurologic status, the occurrence of epileptic seizures and number of antiepileptic drugs were recorded. Results: Between 09/2012 and 09/2019, a total of 27 glioma patients, aged 36.1 ± 11.8 years, were included. Tumor resection was complete in 15, subtotal in 6 and partial in 6 patients, respectively. While preoperatively impairment in at least one neurocognitive domain was found in 37.0% of patients, postoperatively, in the short-term, 36.4% of patients presented a significant deterioration in word fluency (p=0.009) and 34.8% of patients in executive functions (p=0.049). Over the long-term, scores improved to preoperative baseline levels. The number of patients with mood disturbances significantly declined from 66.7% to 34.8% after surgery (p=0.03). Regarding seizures, these were present in 18 (66.7%) patients prior to surgery. Postoperatively, 22 (81.5%) patients were treated with antiepileptic drugs with all patients presenting seizure-freedom. Conclusions: In patients suffering from gliomas in eloquent areas, the combination of awake surgery, regular neurocognitive assessment - considering individual patients´ functional outcome and rehabilitation needs - and the individual adjustment of antiepileptic therapy results in excellent patient outcome in the long-term course.

Neurocognitive deficits in patients suffering from glioma in speech-relevant areas of the left hemisphere.

OBJECTIVE: Patients with brain tumors frequently present neurocognitive deficits. Aiming at better understanding the impact of tumor localization on neurocognitive processes, we evaluated neurocognitive function prior to glioma surgery within one of four specific regions in the left speech-dominant hemisphere. METHODS: Between 04/2011 and 12/2019, 43 patients undergoing neurocognitive evaluation prior to awake surgery for gliomas (WHO grade I: 2; II: 6; III: 23; IV: 11) in the inferior frontal gyrus (IFG; n = 20), the anterior temporal lobe (ATL; n = 6), the posterior superior temporal region/supramarginal gyrus (pST/SMG; n = 7) or the posterior middle temporal gyrus (pMTG; n = 10) of the language dominant left hemisphere were prospectively included in the study. Cognitive performances were analyzed regarding an influence of patient characteristics and tumor localization. RESULTS: Severe impairment in at least one neurocognitive domain was found in 36 (83.7%) patients. Anxiety and depression were observed most frequently, followed by verbal memory impairments. Verbal memory was more strongly affected in patients with ATL or pST/SMG tumors compared to IFG tumors (p = 0.004 and p = 0.013, resp.). Overall, patients suffering from tumors in the ATL were most frequently and severely impaired. CONCLUSION: Patients suffering from gliomas involving different regions within the language dominant hemisphere frequently present impairments in neurocognitive domains also other than language. Considering individual functions at risk may help in better advising patients prior to treatment and in tailoring the individual therapeutic strategy to preserve patients' quality of life.

Local Anesthetic-Induced Central Nervous System Toxicity during Interscalene Brachial Plexus Block: A Case Series Study of Three Patients.

Local anesthetics are commonly administered by nuchal infiltration to provide a temporary interscalene brachial plexus block (ISB) in a surgical setting. Although less commonly reported, local anesthetics can induce central nervous system toxicity. In this case study, we present three patients with acute central nervous system toxicity induced by local anesthetics applied during ISB with emphasis on neurological symptoms, key neuroradiological findings and functional outcome. Medical history, clinical and imaging findings, and outcome of three patients with local anesthetic-induced toxic left hemisphere syndrome during left ISB were analyzed. All patients were admitted to our neurological intensive care unit between November 2016 and September 2019. All three patients presented in poor clinical condition with impaired consciousness and left hemisphere syndrome. Electroencephalography revealed slow wave activity in the affected hemisphere of all patients. Seizure activity with progression to status epilepticus was observed in one patient. In two out of three patients, cortical FLAIR hyperintensities and restricted diffusion in the territory of the left internal carotid artery were observed in magnetic resonance imaging. Assessment of neurological severity scores revealed spontaneous partial reversibility of neurological symptoms. Local anesthetic-induced CNS toxicity during ISB can lead to severe neurological impairment and anatomically variable cerebral lesions.

[Aphasia associated with lacunar infarctions]. / Aphasien bei lakunären Hirninfarkten.

BACKGROUND: Typical lacunar syndromes do not include aphasia but aphasia has been reported in rare atypical lacunar syndromes. OBJECTIVE: Description of the phenomenology and of affected fiber tracts. MATERIAL AND METHODS: Case series of three patients with lacunar stroke as evidenced by magnetic resonance imaging. Identification of affected fiber tracts via fiber tracking from coregistered lesion sites in brains of two healthy participants. RESULTS: The lacunar strokes that produced aphasia were located in the very lateral territory of perforating branches of the middle cerebral artery and extended along the external capsule into its most rostrodorsal aspect. Even though the cortex, thalamus and most parts of the basal ganglia were unaffected, patients exhibited a mild to moderate nonfluent aphasia with syntactic deficits. Fiber tracking revealed that in contrast to the nonaphasic control patient with a neighboring lacunar stroke, the aphasic patient strokes involved particularly fibers of the left arcuate fascicle as well as fibers of the frontostriatal and frontal aslant tracts. CONCLUSION: Left lateral lacunar stroke can cause clinically relevant aphasia through disruption of speech-relevant fiber tracts.

Observation and assessment of acoustic contamination of electrophysiological brain signals during speech production and sound perception.

OBJECTIVE: A current challenge of neurotechnologies is to develop speech brain-computer interfaces aiming at restoring communication in people unable to speak. To achieve a proof of concept of such system, neural activity of patients implanted for clinical reasons can be recorded while they speak. Using such simultaneously recorded audio and neural data, decoders can be built to predict speech features using features extracted from brain signals. A typical neural feature is the spectral power of field potentials in the high-gamma frequency band, which happens to overlap the frequency range of speech acoustic signals, especially the fundamental frequency of the voice. Here, we analyzed human electrocorticographic and intracortical recordings during speech production and perception as well as a rat microelectrocorticographic recording during sound perception. We observed that several datasets, recorded with different recording setups, contained spectrotemporal features highly correlated with those of the sound produced by or delivered to the participants, especially within the high-gamma band and above, strongly suggesting a contamination of electrophysiological recordings by the sound signal. This study investigated the presence of acoustic contamination and its possible source. APPROACH: We developed analysis methods and a statistical criterion to objectively assess the presence or absence of contamination-specific correlations, which we used to screen several datasets from five centers worldwide. MAIN RESULTS: Not all but several datasets, recorded in a variety of conditions, showed significant evidence of acoustic contamination. Three out of five centers were concerned by the phenomenon. In a recording showing high contamination, the use of high-gamma band features dramatically facilitated the performance of linear decoding of acoustic speech features, while such improvement was very limited for another recording showing no significant contamination. Further analysis and in vitro replication suggest that the contamination is caused by the mechanical action of the sound waves onto the cables and connectors along the recording chain, transforming sound vibrations into an undesired electrical noise affecting the biopotential measurements. SIGNIFICANCE: Although this study does not per se question the presence of speech-relevant physiological information in the high-gamma range and above (multiunit activity), it alerts on the fact that acoustic contamination of neural signals should be proofed and eliminated before investigating the cortical dynamics of these processes. To this end, we make available a toolbox implementing the proposed statistical approach to quickly assess the extent of contamination in an electrophysiological recording (https://doi.org/10.5281/zenodo.3929296).

Differential contributions of the two cerebral hemispheres to temporal and spectral speech feedback control.

Proper speech production requires auditory speech feedback control. Models of speech production associate this function with the right cerebral hemisphere while the left hemisphere is proposed to host speech motor programs. However, previous studies have investigated only spectral perturbations of the auditory speech feedback. Since auditory perception is known to be lateralized, with right-lateralized analysis of spectral features and left-lateralized processing of temporal features, it is unclear whether the observed right-lateralization of auditory speech feedback processing reflects a preference for speech feedback control or for spectral processing in general. Here we use a behavioral speech adaptation experiment with dichotically presented altered auditory feedback and an analogous fMRI experiment with binaurally presented altered feedback to confirm a right hemisphere preference for spectral feedback control and to reveal a left hemisphere preference for temporal feedback control during speaking. These results indicate that auditory feedback control involves both hemispheres with differential contributions along the spectro-temporal axis.

Differential contributions of the two human cerebral hemispheres to action timing.

Rhythmic actions benefit from synchronization with external events. Auditory-paced finger tapping studies indicate the two cerebral hemispheres preferentially control different rhythms. It is unclear whether left-lateralized processing of faster rhythms and right-lateralized processing of slower rhythms bases upon hemispheric timing differences that arise in the motor or sensory system or whether asymmetry results from lateralized sensorimotor interactions. We measured fMRI and MEG during symmetric finger tapping, in which fast tapping was defined as auditory-motor synchronization at 2.5 Hz. Slow tapping corresponded to tapping to every fourth auditory beat (0.625 Hz). We demonstrate that the left auditory cortex preferentially represents the relative fast rhythm in an amplitude modulation of low beta oscillations while the right auditory cortex additionally represents the internally generated slower rhythm. We show coupling of auditory-motor beta oscillations supports building a metric structure. Our findings reveal a strong contribution of sensory cortices to hemispheric specialization in action control.

"Spontaneous" late recovery from stuttering: Dimensions of reported techniques and causal attributions.

PURPOSE: (1) To survey the employed techniques and the reasons/occasions which adults who had recovered from stuttering after age 11 without previous treatment reported as causal to overcome stuttering, (2) to investigate whether the techniques and causal attributions can be reduced to coherent (inherently consistent) dimensions, and (3) whether these dimensions reflect common therapy components. METHODS: 124 recovered persons from 8 countries responded by SurveyMonkey or paper-and-pencil to rating scale questions about 49 possible techniques and 15 causal attributions. RESULTS: A Principal Component Analysis of 110 questionnaires identified 6 components (dimensions) for self-assisted techniques (Speech Restructuring; Relaxed/Monitored Speech; Elocution; Stage Performance; Sought Speech Demands; Reassurance; 63.7% variance explained), and 3 components of perceived causal attributions of recovery (Life Change, Attitude Change, Social Support; 58.0% variance explained). DISCUSSION: Two components for self-assisted techniques (Speech Restructuring; Elocution) reflect treatment methods. Another component (Relaxed/Monitored Speech) consists mainly of items that reflect a common, non-professional understanding of effective management of stuttering. The components of the various perceived reasons for recovery reflect differing implicit theories of causes for recovery from stuttering. These theories are considered susceptible to various biases. This identification of components of reported techniques and of causal attributions is novel compared to previous studies who just list techniques and attributions. CONCLUSION: The identified dimensions of self-assisted techniques and causal attributions to reduce stuttering as extracted from self-reports of a large, international sample of recovered formerly stuttering adults may guide the application of behavioral stuttering therapies.

Low-Frequency Oscillations Code Speech during Verbal Working Memory.

The way the human brain represents speech in memory is still unknown. An obvious characteristic of speech is its evolvement over time. During speech processing, neural oscillations are modulated by the temporal properties of the acoustic speech signal, but also acquired knowledge on the temporal structure of language influences speech perception-related brain activity. This suggests that speech could be represented in the temporal domain, a form of representation that the brain also uses to encode autobiographic memories. Empirical evidence for such a memory code is lacking. We investigated the nature of speech memory representations using direct cortical recordings in the left perisylvian cortex during delayed sentence reproduction in female and male patients undergoing awake tumor surgery. Our results reveal that the brain endogenously represents speech in the temporal domain. Temporal pattern similarity analyses revealed that the phase of frontotemporal low-frequency oscillations, primarily in the beta range, represents sentence identity in working memory. The positive relationship between beta power during working memory and task performance suggests that working memory representations benefit from increased phase separation.SIGNIFICANCE STATEMENT Memory is an endogenous source of information based on experience. While neural oscillations encode autobiographic memories in the temporal domain, little is known on their contribution to memory representations of human speech. Our electrocortical recordings in participants who maintain sentences in memory identify the phase of left frontotemporal beta oscillations as the most prominent information carrier of sentence identity. These observations provide evidence for a theoretical model on speech memory representations and explain why interfering with beta oscillations in the left inferior frontal cortex diminishes verbal working memory capacity. The lack of sentence identity coding at the syllabic rate suggests that sentences are represented in memory in a more abstract form compared with speech coding during speech perception and production.

Cognitive effects of rhythmic auditory stimulation in Parkinson's disease: A P300 study.

Rhythmic auditory stimulation (RAS) may compensate dysfunctions of the basal ganglia (BG), involved with intrinsic evaluation of temporal intervals and action initiation or continuation. In the cognitive domain, RAS containing periodically presented tones facilitates young healthy participants' attention allocation to anticipated time points, indicated by better performance and larger P300 amplitudes to periodic compared to random stimuli. Additionally, active auditory-motor synchronization (AMS) leads to a more precise temporal encoding of stimuli via embodied timing encoding than stimulus presentation adapted to the participants' actual movements. Here we investigated the effect of RAS and AMS in Parkinson's disease (PD). 23 PD patients and 23 healthy age-matched controls underwent an auditory oddball task. We manipulated the timing (periodic/random/adaptive) and setting (pedaling/sitting still) of stimulation. While patients elicited a general timing effect, i.e., larger P300 amplitudes for periodic versus random tones for both, sitting and pedaling conditions, controls showed a timing effect only for the sitting but not for the pedaling condition. However, a correlation between P300 amplitudes and motor variability in the periodic pedaling condition was obtained in control participants only. We conclude that RAS facilitates attentional processing of temporally predictable external events in PD patients as well as healthy controls, but embodied timing encoding via body movement does not affect stimulus processing due to BG impairment in patients. Moreover, even with intact embodied timing encoding, such as healthy elderly, the effect of AMS depends on the degree of movement synchronization performance, which is very low in the current study.

Endogenous modulation of human visual cortex activity improves perception at twilight.

Perception, particularly in the visual domain, is drastically influenced by rhythmic changes in ambient lighting conditions. Anticipation of daylight changes by the circadian system is critical for survival. However, the neural bases of time-of-day-dependent modulation in human perception are not yet understood. We used fMRI to study brain dynamics during resting-state and close-to-threshold visual perception repeatedly at six times of the day. Here we report that resting-state signal variance drops endogenously at times coinciding with dawn and dusk, notably in sensory cortices only. In parallel, perception-related signal variance in visual cortices decreases and correlates negatively with detection performance, identifying an anticipatory mechanism that compensates for the deteriorated visual signal quality at dawn and dusk. Generally, our findings imply that decreases in spontaneous neural activity improve close-to-threshold perception.

Speaking-related changes in cortical functional connectivity associated with assisted and spontaneous recovery from developmental stuttering.

We previously reported speaking-related activity changes associated with assisted recovery induced by a fluency shaping therapy program and unassisted recovery from developmental stuttering (Kell et al., Brain 2009). While assisted recovery re-lateralized activity to the left hemisphere, unassisted recovery was specifically associated with the activation of the left BA 47/12 in the lateral orbitofrontal cortex. These findings suggested plastic changes in speaking-related functional connectivity between left hemispheric speech network nodes. We reanalyzed these data involving 13 stuttering men before and after fluency shaping, 13 men who recovered spontaneously from their stuttering, and 13 male control participants, and examined functional connectivity during overt vs. covert reading by means of psychophysiological interactions computed across left cortical regions involved in articulation control. Persistent stuttering was associated with reduced auditory-motor coupling and enhanced integration of somatosensory feedback between the supramarginal gyrus and the prefrontal cortex. Assisted recovery reduced this hyper-connectivity and increased functional connectivity between the articulatory motor cortex and the auditory feedback processing anterior superior temporal gyrus. In spontaneous recovery, both auditory-motor coupling and integration of somatosensory feedback were normalized. In addition, activity in the left orbitofrontal cortex and superior cerebellum appeared uncoupled from the rest of the speech production network. These data suggest that therapy and spontaneous recovery normalizes the left hemispheric speaking-related activity via an improvement of auditory-motor mapping. By contrast, long-lasting unassisted recovery from stuttering is additionally supported by a functional isolation of the superior cerebellum from the rest of the speech production network, through the pivotal left BA 47/12.

Assisted and unassisted recession of functional anomalies associated with dysprosody in adults who stutter.

PURPOSE: Speech in persons who stutter (PWS) is associated with disturbed prosody (speech melody and intonation), which may impact communication. The neural correlates of PWS' altered prosody during speaking are not known, neither is how a speech-restructuring therapy affects prosody at both a behavioral and a cerebral level. METHODS: In this fMRI study, we explored group differences in brain activation associated with the production of different kinds of prosody in 13 male adults who stutter (AWS) before, directly after, and at least 1 year after an effective intensive fluency-shaping treatment, in 13 typically fluent-speaking control participants (CP), and in 13 males who had spontaneously recovered from stuttering during adulthood (RAWS), while sentences were read aloud with 'neutral', instructed emotional (happy), and linguistically driven (questioning) prosody. These activations were related to speech production acoustics. RESULTS: During pre-treatment prosody generation, the pars orbitalis of the left inferior frontal gyrus and the left anterior insula were activated less in AWS than in CP. The degree of hypo-activation correlated with acoustic measures of dysprosody. Paralleling the near-normalization of free speech melody following fluency-shaping therapy, AWS normalized the inferior frontal hypo-activation, sooner after treatment for generating emotional than linguistic prosody. Unassisted recovery was associated with an additional recruitment of cerebellar resources. CONCLUSIONS: Fluency shaping therapy may restructure prosody, which approaches that of typically fluent-speaking people. Such a process may benefit from additional training of instructed emotional and linguistic prosody by inducing plasticity in the inferior frontal region which has developed abnormally during childhood in PWS.

Non-linear Relationship between BOLD Activation and Amplitude of Beta Oscillations in the Supplementary Motor Area during Rhythmic Finger Tapping and Internal Timing.

Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region.

Personalized translational epilepsy research - Novel approaches and future perspectives: Part II: Experimental and translational approaches.

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1].

Personalized translational epilepsy research - Novel approaches and future perspectives: Part I: Clinical and network analysis approaches.

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. Part I includes the clinical phenotyping and diagnostic methods, EEG network-analysis, biomarkers, and personalized treatment approaches. In Part II, experimental and translational approaches will be discussed (Bauer et al., 2017) [1].

Functional hemispheric asymmetries during the planning and manual control of virtual avatar movements.

Both hemispheres contribute to motor control beyond the innervation of the contralateral alpha motoneurons. The left hemisphere has been associated with higher-order aspects of motor control like sequencing and temporal processing, the right hemisphere with the transformation of visual information to guide movements in space. In the visuomotor context, empirical evidence regarding the latter has been limited though the right hemisphere's specialization for visuospatial processing is well-documented in perceptual tasks. This study operationalized temporal and spatial processing demands during visuomotor processing and investigated hemispheric asymmetries in neural activation during the unimanual control of a visual cursor by grip force. Functional asymmetries were investigated separately for visuomotor planning and online control during functional magnetic resonance imaging in 19 young, healthy, right-handed participants. The expected cursor movement was coded with different visual trajectories. During planning when spatial processing demands predominated, activity was right-lateralized in a hand-independent manner in the inferior temporal lobe, occipito-parietal border, and ventral premotor cortex. When temporal processing demands overweighed spatial demands, BOLD responses during planning were left-lateralized in the temporo-parietal junction. During online control of the cursor, right lateralization was not observed. Instead, left lateralization occurred in the intraparietal sulcus. Our results identify movement phase and spatiotemporal demands as important determinants of dynamic hemispheric asymmetries during visuomotor processing. We suggest that, within a bilateral visuomotor network, the right hemisphere exhibits a processing preference for planning global spatial movement features whereas the left hemisphere preferentially times local features of visual movement trajectories and adjusts movement online.