Changes in attentional resources during the acquisition of laparoscopic surgical skills.

BACKGROUND: Increasing familiarity and practice might free up mental resources during laparoscopic surgical skills training. The aim of the study was to track changes in mental resource allocation during acquisition of laparoscopic surgical skills. METHODS: Medical students with no previous experience in laparoscopic surgery took part in a 5-week laparoscopic training curriculum. At the beginning and end of the training period, one of the training tasks was combined with a secondary auditory detection task that required pressing a foot switch for defined target tones, creating a dual-task situation. During execution of the two concurrent tasks, continuous electroencephalographic measurements were made, with special attention to the P300 component, an index of mental resources. Accuracy and reaction times of the secondary task were determined. RESULTS: All 14 participants successfully completed the training curriculum. Target times for successful completion of individual tasks decreased significantly during training sessions (P <0.001 for all tasks). Comparing results before and after training showed a significant decrease in event-related brain potential amplitude at the parietal electrode cluster (P300 component, W = 67, P = 0.026), but there were no differences in accuracy (percentage correct responses: W = 48, P = 0.518) or reaction times (W = 42, P = 0.850) in the auditory detection task. CONCLUSION: The P300 decrease in the secondary task over training demonstrated a shift of mental resources to the primary task: the surgical exercise. This indicates that, with more practice, mental resources are freed up for additional tasks.

Brain stimulation in obesity.

Obesity is taking up epidemic proportions worldwide with significant impacts on the health of both the affected individual and on society as a whole. Treatment approaches consist of behavioural and pharmacological approaches, however, these are often found to be ineffective. In severe obesity, bariatric surgery is frequently performed. Unfortunately, 40% of patients show substantial weight gain over the long term or display the associated metabolic syndrome, making the development of novel therapies necessary. This review summarizes some of the current conceptual models, in particularly the 'food addiction' model, and then discusses specific therapeutic targets of brain stimulation, both non-invasive (transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and transcutaneous vagus nerve stimulation (VNS)) and invasive (deep brain stimulation and invasive VNS). As we will show, neuromodulatory approaches represent a promising tool for targeting specific brain structures implicated in the pathophysiology of obesity. Non-invasive techniques such as TMS, tDCS and transcutaneous VNS need further investigation before they may become ready for clinical usage. The currently available study data suggest that deep brain stimulation may become an effective and acceptable therapy for otherwise treatment-resistant obese patients. The results of the currently undergoing clinical trials are eagerly awaited.

Striatal dysfunction in X-linked dystonia-parkinsonism is associated with disease progression.

BACKGROUND AND PURPOSE: X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset movement disorder associated with striatal atrophy. As the dopaminergic system has not yet been systemically studied in this basal ganglia model disease, it is unclear whether nigrostriatal dysfunction contributes to parkinsonism in XDP. METHODS: Pre- and post-synaptic dopaminergic function was assessed in XDP. A total of 10 123 jod-benzamide (IBZM) single-photon emission computed tomography (SPECT) images were obtained for nine patients aged 42.3 ± 9.5 years (SD; range 30-52) and one asymptomatic mutation carrier (38 years), and four ioflupane (FP-CIT) SPECT images were obtained for four patients, aged 41.5 ± 11.6 years (range 30-52 years). Structural magnetic resonance imaging was also performed for all mutation carriers and 10 matched healthy controls. RESULTS: All patients were men who suffered from severe, disabling segmental or generalized dystonia and had varying degrees of parkinsonism. IBZM SPECT images were pathological in 8/9 symptomatic patients with distinct reduced post-synaptic tracer uptake in the caudate nucleus and putamen, and unremarkable in the asymptomatic mutation carrier. Longer disease duration was correlated with lower IBZM binding ratios. All subjects exhibited slightly reduced FP-CIT uptake values compared to controls for each analyzed region (-37% to -41%) which may be linked to basal ganglia volume loss. Visual inspection revealed physiological FP-CIT uptake in 1/4 patients. CONCLUSIONS: This nuclear imaging study provides evidence that the functional decline of post-synaptic dopaminergic neurotransmission is related to disease duration and ongoing neurodegeneration. Given the severe striatal cell loss which could be verified with post-synaptic nuclear imaging, both parkinsonism and dystonia in XDP are probably mainly due to striatal dysfunction.

Mild Thyrotoxicosis Leads to Brain Perfusion Changes: An Arterial Spin Labelling Study.

Hypo- and hyperthyroidism have effects on brain structure and function, as well as cognitive processes, including memory. However, little is known about the influence of thyroid hormones on brain perfusion and the relationship of such perfusion changes with cognition. The present study aimed to demonstrate the effect of short-term experimental hyperthyroidism on brain perfusion in healthy volunteers and to assess whether perfusion changes, if present, are related to cognitive performance. It is known that an interaction exists between brain perfusion and cerebral oxygen consumption rate and it is considered that neural activation increases cerebral regional perfusion rate in brain areas associated with memory. Measuring cerebral blood flow may therefore represent a proxy for neural activity. Therefore, arterial spin labelling (ASL) measurements were conducted and later analysed to evaluate brain perfusion in 29 healthy men before and after ingesting thyroid hormones for 8 weeks. Psychological tests concerning memory were performed at the same time-points and the results were correlated with the imaging results. In the hyperthyroid condition, perfusion was increased in the posterior cerebellum in regions connected with cerebral networks associated with cognitive control and the visual cortex compared to the euthyroid condition. In addition, these perfusion changes were positively correlated with changes of performance in the German version of the Auditory Verbal Learning Task [AVLT, Verbaler Lern-und-Merkfähigkeits-Test (VLMT)]. Cerebellar perfusion and function therefore appears to be modulated by thyroid hormones, likely because the cerebellum hosts a high number of thyroid hormone receptors.

Music supported therapy promotes motor plasticity in individuals with chronic stroke.

Novel rehabilitation interventions have improved motor recovery by induction of neural plasticity in individuals with stroke. Of these, Music-supported therapy (MST) is based on music training designed to restore motor deficits. Music training requires multimodal processing, involving the integration and co-operation of visual, motor, auditory, affective and cognitive systems. The main objective of this study was to assess, in a group of 20 individuals suffering from chronic stroke, the motor, cognitive, emotional and neuroplastic effects of MST. Using functional magnetic resonance imaging (fMRI) we observed a clear restitution of both activity and connectivity among auditory-motor regions of the affected hemisphere. Importantly, no differences were observed in this functional network in a healthy control group, ruling out possible confounds such as repeated imaging testing. Moreover, this increase in activity and connectivity between auditory and motor regions was accompanied by a functional improvement of the paretic hand. The present results confirm MST as a viable intervention to improve motor function in chronic stroke individuals.

Dissociable cerebellar activity during spatial navigation and visual memory in bilateral vestibular failure.

OBJECTIVE: Spatial orientation and navigation depends on information from the vestibular system. Previous work suggested impaired spatial navigation in patients with bilateral vestibular failure (BVF). The aim of this study was to investigate event-related brain activity by functional magnetic resonance imaging (fMRI) during spatial navigation and visual memory tasks in BVF patients. METHODS: Twenty-three BVF patients and healthy age- and gender matched control subjects performed learning sessions of spatial navigation by watching short films taking them through various streets from a driver's perspective along a route to the Cathedral of Cologne using virtual reality videos (adopted and modified from Google Earth). In the scanner, participants were asked to respond to questions testing for visual memory or spatial navigation while they viewed short video clips. From a similar but not identical perspective depicted video frames of routes were displayed which they had previously seen or which were completely novel to them. RESULTS: Compared with controls, posterior cerebellar activity in BVF patients was higher during spatial navigation than during visual memory tasks, in the absence of performance differences. This cerebellar activity correlated with disease duration. CONCLUSIONS: Cerebellar activity during spatial navigation in BVF patients may reflect increased non-vestibular efforts to counteract the development of spatial navigation deficits in BVF. Conceivably, cerebellar activity indicates a change in navigational strategy of BVF patients, i.e. from a more allocentric, landmark or place-based strategy (hippocampus) to a more sequence-based strategy. This interpretation would be in accord with recent evidence for a cerebellar role in sequence-based navigation.

Transcranial magnetic stimulation reveals complex cognitive control representations in the rostral frontal cortex.

Convergent evidence suggests that the lateral frontal cortex is at the heart of a brain network subserving cognitive control. Recent theories assume a functional segregation along the rostro-caudal axis of the lateral frontal cortex based on differences in the degree of complexity of cognitive control. However, the functional contribution of specific rostral and caudal sub-regions remains elusive. Here we investigate the impact of disrupting rostral and caudal target regions on cognitive control processes, using Transcranial Magnetic Stimulation (TMS). Participants performed three different task-switching conditions that assessed differences in the degree of complexity of cognitive control processes, after temporally disrupting rostral, or caudal target regions, or a control region. Disrupting the rostral lateral frontal region specifically impaired behavioral performance of the most complex task-switching condition, in comparison to the caudal target region and the control region. These novel findings shed light on the neuroanatomical architecture supporting control over goal-directed behavior.

The neural bases of the pseudohomophone effect: Phonological constraints on lexico-semantic access in reading.

We investigated phonological processing in normal readers to answer the question to what extent phonological recoding is active during silent reading and if or how it guides lexico-semantic access. We addressed this issue by looking at pseudohomophone and baseword frequency effects in lexical decisions with event-related functional magnetic resonance imaging (fMRI). The results revealed greater activation in response to pseudohomophones than for well-controlled pseudowords in the left inferior/superior frontal and middle temporal cortex, left insula, and left superior parietal lobule. Furthermore, we observed a baseword frequency effect for pseudohomophones (e.g., FEAL) but not for pseudowords (e.g., FEEP). This baseword frequency effect was qualified by activation differences in bilateral angular and left supramarginal, and bilateral middle temporal gyri for pseudohomophones with low- compared to high-frequency basewords. We propose that lexical decisions to pseudohomophones involves phonology-driven lexico-semantic activation of their basewords and that this is converging neuroimaging evidence for automatically activated phonological representations during silent reading in experienced readers.

Performance monitoring and behavioral adaptation during task switching: an fMRI study.

Despite significant advances, the neural correlates and neurochemical mechanisms involved in performance monitoring and behavioral adaptation are still a matter for debate. Here, we used a modified Eriksen-Flanker task in a magnetic resonance imaging (MRI) study that required the participants to derive the correct stimulus-response association based on a feedback given after each flanker stimulus. Participants had to continuously monitor and adapt their performance as the stimulus-response association switched after a jittered time interval without notice. After every switch an increase of reaction times was observed. At the neural level, the feedback indicating the need to switch was associated with activation of the precuneus, the cingulate cortex, the insula and a brainstem region tentatively identified as the locus coeruleus. This brainstem system appears to interact with this cortical network and seems to be essential for performance monitoring and behavioral adaptation. In contrast, the cerebellum crus and prefrontal areas are activated during error feedback processing. Furthermore we found activations of the hippocampus and parahippocampal gyrus bilaterally after a correct feedback in learnable stimulus-response associations. These results highlight the contribution of brainstem nuclei to performance adaptation.

Audiovisual perception of natural speech is impaired in adult dyslexics: an ERP study.

The present study used event-related brain potentials (ERPs) to investigate audiovisual integration processes in the perception of natural speech in a group of German adult developmental dyslexic readers. Twelve dyslexic and twelve non-dyslexic adults viewed short videos of a male German speaker. Disyllabic German nouns served as stimulus material. The auditory and the visual stimulus streams were segregated to create four conditions: in the congruent condition, the spoken word and the auditory word were identical. In the incongruent condition, the auditory and the visual word (i.e., the lip movements of the utterance) were different. Furthermore, on half of the trials, white noise (45 dB SPL) was superimposed on the auditory trace. Subjects had to say aloud the word they understood after they viewed the video. Behavioral data. Dyslexic readers committed more errors compared to normal readers in the noise conditions, and this effect was particularly present for congruent trials. ERPs showed a distinct N170 component at temporo-parietal electrodes that was smaller in amplitude for dyslexic readers. Both, normal and dyslexic readers, showed a clear effect of noise at centro-parietal electrodes between 300 and 600 ms. An analysis of error trials reflecting audiovisual integration (verbal responses in the incongruent noise condition that are a mix of the visual and the auditory word) revealed more positive ERPs for dyslexic readers at temporo-parietal electrodes 200-500 ms poststimulus. For normal readers, no such effect was present. These findings are discussed as reflecting increased effort in dyslexics under circumstances of distorted acoustic input. The superimposition of noise leads dyslexics to rely more on the integration of auditory and visual input (lip reading). Furthermore, the smaller N170-amplitudes indicate deficits in the processing of moving faces in dyslexic adults.

A network analysis of audiovisual affective speech perception.

In this study we were interested in the neural system supporting the audiovisual (AV) integration of emotional expression and emotional prosody. To this end normal participants were exposed to short videos of a computer-animated face voicing emotionally positive or negative words with the appropriate prosody. Facial expression of the face was either neutral or emotionally appropriate. To reveal the neural network involved in affective AV integration, standard univariate analysis of functional magnetic resonance (fMRI) data was followed by a random-effects Granger causality mapping (RFX-GCM). The regions that distinguished emotional from neutral facial expressions in the univariate analysis were taken as seed regions. In trials showing emotional expressions compared to neutral trials univariate analysis showed activation primarily in bilateral amygdala, fusiform gyrus, middle temporal gyrus/superior temporal sulcus and inferior occipital gyrus. When employing either the left amygdala or the right amygdala as a seed region in RFX-GCM we found connectivity with the right hemispheric fusiform gyrus, with the indication that the fusiform gyrus sends information to the Amygdala. These results led to a working model for face perception in general and for AV-affective integration in particular which is an elaborated adaptation of existing models.

Preattentive mechanisms of change detection in early auditory cortex: a 7 Tesla fMRI study.

The auditory system continuously monitors the environment for irregularities in an automatic, preattentive fashion. This is presumably accomplished by two mechanisms: a sensory mechanism detects a deviant sound on the basis of differential refractoriness of neural populations sensitive to the standard and deviant sounds, whereas the cognitive mechanism reveals deviance by comparing incoming auditory information with a template derived from previous input. Using fast event-related high-resolution functional magnetic resonance imaging at 7 Tesla we show that both mechanisms can be mapped to different parts of the auditory cortex both at the group level and the single-subject level. The sensory mechanism is supported by primary auditory areas in Heschl's gyrus whereas the cognitive mechanism is implemented in more anterior secondary auditory areas. Both mechanisms are equally engaged by simple sine-wave tones and speech-related phonemes indicating that streams of speech and non-speech stimuli are processed in a similar fashion.

Maladaptive connectivity of Broca's area in schizophrenia during audiovisual speech perception: an fMRI study.

Speech comprehension relies on auditory as well as visual information, and is enhanced in healthy subjects, when audiovisual (AV) information is present. Patients with schizophrenia have been reported to have problems regarding this AV integration process, but little is known about which underlying neural processes are altered. Functional magnetic resonance imaging was performed in 15 schizophrenia patients (SP) and 15 healthy controls (HC) to study functional connectivity of Broca's area by means of a beta series correlation method during perception of audiovisually presented bisyllabic German nouns, in which audio and video either matched or did not match. Broca's area of SP showed stronger connectivity with supplementary motor cortex for incongruent trials whereas HC connectivity was stronger for congruent trials. The right posterior superior temporal sulcus (RpSTS) area showed differences in connectivity for congruent and incongruent trials in HC in contrast to SP where the connectivity was similar for both conditions. These smaller differences in connectivity in SP suggest a less adaptive processing of audiovisually congruent and incongruent speech. The findings imply that AV integration problems in schizophrenia are associated with maladaptive connectivity of Broca's and RpSTS area in particular when confronted with incongruent stimuli. Results are discussed in light of recent AV speech perception models.

Tracking post-error adaptation in the motor system by transcranial magnetic stimulation.

The commission of an error triggers cognitive control processes dedicated to error correction and prevention. Post-error adjustments leading to response slowing following an error ("post-error slowing"; PES) might be driven by changes in excitability of the motor regions and the corticospinal tract (CST). The time-course of such excitability modulations of the CST leading to PES is largely unknown. To track these presumed excitability changes after an error, single pulse transcranial magnetic stimulation (TMS) was applied to the motor cortex ipsilateral to the responding hand, while participants were performing an Eriksen flanker task. A robotic arm with a movement compensation system was used to maintain the TMS coil in the correct position during the experiment. Magnetic pulses were delivered over the primary motor cortex ipsilateral to the active hand at different intervals (150, 300, 450 ms) after correct and erroneous responses, and the motor-evoked potentials (MEP) of the first dorsal interosseous muscle (FDI) contralateral to the stimulated hemisphere were recorded. MEP amplitude was increased 450 ms after the error. Two additional experiments showed that this increase was neither associated to the correction of the erroneous responses nor to the characteristics of the motor command. To the extent to which the excitability of the motor cortex ipsi- and contralateral to the response hand are inversely related, these results suggest a decrease in the excitability of the active motor cortex after an erroneous response. This modulation of the activity of the CST serves to prevent further premature and erroneous responses. At a more general level, the study shows the power of the TMS technique for the exploration of the temporal evolution of post-error adjustments within the motor system.

[The presymptomatic stage of neurodegenerative disorders]. / Das präsymptomatische Stadium neurodegenerativer Erkrankungen.

Neurodegenerative disorders, such as Huntington's disease, spinocerebellar ataxias, Parkinson's disease or Alzheimer's disease, manifest in adult age with insidiously developing, slowly progressing symptoms. At this stage, most patients consult a doctor, and a definite diagnosis can be made. It is, however, well established that the manifest disease is preceded by a presymptomatic disease stage that may last for years. A striking example is Parkinson's disease, in which more than half of the dopaminergic neurons of the substantia nigra are lost before motor symptoms appear. Studies of the presymptomatic stage of neurodegenerative disorders are pivotal for an advanced understanding of these disorders and the development of preventive strategies aimed at postponing the clinical onset of these disorders. It is therefore important to identify the earliest and most sensitive clinical signs and biological markers that herald the onset of the illness. Furthermore, studies of presymptomatic disease stages are important because they may help to unravel compensatory mechanisms responsible for apparently normal brain function despite ongoing neurodegeneration.

Human hypothalamus shows differential responses to basic motivational stimuli--an invasive electrophysiology study.

The hypothalamus supports basic motivational behaviours such as mating and feeding. Recording directly from the posterior inferior hypothalamus in a male patient receiving a deep brain stimulation (DBS) electrode for the alleviation of cluster headache, we tested the hypothalamic response to different classes of motivational stimuli (sexually relevant: pictures of dressed and undressed women; pictures of food) and pictures of common objects as control. Averaged local field potentials (LFP) to sexually relevant stimuli were characterized by a biphasic significantly enhanced response (relative to objects; bootstrapping statistics) with a first phase starting at around 200 ms and a second phase peaking at around 600 ms. Sexually relevant stimuli also showed a greatly enhanced positivity relative to other stimulus classes in surface event-related potentials in a group of 11 male control participants. It is suggested that the hypothalamus is involved in the recruitment of attentional resources by sexually relevant stimuli reflected in this surface positivity. In a second session, the response to food stimuli relative to objects was tested in two states: after fasting for 14 h, LFPs to food and object stimuli showed significant differences in between 300 and 850 ms, which disappeared after a full high-calorie meal, thus replicating classic studies in monkeys [Rolls et al., Brain Res (1976) 111:53-66]. The current data are the first to demonstrate hypothalamic responses to the sight of motivational stimuli in man and thus shows that recording from DBS electrodes might provide important information about the cognitive functions of subcortical structures.

Neural reorganization underlies improvement in stroke-induced motor dysfunction by music-supported therapy.

Motor impairments are common after stroke, but efficacious therapies for these dysfunctions are scarce. By extending an earlier study on the effects of music-supported therapy, behavioral indices of motor function as well as electrophysiological measures were obtained before and after a series of therapy sessions to assess whether this new treatment leads to neural reorganization and motor recovery in patients after stroke. The study group comprised 32 stroke patients in a large rehabilitation hospital; they had moderately impaired motor function and no previous musical experience. Over a period of 3 weeks, these patients received 15 sessions of music-supported therapy using a manualized step-by-step approach. For comparison 30 additional patients received standard rehabilitation procedures. Fine as well as gross motor skills were trained by using either a MIDI-piano or electronic drum pads programmed to emit piano tones. Motor functions were assessed by an extensive test battery. In addition, we studied event-related desynchronization/synchronization and coherences from all 62 patients performing self-paced movements of the index finger (MIDI-piano) and of the whole arm (drum pads). Results showed that music-supported therapy yielded significant improvement in fine as well as gross motor skills with respect to speed, precision, and smoothness of movements. Neurophysiological data showed a more pronounced event-related desynchronization before movement onset and a more pronounced coherence in the music-supported therapy group in the post-training assessment, whereas almost no differences were observed in the control group. Thus we see that music-supported therapy leads to marked improvements of motor function after stroke and that these are accompanied by electrophysiological changes indicative of a better cortical connectivity and improved activation of the motor cortex.

Audiovisual integration of speech is disturbed in schizophrenia: an fMRI study.

Speech perception is an essential part of social interaction. Visual information (lip movements, facial expression) may supplement auditory information in particular under inadvertent listening situations. Schizophrenia patients have been shown to have a deficit in integrating articulatory motions with the auditory speech input. The goal of this study was to investigate the neural basis of this deficit in audiovisual speech processing in schizophrenia patients by using fMRI. Disyllabic nouns were presented in congruent (audio matches visual information) and incongruent conditions in a slow event related fMRI design. Schizophrenia patients (n=15) were compared to age and gender matched control participants. The statistical examination was conducted by analysis of variance with main factors: audiovisual congruency and group membership. The patients' brain activity differed from the control group as evidenced by congruency by group interaction effects. The pertinent brain sites were located predominantly in the right hemisphere and comprised the pars opercularis, middle frontal sulcus, and superior temporal gyrus. In addition, we observed interactions bilaterally in the fusiform gyrus and the nucleus accumbens. We suggest that schizophrenia patients' deficits in audiovisual integration during speech perception are due to a dysfunction of the speech motor system in the right hemisphere. Furthermore the results can be also seen as a reflection of reduced lateralization of language functions to the left hemisphere in schizophrenia.

Sensory MEG responses predict successful and failed inhibition in a stop-signal task.

In the present study magnetoencephalographic recordings were performed to investigate the neural mechanisms underlying the stopping of manual responses. Subjects performed in a Stop-signal task in which Go-stimuli (S1), requiring a rapid motor response, were sometimes rapidly followed by a Stop-stimulus (S2) indicating to withhold the already initiated response to S1. Success of stopping strongly depended on the early perceptual processing of S1 and S2 reflected by the magnetic N1 component. Enhanced processing of S1 facilitated the execution of the movement, whereas enhanced processing of S2 favored its inhibition. This suggests that the processing resources for the subsequent stimuli are limited and need to be shared. This sharing of resources appeared to arise from adjustments made on a trial-by-trial basis, in that systematic reaction time prolongations on Go-trials following Stop-trials versus following Go-trials were accompanied by attenuated sensory processing to the Go-stimulus similar to that seen in successful versus unsuccessful stopping in Stop-trials.