fMRI and acoustic analyses reveal neural correlates of gestural complexity and articulatory effort within bilateral inferior frontal gyrus during speech production.

In an event-related fMRI study of overt speech production, we investigated the relationship between gestural complexity and underlying brain activity within bilateral inferior frontal gyrus (IFG). We operationalized gestural complexity as the number of active articulatory tiers (glottal, oral, nasal) and the degree of fine-grained temporal coordination between tiers (low, high). Forty-three neurotypical participants produced three types of highly-frequent non-word CV-syllable sequences, which differ systematically in gestural complexity (simple: ['dadada], intermediate: ['tatata], complex: ['nanana]). Comparing blood oxygen level-dependent (BOLD) responses across complexity conditions revealed that syllables with greater gestural complexity elicited increased activation patterns. Moreover, when durational parameters were included as covariates in the analyses, significant effects of articulatory effort were found over and above the effects of complexity. The results suggest that these differences in BOLD-response reflect the differential contribution of articulatory mechanisms that are required to produce phonologically distinct speech sounds.

Is it still speech? Different processing strategies in learning to discriminate stimuli in the transition from speech to non-speech including feedback evaluation.

Processing of speech was investigated by using stimuli gradually changing from speech (vowels) to non-speech (spectral rotated vowels). Stimuli were presented in descending levels of vocalization blends, from pure speech to non-speech, through step-wise combinations, resulting in ambiguous versions of the sounds. Participants performed a two-alternative forced choice task: categorization of sounds were made according to whether they contained more speech or non-speech. Performance feedback was presented visually on each trial. Reaction times (RT) after sound presentation, and functional magnetic resonance imaging (fMRI) data during auditory and visual processing, were analyzed. RT data suggested individual differences with a distinct group, good performers, functioning better in distinguishing stimuli with a higher degree of ambiguous blends compared to poor performers, who were not able to distinguish these stimuli correctly. fMRI data confirmed this finding. During auditory stimulation, good performers showed neural activation in the ventral auditory pathway, including the primary auditory cortex and the anterior superior temporal sulcus (responsible for speech processing). Poor performers, in contrast, showed neural activation in the dorsal auditory pathway, including the bilateral superior temporal gyrus. Group differences were also found for visual feedback processing. Differences observed between the groups were interpreted as reflecting different neural processing strategies.

Heidelberg Neuro-Music Therapy Restores Attention-Related Activity in the Angular Gyrus in Chronic Tinnitus Patients.

Background: Tinnitus is the perception of a phantom sound without external acoustic stimulation. Recent tinnitus research suggests a relationship between attention processes and tinnitus-related distress. It has been found that too much focus on tinnitus comes at the expense of the visual domain. The angular gyrus (AG) seems to play a crucial role in switching attention to the most salient stimulus. This study aims to evaluate the involvement of the AG during visual attention tasks in tinnitus sufferers treated with Heidelberg Neuro-Music Therapy (HNMT), an intervention that has been shown to reduce tinnitus-related distress. Methods: Thirty-three patients with chronic tinnitus, 45 patients with recent-onset tinnitus, and 35 healthy controls were tested. A fraction of these (21/21/22) were treated with the "compact" version of the HNMT lasting 1 week with intense treatments, while non-treated participants were included as passive controls. Visual attention was evaluated during functional Magnet-Resonance Imaging (fMRI) by a visual Continous Performance Task (CPT) using letter-based alarm cues ("O" and "X") appearing in a sequence of neutral letters, "A" through "H." Participants were instructed to respond via button press only if the letter "O" was followed by the letter "X" (GO condition), but not to respond if a neutral letter appeared instead (NOGO condition). All participants underwent two fMRI sessions, before and after a 1-week study period. Results: The CPT results revealed a relationship between error rates and tinnitus duration at baseline whereby the occurrence of erroneous "GO omissions" and the reaction time increased with tinnitus duration. Patients with chronic tinnitus who were treated with HNMT had decreasing error rates (fewer GO omissions) compared to treated recent-onset patients. fMRI analyses confirmed greater activation of the AG during CPT in chronic patients after HNMT treatment compared to treated recent-onset patients. Conclusions: Our findings suggest that HNMT treatment helps shift the attention from the auditory phantom percept toward visual cues in chronic tinnitus patients and that this shift in attention may involve the AG.

Heidelberg Neuro-Music Therapy Enhances Task-Negative Activity in Tinnitus Patients.

Background: Suffering from tinnitus causes mental distress in most patients. Recent findings point toward a diminished activity of the brain's default-mode network (DMN) in subjects with mental disorders including depression or anxiety and also recently in subjects with tinnitus-related distress. We recently developed a therapeutic intervention, namely the Heidelberg Neuro-Music Therapy (HNMT), which shows an effective reduction of tinnitus-related distress following a 1-week short-term treatment. This approach offers the possibility to evaluate the neural changes associated with the improvements in tinnitus distress. We previously reported gray matter (GM) reorganization in DMN regions and in primary auditory areas following HNMT in cases of recent-onset tinnitus. Here we evaluate on the same patient group, using functional MRI (fMRI), the activity of the DMN following the improvements tinnitus-related distress related to the HNMT intervention. Methods: The DMN activity was estimated by the task-negative activation (TNA) during long inter-trial intervals in a word recognition task. The level of TNA was evaluated twice, before and after the 1-week study period, in 18 treated tinnitus patients ("treatment group," TG), 21 passive tinnitus controls (PTC), and 22 active healthy controls (AC). During the study, the participants in TG and AC groups were treated with HNMT, whereas PTC patients did not receive any tinnitus-specific treatment. Therapy-related effects on DMN activity were assessed by comparing the pairs of fMRI records from the TG and PTC groups. Results: Treatment of the TG group with HNMT resulted in an augmented DMN activity in the PCC by 2.5% whereas no change was found in AC and PTC groups. This enhancement of PCC activity correlated with a reduction in tinnitus distress (Spearman Rho: -0.5; p < 0.005). Conclusion: Our findings show that an increased DMN activity, especially in the PCC, underlies the improvements in tinnitus-related distress triggered by HNMT and identify the DMN as an important network involved in therapeutic improvements.

SNARC meets SPARC in fMRI--Interdependence of compatibility effects depends on semantic content.

BACKGROUND: Stimulus-response compatibility (SRC) plays a major role in choice-reaction tasks. In specific cases, SRC leads to phenomena like the Spatial Numerical Association of Response Codes (SNARC) or the Spatial Pitch Association of Response Codes (SPARC) effect: small numbers or low pitches lead to faster responses when answered with the left hand, whereas large numbers or high pitches lead to faster responses when answered with the right hand. The previous study, investigating the combination of SNARC and SPARC with numbers spoken in different pitch heights, points towards an interdependency of both SNARC and SPARC compatibility effects, suggesting an automatic process. METHODS: In the present event-related functional magnetic resonance imaging (fMRI) study, we investigated the underlying neural activity when SNARC and SPARC are combined within the same auditory stimulus (numerical condition). Additionally, we included a categorical condition (the words "small" and "large") as variation of the stimulus type. RESULTS: We found neither an effect for SNARC nor for SPARC Compatibility in the neuronal data, whereas SNARC Compatibility was found in the behavioral data. According to the behavioral as well as the neuronal data, in the bilateral auditory cortex, SNARC and SPARC Compatibility interacts with Stimulus Type, i.e., whether numerical or categorical stimuli were presented. CONCLUSIONS: We concluded that both effects are interdependent and that this interaction strongly depends on the semantic information.

Cortical reorganization in recent-onset tinnitus patients by the Heidelberg Model of Music Therapy.

Pathophysiology and treatment of tinnitus still are fields of intensive research. The neuroscientifically motivated Heidelberg Model of Music Therapy, previously developed by the German Center for Music Therapy Research, Heidelberg, Germany, was applied to explore its effects on individual distress and on brain structures. This therapy is a compact and fast application of nine consecutive 50-min sessions of individualized therapy implemented over 1 week. Clinical improvement and long-term effects over several years have previously been published. However, the underlying neural basis of the therapy's success has not yet been explored. In the current study, the therapy was applied to acute tinnitus patients (TG) and healthy active controls (AC). Non-treated patients were also included as passive controls (PTC). As predicted, the therapeutic intervention led to a significant decrease of tinnitus-related distress in TG compared to PTC. Before and after the study week, high-resolution MRT scans were obtained for each subject. Assessment by repeated measures design for several groups (Two-Way ANOVA) revealed structural gray matter (GM) increase in TG compared to PTC, comprising clusters in precuneus, medial superior frontal areas, and in the auditory cortex. This pattern was further applied as mask for general GM changes as induced by the therapy week. The therapy-like procedure in AC also elicited similar GM increases in precuneus and frontal regions. Comparison between structural effects in TG vs. AC was calculated within the mask for general GM changes to obtain specific effects in tinnitus patients, yielding GM increase in right Heschl's gyrus, right Rolandic operculum, and medial superior frontal regions. In line with recent findings on the crucial role of the auditory cortex in maintaining tinnitus-related distress, a causative relation between the therapy-related GM alterations in auditory areas and the long-lasting therapy effects can be assumed.

Proximal protection with the Gore PAES can reduce DWI lesion size in high-grade stenosis during carotid stenting.

AIMS: The aim was to determine the incidence of new ischaemic lesions on diffusion-weighted MR imaging (DWI) in a non-randomised cohort of patients after protected and unprotected carotid artery stent placement using the Parodi Anti-Emboli System (PAES). METHODS AND RESULTS: A retrospective review was conducted on 269 patients who received DWI prior to, and 24-72 hours after, stent placement. All patients were enrolled in one centre. Forty patients stented with the PAES device were matched with 229 patients stented without protection (control group). New diffusion restriction on DWI was detected in 25.8% (PAES) versus 32.3% (control group); p=0.64. On average there were 0.7 lesions (PAES) versus 0.8 lesions (control group) per patient. The area of lesions was 1.7 (PAES) versus 5.6 mm2. In a subanalysis of patients (32 PAES, 148 non-protected) with >80% stenosis, the area of restricted diffusion was less when proximal protection was used (p<0.05). The number and area of DWI lesions did not differ on the contralateral, non-stented side. When the PAES system was used, patients were more likely not to have any lesion at all (p=0.028). CONCLUSIONS: In high-grade stenosis, the use of the Gore PAES device significantly reduced the area of new DWI lesions and patients were more likely not to have any new DWI lesion at all.

Visual processing of biological motion in children and adolescents with attention-deficit/hyperactivity disorder: an event related potential-study.

Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by problems in social behaviour, which are sometimes similar to some symptoms of autism-spectrum disorders (ASD). However, neuronal mechanisms of ASD-like deficits in ADHD have rarely been studied. The processing of biological motion-recently discussed as a marker of social cognition-was found to be disrupted in ASD in several studies. Thus in the present study we tested if biological motion processing is disrupted in ADHD. We used 64-channel EEG and spatio-temporal source analysis to assess event-related potentials associated with human motion processing in 21 children and adolescents with ADHD and 21 matched typically developing controls. On the behavioural level, all subjects were able to differentiate between human and scrambled motion. But in response to both scrambled and biological motion, the N200 amplitude was decreased in subjects with ADHD. After a spatio-temporal dipole analysis, a human motion specific activation was observable in occipital-temporal regions with a reduced and more diffuse activation in ADHD subjects. These results point towards neuronal determined alterations in the processing of biological motion in ADHD.

Selective transfer of visual working memory training on Chinese character learning.

Previous research has shown a systematic relationship between phonological working memory capacity and second language proficiency for alphabetic languages. However, little is known about the impact of working memory processes on second language learning in a non-alphabetic language such as Mandarin Chinese. Due to the greater complexity of the Chinese writing system we expect that visual working memory rather than phonological working memory exerts a unique influence on learning Chinese characters. This issue was explored in the present experiment by comparing visual working memory training with an active (auditory working memory training) control condition and a passive, no training control condition. Training induced modulations in language-related brain networks were additionally examined using functional magnetic resonance imaging in a pretest-training-posttest design. As revealed by pre- to posttest comparisons and analyses of individual differences in working memory training gains, visual working memory training led to positive transfer effects on visual Chinese vocabulary learning compared to both control conditions. In addition, we found sustained activation after visual working memory training in the (predominantly visual) left infero-temporal cortex that was associated with behavioral transfer. In the control conditions, activation either increased (active control condition) or decreased (passive control condition) without reliable behavioral transfer effects. This suggests that visual working memory training leads to more efficient processing and more refined responses in brain regions involved in visual processing. Furthermore, visual working memory training boosted additional activation in the precuneus, presumably reflecting mental image generation of the learned characters. We, therefore, suggest that the conjoint activity of the mid-fusiform gyrus and the precuneus after visual working memory training reflects an interaction of working memory and imagery processes with complex visual stimuli that fosters the coherent synthesis of a percept from a complex visual input in service of enhanced Chinese character learning.

Performance of repetitive alternating elbow movements in Parkinson's disease.

BACKGROUND: Bradydiadochokinesia is one main clinical symptom in idiopathic Parkinson's disease (IPD). The pathogenesis of bradydiadochokinesia is not completely clear. METHODS: Fifteen patients with IPD and 15 age-matched healthy volunteers had to perform rhythmic alternating flexion and extension movements in the elbow joint. The rhythm was provided auditorily by a click tone stimulator. Six maneuvers (spatial extents of 48 and 83° at frequencies of 0.45, 0.75 and 1.25 Hz) had to be absolved. The potentiometer converted the horizontal forearm movements into a variable voltage. RESULTS: The duration of single movements varied more significantly in patients than in controls (p < 0.05; Mann-Whitney U test). Patients executed all conditions more slowly than controls, but this difference was only significant at the most difficult condition (83° at 1.25 Hz; p < 0.01). The movement amplitudes or their variability were not significantly different at any condition. No parameter correlated significantly with the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) or with the duration of disease. CONCLUSION: An insufficient temporal coordination contributes to bradydiadochokinesia in IPD. This deficit occurs independently of other parkinsonian cardinal motor symptoms.

Visual event-related potentials to biological motion stimuli in autism spectrum disorders.

Atypical visual processing of biological motion contributes to social impairments in autism spectrum disorders (ASD). However, the exact temporal sequence of deficits of cortical biological motion processing in ASD has not been studied to date. We used 64-channel electroencephalography to study event-related potentials associated with human motion perception in 17 children and adolescents with ASD and 21 typical controls. A spatio-temporal source analysis was performed to assess the brain structures involved in these processes. We expected altered activity already during early stimulus processing and reduced activity during subsequent biological motion specific processes in ASD. In response to both, random and biological motion, the P100 amplitude was decreased suggesting unspecific deficits in visual processing, and the occipito-temporal N200 showed atypical lateralization in ASD suggesting altered hemispheric specialization. A slow positive deflection after 400 ms, reflecting top-down processes, and human motion-specific dipole activation differed slightly between groups, with reduced and more diffuse activation in the ASD-group. The latter could be an indicator of a disrupted neuronal network for biological motion processing in ADS. Furthermore, early visual processing (P100) seems to be correlated to biological motion-specific activation. This emphasizes the relevance of early sensory processing for higher order processing deficits in ASD.

Mechanical recanalization with flow restoration in acute ischemic stroke: the ReFlow (mechanical recanalization with flow restoration in acute ischemic stroke) study.

OBJECTIVES: This study sought to assess the feasibility and safety of a recently described technique of mechanical recanalization with the help of a stent-like device. BACKGROUND: In the special group of acute stroke patients with an intracranial large vessel occlusion, intravenous tissue-type plasminogen activator on its own leads to a good clinical outcome (mRS ≤ 2) in only 15% to 25% of cases. The aforementioned technique of mechanical recanalization showed very promising clinical results. METHODS: Forty patients presenting within 6 h from stroke symptom onset were enrolled. Mechanical recanalization was performed using a Solitaire FR revascularization device. The primary endpoint of the study was the clinical outcome rated with the help of the modified Rankin Scale (mRS) after 90 days. RESULTS: Twenty-four patients (60%) showed a good clinical outcome (mRS ≤ 2) at 90 days. One symptomatic hemorrhage was detected on follow-up computed tomography. The death rate was 12.5% (5 patients). Successful recanalization (Thrombolysis In Cerebral Infarction score ≥ 2b) of the target vessel was achieved in 95% of the patients with a mean of 1.8 runs with the device. CONCLUSIONS: The ReFlow (Mechanical Recanalization With Flow Restoration in Acute Ischemic Stroke) study shows that mechanical recanalization with flow restoration is highly effective in stroke patients with a large intracranial vessel occlusion presenting within 4.5 h after symptom onset. (Mechanical Recanalization With Flow Restoration in Acute Ischemic Stroke [ReFlow]; NCT01210729).

Different factors influence recanalisation rate after coiling in ruptured and unruptured intracranial aneurysms.

BACKGROUND: Most studies evaluating long-term efficacy after coil embolisation of intracranial aneurysms have not differentiated between ruptured and unruptured aneurysms. OBJECTIVES: The aim of this study was to analyse factors that influence recanalisation in ruptured and unruptured aneurysms. METHODS: We performed a retrospective analysis of 182 (98 ruptured, 84 unruptured) aneurysms, treated with coil embolisation alone that received follow-up with digital substraction angiography (DSA). RESULTS: At 6 months 26% of the aneurysms showed recanalisation. Multivariate variance analysis revealed that different factors influenced recanalisation in ruptured and unruptured aneurysms. In ruptured aneurysms patient age was a determinant, with younger patients recanalising more frequently than older ones (p = 0.016). Also, low initial packing density led to higher recanalisation rates (p = 0.015) than higher packing. In the unruptured aneurysm group these factors were not significant. Here, only a larger aneurysm volume led to higher recanalisation rates (p = 0.027). CONCLUSIONS: Our data suggest that in ruptured aneurysms, high packing density is a key factor to prevent recanalisation, while in unruptured aneurysms, aneurysm volume is the main predictor for recanalisation.

Gains of item-specific training in visual working memory and their neural correlates.

Experts sometimes show higher working memory performance than novices but contrary to this finding, evidence for a positive effect of item-specific training is rare. This study provides evidence for item-specific training gains. We presented Chinese characters and artificial patterns (spotted figures) in a change detection task before and after training (varying set size from 1 to 3). A part of the Chinese characters were trained; others and the spotted figures were not trained. Memory capacity was between one and two items. For set size two, memory performance for trained characters was higher than for untrained characters and they were processed faster. Within superior intraparietal sulcus and middle occipital cortex (part of the putative posterior working memory network), the neural activity asymptotically increased with set size. Untrained items reached the activation maximum already at set size two. For this set size, the activity was significantly reduced for trained items so that a further increase from two to three items was observed. We interpret this difference as a correlate of a gain in neural efficiency. The size of this difference correlated with the training gain in memory. We assume that training causes a more efficient neural representation of trained items supported by long-term memory and this allows holding more items in working memory.

Neural correlates of recognition memory in children with febrile seizures: evidence from functional magnetic resonance imaging.

Febrile seizures (FS) are assumed to not have adverse long-term effects on cognitive development. Nevertheless, FS are often associated with hippocampal sclerosis which can imply episodic memory deficits. This interrelation has hardly been studied so far. In the current study 13 children who had suffered from FS during infancy and 14 control children (7 to 9-years-old) were examined for episodic and semantic memory with standardized neuropsychological tests. Furthermore, using functional magnetic resonance imaging (fMRI) we studied neuronal activation while the children performed a continuous recognition memory task. The analysis of the behavioral data of the neuropsychological tests and the recognition memory experiment did not reveal any between-group differences in memory performance. Consistent with other studies fMRI revealed repetition enhancement effects for both groups in a variety of brain regions (e.g., right middle frontal gyrus, left parahippocampal gyrus) and a repetition suppression effect in the right superior temporal gyrus. Different neural activation patterns between both groups were obtained selectively within the right supramarginal gyrus (BA 40). In the control group correct rejections of new items were associated with stronger activation than correctly identified old items (HITs) whereas in the FS group no difference occurred. On the background that the right supramarginal gyrus is assumed to mediate a top-down process to internally direct attention toward recollected information, the results could indicate that control children used strategic recollection in order to reject new items (recall-to-reject). In contrast, the missing effect in the FS group could reflect a lack of strategy use, possibly due to impaired recollective processing. This study demonstrates that FS, even with mainly benign courses, can be accompanied by selective modifications in the neural structures underlying recognition memory.

Separating intra-modal and across-modal training effects in visual working memory: an fMRI investigation.

Working memory training is a useful tool to examine dissociations between specific working memory processes. Although current models propose a distinction between modality-specific working memory processes, to our knowledge no study has directly examined the effects of visual versus auditory working memory training. Functional magnetic resonance imaging was used to investigate whether visual working memory processes can be trained specifically and whether those effects can be separated from across-modal training effects. We found decidedly larger training gains after visual working memory training compared with auditory or no training on a visual 2-back task. These effects were accompanied by specific training-related decreases in the right middle frontal gyrus arising from visual training only. Likewise, visual and auditory training led to decreased activations in the superior portion of the right middle frontal gyrus and the right posterior parietal lobule. We infer that the combination of effects resulted from increased neural efficiency of intra-modal (visual) processes on the one hand and of across-modal (general control) processes on the other hand. Therefore, visual processes of working memory can be trained specifically, and these effects can be functionally dissociated from alterations in general control processes common to both working memory trainings.

fMRI correlates of working memory: specific posterior representation sites for motion and position information.

We assume that working memory is provided by a network comprising domain-general anterior and different domain-specific posterior brain areas depending on the type of stimulus and the task demands. Based on imaging studies from perception, we hypothesized that dynamic spatial (motion) and static spatial (position) information can be dissociated during retention in working memory. Participants were presented with a moving dot. About one second after stimulus presentation, a cue indicated whether its motion or end position should be held in memory. Six seconds later, a second stimulus was shown which was to be compared with the first one with respect to identity on the cued dimension. In the baseline condition, the cue indicated that no memory task would follow. We contrasted activity during maintenance of the different features. Differential activations in regions related to motion perception (area hMT/V5+, superior temporal sulcus) were observed in the motion working memory task. For position working memory, enhanced activations in a right brain region at the temporo-parieto-occipital junction emerged. The results are discussed with respect to domain-specific regions active in perception and how they can be also involved in short term retention for those very features. It is suggested that two types of spatial information categories can be dissociated: dynamic spatial (motion) and static spatial (position) information seem to be processed by different working memory structures.

Impairment of fronto-striatal and parietal cerebral networks correlates with attention deficit hyperactivity disorder (ADHD) psychopathology in adults - a functional magnetic resonance imaging (fMRI) study.

Attention deficit hyperactivity disorder (ADHD) is a common, genetically transmitted common childhood-onset disorder with a high rate of persistence in adulthood. Although many studies have shown anatomical and functional abnormalities in children and adolescents, studies with adult patients are rare. Nineteen adults with ADHD (11 ADHD, combined type; 8 ADHD, partially remitted) and 17 controls were included in this functional magnetic resonance imaging (fMRI) study. Brain activation was investigated with a continuous performance test (CPT). Impaired activation of a fronto-striatal and a parietal attentional network was observed during the NoGo condition in ADHD subjects. Correlations of reduced activity of the caudate nuclei, the anterior cingulate cortex, and parietal cortical structures, as well as increased activity in the insular cortex, with inattention and impulsivity symptom scores were found. The activation patterns were similar to those known from children and adolescents with ADHD. In conclusion we found not only a widespread dysfunction of brain regions that are involved in cognitive processing in adults with ADHD compared with controls, but also correlations between symptom severity and dysfunction of neuronal systems across adult subjects with a history of ADHD in childhood but whose symptoms did (persistent ADHD) and did not (not persistent ADHD) qualify for a full diagnosis of ADHD in adulthood.

Influence of carotid artery stenting on cognitive function.

INTRODUCTION: There have only been a few studies on cognitive changes in patients with carotid occlusive disease, and the results of these show major discrepancies in the extent to which treatment affects neuropsychological function. We sought to clarify these discrepancies by evaluating the effects of carotid artery stenting (CAS) on the cognitive function. METHODS: Forty-one asymptomatic CAS patients were administered a test battery of neuropsychological tests measuring cognitive speed and memory function before and 3 months after the procedure. A control group was also evaluated. To test for thromboembolic lesions, diffusion-weighted imaging was used. RESULTS: CAS led to a significant increase in cognitive speed (p<0.001) but did not afford any change in memory function. This was regardless of the degree or side of stenosis or patient age or gender. CONCLUSION: CAS significantly improved functions that involve cognitive speed. Earlier studies did not differentiate between speed and memory tests and thus might have missed these changes. Further studies correlating changes in brain perfusion with increase in cognitive speed are needed.