Temporoparietal Cortex Research Articles

Interhemispheric Asymmetry of Network Connecting Between Frontal and Temporoparietal Cortices: A Corticocortical-Evoked Potential Study

The connection between the ventrolateral frontal and temporoparietal cortices has an important role in language function on the language-dominant side and spatial awareness on the nondominant side. However, the laterality of these pathways remains controversial. We investigated the laterality of this connection using corticocortical-evoked potentials (CCEPs). From April 2014 to March 2016, 27 patients who had undergone frontotemporal craniotomy were enrolled. With the patients under general anesthesia, subdural electrodes were placed on both frontal and temporoparietal areas intraoperatively. Alternating 1-Hz electrical stimuli were delivered to the pars opercularis and pars triangularis with a stimulus intensity of 10 mA. CCEPs were obtained from temporoparietal areas by averaging the electrocorticogram time-locked to the stimulus onset. The amplitudes and latencies of the CCEP N1 components were compared between the dominant and nondominant sides. The median amplitudes of the CCEPs were 335.1 μV (range, 60.2-750) and 125.65 μV (range, 55.1-634) on the dominant and nondominant sides, respectively. The CCEP amplitudes were significantly larger on the dominant side than on the nondominant side (P= 0.013). In contrast, the median latency was 27.8 ms (range, 19.3-36.6) on the language-dominant side and 28.9 ms (range, 8.9-38.5) on the nondominant side. The latencies were not significantly different between the 2 sides (P= 0.604). The CCEP amplitudes were significantly larger in the dominant hemisphere. These findings can lead to better hypotheses regarding the relationship between language functions and the development of the network connecting the frontal and temporoparietal cortices.

Sex-Related Reserve Hypothesis in Alzheimer’s Disease: Changes in Cortical Thickness with a Five-Year Longitudinal Follow-Up

Sex effects on the progression of Alzheimer's disease (AD) have received less attention than other demographic factors, including onset age and education. The aim of this study was to investigate whether sex affected cortical thinning in the disease progression of AD. We prospectively recruited 36 patients with early-stage AD and 14 people with normal cognition. All subjects were assessed with magnetic resonance imaging at baseline, Year 1, Year 3, and Year 5. We performed cortical thickness analyses using surface-based morphometry on magnetic resonance imaging. Women with AD showed more rapid cortical thinning in the left dorsolateral frontal cortex, left superior temporal gyrus, bilateral temporo-parietal association cortices, bilateral anterior cingulate gyri, bilateral medial frontal cortices, and bilateral occipital cortices over 5 years than men with AD, even though there was no difference in cortical thickness at baseline. In contrast, there were no regions of significantly more rapid atrophy in men with AD. Our findings suggest that women deteriorate faster than men in the progression of AD.

Cerebral and behavioural response to human voices is mediated by sex and sexual orientation

Several studies report sex differences in sensitivity to gendered stimuli. We assume many of these to reflect differences as to the sex to which one feels attracted rather than to biological sex per se. Investigating voice perception, a function of high social relevance, we show that the behavioural and neural (BOLD) responses to male and female voices are mediated by sex and sexual orientation. In heterosexual men and women, we found an opposite-sex effect, reflected in higher classification accuracy for and a response bias towards voices of the other sex, while the effect became apparent as same-sex effect in homosexual men and women. Overall, sexual orientation had a greater impact in women than in men and homosexual women were closer to men in their behavioural responses to female voices. The activation patterns were similar for hetero- and homosexual men, both groups showing increased activation in response to male compared to female voices in regions distributed across the temporo-parietal and insular cortex. In contrast, women had increased activation in response to voices of the desired sex. It appears that both sex and sexual orientation impact on a function as basal as voice perception. Our results underline the need to assess sexual orientation in study participants if conclusions on sex differences shall be drawn. Many of the reported sex differences in behaviour and brain function might be mediated by sexual orientation and we encourage further research into the interplay between sex and sexual orientation.

Shared endo-phenotypes of default mode dysfunction in attention deficit/hyperactivity disorder and autism spectrum disorder

Categorical diagnoses from the Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) manuals are increasingly found to be incongruent with emerging neuroscientific evidence that points towards shared neurobiological dysfunction underlying attention deficit/hyperactivity disorder and autism spectrum disorder. Using resting-state functional magnetic resonance imaging data, functional connectivity of the default mode network, the dorsal attention and salience network was studied in 1305 typically developing and diagnosed participants. A transdiagnostic hierarchical Bayesian modeling framework combining Indian Buffet Processes and Latent Dirichlet Allocation was proposed to address the urgent need for objective brain-derived measures that can acknowledge shared brain network dysfunction in both disorders. We identified three main variation factors characterized by distinct coupling patterns of the temporoparietal cortices in the default mode network with the dorsal attention and salience network. The brain-derived factors were demonstrated to effectively capture the underlying neural dysfunction shared in both disorders more accurately, and to enable more reliable diagnoses of neurobiological dysfunction. The brain-derived phenotypes alone allowed for a classification accuracy reflecting an underlying neuropathology of 67.33% (+/−3.07) in new individuals, which significantly outperformed the 46.73% (+/−3.97) accuracy of categorical diagnoses. Our results provide initial evidence that shared neural dysfunction in ADHD and ASD can be derived from conventional brain recordings in a data-led fashion. Our work is encouraging to pursue a translational endeavor to find and further study brain-derived phenotypes, which could potentially be used to improve clinical decision-making and optimize treatment in the future.

Orthographic and phonological selectivity across the reading system in deaf skilled readers

People who are born deaf often have difficulty learning to read. Recently, several studies have examined the neural substrates involved in reading in deaf people and found a left lateralized reading system similar to hearing people involving temporo-parietal, inferior frontal, and ventral occipito-temporal cortices. Previous studies in typical hearing readers show that within this reading network there are separate regions that specialize in processing orthography and phonology. We used fMRI rapid adaptation in deaf adults who were skilled readers to examine neural selectivity in three functional ROIs in the left hemisphere: temporoparietal cortex (TPC), inferior frontal gyrus (IFG), and the visual word form area (VWFA). Results show that in deaf skilled readers, the left VWFA showed selectivity for orthography similar to what has been reported for hearing readers, the TPC showed less sensitivity to phonology than previously reported for hearing readers using the same paradigm, and the IFG showed selectivity to orthography, but not phonology (similar to what has been reported previously for hearing readers). These results provide evidence that while skilled deaf readers demonstrate coarsely tuned phonological representations in the TPC, they develop finely tuned representations for the orthography of written words in the VWFA and IFG. This result suggests that phonological tuning in the TPC may have little impact on the neural network associated with skilled reading for deaf adults.

Self-Reported Physical Activity is Associated with Tau Burden Measured by Positron Emission Tomography.

Numerous animal studies have reported exercise reduces the accumulation of Alzheimer's disease pathology, including amyloid-β (Aβ) and tau. Furthermore, we previously reported a relationship between higher levels of physical activity (PA) and lower brain Aβ burden in a human population. The recent advent of tau positron emission tomography (PET) tracers enables us to extend our investigations into the evaluation of the relationship between PA and brain tau burden. Utilizing data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, we have examined the cross-sectional relationship between habitual PA and PET-quantified tau burden. Forty-three cognitively healthy older adults were categorized into low-moderate PA (LMPA; n = 16) or high PA (HPA; n = 27), based on self-reported PA levels. Tau PET imaging with the AV1451 tracer was conducted on all participants. The LMPA group had significantly higher neocortical tau burden (presented as a z-score; 1.22±1.98), compared to the HPA group (z-score: - 0.28±1.18). The difference between the LMPA and HPA groups was also evident when examining regional tau burden in the temporoparietal cortex and the prefrontal cortex. Our results suggest an association between self-reported PA level and brain tau burden. Future longitudinal and interventional studies utilizing larger samples sizes are vital to further investigate the nature of the relationship between tau and PA.

Defining visual illusions in Parkinson's disease: Kinetopsia and object misidentification illusions

ObjectiveTo identify the phenomenological features and neural correlates of visual illusions in Parkinson's disease (PD). MethodsNinety-three patients with PD were assessed via questionnaires regarding visual illusions and behavioral symptoms, and neuropsychological tests, motor assessments and 18-F fluorodeoxyglucose-positron emission tomography (FDG-PET) were performed. The relationship between visual illusions or hallucinations and regional cerebral glucose metabolism was investigated using partial least squares (PLS) correlation and conventional mass-univariate analyses. ResultsKinetopsia, in which stationary objects are perceived as being in motion, and object misidentification illusions, in which objects are misperceived as different objects, were the most common types of visual illusions. Kinetopsia and object misidentification illusions were identified in 24 patients (25.8%) and 17 patients (18.3%), respectively. Eleven patients with kinetopsia and 9 patients with object misidentification illusions had visual hallucinations. Kinetopsia and visual hallucinations were associated with hypometabolism in the temporo-parietal cortices, whereas object misidentification illusions were associated with hypometabolism in the early visual cortex, as well as the temporo-parietal cortices. ConclusionsOur findings suggest that kinetopsia and object misidentification illusions are the most common types of visual illusions in PD. Despite the phenomenological diversity of visual illusions and hallucinations in PD, all of these symptoms are associated with dysfunction of the temporo-parietal cortices, which support visual spatial processing, rather than dysfunction of the ventral temporo-occipital cortices, which supports visual object recognition.

S142. Attentional gradient in touch: An MEG study

Introduction Previous studies have demonstrated the cortical mechanisms for the gradient of spatial attention in vision and audition, whereas those for touch have yet to be elucidated in detail. We used magnetoencephalography (MEG) to examine the within-hand gradient of tactile spatial attention in the cerebral cortex. Methods We recorded cortical responses to an electrocutaneous stimulation presented randomly to any of the five fingers of the right hand at a random interstimulus interval (750–1250 ms). Participants attended to the index finger, ring finger, or both to detect a rare target stimulus presented there by silent counting. Results Neuromagnetic responses around the contralateral primary and secondary somatosensory cortices (SIc and SIIc) for the stimulation of the index or middle finger were stronger when that finger was attended than when the distant finger was attended. The SIIc response to the task-irrelevant stimulation of the thumb or little finger increased when the index or ring finger was attended, respectively, suggesting an across-finger gradient of tactile attention. Simultaneous attention to the index and ring fingers decreased the SIIc response to the task-irrelevant stimulation of the intervening middle finger more than that with attention to either one of the two fingers. Furthermore, late responses in the temporo-parietal junction (TPJ) and prefrontal cortex (PFC) were stronger with the stimulation of the unattended finger than with that of the attended finger. Conclusion The present study provides cortical evidence for the adaptive control of the within-hand, across-finger gradient of tactile attention that depends on whether attention is focused on a single finger or divided into non-adjacent different fingers.

Lower Choline and Myo-Inositol in Temporo-Parietal Cortex Is Associated With Apathy in Amnestic MCI.

Apathy is a common symptom in patients with amnestic mild cognitive impairment (aMCI) and is associated with an increased risk of progression to Alzheimer’s disease (AD). The neural substrates underlying apathy in aMCI may involve multiple brain regions, including the anterior cingulate cortex and the temporo-parietal region. Here we investigated neurometabolites in brain regions that may underlie apathy in aMCI patients using proton magnetic resonance spectroscopy (1H-MRS). Twenty-eight aMCI patients with varying degrees of apathy and 20 matched controls underwent 1H-MRS. Spectra were acquired from single voxels in the posterior cingulate cortex (PCC), dorsal anterior cingulate cortex (DACC), right dorsolateral prefrontal cortex (DLPFC), and right temporo-parietal cortex (TPC). Apathy was measured with the Apathy Evaluation Scale (AES). Spearman partial correlations between metabolite concentrations in each region and severity of apathy were determined. Additionally, analyses of covariance (ANCOVA) were performed to determine whether metabolite changes differed between patients with or without clinically-diagnosed apathy. The degree of apathy was found to be negatively correlated with choline and myo-inositol (mI) in the TPC. Additional exploratory analyses suggested that N-acetylaspartate (NAA)/mI ratio was reduced in aMCI without clinical apathy but not in aMCI with clinical apathy. In the DACC, glutamate and glutamine (Glx) levels tended to be higher in the aMCI with apathy group compared to controls and reduced in association with depression scores. In conclusion, apathy in aMCI patients was associated with neurometabolite changes indicative of altered membranal integrity and glial function in the right TPC. Findings also indicated that in a clinically-diagnosed aMCI cohort, apathy symptoms may be suggestive of neural changes that are distinct from aMCI without apathy.

Frontotemporal stimulation modulates semantically-guided visual search during confrontation naming: A combined tDCS and eye tracking investigation

Transcranial direct current stimulation (tDCS) was paired with eye tracking to elucidate contributions of frontal, temporoparietal and anterior temporal cortex to early visual search patterns during picture naming (e.g., rapid visual scanning to diagnostic semantic features). Neurotypical adults named line drawings of objects prior to and following tDCS in three separate sessions, each employing a unique electrode montage. The gaze data revealed montage by stimulation (pre/post) interaction effects characterized by longer initial visual fixations (mean difference = 89 ms; Cohen’s d = .8) and cumulative fixation durations (mean difference = 98 ms; Cohen’s d = .9) on key semantic features (e.g., the head of an animal) after cathodal frontotemporal stimulation relative to the pre-stimulation baseline. We interpret these findings as reflecting a tDCS-induced modulation of semantic contributions of the anterior temporal lobe(s) to top-down influences on object recognition. Further, we discuss implications for the optimization of tDCS for the treatment of anomia in aphasia.

T221. Sensorimotor Induction of Auditory Misattribution in Psychosis is Linked to Neural Disconnectivity

Schneiderian first rank symptoms (FRS) are characterized by a diminished demarcation of self-other boundaries, causing misattribution of self-generated thoughts and actions to external sources. We have shown that introducing sensorimotor prediction error (SPE) by a robotic device in healthy subjects can induce a Feeling of a Presence (FoP) which is related to the FRS (Blanke et al. 2014). Here, we tested if SPE may induce auditory misattribution in psychotic patients and if this is related to neural connectivity in the temporoparietal cortex, insular cortex and fronto-parietal cortex (FoP Network).

Brain Structural Networks in Mouse Exposed to Chronic Maternal Undernutrition

Brain structural connectivity is known to be altered in cases of intrauterine growth restriction and premature birth, although the specific effect of maternal nutritional restriction, a common burden in human populations, has not been assessed yet. Here we analyze the effects of maternal undernutrition during pregnancy and lactation by establishing three experimental groups of female mice divided according to their diet: control (Co), moderate calorie-protein restriction (MCP) and severe protein restriction (SP). Nutritionally restricted dams gained relatively less weight during pregnancy and the body weight of the offspring was also affected by maternal undernutrition, showing global growth restriction. We performed magnetic resonance imaging (MRI) of the offspring’s brains after weaning and analyzed their connectivity patterns using complex graph theory. In general, changes observed in the MCP group were more subtle than in SP. Results indicated that brain structures were not homogeneously affected by early nutritional stress. In particular, the growth of central brain regions, such as the temporo-parietal cortex, and long integrative myelinated tracts were relatively preserved, while the frequency of short tracts was relatively reduced. We also found a differential effect on network parameters: network degree, clustering, characteristic path length and small-worldness remained mainly unchanged, while the rich-club index was lower in nutritionally restricted animals. Rich-club decrease reflects an impairment in the structure by which brain regions with large number of connections tend to be more densely linked among themselves. Overall, the findings presented here support the hypothesis that chronic nutritional stress produces long-term changes in brain structural connectivity.

Opposite effects of lateralised transcranial alpha versus gamma stimulation on auditory spatial attention

BackgroundSpatial attention relatively increases the power of neural 10-Hz alpha oscillations in the hemisphere ipsilateral to attention, and decreases alpha power in the contralateral hemisphere. For gamma oscillations (>40 Hz), the opposite effect has been observed. The functional roles of lateralised oscillations for attention are currently unclear. HypothesisIf lateralised oscillations are functionally relevant for attention, transcranial stimulation of alpha versus gamma oscillations in one hemisphere should differentially modulate the accuracy of spatial attention to the ipsi-versus contralateral side. Methods20 human participants performed a dichotic listening task under continuous transcranial alternating current stimulation (tACS, vs sham) at alpha (10 Hz) or gamma (47 Hz) frequency. On each trial, participants attended to four spoken numbers on the left or right ear, while ignoring numbers on the other ear. In order to stimulate a left temporo-parietal cortex region, which is known to show marked modulations of alpha power during auditory spatial attention, tACS (1 mA peak-to-peak amplitude) was applied at electrode positions TP7 and FC5 over the left hemisphere. ResultsAs predicted, unihemispheric alpha-tACS relatively decreased the recall of targets contralateral to stimulation, but increased recall of ipsilateral targets. Importantly, this spatial pattern of results was reversed for gamma-tACS. ConclusionsResults provide a proof of concept that transcranially stimulated oscillations can enhance spatial attention and facilitate attentional selection of speech. Furthermore, opposite effects of alpha versus gamma stimulation support the view that states of high alpha are incommensurate with active neural processing as reflected by states of high gamma.

Exploring the Role of Temporoparietal Cortex in Upright Perception and the Link With Torsional Eye Position.

Upright perception is a key aspect of orientation constancy, as we maintain a stable perception of the world despite continuous movements of our eyes, head, and body. Torsional position of the eyes can impact perception of upright by changing orientation of the images on the retina relative to gravity. Here, we investigated the role of temporoparietal cortex in upright perception with respect to ocular torsion, by means of the inhibitory effect of continuous theta burst transcranial magnetic stimulation (TMS). We used a subjective visual vertical (SVV) paradigm to track changes in upright perception, and a custom video method to track ocular torsion simultaneously. Twelve participants were tested during a lateral head tilt of 20° to the left. TMS at the posterior aspect of the supramarginal gyrus (SMGp) resulted in an average SVV shift in the opposite direction of the head tilt compared to a sham stimulation (1.8°). Ocular torsion following TMS at SMGp showed no significant change compared to the sham stimulation (−0.1°). Thus, changes in upright perception at SMGp were dissociated from ocular torsion. This finding suggests that perception of upright at SMGp is primarily related to sensory processing for spatial orientation, as opposed to subcortical regions that have direct influence on ocular torsion.

F209. TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) IN A NON-CLINICAL POPULATION AS A MODEL FOR TREATMENT OF AUDITORY VERBAL HALLUCINATIONS IN SCHIZOPHRENIA

BackgroundWe used transcranial direct current stimulation (tDCS) in a non-clinical population to simulate a model of tDCS-treatment for auditory verbal hallucinations (AVH) in schizophrenia. In tDCS, a low current is induced via two electrodes attached to the scalp. The anode and cathode typically up- and downregulate neuronal activity, respectively. It was suggested that AVH arise due to two main neuronal pathways: hyper-activity in the language areas in the temporo-parietal cortex and hypo-activity of the cognitive control areas in the dorsolateral prefrontal cortex. Accordingly, it was further hypothesized that by reducing activity in the temporo-parietal cortex through cathodal tDCS and simultaneously increasing neuronal activity in the dorsolateral prefrontal cortex with anodal tDCS, AVH could be reduced. Patients with schizophrenia, particularly those with AVH show additionally deficits on language and cognitive control tasks, which are known to draw on temporo-parietal and dorsolateral prefrontal cortex regions, respectively. In order to test the model we thus reversed the electrode montage in non-clinical participants and tested whether they would show similar deficits as schizophrenia patients. In addition, the healthy participants underwent magnetic resonance spectroscopy (MRS) to test whether, in accordance with the model, glutamate levels increase under the anode, and decrease under the cathode area.MethodsEighteen participants were recruited in a convenience sample (7 male/ 11 female) with a mean age of 26 years. They were tested twice with a mean interval of 8 days. In one session they received real 2mA tDCS for 20 min, while in an MRI scanner (GE 750, 3T). The other session was a sham stimulation control. The order of real/sham stimulation was counterbalanced and stimulation was double-blind. In each session, MRS was measured using a PRESS sequence (TE=35ms, 1500ms) before and after stimulation. MRS data were acquired from two voxels, one in the left dorsolateral prefrontal cortex (22ml) and one in the left temporo parietal cortex (25ml), right underneath anode and cathode electrodes, respectively. MRS data were analyzed using LCModel software; water-scaled estimates for glutamate and glutamine combined (Glx) are reported herein, with N-Acetylaspartate (NAA) and creatine (Cre) inspected to ensure stability of the Glx measure. Glx levels were subjected to a 2x2x2 ANOVA with the within-participant factors Stimulation (real vs sham), Stimulation area (dorsolateral prefrontal cortex versus temporo-parietal cortex), and Time (Pre and Post stimulation).ResultsTwo datasets where excluded from analysis due to poor spectral quality. As expected, NAA (F1,16=.809, p=.382) and Cre (F1,16=.005, p=.944) did not show significant changes. There was a trend for Glx to be higher during real as compared to sham stimulation (main effect Stimulation F1,16=3.867, p=.067) and for Glx to be higher after than before stimulation (main effect Time F1,16=1.396, p=.078).DiscussionGlx was increased during real compared to sham tDCS, and before compared to after stimulation. This could indicate that tDCS overall changes neuronal firing thresholds. However, we did not observe the expected three-way interaction of reduced glutamate levels in the dorsolateral prefrontal cortex and increased glutamate levels in the temporo-parietal cortex. This could be due to the relatively small sample. However, the present data analysis is preliminary and we aim to report findings for a larger dataset.

A Pilot Study of Peripheral Muscle Magnetic Stimulation as Add-on Treatment to Repetitive Transcranial Magnetic Stimulation in Chronic Tinnitus.

While brain stimulation techniques have been examined as treatment options for chronic tinnitus for many years, they have recently been extended to multimodal treatment approaches. As chronic tinnitus is often accompanied by comorbid muscular tension in the neck and back, we performed a one-arm pilot study to explore the feasibility of a new multimodal treatment approach. In detail, repetitive peripheral magnetic stimulation (rPMS) of the back was performed before and after each session of repetitive transcranial magnetic stimulation (rTMS) of the brain. Data of 41 patients were analyzed, all of which were treated with ten sessions of rTMS of the left prefrontal and left temporoparietal cortex followed by rPMS of the neck and back muscles. Tinnitus severity was measured using the tinnitus questionnaire (TQ). Neck pain was assessed using the neck pain and disability scale (NPAD). The new treatment approach was feasible and well accepted by the majority of patients. However, the overall patient group did not improve significantly in either of the questionnaires. If patients were divided in different subgroups depending on whether they were suffering from neck pain or somatosensory tinnitus, explorative post-hoc tests suggested differential effects: patients with both neck pain and somatosensory tinnitus had better outcomes than patients without those conditions or with neck pain only. This was true for both the TQ and the NPAD. This effect was of transient nature though: the TQ score went back to its baseline level after a follow-up period of 12 weeks. Based on our results we recommend that in studies that investigate tinnitus treatments targeting somatosensory afferents patients should be stratified according to somatic co-morbidities and somatosensory influence on the tinnitus percept.Clinical trial registration: www.clinicaltrials.gov, NCT02306447.

Electrocorticographic high-gamma modulation with passive listening paradigm for pediatric extraoperative language mapping.

This prospective study compared the topography of high-gamma modulation (HGM) during a story-listening task requiring negligible patient cooperation, with the conventional electrical stimulation mapping (ESM) using a picture-naming task, for presurgical language localization in pediatric drug-resistant epilepsy. Patients undergoing extraoperative monitoring with subdural electrodes were included. Electrocorticographic signals were recorded during quiet baseline and a story-listening task. The likelihood of 70- to 150-Hz power modulation during the listening task relative to the baseline was estimated for each electrode and plotted on a cortical surface model. Sensitivity, specificity, accuracy, and diagnostic odds ratio (DOR) were estimated compared to ESM, using a meta-analytic framework. Nineteen patients (10 with left hemisphere electrodes) aged 4-19 years were analyzed. HGM during story listening was observed in bilateral posterior superior temporal, angular, supramarginal, and inferior frontal gyri, along with anatomically defined language association areas. Compared to either cognitive or both cognitive and orofacial sensorimotor interference with naming during ESM, left hemisphere HGM showed high specificity (0.82-0.84), good accuracy (0.66-0.70), and DOR of 2.23 and 3.24, respectively. HGM was a better classifier of ESM language sites in the left temporoparietal cortex compared to the frontal lobe. Incorporating visual naming with the story-listening task substantially improved the accuracy (0.80) and DOR (13.61) of HGM mapping, while the high specificity (0.85) was retained. In the right hemisphere, no ESM sites for aphasia were seen, and the results of HGM and ESM comparisons were not significant. HGM associated with story listening is a specific determinant of left hemisphere ESM language sites. It can be used for presurgical language mapping in children who cannot cooperate with conventional language tasks requiring active engagement. Incorporation of additional language tasks, if feasible, can further improve the diagnostic accuracy of language localization with HGM.

Global orientation in space and the lateralization of brain functions.

The functional role of the vestibular system for multisensory orientation and sensorimotor control is reviewed with a special focus on hemispherical lateralization and its consequences for neurological disorders of higher cortical function. The peripheral and central vestibular systems are bilaterally organized with ipsilateral and contralateral ascending pathways and two multisensory cortical networks in the right and left hemisphere. The vestibular cortical system shows a structural and functional lateralization with a dominance of the right hemisphere in right-handers and the left hemisphere in left-handers. Although the vestibular brainstem pathways are evenly distributed at lower pontine level, an increasing lateralization builds up because of an asymmetric number of pontine and mesencephalic crossing fibers from left to right in right-handers. This vestibular lateralization causes more frequent and more severe disorders of higher sensorimotor dysfunction in lesions of the right hemisphere such as in hemispatial neglect and the pusher syndrome. There is evidence that multisensory higher vestibular functions including large-scale spatial orientation, spatial memory and navigation are dominated by the right temporo-parietal cortex. A beneficial result of lateralization of brain functions in healthy individuals is that it enables the individual to produce a global sensorimotor response even in case of a mismatch of the actual right and left sensory inputs. The consequence for neurology, however, is that lesions in the dominant hemisphere cause more frequently and more severe disorders such as the visuo-spatial hemineglect and the pusher syndrome.

Cathodal tDCS of the bilateral anterior temporal lobes facilitates semantically-driven verbal fluency

In a verbal fluency task, a person is required to produce as many exemplars of a given category (e.g., ‘animals’, or words starting with ‘f’) as possible within a fixed duration. Successful verbal fluency performance relies both on the depth of search within semantic/phonological neighborhoods (‘clustering’) and the ability to flexibly disengage between exhausted clusters (‘switching’). Convergent evidence from functional imaging and neuropsychology suggests that cluster-switch behaviors engage dissociable brain regions. Switching has been linked to a frontoparietal network dedicated to executive functioning and controlled lexical retrieval, whereas clustering is more commonly associated with temporal lobe regions dedicated to semantic and phonological processing. Here we attempted to modulate cluster-switch dynamics among neurotypical adults (N = 24) using transcranial direct current stimulation (tDCS) delivered at three sites: a) anterior temporal cortex; b) frontal cortex; and c) temporoparietal cortex. Participants completed letter-guided and semantic category verbal fluency tasks pre/post stimulation. Cathodal stimulation of anterior temporal cortex facilitated the total number of words generated and the number of words generated within clusters during semantic category verbal fluency. These neuromodulatory effects were specific to stimulation of the one anatomical site. Our findings highlight the role of the anterior temporal lobes in representing semantic category structure and support the claim that clustering and switching behaviors have distinct substrates. We discuss implications both for theory and application to neurorehabilitation.

Interactions Between Oxytocin Receptor Gene Methylation and Callous-Unemotional Traits Impact Socioaffective Brain Systems in Conduct-Disordered Offenders

BackgroundThe developmental trajectory of psychopathy seemingly begins early in life and includes the presence of callous-unemotional (CU) traits (e.g., perturbed socioaffective reactivity and empathy, callousness) in youths with conduct disorder (CD). Whereas oxytocin receptor gene methylation (OXTRMeth) and its downstream neuromodulatory effects are deemed relevant to CU traits, nothing is known of how OXTRMeth interacts with CU traits to impact socioaffective brain systems in youngsters with CD. MethodsHence, we uniquely probed OXTRMeth × CU trait interactions on corticolimbic activity and amygdala subregional connections during recognition and resonance of distressing socioaffective stimuli (angry and fearful faces), in juvenile offenders with CD (n = 39) versus matched healthy control youths (n = 27). ResultsRelative to healthy control youths, elevated OXTRMeth and CU levels in youths with CD essentially interacted to predict frontoparietal hyperactivity and amygdalo-frontoparietal disconnection during task performance. Specifically, increasing OXTRMeth and CU levels in youths with CD interactively predicted midcingulate hyperactivity during both emotion conditions, with insular, temporoparietal, and precuneal hyperactivity additionally emerging during emotion recognition. Interactions between high OXTRMeth and CU levels in youths with CD additionally predicted centromedial amygdala decoupling from ventromedial/orbitofrontal regions during emotion recognition, along with basolateral amygdala decoupling from precuneal and temporoparietal cortices during emotion resonance. ConclusionsThese results uniquely suggest that interactions between OXTRMeth and CU traits in youths with CD may affect brain systems critical to decoding and integrating socioaffective information. Developmental models of CU traits and psychopathy could thus possibly advance by further examining OXTR epigenetic effects, which may hold promise for indicated prevention and personalized treatment by targeting oxytocinergic function.