This study investigates the cognitive and neural mechanisms involved in the linearization of events during language production, focusing on the processing of temporal conjunctions "before" and "after." While natural language typically presents events in chronological order, non-chronological sequences, as required by "before" sentences, impose additional cognitive demands. Using an adapted network task, we recorded event-related potentials (ERPs) in 24 healthy German speaking participants to examine the brain activity associated with these demands. Results showed that "before" sentences elicited early positivity and later negativity in ERPs, particularly over left temporal and frontocentral regions, suggesting increased working memory requirements for reordering events. These findings align with previous behavioral and neuroimaging studies, indicating that both language production and comprehension of "before" sentences necessitate more complex cognitive processing than "after" sentences. This research highlights the significant role of working memory during the conceptualization stage of language production exemplified by the brain’s handling of non-chronological sequences.

OBJECTIVE:Sensitivity to sublexical speech features is important for successful reading development. Here we assessed the processing of formal (phonological) and temporal (syllable stress) sublexical speech regularities in typical and dyslexic readers. METHODS:We tested Dutch-speaking, typical and dyslexic adult readers in a passive EEG oddball paradigm, manipulating phonotactic probability (formal) and syllable stress (temporal) in Dutch pseudowords. We assessed the mismatch negativity (MMN) as a marker for experience-dependent change detection, as well as the associated phase-reset in the theta frequency band. RESULTS:Both deviant types elicited an MMN. Dyslexic readers exhibited reduced neural sensitivity to phonotactic, but not to stress regularities. Time-frequency analyses suggest distinct processes underlying change detection for different deviant types, with increased delta/theta inter-trial coherence (ITC) for formal deviants, which was enhanced in dyslexic readers, and a decrease for temporal deviants, which did not differ between groups. CONCLUSION:Results suggest atypical sensitivity to phonological but not temporal speech regularities in dyslexic readers, and distinct oscillatory correlates underlying change detection for different deviant types. SIGNIFICANCE:This is the first study to simultaneously assess neural sensitivity to phonological and temporal regularities in Dutch adult dyslexic readers and highlights distinct change detection for different sublexical features.

Pronouns create cohesive links in discourse by referring to previously mentioned elements. Here, we focus on pronominalization during speech production in three experiments employing ERP and fMRI methodologies. Participants were asked to produce two short sentences describing a man or woman using an object. In the second sentence, they were instructed to use a pronoun to refer to the same person and a noun to refer to a different person. The first ERP experiment revealed that noun conditions elicited more negative ERPs starting at 220 ms, with significant differences in early and later time windows, particularly in the left hemisphere. The second ERP experiment showed divergence at 280 ms, with significant differences between 300 and 400 ms at midline electrodes, again indicating more negative ERPs for nouns. The fMRI experiment identified greater activations for nouns than pronouns in regions like the superior temporal gyrus (STG) and cerebellar vermis, suggesting higher working memory load and lexical retrieval demands for nouns compared to pronouns. Moreover, pronouns elicited an enhanced centro-parietal positivity, indicating increased attentional demands. These findings suggest that while noun processing requires greater working memory and lexical retrieval, pronoun processing engages more attentional resources. This study advances our understanding of the neural mechanisms underlying pronominalization during speech production, highlighting distinct neural responses for nouns and pronouns.

Classical galactosaemia (CG) is a hereditary disease in galactose metabolism that despite dietary treatment is characterized by a wide range of cognitive deficits, among which is language production. CG brain functioning has been studied with several neuroimaging techniques, which revealed both structural and functional atypicalities. In the present study, for the first time, we compared the oscillatory dynamics, especially the power spectrum and time-frequency representations (TFR), in the electroencephalography (EEG) of CG patients and healthy controls while they were performing a language production task. Twenty-one CG patients and 19 healthy controls described animated scenes, either in full sentences or in words, indicating two levels of complexity in syntactic planning. Based on previous work on the P300 event related potential (ERP) and its relation with theta frequency, we hypothesized that the oscillatory activity of patients and controls would differ in theta power and TFR. With regard to behavior, reaction times showed that patients are slower, reflecting the language deficit. In the power spectrum, we observed significant higher power in patients in delta (1-3 Hz), theta (4-7 Hz), beta (15-30 Hz) and gamma (30-70 Hz) frequencies, but not in alpha (8-12 Hz), suggesting an atypical oscillatory profile. The time-frequency analysis revealed significantly weaker event-related theta synchronization (ERS) and alpha desynchronization (ERD) in patients in the sentence condition. The data support the hypothesis that CG language difficulties relate to theta-alpha brain oscillations.

During ongoing narratives, event boundaries trigger processes relevant for subsequent memory. Previous work has shown that novel, unrelated input presented at an event boundary can retroactively interfere with short-term retention of the preceding event. This interference was attributed to a perturbation of offset-related processes taking place within seconds after encoding and supporting the binding of elements into a coherent event memory. However, the temporal specificity of this memory interference and whether its impact extends to longer retention delays has not been addressed. Here, participants viewed either individual or pairs of short narrative movie clips. Susceptibility to interference at event boundaries was probed by presenting the second clip either immediately after the first, or with a 2s encoding delay. In free and cued recall, after 20 min and 24 h, only memory for movie clips that were immediately followed by a second clip was reduced compared to clips shown in isolation. Intact offset-related processes (as indexed by successful recall of the first movie) did not negatively affect encoding of the subsequent clip. Together, these results indicate that the 2s time-window immediately after an event is relevant for successful consolidation and long-term retention of memory.

Patients with classic galactosemia (CG), an inborn error of galactose metabolism, suffer from impairments in cognition, including language processing. Potential causes are atypical brain oscillations. Recent electroencephalogram (EEG) showed differences in the P300 event-related-potential (ERP) and alterations in the alpha/theta-range during speech planning. This study investigated whether transcranial alternating current stimulation (tACS) at theta-frequency compared to sham can cause a normalization of the ERP post stimulation and improves language performance. Eleven CG patients and fourteen healthy controls participated in two tACS-sessions (theta 6.5 Hz/sham). They were engaged in an active language task, describing animated scenes at three moments, that is, pre/during/post stimulation. Pre and post stimulation, behavior (naming accuracy, voice-onset-times; VOT) and mean-amplitudes of ERP were compared, by means of a P300 time-window analysis and cluster-based-permutation testing during speech planning. The results showed that theta stimulation, not sham, significantly reduced naming error-percentage in patients, not in controls. Theta did not systematically speed up naming beyond a general learning effect, which was larger for the patients. The EEG analysis revealed a significant pre-post stimulation effect (P300/late positivity), in patients and during theta stimulation only. In conclusion, theta-tACS improved accuracy in language performance in CG patients compared to controls and altered the P300 and late positive ERP-amplitude, suggesting a lasting effect on neural oscillation and behavior.

AIMS:To measure brain activity in patients with bruxism and temporomandibular disorder (TMD)-related pain in comparison to controls using functional magnetic resonance imaging (fMRI) and to investigate whether modulations in jaw clenching led to different pain reports and/or changes in neural activity in motor and pain processing areas within and between both groups.METHODS:A total of 40 participants (21 patients with bruxism and TMD-related pain and 19 healthy controls) performed a tooth-clenching task while lying inside a 3T MRI scanner. Participants were instructed to mildly or strongly clench their teeth for brief periods of 12 seconds and to subsequently rate their clenching intensity and pain experience after each clenching period.RESULTS:Patients reported significantly more pain during strong clenching compared to mild clenching. Further results showed significant differences between patients and controls in activity in areas of brain networks commonly associated with pain processing, which were also correlated with reported pain intensity. There was no evidence for differences in activity in motor-related areas between groups, which contrasts with findings of previous research.CONCLUSIONS:Brain activity in patients with bruxism and TMD-related pain is correlated more with pain processing than with motoric differences.

Several theories of predictive processing propose reduced sensory and neural responses to anticipated events. Support comes from magnetoencephalography/electroencephalography (M/EEG) studies, showing reduced auditory N1 and P2 responses to self-generated compared to externally generated events, or when the timing and form of stimuli are more predictable. The current study examined the sensitivity of N1 and P2 responses to statistical speech regularities. We employed a motor-to-auditory paradigm comparing event-related potential (ERP) responses to externally and self-triggered pseudowords. Participants were presented with a cue indicating which button to press (motor-auditory condition) or which pseudoword would be presented (auditory-only condition). Stimuli consisted of the participant's own voice uttering pseudowords that varied in phonotactic probability and syllable stress. We expected to see N1 and P2 suppression for self-triggered stimuli, with greater suppression effects for more predictable features such as high phonotactic probability and first-syllable stress in pseudowords. In a temporal principal component analysis (PCA), we observed an interaction between syllable stress and condition for the N1, where second-syllable stress items elicited a larger N1 than first-syllable stress items, but only for externally generated stimuli. We further observed an effect of syllable stress on the P2, where first-syllable stress items elicited a larger P2. Strikingly, we did not observe motor-induced suppression for self-triggered stimuli for either the N1 or P2 component, likely due to the temporal predictability of the stimulus onset in both conditions. Taking into account previous findings, the current results suggest that sensitivity to syllable stress regularities depends on task demands.

Sleep spindles (8 - 16 Hz) are transient electrophysiological events during non-rapid eye movement sleep. While sleep spindles are routinely observed in the cortex using scalp electroencephalography (EEG), recordings of their thalamic counterparts have not been widely studied in humans. Based on a few existing studies, it has been hypothesized that spindles occur as largely local phenomena. We investigated intra-thalamic and thalamocortical spindle co-occurrence, which may underlie thalamocortical communication. We obtained scalp EEG and thalamic recordings from 7 patients that received bilateral deep brain stimulation (DBS) electrodes to the anterior thalamus for the treatment of drug resistant focal epilepsy. Spindles were categorized into subtypes based on their main frequency (i.e., slow (10±2 Hz) or fast (14±2 Hz)) and their level of thalamic involvement (spanning one channel, or spreading uni- or bilaterally within the thalamus). For the first time, we contrasted observed spindle patterns with permuted data to estimate random spindle co-occurrence. We found that multichannel spindle patterns were systematically coordinated at the thalamic and thalamocortical level. Importantly, distinct topographical patterns of thalamocortical spindle overlap were associated with slow and fast subtypes of spindles. These observations provide further evidence for coordinated spindle activity in thalamocortical networks.

Despite good control of phenylalanine (Phe) levels during childhood and adolescence, adults with phenylketonuria (PKU) often show abnormalities in the white matter of the brain, which have been associated with poorer cognitive performance. However, whether such a relationship exists with cortical gray matter is still unknown. Therefore, we investigated cortical thickness and surface area in adults with early-treated PKU and their relationship to cognitive functions and metabolic control. We included 30 adult patients with early-treated and metabolically well-controlled PKU (median age: 35.5 years) and 54 healthy controls (median age: 29.3 years). Surface-based morphometry was derived from T1-weighted magnetic resonance images using FreeSurfer, and general intelligence, executive functions, and attention were assessed. Concurrent plasma Phe, tyrosine, and tryptophan levels were measured in patients. In addition, Phe levels were collected retrospectively to calculate the index of dietary control. Patients showed a thinner cortex than controls in regions of the bilateral temporal, parietal, and occipital lobes (effect size r = -0.34 to -0.42, p < 0.05). No group differences in surface area were found. In patients, accuracy in the working memory task was positively correlated with thickness in the left insula (r = 0.45, p = 0.013), left fusiform gyrus (r = 0.39, p = 0.032), and right superior temporal gyrus (r = 0.41, p = 0.024), but did not survive false discovery rate correction. Neither concurrent nor historical metabolic parameters were related to cortical thickness. Taken together, adults with PKU showed widespread reductions in cortical thickness despite good metabolic control in childhood and adolescence. However, alterations in cortical thickness were unrelated to metabolic parameters and cognitive performance.

ABSTRACT Some theories of predictive processing propose reduced sensory and neural responses to anticipated events. Support comes from M/EEG studies, showing reduced auditory N1 and P2 responses to self-compared to externally generated events, or when stimulus properties are more predictable (e.g. prototypical). The current study examined the sensitivity of N1 and P2 responses to statistical regularities of speech. We employed a motor-to-auditory paradigm comparing ERP responses to externally and self-generated pseudowords, varying in phonotactic probability and syllable stress. We expected to see N1 and P2 suppression for self-generated stimuli, with greater suppression effect for more predictable features such as high phonotactic probability and first syllable stress in pseudowords. We observe an interaction between phonotactic probability and condition on the N1 amplitude, with an enhanced effect of phonotactic probability in processing self-generated stimuli. However, the directionality of this effect was reversed compared to what was expected, namely a larger N1 amplitude for high probability items, possibly indicating a perceptual bias toward the more predictable item. We further observed an effect of syllable stress on the P2 amplitude, with greater amplitudes in response to first syllable stress items. The current results suggest that phonotactic probability plays an important role in processing self-generated speech, supporting feedforward models involved in speech production.

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping (ESM) is the gold standard for the identification of “eloquent” areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity (55–200 Hz) recorded with extraoperative electrocorticography (ECoG) during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha (8–12 Hz) and beta (15–25 Hz) bands could further improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy (age: 35.9 ± 9.1 years, range: 22–48, 8 females, 9 right handed) participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model (GLM) approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic (ROC) curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient’s degree of attention to the stimulus. We show that diagnostic ability can be increased by 3–5% by combining gamma and alpha and by 7.5–11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy.

Predictions of our sensory environment facilitate perception across domains. During speech perception, formal and temporal predictions may be made for phonotactic probability and syllable stress patterns, respectively, contributing to the efficient processing of speech input. The current experiment employed a passive EEG oddball paradigm to probe the neurophysiological processes underlying temporal and formal predictions simultaneously. The component of interest, the mismatch negativity (MMN), is considered a marker for experience-dependent change detection, where its timing and amplitude are indicative of the perceptual system’s sensitivity to presented stimuli. We hypothesized that more predictable stimuli (i.e. high phonotactic probability and first syllable stress) would facilitate change detection, indexed by shorter peak latencies or greater peak amplitudes of the MMN. This hypothesis was confirmed for phonotactic probability: high phonotactic probability deviants elicited an earlier MMN than low phonotactic probability deviants. We do not observe a significant modulation of the MMN to variations in syllable stress. Our findings confirm that speech perception is shaped by formal and temporal predictability. This paradigm may be useful to investigate the contribution of implicit processing of statistical regularities during (a)typical language development.

Electrical stimulation mapping (ESM) is the gold standard for identification of “eloquent” areas prior to resection of epileptogenic tissue, however, it is time consuming and may cause side effects, especially stimulation-induced seizures and after-discharges. Broadband gamma activity (55 – 200 Hz) recorded with subdural electrocorticography (ECoG) during cognitive tasks has been proposed as an attractive tool for mapping cortical areas with specific function but until now has not proven definitive clinical value. Fewer studies have addressed whether the alpha (8 – 12 Hz) and beta (15 – 25 Hz) band activity could also be used to improve eloquent cortex identification. We compared alpha, beta and broadband gamma activity, and their combination for the identification of eloquent cortical areas defined by ESM. Ten patients participated in a delayed-match-to-sample task, where syllable sounds were matched to visually presented letters and responses given by keyboard. We used a generalized linear model (GLM) approach to find the optimal weighting of low frequency bands and broadband gamma power to predict the ESM categories. Broadband gamma activity increased more in eloquent areas than in non-eloquent areas and this difference had a diagnostic ability (area under (AU) the receiving operating characteristic curve - AUROC) of ∼70%. Both alpha and beta power decreased more in eloquent areas. Alpha power had lower AUROC than broadband gamma while beta had similar AUROC. AUROC was enhanced by the combination of alpha and broadband gamma (3% improvement) and by the combination of beta and broadband gamma (7% improvement) over the use of broadband gamma alone. Further analysis showed that the relative performance of broadband gamma and low frequency bands depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient’s attention to the stimulus. However, the combination of beta band and broadband gamma always gave the best performance. We show how ECoG power modulation from cognitive testing periods can be used to map the probability of eloquence by ESM and how this probability can be used as an aid for optimal ESM planning. We conclude that low frequency power during cognitive testing can contribute to the identification of eloquent areas in patients with focal refractory epilepsy improving its precision but does not replace the need of ESM. Highlights Gamma, alpha and beta band activity has significant diagnostic ability to identify ESM defined eloquent cortical areas. We present a novel method to combine gamma and low frequency activity for enhanced identification. We quantify how identification is dependent on analysis time window, cortical function, and patient’s attentional engagement. With further development, this approach may offer an alternative to ESM mapping with reduced burden for patients.

Activation of neuronal networks is typically associated with a change in spectral power in electric signals within the network. The role of different spectral bands in mediating cognitive processes is still not fully understood. In human language networks, a hierarchical model has been suggested in which different types of linguistic information is transferred in different oscillatory bands. Within that model, attention is assumed to correlate with increase in gamma and decrease in alpha band power. Electrocorticography (ECoG) allows the segregation of neural representations independently of stimulus variation. Here, for the first time, we investigate whether selective attention to the different components of a syllable (i.e., consonants or vowels) modulates the spectral power of oscillatory activity (i.e., broadband gamma and alpha) and whether these changes relate to behavioral performance. To address this issue, we measured ECoG signals in 11 patients with refractory epilepsy who were undergoing pre-surgical screening. Neuronal responses were measured with intracranial electrodes (i.e., grids, strips, and depth hippocampal electrodes). The patients engaged in cognitive testing in which auditory consonant–vowel syllable sounds were compared with written letters (i.e., delay match-to-sample task). The behavioral relevance of different components of the syllables was manipulated in four levels; attention was directed either to the complete syllable, only to the vowel, only to the consonant, or the syllable sound was irrelevant. We calculated: (a) bipolar differentials between each pair of neighboring channels; (b) time–frequency representations of power between 2 and 150 Hz; (c) an index of power change, per trial, relative to power during pre-stimulus baseline period; and (d) average power modulation for two frequency bands (i.e., 5–15 and 70–150 Hz). Presentation of stimuli was associated with an increase in broadband gamma (70–150 Hz) and a decrease in alpha (5–15 Hz) over sensory cortex (i.e., auditory cortex for auditory stimuli, and visual cortex for visual stimuli), while alpha power was increased in domain unspecific cortical areas. Gamma band activity could be robustly mapped to stimulus parameters but was only weakly related to attentional state or behavioral performance. Alpha band activity was more related to cognitive state and performance than to stimulus features. Broadband gamma power changes were related to stimulus physical properties. These results give new insights into the interplay between alpha and gamma oscillations within the human language network, here with a focus on phonological aspects, and the possible role of these oscillations in the processing of sensory stimuli and behavioral performance during selective attention.

Sensorimotor integration, the translation between acoustic signals and motoric programs, may constitute a crucial mechanism for speech. During speech perception, the acoustic-motoric translations include the recruitment of cortical areas for the representation of speech articulatory features, such as place of articulation. Selective attention can shape the processing and performance of speech perception tasks. Whether and where sensorimotor integration takes place during attentive speech perception remains to be explored. Here, we investigate articulatory feature representations of spoken consonant-vowel (CV) syllables during two distinct tasks. Fourteen healthy humans attended to either the vowel or the consonant within a syllable in separate delayed-match-to-sample tasks. Single-trial fMRI blood oxygenation level-dependent (BOLD) responses from perception periods were analyzed using multivariate pattern classification and a searchlight approach to reveal neural activation patterns sensitive to the processing of place of articulation (i.e., bilabial/labiodental vs. alveolar). To isolate place of articulation representation from acoustic covariation, we applied a cross-decoding (generalization) procedure across distinct features of manner of articulation (i.e., stop, fricative, and nasal). We found evidence for the representation of place of articulation across tasks and in both tasks separately: for attention to vowels, generalization maps included bilateral clusters of superior and posterior temporal, insular, and frontal regions; for attention to consonants, generalization maps encompassed clusters in temporoparietal, insular, and frontal regions within the right hemisphere only. Our results specify the cortical representation of place of articulation features generalized across manner of articulation during attentive syllable perception, thus supporting sensorimotor integration during attentive speech perception and demonstrating the value of generalization.

Patients with classic galactosemia, a genetic metabolic disorder, encounter cognitive impairments, including motor (speech), language, and memory deficits. We used functional magnetic resonance imaging to evaluate spontaneous functional connectivity during rest to investigate potential abnormalities in neural networks. We characterized networks using seed-based correlation analysis in 13 adolescent patients and 13 matched controls. Results point towards alterations in several networks, including well-known resting-state networks (e.g. default mode, salience, visual network). Particularly, patients showed alterations in networks encompassing medial prefrontal cortex, parietal lobule and (pre)cuneus, involved in spatial orientation and attention. Furthermore, altered connectivity of networks including the insula and superior frontal gyrus -important for sensory-motor integration and motor (speech) planning- was demonstrated. Lastly, abnormalities were found in networks involving occipital regions, linked to visuospatial capacities and working memory. Importantly, across several seeds, altered functional connectivity to the superior frontal cortex, anterior insula, parietal lobule and the (pre)cuneus was observed in patients, suggesting special importance of these brain regions. Moreover, these alterations correlated with neurocognitive test results, supporting a relation with the clinical phenotype. Our findings contribute to improved characterization of brain impairments in classic galactosemia and provide directions for further investigations.

The evident degree of heterogeneity observed in reading disabled children has puzzled reading researchers for decades. Recent advances in the genetic underpinnings of reading disability have indicated that the heritable, familial risk for dyslexia is a major risk factor. The present data-driven, classification attempt aims to revisit the possibility of identifying distinct cognitive deficit profiles in a large sample of second to fourth grade reading disabled children. In this sample, we investigated whether genetic and environmental risk factors are able to distinguish between poor reader subtypes. In this profile, we included reading-related measures of phonemic awareness, letter-speech sound processing and rapid naming, known as candidate vulnerability markers associated with dyslexia and familial risk for dyslexia, as well as general cognitive abilities (non-verbal IQ and vocabulary). Clustering was based on a 200 multi-start K-means approach. Results revealed four emerging subtypes of which the first subtype showed no cognitive deficits underlying their poor reading skills (Reading-only impaired poor readers). The other three subtypes shared a core phonological deficit (PA) with a variable and discriminative expression across the other underlying vulnerability markers. More specific, type 2 showed low to poor performance across all reading-related and general cognitive abilities (general poor readers), type 3 showed a specific letter-speech sound mapping deficit next to a PA deficit (PA-LS specific poor readers) and type 4 showed a specific rapid naming deficit complementing their phonological weakness (PA-RAN specific poor readers). The first three poor reader profiles were more characterized by variable environmental risk factor, while the fourth, PA-RAN poor reader subtype showed a significantly strong familial risk for dyslexia. Overall, when we zoom in on the heterogeneous phenomenon of reading disability, unique and distinct cognitive subtypes can be identified, distinguishing between those poor readers more influences by the role of genes and those more influenced by environmental risk factors. Taking into account this diversity of distinct cognitive subtypes, instead of looking at the reading disabled sample as a whole, will help tailor future diagnostic and intervention efforts more specifically to the needs of children with such a specific deficit and risk pattern, as well as providing a more promising way forward for genetic studies of dyslexia.

Brain impairments have been observed in patients with classic galactosemia, an inherited metabolic disorder resulting in a particular neuro-cognitive profile. Neuroimaging studies showed abnormalities such as diffuse white mater (WM) abnormalities and grey matter (GM) atrophy. Our current study analysed grey matter density using voxel-based morphometry (VBM) and compared the brains of eight adolescent patients with classic galactosemia with eight healthy gender- and aged-matched controls. GM density differences were found in several regions. Decreased GM density was found in the patients in the bilateral putamen and bilateral occipital cortex. Increased GM density in the patients, on the other hand, was found in the bilateral inferior frontal and medial prefrontal cortex. The anatomical profile of the abnormalities is in line with the neuro-cognitive profile of patients with classic galactosemia, including motor dysfunction, speech and language difficulties and higher order cognitive problems. Less favourable GM densities in patients (either increased or decreased compared to controls) correlated with younger age, a worse visual working memory performance, and an older age at initiation of the galactose-restricted diet. To conclude, this explorative study is the first to analyse the GM using VBM in this population, and demonstrates a mixed profile of both increased and decreased GM density in these patients.

In a shooting video game we investigated whether increased distance reduces moral conflict. We measured and analyzed the event related potential (ERP), including the N2 component, which has previously been linked to cognitive conflict from competing decision tendencies. In a modified Go/No-go task designed to trigger moral conflict participants had to shoot suddenly appearing human like avatars in a virtual reality scene. The scene was seen either from an ego perspective with targets appearing directly in front of the participant or from a bird's view, where targets were seen from above and more distant. To control for low level visual features, we added a visually identical control condition, where the instruction to “shoot” was replaced by an instruction to “detect.” ERP waveforms showed differences between the two tasks as early as in the N1 time-range, with higher N1 amplitudes for the close perspective in the “shoot” task. Additionally, we found that pre-stimulus alpha power was significantly decreased in the ego, compared to the bird's view only for the “shoot” but not for the “detect” task. In the N2 time window, we observed main amplitude effects for response (No-go > Go) and distance (ego > bird perspective) but no interaction with task type (shoot vs. detect). We argue that the pre-stimulus and N1 effects can be explained by reduced attention and arousal in the distance condition when people are instructed to “shoot.” These results indicate a reduced moral engagement for increased distance. The lack of interaction in the N2 across tasks suggests that at that time point response execution dominates. We discuss potential implications for real life shooting situations, especially considering recent developments in drone shootings which are per definition of a distant view.