Search

Contextual cues and prior evidence guide human goal-directed behavior. To date, the neurophysiological mechanisms that implement contextual priors to guide subsequent actions remain unclear. Here we demonstrate that increasing behavioral uncertainty introduces a shift from an oscillatory to a continuous processing mode in human prefrontal cortex. At the population level, we found that oscillatory and continuous dynamics reflect dissociable signatures that support distinct aspects of encoding, transmission and execution of context-dependent action plans. We show that prefrontal population activity encodes predictive context and action plans in serially unfolding orthogonal subspaces, while prefrontal-motor theta oscillations synchronize action-encoding population subspaces to mediate the hand-off of action plans. Collectively, our results reveal how two key features of large-scale population activity, namely continuous population trajectories and oscillatory synchrony, operate in concert to guide context-dependent human behavior.

The brain excels at processing sensory input, even in rich or chaotic environments. Mounting evidence attributes this to the creation of sophisticated internal models of the environment that draw on statistical structures in the unfolding sensory input. Understanding how and where this modeling takes place is a core question in statistical learning and predictive processing. In this context, we address the role of transitional probabilities as an implicit structure supporting the encoding of a random auditory stream. Leveraging information-theoretical principles and the high spatiotemporal resolution of intracranial electroencephalography, we analyzed the trial-by-trial high-frequency activity representation of transitional probabilities. This unique approach enabled us to demonstrate how the brain continuously encodes structure in random stimuli and revealed the involvement of a network outside of the auditory system, including hippocampal, frontal, and temporal regions. Linking the frame-works of statistical learning and predictive processing, our work illuminates an implicit process that can be crucial for the swift detection of patterns and unexpected events in the environment.

IntroductionIntracranial electrodes are implanted in patients with drug-resistant epilepsy as part of their pre-surgical evaluation. This allows the investigation of normal and pathological brain functions with excellent spatial and temporal resolution. The spatial resolution relies on methods that precisely localize the implanted electrodes in the cerebral cortex, which is critical for drawing valid inferences about the anatomical localization of brain function. Multiple methods have been developed to localize the electrodes, mainly relying on pre-implantation MRI and post-implantation computer tomography (CT) images. However, they are hard to validate because there is no ground truth data to test them and there is no standard approach to systematically quantify their performance. In other words, their validation lacks standardization. Our work aimed to model intracranial electrode arrays and simulate realistic implantation scenarios, thereby providing localization algorithms with new ways to evaluate and optimize their performance.ResultsWe implemented novel methods to model the coordinates of implanted grids, strips, and depth electrodes, as well as the CT artifacts produced by these. We successfully modeled realistic implantation scenarios, including different sizes, inter-electrode distances, and brain areas. In total, ∼3,300 grids and strips were fitted over the brain surface, and ∼850 depth electrode arrays penetrating the cortical tissue were modeled. Realistic CT artifacts were simulated at the electrode locations under 12 different noise levels. Altogether, ∼50,000 thresholded CT artifact arrays were simulated in these scenarios, and validated with real data from 17 patients regarding the coordinates’ spatial deformation, and the CT artifacts’ shape, intensity distribution, and noise level. Finally, we provide an example of how the simulation platform is used to characterize the performance of two cluster-based localization methods.ConclusionWe successfully developed the first platform to model implanted intracranial grids, strips, and depth electrodes and realistically simulate thresholded CT artifacts and their noise. These methods provide a basis for developing more complex models, while simulations allow systematic evaluation of the performance of electrode localization techniques. The methods described in this article, and the results obtained from the simulations, are freely available via open repositories. A graphical user interface implementation is also accessible via the open-source iElectrodes toolbox.

Introduction Functional networks develop throughout adolescence when anorexia nervosa (AN) normally debuts. In AN, cerebral structural alterations are found in most brain regions and may be related to the observed functional brain changes. Few studies have investigated the functional networks of the brain in adolescent AN patients.. The aim of this explorative study was to investigate multiple functional networks in adolescent AN patients compared to healthy age-matched controls (HC) and the relationship with age, eating disorder symptoms and structural alterations. Methods Included were 29 female inpatients with restrictive AN, and 27 HC. All participants were between the ages of 12 to 18 years. Independent component analysis (ICA) identified 21 functional networks that were analyzed with multivariate and univariate analyses of components and group affiliation (AN vs HC). Age, age × group interaction and AN symptoms were included as covariates. Follow-up correlational analyses of selected components and structural measures (cortical thickness and subcortical volume) were carried out. Results Decreased functional connectivity (FC) in AN patients was found in one cortical network, involving mainly the precuneus, and identified as a default mode network (DMN). Cortical thickness in the precuneus was significantly correlated with functional connectivity in this network. Significant group differences were also found in two subcortical networks involving mainly the hippocampus and the amygdala respectively, and a significant interaction effect of age and group was found in both these networks. There were no significant associations between FC and the clinical measures used in the study. Conclusion The findings from the present study may imply that functional alterations are related to structural alterations in selected regions and that the restricted food intake in AN patients disrupt normal age-related development of functional networks involving the amygdala and hippocampus.

Johnson et al. show that orbitofrontal cortex (OFC) lesions reduce working memory for temporal order but not spatial position, and individual behavioral deficits are commensurate with lesion size. Findings suggest that OFC supports understanding of the order of events.

Attending to our inner world is a fundamental cognitive phenomenon1-3, yet its neural underpinnings remain largely unknown. Neuroimaging evidence implicates the default network (DN) and frontoparietal control network (FPCN)4; however, the electrophysiological basis for the interaction between these networks is unclear. Here we recorded intracranial electroencephalogram from DN and FPCN electrodes implanted in individuals undergoing presurgical monitoring for refractory epilepsy. Subjects performed an attention task during which they attended to tones (that is, externally directed attention) or ignored the tones and thought about whatever came to mind (that is, internally directed attention). Given the emerging role of theta band connectivity in attentional processes5,6, we examined the theta power correlation between DN and two subsystems of the FPCN as a function of attention states. We found increased connectivity between DN and FPCNA during internally directed attention compared to externally directed attention, which positively correlated with attention ratings. There was no statistically significant difference between attention states in the connectivity between DN and FPCNB. Our results indicate that enhanced theta band connectivity between the DN and FPCNA is a core electrophysiological mechanism that underlies internally directed attention.

Contains fulltext : 232781.pdf (Publisher’s version ) (Open Access) Damage to the ventromedial PFC (VMPFC) can cause maladaptive social behavior, but the cognitive processes underlying these behavioral changes are still uncertain. Here, we tested whether patients with acquired VMPFC lesions show altered approach–avoidance tendencies to emotional facial expressions. Thirteen patients with focal VMPFC lesions and 31 age- and gender-matched healthy controls performed an implicit approach–avoidance task in which they either pushed or pulled a joystick depending on stimulus color. Whereas controls avoided angry faces, VMPFC patients displayed an incongruent response pattern characterized by both increased approach and reduced avoidance of angry facial expressions. The approach bias was stronger in patients with higher self-reported impulsivity and disinhibition and in those with larger lesions. We further used linear ballistic accumulator modeling to investigate latent parameters underlying approach-avoidance decisions. Controls displayed negative drift rates when approaching angry faces, whereas VMPFC lesions abolished this pattern. In addition, VMPFC patients had weaker response drifts than controls during avoidance. Finally, patients showed reduced drift rate variability and shorter nondecision times, indicating impulsive and rigid decision-making. Our findings thus suggest that VMPFC damage alters the pace of evidence accumulation in response to social signals, eliminating a default, protective avoidant bias and facilitating a dysfunctional approach behavior. 13 p.

Visual search is a fundamental human behavior, providing a gateway to understanding other sensory domains as well as the role of search in higher-order cognition. Search has been proposed to include two component processes: inefficient search (search) and efficient search (pop-out). According to extant research, these two processes map onto two separable neural systems located in the frontal and parietal association cortices. In this study, we use intracranial recordings from 23 participants to delineate the neural correlates of search and pop-out with an unprecedented combination of spatiotemporal resolution and coverage across cortical and subcortical structures. First, we demonstrate a role for the medial temporal lobe in visual search, on par with engagement in frontal and parietal association cortex. Second, we show a gradient of increasing engagement over anatomical space from dorsal to ventral lateral frontal cortex. Third, we confirm previous intracranial work demonstrating nearly complete overlap in neural engagement across cortical regions in search and pop-out. We further demonstrate pop-out selectivity, manifesting as activity increase in pop-out as compared to search, in a distributed set of sites including frontal cortex. This result is at odds with the view that pop-out is implemented in low-level visual cortex or parietal cortex alone. Finally, we affirm a central role for the right lateral frontal cortex in search.

BackgroundIntracranial electrodes are implanted in patients with drug-resistant epilepsy as part of their pre-surgical evaluation. This allows investigation of normal and pathological brain functions with excellent spatial and temporal resolution. The spatial resolution relies on methods that precisely localize the implanted electrodes in the cerebral cortex, which is critical for drawing valid anatomical inferences about brain function.Multiple methods have been developed to localize implanted electrodes, mainly relying on pre-implantation MRI and post-implantation CT images. However, there is no standard approach to quantify the performance of these methods systematically.The purpose of our work is to model intracranial electrodes to simulate realistic implantation scenarios, thereby providing methods to optimize localization algorithm performance.ResultsWe implemented novel methods to model the coordinates of implanted grids, strips, and depth electrodes, as well as the CT artifacts produced by these.We successfully modeled a large number of realistic implantation “scenarios”, including different sizes, inter-electrode distances, and brain areas. In total, more than 3300 grids and strips were fitted over the brain surface, and more than 850 depth electrode arrays penetrating the cortical tissue were modeled. More than 37000 simulations of electrode array CT artifacts were performed in these “scenarios”, mimicking the intensity profile and orientation of real artifactual voxels. Realistic artifacts were simulated by introducing different noise levels, as well as overlapping electrodes.ConclusionsWe successfully developed the first platform to model implanted intracranial grids, strips, and depth electrodes and realistically simulate CT artifacts and noise.These methods set the basis for developing more complex models, while simulations allow the performance evaluation of electrode localization techniques systematically.The methods described in this article, and the results obtained from the simulations, are freely available via open repositories. A graphical user interface implementation is also accessible via the open-source iElectrodes toolbox.

Previous research has shown that the autonomic nervous system provides essential constraints over ongoing cognitive function. However, there is currently a relative lack of direct empirical evidence for how this interaction manifests in the brain at the macroscale level. Here, we examine the role of ascending arousal and attentional load on large-scale network dynamics by combining pupillometry, functional MRI, and graph theoretical analysis to analyze data from a visual motion-tracking task with a parametric load manipulation. We found that attentional load effects were observable in measures of pupil diameter and in a set of brain regions that parametrically modulated their BOLD activity and mesoscale network-level integration. In addition, the regional patterns of network reconfiguration were correlated with the spatial distribution of the α2a adrenergic receptor. Our results further solidify the relationship between ascending noradrenergic activity, large-scale network integration, and cognitive task performance., Author Summary In our daily lives, it is usual to encounter highly demanding cognitive tasks. They have been traditionally regarded as challenges that are solved mainly through cerebral activity, specifically via information-processing steps carried by neurons in the cerebral cortex. Activity in cortical networks thus constitutes a key factor for improving our understanding of cognitive processes. However, recent evidence has shown that evolutionary older players in the central nervous system, such as brain stem’s ascending modulatory systems, might play an equally important role in diverse cognitive mechanisms. Our article examines the role of the ascending arousal system on large-scale network dynamics by combining pupillometry, functional MRI, and graph theoretical analysis.

Objective - Reduction in cerebral volume is often found in underweight patients with anorexia nervosa (AN), but few studies have investigated other morphological measures. Cortical thickness (CTh) and surface area (CSA), often used to produce the measure of cortical volume, are developmentally distinct measures that may be differentially affected in AN, particularly in the developing brain. In the present study, we investigated CTh and CSA both separately and jointly to gain further insight into structural alterations in adolescent AN patients. Method - Thirty female AN inpatients 12–18 years of age, and 27 age‐matched healthy controls (HC) underwent structural magnetic resonance imaging. Group differences in CTh and CSA were investigated separately and jointly with a permutation‐based nonparametric combination method (NPC) which may be more sensitive in detecting group differences compared to traditional volumetric methods. Results - Results showed significant reduction in in both CTh and CSA in several cortical regions in AN compared to HC and the reduction was related to BMI. Different results for the two morphological measures were found in a small number of cortical regions. The joint NPC analyses showed significant group differences across most of the cortical mantle. Discussion - Results from this study give novel insight to areal reduction in adolescent AN patients and indicate that both CTh and CSA reduction is related to BMI. The study is the first to use the NPC method to reveal large structural alterations covering most of the brain in adolescent AN.

Visual search is a fundamental human behavior, which has been proposed to include two component processes: inefficient search (Search) and efficient search (Pop-out). According to extant research, these two processes map onto two separable neural systems located in the frontal and parietal association cortices. In the present study, we use intracranial recordings from 23 participants to delineate the neural correlates of Search and Pop-out with an unprecedented combination of spatiotemporal resolution and coverage across cortical and subcortical structures. First, we demonstrate a role for the medial temporal lobe in visual search, on par with engagement in frontal and parietal association cortex. Second, we show a gradient of increasing engagement over anatomical space from dorsal to ventral lateral frontal cortex. Third, we confirm previous work demonstrating nearly complete overlap in neural engagement across cortical regions in Search and Pop-out. We further demonstrate Pop-out selectivity manifesting as activity increase in Pop-out as compared to Search in a distributed set of sites including frontal cortex. This result is at odds with the view that Pop-out is implemented in low-level visual cortex or parietal cortex alone. Finally, we affirm a central role for the right lateral frontal cortex in Search.

BackgroundNeurobiological models of stress and stress-related mental illness, including post-traumatic stress disorder, converge on the amygdala and the prefrontal cortex (PFC). While a surge of research has reported altered structural and functional connectivity between amygdala and the medial PFC following severe stress, few have addressed the underlying neurochemistry.MethodsWe combined resting-state functional magnetic resonance imaging measures of amygdala connectivity with in vivo MR-spectroscopy (1H-MRS) measurements of glutamate in 26 survivors from the 2011 Norwegian terror attack and 34 control subjects.ResultsTraumatized youths showed altered amygdala–anterior midcingulate cortex (aMCC) and amygdala–ventromedial prefrontal cortex (vmPFC) connectivity. Moreover, the trauma survivors exhibited reduced levels of glutamate in the vmPFC which fits with the previous findings of reduced levels of Glx (glutamate + glutamine) in the aMCC (Ousdal et al., 2017) and together suggest long-term impact of a traumatic experience on glutamatergic pathways. Importantly, local glutamatergic metabolite levels predicted the individual amygdala–aMCC and amygdala–vmPFC functional connectivity, and also mediated the observed group difference in amygdala–aMCC connectivity.ConclusionsOur findings suggest that traumatic stress may influence amygdala–prefrontal neuronal connectivity through an effect on prefrontal glutamate and its compounds. Understanding the neurochemical underpinning of altered amygdala connectivity after trauma may ultimately lead to the discovery of new pharmacological agents which can prevent or treat stress-related mental illness.

A significant number of adolescents have been exposed to traumatic life events. However, knowledge about the specific sleep disturbance that occurs in individuals after trauma exposure is predominantly based on studies of adults. This study reports specific sleep disturbance in 42 survivors of the 2011 mass shooting at a youth summer camp on the Norwegian island Utoya, mean age = 20.91 years, SD = 2.32, 62.5% females. When compared with matched controls, significantly more survivors reported having sleep disturbances, 52.4% versus 13.6%, d = 0.93, of which onset began at the time of the shooting, χ2 = 14.9, p 1.7, ps = .044 to .028. These results corroborate the effects of a life threat on the range and extent of sleep disturbances, and emphasize the need to better assess and treat sleep disorders in adolescents exposed to trauma.

The human insula is known to be involved in auditory processing, but knowledge about its precise functional role and the underlying electrophysiology is limited. To assess its role in automatic auditory deviance detection we analyzed the EEG high frequency activity (HFA; 75–145 Hz) and ERPs from 90 intracranial insular channels across 16 patients undergoing pre-surgical intracranial monitoring for epilepsy treatment. Subjects passively listened to a stream of standard and deviant tones differing in four physical dimensions: intensity, frequency, location or time. HFA responses to auditory stimuli were found in the short and long gyri, and the anterior, superior, and inferior segments of the circular sulcus of the insular cortex. Only a subset of channels in the inferior segment of the circular sulcus of the insula showed HFA deviance detection responses, i.e., a greater and longer latency response to specific deviants relative to standards. Auditory deviancy processing was also later in the insula when compared with the superior temporal cortex. ERP results were more widespread and supported the HFA insular findings. These results provide evidence that the human insula is engaged during auditory deviance detection. Fil: Blenkmann, Alejandro Omar. University of Oslo; Noruega. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Collavini, Santiago. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Lubell, James. University of Oslo; Noruega Fil: Llorens, Anaïs. University of Oslo; Noruega Fil: Funderud, Ingrid. University of Oslo; Noruega Fil: Ivanovic, Jugoslav. University of Oslo; Noruega Fil: Larsson, Pål G.. University of Oslo; Noruega Fil: Meling, Torstein R.. University of Oslo; Noruega Fil: Bekinschtein, Tristán Andrés. University of Cambridge; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Kochen, Sara Silvia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Endestad, Tor. University of Oslo; Noruega Fil: Knight, Robert T.. University of California at Berkeley; Estados Unidos Fil: Solbakk, Anne Kristin. University of Oslo; Noruega

The brain responds to violations of expected rhythms, due to extraction- and prediction of the temporal structure in auditory input. Yet, it is unknown how probability of rhythm violations affects the overall rhythm predictability. Another unresolved question is whether predictive processes are independent of attention processes. In this study, EEG was recorded while subjects listened to rhythmic sequences. Predictability was manipulated by changing the stimulus-onset-asynchrony (SOA deviants) for given tones in the rhythm. When SOA deviants were inserted rarely, predictability remained high, whereas predictability was lower with more frequent SOA deviants. Dichotic tone-presentation allowed for independent manipulation of attention, as specific tones of the rhythm were presented to separate ears. Attention was manipulated by instructing subjects to attend to tones in one ear only, while keeping the rhythmic structure of tones constant. The analyses of event-related potentials revealed an attenuated N1 for tones when rhythm predictability was high, while the N1 was enhanced by attention to tones. Bayesian statistics revealed no interaction between predictability and attention. A right-lateralization of attention effects, but not predictability effects, suggested potentially different cortical processes. This is the first study to show that probability of rhythm violation influences rhythm predictability, independent of attention.

Objective Behavioral studies have shown that anorexia nervosa (AN) is associated with attentional bias to general threat cues. The neurobiological underpinnings of attentional bias to threat in AN are unknown. This study investigated the neural responses associated with threat-detection and attentional bias to threat in AN. Methods We measured neural responses to a dot-probe task, involving pairs of angry and neutral face stimuli, in 22 adult women recovered from AN and 21 comparison women. Results Recovered AN women did not exhibit a behavioral attentional bias to threat. In response to angry faces, recovered women showed significant hypoactivation in the extrastriate cortex. During attentional bias to angry faces, recovered women showed significant hyperactivation in the medial prefrontal cortex. This was because of significant deactivation in comparison women, which was absent in recovered AN women. Conclusions Women recovered from AN are characterized by altered neural responses to threat cues. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

The pathophysiology of anorexia nervosa (AN) is not completely understood, but research suggests that alterations in brain circuits related to cognitive control and emotion are central. The aim of this study was to explore neural responses to an emotional conflict task in women recovered from AN. Functional magnetic resonance imaging was used to measure neural responses to an emotional conflict task in 22 women recovered from AN and 21 age-matched healthy controls. The task involved categorizing affective faces while ignoring affective words. Face and word stimuli were either congruent (non-conflict) or incongruent (conflict). Brain responses to emotional conflict did not differ between groups. However, in response to emotional non-conflict, women recovered from AN relative to healthy controls showed significantly less activation in the bilateral amygdala. Specifically, while emotional non-conflict evoked significant activations of the amygdala in healthy controls, recovered AN women did not show such activations. Similar significant group differences were also observed in the hippocampus and basal ganglia. These results suggest that women recovered from AN are characterized by alterations within emotion-related brain circuits. Recovered women's absence of amygdala and hippocampus activation during non-conflict trials possibly reflects an impaired ability to process emotional significant stimuli.

Patients with anorexia nervosa (AN) exhibit volume reduction in cerebral gray matter (GM), and several studies report reduced hippocampus volume. The hippocampal subfields (HS) are functionally and structurally distinct, and appear to respond differently to neuropathology. The aim of this study was to investigate HS volumes in adolescent females with restrictive AN compared to a healthy age-matched control group (HC). The FreeSurfer v6.0 package was used to extract brain volumes, and segment HS in 58 female adolescents (AN = 30, HC = 28). We investigated group differences in GM, white matter (WM), whole hippocampus and 12 HS volumes. AN patients had significantly lower total GM and total hippocampal volume. No group difference was found in WM. Volume reduction was found in 11 of the 12 HS, and most results remained significant when adjusting for global brain volume reduction. Investigations of clinical covariates revealed statistically significant relationships between the whole hippocampus, several HS and scores on depression and anxiety scales in AN. Results from this study show that young AN patients exhibit reduced volume in most subfields of the hippocampus, and that this reduction may be more extensive than the observed global cerebral volume loss.

Retention of features in visual short-term memory (VSTM) involves maintenance of sensory traces in early visual cortex. However, the mechanism through which this is accomplished is not known. Here, we formulate specific hypotheses derived from studies on feature-based attention to test the prediction that visual cortex is recruited by attentional mechanisms during VSTM of low-level features. Functional magnetic resonance imaging (fMRI) of human visual areas revealed that neural populations coding for task-irrelevant feature information are suppressed during maintenance of detailed spatial frequency memory representations. The narrow spectral extent of this suppression agrees well with known effects of feature-based attention. Additionally, analyses of effective connectivity during maintenance between retinotopic areas in visual cortex show that the observed highlighting of task-relevant parts of the feature spectrum originates in V4, a visual area strongly connected with higher-level control regions and known to convey top–down influence to earlier visual areas during attentional tasks. In line with this property of V4 during attentional operations, we demonstrate that modulations of earlier visual areas during memory maintenance have behavioral consequences, and that these modulations are a result of influences from V4.

BackgroundDisturbances in Pavlovian valuation systems are reported to follow traumatic stress exposure. However, motivated decisions are also guided by instrumental mechanisms, but to date the effect of traumatic stress on these instrumental systems remain poorly investigated. Here, we examine whether a single episode of severe traumatic stress influences flexible instrumental decisions through an impact on a Pavlovian system.MethodsTwenty-six survivors of the 2011 Norwegian terror attack and 30 matched control subjects performed an instrumental learning task in which Pavlovian and instrumental associations promoted congruent or conflicting responses. We used reinforcement learning models to infer how traumatic stress affected learning and decision-making. Based on the importance of dorsal anterior cingulate cortex (dACC) for cognitive control, we also investigated if individual concentrations of Glx (=glutamate + glutamine) in dACC predicted the Pavlovian bias of choice.ResultsSurvivors of traumatic stress expressed a greater Pavlovian interference with instrumental action selection and had significantly lower levels of Glx in the dACC. Across subjects, the degree of Pavlovian interference was negatively associated with dACC Glx concentrations.ConclusionsExperiencing traumatic stress appears to render instrumental decisions less flexible by increasing the susceptibility to Pavlovian influences. An observed association between prefrontal glutamatergic levels and this Pavlovian bias provides novel insight into the neurochemical basis of decision-making, and suggests a mechanism by which traumatic stress can impair flexible instrumental behaviours.

Structural brain changes associated with starvation and clinical measurements were explored in four females with anorexia nervosa with different clinical course, at baseline and 1-year follow-up, after receiving intensive inpatient treatment at a specialized eating disorder unit. Global volume alterations were associated with weight changes. Regional volume alterations were also associated with weight changes, with the largest changes occurring in the nucleus accumbens, amygdala, pallidum, and putamen. Largest changes in cortical thickness occurred in the frontal and temporal lobes. The results are preliminary; however, they show that fluctuations in weight are associated with brain volume alterations, especially gray matter. We suggest that these parts of the brain are vulnerable to starvation and malnutrition, and could be a part of the pathophysiology of AN.

The prefrontal cortex (PFC) plays a central role in preparatory and anticipatory attentional processes. To investigate whether subregions of the PFC play differential roles in these processes we investigated the effect of focal lesions to either lateral prefrontal (lateral PFC; n=11) or orbitofrontal cortex (OFC; n=13) on the contingent negative variation (CNV), an electrophysiological index of preparatory brain processes. The CNV was studied using a Go/NoGo delayed response task where an auditory S1 signaled whether or not an upcoming visual S2 was a Go or a NoGo stimulus. Neither early (500-1000 ms) nor late (3200-3700 ms) phase Go trial CNV amplitude was reduced for any of the patient groups in comparison to controls. However, the lateral PFC group showed enhanced Go trial early CNV and reduced late CNV Go/NoGo differentiation. These data suggests that normal orienting and evaluation as reflected by the CNV is intact after OFC lesions. The enhanced early CNV after lateral PFC damage may be due to failure in inhibition and the reduced late CNV difference wave confirms a deficit in preparatory attention after damage to this frontal subregion.

Background We examined women with recurrent brief depression (RBD) with and without episodes of hypomania with an n -back working memory paradigm to assess how working memory load affects the neurological network corresponding to working memory for these groups. Method Participants ( n =33) were medication-free and mostly euthymic while performing a 1-back and a 2-back task in the fMRI scanner. Differential activation results between the tasks were assessed globally and within seven predefined regions of interest associated with working memory activation. The patient groups were compared with healthy women and matched for age, handedness, and length of education. Results Poor task modulation was observed in both RBD groups in the prefrontal cortex (BA9) in the 1-back task and activation during the 2-back task, particularly in a subgroup with a history of brief hypomanic episodes (RBD-H) compared with the subgroup without such episodes (RBD-O). Task modulation in the right parahippocampal gyrus (BA27) distinguished the RBD-O group, and task modulation in the right insula clearly distinguished the RBD-H group. Limitations Small sample size and recruitment of most patients through media that may induce a selection bias towards better-functioning subjects. Conclusion The observed lack of deactivation within the right insula has also been reported in patients with bipolar I disorders. Activation differences in BA9 and the parahippocampal region between RBD patients with and without a history of hypomania suggest different functional hypersensitivity of early limbic regions and ability to sustain attention and working memory, respectively, possibly identifying functional differences between the two subgroups.

Impaired monitoring of internally generated information has been proposed to be one component in the development and maintenance of delusions. The present study investigated the neural correlates underlying the monitoring processes and whether they were associated with delusions.Twenty healthy controls and 19 patients with schizophrenia spectrum disorders were administrated a reality monitoring paradigm during functional magnetic resonance imaging. During encoding participants were instructed to associate a statement with either a presented (viewed condition) or an imagined picture (imagined condition). During the monitoring session in the scanner, participants were presented with old and new statements and their task was to identify whether a given statement was associated with the viewed condition, imagined condition, or if it was new.Patients showed significantly reduced accuracy in the imagined condition with performance negatively associated with degree of delusions. This was accompanied with reduced activity in the left dorsolateral prefrontal cortex and left hippocampus in the patient group. The severity of delusions was negatively correlated with the blood-oxygenation-level dependent response in the left hippocampus.The results suggest that weakened monitoring is associated with delusions in patients with schizophrenia spectrum disorder, and that this may be mediated by a frontotemporal dysfunction.

Down regulation of serotonin transporter (5-HTT) expression has been associated with brain function and major depression. The aim of this study was to explore the allelic variation (short and long) of the 5-HTTLPR polymorphism in attention bias associated with top-down processing of emotion. One hundred sixty-two healthy participants underwent genotyping (5-HTTLPR), background interviews, psychological screening, and a computerised test session (The Emo 1-back task). Carriers of the short 5-HTTLPR alleles in the serotonin transporter gene (SLC6A4) demonstrated less accuracy in The Emo 1-back task when presented with successive images of sad or fearful faces, but not for happy or neutral emotional faces. The study suggests an association between 5-HTTLPR variation in the serotonin transporter gene and altered emotion processing.

Objective: Studies point to white matter (WM) microstructure alterations in both adolescent and adult patients with anorexia nervosa (AN). These include reduced fractional anisotropy in several WM fiber tracts, suggesting reduced WM integrity. The extent to which these alterations are reversible with recovery from AN is unclear. There is a paucity of research investigating the presence of WM microstructure alterations in recovered AN patients, and results are inconsistent. This study aimed to investigate the presence of WM microstructure alterations in women long-term recovered from AN. Method: Twenty-one adult women who were recovered from AN for at least one year were compared to 21 adult comparison women. Participants were recruited via user-organizations for eating disorders, local advertisements, and online forums. Diffusion tensor imaging was used to compare WM microstructure between groups. Correlations between WM microstructure and clinical characteristics were also explored. Results: There were no statistically significant between-group differences in WM microstructure. These null-findings remained when employing liberal alpha level thresholds. Furthermore, there were no statistically significant correlations between WM microstructure and clinical characteristics. Discussion: Our findings showed normal WM microstructure in long-term recovered patients, indicating the alterations observed during the acute phase are reversible. Given the paucity of research and inconsistent findings, future studies are warranted to determine the presence of WM microstructure alterations following recovery from AN. The final version of this research has been published in the Journal of Eating Disorders. © 2017 BioMed Central

Impairments in cognition, pain intolerance, and physical inactivity characterize adolescent chronic fatigue syndrome (CFS), yet little is known about its neurobiology. The right dorsal anterior insular (dAI) connectivity of the salience network provides a motivational context to stimuli. In this study, we examined regional functional connectivity (FC) patterns of the right dAI in adolescent CFS patients and healthy participants. Eighteen adolescent patients with CFS and 18 aged-matched healthy adolescent control participants underwent resting-state functional magnetic resonance imaging. The right dAI region of interest was examined in a seed-to-voxel resting-state FC analysis using SPM and CONN toolbox. Relative to healthy adolescents, CFS patients demonstrated reduced FC of the right dAI to the right posterior parietal cortex (PPC) node of the central executive network. The decreased FC of the right dAI–PPC might indicate impaired cognitive control development in adolescent CFS. Immature FC of the right dAI–PPC in patients also lacked associations with three known functional domains: cognition, pain and physical activity, which were observed in the healthy group. These results suggest a distinct biological signature of adolescent CFS and might represent a fundamental role of the dAI in motivated behavior. Norwegian Research Council, http:// www.forskningsradet.no/en (VBW, grant number 228874); South-Eastern Norway Regional Health Authority, https://www.helse-sorost.no/south- eastern-norway-regional-health-authority (VBW); and the University of Oslo, http://www.uio.no/ english/ (VBW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The ability to represent and select information in working memory provides the neurobiological infrastructure for human cognition. For 80 years, dominant views of working memory have focused on the key role of prefrontal cortex (PFC) [1–8]. However, more recent work has implicated posterior cortical regions [9–12], suggesting that PFC engagement during working memory is dependent on the degree of executive demand. We provide evidence from neurological patients with discrete PFC damage that challenges the dominant models attributing working memory to PFC-dependent systems. We show that neural oscillations, which provide a mechanism for PFC to communicate with posterior cortical regions [13], independently subserve communications both to and from PFC – uncovering parallel oscillatory mechanisms for working memory. Fourteen PFC patients and 20 healthy, age-matched controls performed a working memory task where they encoded, maintained, and actively processed information about pairs of common shapes. In controls, the electroencephalogram (EEG) exhibited oscillatory activity in the low-theta range over PFC and directional connectivity from PFC to parieto-occipital regions commensurate with executive processing demands. Concurrent alpha-beta oscillations were observed over parieto-occipital regions, with directional connectivity from parieto-occipital regions to PFC, regardless of processing demands. Accuracy, PFC low-theta activity, and PFC ➔ parieto-occipital connectivity were attenuated in patients, revealing a PFC-independent, alpha-beta system. The PFC patients still demonstrated task proficiency, which indicates that the posterior alpha-beta system provides sufficient resources for working memory. Taken together, our findings reveal neurologically dissociable PFC and parieto-occipital systems, and suggest that parallel, bidirectional oscillatory systems form the basis of working memory.

Humans are highly social beings that interact with each other on a daily basis. In these complex interactions, we get along by being able to identify others' actions and infer their intentions, thoughts and feelings. One of the major theories accounting for this critical ability assumes that the understanding of social signals is based on a primordial tendency to simulate observed actions by activating a mirror neuron system. If mirror neuron regions are important for action and emotion recognition, damage to regions in this network should lead to deficits in these domains. In the current behavioural and EEG study, we focused on the lateral prefrontal cortex including dorsal and ventral prefrontal cortex and utilized a series of task paradigms, each measuring a different aspect of recognizing others' actions or emotions from body cues. We examined 17 patients with lesions including (n = 8) or not including (n = 9) the inferior frontal gyrus, a core mirror neuron system region, and compared their performance to matched healthy control subjects (n = 18), in behavioural tasks and in an EEG observation-execution task measuring mu suppression. Our results provide support for the role of the lateral prefrontal cortex in understanding others' emotions, by showing that even unilateral lesions result in deficits in both accuracy and reaction time in tasks involving the recognition of others' emotions. In tasks involving the recognition of actions, patients showed a general increase in reaction time, but not a reduction in accuracy. Deficits in emotion recognition can be seen by either direct damage to the inferior frontal gyrus, or via damage to dorsal lateral prefrontal cortex regions, resulting in deteriorated performance and less EEG mu suppression over sensorimotor cortex.

Citation: Laura Anne Wortinger, Tor Endestad, Annika Maria D Melinder, Merete Glenne Øie, Dag Sulheim, Even Fagermoen & Vegard Bruun Wyller (2016) Emotional conflict processing in adolescent chronic fatigue syndrome: A pilot study using functional magnetic resonance imaging, Journal of Clinical and Experimental Neuropsychology, 39:4, 355-368, DOI: 10.1080/13803395.2016.1230180 Introduction: Studies of neurocognition suggest that abnormalities in cognitive control contribute to the pathophysiology of chronic fatigue syndrome (CFS) in adolescents, yet these abnormalities remain poorly understood at the neurobiological level. Reports indicate that adolescents with CFS are significantly impaired in conflict processing, a primary element of cognitive control. Method: In this study, we examine whether emotional conflict processing is altered on behavioral and neural levels in adolescents with CFS and a healthy comparison group. Fifteen adolescent patients with CFS and 24 healthy adolescent participants underwent functional magnetic resonance imaging (fMRI) while performing an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect labeled words. Results: Adolescent CFS patients were less able to engage the left amygdala and left midposterior insula (mpINS) in response to conflict than the healthy comparison group. An association between accuracy interference and conflict-related reactivity in the amygdala was observed in CFS patients. A relationship between response time interference and conflict-related reactivity in the mpINS was also reported. Neural responses in the amygdala and mpINS were specific to fatigue severity. Conclusions: These data demonstrate that adolescent CFS patients displayed deficits in emotional conflict processing. Our results suggest abnormalities in affective and cognitive functioning of the salience network, which might underlie the pathophysiology of adolescent CFS. This study is part of the NorCAPITAL-project (The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial) (Clinical Trials ID: NCT01040429). It was conducted at the Department of Pediatrics, Oslo University Hospital, Norway, which is a national referral center for young CFS patients. The current study is based on cross-sectional data collected during the first clinical in-hospital day of NorCAPITAL, from March 2010 to May 2012. All participants received a gift-card worth NOK 200. This work was supported by the Norwegian Research Council (VBW, grant number 228874); 498 Health South–East Hospital Trust (VBW); and the University of Oslo (VBW).

Behavioral studies have shown that anorexia nervosa (AN) is associated with attentional bias to general threat cues. The neurobiological underpinnings of attentional bias to threat in AN are unknown. This study investigated the neural responses associated with threat-detection and attentional bias to threat in AN.We measured neural responses to a dot-probe task, involving pairs of angry and neutral face stimuli, in 22 adult women recovered from AN and 21 comparison women.Recovered AN women did not exhibit a behavioral attentional bias to threat. In response to angry faces, recovered women showed significant hypoactivation in the extrastriate cortex. During attentional bias to angry faces, recovered women showed significant hyperactivation in the medial prefrontal cortex. This was because of significant deactivation in comparison women, which was absent in recovered AN women.Women recovered from AN are characterized by altered neural responses to threat cues. Copyright © 2016 John WileySons, Ltd and Eating Disorders Association.

This is an Open Access article licensed under the Creative Commons Attribution License 3.0 (CC BY 3.0) and originally published in European Journal of Psychotraumatology. You can access the article by following this link: http://dx.doi.org10.3402/ejpt.v7.31314 Dette er en vitenskapelig, fagfellevurdert artikkel som opprinnelig ble publisert i European Journal of Psychotraumatology. Artikkelen er publisert under lisensen Creative Commons Attribution License 3.0 (CC BY 3.0). Du kan også få tilgang til artikkelen ved å følge denne lenken: http://dx.doi.org10.3402/ejpt.v7.31314 Background: In studies employing physiological measures such as magnetic resonance imaging (MRI), it is often hard to distinguish what constitutes risk-resilience factors to posttraumatic stress disorder (PTSD) following trauma exposure and what the effects of trauma exposure and PTSD are. Objective: We aimed to investigate whether there were observable morphological differences in cortical and sub-cortical regions of the brain, 7–8 years after a single potentially traumatic event. Methods: Twenty-four participants, who all directly experienced the 2004 Indian Ocean Tsunami, and 25 controls, underwent structural MRI using a 3T scanner. We generated cortical thickness maps and parcellated sub-cortical volumes for analysis. Results: We observed greater cortical thickness for the trauma-exposed participants relative to controls, in a right lateralized temporal lobe region including anterior fusiform gyrus, and superior, middle, and inferior temporal gyrus. Conclusions: We observed greater thickness in the right temporal lobe which might indicate that the region could be implicated in resilience to the long-term effects of a traumatic event. We hypothesize this is due to altered emotional semantic memory processing. However, several methodological and confounding issues warrant caution in interpretation of the results.

Background Anorexia nervosa (AN) is a severe mental illness, with an unknown etiology. Magnetic resonance imaging studies show reduced brain volumes and cortical thickness in patients compared to healthy controls. However, findings are inconsistent, especially concerning the anatomical location and extent of the differences. The purpose of this study was to estimate and compare brain volumes and regional cortical thickness in young females with AN and healthy controls. Methods Magnetic resonance imaging data was acquired from young females with anorexia nervosa (n = 23) and healthy controls (n = 28). Two different scanner sites were used. BMI varied from 13.5 to 20.7 within the patient group, and 11 patients had a BMI > 17.5. FreeSurfer was used to estimate brain volumes and regional cortical thickness. Results There were no differences between groups in total cerebral cortex volume, white matter volume, or lateral ventricle volume. There were also no volume differences in subcortical grey matter structures. However the results showed reduced cortical thickness bilaterally in the superior parietal gyrus, and in the right inferior parietal and superior frontal gyri. Conclusions The functional significance of the findings is undetermined as the majority of the included patients was already partially weight-restored. We discuss whether these regions could be related to predisposing factors of the illness, or whether they are regions that are more vulnerable to starvation, malnutrition or associated processes in AN.

Executive dysfunction is a common consequence of acquired brain injury (ABI), causing significant disability in daily life. This randomized controlled trial investigated the efficacy of Goal Management TrainingTM(GMT) in improving executive functioning in patients with chronic ABI. Seventy patients with a verified ABI and executive dysfunction were randomly allocated to GMT (n=33) or a psycho-educative active control condition, Brain Health Workshop (BHW) (n=37). In addition, all participants received external cueing by text messages. Neuropsychological tests and self-reported questionnaires of executive functioning were administered pre-intervention, immediately after intervention, and at 6 months follow-up. Assessors were blinded to group allocation. Questionnaire measures indicated significant improvement of everyday executive functioning in the GMT group, with effects lasting at least 6 months post-treatment. Both groups improved on the majority of the applied neuropsychological tests. However, improved performance on tests demanding executive attention was most prominent in the GMT group. The results indicate that GMT combined with external cueing is an effective metacognitive strategy training method, ameliorating executive dysfunction in daily life for patients with chronic ABI. The strongest effects were seen on self-report measures of executive functions 6 months post-treatment, suggesting that strategies learned in GMT were applied and consolidated in everyday life after the end of training. Furthermore, these findings show that executive dysfunction can be improved years after the ABI. (JINS, 2016,22, 436–452)

A significant number of adolescents have been exposed to traumatic life events. However, knowledge about the specific sleep disturbance that occurs in individuals after trauma exposure is predominantly based on studies of adults. This study reports specific sleep disturbance in 42 survivors of the 2011 mass shooting at a youth summer camp on the Norwegian island Utøya, mean age = 20.91 years, SD = 2.32, 62.5% females. When compared with matched controls, significantly more survivors reported having sleep disturbances, 52.4% versus 13.6%, d = 0.93, of which onset began at the time of the shooting, χ

Objective: This study examined the effects of chronic focal lesions to the lateral prefrontal cortex (LPFC) or orbitofrontal cortex (OFC) on neuropsychological test performance and self-reported executive functioning in everyday living. Methods: Fourteen adults with OFC lesions were compared to 10 patients with LPFC injuries and 21 healthy controls. Neuropsychological tests with emphasis on measures of cognitive executive function were administered along with the Behavior Rating Inventory of Executive Functions (BRIEF-A) and a psychiatric screening instrument. Results: The LPFC group differed from healthy controls on neuropsychological tests of sustained mental effort, response inhibition, working memory and mental switching, while the BRIEF-A provided more clinically important information on deficits in everyday life in the OFC group compared to the LPFC group. Correlations between neuropsychological test results and BRIEF-A were weak, while the BRIEF-A correlated strongly with emotional distress. Conclusions: It was demonstrated that LPFC damage is particularly prone to cause cognitive executive deficit, while OFC injury is more strongly associated with self-reported dysexecutive symptoms in everyday living. The study illustrates the challenge of identifying executive deficit in individual patients and the lack of strong anatomical specificity of the currently employed methods. There is a need for an integrative methodological approach where standard testing batteries are supplemented with neuropsychiatric and frontal-specific rating scales.

We recorded by use of an infrared eye-tracker the pupil diameters of participants while they observed visual illusions of lightness or brightness. Four original illusions {based on Gaetano Kanisza's [Kanizsa G (1976) Subjective contours. Sci Am 234:48–52] and Akiyoshi Kitaoka's [Kitaoka A. (2005) Trick Eyes (Barnes & Noble, New Providence, NJ).] examples} were manipulated to obtain control conditions in which the perceived illusory luminance was either eliminated or reduced. All stimuli were equiluminant so that constrictions in pupillary size could not be ascribed to changes in light energy. We found that the pupillary diameter rapidly varied according to perceived brightness and lightness strength. Differences in local contrast information could be ruled out as an explanation because, in a second experiment, the observers maintained eye fixation in the center of the display; thus, differential stimulation of the fovea by local contrast changes could not be responsible for the pupillary differences. Hence, the most parsimonious explanation for the present findings is that pupillary responses to ambient light reflect the perceived brightness or lightness of the scene and not simply the amount of physical light energy entering the eye. Thus, the pupillary physiological response reflects the subjective perception of light and supports the idea that the brain's visual circuitry is shaped by visual experience with images and their possible sources.

The concept of perceptual memory refers to the neural and cognitive processes underlying the storage of specific stimulus features such as spatial frequency, orientation, shape, contrast, and color. Psychophysical studies of perceptual memory indicate that observers can retain visual information about the spatial frequency of Gabor patterns independent of the orientation with which they are presented. Compared to discrimination of gratings with the same orientation, reaction times to orthogonally oriented gratings, however, increase suggesting additional processing. Using event-related fMRI we examined the pattern of neural activation evoked when subjects discriminated the spatial frequency of Gabors presented with the same or orthogonal orientation. Blood-oxygen level dependent BOLD fMRI revealed significantly elevated bilateral activity in visual areas (V1, V2) when the gratings to be compared had an orthogonal orientation, compared to when they had the same orientation. These findings suggest that a change in an irrelevant stimulus dimension requires additional processing in primary and secondary visual areas. The finding that the task-irrelevant stimulus property (orientation) had no significant effect on the prefrontal and intraparietal cortex supports a model of working memory in which discrimination and retention of basic stimulus dimensions is based on low-level perceptual memory stores that are located at an early stage in the visual process. Our findings suggest that accessing different stores requires time and has higher metabolic costs.

This study investigated whether treatment naïve adults with Attention Deficit Hyperactivity Disorder (ADHD; n = 33; 19 female) differed from healthy controls (n = 31; 17 female) in behavioral performance, event-related potential (ERP) indices of preparatory attention (CueP3 and late CNV), and reactive response control (Go P3, NoGo N2, and NoGo P3) derived from a visual cued Go/NoGo task. On several critical measures, Cue P3, late CNV, and NoGo N2, there were no significant differences between the groups. This indicated normal preparatory processes and conflict monitoring in ADHD patients. However, the patients had attenuated Go P3 and NoGoP3 amplitudes relative to controls, suggesting reduced allocation of attentional resources to processes involved in response control. The patients also had a higher rate of Go signal omission errors, but no other performance decrements compared with controls. Reduced Go P3 and NoGo P3 amplitudes were associated with poorer task performance, particularly in the ADHD group. Notably, the ERPs were not associated with self-reported mood or anxiety. The results provide electrophysiological evidence for reduced effortful engagement of attentional resources to both Go and NoGo signals when reactive response control is needed. The absence of group differences in ERP components indexing proactive control points to impairments in specific aspects of cognitive processes in an untreated adult ADHD cohort. The associations between ERPs and task performance provided additional support for the altered electrophysiological responses. Copyright: © 2016 Grane et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

There are values missing from the SD column in Table 1. Please see the corrected Table 1 here.

Terror attacks cause variation in everyday functioning across several domains. This paper focuses on the individual long-term costs in terms of clinical symptoms and cognitive (e.g., shifting, inhibition, and spatial working memory) difficulties associated with these symptoms in 24 survivors of a terror attack in Norway. Another 24 controls were included for comparison purposes. Participants were administered a battery of clinical and neurocognitive tests. RESULTS showed that all clinical variables differed as a function of group, ps ≤.001, η2 ≥.64, but no significant differences were revealed for the neurocognitive measures. In the survivor group, shifting capacity and its interaction with gender predicted intrusion symptoms, p =.045, ηp2 =.338, and symptoms of avoidance, p =.008, ηp2 =.453. We discuss the findings in relation to theoretical models and therapeutic interventions. (PsycINFO Database Record Language: en

The development of episodic memory, its relation to theory of mind (ToM), executive functions (e.g., cognitive inhibition), and to suggestibility was studied. Children (n= 115) between 3 and 6 years of age saw two versions of a video film and were tested for their memory of critical elements of the videos. Results indicated similar developmental trends for all memory measures, ToM, and inhibition, but ToM and inhibition were not associated with any memory measures. Correlations involving source memory was found in relation to specific questions, whereas inhibition and ToM were significantly correlated to resistance to suggestions. A regression analysis showed that age was the main contributor to resistance to suggestions, to correct source monitoring, and to correct responses to specific questions. Inhibition was also a significant main predictor of resistance to suggestive questions, whereas the relative contribution of ToM was wiped out when an extended model was tested.

The recognition memory of words and pictures was tested following a study session where the stimuli entered metaphorical or literal decision tasks. The results confirmed a picture superiority effect in the sense that the memory for pictures under all conditions was better than the memory for words. However, a metaphorical task at study had opposite effects on the long-term memory for pictures and words, producing better memory for words and poorer memory for pictures compared to a literal decision task at study. The results are interpreted within the concept of dual coding.

Functional neuroimaging studies consistently report language-related cerebellar activations, but evidence from the clinical literature is less conclusive. Here, we attempt to bridge this gap by testing the effect of focal cerebellar lesions on cerebral activations in a reading task previously shown to involve distinct cerebellar regions. Patients (N = 10) had lesions primarily affecting medial cerebellum, overlapping cerebellar regions activated during the presentation of random word sequences, but distinct from activations related to semantic prediction generation and prediction error processing. In line with this pattern of activation–lesion overlap, patients did not differ from matched healthy controls (N = 10) in predictability-related activations. However, whereas controls showed increased activation in bilateral auditory cortex and parietal operculum when silently reading familiar words relative to viewing letter strings, this effect was absent in the patients. Our results highlight the need for careful lesion mapping and suggest possible roles for the cerebellum in visual-to-auditory mapping and/or inner speech.