Loss, gain and choice difficulty in gambling patients: Neural and behavioural processes.

Impaired decision-making is often displayed by individuals suffering from gambling disorder (GD). Since there are a variety of different phenomena influencing decision-making, we focused in this study on the effects of GD on neural and behavioural processes related to loss aversion and choice difficulty. Behavioural responses as well as brain images of 23 patients with GD and 20 controls were recorded while they completed a mixed gambles task, where they had to decide to either accept or reject gambles with different amounts of potential gain and loss. We found no behavioural loss aversion in either group and no group differences regarding loss and gain-related choice behaviour, but there was a weaker relation between choice difficulty and decision time in patients with GD. Similarly, we observed no group differences in processing of losses or gains, but choice difficulty was weaker associated with brain activity in the right anterior insula and anterior cingulate cortex in patients with GD. Our results showed for the first time the effects of GD on neural processes related to choice difficulty. In addition, our findings on choice difficulty give new insights on the psychopathology of GD and on neural processes related to impaired decision-making in GD.

The vascular locked-in and locked-in-plus syndrome: A retrospective case series.

The locked-in syndrome (LiS) is defined as the loss of most voluntary muscle movements with preserved cognitive abilities due to a ventral pontine lesion. However, some patients may also have severe impairment of consciousness [locked-in plus syndrome (LiPS)]. Here we aimed to explore structural differences between LiS and LiPS patients of vascular aetiology, focusing on lesion patterns and locations to better delineate the clinical spectrum of LiS and LiPS. In this retrospective case series study, we report nine patients (two women), ages 29-74 years (median 50) with LiS and LiPS who were diagnosed between 2007 and 2021. Clinical parameters, MRI findings including the lesioned structures, and a shape feature calculation are presented for every patient. The lesioned structures were determined by a senior neuroradiologist. Two of nine patients had fully retained consciousness (LiS) and seven showed various degrees of impaired consciousness (LiPS). Lesions of LiS patients are round and confined to the pons, whereas lesions of LiPS patients are more elongated and reach neighbouring areas such as the mesencephalon, thalamus or ascending reticular activating system. Lesions involving the mesencephalon and the thalamus are strong indicators of LiPS, whereas for lesions restricted to the pons, the dorsal extension and the associated damage to the ascending reticular activating system are crucial to differentiate LiS from LiPS. Recognizing LiPS using clinical and radiological findings is important as these patients may need different therapies and care and, most importantly, should not be mistaken as unresponsive wakefulness syndrome.

Recognition and perception of emotions in juvenile myoclonic epilepsy.

OBJECTIVE: Perception and recognition of emotions are fundamental prerequisites of human life. Patients with juvenile myoclonic epilepsy (JME) may have emotional and behavioral impairments that might influence socially desirable interactions. We aimed to investigate perception and recognition of emotions in patients with JME by means of neuropsychological tests and functional magnetic resonance imaging (fMRI). METHODS: Sixty-five patients with JME (median age = 27 years, interquartile range [IQR] = 23-34) were prospectively recruited at the Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria. Patients were compared to 68 healthy controls (median age = 24 years, IQR = 21-31), matched for sex, age, and education. All study participants underwent the Networks of Emotion Processing test battery (NEmo), an fMRI paradigm of "dynamic fearful faces," a structured interview for psychiatric and personality disorders, and comprehensive neuropsychological testing. RESULTS: JME patients versus healthy controls demonstrated significant deficits in emotion recognition in facial and verbal tasks of all emotions, especially fear. fMRI revealed decreased amygdala activation in JME patients as compared to healthy controls. Patients were at a higher risk of experiencing psychiatric disorders as compared to healthy controls. Cognitive evaluation revealed impaired attentional and executive functioning, namely psychomotor speed, tonic alertness, divided attention, mental flexibility, and inhibition of automated reactions. Duration of epilepsy correlated negatively with parallel prosodic and facial emotion recognition in NEmo. Deficits in emotion recognition were not associated with psychiatric comorbidities, impaired attention and executive functions, types of seizures, and treatment. SIGNIFICANCE: This prospective study demonstrated that as compared to healthy subjects, patients with JME had significant deficits in recognition and perception of emotions as shown by neuropsychological tests and fMRI. The results of this study may have importance for psychological/psychotherapeutic interventions in the management of patients with JME.

Ageing as risk factor for tinnitus and its complex interplay with hearing loss-evidence from online and NHANES data.

BACKGROUND: Tinnitus affects 10 to 15% of the population, but its underlying causes are not yet fully understood. Hearing loss has been established as the most important risk factor. Ageing is also known to accompany increased prevalence; however, the risk is normally seen in context with (age-related) hearing loss. Whether ageing per se is a risk factor has not yet been established. We specifically focused on the effect of ageing and the relationship between age, hearing loss, and tinnitus. METHODS: We used two samples for our analyses. The first, exploratory analyses comprised 2249 Austrian individuals. The second included data from 16,008 people, drawn from a publicly available dataset (NHANES). We used logistic regressions to investigate the effect of age on tinnitus. RESULTS: In both samples, ageing per se was found to be a significant predictor of tinnitus. In the more decisive NHANES sample, there was an additional interaction effect between age and hearing loss. Odds ratio analyses show that per unit increase of hearing loss, the odds of reporting tinnitus is higher in older people (1.06 vs 1.03). CONCLUSIONS: Expanding previous findings of hearing loss as the main risk factor for tinnitus, we established ageing as a risk factor in its own right. Underlying mechanisms remain unclear, and this work calls for urgent research efforts to link biological ageing processes, hearing loss, and tinnitus. We therefore suggest a novel working hypothesis that integrates these aspects from an ageing brain viewpoint.

Age-related differences in interference control in the context of a finger-lifting task: an fMRI study.

Humans tend to automatically imitate others and their actions while also being able to control such imitative tendencies. Interference control, necessary to suppress own imitative tendencies, develops rapidly in childhood and adolescence, plateaus in adulthood and slowly declines with advancing age. It remains to be shown though which neural processes underpin these differences across the lifespan. In a cross-sectional functional magnetic resonance imaging study with three age groups (adolescents (ADs) 14-17 years, young adults (YAs) 21-31, older adults (OAs) 56-76, N = 91 healthy female participants), we investigated the behavioral and neural correlates of interference control in the context of automatic imitation using the finger-lifting task. ADs showed the most efficient interference control, while no significant differences emerged between YAs and OAs, despite OAs showing longer reaction times. On the neural level, all age groups showed engagement of the right temporoparietal junction, right supramarginal gyrus and bilateral insula, aligning well with studies previously using this task. However, our analyses did not reveal any age-related differences in brain activation, neither in these nor in other areas. This suggests that ADs might have a more efficient use of the engaged brain networks and, on the other hand, OAs' capacity for interference control and the associated brain functions might be largely preserved.

Intrinsic neural timescales in autism spectrum disorder and schizophrenia. A replication and direct comparison study.

Intrinsic neural timescales (INT) reflect the duration for which brain areas store information. A posterior-anterior hierarchy of increasingly longer INT has been revealed in both typically developed individuals (TD), as well as persons diagnosed with autism spectrum disorder (ASD) and schizophrenia (SZ), though INT are, overall, shorter in both patient groups. In the present study, we aimed to replicate previously reported group differences by comparing INT of TD to ASD and SZ. We partially replicated the previously reported result, showing reduced INT in the left lateral occipital gyrus and the right post-central gyrus in SZ compared to TD. We also directly compared the INT of the two patient groups and found that these same two areas show significantly reduced INT in SZ compared to ASD. Previously reported correlations between INT and symptom severity were not replicated in the current project. Our findings serve to circumscribe the brain areas that can potentially play a determinant role in observed sensory peculiarities in ASD and SZ.

Differential Orbitofrontal Cortex Responses to Chocolate Images While Performing an Approach-Avoidance Task in the MRI Environment.

Background: Chocolate is one of the most frequently craved foods, and it often challenges self-regulation. These cravings may be underpinned by a neural facilitation of approach behavior toward chocolate. This preregistered study investigated the behavioral and neural correlates of such a bias using functional magnetic resonance imaging (fMRI) and reaction times (RTs). Methods: A total of n = 30 frequent chocolate eaters performed a relevant-feature approach-avoidance task (AAT) in the MRI scanner using buttons to enlarge (approach) or to shrink (avoid) pictures of chocolate and inedible control objects. We tested (a) whether implicit RT-based approach biases could be measured in a supine position in the scanner, (b) whether those biases were associated with activity in reward-related brain regions such as the insula, amygdala, striatum, and orbitofrontal cortex (OFC), and (c) whether individual RT-based bias-scores correlated with measures of chocolate craving. Results: Behaviorally, we found a highly reliable approach bias toward chocolate, defined by faster RTs in the compatible conditions (approach chocolate, avoid objects) compared to the incompatible conditions (avoid chocolate, approach objects). Neurally, this compatibility effect involved activity in the left medial OFC, a neural response that was positively correlated with individual approach bias scores. Conclusions: This study shows that the relevant feature AAT can be implemented in an fMRI setting in a supine position using buttons. An approach bias toward chocolate seems related to medial OFC activation that might serve to devalue chocolate when it has to be avoided. Our demonstration of neural and behavioral approach biases for chocolate underscores the need for stimulus-specific cognitive trainings to support healthy consumption and successful self-regulation.

Emotional Word Processing in Patients With Juvenile Myoclonic Epilepsy.

Objective: According to Panksepp's hierarchical emotion model, emotion processing relies on three functionally and neuroanatomically distinct levels. These levels comprise subcortical networks (primary level), the limbic system (secondary level), and the neocortex (tertiary level) and are suggested to serve differential emotional processing. We aimed to validate and extend previous evidence of discrete and dimensional emotion processing in patient with juvenile myoclonic epilepsy (JME). Methods: We recorded brain activity of patients with JME and healthy controls in response to lexical decisions to words reflecting the discrete emotion fear and the affective dimension negativity previously suggested to rely on different brain regions and to reflect different levels of processing. In all study participants, we tested verbal cognitive functions, as well as the relationship of psychiatric conditions, seizure types and duration of epilepsy and emotional word processing. Results: In support of the hierarchical emotion model, we found an interaction of discrete emotion and affective dimensional processing in the right amygdala likely to reflect secondary level processing. Brain activity related to affective dimensional processing was found in the right inferior frontal gyrus and is suggested to reflect tertiary level processing. Psychiatric conditions, type of seizure nor mono- vs. polytherapy and duration of epilepsy within patients did not have any effect on the processing of emotional words. In addition, no differences in brain activity or response times between patients and controls were observed, despite neuropsychological testing revealed slightly decreased verbal intelligence, verbal fluency and reading speed in patients with JME. Significance: These results were interpreted to be in line with the hierarchical emotion model and to highlight the amygdala's role in processing biologically relevant stimuli, as well as to suggest a semantic foundation of affective dimensional processing in prefrontal cortex. A lack of differences in brain activity of patients with JME and healthy controls in response to the emotional content of words could point to unaffected implicit emotion processing in patients with JME.

Oral Contraceptives Modulate the Relationship Between Resting Brain Activity, Amygdala Connectivity and Emotion Recognition - A Resting State fMRI Study.

Recent research into the effects of hormonal contraceptives on emotion processing and brain function suggests that hormonal contraceptive users show (a) reduced accuracy in recognizing emotions compared to naturally cycling women, and (b) alterations in amygdala volume and connectivity at rest. To date, these observations have not been linked, although the amygdala has certainly been identified as core region activated during emotion recognition. To assess, whether volume, oscillatory activity and connectivity of emotion-related brain areas at rest are predictive of participant's ability to recognize facial emotional expressions, 72 participants (20 men, 20 naturally cycling women, 16 users of androgenic contraceptives, 16 users of anti-androgenic contraceptives) completed a brain structural and resting state fMRI scan, as well as an emotion recognition task. Our results showed that resting brain characteristics did not mediate oral contraceptive effects on emotion recognition performance. However, sex and oral contraceptive use emerged as a moderator of brain-behavior associations. Sex differences did emerge in the prediction of emotion recognition performance by the left amygdala amplitude of low frequency oscillations (ALFF) for anger, as well as left and right amygdala connectivity for fear. Anti-androgenic oral contraceptive users (OC) users stood out in that they showed strong brain-behavior associations, usually in the opposite direction as naturally cycling women, while androgenic OC-users showed a pattern similar to, but weaker, than naturally cycling women. This result suggests that amygdala ALFF and connectivity have predictive values for facial emotion recognition. The importance of the different connections depends heavily on sex hormones and oral contraceptive use.

Neuroscientific evidence for pain being a classically conditioned response to trauma- and pain-related cues in humans.

ABSTRACT: Psychological trauma is typically accompanied by physical pain, and posttraumatic stress disorder (PTSD) often cooccurs with chronic pain. Clinical reports suggest that pain after trauma may be part of re-experiencing symptomatology. Classical conditioning can underlie visual re-experiencing because intrusions can occur as conditioned responses (CRs) to trauma-related cues. If individuals also experience pain to cues previously paired with, but not inflicting nociceptive stimulation anymore (ie, conditioned stimuli, CS), conditioning could also explain re-experiencing of pain. Sixty-five participants underwent classical conditioning, where painful electrocutaneous stimulation and aversive film clips served as unconditioned stimuli (US) in a 2 (pain/no pain) × 2 (aversive/neutral film) design. Conditioned stimuli were neutral pictures depicting contextual details from the films. One day later, participants were re-exposed to CS during a memory-triggering task (MTT). We assessed pain-CRs by self-report and an fMRI-based marker of nociceptive pain, the neurological pain signature (NPS), and recorded spontaneous daily-life pain intrusions with an e-diary. During conditioning, pain-signaling CS elicited more self-reported pain and NPS responses than no-pain-signaling CS. Possibly because the aversive film masked differences in participants' responses to pain-signaling CS vs no pain-signaling CS, pain-CRs during acquisition were most evident within the neutral film condition. When participants were re-exposed to CS during MTT, self-reported pain-CRs during the neutral film condition and, although more uncertain, NPS-CRs during the aversive film condition persisted. Of importance, participants with stronger pain-CRs showed a greater probability and severity of experiencing spontaneous pain intrusions during daily life. Our data support that spatiotemporally associating innocuous cues with pain (CS) endows these cues to elicit conditioned pain responses in the absence of noxious stimulation. In this way pain can emerge as a CR with emotional and sensory components. Classical conditioning presents a possible mechanism explaining pain intrusions and, more broadly, pain experienced without a nociceptive input.

The role of right supra-marginal gyrus and secondary somatosensory cortex in age-related differences in human emotional egocentricity.

Emotional egocentric bias (EEB) occurs when, due to a partial failure in self-other distinction, empathy for another's emotion is influenced by our own emotional state. Recent studies have revealed a higher EEB in children, adolescents and older adults compared to young adults, but the neural correlates of this finding are largely unknown. We asked female participants (N = 95) from three different age groups (adolescents, young and older adults) to perform a well-validated EEB task in an MRI scanner. We assessed task-based changes in activity and effective connectivity as well as morphometric changes in regions of interest to pinpoint functional and structural age-related differences. Results revealed higher EEB in older compared to young adults and adolescents. Connectivity between right supramarginal gyrus (rSMG) and somatosensory cortices acted as a partial mediator between age and EEB. The findings suggest that an intact connectivity of rSMG, rather than its regional activity, with sensory-perceptual brain areas is crucial for overcoming egocentric biases of empathic judgments.

Reduced intrinsic neural timescales in schizophrenia along posterior parietal and occipital areas.

We computed intrinsic neural timescales (INT) based on resting-state functional magnetic resonance imaging (rsfMRI) data of healthy controls (HC) and patients with schizophrenia spectrum disorder (SZ) from three independently collected samples. Five clusters showed decreased INT in SZ compared to HC in all three samples: right occipital fusiform gyrus (rOFG), left superior occipital gyrus (lSOG), right superior occipital gyrus (rSOG), left lateral occipital cortex (lLOC) and right postcentral gyrus (rPG). In other words, it appears that sensory information in visual and posterior parietal areas is stored for reduced lengths of time in SZ compared to HC. Finally, we found that symptom severity appears to modulate INT of these areas in SZ.

Pathologically reduced neural flexibility recovers during psychotherapy of OCD patients.

Flexibility is a key feature of psychological health, allowing the individual to dynamically adapt to changing environmental demands, which is impaired in many psychiatric disorders like obsessive-compulsive disorder (OCD). Adequately responding to varying demands requires the brain to switch between different patterns of neural activity, which are represented by different brain network configurations (functional connectivity patterns). Here, we operationalize neural flexibility as the dissimilarity between consecutive connectivity matrices of brain regions (jump length). In total, 132 fMRI scans were obtained from 17 patients that were scanned four to five times during inpatient psychotherapy, and from 17 controls that were scanned at comparable time intervals. Significant negative correlations were found between the jump lengths and the symptom severity scores of OCD, depression, anxiety, and stress, suggesting that high symptom severity corresponds to inflexible brain functioning. Further analyses revealed that impaired reconfiguration (pattern stability) of the brain seems to be more related to general psychiatric impairment rather than to specific symptoms, e.g., of OCD or depression. Importantly, the group × time interaction of a repeated measures ANOVA was significant, as well as the post-hoc paired t-tests of the patients (first vs. last scan). The results suggest that psychotherapy is able to significantly increase the neural flexibility of patients. We conclude that psychiatric symptoms like anxiety, stress, depression, and OCD are associated with an impaired adaptivity of the brain. In general, our results add to the growing evidence that dynamic functional connectivity captures meaningful properties of brain functioning.

Effective Connectivity of the Hippocampus Can Differentiate Patients with Schizophrenia from Healthy Controls: A Spectral DCM Approach.

We applied spectral dynamic causal modelling (Friston et al. in Neuroimage 94:396-407. https://doi.org/10.1016/j.neuroimage.2013.12.009 , 2014) to analyze the effective connectivity differences between the nodes of three resting state networks (i.e. default mode network, salience network and dorsal attention network) in a dataset of 31 male healthy controls (HC) and 25 male patients with a diagnosis of schizophrenia (SZ). Patients showed increased directed connectivity from the left hippocampus (LHC) to the: dorsal anterior cingulate cortex (DACC), right anterior insula (RAI), left frontal eye fields and the bilateral inferior parietal sulcus (LIPS & RIPS), as well as increased connectivity from the right hippocampus (RHC) to the: bilateral anterior insula (LAI & RAI), right frontal eye fields and RIPS. In SZ, negative symptoms predicted the connectivity strengths from the LHC to: the DACC, the left inferior parietal sulcus (LIPAR) and the RHC, while positive symptoms predicted the connectivity strengths from the LHC to the LIPAR and from the RHC to the LHC. These results reinforce the crucial role of hippocampus dysconnectivity in SZ pathology and its potential as a biomarker of disease severity.

Preserved intention understanding during moral judgments in schizophrenia.

INTRODUCTION: Although there is convincing evidence for socio-cognitive impairments in schizophrenia spectrum disorder (SSD), little evidence is found for deficient moral cognition. We investigated whether patients with SSD showed altered moral judgments in a story task where the protagonist either had a neutral or malicious intention towards another person. This paradigm examined whether SSD relates to altered moral cognition in general or specifically to impaired integration of prior information (such as beliefs) in moral judgments. METHODS: 23 patients and 32 healthy controls read vignettes created in a 2 x 2 design. The protagonist in each story either had a neutral or negative intention towards another person which, as a result, either died (negative outcome) or did not die (neutral outcome). Participants rated the moral permissibility of the protagonist's action. Standard null hypothesis significance testing and equivalent Bayes analyses are reported. RESULTS: Schizophrenia patients did not differ significantly in permissibility ratings from healthy controls. This finding was supported by the Bayes analyses which favoured the null hypothesis. Task performance was not related to symptom severity or medication. CONCLUSIONS: The current findings do not support the notion that moral judgments are deficient in schizophrenia. Furthermore, the current study shows that patients do not have observable difficulties in integrating the protagonist's belief in the rating of the moral permissibility of the action-outcome.

Cortical Morphometry and Its Relationship with Cognitive Functions in Children after non-CNS Cancer.

Background: Childhood cancer survivors (Ccs) are at risk for cognitive late-effects, which might result from cortical alterations, even if cancer does not affect the brain. The study aimed to examine gray and white matter volume and its relationship to cognition. Methods: Forty-three Ccs of non-central nervous system cancers and 43 healthy controls, aged 7-16 years, were examined. Cognitive functions and fine motor coordination were assessed and T1-weighted images were collected for voxel-based morphometry. Results: Executive functions (p = .024, d = .31) were poorer in Ccs than controls, however still within the normal range. The volume of the amygdala (p = .011, ŋ2 = .117) and the striatum (p = .03, ŋ2 = .102) was reduced in Ccs. No significant structure-function correlations were found, neither in patients nor controls. Conclusion: Non-CNS childhood cancer and its treatment impacts on brain structures relevant to emotion processing.

Cloze enough? Hemodynamic effects of predictive processing during natural reading.

Evidence accrues that readers form multiple hypotheses about upcoming words. The present study investigated the hemodynamic effects of predictive processing during natural reading by means of combining fMRI and eye movement recordings. In particular, we investigated the neural and behavioral correlates of precision-weighted prediction errors, which are thought to be indicative of subsequent belief updating. Participants silently read sentences in which we manipulated the cloze probability and the semantic congruency of the final word that served as an index for precision and prediction error respectively. With respect to the neural correlates, our findings indicate an enhanced activation within the left inferior frontal and middle temporal gyrus suggesting an effect of precision on prediction update in higher (lexico-)semantic levels. Despite being evident at the neural level, we did not observe any evidence that this mechanism resulted in disproportionate reading times on participants' eye movements. The results speak against discrete predictions, but favor the notion that multiple words are activated in parallel during reading.

Emotional Recognition in Patients With Mesial Temporal Epilepsy Associated With Enlarged Amygdala.

BACKGROUND: Amygdalae play a central role in emotional processing by interconnecting frontal cortex and other brain structures. Unilateral amygdala enlargement (AE) is associated with mesial temporal lobe epilepsy (mTLE). In a relatively large sample of patients with mTLE and AE, we aimed to evaluate functional integration of AE in emotion processing and to determine possible associations between fMRI activation patterns in amygdala and deficits in emotion recognition as assessed by neuropsychological testing. METHODS: Twenty-two patients with drug resistant unilateral mTLE due to ipsilateral AE were prospectively recruited in a large epilepsy unit and compared with 17 healthy control subjects in terms of amygdala volume, fMRI activation patterns and performance in emotion recognition as assessed by comprehensive affect testing system (CATS) and Ekman faces. All patients underwent structural and functional 1.5 Tesla MRI, electro-clinical assessment and neuropsychological testing. RESULTS: We observed BOLD signal ipsilateral to AE (n = 7; group PAT1); contralateral to AE (n = 6; group PAT2) and no activation (n = 9; group PAT3). In the region of interest (ROI) analysis, beta estimates for fearful face > landscape contrast in the left amygdala region did not differ significantly in patients with left TLE vs. patients with right TLE [T (16) = -1.481; p = 0.158]. However, beta estimates for fearful face > landscape contrast in the right amygdala region were significantly reduced in patients with right TLE vs. patients with left TLE [T (16) = -2,922; p = 0.010]. Patients showed significantly lower total scores in CATS and Ekman faces compared to healthy controls. CONCLUSION: In our cohort, patients with unilateral mesial TLE and ipsilateral AE, an amygdala could display either functional integration in emotion recognition or dysfunction as demonstrated by fMRI. Perception and recognition of emotions were impaired more in right-sided mTLE as compared to left-sided mTLE. Neuropsychological tests showed deficits in emotion recognition in patients as compared to healthy controls.

Impact of non-CNS childhood cancer on resting-state connectivity and its association with cognition.

INTRODUCTION: Non-central nervous system cancer in childhood (non-CNS CC) and its treatments pose a major threat to brain development, with implications for functional networks. Structural and functional alterations might underlie the cognitive late-effects identified in survivors of non-CNS CC. The present study evaluated resting-state functional networks and their associations with cognition in a mixed sample of non-CNS CC survivors (i.e., leukemia, lymphoma, and other non-CNS solid tumors). METHODS: Forty-three patients (off-therapy for at least 1 year and aged 7-16 years) were compared with 43 healthy controls matched for age and sex. High-resolution T1-weighted structural magnetic resonance and resting-state functional magnetic resonance imaging were acquired. Executive functions, attention, processing speed, and memory were assessed outside the scanner. RESULTS: Cognitive performance was within the normal range for both groups; however, patients after CNS-directed therapy showed lower executive functions than controls. Seed-based connectivity analyses revealed that patients exhibited stronger functional connectivity between fronto- and temporo-parietal pathways and weaker connectivity between parietal-cerebellar and temporal-occipital pathways in the right hemisphere than controls. Functional hyperconnectivity was related to weaker memory performance in the patients' group. CONCLUSION: These data suggest that even in the absence of brain tumors, non-CNS CC and its treatment can lead to persistent cerebral alterations in resting-state network connectivity.