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1.
Hum Brain Mapp ; 45(3): e26576, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38401139

ABSTRACT

Internalizing symptoms such as elevated stress and sustained negative affect can be important warning signs for developing mental disorders. A recent theoretical framework suggests a complex interplay of empathy, theory of mind (ToM), and negative thinking processes as a crucial risk combination for internalizing symptoms. To disentangle these relationships, this study utilizes neural, behavioral, and self-report data to examine how the interplay between empathy, ToM, and negative thinking processes relates to stress and negative affect. We reanalyzed the baseline data of N = 302 healthy participants (57% female, Mage = 40.52, SDage = 9.30) who participated in a large-scale mental training study, the ReSource project. Empathy and ToM were assessed using a validated fMRI paradigm featuring naturalistic video stimuli and via self-report. Additional self-report scales were employed to measure internalizing symptoms (perceived stress, negative affect) and negative thinking processes (rumination and self-blame). Our results revealed linear associations of self-reported ToM and empathic distress with stress and negative affect. Also, both lower and higher, compared to average, activation in the anterior insula during empathic processing and in the middle temporal gyrus during ToM performance was significantly associated with internalizing symptoms. These associations were dependent on rumination and self-blame. Our findings indicate specific risk constellations for internalizing symptoms. Especially people with lower self-reported ToM and higher empathic distress may be at risk for more internalizing symptoms. Quadratic associations of empathy- and ToM-related brain activation with internalizing symptoms depended on negative thinking processes, suggesting differential effects of cognitive and affective functioning on internalizing symptoms. Using a multi-method approach, these findings advance current research by shedding light on which complex risk combinations of cognitive and affective functioning are relevant for internalizing symptoms.


Subject(s)
Pessimism , Theory of Mind , Humans , Female , Adult , Child , Male , Empathy , Theory of Mind/physiology , Brain/diagnostic imaging , Brain/physiology , Risk Factors
2.
Sci Rep ; 13(1): 14577, 2023 09 04.
Article in English | MEDLINE | ID: mdl-37666926

ABSTRACT

Cues of social rejection and affiliation represent proximal risk and protective factors in the onset and maintenance of depression. Such cues are thought to activate an evolutionarily primed neuro-cognitive alarm system, alerting the agent to the benefits of inclusion or the risk of social exclusion within social hierarchies focused on ensuring continued access to resources. In tandem, autobiographical memory is thought to be over-general and negatively biased in Major Depressive Disorder (MDD) which can contribute to maintenance and relapse. How memories of social rejection and affiliation are experienced and processed in MDD remains unexplored. Eighteen participants with recurrent and chronic MDD and 18 never-depressed controls listened to and vividly revisited autobiographical social experiences in an ecologically valid script-driven imagery paradigm using naturalistic memory narratives in an fMRI paradigm. Memories of Social Inclusion and Social Rejection broadly activated a common network of regions including the bilateral insula, thalamus and pre/postcentral gyrus across both groups. However, having a diagnosis of MDD was associated with an increased activation of the right middle frontal gyrus irrespective of memory type. Changes in positive affect were associated with activity in the dorsal ACC in the MDD group and in the insular cortex of the Control group. Our findings add to the evidence for complex representations for both positive and negative social signals in MDD and suggest neural sensitivity in MDD towards any socially salient information as opposed to selective sensitivity towards negative social experiences.


Subject(s)
Depressive Disorder, Major , Memory, Episodic , Humans , Auditory Perception , Cues , Frontal Lobe
3.
Sci Rep ; 13(1): 7189, 2023 05 03.
Article in English | MEDLINE | ID: mdl-37138001

ABSTRACT

Research suggests affective symptoms are associated with reduced habitual use of reappraisal as an emotion regulation strategy in individuals with mental health problems. Less is known, however, about whether mental health problems are related to reduced reappraisal capacity per se. The current study investigates this question using a film-based emotion regulation task that required participants to use reappraisal to downregulate their emotional response to highly evocative real-life film footage. We pooled data (N = 512, age: 18-89 years, 54% female) from 6 independent studies using this task. In contrast to our predictions, symptoms of depression and anxiety were unrelated to self-reported negative affect after reappraisal or to emotional reactivity to negative films. Implications for the measurement of reappraisal as well as future directions for research in the field of emotion regulation are discussed.


Subject(s)
Emotional Regulation , Emotions , Humans , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Male , Emotions/physiology , Anxiety , Anxiety Disorders/psychology , Affective Symptoms/psychology , Emotional Regulation/physiology
4.
J Psychopathol Clin Sci ; 132(2): 156-164, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36808959

ABSTRACT

Evolutionary models of depression posit that depressed mood represents an adaptive response to unacceptably low social status, motivating the inhibition of social risk-taking in favor of submissive behaviors which reduce the likelihood of social exclusion. We tested the hypothesis of reduced social risk taking using a novel adaptation of the Balloon Analogue Risk Task (BART) in participants with major depressive disorder (MDD; n = 27) and never-depressed comparison participants (n = 35). The BART requires participants to pump up virtual balloons. The more the balloon is pumped up, the more money a participant gains on that trial. However, more pumps also increase the risk the balloon will burst such that all money is lost. Prior to performing the BART, participants took part in a team induction in small groups in order to prime social-group membership. Participants then completed two conditions of the BART: an Individual condition where they risked only their own money, and a Social condition, where they risked the money of their social group. The groups did not differ in their performance in the individual condition (Cohen's d = 0.07). However, the MDD group risked fewer pumps in the Social condition than the never-depressed group (d = 0.57). The study supports the notion of an aversion to social risk-taking in depression. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Decision Making , Depressive Disorder, Major , Humans , Decision Making/physiology , Depression , Risk-Taking , Affect
5.
J Neurosci ; 42(16): 3461-3472, 2022 04 20.
Article in English | MEDLINE | ID: mdl-35256529

ABSTRACT

Aging is associated with a bias in attention and memories toward positive and away from negative emotional content. In addition, emotion regulation appears to improve with age, despite concomitant widespread cognitive decline coupled with gray matter volume loss in cortical and subcortical regions thought to subserve emotion regulation. Here, we address this emotion-aging paradox using the behavioral data of an emotion regulation task from a population-derived, male and female, human sample (CamCAN) and use structural equation modeling together with multivariate analysis of structural MRI images of the same sample to investigate brain-behavior relationships. In a series of measurement models, we show the relationship between age and emotionality is best explained by a four-factor model, compared with single and hierarchical factor models. These four latent factors are interpreted as Basal Negative Affect, Positive Reactivity, Negative Reactivity and Positive Regulation (upregulating positive emotion to negative content). Increasing age uniquely contributes to increased Basal Negative Affect, Positive Reactivity, and Positive Regulation, but not Negative Reactivity. Furthermore, we show gray matter volumes, namely in the bilateral frontal operculum, medial frontal gyrus, bilateral hippocampal complex, bilateral middle temporal gyri, and bilateral angular gyrus, are distinctly related to these four latent factors. Finally, we show that a subset of these brain-behavior relationships remain significant when accounting for age and demographic data. Our results support the notion of an age-related increase in positivity and are interpreted in the context of the socioemotional selectivity theory of improved emotion regulation in older age.SIGNIFICANCE STATEMENT Aging is associated with a paradoxical increase in well-being and improved emotion regulation despite widespread cognitive decline and gray matter volume loss in neural regions that underlie emotion regulation. Using a population-derived sample, we test the theories behind this emotion/aging paradox with an emotion regulation task and structural MRI data. We report robust age-related increases in positivity across the life span and show structural neural integrity influences this relationship with increasing age. Several brain-behavior relationships remained unaffected by age and may represent empirically derived neural markers to explore the paradox of increased well-being in old age. The results support the predictions of socioemotional selectivity theory of improved emotion regulation in older age and challenge the amygdala-focused neural predictions of the aging brain model.


Subject(s)
Brain , Longevity , Aging/physiology , Brain/diagnostic imaging , Emotions/physiology , Female , Gray Matter/diagnostic imaging , Humans , Latent Class Analysis , Magnetic Resonance Imaging , Male
6.
Memory ; 30(5): 650-657, 2022 05.
Article in English | MEDLINE | ID: mdl-35129427

ABSTRACT

Hierarchies pervade human society, characterising its members along diverse dimensions ranging from their abilities or skills in a particular domain to their economic status or physical stature. One intriguing aspect of the centrality of hierarchies, relative to egalitarian constructs, is that hierarchically-organised social information appears to be remembered more easily than non-hierarchically-organised information. However, it is not yet clear how one's social rank within a hierarchy influences processing. In a pre-registered study with 66 healthy participants, we examined memory recall for hierarchical information when participants themselves were positioned higher in the hierarchy versus lower in the hierarchy, both relative to an egalitarian control condition. The results replicate previous work showing that hierarchical information is memorised faster relative to the egalitarian control. Importantly, this effect was modulated by the participant's position within the hierarchy, with higher positioned participants memorising information faster than lower-positioned participants. This study provides new evidence showing biases in memory will favour hierarchical information if modulated by perceptions of one's own social rank.


Subject(s)
Hierarchy, Social , Bias , Humans
7.
J Affect Disord ; 294: 661-670, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34333174

ABSTRACT

BACKGROUND: The risk of depressive relapse and recurrence is associated with social risk factors that may be amplified by a submissive socio-cognitive profile. METHODS: In Study 1 we aimed to identify perceptions of low social status in a community sample (N = 613) with a self-reported history of mental health difficulties (n = 232) and, more specifically in Study 2 (N = 122), in individuals in clinical remission from depression (n = 18), relative to a never-depressed control group (n = 64), and relative to a group experiencing a current depressive episode (n = 40). RESULTS: In Study 1, a total of 225 of the 232 participants in the self-reported mental health difficulties group opted to provide further information regarding their mental health history, of whom 153 (68%) reported a history of anxiety, 168 (74.7%) reported a history of depression, and 13 (5.8%) reported an unspecified mental health history. Elevated depressive symptoms were associated with perceptions of low social status which significantly differed between individuals with and without a self-reported history of mental health difficulties. In Study 2 we found enduring perceptions of low social status in remitted depressed individuals. LIMITATIONS: We were unable to discern between historical or current clinical diagnosis in the community sample of Study 1, as we were reliant on self-report. We were unable to explore the effects of medication or causal relationships between depressive symptoms and social status as the studies were cross-sectional in nature. CONCLUSIONS: These findings suggest that evolutionarily rooted socio-cognitive profiles could impact affiliative processes and may confer increased vulnerability to future depressive episodes.


Subject(s)
Depression , Psychological Distance , Anxiety , Cross-Sectional Studies , Depression/epidemiology , Humans , Perception
8.
Brain Behav ; 11(5): e02005, 2021 05.
Article in English | MEDLINE | ID: mdl-33662187

ABSTRACT

INTRODUCTION: Understanding the emotional responsivity style and neurocognitive profiles of depression-related processes in at-risk youth may be helpful in revealing those most likely to develop affective disorders. However, the multiplicity of biopsychosocial risk factors makes it difficult to disentangle unique and combined effects at a neurobiological level. METHODS: In a population-derived sample of 56 older adolescents (aged 17-20), we adopted partial least squares regression and correlation models to explore the relationships between multivariate biopsychosocial risks for later depression, emotional response style, and fMRI activity, to rejecting and inclusive social feedback. RESULTS: Behaviorally, higher depressive risk was associated with both reduced negative affect following negative social feedback and reduced positive affect following positive social feedback. In response to both cues of rejection and inclusion, we observed a general neural pattern of increased cingulate, temporal, and striatal activity in the brain. Secondly, in response to rejection only, we observed a pattern of activity in ostensibly executive control- and emotion regulation-related brain regions encompassing fronto-parietal brain networks including the angular gyrus. CONCLUSION: The results suggest that risk for depression is associated with a pervasive emotional insensitivity in the face of positive and negative social feedback.


Subject(s)
Emotional Regulation , Emotions , Adolescent , Attention , Brain/diagnostic imaging , Humans , Magnetic Resonance Imaging
9.
Dev Psychopathol ; 32(2): 411-423, 2020 05.
Article in English | MEDLINE | ID: mdl-30895920

ABSTRACT

Childhood adversity (CA) increases the risk of subsequent mental health problems. Adolescent social support (from family and/or friends) reduces the risk of mental health problems after CA. However, the mechanisms of this effect remain unclear, and we speculate that they are manifested on neurodevelopmental levels. Therefore, we investigated whether family and/or friendship support at ages 14 and 17 function as intermediate variables for the relationship between CA before age 11 and affective or neural responses to social rejection feedback at age 18. We studied 55 adolescents with normative mental health at age 18 (26 with CA and therefore considered "resilient"), from a longitudinal cohort. Participants underwent a Social Feedback Task in the magnetic resonance imaging scanner. Social rejection feedback activated the dorsal anterior cingulate cortex and the left anterior insula. CA did not predict affective or neural responses to social rejection at age 18. Yet, CA predicted better friendships at age 14 and age 18, when adolescents with and without CA had comparable mood levels. Thus, adolescents with CA and normative mood levels have more adolescent friendship support and seem to have normal mood and neural responses to social rejection.


Subject(s)
Magnetic Resonance Imaging , Psychological Distance , Adolescent , Affect , Child , Friends , Gyrus Cinguli , Humans
10.
Soc Cogn Affect Neurosci ; 14(6): 623-631, 2019 08 07.
Article in English | MEDLINE | ID: mdl-31119296

ABSTRACT

Human older age ushers in functional decline across the majority of cognitive domains. A notable exception seems to be affective processing, with older people reporting higher levels of emotional well-being. Here we evaluated age-related changes in emotional reactivity and regulation in a representative subsample (N = 104; age range: 23-88 years) of the population-derived Cambridge Centre for Ageing and Neuroscience cohort. Performance on a film-based emotion reactivity and regulation task in the magnetic resonance imaging scanner showed an age-related decline in positive reactivity, alongside a similar decline in the capacity to down-regulate negative affect. Decreased positivity with age was associated with reduced activation in the middle frontal gyrus. These findings, from the largest neuroimaging investigation to-date, provide no support for age-related increases in positive emotional reactivity.


Subject(s)
Aging/psychology , Brain/diagnostic imaging , Emotional Regulation/physiology , Emotions/physiology , Adult , Aged , Aged, 80 and over , Female , Functional Neuroimaging , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Young Adult
11.
Epilepsy Res ; 152: 59-66, 2019 05.
Article in English | MEDLINE | ID: mdl-30909053

ABSTRACT

OBJECTIVE: Predictors of psychiatric outcome following TLE surgery have proved elusive and represent a current challenge in the practice of TLE surgery. This prospective study investigated whether frontal lobe dysfunction is predictive of poorer psychiatric outcomes. METHODS: Forty-nine unilateral TLE surgical patients were assessed using the Beck Depression Inventory-Fast Screen (BDI-FS) and Beck Anxiety Inventory (BAI) preoperatively and 6 and 12 months postoperatively. Measures of intellectual function, semantic knowledge, memory and executive function were completed preoperatively, at 6 and 12 months following surgery. RESULTS: Preoperatively, 33 (67%) patients had minimal depressive symptoms, 8 (16%) were mildly depressed, 2 (4%) were moderately depressed, and 6 (12%) reported severe depressive morbidity. Twenty-three (47%) patients reported minimal anxiety, 18 (37%) were mildly anxious, 6 (12%) were moderately anxious and 2 (4%) patients reported severe anxiety symptoms. A mixed-model repeated-measures analysis was performed on the BDI-FS and BAI scores, adjusting for pertinent covariates identified in univariable analyses. At a year following TLE surgery, anxiety symptoms significantly improved but depressive morbidity did not. Indicators of frontal lobe dysfunction moderated the magnitude and direction of mood change. Specifically, pre-surgical cognitive measures of frontal lobe dysfunction predicted increased depression and anxiety symptoms following surgery. There was no relationship between preoperative BDI-FS or BAI scores and seizure outcome at 12 months or change in affective morbidity and seizure outcome. SIGNIFICANCE: This is the first longitudinal study to provide evidence that specific pre-surgical cognitive and behavioural indices of frontal dysfunction are predictive of poorer psychiatric outcome following TLE surgery. In addition, our findings highlight the potential utility of a dysexecutive behavioural rating scale (DEX) as an assessment tool in epilepsy. Examination of executive functioning in pre-surgical evaluations may lead to an increase in the power of prognostic models used to predict the psychiatric outcome of TLE surgery.


Subject(s)
Anxiety/diagnosis , Depression/diagnosis , Epilepsy, Temporal Lobe/psychology , Epilepsy, Temporal Lobe/surgery , Frontal Lobe/pathology , Neurosurgery/methods , Postoperative Complications/physiopathology , Adolescent , Adult , Aged , Anxiety/etiology , Anxiety/psychology , Cognition/physiology , Depression/etiology , Depression/psychology , Epilepsy, Temporal Lobe/complications , Epilepsy, Temporal Lobe/diagnostic imaging , Female , Frontal Lobe/diagnostic imaging , Frontal Lobe/physiopathology , Functional Laterality/physiology , Humans , Logistic Models , Longitudinal Studies , Magnetic Resonance Imaging , Male , Memory/physiology , Middle Aged , Neuropsychological Tests , Postoperative Complications/diagnostic imaging , Postoperative Complications/psychology , Psychiatric Status Rating Scales , Semantics , Young Adult
12.
CNS Neurosci Ther ; 25(2): 223-232, 2019 02.
Article in English | MEDLINE | ID: mdl-29952080

ABSTRACT

INTRODUCTION: Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%-40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups. AIMS: We examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE. METHODS: In this study, we investigated the association of Val66Met polymorphism with cognitive performance (n = 276), postoperative cognitive change (n = 126) and fMRI activation patterns during memory encoding and language paradigms in 2 groups of patients with mTLE (n = 37 and 34). RESULTS: mTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task-related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients. CONCLUSIONS: Although cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE.


Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Cognitive Dysfunction/etiology , Cognitive Dysfunction/psychology , Drug Resistant Epilepsy/genetics , Drug Resistant Epilepsy/psychology , Epilepsies, Partial/genetics , Epilepsies, Partial/psychology , Epilepsy, Temporal Lobe/genetics , Epilepsy, Temporal Lobe/psychology , Nerve Net/physiopathology , Polymorphism, Genetic/genetics , Adult , Drug Resistant Epilepsy/physiopathology , England/epidemiology , Epilepsies, Partial/physiopathology , Epilepsy, Temporal Lobe/physiopathology , Female , Gene Frequency , Genotype , Hippocampus/physiopathology , Humans , Magnetic Resonance Imaging , Male , Memory , Neuropsychological Tests , Neurosurgical Procedures , Psychomotor Performance
13.
Sci Rep ; 7: 42010, 2017 02 07.
Article in English | MEDLINE | ID: mdl-28169323

ABSTRACT

Social interaction inherently involves the subjective evaluation of cues salient to social inclusion and exclusion. Testifying to the importance of such social cues, parts of the neural system dedicated to the detection of physical pain, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been shown to be equally sensitive to the detection of social pain experienced after social exclusion. However, recent work suggests that this dACC-AI matrix may index any socially pertinent information. We directly tested the hypothesis that the dACC-AI would respond to cues of both inclusion and exclusion, using a novel social feedback fMRI paradigm in a population-derived sample of adolescents. We show that the dACC and left AI are commonly activated by feedback cues of inclusion and exclusion. Our findings suggest that theoretical accounts of the dACC-AI network as a neural alarm system restricted within the social domain to the processing of signals of exclusion require significant revision.


Subject(s)
Brain/physiopathology , Neural Pathways , Pain/physiopathology , Psychological Distance , Social Environment , Stress, Psychological , Adolescent , Adult , Brain Mapping , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Task Performance and Analysis , Young Adult
14.
Brain ; 139(Pt 2): 415-30, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26754787

ABSTRACT

Anterior temporal lobe resection can control seizures in up to 80% of patients with temporal lobe epilepsy. Memory decrements are the main neurocognitive complication. Preoperative functional reorganization has been described in memory networks, but less is known of postoperative reorganization. We investigated reorganization of memory-encoding networks preoperatively and 3 and 12 months after surgery. We studied 36 patients with unilateral medial temporal lobe epilepsy (19 right) before and 3 and 12 months after anterior temporal lobe resection. Fifteen healthy control subjects were studied at three equivalent time points. All subjects had neuropsychological testing at each of the three time points. A functional magnetic resonance imaging memory-encoding paradigm of words and faces was performed with subsequent out-of-scanner recognition assessments. Changes in activations across the time points in each patient group were compared to changes in the control group in a single flexible factorial analysis. Postoperative change in memory across the time points was correlated with postoperative activations to investigate the efficiency of reorganized networks. Left temporal lobe epilepsy patients showed increased right anterior hippocampal and frontal activation at both 3 and 12 months after surgery relative to preoperatively, for word and face encoding, with a concomitant reduction in left frontal activation 12 months postoperatively. Right anterior hippocampal activation 12 months postoperatively correlated significantly with improved verbal learning in patients with left temporal lobe epilepsy from preoperatively to 12 months postoperatively. Preoperatively, there was significant left posterior hippocampal activation that was sustained 3 months postoperatively at word encoding, and increased at face encoding. For both word and face encoding this was significantly reduced from 3 to 12 months postoperatively. Patients with right temporal lobe epilepsy showed increased left anterior hippocampal activation on word encoding from 3 to 12 months postoperatively compared to preoperatively. On face encoding, left anterior hippocampal activations were present preoperatively and 12 months postoperatively. Left anterior hippocampal and orbitofrontal cortex activations correlated with improvements in both design and verbal learning 12 months postoperatively. On face encoding, there were significantly increased left posterior hippocampal activations that reduced significantly from 3 to 12 months postoperatively. Postoperative changes occur in the memory-encoding network in both left and right temporal lobe epilepsy patients across both verbal and visual domains. Three months after surgery, compensatory posterior hippocampal reorganization that occurs is transient and inefficient. Engagement of the contralateral hippocampus 12 months after surgery represented efficient reorganization in both patient groups, suggesting that the contralateral hippocampus contributes to memory outcome 12 months after surgery.


Subject(s)
Magnetic Resonance Imaging/methods , Memory/physiology , Nerve Net/physiology , Neuronal Plasticity/physiology , Temporal Lobe/physiology , Temporal Lobe/surgery , Adult , Epilepsy, Temporal Lobe/diagnosis , Epilepsy, Temporal Lobe/surgery , Female , Humans , Longitudinal Studies , Male , Middle Aged , Young Adult
15.
Soc Cogn Affect Neurosci ; 11(2): 272-81, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26341903

ABSTRACT

Individuals exposed to childhood adversities (CA) present with emotion regulation (ER) difficulties in later life, which have been identified as risk and maintenance factors for psychopathologies. However, it is unclear if CA negatively impacts on ER capacity per se or whether observed regulation difficulties are a function of the challenging circumstances in which ER is being deployed. In this longitudinal study, we aimed to clarify this association by investigating the behavioral and neural effects of exposure to common moderate CA (mCA) on a laboratory measure of ER capacity in late adolescence/young adulthood. Our population-derived samples of adolescents/young adults (N = 53) were administered a film-based ER-task during functional magnetic resonance imaging that allowed evaluation of ER across mCA-exposure. mCA-exposure was associated with enhanced ER capacity over both positive and negative affect. At the neural level, the better ER of negative material in those exposed to mCA was associated with reduced recruitment of ER-related brain regions, including the prefrontal cortex and temporal gyrus. In addition mCA-exposure was associated with a greater down-regulation of the amygdala during ER of negative material. The implications of these findings for our understanding of the effects of mCA on the emergence of resilience in adolescence are discussed.


Subject(s)
Adult Survivors of Child Adverse Events/psychology , Brain/physiology , Emotions/physiology , Brain Mapping , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging/methods , Male , Young Adult
16.
Neurology ; 84(15): 1512-9, 2015 Apr 14.
Article in English | MEDLINE | ID: mdl-25770199

ABSTRACT

OBJECTIVE: To develop a clinically applicable memory functional MRI (fMRI) method of predicting postsurgical memory outcome in individual patients. METHODS: In this prospective cohort study, 50 patients with temporal lobe epilepsy (23 left) and 26 controls underwent an fMRI memory encoding paradigm of words with a subsequent out-of-scanner recognition assessment. Neuropsychological assessment was performed preoperatively and 4 months after anterior temporal lobe resection, and at equal time intervals in controls. An event-related analysis was used to explore brain activations for words remembered and change in verbal memory scores 4 months after surgery was correlated with preoperative activations. Individual lateralization indices were calculated within a medial temporal and frontal region and compared with other clinical parameters (hippocampal volume, preoperative verbal memory, age at onset of epilepsy, and language lateralization) as a predictor of verbal memory outcome. RESULTS: In left temporal lobe epilepsy patients, left frontal and anterior medial temporal activations correlated significantly with greater verbal memory decline, while bilateral posterior hippocampal activation correlated with less verbal memory decline postoperatively. In a multivariate regression model, left lateralized memory lateralization index (≥0.5) within a medial temporal and frontal mask was the best predictor of verbal memory outcome after surgery in the dominant hemisphere in individual patients. Neither clinical nor functional MRI parameters predicted verbal memory decline after nondominant temporal lobe resection. CONCLUSION: We propose a clinically applicable memory fMRI paradigm to predict postoperative verbal memory decline after surgery in the language-dominant hemisphere in individual patients.


Subject(s)
Anterior Temporal Lobectomy/adverse effects , Cerebral Cortex/physiopathology , Cerebral Cortex/surgery , Epilepsy, Temporal Lobe/surgery , Functional Laterality/physiology , Memory Disorders/physiopathology , Postoperative Complications/physiopathology , Adult , Brain Mapping , Frontal Lobe/physiopathology , Hippocampus/physiopathology , Hippocampus/surgery , Humans , Magnetic Resonance Imaging , Memory Disorders/etiology , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Temporal Lobe/physiopathology , Temporal Lobe/surgery
17.
Neurology ; 83(17): 1508-12, 2014 Oct 21.
Article in English | MEDLINE | ID: mdl-25253743

ABSTRACT

OBJECTIVE: We used functional MRI (fMRI) and a left-lateralizing verbal and a right-lateralizing visual-spatial working memory (WM) paradigm to investigate the effects of levetiracetam (LEV) on cognitive network activations in patients with drug-resistant temporal lobe epilepsy (TLE). METHODS: In a retrospective study, we compared task-related fMRI activations and deactivations in 53 patients with left and 54 patients with right TLE treated with (59) or without (48) LEV. In patients on LEV, activation patterns were correlated with the daily LEV dose. RESULTS: We isolated task- and syndrome-specific effects. Patients on LEV showed normalization of functional network deactivations in the right temporal lobe in right TLE during the right-lateralizing visual-spatial task and in the left temporal lobe in left TLE during the verbal task. In a post hoc analysis, a significant dose-dependent effect was demonstrated in right TLE during the visual-spatial WM task: the lower the LEV dose, the greater the abnormal right hippocampal activation. At a less stringent threshold (p < 0.05, uncorrected for multiple comparisons), a similar dose effect was observed in left TLE during the verbal task: both hippocampi were more abnormally activated in patients with lower doses, but more prominently on the left. CONCLUSIONS: Our findings suggest that LEV is associated with restoration of normal activation patterns. Longitudinal studies are necessary to establish whether the neural patterns translate to drug response. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with drug-resistant TLE, levetiracetam has a dose-dependent facilitation of deactivation of mesial temporal structures.


Subject(s)
Anticonvulsants/therapeutic use , Brain/drug effects , Epilepsy, Temporal Lobe/drug therapy , Epilepsy, Temporal Lobe/pathology , Piracetam/analogs & derivatives , Adult , Brain/blood supply , Brain/pathology , Chi-Square Distribution , Female , Humans , Image Processing, Computer-Assisted , Levetiracetam , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Oxygen/blood , Piracetam/therapeutic use , Young Adult
18.
Epilepsia ; 55(10): 1504-11, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25182478

ABSTRACT

OBJECTIVE: Assessment of language dominance using functional magnetic resonance imaging (fMRI) is a standard tool to estimate the risk of language function decline after epilepsy surgery. Although there has been considerable research in the characterization of language networks in bilingual individuals; little is known about the clinical usefulness of language mapping in a secondary language in patients with epilepsy, and how language lateralization assessed by fMRI may differ by the use of native or a secondary language paradigms. In this study we investigate language representation in a population of nonnative English speakers to assess differences in fMRI language lateralization between the first (native) and second language (English). METHODS: Sixteen nonnative English-speaking patients with focal drug-resistant epilepsy underwent language fMRI in their first (native) language (L1) and in English (L2). Differences between language maps using L1 and L2 paradigms were examined at the single subject level by comparing within-subject lateralization indexes obtained for each language. Differences at the group level were examined for each of the tasks and languages. RESULTS: Group maps for the second language (English) showed overlapping areas of activation with the native language, but with larger clusters, and more bilaterally distributed than for the first language. However, at the individual level, lateralization indexes were concordant between the two languages, except for one patient with bilateral hippocampal sclerosis who was left dominant in English and showed bilateral dominance for verb generation and right dominance for verbal fluency in his native tongue. SIGNIFICANCE: Language lateralization can generally be reliably derived from fMRI tasks in a second language provided that the subject can follow the task. Subjects with greater likelihood of atypical language representation should be evaluated more carefully, using more than one language paradigm.


Subject(s)
Brain/physiology , Dominance, Cerebral/physiology , Functional Neuroimaging , Magnetic Resonance Imaging , Multilingualism , Adult , Age Factors , Female , Humans , Language , Male , Middle Aged , Reproducibility of Results , Young Adult
19.
Neurology ; 83(7): 604-11, 2014 Aug 12.
Article in English | MEDLINE | ID: mdl-25015363

ABSTRACT

OBJECTIVE: We assessed whether display of optic radiation tractography during anterior temporal lobe resection (ATLR) for refractory temporal lobe epilepsy (TLE) can reduce the severity of postoperative visual field deficits (VFD) and increase the proportion of patients who can drive and whether correction for brain shift using intraoperative MRI (iMRI) is beneficial. METHODS: A cohort of 21 patients underwent ATLR in an iMRI suite. Preoperative tractography of the optic radiation was displayed on the navigation and operating microscope displays either without (9 patients) or with (12 patients) correction for brain shift. VFD were quantified using Goldmann perimetry and eligibility to drive was assessed by binocular Esterman perimetry 3 months after surgery. Secondary outcomes included seizure freedom and extent of hippocampal resection. The comparator was a cohort of 44 patients who underwent ATLR without iMRI. RESULTS: The VFD in the contralateral superior quadrant were significantly less (p = 0.043) with iMRI guidance (0%-49.2%, median 14.5%) than without (0%-90.9%, median 24.0%). No patient in the iMRI cohort developed a VFD that precluded driving whereas 13% of the non-iMRI cohort failed to meet UK driving criteria. Outcome did not differ between iMRI guidance with and without brain shift correction. Seizure outcome and degree of hippocampal resection were unchanged. CONCLUSIONS: Display of the optic radiation with image guidance reduces the severity of VFD and did not affect seizure outcome or hippocampal resection. Correction for brain shift is possible but did not further improve outcome. Future work to incorporate tractography into conventional neuronavigation systems will make the work more widely applicable.


Subject(s)
Epilepsy, Temporal Lobe/surgery , Magnetic Resonance Imaging/methods , Neuronavigation/methods , Neurosurgical Procedures/adverse effects , Perceptual Disorders/prevention & control , Temporal Lobe/surgery , Visual Fields , Adolescent , Adult , Aged , Cohort Studies , Epilepsy, Temporal Lobe/pathology , Female , Hippocampus/pathology , Humans , Male , Middle Aged , Seizures/pathology , Seizures/surgery , Temporal Lobe/pathology , Treatment Outcome , Visual Pathways/pathology , Visual Pathways/surgery , Young Adult
20.
Brain ; 137(Pt 5): 1439-53, 2014 May.
Article in English | MEDLINE | ID: mdl-24691395

ABSTRACT

Working memory is a crucial cognitive function that is disrupted in temporal lobe epilepsy. It is unclear whether this impairment is a consequence of temporal lobe involvement in working memory processes or due to seizure spread to extratemporal eloquent cortex. Anterior temporal lobe resection controls seizures in 50-80% of patients with drug-resistant temporal lobe epilepsy and the effect of surgery on working memory are poorly understood both at a behavioural and neural level. We investigated the impact of temporal lobe resection on the efficiency and functional anatomy of working memory networks. We studied 33 patients with unilateral medial temporal lobe epilepsy (16 left) before, 3 and 12 months after anterior temporal lobe resection. Fifteen healthy control subjects were also assessed in parallel. All subjects had neuropsychological testing and performed a visuospatial working memory functional magnetic resonance imaging paradigm on these three separate occasions. Changes in activation and deactivation patterns were modelled individually and compared between groups. Changes in task performance were included as regressors of interest to assess the efficiency of changes in the networks. Left and right temporal lobe epilepsy patients were impaired on preoperative measures of working memory compared to controls. Working memory performance did not decline following left or right temporal lobe resection, but improved at 3 and 12 months following left and, to a lesser extent, following right anterior temporal lobe resection. After left anterior temporal lobe resection, improved performance correlated with greater deactivation of the left hippocampal remnant and the contralateral right hippocampus. There was a failure of increased deactivation of the left hippocampal remnant at 3 months after left temporal lobe resection compared to control subjects, which had normalized 12 months after surgery. Following right anterior temporal lobe resection there was a progressive increase of activation in the right superior parietal lobe at 3 and 12 months after surgery. There was greater deactivation of the right hippocampal remnant compared to controls between 3 and 12 months after right anterior temporal lobe resection that was associated with lesser improvement in task performance. Working memory improved after anterior temporal lobe resection, particularly following left-sided resections. Postoperative working memory was reliant on the functional capacity of the hippocampal remnant and, following left resections, the functional reserve of the right hippocampus. These data suggest that working memory following temporal lobe resection is dependent on the engagement of the posterior medial temporal lobes and eloquent cortex.


Subject(s)
Hippocampus/blood supply , Magnetic Resonance Imaging , Memory Disorders/surgery , Memory, Short-Term/physiology , Neuronal Plasticity/physiology , Parietal Lobe/blood supply , Adult , Anterior Temporal Lobectomy/methods , Epilepsy, Temporal Lobe/complications , Epilepsy, Temporal Lobe/surgery , Follow-Up Studies , Functional Laterality/physiology , Hippocampus/physiology , Humans , Image Processing, Computer-Assisted , Memory Disorders/etiology , Memory Disorders/pathology , Middle Aged , Neuropsychological Tests , Oxygen/blood , Space Perception , Time Factors , Young Adult
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