Papers by Kalina Michalska

Background: Deficient empathic processing is thought to foster conduct disorder (CD). It is impor... more Background: Deficient empathic processing is thought to foster conduct disorder (CD). It is important to determine the extent to which neural response associated with perceiving harm to others predicts CD symptoms and callous disregard for others. Methods: A total of 107 9-to 11-year-old children (52 female) were recruited from pediatric and mental health clinics, representing a wide range of CD symptoms. Children were scanned with functional magnetic resonance imaging while viewing brief video clips of persons being harmed intentionally or accidentally. Results: Perceiving harm evoked increased hemodynamic response in the anterior insula (aINS), anterior cingulate cortex (ACC), amygdala, periaqueductal gray (PAG), caudate, and inferior parietal lobe (IPL) across all participants. Intentionally caused, relative to unintentional harm was associated with greater activity in the aINS, amygdala, and temporal pole. There was an inverse association of number of CD symptoms with right posterior insula in both the Harm > No Harm and the Intentional > Unintentional Harm contrasts. Furthermore, an inverse association between callousness and posterior insula activation was found in the Harm > No Harm contrast, with the opposite pattern for reactive aggression scores. An interaction revealed a stronger association in girls between CD symptoms and the right posterior superior temporal sulcus (pSTS) in the Intentional Harm versus Unintentional Harm contrast. Conclusions: Children with greater CD and callousness exhibit dampened hemodynamic response to viewing others being harmed in the insula, a region which plays a key role in empathy and emotional awareness. Sex differences in the neural correlates of CD were observed.

The current study examined developmental changes in fear learning and generalization in 54 health... more The current study examined developmental changes in fear learning and generalization in 54 healthy 5-10-year old children using a novel fear conditioning paradigm. In this task, the conditioned stimuli (CS+/CS-) were two blue and yellow colored cartoon bells, and the unconditioned stimulus was an unpleasant loud alarm sound presented with a red cartoon bell. Physiological and subjective data were acquired. Three weeks after conditioning, 48 of these participants viewed the CS-, CS+, and morphed images resembling the CS+. Participants made threat-safety discriminations while appraising threat and remembering the CS+. Although no age-related differences in fear learning emerged, patterns of generalization were qualified by child age. Older children demonstrated better discrimination between the CS+ and CS morphs than younger age groups and also reported more fear to stimuli resembling the CS+ than younger children. Clinical implications and future directions are discussed.
Neuroscience Letters, 2012
Harsh parenting is a risk factor for mental and physical health problems in humans. The ESR1 rece... more Harsh parenting is a risk factor for mental and physical health problems in humans. The ESR1 receptor is critical to adaptive maternal behavior in nonhuman mammals. ESR1 genotype predicted human neural responses to children and maternal parenting. Future study of ESR1, neural responses to child stimuli, and child abuse is warranted.

Because youth with aggressive conduct disorder (CD) often inflict pain on others, it is important... more Because youth with aggressive conduct disorder (CD) often inflict pain on others, it is important to determine if they exhibit atypical empathic responses to viewing others in pain. In this initial functional magnetic resonance imaging (fMRI) study, 8 adolescents with aggressive CD and 8 matched controls were scanned while watching animated visual stimuli depicting other people experiencing pain or not experiencing pain. Furthermore, these situations involved either an individual whose pain was caused by accident or an individual whose pain was inflicted on purpose by another person. After scanning, participants rated how painful the situations were. In both groups the perception of others in pain was associated with activation of the pain matrix, including the ACC, insula, somatosensory cortex, supplementary motor area and periaqueductal gray. The pain matrix was activated to a significantly greater extent in participants with CD, who also showed strong amygdala, ventral striatum, and temporal pole activation. When watching situations in which pain was intentionally inflicted, control youth also exhibited signal increase in the medial prefrontal frontal cortex, lateral obitofrontal cortex, and temporoparietal junction, whereas youth with CD only exhibited activation in the insula. Furthermore, connectivity analyses demonstrated that youth with CD exhibited less amygdala/prefrontal coupling when watching pain inflicted by another than did control youth. These preliminary findings suggest that youth with aggressive CD exhibit an atypical pattern of neural response to viewing others in pain that should be explored in further studies.

Abstract
Because the disruptive behavior disorders are highly impairing conditions, it is importa... more Abstract
Because the disruptive behavior disorders are highly impairing conditions, it is important to determine if structural variations in brain are associated early in life with these problems among children.
Structural MRI data were acquired from 111 9–11 year olds (58 girls and 53 boys), 43 who met diagnostic criteria for oppositional defiant disorder and/or conduct disorder and 68 healthy controls. Voxel-based morphometry was used to examine associations of behavioral measures with gray matter volumes in whole-brain analyses.
Unlike previous studies, variation in gray matter volume was not found to be associated with a disruptive behavior disorder diagnosis in any brain region at p < .05 with FWE correction. Nonetheless, an inverse nonlinear association of the number of conduct disorder (CD) symptoms with gray matter volume along the left superior temporal sulcus was significant in the full sample (p < .05 with FWE correction), with a trend in the right hemisphere (p < 0.001 uncorrected). There also was a trend toward a stronger association of the number of CD symptoms with gray matter volume along the left superior temporal sulcus in girls than boys.
The present findings did not replicate previous findings of reduced gray matter volumes in the anterior insula, amygdala, and frontal cortex in youth with CD, but are consistent with previous findings of reduced gray matter volumes in temporal regions, particularly in girls.

Background
Deficient empathic processing is thought to foster conduct disorder (CD). It is import... more Background
Deficient empathic processing is thought to foster conduct disorder (CD). It is important to determine the extent to which neural response associated with perceiving harm to others predicts CD symptoms and callous disregard for others.
Methods
A total of 107 9- to 11-year-old children (52 female) were recruited from pediatric and mental health clinics, representing a wide range of CD symptoms. Children were scanned with functional magnetic resonance imaging while viewing brief video clips of persons being harmed intentionally or accidentally.
Results
Perceiving harm evoked increased hemodynamic response in the anterior insula (aINS), anterior cingulate cortex (ACC), amygdala, periaqueductal gray (PAG), caudate, and inferior parietal lobe (IPL) across all participants. Intentionally caused, relative to unintentional harm was associated with greater activity in the aINS, amygdala, and temporal pole. There was an inverse association of number of CD symptoms with right posterior insula in both the Harm > No Harm and the Intentional > Unintentional Harm contrasts. Furthermore, an inverse association between callousness and posterior insula activation was found in the Harm > No Harm contrast, with the opposite pattern for reactive aggression scores. An interaction revealed a stronger association in girls between CD symptoms and the right posterior superior temporal sulcus (pSTS) in the Intentional Harm versus Unintentional Harm contrast.
Conclusions
Children with greater CD and callousness exhibit dampened hemodynamic response to viewing others being harmed in the insula, a region which plays a key role in empathy and emotional awareness. Sex differences in the neural correlates of CD were observed.
Background: Well-validated models of maternal behavior in small-brain mammals posit a central rol... more Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation.

Background: Well-validated models of maternal behavior in small-brain mammals posit a central rol... more Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation.
Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4–6 years old.
Results: In response to child stimuli during functional magnetic resonance imaging (fMRI), hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (SNPs) (rs53576 and rs1042778) in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus.
Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods.

Developmental Science, 2009
Empathy and sympathy play crucial roles in much of human social interaction and are necessary com... more Empathy and sympathy play crucial roles in much of human social interaction and are necessary components for healthy coexistence. Sympathy is thought to be a proxy for motivating prosocial behavior and providing the affective and motivational base for moral development. The purpose of the present study was to use functional MRI to characterize developmental changes in brain activation in the neural circuits underpinning empathy and sympathy. Fifty-seven individuals, whose age ranged from 7 to 40 years old, were presented with short animated visual stimuli depicting painful and non-painful situations. These situations involved either a person whose pain was accidentally caused or a person whose pain was intentionally inflicted by another individual to elicit empathic (feeling as the other) or sympathetic (feeling concern for the other) emotions, respectively. Results demonstrate monotonic age-related changes in the amygdala, supplementary motor area, and posterior insula when participants were exposed to painful situations that were accidentally caused. When participants observed painful situations intentionally inflicted by another individual, age-related changes were detected in the dorsolateral prefrontal and ventromedial prefrontal cortex, with a gradual shift in that latter region from its medial to its lateral portion. This pattern of activation reflects a change from a visceral emotional response critical for the analysis of the affective significance of stimuli to a more evaluative function. Further, these data provide evidence for partially distinct neural mechanisms subserving empathy and sympathy, and demonstrate the usefulness of a developmental neurobiological approach to the new emerging area of moral neuroscience.
Emotion Review, 2011
Though traditional accounts of moral development focus on the development of rational and deliber... more Though traditional accounts of moral development focus on the development of rational and deliberate thinking, recent work in developmental affective neuroscience suggests that moral cognition is tightly related to affective and emotional processing. Functional magnetic resonance imaging studies show age-related changes in response to empathy-eliciting stimuli, with a gradual shift from the monitoring of somatovisceral responses in young children mediated by the amygdala, insula and medial aspect of the orbitofrontal cortex, to the executive control and evaluation of emotion processing implemented by the ventromedial prefrontal cortex in older participants. These data indicate that the development of moral reasoning involves the increasing integration of empathic emotion-related somatovisceral responses with more complex social-reasoning abilities.

Behavioral research indicates that human females are more empathic than males, a disparity that w... more Behavioral research indicates that human females are more empathic than males, a disparity that widens from childhood to adulthood. Nevertheless, the extent to which such sex differences are an artifact of self-report indices is unclear. The present study compared age-related sex differences in both self-report and neurophysiological measures of empathic arousal, a primary building block of empathy. Participants included sixty-five 4–17-year-old children (mean 11.5 ± 3.5 years) who completed the Bryant Empathy Scale, and were scanned while viewing animated clips depicting people being hurt. Female participants scored higher than males on self-reported dispositional empathy, a difference that increased with age. In contrast, no sex-related differential changes were detected in hemodynamic responses or in pupil dilation, with no interaction between sex and age. Results suggest a dissociation between explicit ratings and neurophysiological measures of empathic arousal. Past observed sex differences in empathy may reflect females’ greater willingness to report empathic experiences. Findings are also discussed in terms of discrepancies in the methods used to assess affective responding and how they relate to the multi-faceted construct of empathy.
A failure of neural changes initiated by the estrogen surge in late pregnancy to reverse the vale... more A failure of neural changes initiated by the estrogen surge in late pregnancy to reverse the valence of infant stimuli from aversive to rewarding is associated with dysfunctional maternal behavior in nonhuman mammals. Estrogen receptor- plays the crucial role in mediating these neural effects of estrogen priming. This preliminary study examines associations between estrogen receptor- gene polymorphisms and human maternal behavior. Two polymorphisms were associated with human negative maternal parenting. Furthermore, hemodynamic responses in functional magnetic resonance imaging to child stimuli in neural regions associated with social cognition fully mediated the association between genetic variation and negative parenting. This suggests testable hypotheses regarding a biological pathway between genetic variants and dysfunctional human maternal parenting.

Whether emotion is a source of moral judgments remains
controversial. This study combined neuroph... more Whether emotion is a source of moral judgments remains
controversial. This study combined neurophysiological measures,
including functional magnetic resonance imaging, eye-tracking, and pupillary response with behavioral measures assessing affective and moral judgments across age. One hundred and twenty-six participants aged between 4 and 37 years viewed scenarios depicting intentional versus accidental actions that caused harm/ damage to people and objects. Morally, salient scenarios evoked stronger empathic sadness in young participants and were associated with enhanced activity in the amygdala, insula, and temporal poles. While intentional harm was evaluated as equally wrong across all participants, ratings of deserved punishments and malevolent intent gradually became more differentiated with age.
Furthermore, age-related increase in activity was detected in the
ventromedial prefrontal cortex in response to intentional harm to
people, as well as increased functional connectivity between this
region and the amygdala. Our study provides evidence that moral
reasoning involves a complex integration between affective and
cognitive processes that gradually changes with age and can be
viewed in dynamic transaction across the course of ontogenesis.
The findings support the view that negative emotion alerts the
individual to the moral salience of a situation by bringing discomfort and thus can serve as an antecedent to moral judgment.

Empathy and sympathy play crucial roles in much of human social interaction and are necessary com... more Empathy and sympathy play crucial roles in much of human social interaction and are necessary components for healthy coexistence. Sympathy is thought to be a proxy for motivating prosocial behavior and providing the affective and motivational base for moral development. The purpose of the present study was to use functional MRI to characterize developmental changes in brain activation in the neural circuits underpinning empathy and sympathy. Fifty-seven individuals, whose age ranged from 7 to 40 years old, were presented with short animated visual stimuli depicting painful and non-painful situations. These situations involved either a person whose pain was accidentally caused or a person whose pain was intentionally inflicted by another individual to elicit empathic (feeling as the other) or sympathetic (feeling concern for the other) emotions, respectively. Results demonstrate monotonic age-related changes in the amygdala, supplementary motor area, and posterior insula when participants were exposed to painful situations that were accidentally caused. When participants observed painful situations intentionally inflicted by another individual, age-related changes were detected in the dorsolateral prefrontal and ventromedial prefrontal cortex, with a gradual shift in that latter region from its medial to its lateral portion. This pattern of activation reflects a change from a visceral emotional response critical for the analysis of the affective significance of stimuli to a more evaluative function. Further, these data provide evidence for partially distinct neural mechanisms subserving empathy and sympathy, and demonstrate the usefulness of a developmental neurobiological approach to the new emerging area of moral neuroscience.
Cognitive and …, Jan 1, 2003

Use of a False Recognition Paradigm In An Alzheimer's Disease Clinical Trial: A Pilot Study
American Journal of …, Jan 1, 2002
We report the first use of a false recognition memory test in a clinical trial of patients with A... more We report the first use of a false recognition memory test in a clinical trial of patients with Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD). Tests of false recognition allow measurement of two components of memory: the specific details of a prior encounter with a particular item (item-specific recollection) and the general meaning, idea, or gist conveyed by a collection of items (gist memory). We used a false recognition paradigm with categorized pictures to study the effects of an experimental medication in patients with AD. Because medications to treat AD may preferentially improve gist memory or item-specific recollection, use of this type of paradigm may improve sensitivity for detection of drug effects more than standard memory tests.
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Papers by Kalina Michalska
Because the disruptive behavior disorders are highly impairing conditions, it is important to determine if structural variations in brain are associated early in life with these problems among children.
Structural MRI data were acquired from 111 9–11 year olds (58 girls and 53 boys), 43 who met diagnostic criteria for oppositional defiant disorder and/or conduct disorder and 68 healthy controls. Voxel-based morphometry was used to examine associations of behavioral measures with gray matter volumes in whole-brain analyses.
Unlike previous studies, variation in gray matter volume was not found to be associated with a disruptive behavior disorder diagnosis in any brain region at p < .05 with FWE correction. Nonetheless, an inverse nonlinear association of the number of conduct disorder (CD) symptoms with gray matter volume along the left superior temporal sulcus was significant in the full sample (p < .05 with FWE correction), with a trend in the right hemisphere (p < 0.001 uncorrected). There also was a trend toward a stronger association of the number of CD symptoms with gray matter volume along the left superior temporal sulcus in girls than boys.
The present findings did not replicate previous findings of reduced gray matter volumes in the anterior insula, amygdala, and frontal cortex in youth with CD, but are consistent with previous findings of reduced gray matter volumes in temporal regions, particularly in girls.
Deficient empathic processing is thought to foster conduct disorder (CD). It is important to determine the extent to which neural response associated with perceiving harm to others predicts CD symptoms and callous disregard for others.
Methods
A total of 107 9- to 11-year-old children (52 female) were recruited from pediatric and mental health clinics, representing a wide range of CD symptoms. Children were scanned with functional magnetic resonance imaging while viewing brief video clips of persons being harmed intentionally or accidentally.
Results
Perceiving harm evoked increased hemodynamic response in the anterior insula (aINS), anterior cingulate cortex (ACC), amygdala, periaqueductal gray (PAG), caudate, and inferior parietal lobe (IPL) across all participants. Intentionally caused, relative to unintentional harm was associated with greater activity in the aINS, amygdala, and temporal pole. There was an inverse association of number of CD symptoms with right posterior insula in both the Harm > No Harm and the Intentional > Unintentional Harm contrasts. Furthermore, an inverse association between callousness and posterior insula activation was found in the Harm > No Harm contrast, with the opposite pattern for reactive aggression scores. An interaction revealed a stronger association in girls between CD symptoms and the right posterior superior temporal sulcus (pSTS) in the Intentional Harm versus Unintentional Harm contrast.
Conclusions
Children with greater CD and callousness exhibit dampened hemodynamic response to viewing others being harmed in the insula, a region which plays a key role in empathy and emotional awareness. Sex differences in the neural correlates of CD were observed.
Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4–6 years old.
Results: In response to child stimuli during functional magnetic resonance imaging (fMRI), hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (SNPs) (rs53576 and rs1042778) in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus.
Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods.
controversial. This study combined neurophysiological measures,
including functional magnetic resonance imaging, eye-tracking, and pupillary response with behavioral measures assessing affective and moral judgments across age. One hundred and twenty-six participants aged between 4 and 37 years viewed scenarios depicting intentional versus accidental actions that caused harm/ damage to people and objects. Morally, salient scenarios evoked stronger empathic sadness in young participants and were associated with enhanced activity in the amygdala, insula, and temporal poles. While intentional harm was evaluated as equally wrong across all participants, ratings of deserved punishments and malevolent intent gradually became more differentiated with age.
Furthermore, age-related increase in activity was detected in the
ventromedial prefrontal cortex in response to intentional harm to
people, as well as increased functional connectivity between this
region and the amygdala. Our study provides evidence that moral
reasoning involves a complex integration between affective and
cognitive processes that gradually changes with age and can be
viewed in dynamic transaction across the course of ontogenesis.
The findings support the view that negative emotion alerts the
individual to the moral salience of a situation by bringing discomfort and thus can serve as an antecedent to moral judgment.