Anna Tyborowska

Gray and white matter correlates of navigational ability in humans

Humans differ widely in their navigational abilities. Studies have shown that self‐reports on navigational abilities are good predictors of performance on navigation tasks in real and virtual environments. The caudate nucleus and medial temporal lobe regions have been suggested to subserve different navigational strategies. The ability to use different strategies might underlie navigational ability differences. This study examines the anatomical correlates of self‐reported navigational ability in both gray and white matter. Local gray matter volume was compared between a group (N = 134) of good and bad navigators using voxel‐based morphometry (VBM), as well as regional volumes. To compare between good and bad navigators, we also measured white matter anatomy using diffusion tensor imaging (DTI) and looked at fractional anisotropy (FA) values. We observed a trend toward higher local GM volume in right anterior parahippocampal/rhinal cortex for good versus bad navigators. Good male navigators showed significantly higher local GM volume in right hippocampus than bad male navigators. Conversely, bad navigators showed increased FA values in the internal capsule, the white matter bundle closest to the caudate nucleus and a trend toward higher local GM volume in the caudate nucleus. Furthermore, caudate nucleus regional volume correlated negatively with navigational ability. These convergent findings across imaging modalities are in line with findings showing that the caudate nucleus and the medial temporal lobes are involved in different wayfinding strategies. Our study is the first to show a link between self‐reported large‐scale navigational abilities and different measures of brain anatomy. Hum Brain Mapp 35:2561–2572, 2014.

Encoding and retrieval of landmark‐related spatial cues during navigation: An fMRI study

To successfully navigate, humans can use different cues from their surroundings. Learning locations in an environment can be supported by parallel subsystems in the hippocampus and the striatum. We used fMRI to look at differences in the use of object‐related spatial cues while 47 participants actively navigated in an open‐field virtual environment. In each trial, participants navigated toward a target object. During encoding, three positional cues (columns) with directional cues (shadows) were available. During retrieval, the removed target had to be replaced while either two objects without shadows (objects trial) or one object with a shadow (shadow trial) were available. Participants were informed in blocks about which type of retrieval trial was most likely to occur, thereby modulating expectations of having to rely on a single landmark or on a configuration of landmarks. How the spatial learning systems in the hippocampus and caudate nucleus were involved in these landmark‐based encoding and retrieval processes were investigated. Landmark configurations can create a geometry similar to boundaries in an environment. It was found that the hippocampus was involved in encoding when relying on configurations of landmarks, whereas the caudate nucleus was involved in encoding when relying on single landmarks. This might suggest that the observed hippocampal activation for configurations of objects is linked to a spatial representation observed with environmental boundaries. Retrieval based on configurations of landmarks activated regions associated with the spatial updation of object locations for reorientation. When only a single landmark was available during retrieval, regions associated with updating the location of oneself were activated. There was also evidence that good between‐participant performance was predicted by right hippocampal activation. This study therefore sheds light on how the brain deals with changing demands on spatial processing related purely to landmarks.

Testosterone during Puberty Shifts Emotional Control from Pulvinar to Anterior Prefrontal Cortex

Increased limbic and striatal activation in adolescence has been attributed to a relative delay in the maturation of prefrontal areas, resulting in the increase of impulsive reward-seeking behaviors that are often observed during puberty. However, it remains unclear whether and how this general developmental pattern applies to the control of social emotional actions, a fundamental adult skill refined during adolescence. This domain of control pertains to decisions involving emotional responses. When faced with a social emotional challenge (e.g., an angry face), we can follow automatic response tendencies and avoid the challenge or exert control over those tendencies by selecting an alternative action. Using an fMRI-adapted social approach-avoidance task, this study identifies how the neural regulation of emotional action control changes as a function of human pubertal development in 14-year-old adolescents (n = 47). Pubertal maturation, indexed by testosterone levels, shifted neural regulation of emotional actions from the pulvinar nucleus of the thalamus and the amygdala to the anterior prefrontal cortex (aPFC). Adolescents with more advanced pubertal maturation showed greater aPFC activity when controlling their emotional action tendencies, reproducing the same pattern consistently observed in adults. In contrast, adolescents of the same age, but with less advanced pubertal maturation, showed greater pulvinar and amygdala activity when exerting similarly effective emotional control. These findings qualify how, in the domain of social emotional actions, executive control shifts from subcortical to prefrontal structures during pubertal development. The pulvinar and the amygdala are suggested as the ontogenetic precursors of the mature control system centered on the anterior prefrontal cortex. SIGNIFICANCE STATEMENT Adolescents can show distinct behavioral problems when emotionally aroused. This could be related to later development of frontal regions compared with deeper brain structures. This study found that when the control of emotional actions needs to be exerted, more mature adolescents, similar to adults, recruit the anterior prefrontal cortex (aPFC). Less mature adolescents recruit specific subcortical regions, namely the pulvinar and amygdala. These findings identify the subcortical pulvino–amygdalar pathway as a relevant precursor of a mature aPFC emotional control system, opening the way for a neurobiological understanding of how emotion control-related disorders emerge during puberty.

The brain‐derived neurotrophic factor Val66Met polymorphism affects encoding of object locations during active navigation

The brain‐derived neurotrophic factor (BDNF) was shown to be involved in spatial memory and spatial strategy preference. A naturally occurring single nucleotide polymorphism of the BDNF gene (Val66Met) affects activity‐dependent secretion of BDNF. The current event‐related fMRI study on preselected groups of ‘Met’ carriers and homozygotes of the ‘Val’ allele investigated the role of this polymorphism on encoding and retrieval in a virtual navigation task in 37 healthy volunteers. In each trial, participants navigated toward a target object. During encoding, three positional cues (columns) with directional cues (shadows) were available. During retrieval, the invisible target had to be replaced while either two objects without shadows (objects trial) or one object with a shadow (shadow trial) were available. The experiment consisted of blocks, informing participants of which trial type would be most likely to occur during retrieval. We observed no differences between genetic groups in task performance or time to complete the navigation tasks. The imaging results show that Met carriers compared to Val homozygotes activate the left hippocampus more during successful object location memory encoding. The observed effects were independent of non‐significant performance differences or volumetric differences in the hippocampus. These results indicate that variations of the BDNF gene affect memory encoding during spatial navigation, suggesting that lower levels of BDNF in the hippocampus results in less efficient spatial memory processing.

Early-life and pubertal stress differentially modulate grey matter development in human adolescents

Animal and human studies have shown that both early-life traumatic events and ongoing stress episodes affect neurodevelopment, however, it remains unclear whether and how they modulate normative adolescent neuro-maturational trajectories. We characterized effects of early-life (age 0–5) and ongoing stressors (age 14–17) on longitudinal changes (age 14 to17) in grey matter volume (GMV) of healthy adolescents (n = 37). Timing and stressor type were related to differential GMV changes. More personal early-life stressful events were associated with larger developmental reductions in GMV over anterior prefrontal cortex, amygdala and other subcortical regions; whereas ongoing stress from the adolescents’ social environment was related to smaller reductions over the orbitofrontal and anterior cingulate cortex. These findings suggest that early-life stress accelerates pubertal development, whereas an adverse adolescent social environment disturbs brain maturation with potential mental health implications: delayed anterior cingulate maturation was associated with more antisocial traits – a juvenile precursor of psychopathy.

Effects of stress on bodily freezing in adolescents

Freezing is a major defensive stress-response, characterized by reduced body-sway and heart rate. Exacerbated freezing in threatening situations has been associated with increased basal and stress-induced glucocorticoid levels and with long-lasting stress-related symptoms in animals. However, the effects of stress-induced changes on human freezing are unknown. A new measure has been developed to quantify freezing-like behavior in humans using a stabilometric force-platform such that shifts in body-sway can be assessed with high temporal and spatial accuracy. Previous research has shown that exposure to angry (vs. neutral) faces can induce reductions in body-sway and heart rate in humans. In our study, we used this method to assess the effects of stress and stress-induced cortisol on human freezing responses to angry versus happy and neutral faces. Participants were 90 adolescents (age 17) who were tested at three time points: prior to, immediately after, and 55 min after the Maastricht Acute Stress Test. To ascertain stress-induction, self-reported, physiological, and hormonal measures were collected prior to, immediately after, and 20, 30, 40, and 55 min after stress-onset. Preliminary analyses of the self-report and blood pressure measures indicated a successful stress-induction. Additionally, we predicted that stress-induced cortisol levels are associated with increased freezing. Finally, we will explore the association between stress-induced freezing and affective symptoms (e.g., anxiety) to gain a better understanding why adolescence is a phase of increased vulnerability for stress-related symptoms. We will discuss our results in terms of the translation between animal and human models of stress and defensive responses to threat.

Investigation of the stability of human freezing-like responses to social threat from mid to late adolescence

Freezing behavior, a commonly observed defensive stress response, shows relatively high stability over time in animals. Given the relevance of freezing for stress-coping and human psychopathology, it is relevant to know whether freezing behavior is also stable in humans, particularly during adolescence, when most affective symptoms develop. In a prospective longitudinal study, we investigated freezing-like behavior in response to social threat in 75 adolescents at age 14, repeated 3 years later at age 17. We used a well-established method combining electrocardiography (ECG; heart rate) and posturography (body sway) in response to emotional picture-viewing of angry, happy, and neutral faces. We hypothesized that individual differences in freezing-like behavior in response to social threat—operationalized by contrasting angry vs. neutral faces—would be relatively stable over time. Our results indeed showed relative stability between ages 14 and 17 in individual differences in freezing-like behavior in heart rate (r = 0.82), as well as in combined heart rate and body sway measures (r = 0.65). These effects were not specific for the angry vs. neutral contrast; they were also visible in other emotion contrasts. Exploratory analysis in males and females separately showed stability in body sway specifically for angry vs. neutral faces only in females. Together, these results suggest moderate to strong stability in human freezing-like behavior in response to social threat from mid to late adolescence (with exception for the body sway measure in males). This relative stability was not specific for threat-induction and may reflect a general stability that is particularly strong for heart rate. The fact that this relative stability was found over a relatively long time range of 3 years is promising for studies aiming to use freezing-like behavior as a marker for internalizing symptoms in adolescent development.

Defensive freezing links Hypothalamic-Pituitary-Adrenal-axis activity and internalizing symptoms in humans

The Hypothalamic-Pituitary-Adrenal (HPA)-axis plays an important role in the expression of defensive freezing. Adaptive freezing reactivity, characterized by an immediate increase in acute stress and timely termination upon threat offset or need to act, is essential for adequate stress coping. Blunted HPA-axis activity in animals is associated with blunted freezing reactivity and internalizing symptoms. Despite their potential relevance, it remains unknown whether these mechanisms apply to humans and human psychopathology. Using a well-established method combining electrocardiography and posturography, we assessed freezing before, immediately after, and one hour after a stress induction in 92 human adolescents. In line with animal models, human adolescents showed stress-induced freezing, as quantified by relative reductions in heart rate and body sway after, as compared to before, stress. Moreover, relatively lower basal cortisol was associated with reduced stress-induced freezing reactivity (i.e., less immediate freezing and less recovery). Path analyses showed that decreased freezing recovery in individuals with reduced cortisol levels was associated with increased levels of internalizing symptoms. These findings suggest that reduced freezing recovery may be a promising marker for the etiology of internalizing symptoms.