Intentions to quit upper secondary education among first generation immigrants and native Norwegians: the role of loneliness and peer victimization

Dropout from upper secondary education is a persistent educational problem, particularly among first-generation immigrant youth. This study examined factors associated with intentions to dropout to gain further insight into the process of leaving upper secondary education. The analyses of 1299 Norwegian first-year upper secondary school students’ (88% native Norwegians, 12% first-generation immigrants) self-reported intentions to quit school, loneliness, and peer victimization in school showed that first-generation immigrants experienced higher levels of loneliness than native Norwegians. In contrast, there were no differences in the levels of peer victimization and intentions to quit between native Norwegians and first-generation immigrants. However, loneliness showed a significantly stronger association with intentions to quit among first-generation immigrants. The results underscore the importance of tackling first-generation immigrants’ loneliness in school to reduce their intentions to quit upper secondary education and thus potentially improve conditions for school completion.

     

Is There Savings for Pavlovian Fear Conditioning after Neurotoxic Basolateral Amygdala Lesions in Rats?

Considerable evidence indicates an important role for amygdaloid nuclei in both the acquisition and expression of Pavlovian fear conditioning. Recent reports from my laboratory have focused on the impact of neurotoxic lesions of the basolateral complex of the amygdala (BLA) on conditional freezing behavior in rats. In these studies, I have observed severe effects of posttraining BLA lesions on the expression of conditional freezing even after extensive presurgical overtraining (25-75 trials). Moreover, I have found no evidence for sparing of fear memory (i.e., savings) in these rats when I assess their rate of reacquisition relative to BLA rats receiving minimal training (1 trial). In these experiments, freezing behavior was assessed using a conventional time-sampling procedure and expressed as a response probability. Although this measure is well established in the literature, it is conceivable that it is not sensitive to spared memory in rats with BLA lesions. To address this issue, I present a more detailed analysis of freezing behavior that quantifies latency to freeze, the number of freezing bouts, the duration of freezing bouts, and the probability distribution of bout lengths. I also include control data from untrained (no-shock) rats. Consistent with my earlier reports, I find no evidence of savings of fear memory in rats with neurotoxic BLA lesions using several measures of freezing behavior. These results reiterate the conclusion that fear memory, as it is expressed in freezing behavior, requires neurons in the BLA.     

Nuclear disconnection within the amygdala reveals a direct pathway to fear

It is widely believed that a descending serial circuit consisting of neural projections from the basolateral complex (BLA) to the central nucleus (CEA) of the amygdala mediates fear expression. Here we directly test this hypothesis and show that disconnecting the BLA and CEA with asymmetric neurotoxic lesions after Pavlovian fear conditioning in rats completely abolishes the expression of conditional freezing. These results demonstrate that neural projections from the BLA to CEA are essential for the expression of learned fear responses.Long-standing anatomical models of the brain circuitry underlying learned fear posit serial flow of information through the amygdala to engage the expression of fear responses (LeDoux 2000; Maren 2001). Specifically, conditioning-induced plasticity in the lateral nucleus of the amygdala (LA) is thought to drive learned fear through excitatory axonal projections to the basal nuclei of the amygdala (BA; basolateral and basomedial nuclei), which in turn send unidirectional and excitatory synaptic projections to the medial division of the central nucleus of the amygdala (CEm). Neurons in the CEm project to brain structures involved in the production of a variety of fear responses (Pitkänen et al. 1997; Swanson and Petrovich 1998). Alternatively, neurons in LA might excite neurons in CEm by limiting inhibitory input from the intercalated cell masses (ITC) interposed between the basolateral complex (BLA; lateral and basal nuclei) and the central nucleus of the amygdala (CEA) (Paré et al. 2004). In either case, the BLA is well positioned to drive learned fear responses via anatomical connections with the CEA.Although an extensive literature demonstrates the importance of both the BLA and CEA in the acquisition and expression of fear (LeDoux et al. 1990; Lee et al. 1996; Amorapanth et al. 2000; Goosens and Maren 2001), it is not known whether a functional connection between the two structures is essential for the expression of learned fear. Indeed, the BLA and CEA make independent contributions to aversively motivated learning under some conditions (Killcross et al. 1997; Amorapanth et al. 2000). Moreover, recent work in appetitive conditioning paradigms challenges the necessity of serial circuits in the amygdala for associative learning processes (Holland and Gallagher 1999; Everitt et al. 2003; Balleine and Killcross 2006). It is therefore essential to determine whether serial connections between the BLA and CEA are involved in the expression of fear memories as widely assumed in the literature.To address this issue, we made asymmetric neurotoxic lesions of the BLA and CEA after Pavlovian fear conditioning in rats. That is, we placed BLA lesions in one hemisphere and CEA lesions in the contralateral hemisphere, thereby producing a functional disconnection of the two brain regions. Control animals received neurotoxic BLA and CEA lesions in the same hemisphere, thereby leaving both structures and their connections intact in one hemisphere. This disconnection strategy (e.g., Olton et al. 1982) capitalizes on the fact that projections from the BLA to CEA are both ipsilateral and unidirectional (Pitkänen et al. 1997). It has been used by several groups to assess the contribution of connections between brain areas to learning and memory processes, including conditioned stimulus processing (Han et al. 1999) and appetitive spatial learning (Ito et al. 2008), for example.Fear conditioning was conducted in standard observation chambers (see Supplemental Methods) and consisted of five pairings of an auditory conditional stimulus (CS) (2 kHz, 10 sec, 80 dB) with a footshock unconditioned stimulus (US) (2 sec, 1 mA); the intertrial interval (ITI) was 1 min. Freezing behavior served as the measure of conditional fear. Twenty-four hours after fear conditioning, the rats were deeply anesthetized, and amygdala lesions were made by infusing N-methyl-d-aspartate (NMDA; 20 mg/mL in 100 mM phosphate buffered saline with a pH 7.4; Sigma) into the CEA and BLA through a 28-g injection cannula attached to a Hamilton syringe via polyethylene tubing. Control rats received unilateral lesions of the BLA and CEA in the same hemisphere (IPSI, n = 13) or sham surgery (SHAM, n = 16), whereas experimental rats received the unilateral BLA and CEA lesions in opposite hemispheres (CONTRA, n = 11). Hence, functional connectivity between the BLA and CEA was left intact in one hemisphere among rats in the IPSI group, whereas the asymmetric lesions in rats in the CONTRA group eliminated this connection. Retention tests assessing fear to the conditioning context and tone CS were conducted in separate sessions one week after recovery from surgery. Histological examination of coronal brain sections obtained from the subjects after the experiment revealed selective CEA and BLA lesions in each group; representative lesions are illustrated in Figure 1, A and B. The lesions spared fibers of passage (Fig. 1C).Open in a separate windowFigure 1.Disconnection of the BLA and CEA impairs the expression of conditional fear. (A) Schematic representation of a typical BLA (shaded) and CEA (black) lesions among rats with unilateral lesions placed in the same hemisphere (IPSI) or in opposite hemispheres (CONTRA). (B) Photomicrograph of a thionin-stained coronal section from a representative rat in the CONTRA group. The image has been cropped to include only the left and right amygdale. Broken lines encircle CEA and BLA lesions in the left and right hemispheres, respectively. (C, left) Photomicrograph of a thionin-stained coronal section from a representative rat in the IPSI group. The image has been cropped to focus on the lesion in the right amygdala. Broken lines encircle the CEA and BLA lesions. (C, right) Photomicrograph of an AuCl-stained coronal section adjacent to that shown at left indicates that NMDA infusions into the amygdala did not damage myelinated axons in the vicinity of the lesion. (D) Mean percentage of freezing (± SEM) during the conditioning session (collapsed across CSs and ITIs) and retention tests in rats in each of the three groups. The expression of fear to the conditioning context and tone CS was severely impaired by disconnection of the BLA and CEA in the CONTRA group. *P < 0.05.As shown in Figure 1D (left panel), all rats acquired similar levels of conditional freezing (collapsed across the CS and ITI for each trial) by the end of the presurgical fear conditioning session (main effect of trial, F_(5,185) = 42.1, P < 0.0001); there was neither a main effect of group (F < 1) nor a group × trial interaction (F < 1.3). One week after recovery from surgery, conditional freezing to the conditioning context and the auditory CS was assessed in separate retention tests. Importantly, functional disconnection of the BLA and the CEA after fear conditioning severely impaired the expression of conditioned freezing to both the conditioning context and the auditory CS (Fig. 1D, right). Indeed, the expression of fear to the auditory CS was essentially abolished. Freezing among rats in the CONTRA group was significantly lower than that in both the SHAM and IPSI groups during both retention tests (main effect of group, F_(2,37) = 9.98, P < 0.001), and this difference did not interact with the nature of the retention test (F < 1). Hence, functional disconnection of the BLA and CEA produced an impairment in the expression of conditional fear that was much greater than that produced by comparable lesions that spared this connection.The logic of the disconnection procedure requires that focal CEA and BLA lesions in each hemisphere do not damage the adjacent BLA or CEA, respectively. For instance, if CEA lesions produce retrograde degeneration in the neighboring BLA, rats in the CONTRA group would effectively have bilateral lesions in the BLA. Such an outcome would be expected to yield the massive deficits in conditional freezing that we have observed. Inspection of thionin-stained coronal sections suggested that, as in previous studies (Goosens and Maren 2001), our lesions were indeed selective for the targeted areas (Fig. 1B). However, to increase our confidence that the BLA adjacent to a CEA lesion was in fact functional, we performed c-fos immunohistochemistry on brain sections obtained from a separate group of rats trained and tested as previously described (SHAM, CONTRA, and IPSI groups; n = 8 per group). In addition to these rats, we included a group of rats that were not conditioned (NO-SHOCK, n = 8) to quantify fear-induced increases in c-fos expression. All rats were sacrificed 90 min after the retention test to the auditory CS. Amygdaloid c-fos expression in the SHAM rats and the intact hemisphere of the IPSI rats did not differ, and these groups were therefore collapsed into a single SHAM group.As shown in Figure 2, SHAM rats exhibited a greater density of c-fos positive nuclei in both the CEA and BLA relative to nonshocked controls. Quantification of these data confirmed this observation and revealed significant differences in c-fos expression among the groups in both the CEA (Fig. 2, left; F_(2,40) = 5.59, P < 0.01) and the BLA (Fig. 2, right; F_(2,40) = 5.07, P < 0.01). Importantly, BLA c-fos expression adjacent to CEA lesions in the CONTRA group was similar to that in intact SHAM rats, and significantly greater than that in nonshocked controls (Fig. 2B, right). This suggests that the failure of CONTRA rats to express conditional fear responses was not due to a failure to engage the intact BLA but rather to the functional disconnection of BLA activity from CEA output. Indeed, the CEA adjacent to a BLA lesion exhibited a marked reduction in c-fos expression relative to SHAM controls (Fig. 2, left), indicating that BLA lesions failed to drive ipsilateral CEA neurons important for the expression of learned fear. It is possible that the absence of c-fos expression in the CEA, in this case, is due to encroachment of the adjacent BLA lesion. However, thionin-stained sections revealed that BLA lesions were selective. Moreover, we observed intact BLA c-fos expression in rats with adjacent CEA lesions suggesting that nearby lesions per se do not disrupt c-fos expression.Open in a separate windowFigure 2.Functional disconnection of the BLA and CEA revealed by c-fos expression. Mean density (± SEM) of c-fos positive nuclei in the CEA (left) and BLA (right) in rats from each of the three groups. Disconnection of the BLA and CEA eliminated fear-related increases in c-fos expression in the CEA (left), but not the BLA (right). *P < 0.05.These results reveal that a functional connection between the BLA and CEA is required for the expression of learned fear. Considering that BLA projections to the CEA are largely unidirectional, our data reveal that a serial circuit from the BLA to the CEA mediates the expression of conditional fear responses. Consistent with this view, there are numerous reports that permanent lesions or reversible inactivation of either the BLA or CEA prevent the expression of conditioned fear (Lee et al. 1996; Maren 1999; Zimmerman et al. 2007). It is now apparent that the necessity for both the BLA and CEA in fear expression arises from the functional connectivity between them. Anatomically, this connection might involve a direct excitatory projection from BA to CEm (Paré et al. 1999) or indirect projections from LA to ITC and the lateral division of the central nucleus (CEl), both of which project to CEm (Smith and Paré 1994; Paré et al. 2004). Recent data reveal, however, that selective immunotoxic lesions of the ITC do not impair the expression of conditioned freezing (Likhtik et al. 2008). Moreover, CEl projections to CEm are inhibitory, making it unlikely that that an LA-CEl projection drives learned fear responses via CEm (Paré et al. 2004). Hence, it appears that the most likely route by which fear CSs drive learned fear involves projections from BA to CEm. Consistent with this, selective BA lesions disrupt the expression of conditioned freezing when made either before (Goosens and Maren 2001) or after (Anglada-Figueroa and Quirk 2005) fear conditioning.The dependence of conditional fear on a serial circuit between the BLA and CEA stands in contrast to the independent roles these areas have been proposed to play in appetitive conditioning paradigms (Holland and Gallagher 1999; Everitt et al. 2003; Balleine and Killcross 2006). For example, CEA, but not BLA, lesions have been reported to produce deficits in the acquisition and expression of autoshaped conditioned responses (CRs), indicating that the CEA has an independent contribution to CR expression for food-motivated responses (Parkinson et al. 2000). Moreover, the BLA has a role in the attribution of incentive salience to rewarding stimuli independent of the generation of CRs to those stimuli (Hatfield et al. 1996). However, in aversive conditioning, it appears that the BLA may not encode the motivational properties of the shock US (Rabinak and Maren 2008), but rather CS–US associations that are essential for organizing conditional fear responses by the CEA. Indeed, there is an emerging body of data suggesting that these associations may be established not only in sensory afferents in the BLA but also in the CEA (Wilensky et al. 2006; Zimmerman et al. 2007). Synaptic plasticity in projections from BA to CEm may be the essential substrate underlying the functional connectivity between these structures that is essential for the expression of fear memory.     

Reciprocal patterns of c-Fos expression in the medial prefrontal cortex and amygdala after extinction and renewal of conditioned fear

After extinction of conditioned fear, memory for the conditioning and extinction experiences becomes context dependent. Fear is suppressed in the extinction context, but renews in other contexts. This study characterizes the neural circuitry underlying the context-dependent retrieval of extinguished fear memories using c-Fos immunohistochemistry. After fear conditioning and extinction to an auditory conditioned stimulus (CS), rats were presented with the extinguished CS in either the extinction context or a second context, and then sacrificed. Presentation of the CS in the extinction context yielded low levels of conditioned freezing and induced c-Fos expression in the infralimbic division of the medial prefrontal cortex, the intercalated nuclei of the amygdala, and the dentate gyrus (DG). In contrast, presentation of the CS outside of the extinction context yielded high levels of conditioned freezing and induced c-Fos expression in the prelimbic division of the medial prefrontal cortex, the lateral and basolateral nuclei of the amygdala, and the medial division of the central nucleus of the amygdala. Hippocampal areas CA1 and CA3 exhibited c-Fos expression when the CS was presented in either context. These data suggest that the context specificity of extinction is mediated by prefrontal modulation of amygdala activity, and that the hippocampus has a fundamental role in contextual memory retrieval.Considerable interest has emerged in recent years in the neural mechanisms underlying the associative extinction of learned fear (Maren and Quirk 2004; Myers et al. 2006; Quirk and Mueller 2008). Notably, extinction is a useful model for important aspects of exposure-based therapies for the treatment of human anxiety disorders such as panic disorder and post-traumatic stress disorder (PTSD) (Bouton et al. 2001, 2006). During extinction, a conditioned stimulus (CS) is repeatedly presented in the absence of the unconditioned stimulus (US), a procedure that greatly reduces the magnitude and probability of the conditioned response (CR). After the extinction of fear, there is substantial evidence that extinction does not erase the original fear memory, but results in a transient inhibition of fear. For example, extinguished fear responses return after the mere passage of time (i.e., spontaneous recovery) or after a change in context (i.e., renewal) (Bouton et al. 2006; Ji and Maren 2007). In other words, extinguished fear is context specific. The return of fear after extinction is a considerable challenge for maintaining long-lasting fear suppression after exposure-based therapies (Rodriguez et al. 1999; Hermans et al. 2006; Effting and Kindt 2007; Quirk and Mueller 2008).In the last several years, considerable progress has been made in understanding the neural mechanisms underlying the context specificity of fear extinction. For example, lesions or inactivation of the hippocampus prevent the renewal of fear when an extinguished CS is presented outside of the extinction context (Corcoran and Maren 2001, 2004; Corcoran et al. 2005; Ji and Maren 2005, 2008; Hobin et al. 2006). In addition, neurons in the basolateral complex of the amygdala exhibit context-specific spike firing to extinguished CSs (Hobin et al. 2003; Herry et al. 2008), and this requires hippocampal input (Maren and Hobin 2007). Indeed, amygdala neurons that fire more to extinguished CSs outside of the extinction context are monosynaptically excited by hippocampal stimulation (Herry et al. 2008). In contrast, neurons that responded preferentially to extinguished CSs in the extinction context receive synaptic input from the medial prefrontal cortex (Herry et al. 2008).The prevalent theory of the interactions between the prefrontal cortex, hippocampus, and amygdala that lead to regulation of fear by context assumes that when animals experience an extinguished CS in the extinction context, the hippocampus drives prefrontal cortex inhibition of the amygdala to suppress fear (Hobin et al. 2003; Maren and Quirk 2004; Maren 2005). When animals encounter an extinguished CS outside of the extinction context, the hippocampus is posited to inhibit the prefrontal cortex and thereby promote amygdala activity required to renew fear. The hippocampus may also drive fear renewal through its direct projections to the basolateral amygdala (Herry et al. 2008). Although this model accounts for much of the extant literature on the context specificity of extinction, it is not known whether the nodes of this hypothesized neural network are coactive during the retrieval of fear and extinction memories. As a first step in addressing this issue, we used ex vivo c-Fos immunohistochemistry (e.g., Knapska et al. 2007) to generate a functional map of the neural circuits involved in the contextual retrieval of fear memory after extinction. Our results reveal reciprocal activity in prefrontal-amygdala circuits involved in extinction and renewal and implicate the hippocampus in hierarchical control of contextual memory retrieval within these circuits.     

Glutamate receptors in the medial geniculate nucleus are necessary for expression and extinction of conditioned fear in rats

Auditory fear conditioning requires anatomical projections from the medial geniculate nucleus (MGN) of the thalamus to the amygdala. Several lines of work indicate that the MGN is a critical sensory relay for auditory information during conditioning, but is not itself involved in the encoding of long-term fear memories. In the present experiments, we examined whether the MGN plays a similar role in the extinction of conditioned fear. Twenty-four hours after Pavlovian fear conditioning, rats received bilateral intra-thalamic infusions of either with NBQX (an AMPA receptor antagonist; Experiment 1) or MK-801 (an NMDA receptor antagonist; Experiment 1), anisomycin (a protein synthesis inhibitor; Experiment 2) or U0126 (a MEK inhibitor; Experiment 3) immediately prior to an extinction session in a novel context. The next day rats received a tone test in a drug-free state to assess their extinction memory; freezing served as an index of fear. Glutamate receptor antagonism prevented both the expression and extinction of conditioned fear. In contrast, neither anisomycin nor U0126 affected extinction. These results suggest that the MGN is a critical sensory relay for auditory information during extinction training, but is not itself a site of plasticity underlying the formation of the extinction memory.     

Hippocampal regulation of context-dependent neuronal activity in the lateral amygdala

Pavlovian fear conditioning is a robust and enduring form of emotional learning that provides an ideal model system for studying contextual regulation of memory retrieval. After extinction the expression of fear conditional responses (CRs) is context-specific: A conditional stimulus (CS) elicits greater conditional responding outside compared with inside the extinction context. Dorsal hippocampal inactivation with muscimol attenuates context-specific CR expression. We have previously shown that CS-elicited spike firing in the lateral nucleus of the amygdala is context-specific after extinction. The present study examines whether dorsal hippocampal inactivation with muscimol disrupts context-specific firing in the lateral amygdala. We conditioned rats to two separate auditory CSs and then extinguished each CS in separate and distinct contexts. Thereafter, single-unit activity and conditional freezing were tested to one CS in both extinction contexts after saline or muscimol infusion into the dorsal hippocampus. After saline infusion, rats froze more to the CS when it was presented outside of its extinction context, but froze equally in both contexts after muscimol infusion. In parallel with the behavior, lateral nucleus neurons exhibited context-dependent firing to extinguished CSs, and hippocampal inactivation disrupted this activity pattern. These data reveal a novel role for the hippocampus in regulating the context-specific firing of lateral amygdala neurons after fear memory extinction.     

Preschool Executive Control and Internalizing Symptoms in Elementary School

Depression and anxiety are prevalent and impairing forms of psychopathology in children and adolescents. Deficits in early executive control (EC) may contribute to the development of these problems, but longitudinal studies with rigorous measurement across key developmental periods are limited. The current study examines EC in preschool as a predictor of subsequent depression and anxiety symptoms in elementary school in a community sample (N?=?280). Child participants completed a battery of nine developmentally-appropriate tasks designed to measure major aspects of EC at age 5 years, 3 months. Children later participated in an elementary school follow-up phase, during which they completed validated norm-referenced self-report questionnaires of depression and anxiety symptoms in fourth grade. Results indicate that poorer preschool EC was significantly associated with both greater depression and anxiety symptoms in elementary school, controlling for baseline depression and anxiety symptoms in preschool and other relevant variables. These findings suggest that poor EC may be an important risk factor for the development of internalizing psychopathology in childhood. Given emerging evidence for the modifiability of EC, particularly in preschool, EC promotion interventions may hold promise as a potential target in psychopathology prevention.     

Comparing the neural correlates of affective and cognitive theory of mind using fMRI: Involvement of the basal ganglia in affective theory of mind

Theory of Mind (ToM) is the ability to infer other people’s mental states like intentions or desires. ToM can be differentiated into affective (i.e., recognizing the feelings of another person) and cognitive (i.e., inferring the mental state of the counterpart) subcomponents. Recently, subcortical structures such as the basal ganglia (BG) have also been ascribed to the multifaceted concept ToM and most BG disorders have been reported to elicit ToM deficits. In order to assess both the correlates of affective and cognitive ToM as well as involvement of the basal ganglia, 30 healthy participants underwent event-related fMRI scanning, neuropsychological testing, and filled in questionnaires concerning different aspects of ToM and empathy. Directly contrasting affective (aff) as well as cognitive (cog) ToM to the control (phy) condition, activation was found in classical ToM regions, namely parts of the temporal lobe including the superior temporal sulcus, the supplementary motor area, and parietal structures in the right hemisphere. The contrast aff > phy yielded additional activation in the orbitofrontal cortex on the right and the cingulate cortex, the precentral and inferior frontal gyrus and the cerebellum on the left. The right BG were recruited in this contrast as well. The direct contrast aff > cog showed activation in the temporoparietal junction and the cingulate cortex on the right as well as in the left supplementary motor area. The reverse contrast cog > aff however did not yield any significant clusters. In summary, affective and cognitive ToM partly share neural correlates but can also be differentiated anatomically. Furthermore, the BG are involved in affective ToM and thus their contribution is discussed as possibly providing a motor component of simulation processes, particularly in affective ToM.     

Communication styles of children of mothers with affective disorders,chronic medical illness,and normal controls: A contextual perspective

Research has demonstrated impaired parent-child relationships in families with affective disorders. The present study examines the association of children's interactional style during a direct conflict-solving task to both the mother's interactional style and the child's diagnostic status. The sample includes 63 children, ages 8 to 16, of mothers with affective disorders, chronic medical illness, and normal controls. Children's dominant coping style profile (CS) (autonomous, neutral, or critical) was related to their mother's affective style (AS) (benign or negative). Affective disorder in the child at 6-month followup was associated with a critical CS profile at intake, while the child's nonaffective symptomatology was unrelated to CS. Findings indicate that children's affective disturbance is linked to interpersonal deficits in affectively charged situations. Results suggest that the child's CS is more strongly predicted by maternal aa than by either the child's or the mother's diagnostic status.This research was supported in part by an award from the William T. Grant Foundation. We are grateful for the contributions of Dorli Burge, Lori Briganty, Jennifer Kim, and Heidi Fink to the project. We also acknowledge the helpful comments of Angus Strachan and Michael Goldstein.