Findings on white matter micro-structure provide further evidence of different neuromaturational trajectories for boys and girls. In a whole-brain voxel wise DTI study of 106 children and adolescents 5–18 years of age, males had higher FA in bilateral frontal white matter areas, right arcuate fasciculus, and left parietal and occipito-parietal regions, while females showed higher FA in the splenium of the corpus callosum . Females displayed age-related increases in FA in all regions, whereas males did not. Other findings suggest higher FA in the genu in adolescent males compared to females , while fiber tract analysis of 31 children and adolescents documents no sex-related FA differences . It is possible that power differences in voxelwise versus tractography methods and in sample size contribute to discrepant findings. Different mechanisms of white matter growth, specifically, an increase in axonal diameter in males and a growth in myelin content in females, are implicated from magnetization-transfer ratio analysis . Indeed, higher levels of lutenizing hormone is associated with greater white matter content , and increasing testosterone levels may influence axonal diameter in males . Together, these findings suggest a role for sex hormones in developmental trajectories of cortical and white matter maturation.Brain regions with input from the neurotransmitter dopamine that comprise the reward system undergo pronounced developmental changes during adolescence . In particular, the density of dopaminergic connections to the prefrontal cortex increases in this phase of life . Activity of the dopamine degrading enzyme catechol-O-methyltransferase appears to increase in mid-adulthood based on post mortem studies ,hydroponic drain table but does not differ between infants, adolescents, and young adults.
This post-adolescent maturation may facilitate improved dopaminergic transmission to and within the prefrontal cortex. Dopamine synthesis and turnover in portions of the prefrontal cortex that project to sub-cortical regions increase from adolescence to adulthood , and this dopamine balance shift between prefrontal and sub-cortical structures may be due to pruning in the neocortex . In a study from Sweden, binding potential of the dopamine D1 receptor was evaluated in individuals spanning ages 10–30 using positron emission tomography. Binding potential declined non-linearly in all regions, most prominently in cortical regions including the dorsolateral prefrontal cortex during adolescence, with reductions of 26% from adolescence to young adulthood in frontal, anterior cingulate, and occipital cortex over one decade. A slower to flat decline in binding potential was seen for orbitofrontal and posterior cingulate and striatal regions . Expression of the dopamine D2 receptors in the prefrontal cortex peak in infancy then by adolescence reach adult levels . In contrast, prefrontal levels of the dopamine receptor D4 show little change with age . Overall, the development of dopaminergic transmission varies across particular receptor types, with some showing marked changes well into the third decade of life, past the stage typically considered adolescence. The inhibitory GABAergic system also shows development during adolescence. In rats, fibers from the basolateral amygdala continue to form connections with GABAergic interneurons in the prefrontal cortex throughout periadolescence . In non-human primates, GABAergic inputs to pyramidal cells undergo changes during the perinatal period and adolescence in concert with continued maturation of behaviors mediated by the prefrontal cortex . The timing of improved executive functioning and working memory performance appears to correspond with maturing GABAergic inhibitory circuits containing the protein parvalbumin .
In humans, the input to GABAergic interneurons in the prefrontal cortex appears to decrease strongly from adolescence to adulthood . Neurotransmission is influenced by activity in receptors for adrenal and gonadal hormones. Puberty-related hormonal development begins with changes in excitatory and inhibitory inputs to gonadotropin-releasing hormone neurons in the pituitary gland. This activity has clear influences on aggression and sexual behavior, but a less clear role concerning impulsivity and cognition . The neurotransmitter changes occurring during adolescence are in synchrony with the anatomical changes seen in the prefrontal cortex and other brain regions during this stage, as well as maturation of cognition and behavior and the emerging increased risk for psychopathology . Changes in dopamine and reward circuitry arecritical to assigning value and reinforcing behaviors, such as social interaction, food consumption, romantic behaviors, novelty seeking, and alcohol and other drug intake , while ongoing refinement of inhibitory neurotransmission has broad implications for information processing and modulation of impulses.Neuromaturation in the form of brain volume, structure, and neurochemistry changes during adolescence occurs along with numerous behavioral alterations. Among these, the acquisition and demonstration of advanced cognitive skills is particularly notable. Higher-order cognitive functions such as working memory, planning, problem solving, and inhibitory control are developing during adolescence and historically linked to maturation of the frontal lobes . The study of brain structure-function relationships has considerably burgeoned with the use of fiber tractography and fMRI, providing an appreciation for more distributed neural circuitry including frontosub-cortical networks as the seat of complex cognitive and executive skills . The correspondence between white matter development during adolescence and neurocognitive performance has been demonstrated in a number of recent studies. Intellectual functioning in youth is associated with the development of white matter circuitry in bilateral frontal, occipito-parietal, and occipito-temporoparietal regions .
The reading skills of children and adolescents improve with white matter changes in the internal capsule, corona radiata, and temporo-parietal regions , and greater left lateralization of the arcuate fasciculus fibers is associated with improved phonological processing and receptive vocabulary . Better visuospatial construction and psychomotor performance are associated with high corpus callosum FA . Visuospatial working memory capacity is linked to a fronto-intraparietal network , whereas delayed visual memory is linked to temporal and occipital FA . Verbal memory proficiency is related to decreased MD and decreased RD in left uncinate fasciculus and with parietal and cerebellar white matter integrity . As these studies are based on cross-sectional data, we examined whether the extent of white matter maturation during late adolescence would be linked to performance on measures of working memory, executive functioning, and learning and recall. Greater extent of FA increase and RD decrease in the right posterior limb of the internal capsule over time correlated with better complex attention and phonemic fluency in adolescents, and greater increase in MD and AD in the right inferior fronto-occipital fasciculus was associated with improved visuoconstruction ability and learning and recall .The social environment reaches heightened salience in adolescence when self-monitoring, sensitivity to evaluation, and awareness of others’ perspectives become increasingly apparent . Brain structures subserving socio-emotional processing continue to mature in this age group with demonstrable effects in blood-oxygenationlevel-dependent response. Amygdala, orbitofrontal cortex, and anterior cingulate cortex activation to facial affect processing is prominent in adolescence relative to adulthood with shifts toward more dorsolateral prefrontal activation with age . Differences in activation patterns, with girls showing bilateral and boys only right prefrontal response, may underlie sex-related nuances in behavioral response to affect and emotion. Nonetheless, adolescents as a group show elevated activity in bottom-up emotion processing centers ,rolling benches hydroponics suggesting that they are more likely to be influenced by emotional context than adults. As a result, poor decisions are often made in states of emotional reactivity. Although increased frontoamygdala activity during emotional processing habituates with repeated exposure, individuals with higher selfrated trait anxiety show less adaptation over time.Adolescents’ proclivity toward risk-taking behavior and susceptibility to poor decision-making may be related to unique neural characteristics that increase their sensitivity to rewarding outcomes. Two primary theories of reward processing in adolescence have received support, each purporting different functional trends in the striatum. One posits that hypoactivation of the striatal system leads adolescents to engage in reward seeking as a compensatory response. The other suggests that the striatum behaves in a contrasting manner; that its hyperactivity leads to greater reward-seeking behavior. Recent fMRI evidence lends support to the latter hypothesis and is reviewed in detail elsewhere . Briefly, greater ventral striatal activation has been shown in adolescents compared to children and adults in anticipation of reward and during reward receipt . During reward processing, BOLD signal showed attenuations in the ventral striatum when adolescents were required to assess an incentive cue, but showed elevations during reward anticipation , suggesting that adolescents may have limited capacity to assess potential reward outcomes and have exaggerated reactivity when anticipating reward compared with adults.
Underlying the hyperactivation of the striatum is an increase in ventral striatal dopamine release during rewarding events . Greater dopamine release may lead adolescents to seek additional rewards, resulting in a reinforcing cycle of reward-seeking behavior. Pubertal maturation is associated with increases in sensation seeking and may play a role in reward sensitivity. Forbes et al. found less striatal and more medial prefrontal cortex activity in response to reward outcome in adolescents with more advanced pubertal maturation compared to similar-aged adolescents with less advanced pubertal maturation. Further, the putative role of the medial prefrontal cortex in self-processing and social cognition suggests that maturing adolescents may consider the social context and peer influences when responding to reward . Affective status may interact with neural response to reward, as low striatal and high prefrontal activity were linked to depressive symptoms. Indeed, adolescents show an increase in risky behavior when the situation evokes affective processing. Hormone levels may additionally influence reward sensitivity. Higher testosterone levels were associated with reduced reward outcome-related striatal activity for both males and females, implicating a unique contribution of this hormone to reward processing. Due to their neural profiles, adolescents may show a greater propensity for high stakes rewards that incline them toward risk-taking and sensation seeking .Alcohol is by far the most widely used intoxicant among adolescents in the U.S., and rates of use increase dramatically during the teenage years . By 8th grade, 37% of students have tried alcohol, increasing to 72% by 12th grade . Past-month rates of getting drunk increase from 5% to 27%, and having consumed 5 drinks in a row in the past 2 weeks expands from 8% to 25% from 8th to 12th graders. Nicotine is fairly widely used, with 6% of 8th graders reporting any use in the past month, compared to 20% of 12th graders. Marijuana is the second most used intoxicant, with 16% of 8th graders and 42% of 12th graders reporting use at least once in their lifetime , and 21% of high school seniors endorse past month use. Other drug use is not as widespread yet still concerning, with past month use among 12th graders of amphetamines and misused narcotic pain pills at 3% and 4%, respectively . Approximately 8% of those ages 12–17 meet criteria for substance abuse or dependence in the past year, but this peaks between ages 18–25, when 21% meet diagnostic criteria for a substance use disorder . Those with early substance use onset are more likely to continue use into adulthood; individuals who first used alcohol at age 14 or younger have a >5 time increased risk of lifetime alcohol use disorder as compared to those who first used alcohol after the U.S. legal limit of the 21st birthday . Adolescent alcohol and marijuana use has been linked to harmful effects on physiological, social, and psychological functioning . This includes increased delinquency , aggressivity, risky sexual behaviors, hazardous driving, and comorbid substance use .Given the extent of brain maturation occurring during this phase in life, adolescents who use substances appear to be vulnerable to alterations in brain functioning, cognition and behavior. Indication that alcohol and marijuana use may detrimentally influence the developing brain comes from studies showing diminutions in neurocognitive functioning, especially attention, visuospatial functioning, and learning and retrieval of verbal and nonverbal information ; morphological changes ; anisotropic differences in white matter ; and a more distributed functional network and recruitment of alternate brain regions . Heavy alcohol use is associated with a wide range of neural consequences in adults and similar sequelae are implicated in adolescent users. Hippocampal and prefrontal white matter volumes appear smaller in heavy alcohol using adolescents . Alterations in anisotropy in the genu and isthmus of the corpus callosum in alcohol-using teens and in frontal, cerebellar, temporal, and parietal regions in adolescent binge-drinkers lends further support to atypical developmental trajectories. White matter quality appears to relate to drinking in a dose dependent manner, where higher blood alcohol concentrations are associated with poorer tissue integrity in the corpus callosum, internal and external capsules, and superior corona radiata .