Deborah A. Yurgelun-Todd

The Residual Cognitive Effects of Heavy Marijuana Use in College Students

OBJECTIVE To assess whether frequent marijuana use is associated with residual neuropsychological effects. DESIGN Single-blind comparison of regular users vs infrequent users of marijuana. PARTICIPANTS Two samples of college undergraduates: 65 heavy users, who had smoked marijuana a median of 29 days in the last 30 days (range, 22 to 30 days) and who also displayed cannabinoids in their urine, and 64 light users, who had smoked a median of 1 day in the last 30 days (range, 0 to 9 days) and who displayed no urinary cannabinoids. INTERVENTION Subjects arrived at 2 PM on day 1 of their study visit, then remained at our center overnight under supervision. Neuropsychological tests were administered to all subjects starting at 9 AM on day 2. Thus, all subjects were abstinent from marijuana and other drugs for a minimum of 19 hours before testing. MAIN OUTCOME MEASURES Subjects received a battery of standard neuropsychological tests to assess general intellectual functioning, abstraction ability, sustained attention, verbal fluency, and ability to learn and recall new verbal and visuospatial information. RESULTS Heavy users displayed significantly greater impairment than light users on attention/executive functions, as evidenced particularly by greater perseverations on card sorting and reduced learning of word lists. These differences remained after controlling for potential confounding variables, such as estimated levels of premorbid cognitive functioning, and for use of alcohol and other substances in the two groups. CONCLUSIONS Heavy marijuana use is associated with residual neuropsychological effects even after a day of supervised abstinence from the drug. However, the question remains open as to whether this impairment is due to a residue of drug in the brain, a withdrawal effect from the drug, or a frank neurotoxic effect of the drug. from marijuana

Emotional and cognitive changes during adolescence.

Adolescence is a critical period for maturation of neurobiological processes that underlie higher cognitive functions and social and emotional behavior. Recent studies have applied new advances in magnetic resonance imaging to increase understanding of the neurobiological changes that occur during the transition from childhood to early adulthood. Structural imaging data indicate progressive and regressive changes in the relative volumes of specific brain regions, although total brain volume is not significantly altered. The prefrontal cortex matures later than other regions and its development is paralleled by increased abilities in abstract reasoning, attentional shifting, response inhibition and processing speed. Changes in emotional capacity, including improvements in affective modulation and discrimination of emotional cues, are also seen during adolescence. Functional imaging studies using cognitive and affective challenges have shown that frontal cortical networks undergo developmental changes in processing. In summary, brain regions that underlie attention, reward evaluation, affective discrimination, response inhibition and goal-directed behavior undergo structural and functional re-organization throughout late childhood and early adulthood. Evidence from recent imaging studies supports a model by which the frontal cortex adopts an increasingly regulatory role. These neurobiological changes are believed to contribute, in part, to the range in cognitive and affective behavior seen during adolescence.

Early-onset cannabis use and cognitive deficits: what is the nature of the association?

BACKGROUND Individuals who initiate cannabis use at an early age, when the brain is still developing, might be more vulnerable to lasting neuropsychological deficits than individuals who begin use later in life. METHODS We analyzed neuropsychological test results from 122 long-term heavy cannabis users and 87 comparison subjects with minimal cannabis exposure, all of whom had undergone a 28-day period of abstinence from cannabis, monitored by daily or every-other-day observed urine samples. We compared early-onset cannabis users with late-onset users and with controls, using linear regression controlling for age, sex, ethnicity, and attributes of family of origin. RESULTS The 69 early-onset users (who began smoking before age 17) differed significantly from both the 53 late-onset users (who began smoking at age 17 or later) and from the 87 controls on several measures, most notably verbal IQ (VIQ). Few differences were found between late-onset users and controls on the test battery. However, when we adjusted for VIQ, virtually all differences between early-onset users and controls on test measures ceased to be significant. CONCLUSIONS Early-onset cannabis users exhibit poorer cognitive performance than late-onset users or control subjects, especially in VIQ, but the cause of this difference cannot be determined from our data. The difference may reflect (1). innate differences between groups in cognitive ability, antedating first cannabis use; (2). an actual neurotoxic effect of cannabis on the developing brain; or (3). poorer learning of conventional cognitive skills by young cannabis users who have eschewed academics and diverged from the mainstream culture.

Cortical and limbic activation during viewing of high- versus low-calorie foods

Despite the high prevalence of obesity, eating disorders, and weight-related health problems in modernized cultures, the neural systems regulating human feeding remain poorly understood. Therefore, we applied functional magnetic resonance imaging (fMRI) to study the cerebral responses of 13 healthy normal-weight adult women as they viewed color photographs of food. The motivational salience of the stimuli was manipulated by presenting images from three categories: high-calorie foods, low-calorie foods, and nonedible dining-related utensils. Both food categories were associated with bilateral activation of the amygdala and ventromedial prefrontal cortex. High-calorie foods yielded significant activation within the medial and dorsolateral prefrontal cortex, thalamus, hypothalamus, corpus callosum, and cerebellum. Low-calorie foods yielded smaller regions of focal activation within medial orbitofrontal cortex; primary gustatory/somatosensory cortex; and superior, middle, and medial temporal regions. Findings suggest that the amygdala may be responsive to a general category of biologically relevant stimuli such as food, whereas separate ventromedial prefrontal systems may be activated depending on the perceived reward value or motivational salience of food stimuli.

Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study

BACKGROUND Previous studies have shown that major depression is frequently accompanied by hypercortisolemia. There is some evidence suggesting that an increase in the glucocorticoid levels may make hippocampal cells more vulnerable to insults caused by hypoxia, hypoglycemia, or excitatory neurotransmitters. Using magnetic resonance imaging (MRI), the hippocampi of patients with major depression were measured and compared with values observed in control subjects. METHODS Thirty-eight patients with primary unipolar major depression were recruited. Twenty control subjects were matched for age, gender, and years of education. The hippocampal volume was measured from coronal MRI scans in all of the subjects. Patients were also grouped and compared as responders and nonresponders to treatment with fluoxetine of 20 mg/day, for 8 weeks. Hamilton Depression Rating Scale (HDRS) was used to determine the severity of depression. RESULTS No significant differences were observed between the hippocampal volumes of patients with major depression and control subjects; however, a significant correlation was observed between the left hippocampal volume of men and their HDRS baseline values. In addition, female responders had a statistically significant higher mean right hippocampal volume than nonresponders. CONCLUSIONS The results of our study indicate no reduction in the volume of the hippocampus in patients with major depression. Nonetheless, the results do suggest that the effects of disease severity, gender, and treatment response may influence hippocampal volume.

Phenomenologic relationship of eating disorders to major affective disorder

We administered the National Institute of Mental Health Diagnostic Interview Schedule to 41 patients with a lifetime history of anorexia nervosa (25 with and 16 without bulimia) and to 49 patients with bulimia alone. Results showed that 77% of the patients with eating disorders had a lifetime diagnosis of DSM-III major affective disorder, a rate significantly higher than that found in comparison groups composed of the first-degree relatives of probands with schizophrenia and bipolar disorder. High lifetime rates of anxiety disorders, substance use disorders, and kleptomania were also observed. By contrast, few cases of personality disorders and no cases of schizophrenia were found. These findings combine with the results of studies of family history, long-term outcome, response to biological tests, and treatment response to suggest that anorexia nervosa and bulimia may be closely related to major affective disorder.

Functional anatomy of impaired selective attention and compensatory processing in autism

In autism, physiological indices of selective attention have been shown to be abnormal even in situations where behaviour is intact. This divergence between behaviour and physiology suggests the action of some compensatory process of attention, one which may hold clues to the aetiology of autisms characteristic cognitive phenotype. Six subjects with autism spectrum disorders and six normal control subjects were studied with functional magnetic resonance imaging while performing a bilateral visual spatial attention task. In normal subjects, the task evoked activation in a network of cortical regions including the superior parietal lobe (P<0.001), left middle temporal gyrus (P=0.002), left inferior (P<0.001) and middle (P<0.02) frontal gyri, and medial frontal gyrus (P<0.02). Autistic subjects, in contrast, showed activation in the bilateral ventral occipital cortex (P<0.03) and striate cortex (P<0.05). Within the task condition, a region-of-interest comparison of attend-left versus attend-right conditions indicated that modulation of activation in the autistic brain as a function of the lateral focus of spatial attention was abnormally decreased in the left ventral occipital cortex (P<0.03), abnormally increased in the left intraparietal sulcus (P<0.01), and abnormally variable in the superior parietal lobe (P<0.03). These results are discussed in terms of a model of autism in which a pervasive defect of neural and synaptic development produces over-connected neural systems prone to noise and crosstalk, resulting in hyper-arousal and reduced selectivity. These low-level attentional traits may be the developmental basis for higher-order cognitive styles such as weak central coherence.

Sex differences in amygdala activation during the perception of facial affect

The cognitive and affective systems of the cerebral cortex are often more lateralized in males than females, but it is unclear whether these differences extend to subcortical systems. We used fMRI to examine sex differences in lateralized amygdala activity during happy and fearful face perception. Amygdala activation differed for men and women depending on the valence of the expression. Overall, males were more lateralized than females, but the direction differed between valence conditions. Happy faces produced greater right than left amygdala activation for males but not females. Both sexes showed greater left amygdala activation for fearful faces. These findings suggest that the lateralization of affective function may extend beyond the cortex to subcortical regions such as the amygdala.

Sex-specific developmental changes in amygdala responses to affective faces.

It is hypothesized that adolescent development involves a redistribution of cerebral functions from lower subcortical structures to higher regions of the prefrontal cortex to provide greater self-control over emotional behavior. We further hypothesized that this redistribution is likely to be moderated by sex-specific hormonal changes. To examine developmental sex differences in affective processing, 19 children and adolescents underwent fMRI while viewing photographs of faces expressing fear. Males and females differed in the pattern of their amygdala vs prefrontal activation during adolescent maturation. With age, females showed a progressive increase in prefrontal relative to amygdala activation in the left hemisphere, whereas males failed to show a significant age related difference. There appear to be sex differences in the functional maturation of affect-related prefrontal–amygdala circuits during adolescence.

Functional Magnetic Resonance Imaging of Facial Affect Recognition in Children and Adolescents

OBJECTIVE To examine further the role of the amygdala in the recognition of facial expression in adolescents. METHOD Twelve healthy adolescents were studied using functional magnetic resonance imaging technology during a task of facial affect recognition and a visual control task. RESULTS All subjects demonstrated a significant increase in signal intensity in the amygdala for the facial expression recognition task. CONCLUSIONS The data are consistent with previous work in healthy adult subjects implicating the amygdala as essential for the recognition of fearful facial expression.