Michael A. Jenike

Masked Presentations of Emotional Facial Expressions Modulate Amygdala Activity without Explicit Knowledge

Functional magnetic resonance imaging (fMRI) of the human brain was used to study whether the amygdala is activated in response to emotional stimuli, even in the absence of explicit knowledge that such stimuli were presented. Pictures of human faces bearing fearful or happy expressions were presented to 10 normal, healthy subjects by using a backward masking procedure that resulted in 8 of 10 subjects reporting that they had not seen these facial expressions. The backward masking procedure consisted of 33 msec presentations of fearful or happy facial expressions, their offset coincident with the onset of 167 msec presentations of neutral facial expressions. Although subjects reported seeing only neutral faces, blood oxygen level-dependent (BOLD) fMRI signal in the amygdala was significantly higher during viewing of masked fearful faces than during the viewing of masked happy faces. This difference was composed of significant signal increases in the amygdala to masked fearful faces as well as significant signal decreases to masked happy faces, consistent with the notion that the level of amygdala activation is affected differentially by the emotional valence of external stimuli. In addition, these facial expressions activated the sublenticular substantia innominata (SI), where signal increases were observed to both fearful and happy faces—suggesting a spatial dissociation of territories that respond to emotional valence versus salience or arousal value. This study, using fMRI in conjunction with masked stimulus presentations, represents an initial step toward determining the role of the amygdala in nonconscious processing.

Dorsal anterior cingulate cortex: A role in reward-based decision making

Dorsal anterior cingulate cortex (dACC) is a brain region that subserves cognition and motor control, but the mechanisms of these functions remain unknown. Human neuroimaging and monkey electrophysiology studies have provided valuable insights, but it has been difficult to link the two literatures. Based on monkey single-unit recordings, we hypothesized that human dACC is comprised of a mixture of functionally distinct cells that variously anticipate and detect targets, indicate novelty, influence motor responses, encode reward values, and signal errors. As an initial test of this conceptualization, the current event-related functional MRI study used a reward-based decision-making task to isolate responses from a subpopulation of dACC cells sensitive to reward reduction. As predicted, seven of eight subjects showed significant (P < 10−4) dACC activation when contrasting reduced reward (REDrew) trials to fixation (FIX). Confirmatory group analyses then corroborated the predicted ordinal relationships of functional MRI activation expected during each trial type (REDrew > SWITCH > CONrew ≥ FIX). The data support a role for dACC in reward-based decision making, and by linking the human and monkey literatures, provide initial support for the existence of heterogeneity within dACC. These findings should be of interest to those studying reward, cognition, emotion, motivation, and motor control.∥

Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the counting stroop

BACKGROUND The anterior cingulate cognitive division (ACcd) plays a central role in attentional processing by: 1) modulating stimulus selection (i.e., focusing attention) and/or 2) mediating response selection. We hypothesized that ACcd dysfunction might therefore contribute to producing core features of attention-deficit/hyperactivity disorder (ADHD), namely inattention and impulsivity. ADHD subjects have indeed shown performance deficits on the Color Stroop, an attentional/cognitive interference task known to recruit the ACcd. Recently, the Counting Stroop, a Stroop-variant specialized for functional magnetic resonance imaging (fMRI), produced ACcd activation in healthy adults. In the present fMRI study, the Counting Stroop was used to examine the functional integrity of the ACcd in ADHD. METHODS Sixteen unmedicated adults from two groups (8 with ADHD and 8 matched control subjects) performed the Counting Stroop during fMRI. RESULTS While both groups showed an interference effect, the ADHD group, in contrast to control subjects, failed to activate the ACcd during the Counting Stroop. Direct comparisons showed ACcd activity was significantly higher in the control group. ADHD subjects did activate a frontostriatal-insular network, indicating ACcd hypoactivity was not caused by globally poor neuronal responsiveness. CONCLUSIONS The data support a hypothesized dysfunction of the ACcd in ADHD.

The counting stroop: An interference task specialized for functional neuroimaging—validation study with functional MRI

The anterior cingulate cortex has been activated by color Stroop tasks, supporting the hypothesis that it is recruited to mediate response selection or allocate attentional resources when confronted with competing information‐processing streams. The current study used the newly developed “Counting Stroop” to identify the mediating neural substrate of cognitive interference. The Counting Stroop, a Stroop variant allowing on‐line response time measurements while obviating speech, was created because speaking produces head movements that can exceed those tolerated by functional magnetic resonance imaging (fMRI), preventing the collection of vital performance data. During this task, subjects report by button‐press the number of words (1–4) on the screen, regardless of word meaning. Interference trials contain number words that are incongruent with the correct response (e.g., “two” written three times), while neutral trials contain single semantic category common animals (e.g., “bird”). Nine normal right‐handed adult volunteers underwent fMRI while performing the Counting Stroop. Group fMRI data revealed significant (P ≤ 10‐4) activity in the cognitive division of anterior cingulate cortex when contrasting the interference vs. neutral conditions. On‐line performance data showed 1) longer reaction times for interference blocks than for neutral ones, and 2) decreasing reaction times with practice during interference trials (diminished interference effects), indicating that learning occurred. The performance data proved to be a useful guide in analyzing the image data. The relative difference in anterior cingulate activity between the interference and neutral conditions decreased as subjects learned the task. These findings have ramifications for attentional, cognitive interference, learning, and motor control mechanism theories. Hum. Brain Mapping 6:270–282, 1998.

The emotional counting stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division

BACKGROUND The emotional counting Stroop (ecStroop) functional magnetic resonance imaging (fMRI) activation paradigm was designed to recruit the anterior cingulate affective division (ACad). METHODS Nine normal, healthy male and female subjects (mean age 24.2 years) reported via button press the number of neutral and negative words that appeared on a screen while reaction time and fMRI data were acquired. RESULTS We observed a) greater ACad activation for negative versus neutral words during initial presentation blocks; b) lower overall ACad signal intensity during task performance (i.e., both negative and neutral words) compared to the baseline fixation condition; and c) no reaction time increase to negative versus neutral words. CONCLUSIONS In a companion study of a cognitive version of the counting Stroop (Bush et al 1998), these same 9 subjects a) activated the more dorsal anterior cingulate cognitive division; b) also showed the overall decrease in ACad signal intensity; and c) demonstrated a reliable reaction time effect. Taken together, these data offer a within-group spatial dissociation of AC function based upon information content (i.e., cognitive vs. emotional) and/or presence of behavioral interference. We propose that the ecStroop will be a useful fMRI probe of ACad function in anxiety disorders.

Organizational strategies mediate nonverbal memory impairment in obsessive–compulsive disorder

BACKGROUND Previous neuropsychological studies of obsessive-compulsive disorder (OCD) have indicated impaired executive functioning and nonverbal memory. The extent to which impaired executive functioning impacts nonverbal memory has not been established. The current study investigated the mediating effects of organizational strategies used when copying a figure on subsequent nonverbal memory for that figure. METHODS We examined neuropsychological performance in 20 unmedicated subjects with OCD and 20 matched normal control subjects. Subjects were administered the Rey-Osterrieth Complex Figure Test (RCFT) and neuropsychological tests assessing various aspects of executive function. RESULTS OCD subjects differed significantly from healthy control subjects in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in immediate percent recall were significantly mediated by copy organizational strategies. Further exploratory analyses indicated that organizational problems in OCD may be related to difficulties shifting mental and/or spatial set. CONCLUSIONS Immediate nonverbal memory problems in OCD subjects were mediated by impaired organizational strategies used during the initial copy of the RCFT figure. Thus, the primary deficit was one affecting executive function, which then had a secondary effect on immediate memory. These findings are consistent with current theories proposing frontal-striatal system dysfunction in OCD.

The functional neuroanatomy of anxiety: a study of three disorders using positron emission tomography and symptom provocation

Previous neuroimaging research has contributed insights regarding the neural substrates of specific psychiatric disorders. The purpose of this study was to determine the shared mediating neuroanatomy of anxiety symptoms across three different anxiety disorders. Data were pooled from 23 right-handed adult outpatients meeting criteria for obsessive-compulsive disorder, simple phobia, or posttraumatic stress disorder. Relative regional cerebral blood flow (rCBF) was measured using positron emission tomography in the context of symptom provocation paradigms. Symptom severity was measured via self-reports. The analysis of pooled imaging data indicated activation in right inferior frontal cortex, right posterior medial orbitofrontal cortex, bilateral insular cortex, bilateral lenticulate nuclei, and bilateral brain stem foci during the symptomatic versus control conditions. A positive correlation was found between rCBF at one brain stem locus and subjective anxiety scores (r = .744, p < .001). These findings suggest that elements of the paralimbic belt together with right inferior frontal cortex and subcortical nuclei mediate symptoms across different anxiety disorders. In addition, activation at one brain stem locus appears to be associated with the subjective severity of anxiety. Further studies are warranted to determine whether these same brain systems mediate normal anxiety states as well.

Augmentation of Behavior Therapy With d -Cycloserine for Obsessive-Compulsive Disorder

OBJECTIVE This study examined whether d-cycloserine, a partial agonist at the N-methyl-D-aspartate (NMDA) glutamatergic receptor, enhances the efficacy of behavior therapy for obsessive-compulsive disorder (OCD). METHOD A randomized, double-blind, placebo-controlled trial investigating D-cycloserine versus placebo augmentation of behavior therapy was conducted in 23 OCD patients. Patients first underwent a diagnostic interview and pretreatment evaluation, followed by a psychoeducational/treatment planning session. Then they received 10 behavior therapy sessions. Treatment sessions were conducted twice per week. One hour before each of the behavior therapy sessions, the participants received either D-cycloserine, 100 mg, or a placebo. RESULTS Relative to the placebo group, the D-cycloserine groups OCD symptoms were significantly more improved at mid-treatment, and the D-cycloserine groups depressive symptoms were significantly more improved at posttreatment. CONCLUSIONS These data provide support for the use of D-cycloserine as an augmentation of behavior therapy for OCD and extend findings in animals and other human disorders suggesting that behavior therapy acts by way of long-term potentiation of glutamatergic pathways and that the effects of behavior therapy are potentiated by an NMDA agonist.

Long‐term outcome of pediatric obsessive–compulsive disorder: a meta‐analysis and qualitative review of the literature

Objective:  To review the extant literature on the long‐term outcome of child/adolescent‐onset obsessive–compulsive disorder (OCD).

Strategic processing and episodic memory impairment in obsessive compulsive disorder.

There is evidence that nonverbal memory problems in obsessive compulsive disorder (OCD) are mediated by impaired strategic processing. Although many studies have found verbal memory to be normal in OCD, these studies did not use tests designed to stress organizational strategies. This study examined verbal and nonverbal memory performance in 33 OCD patients and 30 normal control participants with the Rey-Osterrieth Complex Figure Test and the California Verbal Learning Test. OCD patients were impaired on verbal and nonverbal measures of organizational strategy and free recall. Multiple regression modeling indicated that free recall problems in OCD were mediated by impaired organizational strategies used during learning trials. Therefore, verbal and nonverbal episodic memory deficits in OCD are affected by impaired strategic processing. Results are consistent with neurobiological models proposing frontal-striatal system dysfunction in OCD.