Michael W. Schlund

Effects of citalopram on worry and brain activation in patients with generalized anxiety disorder

The effects of auditory statements describing a personal worry on brain activation as measured by functional magnetic resonance imaging were examined in patients with generalized anxiety disorder (GAD) before and after anxiety reduction with citalopram. Six patients were imaged while listening to verbal descriptions of a personal worry or a neutral statement before treatment with citalopram and after 7 weeks of treatment. Pre-post drug analyses showed treatment with citalopram reduced self-reported anxiety and reduced BOLD responses to a pathology-specific worry and a neutral stimulus. After treatment, worry sentences, compared to neutral statements, elicit reduced BOLD responses in prefrontal regions, the striatum, insula and paralimbic regions. In addition, contrasts before and after treatment revealed reductions in the differential response that existed between worry and neutral statements. Overall reduction of BOLD response was most prominent during neutral statements, particularly in the left hemisphere. These findings support the clinical impression that GAD patients overreact to both pathology-specific and non-specific cues and that the reduction of anxiety attenuates the response to both types of cues.

Amygdala involvement in human avoidance, escape and approach behavior

Many forms of psychopathology and substance abuse problems are characterized by chronic ritualized forms of avoidance and escape behavior that are designed to control or modify external or internal (i.e., thoughts, emotions, bodily sensations) threats. In this functional magnetic resonance imaging investigation, we examined amygdala reactivity to threatening cues when avoidance responding consistently prevented contact with an upcoming aversive event (money loss). In addition, we examined escape responding that terminated immediate escalating money loss and approach responding that produced a future money gain. Results showed cues prompting avoidance, escape and approach behavior recruited a similar fronto-striatal-parietal network. Within the amygdala, bilateral activation was observed to threatening avoidance and escape cues, even though money loss was consistently avoided, as well as to the reward cue. The magnitude of amygdala responses within subjects was relatively similar to avoidance, escape and approach cues, but considerable between-subject differences were found. The heightened amygdala response to avoidance and escape cues observed within a subset of subjects suggests threat-related responses can be maintained even when aversive events are consistently avoided, which may account for the persistence of avoidance-coping in various clinical disorders. Further assessment of the relation between amygdala reactivity and avoidance-escape behavior may prove useful in identifying individuals with or at risk for neuropsychiatric disorders.

Nothing to fear? Neural systems supporting avoidance behavior in healthy youths

Active avoidance involving controlling and modifying threatening situations characterizes many forms of clinical pathology, particularly childhood anxiety. Presently our understanding of the neural systems supporting human avoidance is largely based on nonhuman research. Establishing the generality of nonhuman findings to healthy children is a needed first step towards advancing developmental affective neuroscience research on avoidance in childhood anxiety. Accordingly, this investigation examined brain activation patterns to threatening cues that prompted avoidance in healthy youths. During functional magnetic resonance imaging, fifteen youths (ages 9-13) completed a task that alternately required approach or avoidance behaviors. On each trial either a threatening Snake cue or a Reward cue advanced towards a bank containing earned points. Directional buttons enabled subjects to move cues away from (Avoidance) or towards the bank (Approach). Avoidance cues elicited activation in regions hypothesized to support avoidance in nonhumans (amygdala, insula, striatum and thalamus). Results also highlighted that avoidance response rates were positively correlated with amygdala activation and negatively correlated with insula and anterior cingulate activation. Moreover, increased amygdala activity was associated with decreased insula and anterior cingulate activity. Our results suggest that nonhuman neurophysiological research findings on avoidance may generalize to neural systems associated with avoidance in childhood. Perhaps most importantly, the amygdala/insula activation observed suggests that threat-related responses can be maintained even when aversive events are consistently avoided, which may account for the persistence of avoidance-coping in childhood anxiety. The present approach may offer developmental affective neuroscience a conceptual and methodological framework for investigating avoidance in childhood anxiety.

Characteristics and outcomes of a home and community-based neurorehabilitation programme

The potential clinical and financial advantages of providing neurorehabilitation directly in patients homes and communities have recently been discussed. However, the specific characteristics and outcomes of a coordinated, interdisciplinary, home-based programme does not currently exist in the rehabilitation literature. The present paper presents patient demographics, type and intensity of services provided, satisfaction measures, and clinical outcomes for 77 brain injured individuals in an attempt to begin to define and evaluate this new level of care. Additionally, the challenges of conducting home-based rehabilitation, and needs for further research are discussed.

Effects of acquired brain injury on adaptive choice and the role of reduced sensitivity to contingencies

The present investigation examined the proposal that brain injury reduces sensitivity to consequences. On a laboratory task, controls and subjects with brain injury made repeated choices between a small amount of money and a larger amount of money followed by a post-reinforcer delay of 3, 12, 18, or 24 seconds. Increasing delays lowered reinforcement densities (i.e. money available per minute) associated with large reinforcers. Consequently, choosing large reinforcers became less adaptive. Results showed subjects with brain injury made less adaptive choices and earned significantly less money than controls, because of a preference for large reinforcers with low reinforcement densities. Maladaptive choice was not attributable to deficits in discriminating reinforcer magnitudes or delays. Results suggest individuals with brain injury may remain sensitive to consequences but fail to discriminate among significant response-consequence relations (i.e. contingencies). This view, emphasizing basic learning processes, may account for some problems in skill acquisition and adaptive choice.

Generalized anxiety modulates frontal and limbic activation in major depression

BackgroundAnxiety is relatively common in depression and capable of modifying the severity and course of depression. Yet our understanding of how anxiety modulates frontal and limbic activation in depression is limited.MethodsWe used functional magnetic resonance imaging and two emotional information processing tasks to examine frontal and limbic activation in ten patients with major depression and comorbid with preceding generalized anxiety (MDD/GAD) and ten non-depressed controls.ResultsConsistent with prior studies on depression, MDD/GAD patients showed hypoactivation in medial and middle frontal regions, as well as in the anterior cingulate, cingulate and insula. However, heightened anxiety in MDD/GAD patients was associated with increased activation in middle frontal regions and the insula and the effects varied with the type of emotional information presented.ConclusionsOur findings highlight frontal and limbic hypoactivation in patients with depression and comorbid anxiety and indicate that anxiety level may modulate frontal and limbic activation depending upon the emotional context. One implication of this finding is that divergent findings reported in the imaging literature on depression could reflect modulation of activation by anxiety level in response to different types of emotional information.

Neural correlates of derived relational responding on tests of stimulus equivalence

BackgroundAn essential component of cognition and language involves the formation of new conditional relations between stimuli based upon prior experiences. Results of investigations on transitive inference (TI) highlight a prominent role for the medial temporal lobe in maintaining associative relations among sequentially arranged stimuli (A > B > C > D > E). In this investigation, medial temporal lobe activity was assessed while subjects completed Stimulus Equivalence (SE) tests that required deriving conditional relations among stimuli within a class (A ≡ B ≡ C).MethodsStimuli consisted of six consonant-vowel-consonant triads divided into two classes (A1, B1, C1; A2, B2, C2). A simultaneous matching-to-sample task and differential reinforcement were employed during pretraining to establish the conditional relations A1:B1 and B1:C1 in class 1 and A2:B2 and B2:C2 in class 2. During functional neuroimaging, recombined stimulus pairs were presented and subjects judged (yes/no) whether stimuli were related. SE tests involved presenting three different types of within-class pairs: Symmetrical (B1 A1; C1 B1; B2 A2; C2 B2), and Transitive (A1 C1; A2 C2) and Equivalence (C1 A1; C2 A2) relations separated by a nodal stimulus. Cross-class Foils consisting of unrelated stimuli (e.g., A1 C2) were also presented.ResultsRelative to cross-class Foils, Transitive and Equivalence relations requiring inferential judgments elicited bilateral activation in the anterior hippocampus while Symmetrical relations elicited activation in the parahippocampus. Relative to each derived relation, Foils generally elicited bilateral activation in the parahippocampus, as well as in frontal and parietal lobe regions.ConclusionActivation observed in the hippocampus to nodal-dependent derived conditional relations (Transitive and Equivalence relations) highlights its involvement in maintaining relational structure and flexible memory expression among stimuli within a class (A ≡ B ≡ C).

Proton magnetic resonance spectroscopy in obsessive-compulsive disorder: A pilot investigation comparing treatment responders and non-responders

Proton magnetic resonance spectroscopic imaging was performed to compare brain metabolism in patients with obsessive-compulsive OCD. Evaluation was done on responders and non-responders to pharmacotherapy and on healthy controls. The results showed significantly lower NAA/Cr ratios in the right basal ganglia in non-responders than in responders or in controls and higher Cho/Cr ratios in the right thalamus in non-responders than responders. Abnormal neuronal metabolism in the right basal ganglia and right thalamus may be indicating lack of response to treatment to selective serotonin reuptake inhibitor.

Relations between traumatic brain injury and the environment: feedback reduces maladaptive behaviour exhibited by three persons with traumatic brain injury

Feedback is a commonly used technique in neurorehabilitation. It functions to strengthen or weaken select relations between individuals behaviour and their environment. The study of behaviour-environment relations is a focus of operant psychology, commonly referred to as behaviour analysis. Central to behaviour analysis is the analysis of interrelations among stimuli, behaviour, and consequences. The focus on behaviour-environment relations may have considerable benefits for designing clinical treatments and accounting for successful and unsuccessful treatments, especially psychological interventions for maladaptive behaviour. In the present investigation, three persons with traumatic brain injuries, diagnosed with depression and presenting mild cognitive impairments, received feedback about their maladaptive behaviour. Weekly feedback resulted in general reductions in the variability and frequency of maladaptive behaviour. The results support the utility of giving equal consideration to relations between persons with traumatic brain injury and their environment, despite existing psychological or cognitive impairments. Future research on variables that influence the development and maintenance of behaviour-environment relations, and more generally operant behaviour, may provide a unique perspective on the effects of traumatic brain injury.

The effects of traumatic brain injury on reporting and responding to causal relations: an investigation of sensitivity to reinforcement contingencies

Impairments in judging and responding to consequences that follow behaviour are often attributed to changes in various cognitive processes. An alternative conceptualization is that impairments may produce a reduction in sensitivity to reinforcement contingencies. The present investigation employed a methodology commonly used in research on judgements of causality to examine the effects of TBI on sensitivity to reinforcement contingencies. Participants were non-injured control subjects and adults with TBI. The experimental task required subjects to press a response key under a series of concurrent response-reinforcer contingencies that periodically delivered money for responding and not responding. Afterwards, subjects provided a judgement about each response-reinforcer contingency by reporting the amount of money earned for responding and for not responding. Results suggest that TBI reduced the sensitivity of judgements and responding under select contingencies. These results lend some support to the view that TBI may reduce sensitivity to reinforcement contingencies. Furthermore, the investigation highlights the potential benefits of employing methods commonly used in human and animal operant research for the study of TBI.