A randomized controlled trial of cognitive-behavior therapy for tinnitus.

This study is a randomized, waitlist-controlled trial testing the effect of a brief, "manualized" cognitive-behavioral group therapy on distress associated with tinnitus, quality of well-being, psychological distress including depression, and internal focus. Cognitive-behavioral therapy (CBT) included training in activity planning, relaxation training and, primarily, cognitive restructuring. Sixty-five participants were recruited, and 41 completed treatment. Participants were randomly assigned to receive 8 weeks of manualized group CBT either immediately or after an 8-week waiting period. Participants completed outcome measures at the time of their random assignment and at 8, 16, and 52 weeks later. Repeated-measure analysis of covariance revealed significant group-by-time interactions on measures of tinnitus distress and depression, indicating that CBT led to greater improvement in those symptoms. The current results suggest that CBT, applied in a group format using a manual, can reduce the negative emotional distress, including depression, associated with tinnitus.

Functional brain asymmetries during visuomotor tracking.

This study examined brain asymmetries elicited during visuomotor tracking. Thirty-two healthy participants performed a fixed gaze, dynamic, pinch force, visuomotor tracking task during a functional magnetic resonance imaging study. The dynamic task required the subject to press a rubber bulb with the thumb to trace a cosine square wave varying in force amplitude from 0-500 cN and having a frequency of 1.5 Hz. Response hand order and direction of the stimulus presentation (right-to-left or left-to-right) were permuted across participants. Two forms of functional cerebral asymmetry were observed, hemispheric specialization and homologous lateralized response. The superior portion of the right middle frontal gyrus and the left supplementary motor area appeared specialized for VM tracking regardless of response hand used or stimulus movement direction. Lateralized effects appeared in the primary sensorimotor hand area, putamen, parietal operculum/posterior insula, dentate nucleus of the cerebellum, precuneus, and middle occipital gyrus. These lateralized areas of activation surfaced when either response hand or direction of stimulus movement was manipulated. The VM task used in this study activated asymmetrical neural activity in the vertically organized skelotomotor system and in sensory systems involving visual attention or proprioception.

A functional magnetic resonance imaging study of cortical asymmetry in bipolar disorder.

OBJECTIVES: Individuals with bipolar disorder (BPD) exhibit motor, perceptual, and cognitive disturbances involving predominantly right hemisphere dysfunction. This asymmetry has been used to advance the hypothesis that the pathogenesis of bipolar disorder may be related to disturbances of the right cerebral hemisphere. We employed functional magnetic resonance imaging to examine hemispheric asymmetries in manic and depressed BPD. A secondary goal of the study was to examine effects of psychotropic medications on blood volume changes in the motor cortices. METHODS: We studied 18 right-handed BPD and 13 right-handed normal healthy comparison subjects. Blood oxygen level dependent (BOLD) responses in the primary motor area (M1) and supplementary motor area (SMA) of both hemispheres were elicited during reaction time (RT) tasks. RESULTS: Healthy subjects activated the SMA in a reciprocal fashion with significantly greater activity in the left SMA for right hand trials and the right SMA for left hand trials. Depressed BPD subjects failed to show this normal reciprocity indicating a failure to suppress unwanted activity in the ipsilateral right SMA, whereas manic BPD subjects failed to suppress unwanted ipsilateral SMA activity in both hemispheres. Manic and depressed BPD subjects exhibited greater activity in the left primary motor area suggesting increased cortical excitability. BPD subjects treated with antipsychotics or mood-stabilizing medications exhibited longer RTs, lower BOLD responses in M1 and SMA, and a loss of normal hemispheric asymmetry in the SMA than untreated subjects. CONCLUSIONS: The presence of a right hemisphere disturbance in BPD is consistent with the hypothesis that the right hemisphere may be dominant in mood regulation. The presence of both left and right hemisphere disturbances in mania may explain the coexisting psychotic and affective symptoms observed in this condition.

Spatial working memory among middle-aged and older patients with schizophrenia and volunteers using fMRI.

OBJECTIVE: Goldman-Rakic and Selemon (Schizophr. Bull. 23 (1997)) hypothesized that many of the symptoms of schizophrenia can be explained by deficits of working memory (WM) that are, in turn, caused by dysfunction of dorsolateral prefrontal cortex (DLPFC). We examined whether older patients with schizophrenia would show an aberrant neural response in the DLPFC or other brain sites when performing a spatial working memory (WM) task adapted from McCarthy et al. (Proc. Natl. Acad. Sci. U. S. A. 91 (1994)). METHOD: Middle-aged and older patients with schizophrenia or schizoaffective disorder and healthy volunteers performed a spatial WM task contrasted with two baselines, passive and active viewing (PV and AV, respectively), while blood oxygen level dependent (BOLD) images were acquired in a functional magnetic resonance study. RESULTS: Patients did not perform significantly less well on the spatial tasks compared to the volunteers. Although we found no significant group effects in spatial WM activation of DLPFC, we did observe areas in medial frontal cortex including the left anterior cingulate gyrus, parietal areas of the both hemispheres, multiple sites within the basal ganglia of the left hemisphere, and the left superior temporal gyrus where healthy volunteers showed greater BOLD response to WM. In a second pattern, patients showed a greater BOLD response to WM in left fusiform gyrus [Brodmann's Area (BA) 19], peri-rolandic areas, medial frontal area; right anterior cerebellum (culmen), middle occipital lobe, and postcentral/supramarginal gyri (BA 2/40). CONCLUSIONS: Middle-aged and older patients with schizophrenia display normal or near-normal spatial WM activation of DLPFC when the processing demands of the WM task are within their performance capacity. Nonetheless, even when patients perform nearly normally, they demonstrate an aberrant pattern of brain response.

An fMRI study of affective state and medication on cortical and subcortical brain regions during motor performance in bipolar disorder.

Structural neuroimaging studies have identified abnormalities in the basal ganglia in patients with bipolar disorder. Findings have been mixed with regard to affective state and have not elaborated on the role of medication on functional brain activity. The aims of the present study were to use functional magnetic resonance imaging (fMRI) to test whether depressed and manic bipolar disorder patients differ in terms of activity in cortical and subcortical brain areas and to examine the effects of psychotropic medication. Twenty-four bipolar disorder subjects and 13 healthy comparison subjects participated in an fMRI study of manual reaction time. Both manic and depressed subjects exhibited abnormally elevated blood oxygen level dependent BOLD responses in cortical and subcortical areas. Manic bipolar subjects had significantly higher BOLD responses in the left globus pallidus and significantly lower BOLD responses in the right globus pallidus compared with depressed bipolar patients. Correlational analyses revealed significant relationships between the severity of mania and activity within the globus pallidus and caudate. Patients off antipsychotic or mood-stabilizing medication exhibited significantly higher BOLD responses throughout the motor cortex, basal ganglia and thalamus compared with patients on these medications. These results suggest that affective state in bipolar disorder may be related to a disturbance of inhibitory regulation within the basal ganglia and that antipsychotics and/or mood stabilizers normalize cortical and subcortical hyperactivity.

BOLD and perfusion response to finger-thumb apposition after acetazolamide administration: differential relationship to global perfusion.

The authors studied the effects of altering global cerebral blood flow on both blood oxygen level-dependent (BOLD) response and perfusion response to finger-thumb apposition. A PICORE/QUIPSS II protocol was used to collect interleaved BOLD-weighted and perfusion-weighted images on eight finger-thumb apposition trials. Subjects were studied on a drug-free day and on a day when acetazolamide was administered between the second and third trials. After acetazolamide administration, resting cortical perfusion increased an average of 20% from preadministration levels, whereas the BOLD response to finger-thumb apposition decreased by an average of 35% in the S1M1 hand area. Contrary to predictions from the exhausted cerebrovascular reserve hypothesis and the oxygen limitation model, an effect of acetazolamide on cerebral blood flow response in the S1M1 hand area was not observed. Across the acetazolamide trials, BOLD response was inversely correlated with resting cortical perfusion for individual subject data. These results suggest that resting perfusion affects the magnitude of the BOLD response and is thus an important confounding factor in fMRI studies, and that the physiologic systems that increase cerebral blood flow in response to acetazolamide administration and systems that increase cerebral blood flow in response to altered neural activity appear to have additive effects.

Pharmacological treatment of psychosis and agitation in elderly patients with dementia: four decades of experience.

A number of studies, using different research designs and assessment instruments, have been conducted to elucidate the differential effects of drug treatments for psychosis, agitation and aggression in elderly patients with dementia. We have reviewed literature published from 1960 to 2000 on this topic; 48 studies that met our selection criteria were identified from Medline and Science Citation Index. Antipsychotic medication was generally effective for the treatment of psychosis and agitation in elderly patients with dementia. In double-blind, placebo-controlled trials in this population, mean improvement rates were 61% with antipsychotics and 35% with placebo. Atypical antipsychotics appeared promising, but the number of well-designed studies has been small so far. Methodological limitations of the studies reviewed are discussed; future trials should ensure adequate sample size and duration and involve direct comparisons of individual medications. In conclusion, conventional antipsychotics are modestly effective for treatment of psychosis and agitation in elderly individuals with dementia, whereas newer treatments such as atypical antipsychotics appear to be at least as effective while having fewer adverse effects. Nonetheless, there is no currently available ideal pharmacotherapy, and psychosocial management is a necessary part of overall treatment. Additional large-scale, well-controlled studies are needed before conclusive statements regarding the value of treatment of psychosis and agitation with atypical antipsychotics and non-antipsychotic agents can be made.

Effects of task structure on category priming in patients with Parkinson's disease and in healthy individuals.

Lexical decision tasks have been used to study both shifts of attention and semantic processing in Parkinson's Disease (PD). Whereas other laboratories have reported normal levels of semantic priming among PD patients, our laboratory has reported abnormally large levels. In this study, two experiments were performed to determine the influence of task structure on the extent of semantic priming during lexical decision-making and pronunciation tasks among PD patients and neurologically healthy controls. In Experiment 1, the effect of Prime Dominance (the ratio of category to neutral trials) on lexical decision-making was studied. Although equal numbers of word and nonword trials were presented, half of the PD patients and controls were studied under Category Prime Dominance (category : neutral prime ratio of 2:1) and half were studied under Neutral Prime Dominance (category : neutral prime ratio of 1:2). In Experiment 2, PD and control participants were studied on lexical decision-making and pronunciation tasks where twice as many words as nonword trials were presented, consistent with other studies from our laboratory. In Experiment 1, we found no group differences in the magnitude of priming and no effect of Prime Dominance. Moreover, the findings were similar in pattern and magnitude to results published by Neely (1977). In Experiment 2, we observed larger priming effects among PD patients than among controls, but only on the lexical decision (LD) task. These results support the hypothesis that abnormally large category-priming effects appear in LD studies of PD patients when the number of word trials exceeds the number of nonword trials. Furthermore, increased lexical priming in PD appears to be due to processes operating during the decision-making period that follows presentation of the lexical target.