Fronto-temporal dysregulation in remitted bipolar patients: An fMRI delayed-non-match-to-sample (DNMS) study

Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Bipolar Disorders (Impact Factor: 4.97). 07/2009; 11(4):351-60. DOI: 10.1111/j.1399-5618.2009.00703.x
Source: PubMed


Bipolar disorder is associated with working memory (WM) impairments that persist during periods of symptomatic remission. However, the neural underpinnings of these deficits are not well understood.
Fifteen clinically remitted bipolar patients and 15 demographically matched healthy controls underwent functional magnetic resonance imaging while performing a novel delayed-non-match-to-sample (DNMS) task. This nonverbal DNMS task involves two conditions, one requiring the organization of existing memory traces ('familiarity'), and one involving the formation of new memory traces ('novelty'). These processes are thought to differentially engage the prefrontal cortex and medial temporal lobe, respectively.
Although behavioral performance did not differ between groups, bipolar patients and controls exhibited significantly different patterns of neural activity during task performance. Patients showed relative hyperactivation in the right prefrontal gyrus and relative hypoactivation in visual processing regions compared to healthy subjects across both task conditions. During the novelty condition, patients showed a pattern of hypoactivation relative to controls in medial temporal regions, with relative hyperactivation in the anterior cingulate.
These findings suggest that disruption in fronto-temporal neural circuitry may underlie memory difficulties frequently observed in patients with bipolar disorder.

7 Reads
  • Source
    • "Apathy scales should be able to give an objective assessment of the patient's motivational state, and the functional deficits around interpersonal relationships and the initiation and maintenance of goal directed activity, whereas depression scores necessarily target the patient's subject experiences. Also, apathy is seldom distressing to the patient, but often exerts significant caregiver burden, while depression distresses the patient [61]. These factors may help explain why our patients underestimated their apathy symptoms. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Apathy has traditionally been conceptualised as part of depression. The appropriateness of this conceptualisation has now been questioned, with the realization that apathy constitutes a distinct neuropsychiatric condition, with separate rehabilitation and patient-care implications to depression. Research on the relationship between apathy and depression has, however, produced mixed results. One reason for this inconsistency may lie behind who does the apathy evaluation. In this study we investigated whether the relationship between apathy and depression would differ when apathy was evaluated by the patients or an informant. A total of 49 brain damaged patients were assessed on self- and informant-rated Apathy Evaluation Scales. The relationship between the apathy scores and depressive symptoms was then investigated. Patient-rated, and not informant-rated apathy significantly correlated with depression. We discuss the implication of these results on the relationship between the two neuropsychiatric conditions and also in relation to the utility of patient self-evaluations in apathy.
    Full-text · Article · May 2012 · Current Gerontology and Geriatrics Research
  • Source
    • "The subgenual prefrontal cortex modulates the affective output of limbic and paralimbic structures and cognitive output from the prefrontal cortex. Recent evidence from functional MRI studies using affective processing paradigms (ie, reacting to stimuli with positive or negative emotional valence) suggests that patients with bipolar disorder may disproportionately engage limbic structures during emotionally valent tasks, regardless of mood state [46, 47], although the direction of effects has not been consistent across studies. Taken together, these studies suggest that corticolimbic dysregulation may underlie the emotional dysregulation and cognitive impairments associated with bipolar disorder [45, 48]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Historically, bipolar disorder has been conceptualized as a disease involving episodic rather than chronic dysfunction. However, increasing evidence indicates that bipolar disorder is associated with substantial inter-episode psychosocial and vocational impairment. Here we review the contributions of neurocognitive deficits and structural and functional neuroanatomic alterations to the observed functional impairments. In particular, compelling evidence now suggests that neurocognitive impairments, particularly in the areas of attention, processing speed, and memory, are associated with functional outcome. Although investigation of the neural correlates of functional disability in bipolar disorder is only in its nascent stages, preliminary evidence suggests that white matter abnormalities may be predictive of poor outcome. A better understanding of the relationship between neurocognitive and neuroimaging assays and functional outcome has the potential to improve current treatment options and provide targets for new treatment strategies in bipolar disorder.
    Full-text · Article · Dec 2010 · Current Psychiatry Reports
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Gender is known to modulate the clinical course and severity of bipolar disorder (BD). Although cognitive abnormalities are an established feature of BD, there is limited information regarding whether gender also influences the pattern and severity of cognitive impairment. We evaluated the performance of 86 remitted patients with BD, type 1, (BD-I) (36 male and 50 female) and 46 healthy participants (21 male and 25 female) on tasks of general intellectual ability, memory encoding, recognition and retrieval, response inhibition and executive function (abstraction and perseveration). The impact of illness severity in patients was assessed using the global assessment of functioning (GAF). We found a gender effect and an interaction between diagnosis and gender on immediate memory, implicating encoding and retrieval processes, both showing male BD-I patients being disadvantaged compared with female patients and healthy controls. Immediate memory correlated with GAF scores and this association was statistically significant for male BD-I patients. Our findings suggest that gender differences in BD-I are associated with memory function, particularly processes relating to encoding and retrieval, and may contribute to poor functional outcome particularly in men.
    Full-text · Article · Nov 2009 · Psychological Medicine
Show more