Systems and Diseases

Permanent URI for this community

http://dspace.alquds.edu:4000/handle/20.500.12213/79
Systems and Diseases

Browse

Browsing Systems and Diseases by Subject "basal ganglia"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Depression Impairs Learning, whereas the Selective Serotonin Reuptake Inhibitor, Paroxetine, Impairs Generalization in Patients with Major Depressive Disorder
    (Elsevier, 2014-11-01) Herzallah, Mohammad M.; Moustafa, Ahmed A.; Natsheh, Joman Y.; Danoun, Omar A.; Simon, Jessica R.; Tayem, Yasin I.; Sehwail, Mahmud A.; Amleh, Ivona; Bannoura, Issam; Petrides, Georgios; Myers, Catherine E.; Gluck, Mark A.
    To better understand how medication status and task demands affect cognition in Major Depressive Disorder (MDD), we evaluated medication-naïve patients with MDD, medicated patients with MDD receiving the Selective Serotonin Reuptake Inhibitors (SSRI) paroxetine, and healthy controls. All three groups were administered a computer-based cognitive task with two phases, an initial phase in which a sequence is learned through reward-based feedback (which our prior studies suggest is striatal-dependent), followed by a generalization phase that involves a change in the context where learned rules are to be applied (which our prior studies suggest is hippocampal-region dependent). Medication-naïve MDD patients were slow to learn the initial sequence but were normal on subsequent generalization of that learning. In contrast, medicated patients learned the initial sequence normally, but were impaired at the generalization phase. We argue that these data suggest (i) an MDD-related impairment in striatal-dependent sequence learning which can be remediated by SSRIs and (ii) an SSRI-induced impairment in hippocampaldependent generalization of past learning to novel contexts, not otherwise seen in the medicationnaïve MDD group. Thus, SSRIs might have a beneficial effect on striatal function required for sequence learning, but a detrimental effect on the hippocampus and other medial temporal lobe structures critical for generalization.
  • Thumbnail Image
    Item
    Hippocampal BOLD Response During Category Learning Predicts Subsequent Performanceon Transfer Generalization
    (Wiley Periodicals, Inc., 2014-10-13) Fera, Francesco; Passamonti, Luca; Myers, Catherine E.; Veltri, Pierangelo; Morganti, Giuseppina; Quattrone, Aldo; Gluck, Mark A.; Herzallah, Mohammad
    To test a prediction of our previous computational model of cortico-hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI-adapted category-learning task that has two phases, an initial phase in which associations are learned through trial-and-error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning-related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands.
  • Thumbnail Image
    Item
    Learning from negative feedback in patients with major depressive disorder is attenuated by SSRI antidepressants
    (2013-09-23) Herzallah, Mohammad M.; Moustafa, Ahmed A.; Natsheh, Joman Y.; Abdellatif, Salam M.; Taha, Mohamad B.; Tayem, Yasin I.; Sehwail, Mahmud A.; Amleh, Ivona; Petrides, Georgios; Myers, Catherine E.; Gluck, Mark A.
    One barrier to interpreting past studies of cognition and major depressive disorder (MDD) has been the failure in many studies to adequately dissociate the effects of MDD from the potential cognitive side effects of selective serotonin reuptake inhibitors (SSRIs) use. To better understand how remediation of depressive symptoms affects cognitive function in MDD, we evaluated three groups of subjects: medication-naïve patients with MDD, medicated patients with MDD receiving the SSRI paroxetine, and healthy control (HC) subjects. All were administered a category-learning task that allows for dissociation between learning from positive feedback (reward) vs. learning from negative feedback (punishment). Healthy subjects learned significantly better from positive feedback than medication-naïve and medicated MDD groups, whose learning accuracy did not differ significantly. In contrast, medicated patients with MDD learned significantly less from negative feedback than medication-naïve patients with MDD and healthy subjects, whose learning accuracy was comparable. A comparison of subject's relative sensitivity to positive vs. negative feedback showed that both the medicated MDD and HC groups conform to Kahneman and Tversky's (1979) Prospect Theory, which expects losses (negative feedback) to loom psychologically slightly larger than gains (positive feedback). However, medicated MDD and HC profiles are not similar, which indicates that the state of medicated MDD is not "normal" when compared to HC, but rather balanced with less learning from both positive and negative feedback. On the other hand, medication-naïve patients with MDD violate Prospect Theory by having significantly exaggerated learning from negative feedback. This suggests that SSRI antidepressants impair learning from negative feedback, while having negligible effect on learning from positive feedback. Overall, these findings shed light on the importance of dissociating the cognitive consequences of MDD from those of SSRI treatment, and from cognitive evaluation of MDD subjects in a medication-naïve state before the administration of antidepressants. Future research is needed to correlate the mood-elevating effects and the cognitive balance between reward- and punishment-based learning related to SSRIs.