Teena D. Moody

Activity-Dependent β-Adrenergic Modulation of Low Frequency Stimulation Induced LTP in the Hippocampal CA1 Region

Abstract β-Adrenergic receptor activation has a central role in the enhancement of memory formation that occurs during heightened states of emotional arousal. Although β-adrenergic receptor activation may enhance memory formation by modulating long-term potentiation (LTP), a candidate synaptic mechanism involved in memory formation, the cellular basis of this modulation is not fully understood. Here, we report that, in the CA1 region of the hippocampus, β-adrenergic receptor activation selectively enables the induction of LTP during long trains of 5 Hz synaptic stimulation. Protein phosphatase inhibitors mimic the effects of β-adrenergic receptor activation on 5 Hz stimulation–induced LTP, suggesting that activation of noradrenergic systems during emotional arousal may enhance memory formation by inhibiting protein phosphatases that normally oppose the induction of LTP.

Postsynaptic Complex Spike Bursting Enables the Induction of LTP by Theta Frequency Synaptic Stimulation

Long-term potentiation (LTP), a persistent enhancement of synaptic transmission that may be involved in some forms of learning and memory, is induced at excitatory synapses in the CA1 region of the hippocampus by coincident presynaptic and postsynaptic activity. Although action potentials back-propagating into dendrites of hippocampal pyramidal cells provide sufficient postsynaptic activity to induce LTP under somein vitro conditions, it is not known whether LTP can be induced by patterns of postsynaptic action potential firing that occur in these cells in vivo. Here we report that a characteristic in vivo pattern of action potential generation in CA1 pyramidal cells known as the complex spike burst enables the induction of LTP during theta frequency synaptic stimulation in the CA1 region of hippocampal slices maintainedin vitro. Our results suggest that complex spike bursting may have an important role in synaptic processes involved in learning and memory formation, perhaps by producing a highly sensitive postsynaptic state during which even low frequencies of presynaptic activity can induce LTP.

An Implicit Learning Task Activates Medial Temporal Lobe in Patients With Parkinson's Disease.

Recent studies provide evidence for an interaction between a declarative memory system, dependent on the medial temporal lobe (MTL), and a habit memory system, dependent on the basal ganglia. Using functional MRI, the authors studied this interaction when 1 system was compromised by neurological disease. Neural activity when performing a habit-learning task was compared in normal controls and subjects with Parkinsons disease (PD). Patients with PD showed less activation in the caudate nucleus and greater activation in a region of prefrontal cortex that has been associated with explicit memory retrieval. Patients with PD also showed activation of the MTL during the weather-prediction task. These findings are consistent with an interaction between memory systems of the MTL and the striatum.

Your Brain on Google: Patterns of Cerebral Activation during Internet Searching

OBJECTIVE Previous research suggests that engaging in mentally stimulating tasks may improve brain health and cognitive abilities. Using computer search engines to find information on the Internet has become a frequent daily activity of people at any age, including middle-aged and older adults. As a preliminary means of exploring the possible influence of Internet experience on brain activation patterns, the authors performed functional magnetic resonance imaging (MRI) of the brain in older persons during search engine use and explored whether prior search engine experience was associated with the pattern of brain activation during Internet use. DESIGN Cross-sectional, exploratory observational study PARTICIPANTS The authors studied 24 subjects (age, 55-76 years) who were neurologically normal, of whom 12 had minimal Internet search engine experience (Net Naive group) and 12 had more extensive experience (Net Savvy group). The mean age and level of education were similar in the two groups. MEASUREMENTS Patterns of brain activation during functional MRI scanning were determined while subjects performed a novel Internet search task, or a control task of reading text on a computer screen formatted to simulate the prototypic layout of a printed book, where the content was matched in all respects, in comparison with a nontext control task. RESULTS The text reading task activated brain regions controlling language, reading, memory, and visual abilities, including left inferior frontal, temporal, posterior cingulate, parietal, and occipital regions, and both the magnitude and the extent of brain activation were similar in the Net Naive and Net Savvy groups. During the Internet search task, the Net Naive group showed an activation pattern similar to that of their text reading task, whereas the Net Savvy group demonstrated significant increases in signal intensity in additional regions controlling decision making, complex reasoning, and vision, including the frontal pole, anterior temporal region, anterior and posterior cingulate, and hippocampus. Internet searching was associated with a more than twofold increase in the extent of activation in the major regional clusters in the Net Savvy group compared with the Net Naive group (21,782 versus 8,646 total activated voxels). CONCLUSION Although the present findings must be interpreted cautiously in light of the exploratory design of this study, they suggest that Internet searching may engage a greater extent of neural circuitry not activated while reading text pages but only in people with prior computer and Internet search experience. These observations suggest that in middle-aged and older adults, prior experience with Internet searching may alter the brains responsiveness in neural circuits controlling decision making and complex reasoning.

Abnormalities of Visual Processing and Frontostriatal Systems in Body Dysmorphic Disorder

CONTEXT Body dysmorphic disorder (BDD) is a psychiatric disorder in which individuals are preoccupied with perceived defects in their appearance, often related to their face. Little is known about its pathophysiology, although early research provides evidence of abnormal visual processing. OBJECTIVE To determine whether patients with BDD have abnormal patterns of brain activation when visually processing their own face with high, low, or normal spatial resolution. DESIGN Case-control study. SETTING A university hospital. PARTICIPANTS Seventeen right-handed medication-free subjects with BDD and 16 matched healthy control subjects. Intervention Functional magnetic resonance imaging while viewing photographs of face stimuli. Stimuli were neutral-expression photographs of the patients own face and a familiar face (control stimuli) that were unaltered, altered to include only high spatial frequency (fine spatial resolution), or altered to include only low spatial frequency (low spatial resolution). MAIN OUTCOME MEASURE Blood oxygen level-dependent signal changes in the BDD and control groups during each stimulus type. RESULTS Subjects with BDD showed relative hyperactivity in the left orbitofrontal cortex and bilateral head of the caudate for the unaltered own-face vs familiar-face condition. They showed relative hypoactivity in the left occipital cortex for the low spatial frequency faces. Differences in activity in frontostriatal systems but not visual cortex covaried with aversiveness ratings of the faces. Severity of BDD symptoms correlated with activity in frontostriatal systems and visual cortex. CONCLUSIONS These results suggest abnormalities in visual processing and frontostriatal systems in BDD. Hypoactivation in the occipital cortex for low spatial frequency faces may indicate either primary visual system abnormalities for configural face elements or top-down modulation of visual processing. Frontostriatal hyperactivity may be associated both with aversion and with symptoms of obsessive thoughts and compulsive behaviors.

Impaired inter-hemispheric integration in bipolar disorder revealed with brain network analyses.

BACKGROUND This represents the first graph theory-based brain network analysis study in bipolar disorder, a chronic and disabling psychiatric disorder characterized by severe mood swings. Many imaging studies have investigated white matter in bipolar disorder, with results suggesting abnormal white matter structural integrity, particularly in the fronto-limbic and callosal systems. However, many inconsistencies remain in the literature, and no study to date has conducted brain network analyses with a graph-theoretic approach. METHODS We acquired 64-direction diffusion-weighted magnetic resonance imaging on 25 euthymic bipolar I disorder subjects and 24 gender- and age-equivalent healthy subjects. White matter integrity measures including fractional anisotropy and mean diffusivity were compared in the whole brain. Additionally, structural connectivity matrices based on whole-brain deterministic tractography were constructed, followed by the computation of both global and local brain network measures. We also designed novel metrics to further probe inter-hemispheric integration. RESULTS Network analyses revealed that the bipolar brain networks exhibited significantly longer characteristic path length, lower clustering coefficient, and lower global efficiency relative to those of control subjects. Further analyses revealed impaired inter-hemispheric but relatively preserved intra-hemispheric integration. These findings were supported by whole-brain white matter analyses that revealed significantly lower integrity in the corpus callosum in bipolar subjects. There were also abnormalities in nodal network measures in structures within the limbic system, especially the left hippocampus, the left lateral orbitofrontal cortex, and the bilateral isthmus cingulate. CONCLUSIONS These results suggest abnormalities in structural network organization in bipolar disorder, particularly in inter-hemispheric integration and within the limbic system.

Common and Dissociable Prefrontal Loci Associated with Component Mechanisms of Analogical Reasoning

The ability to draw analogies requires 2 key cognitive processes, relational integration and resolution of interference. The present study aimed to identify the neural correlates of both component processes of analogical reasoning within a single, nonverbal analogy task using event-related functional magnetic resonance imaging. Participants verified whether a visual analogy was true by considering either 1 or 3 relational dimensions. On half of the trials, there was an additional need to resolve interference in order to make a correct judgment. Increase in the number of dimensions to integrate was associated with increased activation in the lateral prefrontal cortex as well as lateral frontal pole in both hemispheres. When there was a need to resolve interference during reasoning, activation increased in the lateral prefrontal cortex but not in the frontal pole. We identified regions in the middle and inferior frontal gyri which were exclusively sensitive to demands on each component process, in addition to a partial overlap between these neural correlates of each component process. These results indicate that analogical reasoning is mediated by the coordination of multiple regions of the prefrontal cortex, of which some are sensitive to demands on only one of these 2 component processes, whereas others are sensitive to both.

Regional fMRI Hypoactivation and Altered Functional Connectivity During Emotion Processing in Nonmedicated Depressed Patients With Bipolar II Disorder

OBJECTIVE Although the amygdala and ventrolateral prefrontal cortex have been implicated in the pathophysiology of bipolar I disorder, the neural mechanisms underlying bipolar II disorder remain unknown. The authors examined neural activity in response to negative emotional faces during an emotion perception task that reliably activates emotion regulatory regions. METHOD Twenty-one nonmedicated depressed bipolar II patients and 21 healthy comparison subjects underwent functional MRI (fMRI) while performing an emotional face-matching task. Within- and between-group whole-brain fMRI activation and seed-based connectivity analyses were conducted. RESULTS In depressed bipolar II patients, random-effects between-group fMRI analyses revealed a significant reduction in activation in several regions, including the left and right ventrolateral prefrontal cortices (Brodmanns area [BA] 47) and the right amygdala, a priori regions of interest. Additionally, bipolar patients exhibited significantly reduced negative functional connectivity between the right amygdala and the right orbitofrontal cortex (BA 10) as well as the right dorsolateral prefrontal cortex (BA 46) relative to healthy comparison subjects. CONCLUSIONS These findings suggest that bipolar II depression is characterized by reduced regional orbitofrontal and limbic activation and altered connectivity in a fronto-temporal circuit implicated in working memory and emotional learning. While the amygdala hypoactivation observed in bipolar II depression is opposite to the direction seen in bipolar I mania and may therefore be state dependent, the observed orbitofrontal cortex hypoactivation is consistent with findings in bipolar I depression, mania, and euthymia, suggesting a physiologic trait marker of the disorder.

Deficits in inferior frontal cortex activation in euthymic bipolar disorder patients during a response inhibition task.

Townsend JD, Bookheimer SY, Foland‐Ross LC, Moody TD, Eisenberger NI, Fischer JS, Cohen MS, Sugar CA, Altshuler LL. Deficits in inferior frontal cortex activation in euthymic bipolar disorder patients during a response inhibition task. 
Bipolar Disord 2012: 14: 442–450.

Explicit and Implicit Memory in Late-Life Depression

OBJECTIVE Late-life depression has been associated with memory loss and is frequently assumed to be a risk factor for continued cognitive decline. This study examined cognition in patients with late-life depression with a focus on the assessment of the extent and type of memory loss among elderly depressed patients. METHODS Two-year cross-sectional study of elderly depressed (N = 112) and nondepressed (N = 138) individuals at or older than 60 years in an urban area surrounding a major medical center in southern California. Participants had little to moderate stroke risk. Volunteers were screened with the Hamilton Depression Rating Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I Disorders. Patients were diagnosed for major depression by a geriatric psychiatrist using DSM-IV criteria. Volunteers completed neuropsychological testing, a standard battery of laboratory tests, and a neurologic and psychiatric evaluation to rule out a medical burden that might contribute to depression or early dementia. RESULTS Depressed patients showed deficits in attention and processing, executive function, and immediate explicit recall. Implicit learning and episodic recall of the testing procedure, semantic and phonetic fluency, and retention of newly acquired verbal material after a delay period were comparable with controls. CONCLUSION Moderately depressed patients demonstrate a pattern of cognitive deficits suggestive of mild frontal dysfunction during recall tasks. Their retention of material over a delay period and their intact language skills indicate medial hippocampal function similar to controls. Subcortically mediated implicit memory is also at normal levels. These findings support current efforts to identify pathways of frontal and/or striatal compromise during depressive episodes.