Greater Blood Oxygen Level-dependent Response Research Articles

P157 Neurocognitive insights: functional magnetic resonance imaging of spatial working memory and sustained attention in people with systemic lupus erythematous

Abstract Background/Aims Cognitive impairment (CI) is common in people with systemic lupus erythematosus (pwSLE). Treatment options are limited and the effects upon the brain is unclear. Differences in brain structure seen in SLE do not always associate with CI, however significant associations have been found with functional magnetic resonance imaging (fMRI). Using fMRI, this study aims to further explore potential compensatory brain mechanisms used in SLE that help with cognitive function. Methods Participants were recruited into one of two groups;pwSLE (meeting EULAR/ACR criteria) or healthy controls(HC). Demographic, clinical and psychiatric data and patient reported outcome measures were collected.Cognitive function was assessed using the ACR Neuropsychological Battery. Brain scans included two structural and two fMRI scans done during stage 1 and 2 of a cognitive task. Stage 1 of the task had an encoding, retention and working memory (WM) component. Stage 2 of the task examined long-term memory. Differences between task performances were examined using t-tests. The fMRI data was modelled using SPM12 to look for differences in blood-oxygen-level-dependent (BOLD) brain responses between the study groups during the different stages/components of the task. Results To-date 37 pwSLE and 10 HCs have been recruited. The median ages were 36 (HC) and 40 (pwSLE) years. From the pwSLE group the average disease duration was 15 years, the average SLEDAI-2K score was 5 and percentages of those on antimalarials, corticosteroids, and immunosuppressants and biologics were 66%, 32%, and 54%, respectively. There were no differences on task performance between the two groups. Greater BOLD responses were seen in the HC compared to the pwSLE group during stage 1 encoding and WM phases as well as during stage 2 (long-term memory). pwSLE had less attenuated BOLD signals during the stage 1 retention phase compared to HCs (Table 1). Conclusion We found altered brain responses to our cognitive task between pwSLE and HCs. Predominantly the HC group had greater BOLD responses in cognitive regions during the task compared to the pwSLE group. However, we did not find any difference between the two groups in regards to cognitive performance. This study is still ongoing and additional results are expected. Disclosure M. Barraclough: None. M. McCowen: None. S. McKie: None. A. Kafkas: None. B. Parker: None. J. Diaz-Martinez: None. A. Knight: None. K. Bingham: None. M. Li: None. J. Su: None. M. Kakvan: None. C. Munoz Grajales: None. M. Tartaglia: None. L. Ruttan: None. J. Wither: None. D. Bonilla: None. N. Anderson: None. D. Montaldi: None. R. Elliott: None. P. Katz: None. D. Beaton: None. R. Green: None. I. Bruce: None. Z. Touma: None.

Sex moderates family history of alcohol use disorder and childhood maltreatment effects on an fMRI stop-signal task.

Childhood maltreatment (CM) and a family history (FH) of alcohol use disorder (AUD) are each associated with increased impulsivity. However, their unique or shared brain targets remain unknown. Furthermore, both CM and FH demonstrate sex-dependent effects on brain and behavior. We hypothesized that CM and FH interact in brain regions involved in impulsivity with sex-dependent effects. 144 first-year college students (18-19 years old) with varying experiences of CM and/or FH but without current AUD performed an fMRI stop-signal task. We tested interactions between FH, CM, and sex on task performance and blood oxygen level-dependent (BOLD) signal during successful inhibitions. We examined correlations between BOLD response and psychiatric symptoms. Significant three-way interactions of FH, CM, and sex were detected for brain and behavioral data, largely driven by male subjects. In males, CM was associated with poorer response inhibition but only for those with less FH; males with higher levels of both CM and FH demonstrated better response inhibition. Three-way interaction effects on voxel-wise BOLD response during response inhibition were found in bilateral middle frontal gyrus, left inferior frontal gyrus, dorsomedial prefrontal cortex, and posterior cingulate cortex. Network-level analyses implicated the left frontoparietal network, executive control network, and default-mode network. Greater BOLD response in these networks correlated with lower depressive, impulsive, and attentional symptoms, reduced alcohol misuse, greater resilience scores, and heightened trait anxiety. The results highlight sex-divergent effects of heritable and environmental risk factors that may account for sex-dependent expression of psychopathology in response to risk factors.

Neural Signatures of Memory Encoding in Schizophrenia Are Modulated by Antipsychotic Treatment

There is no pharmacological treatment to remediate cognitive impairment in schizophrenia (SZ). It is imperative to characterize underlying pathologies of memory processing in order to effectively develop new treatments. In this longitudinal study, we combined functional magnetic resonance imaging during a memory encoding task with proton MR spectroscopy to measure hippocampal glutamate + glutamine (Glx). Seventeen SZ were scanned while unmedicated and after 6 weeks of treatment with risperidone and compared to a group of matched healthy controls (HC) scanned 6 weeks apart. Unmedicated patients showed reduced blood oxygen level dependent (BOLD) response in several regions, including the hippocampus, and greater BOLD response in regions of the default mode network (DMN) during correct memory encoding. Post hoc contrasts from significant group by time interactions indicated reduced hippocampal BOLD response at baseline with subsequent increase following treatment. Hippocampal Glx was not different between groups at baseline, but at week 6, hippocampal Glx was significantly lower in SZ compared to HC. Finally, in unmedicated SZ, higher hippocampal Glx predicted less deactivation of the BOLD response in regions of the DMN. Using 2 brain imaging modalities allowed us to concurrently investigate different mechanisms involved in memory encoding dysfunction in SZ. Hippocampal pathology during memory encoding stems from decreased hippocampal recruitment and faulty deactivation of the DMN, and hippocampal recruitment during encoding can be modulated by antipsychotic treatment. High Glx in unmedicated patients predicted less deactivation of the DMN; these results suggest a mechanism by which faulty DMN deactivation, a hallmark of pathological findings in SZ, is achieved.

Is brain response to food rewards related to overeating? A test of the reward surfeit model of overeating in children

The reward surfeit model of overeating suggests that heightened brain response to rewards contributes to overeating and subsequent weight gain. However, previous studies have not tested whether brain response to reward is associated with food intake, particularly during childhood, a period of dynamic development in reward and inhibitory control neurocircuitry. We conducted functional magnetic resonance imaging (fMRI) with 7–11-year-old children (n = 59; healthy weight, n = 31; overweight, n = 28; 54% female) while they played a modified card-guessing paradigm to examine blood-oxygen-level-dependent (BOLD) response to anticipating and winning rewards (food, money, neutral). Food intake was assessed at three separate meals that measured different facets of eating behavior: 1) typical consumption (baseline), 2) overindulgence (palatable buffet), and 3) eating in the absence of hunger (EAH). A priori regions of interest included regions implicated in both reward processing and inhibitory control. Multiple stepwise regressions were conducted to examine the relationship between intake and BOLD response to rewards. Corrected results showed that a greater BOLD response in the medial prefrontal cortex for anticipating food compared to money positively correlated with how much children ate at the baseline and palatable buffet meals. BOLD response in the dorsolateral prefrontal cortex for winning food compared to money was positively correlated with intake at the palatable buffet meal and EAH. All aforementioned relationships were independent of child weight status. Findings support the reward surfeit model by showing that increased brain response to food compared to money rewards positively correlates with laboratory measures of food intake in children.

FMRI response during figural memory task performance in college drinkers

Eighteen- to twenty-five-year-olds show the highest rates of alcohol use disorders (AUD) and heavy drinking, which may have critical neurocognitive implications. Regions subserving memory may be particularly susceptible to alcohol-related impairments. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine the neural correlates of visual encoding and recognition among heavy-drinking college students. We predicted that heavy drinkers would show worse memory performance, increased frontal/parietal activation, and decreased hippocampal response during encoding. Participants were 23 heavy drinkers and 33 demographically matched light drinkers, aged 18-20, characterized using quantity/frequency of drinking and AUD diagnosis. Participants performed a figural encoding and recognition task during fMRI. BOLD response during encoding was modeled based on whether each stimulus was subsequently recognized or forgotten (i.e., correct vs. incorrect encoding). There were no group differences in behavioral performance. Compared to light drinkers, heavy drinkers showed (1) greater BOLD response during correct encoding in the right hippocampus/medial temporal, right dorsolateral prefrontal, left inferior frontal, and bilateral posterior parietal cortices; (2) less left inferior frontal activation and greater bilateral precuneus deactivation during incorrect encoding; and (3) less bilateral insula response during correct recognition (clusters >10,233μl, p < 0.05 whole brain). This is the first investigation of the neural substrates of figural memory among heavy-drinking older adolescents. Heavy drinkers demonstrated compensatory hyperactivation of memory-related areas during correct encoding, greater deactivation of default mode regions during incorrect encoding, and reduced recognition-related response. Results could suggest use of different encoding and recognition strategies among heavy drinkers.

Crossing the Line of Pain: fMRI Correlates of Crossed-Hands Analgesia

Crossing the hands over the body midline reduces the perceived intensity of nociceptive stimuli applied to the hands by impairing the ability to localize somatosensory stimuli. The neural basis of this “crossed-hands analgesia” has not been investigated previously, although it has been proposed that the effect may be modulated by multimodal areas. We used functional magnetic resonance imaging to test the hypothesis that crossed-hands analgesia is mediated by higher-order multimodal areas rather than by specific somatosensory ones. Participants lay in the scanner while mechanical painful stimuli were applied to their hands held in either a crossed or uncrossed position. They reported significantly lower perceived intensity of pain when their hands were crossed. Although activations elicited by stimuli applied to the crossed hands revealed significantly greater blood oxygen level–dependent responses in the anterior cingulate cortex, the insula, and the medial frontal gyrus, the blood oxygen level–dependent responses in the superior parietal lobe were greater with the hands uncrossed. Our results provide evidence that crossed-hands analgesia is mediated by higher-order frontoparietal multimodal areas involved in sustaining and updating body and spatial representations. PerspectiveWe found crossed-hands analgesia to be mediated by multimodal areas, such as the posterior parietal, cingulate, and insular cortices, implicated in space and body representation. Our findings highlight how the perceived intensity of painful stimuli is shaped by how we represent our body and the space surrounding it.

Acute Alcohol Effects on Contextual Memory BOLD Response: Differences Based on Fragmentary Blackout History

Contextual memory, or memory for source details, is an important aspect of episodic memory and has been implicated in alcohol-induced fragmentary blackouts (FBs). Little is known, however, about how neural functioning during contextual memory processes may differ between individuals with and without a history of FB. This study examined whether neural activation during a contextual memory task differed by history of FB and acute alcohol consumption. Twenty-four matched individuals with (FB+; n = 12) and without (FB-; n = 12) a history of FBs were recruited from a longitudinal study of alcohol use and behavioral risks and completed a laboratory beverage challenge followed by 2 functional magnetic resonance imaging (fMRI) sessions under no alcohol and alcohol (breath alcohol concentration = 0.08%) conditions. Task performance and brain hemodynamic activity during a block design contextual memory task were examined across 48 fMRI sessions. Groups demonstrated no differences in performance on the contextual memory task, yet exhibited different brain response patterns after alcohol intoxication. A significant FB group by beverage interaction emerged in bilateral dorsolateral prefrontal cortex and posterior parietal cortex with FB- individuals showing greater blood oxygenation level-dependent response after alcohol exposure (p < 0.05). Alcohol had differential effects on neural activity for FB+ and FB- individuals during recollection of contextual information, perhaps suggesting a neurobiological mechanism associated with alcohol-induced FB.

FMRI Correlates of White Matter Hyperintensities in Late-Life Depression

This study tests whether or not the structural white matter lesions that are characteristic of late-life depression are associated with alterations in the functional affective circuits of late-life depression. This study used an emotional faces paradigm that has been shown to engage the affective limbic brain regions. Thirty-three elderly depressed patients and 27 nondepressed comparison subjects participated in this study. The patients were recruited through the NIMH-sponsored Advanced Center for Interventions and Services Research for the Study of Late-Life Mood Disorders at the University of Pittsburgh Center for Bioethics and Health Law. Structural and functional MRI was used to assess white matter hyperintensity (WMH) burden and functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) response on a facial expression affective-reactivity task in both elderly participants with nonpsychotic and nonbipolar major depression (unmedicated) and nondepressed elderly comparison subjects. As expected, greater subgenual cingulate activity was observed in the depressed patients relative to the nondepressed comparison subjects. This same region showed greater task-related activity associated with a greater burden of cerebrovascular white matter change in the depressed group. Moreover, the depressed group showed a significantly greater interaction of WMH by fMRI activity effect than the nondepressed group. The observation that high WMH burden in late-life depression is associated with greater BOLD response on the affective-reactivity task supports the model that white matter ischemia in elderly depressed patients disrupts brain mechanisms of affective regulation and leads to limbic hyperactivation.

Congruence of happy and sad emotion in music and faces modifies cortical audiovisual activation

BackgroundThe powerful emotion inducing properties of music are well-known, yet music may convey differing emotional responses depending on environmental factors. We hypothesized that neural mechanisms involved in listening to music may differ when presented together with visual stimuli that conveyed the same emotion as the music when compared to visual stimuli with incongruent emotional content. MethodsWe designed this study to determine the effect of auditory (happy and sad instrumental music) and visual stimuli (happy and sad faces) congruent or incongruent for emotional content on audiovisual processing using fMRI blood oxygenation level-dependent (BOLD) signal contrast. The experiment was conducted in the context of a conventional block-design experiment. A block consisted of three emotional ON periods, music alone (happy or sad music), face alone (happy or sad faces), and music combined with faces where the music excerpt was played while presenting either congruent emotional faces or incongruent emotional faces. ResultsWe found activity in the superior temporal gyrus (STG) and fusiform gyrus (FG) to be differentially modulated by music and faces depending on the congruence of emotional content. There was a greater BOLD response in STG when the emotion signaled by the music and faces was congruent. Furthermore, the magnitude of these changes differed for happy congruence and sad congruence, i.e., the activation of STG when happy music was presented with happy faces was greater than the activation seen when sad music was presented with sad faces. In contrast, incongruent stimuli diminished the BOLD response in STG and elicited greater signal change in bilateral FG. Behavioral testing supplemented these findings by showing that subject ratings of emotion in faces were influenced by emotion in music. When presented with happy music, happy faces were rated as more happy (p=0.051) and sad faces were rated as less sad (p=0.030). When presented with sad music, happy faces were rated as less happy (p=0.008) and sad faces were rated as sadder (p=0.002). InterpretationHappy–sad congruence across modalities may enhance activity in auditory regions while incongruence appears to impact the perception of visual affect, leading to increased activation in face processing regions such as the FG. We suggest that greater understanding of the neural bases of happy–sad congruence across modalities can shed light on basic mechanisms of affective perception and experience and may lead to novel insights in the study of emotion regulation and therapeutic use of music.

Neural correlates of word production stages delineated by parametric modulation of psycholinguistic variables.

Word production is a complex multistage process linking conceptual representations, lexical entries, phonological forms and articulation. Previous studies have revealed a network of predominantly left-lateralized brain regions supporting this process, but many details regarding the precise functions of different nodes in this network remain unclear. To better delineate the functions of regions involved in word production, we used event-related functional magnetic resonance imaging (fMRI) to identify brain areas where blood oxygen level-dependent (BOLD) responses to overt picture naming were modulated by three psycholinguistic variables: concept familiarity, word frequency, and word length, and one behavioral variable: reaction time. Each of these variables has been suggested by prior studies to be associated with different aspects of word production. Processing of less familiar concepts was associated with greater BOLD responses in bilateral occipitotemporal regions, reflecting visual processing and conceptual preparation. Lower frequency words produced greater BOLD signal in left inferior temporal cortex and the left temporoparietal junction, suggesting involvement of these regions in lexical selection and retrieval and encoding of phonological codes. Word length was positively correlated with signal intensity in Heschl's gyrus bilaterally, extending into the mid-superior temporal gyrus (STG) and sulcus (STS) in the left hemisphere. The left mid-STS site was also modulated by reaction time, suggesting a role in the storage of lexical phonological codes.

The neural basis of scene preferences

What is the neural correlate of preference that governs our spontaneous selection of visual information? With a rapid, event-related functional magnetic resonance imaging design, we showed that the viewing of highly preferred compared to less preferred scenes (as assessed by participant ratings) was associated with greater blood-oxygen level dependent responses in the right parahippocampal cortex but not in the lateral occipital complex, ruling out feed forward and attentional effects. Highly preferred images also produced greater activation in the ventral striatum, suggesting that perceptual preference might engage the conventional reward system. These results are consistent with the hypothesis that high activity in the parahippocampal cortex, an area with a high density of cortical mu-opioid receptors, may be experienced as cognitively pleasurable.