Neural correlates of the sound facilitation effect in the modified Simon task in older adults.

Introduction: The ability to resolve interference declines with age and is attributed to neurodegeneration and reduced cognitive function and mental alertness in older adults. Our previous study revealed that task-irrelevant but environmentally meaningful sounds improve performance on the modified Simon task in older adults. However, little is known about neural correlates of this sound facilitation effect. Methods: Twenty right-handed older adults [mean age = 72 (SD = 4), 11 female] participated in the fMRI study. They performed the modified Simon task in which the arrows were presented either in the locations matching the arrow direction (congruent trials) or in the locations mismatching the arrow direction (incongruent trials). A total of 50% of all trials were accompanied by task-irrelevant but environmentally meaningful sounds. Results: Participants were faster on the trials with concurrent sounds, independently of whether trials were congruent or incongruent. The sound effect was associated with activation in the distributed network of auditory, posterior parietal, frontal, and limbic brain regions. The magnitude of the behavioral facilitation effect due to sound was associated with the changes in activation of the bilateral auditory cortex, cuneal cortex, and occipital fusiform gyrus, precuneus, left superior parietal lobule (SPL) for No Sound vs. Sound trials. These changes were associated with the corresponding changes in reaction time (RT). Older adults with a recent history of falls showed greater activation in the left SPL than those without falls history. Conclusion: Our findings are consistent with the dedifferentiation hypothesis of cognitive aging. The facilitatory effect of sound could be achieved through recruitment of excessive neural resources, which allows older adults to increase attention and mental alertness during task performance. Considering that the SPL is critical for integration of multisensory information, individuals with slower task responses and those with a history of falls may need to recruit this region more actively than individuals with faster responses and those without a fall history to overcome increased difficulty with interference resolution. Future studies should examine the relationship among activation in the SPL, the effect of sound, and falls history in the individuals who are at heightened risk of falls.

Hand Dexterity Is Associated with the Ability to Resolve Perceptual and Cognitive Interference in Older Adults: Pilot Study.

The relationship between hand dexterity and inhibitory control across the lifespan is underexplored. In this pilot study, we examined inhibitory control using a modified Simon task. During the task, participants were presented with right- and left-pointing arrows located either on the right or the left parts of the screen. In the congruent trials, the arrow location and direction matched. In the incongruent trials, they mismatched, thus creating cognitive interference. In 50% of trials, the arrow presentation was accompanied by a task-irrelevant but environmentally meaningful sound that created perceptual interference. Hand dexterity was measured with the 9-hole peg test. Significantly faster reaction time (RT) on the modified Simon task (p < 0.001) was observed in younger adults, trials with concurrent sound stimuli, and congruent trials. Older adults who reported recent falls had greater difficulty resolving cognitive interference than older adults without recent falls. Hand dexterity significantly moderated the effect of sound on RT, but only in the group of older individuals. Interestingly, older individuals with reduced hand dexterity benefited from concurrent sounds more than those with better hand dexterity. Our findings suggest that task-irrelevant but environmentally meaningful sounds may increase alertness and enhance stimulus perception and recognition, thus improving motor performance in older individuals.

Working memory updating in individuals with bipolar and unipolar depression: fMRI study.

Understanding neurobiological characteristics of cognitive dysfunction in distinct psychiatric disorders remains challenging. In this secondary data analysis, we examined neurobiological differences in brain response during working memory updating among individuals with bipolar disorder (BD), those with unipolar depression (UD), and healthy controls (HC). Individuals between 18-45 years of age with BD (n = 100), UD (n = 109), and HC (n = 172) were scanned using fMRI while performing 0-back (easy) and 2-back (difficult) tasks with letters as the stimuli and happy, fearful, or neutral faces as distractors. The 2(n-back) × 3(groups) × 3(distractors) ANCOVA examined reaction time (RT), accuracy, and brain activation during the task. HC showed more accurate and faster responses than individuals with BD and UD. Difficulty-related activation in the prefrontal, posterior parietal, paracingulate cortices, striatal, lateral occipital, precuneus, and thalamic regions differed among groups. Individuals with BD showed significantly lower difficulty-related activation differences in the left lateral occipital and the right paracingulate cortices than those with UD. In individuals with BD, greater difficulty-related worsening in accuracy was associated with smaller activity changes in the right precuneus, while greater difficulty-related slowing in RT was associated with smaller activity changes in the prefrontal, frontal opercular, paracingulate, posterior parietal, and lateral occipital cortices. Measures of current depression and mania did not correlate with the difficulty-related brain activation differences in either group. Our findings suggest that the alterations in the working memory circuitry may be a trait characteristic of reduced working memory capacity in mood disorders. Aberrant patterns of activation in the left lateral occipital and paracingulate cortices may be specific to BD.

Behavioral and neuroimaging evidence prodromal to major depressive disorder onset in a young adult without personal or family history of psychiatric disorder: Case report.

Background: Subthreshold symptoms of major depressive disorder (MDD) may be underreported due to stigma and/or cognitive impairment associated with this illness. Identifying objective behavioral and neural markers prodromal to MDD onset would help overcome this bias. This case study reports prospective behavioral and neuroimaging evidence prodromal to MDD onset in a young adult without prior personal or family history of psychiatric disorders who was identified during a longitudinal study of mood disorders. Methods: The participant completed the SCID-5 and other assessments of depression as well as the Vividness of Visual Imagery Questionnaire at baseline, 6-month follow-up, and 12-month follow-up. The participant completed the Emotion Intensity Rating task and high-resolution structural images were collected using magnetic resonance imaging (MRI) at baseline and 6-month follow-up. The levels of cortical myelin computed as the T1w/T2w ratio were used in a linear discriminant analysis (LDA) to predict participant's diagnostic status at baseline and 6-months. Results: The participant presented as a healthy control at baseline and 6-month but met criteria for MDD at the 12-month follow-up based on the SCID-5. The participant's visual imagery as well as the ability to correctly recognize neutral faces dramatically reduced from baseline to 6-month follow-up. The LDA classified the participant as an individual with depressive disorders at both baseline and 6-month follow-up despite the absence of either subthreshold or clinical symptoms of depression. Conclusions: While preliminary, the results suggest that the measures of cortical myelin, response to neutral and emotional facial expressions, and vividness of visual imagery could be prodromal to illness onset, whereas clinician-administered or self-reported measures of depression symptoms were uninformative.

The effects of mood disorders and childhood trauma on fear of positive and negative evaluation.

Fear of positive and negative evaluation is maladaptive and may result in psychosocial dysfunction. Although being diagnosed with mood disorders or experiencing childhood trauma may potentially affect fear of evaluation, previous studies examined this phenomenon mostly in social anxiety disorders. To fill this gap, we investigated the relationship between childhood trauma and fear of positive and negative evaluation in individuals with bipolar disorder (BD), depressive disorders (DD), and healthy controls (HC). 43 individuals with BD, 89 with DD, and 65 HC completed clinical interviews and self-report assessments. The relationship between participants' diagnoses and presence of trauma on fear of positive and negative evaluation was examined using ANCOVA. Independently of experiencing childhood trauma, fear of positive evaluation was significantly higher in individuals with mood disorders vs. HC. Fear of negative evaluation was significantly associated with diagnosis-by-trauma interaction. Significantly lower scores were observed in individuals with BD without childhood trauma compared to those with childhood trauma and individuals with DD. Compared to HC, more individuals with mood disorders experienced childhood trauma. While experiencing childhood trauma may increase vulnerability to mood disorders in general, it is especially detrimental for individuals with BD by increasing the risk for developing a fear of negative evaluation.

The Relationship Between Default Mode and Dorsal Attention Networks Is Associated With Depressive Disorder Diagnosis and the Strength of Memory Representations Acquired Prior to the Resting State Scan.

Previous research indicates that individuals with depressive disorders (DD) have aberrant resting state functional connectivity and may experience memory dysfunction. While resting state functional connectivity may be affected by experiences preceding the resting state scan, little is known about this relationship in individuals with DD. Our study examined this question in the context of object memory. 52 individuals with DD and 45 healthy controls (HC) completed clinical interviews, and a memory encoding task followed by a forced-choice recognition test. A 5-min resting state fMRI scan was administered immediately after the forced-choice task. Resting state networks were identified using group Independent Component Analysis across all participants. A network modeling analysis conducted on 22 networks using FSLNets examined the interaction effect of diagnostic status and memory accuracy on the between-network connectivity. We found that this interaction significantly affected the relationship between the network comprised of the medial prefrontal cortex, posterior cingulate cortex, and hippocampal formation and the network comprised of the inferior temporal, parietal, and prefrontal cortices. A stronger positive correlation between these two networks was observed in individuals with DD who showed higher memory accuracy, while a stronger negative correlation (i.e., anticorrelation) was observed in individuals with DD who showed lower memory accuracy prior to resting state. No such effect was observed for HC. The former network cross-correlated with the default mode network (DMN), and the latter cross-correlated with the dorsal attention network (DAN). Considering that the DMN and DAN typically anticorrelate, we hypothesize that our findings indicate aberrant reactivation and consolidation processes that occur after the task is completed. Such aberrant processes may lead to continuous "replay" of previously learned, but currently irrelevant, information and underlie rumination in depression.

Aberrant levels of cortical myelin distinguish individuals with depressive disorders from healthy controls.

The association between depressive disorders and measures reflecting myelin content is underexplored, despite growing evidence of associations with white matter tract integrity. We characterized the T1w/T2w ratio using the Glasser atlas in 39 UD and 47 HC participants (ages = 19-44, 75% female). A logistic elastic net regularized regression with nested cross-validation and a subsequent linear discriminant analysis conducted on held-out samples were used to select brain regions and classify patients vs. healthy controls (HC). True-label model performance was compared against permuted-label model performance. The T1w/T2w ratio distinguished patients from HC with 68% accuracy (p < 0.001; sensitivity = 63.8%, specificity = 71.5%). Brain regions contributing to this classification performance were located in the orbitofrontal cortex, anterior cingulate, extended visual, and auditory cortices, and showed statistically significant differences in the T1w/T2w ratio for patients vs. HC. As the T1w/T2w ratio is thought to characterize cortical myelin, patterns of cortical myelin in these regions may be a biomarker distinguishing individuals with depressive disorders from HC.

White matter abnormalities in adults with bipolar disorder type-II and unipolar depression.

Discerning distinct neurobiological characteristics of related mood disorders such as bipolar disorder type-II (BD-II) and unipolar depression (UD) is challenging due to overlapping symptoms and patterns of disruption in brain regions. More than 60% of individuals with UD experience subthreshold hypomanic symptoms such as elevated mood, irritability, and increased activity. Previous studies linked bipolar disorder to widespread white matter abnormalities. However, no published work has compared white matter microstructure in individuals with BD-II vs. UD vs. healthy controls (HC), or examined the relationship between spectrum (dimensional) measures of hypomania and white matter microstructure across those individuals. This study aimed to examine fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) across BD-II, UD, and HC groups in the white matter tracts identified by the XTRACT tool in FSL. Individuals with BD-II (n = 18), UD (n = 23), and HC (n = 24) underwent Diffusion Weighted Imaging. The categorical approach revealed decreased FA and increased RD in BD-II and UD vs. HC across multiple tracts. While BD-II had significantly lower FA and higher RD values than UD in the anterior part of the left arcuate fasciculus, UD had significantly lower FA and higher RD values than BD-II in the area of intersections between the right arcuate, inferior fronto-occipital and uncinate fasciculi and forceps minor. The dimensional approach revealed the depression-by-spectrum mania interaction effect on the FA, RD, and AD values in the area of intersection between the right posterior arcuate and middle longitudinal fasciculi. We propose that the white matter microstructure in these tracts reflects a unique pathophysiologic signature and compensatory mechanisms distinguishing BD-II from UD.

Protocol for a machine learning algorithm predicting depressive disorders using the T1w/T2w ratio.

The T1w/T2w ratio is a novel magnetic resonance imaging (MRI) measure that is thought to be sensitive to cortical myelin. Using this novel measure requires developing novel pipelines for the data quality assurance, data analysis, and validation of the findings in order to apply the T1w/T2w ratio for classification of disorders associated with the changes in the myelin levels. In this article, we provide a detailed description of such a pipeline as well as the reference to the scripts used in our recent report that applied the T1w/T2w ratio and machine learning to classify individuals with depressive disorders from healthy controls.