Task-Related, Low-Frequency Task-Residual, and Resting State Activity in the Default Mode Network Brain Regions

The hypothesis of a default mode network (DMN) of brain function is based on observations of task-independent decreases of brain activity during effort as participants are engaged in tasks in contrast to resting. On the other hand, studies also showed that DMN regions activate rather than deactivate in response to task-related events. Thus, does DMN “deactivate” during effort as compared to resting? We hypothesized that, with high-frequency event-related signals removed, the task-residual activities of the DMN would decrease as compared to resting. We addressed this hypothesis with two approaches. First, we examined DMN activities during resting, task residuals, and task conditions in the stop signal task using independent component analysis (ICA). Second, we compared the fractional amplitude of low-frequency fluctuation (fALFF) signals of DMN in resting, task residuals, and task data. In the results of ICA of 76 subjects, the precuneus and posterior cingulate cortex (PCC) showed increased activation during task as compared to resting and task residuals, indicating DMN responses to task events. Precuneus but not the PCC showed decreased activity during task residual as compared to resting. The latter finding was mirrored by fALFF, which is decreased in the precuneus during task residuals, as compared to resting and task. These results suggested that the low-frequency blood oxygen level-dependent signals of the precuneus may represent a useful index of effort during cognitive performance

Resting State Functional Connectivity of the Lateral and Medial Hypothalamus in Cocaine Dependence: An Exploratory Study

The role of dopamine in cocaine misuse has been extensively documented for the mesocorticolimbic circuit. Preclinical work from earlier lesion studies to recent multidisciplinary investigations has suggested that the hypothalamus is critically involved in motivated behavior, with the lateral and medial hypothalamus each involved in waking/feeding and resting/satiety. However, little is known of hypothalamus function and dysfunction in cocaine misuse. Here, we examined resting state functional connectivity of the lateral and medial hypothalamus in 70 individuals with cocaine dependence (CD) and 70 age as well as gender matched healthy controls (HC). Image pre-processing and analyses followed published work. Compared to HC, CD showed increased lateral hypothalamic connectivity with dorsolateral prefrontal cortex and decreased functional connectivity with the ventral precuneus. CD showed increased medial hypothalamic connectivity with the inferior parietal lobule and decreased connectivity with the ventromedial prefrontal cortex, temporal gyrus, fusiform gyrus, and ventral striatum. Further, at trend level significance, the connectivity strength between lateral hypothalamus and dorsolateral prefrontal cortex was positively correlated with total amount of cocaine use in the past month (p = 0.004, r = 0.35) and the connectivity strength between medial hypothalamus and ventral striatum was negatively correlated with cocaine craving as assessed by the Tiffany Cocaine Craving Questionnaire (p = 0.008, r = −0.33). Together, the findings demonstrated altered resting state functional connectivity of the hypothalamus and may provide new insight on circuit level deficits in cocaine dependence

Inference With Interference Between Units in an fMRI Experiment of Motor Inhibition

An experimental unit is an opportunity to randomly apply or withhold a treatment. There is interference between units if the application of the treatment to one unit may also affect other units. In cognitive neuroscience, a common form of experiment presents a sequence of stimuli or requests for cognitive activity at random to each experimental subject and measures biological aspects of brain activity that follow these requests. Each subject is then many experimental units, and interference between units within an experimental subject is, likely, in part because the stimuli follow one another quickly and in part because human subjects learn or become experienced or primed or bored as the experiment proceeds. We use a recent functional magnetic resonance imaging (fMRI) experiment concerned with the inhibition of motor activity to illustrate and further develop recently proposed methodology for inference in the presence of interference. A simulation evaluates the power of competing procedures

Exploring Age-Related Changes in Resting State Functional Connectivity of the Amygdala: From Young to Middle Adulthood

Functional connectivities of the amygdala support emotional and cognitive processing. Life-span development of resting-state functional connectivities (rsFC) of the amygdala may underlie age-related differences in emotion regulatory mechanisms. To date, age-related changes in amygdala rsFC have been reported through adolescence but not as thoroughly for adulthood. This study investigated age-related differences in amygdala rsFC in 132 young and middle-aged adults (19–55 years). Data processing followed published routines. Overall, amygdala showed positive rsFC with the temporal, sensorimotor and ventromedial prefrontal cortex (vmPFC), insula and lentiform nucleus, and negative rsFC with visual, frontoparietal, and posterior cingulate cortex and caudate head. Amygdala rsFC with the cerebellum was positively correlated with age, and rsFCs with the dorsal medial prefrontal cortex (dmPFC) and somatomotor cortex were negatively correlated with age, at voxel p < 0.001 in combination with cluster p < 0.05 FWE. These age-dependent changes in connectivity appeared to manifest to a greater extent in men than in women, although the sex difference was only evident for the cerebellum in a slope test of age regressions (p = 0.0053). Previous studies showed amygdala interaction with the anterior cingulate cortex (ACC) and vmPFC during emotion regulation. In region of interest analysis, amygdala rsFC with the ACC and vmPFC did not show age-related changes. These findings suggest that intrinsic connectivity of the amygdala evolved from young to middle adulthood in selective brain regions, and may inform future studies of age-related emotion regulation and maladaptive development of the amygdala circuits as an etiological marker of emotional disorders

Altered Functional Connectivity of the Basal Nucleus of Meynert in Mild Cognitive Impairment: A Resting-State fMRI Study

Background: Cholinergic dysfunction plays an important role in mild cognitive impairment (MCI). The basal nucleus of Meynert (BNM) provides the main source of cortical cholinergic innervation. Previous studies have characterized structural changes of the cholinergic basal forebrain in individuals at risk of developing Alzheimer’s disease (AD). However, whether and how functional connectivity of the BNM (BNM-FC) is altered in MCI remains unknown.Objective: The aim of this study was to identify alterations in BNM-FC in individuals with MCI as compared to healthy controls (HCs), and to examine the relationship between these alterations with neuropsychological measures in individuals with MCI.Method: One-hundred-and-one MCI patients and 103 HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI). Imaging data were processed with SPM8 and CONN software. BNM-FC was examined via correlation in low frequency fMRI signal fluctuations between the BNM and all other brain voxels. Group differences were examined with a covariance analysis with age, gender, education level, mean framewise displacement (FD) and global correlation (GCOR) as nuisance covariates. Pearson’s correlation was conducted to evaluate the relationship between the BNM-FC and clinical assessments.Result: Compared with HCs, individuals with MCI showed significantly decreased BNM-FC in the left insula extending into claustrum (insula/claustrum). Furthermore, greater decrease in BNM-FC with insula/claustrum was associated with more severe impairment in immediate recall during Auditory Verbal Learning Test (AVLT) in MCI patients.Conclusion: MCI is associated with changes in BNM-FC to the insula/claustrum in relation to cognitive impairments. These new findings may advance research of the cholinergic bases of cognitive dysfunction during healthy aging and in individuals at risk of developing AD

Activation of the pre-supplementary motor area but not inferior prefrontal cortex in association with short stop signal reaction time – an intra-subject analysis

Abstract Background Our previous work described the neural processes of motor response inhibition during a stop signal task (SST). Employing the race model, we computed the stop signal reaction time (SSRT) to index individuals' ability in inhibitory control. The pre-supplementary motor area (preSMA), which shows greater activity in individuals with short as compared to those with long SSRT, plays a role in mediating response inhibition. In contrast, the right inferior prefrontal cortex (rIFC) showed greater activity during stop success as compared to stop error. Here we further pursued this functional differentiation of preSMA and rIFC on the basis of an intra-subject approach. Results Of 65 subjects who participated in four sessions of the SST, we identified 30 individuals who showed a difference in SSRT but were identical in other aspects of stop signal performance between the first ("early") and last two ("late") sessions. By comparing regional brain activation between the two sessions, we confirmed greater preSMA but not rIFC activity during short as compared to long SSRT session within individuals. Furthermore, putamen, anterior cerebellum and middle/posterior cingulate cortex also showed greater activity in association with short SSRT. Conclusion These results are consistent with a role of medial prefrontal cortex in controlled action and inferior frontal cortex in orienting attention. We discussed these findings with respect to the process of attentional monitoring and inhibitory motor control during stop signal inhibition.</p

Disrupted Functional Connectivity of Cornu Ammonis Subregions in Amnestic Mild Cognitive Impairment: A Longitudinal Resting-State fMRI Study

Background: The cornu ammonis (CA), as part of the hippocampal formation, represents a primary target region of neural degeneration in amnestic mild cognitive impairment (aMCI). Previous studies have revealed subtle structural deficits of the CA subregions (CA1-CA3, bilateral) in aMCI; however, it is not clear how the network function is impacted by aMCI. The present study examined longitudinal changes in resting state functional connectivity (FC) of each CA subregion and how these changes relate to neuropsychological profiles in aMCI.Methods: Twenty aMCI and 20 healthy control (HC) participants underwent longitudinal cognitive assessment and resting state functional MRI scans at baseline and 15 months afterward. Imaging data were processed with published routines in SPM8 and CONN software. Two-way analysis of covariance was performed with covariates of age, gender, education level, follow up interval, gray matter volume, mean FD, as well as global correlation (GCOR). Pearson’s correlation was conducted to evaluate the relationship between the longitudinal changes in CA subregional FC and neuropsychological performance in aMCI subjects.Results: Resting state FC between the right CA1 and right middle temporal gyrus (MTG) as well as between the left CA2 and bilateral cuneal cortex (CC) were decreased in aMCI subjects as compared to HC. Longitudinal decrease in FC between the right CA1 and right MTG was correlated with reduced capacity of episodic memory in aMCI subjects.Conclusion: The current findings suggest functional alterations in the CA subregions. CA1 connectivity with the middle temporal cortex may represent an important neural marker of memory dysfunction in aMCI

Dissociable Processes of Cognitive Control during Error and Non-Error Conflicts: A Study of the Stop Signal Task

Conflict detection and subsequent behavioral adjustment are critical to daily life, and how this process is controlled has been increasingly of interest. A medial cortical region which includes the anterior cingulate cortex (ACC) has been theorized to act as a conflict detector that can direct prefrontal activity for behavioral adjustments. This conflict monitoring hypothesis was supported by many imaging studies of the Stroop task, with a focus on non-error processes. Here we sought to examine whether this circuit could be generalized to the stop signal task (SST), another behavioral paradigm widely used to study cognitive control. In particular, with a procedure to elicit errors in the SST, we examined whether error and non-error control were mediated by the same pathways.In functional magnetic resonance imaging of 60 healthy adults, we demonstrated that the medial cortical activity during stop success (SS) as compared to go success (G) trials is correlated with increased prefrontal activity in post-stop SS as compared to post-go SS trials, though this correlation was not specific to the medial cortical region. Furthermore, thalamic and insular rather than medial cortical activation during stop error (SE) as compared to G trials correlated with increased prefrontal activity in post-stop SS as compared to post-go SS trials.Taken together, these new findings challenge a specific role of the ACC and support distinct pathways for error and non-error conflict processing in cognitive control

The effects of age on cerebral activations: internally versus externally driven processes

Numerous studies using functional magnetic resonance imaging (fMRI) have described increased or decreased regional brain activations in older as compared to younger adults. This seeming inconsistency may reflect differences in the psychological constructs examined across studies. We hypothesized that behavioral tasks/contrasts engaging internally and externally driven processes are each associated with age-related decreases and increases, respectively, in cerebral activations. We examined the fMRI data of 103 healthy adults, 18–72 years of age, performing a stop signal task (SST), in which a frequent “go” signal triggered a prepotent response and a less frequent “stop” signal prompted inhibition of this response. Greater internally driven processes lead to stop successes (SS) as compared to stop errors (SE), and to speeding up instead of slowing down in go trials. Conversely, externally driven processes contribute to SE trials, which resulted from habitual, unmonitored responses triggered by the go signal (as compared to SS trials), and involved perceptual and cognitive processes elicited by the stop signal (as compared to go trials). Consistent with our hypothesis, the results showed age-related decreases and increases in cerebral activations each during these respective internally and externally driven processes. These findings further elucidate the influence of age on cognitive functioning and provide an additional perspective to understand the imaging literature of aging