Characterization of cognitive function in survivors of diffuse gliomas using resting-state functional MRI (rs-fMRI)

As treatments for diffuse gliomas have advanced, survival for patients with gliomas has also increased. However, there remains limited knowledge on the relationships between brain connectivity and the lasting changes to cognitive function that glioma survivors often experience long after completing treatment. This resting-state functional magnetic resonance imaging (rs-fMRI) study explored functional connectivity (FC) alterations associated with cognitive function in survivors of gliomas. In this pilot study, 22 patients (mean age 43.8 ± 11.9) with diffuse gliomas who completed treatment within the past 10 years were evaluated using rs-fMRI and neuropsychological measures. Novel rs-fMRI analysis methods were used to account for missing brain in the resection cavity. FC relationships were assessed between cognitively impaired and non-impaired glioma patients, along with self-reported cognitive impairment, non-work daily functioning, and time with surgery. In the cognitively non-impaired patients, FC was stronger in the medial prefrontal cortex, rostral prefrontal cortex, and intraparietal sulcus compared to the impaired survivors. When examining non-work daily functioning, a positive correlation with FC was observed between the accumbens and the intracalcarine cortices, while a negative correlation with FC was observed between the parietal operculum cortex and the cerebellum. Additionally, worse self-reported cognitive impairment and worse non-work daily functioning were associated with increased FC between regions involved in cognition and sensorimotor processing. These preliminary findings suggest that neural correlates for cognitive and daily functioning in glioma patients can be revealed using rs-fMRI. Resting-state network alterations may serve as a biomarker for patients’ cognition and functioning.

Intolerance of uncertainty is associated with heightened responding in the prefrontal cortex during cue-signalled uncertainty of threat

Heightened responding to uncertain threat is considered a hallmark of anxiety disorder pathology. We sought to determine whether individual differences in self-reported intolerance of uncertainty (IU), a key transdiagnostic dimension in anxiety-related pathology, underlies differential recruitment of neural circuitry during cue-signalled uncertainty of threat (n = 42). In an instructed threat of shock task, cues signalled uncertain threat of shock (50%) or certain safety from shock. Ratings of arousal and valence, skin conductance response (SCR), and functional magnetic resonance imaging were acquired. Overall, participants displayed greater ratings of arousal and negative valence, SCR, and amygdala activation to uncertain threat versus safe cues. IU was not associated with greater arousal ratings, SCR, or amygdala activation to uncertain threat versus safe cues. However, we found that high IU was associated with greater ratings of negative valence and greater activity in the medial prefrontal cortex and dorsomedial rostral prefrontal cortex to uncertain threat versus safe cues. These findings suggest that during cue-signalled uncertainty of threat, individuals high in IU rate uncertain threat as aversive and engage prefrontal cortical regions known to be involved in safety-signalling and conscious threat appraisal. Taken together, these findings highlight the potential of IU in modulating safety-signalling and conscious appraisal mechanisms in situations with cue-signalled uncertainty of threat, which may be relevant to models of anxiety-related pathology.

Neural Concomitants of Remote Memory in a Comedian with Exceptional Verbal Memory

Most studies exploring how remote memory is represented in the brain are based on strong episodic self-related components. Because of methodological reasons, much less is known about how the information concerning the semantic part of autobiographical memory is retrieved, and whether the brain correlates differ according to the autobiographical moment of the memory formation. In the present study, we explored the neural concomitants of the retrieval of texts learnt at different periods of life, in a comedian with exceptional verbal memory skills. This 49-year-old comedian was instructed to recite aloud a total of 30 texts he learnt during three different epochs: before the age of 15 years (E1), between the age of 15 and 25 years (E2), and after the age of 25 years (E3). The most salient activation was observed for memory from the farthest period, with a preponderance of the medial rostral prefrontal cortex (PFC) and of the precuneus. There was no hippocampal activation during text retrieval by comparison to a control condition, whatever the learning period. This study supports the assumption that the recall of remote semantic memories can occur without hippocampal activation. We discussed the activation of the rostral PFC during retrieval of the oldest (and best consolidated) memories as the possible involvement of control meta-memory processes rather than memory processes per se.

Individual Differences in Interoceptive Accuracy Are Correlated With Salience Network Connectivity in Older Adults

Interoceptive accuracy refers to the ability to consciously perceive the physical condition of the inner body, including one’s heartbeat. In younger adults, interoceptive accuracy is correlated with insular and orbitofrontal cortical connectivity within the salience network (SN). As interoceptive accuracy and insular cortex volume are known to decrease with aging, we aimed to evaluate the correlation between SN connectivity and interoceptive accuracy in older adults. 27 older adults (mean age, 77.29 years, SD = 6.24; 19 female) underwent resting-state functional magnetic resonance imaging, followed by a heartbeat counting task and neuropsychological test. We evaluated the correlation between interoceptive accuracy and SN connectivity with age, sex, cognitive function, and total gray matter volume as covariates. Region of interest-to-region of interest analyses showed that interoceptive accuracy was positively correlated with the functional connectivity (FC) of the left rostral prefrontal cortex with the right insular, right orbitofrontal, and anterior cingulate cortices [F(6,16) = 4.52, false discovery rate (FDR)-corrected p < 0.05]. Moreover, interoceptive accuracy was negatively correlated to the FC of the left anterior insular cortex with right intra-calcarine and visual medial cortices (F(6,16) = 2.04, FDR-corrected p < 0.10). These findings suggest that coordination between systems, with a positive correlation between left rostral prefrontal cortex and the SN and a negative correlation between left insular cortex and vision-related exteroceptive brain regions, is important for maintaining interoceptive accuracy in older adults.

Intolerance of uncertainty is associated with heightened responding in the prefrontal cortex during instructed threat of shock

Heightened responding to uncertain threat is associated with anxiety disorder pathology. Here, we sought to determine if individual differences in self-reported intolerance of uncertainty (IU) underlie differential recruitment of neural circuitry during instructed threat of shock (n = 42). During the task, cues signalled uncertain threat of shock (50%) or certain safety from shock. Ratings, skin conductance and functional magnetic resonance imaging was acquired. Overall, participants displayed greater amygdala activation to uncertain threat vs. safe cues, in the absence of an effect of IU. However, we found that high was associated with greater activity in the medial prefrontal cortex and dorsomedial rostral prefrontal cortex to uncertain threat vs safe cues. These findings suggest that, during instructed threat of shock, IU is specifically related, over trait anxiety, to activation in prefrontal cortical regions. Taken together, these findings highlight the potential of self-reported IU in identifying mechanisms that may be related to conscious threat appraisal and anxiety disorder pathology.