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Tilman Schulte

SRI Author

Biomedical sciences publications

Physiological Responses to Acute Psychosocial Stress in Women with Menopausal Insomnia

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Introduction: Insomnia disorder is a common sleep disorder and frequently emerges in the context of menopause, being associated with menopause-specific factors such as hot flashes and other psychosocial variables. Increased vulnerability to stress may also contribute to the development of insomnia in midlife women. Here, we aimed to investigate whether there are differences in physiological reactivity to acute psychosocial stress in women with menopausal insomnia compared with controls.

Methods: We investigated cortisol and heart rate [HR] responses to an acute experimental psychosocial stress (Trier Social Stress Test, TSST) approximately 1 h after waking in the morning in midlife women with ( n = 22) and without ( n = 16) DSM-IV insomnia disorder (Age: 50.05 ± 3.10 years), developed in the context of menopause.

Results: Despite similar perceived stress levels, women with insomnia showed blunted HR increases (~29% HR acceleration) to the TSST compared to controls (~44% HR acceleration) ( p = 0.026). No group differences in HR were detected at baseline or during post-task recovery. Cortisol stress responses were inconclusive, with most of the women (60%) failing to exhibit significant cortisol increases in response to the TSST. A greater magnitude of the cortisol awakening response (CAR) predicted the likelihood of being a non-responder ( p = 0.036), showing the confounding effect of CAR on cortisol stress responses.

Discussion: Women with menopausal insomnia show blunted cardiac responses to stress, suggesting alterations in the autonomic reactivity to acute stress. Whether these alterations are pre-existing or are a consequence of insomnia, needs to be determined.

Biomedical sciences publications

Compromised Frontocerebellar Circuitry Contributes to Nonplanning Impulsivity in Recovering Alcoholics

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Abstract
RATIONALE:
Degradation of frontocerebellar circuitry is a principal neural mechanism of alcoholism-related executive dysfunctions affecting impulse control and cognitive planning.
OBJECTIVE:
We tested the hypothesis that alcoholic patients would demonstrate compromised dorsal anterior cingulate cortex (dACC) -cerebellar functional connectivity when adjusting their strategies to accommodate uncertain conditions and would recruit compensatory brain regions to overcome ineffective response patterns.
METHODS:
Twenty-six alcoholics and 26 healthy participants underwent functional MRI in two sequential runs while performing a decision-making task. The first run required a response regardless of level of ambiguity of the stimuli; the second run allowed a PASS option (i.e., no response choice), which was useful on ambiguous trials.
RESULTS:
Healthy controls demonstrated strong synchronous activity between the dACC and cerebellum while planning and executing a behavioral strategy. By contrast, alcoholics showed synchronous activity between the dACC and the premotor cortex, perhaps enabling successful compensation for accuracy and reaction time in certain conditions; however, a negative outcome of this strategy was rigidity in modifying response strategy to accommodate uncertain conditions. Compared with the alcoholic group, the control group had lower nonplanning impulsiveness, which correlated with using the option PASS to respond in uncertain conditions.
CONCLUSION:
These findings suggest that compromised dACC-cerebellar functional circuitry contributes to recruitment of an alternative network-dACC-premotor cortex- to perform well under low-risk, unambiguous conditions. This compensatory network, however, was inadequate to enable the alcoholics to avert making poor choices in planning and executing an effective behavioral strategy in high-risk, uncertain conditions.

Biomedical sciences publications

Interhemispheric Functional Connectivity Change Is Linked to Callosal Fiber Integrity Change over a 1-Year Follow-up in Chronic Alcoholics

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Chronic alcoholism has deleterious long-term effects on the integrity of callosal white matter fibers connecting the two cerebral hemispheres. We tested whether microstructural fiber changes relate to resting-state functional connectivity changes in alcoholics who have maintained sobriety during a one-year interval, and whether these changes are beyond those potentially exhibited by controls. 12 (7w, 5m) alcoholics (ALC) and 13 (7w, 6m) age-matched controls (CTL) underwent MR diffusion tensor imaging and functional MR imaging at baseline and 1-year follow-up. In ALC, age at alcoholism onset was on average 37 years (range 15-56 years); the average time since last drink before study entry was 3½ months for ALC. Within the 1-year follow-up period, 6 ALC remained sober and 6 resumed drinking at social levels. We examined effects of group (CTL, ALC) and time (baseline, 1 year) on fractional anisotropy (FA) and mean diffusivity (MD) of fiber tufts of the whole corpus callosum and of 7 callosal sectors quantified with fiber tracking. Functional connectivity between the left and right hemisphere was tested for group and time, for 8 bilaterally homologous cortical areas: anterior, dorsolateral, and medial prefrontal, motor, parietal, occipital, medial and lateral temporal. Alcoholics showed poorer callosal fiber integrity (lower FA, higher MD) than CTL, with 3-way interactions for FA and MD indicating continued microstructural decline over the year in ALC relative to CTL that was more pronounced in anterior than posterior callosal sectors. Overall, groups did not differ in interhemispheric functional connectivity strength; a group-by-time interaction indexed a connectivity decline over the year between lateral temporal cortices in ALC relative to CTL. Higher amounts of lifetime alcohol consumption correlated with continued decline in callosal FA and with change to weaker interhemispheric connectivity between motor regions in ALC and between temporal regions over both groups. Within alcoholics, 1-year change to weaker functional connectivity between left and right medial frontal, motor, medial temporal and occipital regions was associated with continued decline in callosal white matter (FA, MD). To the extent that callosal fibers support interhemispheric cortico-cortical functional connectivity, these data suggest that continued fiber degradation is accompanied by decline in interhemispheric functional connectivity strength. Thus, continued decline in callosal fiber integrity occurs in alcoholism despite sobriety and relates to weaker interhemispheric functional connections in ALC, specifically in those with heavier past lifetime drinking.

Biomedical sciences publications

Synchrony of Anterior Cingulate Cortex and Insular-Striatal Activation Predicts Ambiguity Aversion in Individuals with Low Impulsivity

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Personal attitude toward ambiguity contributes to individual differences in decision making in uncertain situations. Operationally, these attitudes reflect the various coping strategies elected to overcome the limited information. A key brain region involved in cognitive control for performance adjustments is the dorsal anterior cingulate cortex (dACC). To test how dACC functional network connectivity would be modulated by uncertainty and differ between individuals, 24 healthy participants underwent functional MRI in 3 sequential runs: 1 resting-state and 2 decision-making task runs. Individuals with lower nonplanning impulsiveness made greater use of a Pass option and avoided uncertain ambiguous situations. Seed-based functional connectivity analysis during the task runs revealed that stronger activation synchrony between the left dACC and the right anterior insula correlated with greater use of a Pass response option. During the resting-state, stronger resting-state functional connectivity between the left dACC and the ventral striatum predicted the adoption of Pass as a behavioral strategy and correlated with stronger task-activated synchrony between the dACC and the right anterior insula. Our findings indicate that that the synchrony between the dACC and insula-striatal circuitry was greater in individuals with low compared with high nonplanning impulsiveness and contributed to adopting Pass as a useful behavioral strategy.

Biomedical sciences publications

Fiber Tract-Driven Topographical Mapping (FTTM) Reveals Microstructural Relevance for Interhemispheric Visuomotor Function in the Aging Brain

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We present a novel approach – DTI-based fiber tract-driven topographical mapping (FTTM) – to map and measure the influence of age on the integrity of interhemispheric fibers and challenge their selective functions with measures of interhemispheric integration of lateralized information. This approach enabled identification of spatially specific topographical maps of scalar diffusion measures and their relation to measures of visuomotor performance. Relative to younger adults, older adults showed lower fiber integrity indices in anterior than posterior callosal fibers. FTTM analysis identified a dissociation in the microstructural-function associates between age groups: in younger adults, genu fiber integrity correlated with interhemispheric transfer time, whereas in older adults, body fiber integrity was correlated with interhemispheric transfer time with topographical specificity along left-lateralized callosal fiber trajectories. Neural co-activation from redundant targets was evidenced by fMRI-derived bilateral extrastriate cortex activation in both groups, and a group difference emerged for a pontine activation cluster that was differently modulated by response hand in older than younger adults. Bilateral processing advantages in older but not younger adults further correlated with fiber integrity in transverse pontine fibers that branch into the right cerebellar cortex, thereby supporting a role for the pons in interhemispheric facilitation. In conclusion, in the face of compromised anterior callosal fibers, older adults appear to use alternative pathways to accomplish visuomotor interhemispheric information transfer and integration for lateralized processing. This shift from youthful associations may indicate recruitment of compensatory mechanisms involving medial corpus callosum fibers and subcortical pathways.