Functional connectivity has been observed to fluctuate across the course of a resting state scan, though the origins and functional relevance of this phenomenon remain to be shown. The present study ...explores the link between endogenous dynamics of functional connectivity and autonomic state in an eyes-closed resting condition. Using a sliding window analysis on resting state fMRI data from 35 young, healthy male subjects, we examined how heart rate variability (HRV) covaries with temporal changes in whole-brain functional connectivity with seed regions previously described to mediate effects of vigilance and arousal (amygdala and dorsal anterior cingulate cortex; dACC). We identified a set of regions, including brainstem, thalamus, putamen, and dorsolateral prefrontal cortex, that became more strongly coupled with the dACC and amygdala seeds during states of elevated HRV. Effects differed between high and low frequency components of HRV, suggesting specific contributions of parasympathetic and sympathetic tone on individual connections. Furthermore, dynamics of functional connectivity could be separated from those primarily related to BOLD signal fluctuations. The present results contribute novel information about the neural basis of transient changes of autonomic nervous system states, and suggest physiological and psychological components of the recently observed non-stationarity in resting state functional connectivity.
► HRV covaried with fluctuations in resting connectivity seeded from dACC and amygdala. ► Distinct effects were found between high-frequency and low-frequency HRV. ► Autonomic fluctuations may contribute to nonstationarity in resting connectivity.
Mnemonic discrimination, the ability to distinguish similar events in memory, relies on subregions in the human medial temporal lobes (MTLs). Tau pathology is frequently found within the MTL of older ...adults and therefore likely to affect mnemonic discrimination, even in healthy older individuals. The MTL subregions that are known to be affected early by tau pathology, the perirhinal-transentorhinal region (area 35) and the anterior-lateral entorhinal cortex (alEC), have recently been implicated in the mnemonic discrimination of objects rather than scenes. Here we used an object-scene mnemonic discrimination task in combination with fMRI recordings and analyzed the relationship between subregional MTL activity, memory performance, and levels of total and phosphorylated tau as well as Aβ42/40 ratio in CSF. We show that activity in alEC was associated with mnemonic discrimination of similar objects but not scenes in male and female cognitively unimpaired older adults. Importantly, CSF tau levels were associated with increased fMRI activity in the hippocampus, and both increased hippocampal activity as well as tau levels were associated with mnemonic discrimination of objects, but again not scenes. This suggests that dysfunction of the alEC-hippocampus object mnemonic discrimination network might be a marker for tau-related cognitive decline.
SIGNIFICANCE STATEMENT
Subregions in the human medial temporal lobe are critically involved in episodic memory and, at the same time, affected by tau pathology. Impaired object mnemonic discrimination performance as well as aberrant activity within the entorhinal-hippocampal circuitry have been reported in earlier studies involving older individuals, but it has thus far remained elusive whether and how tau pathology is implicated in this specific impairment. Using task-related fMRI in combination with measures of tau pathology in CSF, we show that measures of tau pathology are associated with increased hippocampal activity and reduced mnemonic discrimination of similar objects but not scenes. This suggests that object mnemonic discrimination tasks could be promising markers for tau-related cognitive decline.
Background:
Various psychiatric populations are currently investigated with resting state fMRI, with the aim of individualizing diagnostics and treatment options and improving treatment outcomes. ...Many of these studies are conducted in large naturalistic samples, providing rich insights regarding disease-related neural alterations, but with the common psychopharmacological medication limiting interpretations of the results. We therefore investigated the effects of common noradrenergic and anti-dopaminergic medications on local and global resting state activity (rs-activity) in healthy volunteers to further the understanding of the respective effects independent from disease-related alterations.
Methods:
Within a randomized, double-blind, placebo-controlled crossover design, we investigated 19 healthy male subjects by resting state fMRI after the intake of reboxetine (4mg/d), amisulpride (200mg/d), and placebo for 7 days each. Treatment-related differences in local and global rs-activity were measured by the fractional amplitude of low frequency fluctuations (fALFF) and resting state functional connectivity (rs-FC).
Results:
fALFF revealed alterations of local rs-activity within regions of the core noradrenergic pathway, including the locus coeruleus under reboxetine, correlated with its plasma levels. Moreover, reboxetine led to increased rs-FC between regions within this pathway, i.e. the locus coeruleus, tectum, thalamus, and amygdala. Amisulpride modulated local rs-activity of regions within the dopaminergic pathway, with the altered signal in the putamen correlating with amisulpride plasma levels. Correspondingly, amisulpride increased rs-FC between regions of the dopaminergic pathway comprising the substantia nigra and putamen.
Conclusion:
Our data provide evidence of how psychopharmacological agents alter local and global rs-activity within the respective neuroanatomical pathways in healthy subjects, which may help with interpreting data in psychiatric populations.
The brain's default mode network (DMN) and the executive control network (ECN) switch engagement are influenced by the ventral attention network (VAN). Alterations in resting‐state functional ...connectivity (RSFC) within this so‐called triple network have been demonstrated in patients with major depressive disorder (MDD) or anxiety disorders (ADs). This study investigated alterations in the RSFC in patients with comorbid MDD and ADs to better understand the pathophysiology of this prevalent group of patients. Sixty‐eight participants (52.9% male, mean age 35.3 years), consisting of 25 patients with comorbid MDD and ADs (MDD + AD), 20 patients with MDD only (MDD) and 23 healthy controls (HCs) were investigated clinically and with 3T resting‐state fMRI. RSFC utilizing a seed‐based approach within the three networks belonging to the triple network was compared between the groups. Compared with HC, MDD + AD showed significantly reduced RSFC between the ECN and the VAN, the DMN and the VAN and within the ECN. No differences could be found for the MDD group compared with both other groups. Furthermore, symptom severity and medication status did not affect RSFC values. The results of this study show a distinct set of alterations of RSFC for patients with comorbid MDD and AD compared with HCs. This set of dysfunctions might be related to less adequate switching between the DMN and the ECN as well as poorer functioning of the ECN. This might contribute to additional difficulties in engaging and utilizing consciously controlled emotional regulation strategies.
This study highlights alterations of resting‐state functional connectivity within the well‐established triple network model in patients with comorbid depression and anxiety disorders. The clusters found within the cingulate and paracingulate and frontal areas may play an important role in the specific symptomatology of comorbid MDD and AD.
•Dysregulated neuronal circuits are related to inflammation in MDD.•Inflammation is linked to dysregulation between affective and default mode network.•Depression is associated with increased resting ...state functional connectivity.•Findings support the hypothesis of an immune inflammatory subtype of depression.
Several studies in major depressive disorder (MDD) have found inflammation, especially C-reactive protein (CRP), to be consistently associated with MDD and network dysfunction. The aim was to investigate whether CRP is linked to a distinct set of resting-state functional connectivity (RSFC) alterations.
For this reason, we investigated the effects of diagnosis and elevated blood plasma CRP levels on the RSFC in 63 participants (40 females, mean age 31.4 years) of which were 27 patients with a primary diagnosis of MDD and 36 healthy control-subjects (HC), utilizing a seed-based approach within five well-established RSFC networks obtained using fMRI.
Of the ten network pairs examined, five showed increased between-network RSFC-values unambiguously connected either to a diagnosis of MDD or elevated CRP levels. For elevated CRP levels, increased RSFC between DMN and AN was found. Patients showed increased RSFC within DMN areas and between the DMN and ECN and VAN, ECN and AN and AN and DAN.
The results of this study show dysregulated neural circuits specifically connected to elevated plasma CRP levels and independent of other alterations of RSFC in MDD. This dysfunction in neural circuits might in turn result in a certain immune-inflammatory subtype of MDD.
Sexual dysfunction is not only a common symptom in major depression but also a frequent side-effect of antidepressant medication, mainly of the selective serotonin reuptake-inhibitors (SSRI) that are ...often prescribed as a first line treatment option. Despite of the increasing incidence and prescription rates, neuronal mechanisms underlying SSRI-related sexual dysfunction are poorly understood and investigations on this topic are scarce. Neuroimaging techniques, mainly functional magnetic resonance imaging (fMRI), provide a feasible approach to investigate these mechanisms since SSRI-related sexual dysfunction is most likely related to central nervous processes. This review summarizes the recent literature regarding the basic clinical findings and imaging correlates of antidepressant-related sexual dysfunction linking brain regions and networks potentially involved to phases and subcomponents of sexual processing and antidepressant action. In particular, fMRI studies on SSRI antidepressants including paroxetine and SNRIs including bupropion are highlighted.
•Sexual dysfunction is a frequent side-effect of antidepressant (AD) medication.•Neuroimaging techniques allow for investigating the underlying mechanisms.•We summarize recent literature on neural correlates of sexual dysfunction under AD.
The thalamus, a crucial node in the well-described cortico-striatal-thalamo-cortical circuits, has been the focus of functional and structural imaging studies investigating human emotion, cognition ...and memory. Invasive work in animals and post-mortem investigations have revealed the rich cytoarchitectonics and functional specificity of the thalamus. Given current restrictions in the spatial resolution of non-invasive imaging modalities, there is, however, a translational gap between functional and structural information on these circuits in humans and animals as well as between histological and cellular evidence and their relationship to psychological functioning. With the advance of higher field strengths for MR approaches, better spatial resolution is now available promising to overcome this conceptual problem. We here review these two levels, which exist for both neuroscientific and clinical investigations, and then focus on current attempts to overcome conceptual boundaries of these observations with the help of ultra-high resolution imaging.
Introduction
Subjective cognitive decline (SCD) can represent a preclinical stage of Alzheimer’s disease. Diffusion tensor imaging (DTI) could aid an early diagnosis, yet only few monocentric DTI ...studies in SCD have been conducted, reporting heterogeneous results. We investigated microstructural changes in SCD in a larger, multicentric cohort.
Methods
271 participants with SCD, mild cognitive impairment (MCI) or Alzheimer’s dementia (AD) and healthy controls (CON) were included, recruited prospectively at nine centers of the observational DELCODE study. DTI was acquired using identical protocols. Using voxel-based analyses, we investigated fractional anisotropy (FA), mean diffusivity (MD) and mode (MO) in the white matter (WM). Discrimination accuracy was determined by cross-validated elastic-net penalized regression. Center effects were explored using variance analyses.
Results
MO and FA were lower in SCD compared to CON in several anterior and posterior WM regions, including the anterior corona radiata, superior and inferior longitudinal fasciculus, cingulum and splenium of the corpus callosum (
p
< 0.01, uncorrected). MD was higher in the superior and inferior longitudinal fasciculus, cingulum and superior corona radiata (
p
< 0.01, uncorrected). The cross-validated accuracy for discriminating SCD from CON was 67% (
p
< 0.01). As expected, the AD and MCI groups had higher MD and lower FA and MO in extensive regions, including the corpus callosum and temporal brain regions. Within these regions, center accounted for 3–15% of the variance.
Conclusions
DTI revealed subtle WM alterations in SCD that were intermediate between those in MCI and CON and may be useful to detect individuals with an increased risk for AD in clinical studies.
Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased ...subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy.
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