Neural health relies on cortical excitation–inhibition balance (EIB). Previous research suggests a link between increased cortical excitation and neuroplasticity induced by selective serotonin reuptake inhibitors (SSRIs). Whether there are modulations of EIB following SSRI‐administration in the healthy human brain, however, remains unclear. Thus, in a randomized double‐blind study, we administered a clinically relevant dose of 20 mg escitalopram for 7 days (time when steady state is achieved) in 59 healthy women (28 escitalopram, 31 placebo) on oral contraceptives. We acquired resting‐state electroencephalography data at baseline, after a single dose, and at steady state. We assessed 1/f slope of the power spectrum as a marker of EIB, compared individual trajectories of 1/f slope changes contrasting single dose and 1‐week drug intake, and tested the relationship of escitalopram plasma levels and cortical excitatory and inhibitory balance shifts. Escitalopram‐intake was associated with decreased 1/f slope, indicating an EIB shift in favor of excitation. Furthermore, 1/f slope at baseline and after a single dose of escitalopram was associated with 1/f slope at steady state. Higher plasma escitalopram levels at a single dose were associated with better maintenance of these EIB changes throughout the drug administration week. These findings demonstrate the potential for 1/f slope to predict individual cortical responsivity to SSRIs and widen the lens through which we map the human brain by testing an interventional psychopharmacological design in a clearly defined endocrinological state.

Nuclear medicine is defined as the diagnosis and the treatment of disease using radiolabeled compounds known as radiopharmaceuticals. Single-photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography/computer tomography (PET/CT) based radiopharmaceuticals have proven reliable in diagnostic imaging in nuclear medicine and cancer treatment. One of the most critical cancers that also relies on an early diagnosis is gynecological cancer. Given that approximately 25% of all cancers in developing countries are a subset of gynecological cancer, investigating this cancer subtype is of significant clinical worth, particularly in light of its high rate of mortality. With accurate identification of high grade distant abdominal endometrial cancer as well as extra abdominal metastases, 18F-Fluorodeoxyglucose ([¹⁸F]FDG) PET/CT imaging is considered a valuable step forward in the investigation of gynecological cancer. Considering these factors, [¹⁸F]FDG PET/CT imaging can assist in making management of patient therapy more feasible. In this literature review, we will provide a short overview of the role of nuclear medicine in the diagnosis of obstetric and gynecological cancers.

The precuneus is a site of early amyloid-beta (Aβ) accumulation. Previous cross-sectional studies reported increased precuneus fMRI activity in older adults with mild cognitive deficits or elevated Aβ. However, longitudinal studies in early Alzheimer's disease (AD) are lacking and the relationship to the Apolipoprotein-E (APOE) genotype is unclear. Investigating the PREVENT-AD dataset, we assessed how baseline and longitudinal precuneus activity during successful memory retrieval relates to future Aβ and tau burden and change in memory performance. We further studied the moderation by APOE4 genotype. We included 165 older adults (age, 62.8 ± 4.4 years; 113 female; 66 APOE4 carriers) who were cognitively normal at baseline with a family history of AD. All participants performed task-fMRI at baseline and underwent ¹⁸F-flortaucipir-PET and ¹⁸F-NAV4694-Aβ-PET on average 5 years later. We found that higher baseline activity and greater longitudinal increase in precuneus activity were associated with higher Aβ burden in APOE4 carriers but not noncarriers. We observed no effects of precuneus activity on tau burden. Finally, APOE4 noncarriers with low baseline precuneus activity exhibited better longitudinal performance in an independent memory test compared with (1) noncarriers with higher baseline activity and (2) APOE4 carriers. Our findings suggest that higher task-related precuneus activity during memory retrieval at baseline and over time are associated with greater Aβ burden in cognitively normal APOE4 carriers. Our results further indicate that the absence of “hyperactivation” and the absence of the APOE4 allele is related with better future cognitive outcomes in cognitively normal older adults at risk for AD.

Background: Both aging and Alzheimer's disease (AD) affect brain networks, with early disruptions occurring in regions involved in episodic memory. Few studies have, however, focused on distinguishing region-specific effects of AD-biomarker negative “normal” aging and early amyloid- and tau pathology on functional connectivity. Further, longitudinal studies combining imaging, biomarkers, and cognition are rare. Methods: We assessed resting-state functional connectivity (rsFC) strength and graph measures in the episodic memory network including the medial temporal lobe (MTL), posteromedial cortex (PMC), and medial prefrontal cortex alongside cognition over two years. For this preregistered study, we included 100 older adults who were amyloid- and tau-negative using CSF and PET measurements to investigate “normal” aging, and 70 older adults who had longitudinal CSF data available to investigate functional changes related to early AD pathology. All participants were cognitively unimpaired older adults from the PREVENT-AD cohort. We used region of interest (ROI)-to-ROI bivariate correlations, graph analysis, and multiple regression models. Results: In the amyloid- and tau-negative sample, rsFC strength within PMC, between parahippocampal cortex and inferomedial precuneus, and between posterior hippocampus and inferomedial precuneus decreased over time. Additionally, we observed a longitudinal decrease in global efficiency. Further, there was a steeper longitudinal decrease in rsFC and global efficiency with higher baseline age particularly of parahippocampal-gyrus regions. Further, lower rsFC strength within PMC was associated with poorer longitudinal episodic memory performance. In the sample with available CSF data, a steeper increase in rsFC between anterior hippocampus and superior precuneus was related to higher baseline AD pathology. Higher MTL-PMC rsFC strength was differentially associated with episodic memory trajectories depending on APOE4 genotype. Conclusions: Our findings suggest differential effects of aging and AD pathology. Hypoconnectivity within PMC was related to aging and cognitive decline. MTL-PMC hyperconnectivity was related to early AD pathology and cognitive decline in APOE4 carriers. Future studies should investigate more diverse samples, nonetheless, our approach allowed us to identify longitudinal functional changes related to aging and early AD pathology, enhancing cross-sectional research. Hyperconnectivity has been proposed as a mechanism related to early AD pathology before, we now contribute specific functional connections to focus on in future research. Graphical A) “Normal aging” in cognitively unimpaired older adults with a negative amyloid- and tau- biomarker status was characterized by a longitudinal decrease in functional connectivity strength. B) Cognitively unimpaired older adults with more Alzheimer’s pathology at baseline (measured via cerebrospinal fluid) exhibited a longitudinal increase in functional connectivity strength.

Resistance to age-related pathological changes (brain maintenance), including Alzheimer’s disease, cerebrovascular disease, and neurodegeneration may promote cognitive resilience in aging. However, how lifestyle and health profiles relate to successful cognitive and brain aging remains poorly understood. In a novel, deeply phenotyped cohort of 211 cognitively unimpaired older adults (age = 71.0 ± 7.4 years, 46% female), we characterized principal components of lifestyle and health using questionnaire, fitness, and blood data. We estimated cognitive age gap (CAG) based on comprehensive neuropsychological data and brain age gap (BAG) based on brain-pathology markers, including plasma biomarkers of Alzheimer’s pathology (pTau ₂₁₇ and Aβ _1-42 /Aβ _1-40 ), MRI-based measures of white matter hyperintensities, perivascular spaces, and brain atrophy. Regression analyses tested how the observed lifestyle-health profiles were related to CAG and BAG. Seven principal components explained 49% of the variance in health and lifestyle. The second component, characterized by a mentally and physically active life and low cardiovascular risk, was associated with lower CAG ( β = − 0.66, p < 0.001) and BAG ( β = − 0.52, p = 0.003), reflecting a younger-than-expected brain and cognitive age, respectively. The association of an active lifestyle and lower CAG was partially mediated by BAG. Higher CAG was also associated with other lifestyle components characterized by low mental stimulation. APOE-ε4 carriers exhibited higher BAG. In conclusion, a lifestyle combining low cardiovascular risk, high mental engagement throughout life and high physical activity/fitness is jointly associated with less-than-expected brain pathology and better-than-expected cognitive performance, supporting its involvement in brain maintenance and cognitive resilience to aging.

The contribution of selective serotonin reuptake inhibitors to motor learning by inducing motor cortical plasticity remains controversial given diverse findings from positive preclinical data to negative findings in recent clinical trials. To empirically address this translational disparity, we use functional magnetic resonance imaging in a double-blind, randomized controlled study to assess whether 20 mg escitalopram improves sequence-specific motor performance and modulates cortical motor response in 64 healthy female participants. We found decreased left premotor cortex responses during sequence-specific learning performance comparing single dose and steady escitalopram state. Escitalopram plasma levels negatively correlated with the premotor cortex response. We did not find evidence in support of improved motor performance after a week of escitalopram intake. These findings do not support the conclusion that one week escitalopram intake increases motor performance but could reflect early adaptive plasticity with improved neural processing underlying similar task performance when steady peripheral escitalopram levels are reached.