Anterior pituitary gland volume mediates associations between pubertal hormones and changes in transdiagnostic symptoms in youth.

The pituitary gland (PG) plays a central role in the production and secretion of pubertal hormones, with documented links to the emergence and increase in mental health symptoms known to occur during adolescence. Although much of the literature has focused on examining whole PG volume, recent findings suggest that there are associations among pubertal hormone levels, including dehydroepiandrosterone (DHEA), subregions of the PG, and elevated mental health symptoms (e.g., internalizing symptoms) during adolescence. Surprisingly, studies have not yet examined associations among these factors and increasing transdiagnostic symptomology, despite DHEA being a primary output of the anterior PG. Therefore, the current study sought to fill this gap by examining whether anterior PG volume specifically mediates associations between DHEA levels and changes in dysregulation symptoms in an adolescent sample ( N = 114, 9 - 17 years, M age = 12.87, SD = 1.88). Following manual tracing of the anterior and posterior PG, structural equation modeling revealed that greater anterior, not posterior, PG volume mediated the association between greater DHEA levels and increasing dysregulation symptoms across time, controlling for baseline dysregulation symptom levels. These results suggest specificity in the role of the anterior PG in adrenarcheal processes that may confer risk for psychopathology during adolescence. This work not only highlights the importance of separately tracing the anterior and posterior PG, but also suggests that transdiagnostic factors like dysregulation are useful in parsing hormone-related increases in mental health symptoms in youth.

Dehydroepiandrosterone mediates associations between trauma-related symptoms and anterior pituitary volume in children and adolescents.

INTRODUCTION: The anterior pituitary gland (PG) is a potential locus of hypothalamic-pituitary-adrenal (HPA) axis responsivity to early life stress, with documented associations between dehydroepiandrosterone (DHEA) levels and anterior PG volumes. In adults, elevated anxiety/depressive symptoms are related to diminished DHEA levels, and studies have shown a positive relationship between DHEA and anterior pituitary volumes. However, specific links between responses to stress, DHEA levels, and anterior pituitary volume have not been established in developmental samples. METHODS: High-resolution T1-weighted MRI scans were collected from 137 healthy youth (9-17 years; Mage = 12.99 (SD = 1.87); 49% female; 85% White, 4% Indigenous, 1% Asian, 4% Black, 4% multiracial, 2% not reported). The anterior and posterior PGs were manually traced by trained raters. We examined the mediating effects of salivary DHEA on trauma-related symptoms (i.e., anxiety, depression, and posttraumatic) and PG volumes as well as an alternative model examining mediating effects of PG volume on DHEA and trauma-related symptoms. RESULTS: DHEA mediated the association between anxiety symptoms and anterior PG volume. Specifically, higher anxiety symptoms related to lower DHEA levels, which in turn were related to smaller anterior PG. CONCLUSIONS: These results shed light on the neurobiological sequelae of elevated anxiety in youth and are consistent with adult findings showing suppressed levels of DHEA in those with greater comorbid anxiety and depression. Specifically, adolescents with greater subclinical anxiety may exhibit diminished levels of DHEA during the pubertal window, which may be associated with disruptions in anterior PG growth.

Developmental alterations in the neural oscillatory dynamics underlying attentional reorienting.

The neural and cognitive processes underlying the flexible allocation of attention undergo a protracted developmental course with changes occurring throughout adolescence. Despite documented age-related improvements in attentional reorienting throughout childhood and adolescence, the neural correlates underlying such changes in reorienting remain unclear. Herein, we used magnetoencephalography (MEG) to examine neural dynamics during a Posner attention-reorienting task in 80 healthy youth (6-14 years old). The MEG data were examined in the time-frequency domain and significant oscillatory responses were imaged in anatomical space. During the reorienting of attention, youth recruited a distributed network of regions in the fronto-parietal network, along with higher-order visual regions within the theta (3-7 Hz) and alpha-beta (10-24 Hz) spectral windows. Beyond the expected developmental improvements in behavioral performance, we found stronger theta oscillatory activity as a function of age across a network of prefrontal brain regions irrespective of condition, as well as more limited age- and validity-related effects for alpha-beta responses. Distinct brain-behavior associations between theta oscillations and attention-related symptomology were also uncovered across a network of brain regions. Taken together, these data are the first to demonstrate developmental effects in the spectrally-specific neural oscillations serving the flexible allocation of attention.

Comprehensive review of task-based neuroimaging studies of cognitive deficits in Alzheimer's disease using electrophysiological methods.

With an aging population, cognitive decline and neurodegenerative disorders are an emerging public health crises with enormous, yet still under-recognized burdens. Alzheimer's disease (AD) is the most common type of dementia, and the number of cases is expected to dramatically rise in the upcoming decades. Substantial efforts have been placed into understanding the disease. One of the primary avenues of research is neuroimaging, and while positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are most common, crucial recent advancements in electrophysiological methods such as magnetoencephalography (MEG) and electroencephalography (EEG) have provided novel insight into the aberrant neural dynamics at play in AD pathology. In this review, we outline task-based M/EEG studies published since 2010 using paradigms probing the cognitive domains most affected by AD, including memory, attention, and executive functioning. Furthermore, we provide important recommendations for adapting cognitive tasks for optimal use in this population and adjusting recruitment efforts to improve and expand future neuroimaging work.

Signatures of somatosensory cortical dysfunction in Alzheimer's disease and HIV-associated neurocognitive disorder.

Alzheimer's disease is the most common type of dementia in the general population, while HIV-associated neurocognitive disorder is the most common neurological comorbidity in those infected with HIV and affects between 40 and 70% of this population. Both conditions are associated with cognitive impairment and have been associated with aberrant functioning in sensory cortices, but far less is known about their disparate effects on neural activity. Identifying such disparate effects is important because it may provide critical data on the similarities and differences in the neuropathology underlying cognitive decline in each condition. In the current study, we utilized magnetoencephalography, extensive neuropsychological testing and a paired-pulse somatosensory gating paradigm to probe differences in somatosensory processing in participants from two ongoing magnetoencephalography studies. The resulting participant groups included 27 cognitively normal controls, 26 participants with HIV-associated neurocognitive disorder and 21 amyloid biomarker-confirmed patients with Alzheimer's disease. The data were imaged using a beamformer and voxel time series were extracted to identify the oscillatory dynamics serving somatosensory processing, as well as the amplitude of spontaneous cortical activity preceding stimulation onset. Our findings indicated that people with Alzheimer's disease and HIV-associated neurocognitive disorder exhibit normal somatosensory gating but have distinct aberrations in other elements of somatosensory cortical function. Essentially, those with Alzheimer's disease exhibited accentuated neural responses to somatosensory stimulation, along with spontaneous gamma activity preceding stimulus onset. In contrast, those with HIV-associated neurocognitive disorder exhibited normal responses to somatosensory stimulation but had sharply elevated spontaneous gamma activity prior to stimulus onset. These distinct aberrations may reflect the impact of different neuropathological mechanisms underlying each condition. Further, given the differential pattern of deficits in somatosensory cortical function, these measures may function as unique biomarkers in each condition and be useful in identifying persons with HIV who may go on to develop Alzheimer's disease.

Somatosensory dysfunction is masked by variable cognitive deficits across patients on the Alzheimer's disease spectrum.

BACKGROUND: Alzheimer's disease (AD) is generally thought to spare primary sensory function; however, such interpretations have drawn from a literature that has rarely taken into account the variable cognitive declines seen in patients with AD. As these cognitive domains are now known to modulate cortical somatosensory processing, it remains possible that abnormalities in somatosensory function in patients with AD have been suppressed by neuropsychological variability in previous research. METHODS: In this study, we combine magnetoencephalographic (MEG) brain imaging during a paired-pulse somatosensory gating task with an extensive battery of neuropsychological tests to investigate the influence of cognitive variability on estimated differences in somatosensory function between biomarker-confirmed patients on the AD spectrum and cognitively-normal older adults. FINDINGS: We show that patients on the AD spectrum exhibit largely non-significant differences in somatosensory function when cognitive variability is not considered (p-value range: .020-.842). However, once attention and processing speed abilities are considered, robust differences in gamma-frequency somatosensory response amplitude (p < .001) and gating (p = .004) emerge, accompanied by significant statistical suppression effects. INTERPRETATION: These findings suggest that patients with AD exhibit insults to functional somatosensory processing in primary sensory cortices, but these effects are masked by variability in cognitive decline across individuals. FUNDING: National Institutes of Health, USA; Fremont Area Alzheimer's Fund, USA.

Impact of HIV-infection on human somatosensory processing, spontaneous cortical activity, and cortical thickness: A multimodal neuroimaging approach.

HIV-infection has been associated with widespread alterations in brain structure and function, although few studies have examined whether such aberrations are co-localized and the degree to which clinical and cognitive metrics are related. We examine this question in the somatosensory system using high-resolution structural MRI (sMRI) and magnetoencephalographic (MEG) imaging of neural oscillatory activity. Forty-four participants with HIV (PWH) and 55 demographically-matched uninfected controls completed a paired-pulse somatosensory stimulation paradigm during MEG and underwent 3T sMRI. MEG data were transformed into the time-frequency domain; significant sensor level responses were imaged using a beamformer. Virtual sensor time series were derived from the peak responses. These data were used to compute response amplitude, sensory gating metrics, and spontaneous cortical activity power. The T1-weighted sMRI data were processed using morphological methods to derive cortical thickness values across the brain. From these, the cortical thickness of the tissue coinciding with the peak response was estimated. Our findings indicated both PWH and control exhibit somatosensory gating, and that spontaneous cortical activity was significantly stronger in PWH within the left postcentral gyrus. Interestingly, within the same tissue, PWH also had significantly reduced cortical thickness relative to controls. Follow-up analyses indicated that the reduction in cortical thickness was significantly correlated with CD4 nadir and mediated the relationship between HIV and spontaneous cortical activity within the left postcentral gyrus. These data indicate that PWH have abnormally strong spontaneous cortical activity in the left postcentral gyrus and such elevated activity is driven by locally reduced cortical gray matter thickness.