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Interleukin-6 (IL-6) is a pro-inflammatory cytokine produced by immune cells and other cell types such as microglia throughout the brain. Higher levels of IL-6 in older adults have been cross-sectionally and longitudinally associated with physical and cognitive impairment, as well as increased dementia risk. The association between IL-6 levels and structural and functional brain changes is less clear. In the present study, we investigated the relationship between IL-6 concentrations and cortical thinning with aging. Magnetic Resonance Imaging (MRI) scans from the Baltimore Longitudinal Study of Aging were analyzed for 121 older subjects (M = 69.3; SD = 7.3; range = 56.1–85.9 yrs) who were repeatedly tested over an average period of 7.5 yrs, and who remained non-demented for the entire follow-up period. The Freesurfer longitudinal processing stream was utilized for image processing, and IL-6 measures were based on serum ELISA assays averaged across time points. Results showed that higher mean IL-6 concentrations were associated with accelerated annual rates of cortical thinning in the inferior temporal poles bilaterally. Additional pronounced regions of IL-6 -accelerated thinning included the transverse frontopolar gyri within the left hemisphere, and subcentral gyrus and sulcus within the right hemisphere. Our results indicate that sustained high levels of the inflammatory biomarker IL-6 are associated with regionally increased rates of age-related cortical thinning. These data build on previous findings that link IL-6 to chronic disease and demonstrate one mechanism through which high levels of inflammation may have adverse effects on physical and cognitive function.

Spinal muscular atrophy (SMA), the most common genetic cause of infant death, is a neurodegenerative disorder affecting motor neurons. SMA results from a loss in full-length survival of motor neuron (SMN) protein due to deletions/mutations in the SMN1 gene. In this study, we assessed the ability of cell-penetrating peptides (CPP) to deliver recombinant SMN protein to cultured neurons as a prelude for a potential therapeutic to treat SMA. Firstly, we confirmed that E. coli produced recombinant GFP protein fused to TAT (YGRKKRRQRRR; TAT-GFP) transduced rat cortical neurons in a concentration dependent manner. However, due to low yields of recombinant TATSMN protein obtainable from E. coli, we investigated the potential of a modified TAT (TATκ: YARKAARQARA) or R9 (RRRRRRRRR) peptide downstream of the fibronectin (FIB) secretory signal peptide to generate recombinant CPP-fused SMN protein. While U251 cells transduced with an adenoviral vector expressing CMV-FIB-TATκ-SMN secreted recombinant TATκ-SMN protein, we did not detect TATκ-SMN protein transduction of cortical neurons. Further, purified TATκ-SMN was unable to transduce SH-SY5Y cells, nor block apoptosis following LY294002 treatment of these cells. Our findings indicate that TATκ is not a suitable CPP to deliver SMN protein to neurons. Nonetheless, we have developed a novel method to generate full-length recombinant SMN protein using a mammalian expression system, which can be used to explore the application of other CPPs to deliver SMN protein as a treatment for SMA.

MRI studies on abnormal brain development are dependent on the quality, quantity, and type of normative development data available for comparison. Limitations affecting previous studies on normative development include small sample sizes, lack of demographic representation, heterogeneous subject populations, and inadequate longitudinal data. The National Institutes of Health Pediatric MRI Data Repository (NIHPD) for normative development was designed to address the aforementioned issues in reliability measures of control subjects for comparison studies. The subjects were recruited from six Pediatric Study Centers nationwide to create the largest, non-biased, longitudinal database of the developing brain. Using the NIHPD, we applied a 3D shape analysis method involving spherical harmonics to identify the cortical surface complexity of 396 subjects (210 female; 186 male) between the ages of 4.8 y and 22.3 y. MRI data had been obtained at one, two, or three time points approximately two years apart. A total of 144 participants (79 female; 65 male) provided MRI data from all time points. Our results confirm a direct correlation between cortical complexity and age in both males and females. Additionally, within the examined age range, females displayed consistently and significantly greater cortical complexity than males. Findings suggest that the underlying neural circuitry within male and female brains is different, possibly explaining observations of sexual dimorphism in social interaction, communication, and higher cognitive processes.

Studies in both rodents and humans have made much progress in shedding light on how fluctuations in ovarian hormones can affect memory in women across the lifespan. Specifically, advances in neuroscience have identified multiple memory systems that are each mediated by different brain areas. Two memory systems used to navigate an environment are ‘place’ and ‘response’ memory. They are defined as either using an allocentric strategy: using a spatial or cognitive map of the surroundings, or an egocentric strategy: using habitual-turns/movements, respectively. Studies in neuroendocrinology have shown that estrogen levels can bias a female to use one memory system over another to solve a task, such that high estrogen levels are associated with using place memory and low levels with using response memory. Furthermore, recent advances in identifying and localizing estrogen receptors in the rodent brain are uncovering which brain regions are affected by estrogen and providing insight into how hormonal fluctuations during the menstrual cycle, pregnancy, and menopause might affect which memory system is facilitated or impaired in women at different life stages. These studies can help point the way to improving cognitive health in women.

Recent advances along clinical and neuropathological lines, as well as in our ability to detect the deposition of β-amyloid (Aβ) in vivo using positron emission tomography (PET), have helped redefine Alzheimer’s disease (AD) as a dynamic clinicobiological entity. On the basis of these advances, AD is now conceptualized as a continuum comprising asymptomatic, minimally symptomatic, and dementia phases, with detection of brain Aβ — in particular, via PET amyloid imaging — central to the diagnostic process. In this respect, [18F]florbetapir (Amyvid™) and [18F]flutemetamol (Vizamyl™) have recently received approval for clinical use from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), with additional radiofluorinated tracers for detection of Aβ in phase III trials. Recent initiatives such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) suggest that Aβ production, oligomerization and aggregation begins many years, possibly decades, before detectable cognitive impairment, with Aβ shown to associate with cognitive decline and conversion to dementia. While personalized medicine has now emerged as a prospect for the field, the recent decision by the Centers for Medicare & Medicaid Services (CMS) — who declined to cover the cost of amyloid PET imaging citing insufficient evidence to support its clinical utility — highlights that such a move may be premature.

Understanding the automatic process of love oriented to a participant by his or her own lover helps to build a normal loving relationship. It also helps to elucidate some of the underlying mechanisms of pathological love, which involves both repetitive and uncontrolled attention and care. Previous studies have addressed the late-stage process of love, but its early or automatic stage has been studied less. When processing a change in speech from “love” to “love you” from their own lover, participants showed a more prefrontal-frontal distribution of cerebral mismatch negativity. Source analysis showed that the left superior temporal gyrus was involved in all participants. The right inferior frontal gyrus was additionally involved in some participants who evaluated love as more intense. Brain areas activated in process might inversely indicate how much a participant cares about the love oriented by their lover.

In theoretical accounts of the neurosciences, investigative research programs have often been separated into the morphological and physiological tradition. The morphological tradition is seen as describing the structure and form of the external and interior parts of the brain and spinal cord. The physiological tradition is interpreted as a compilation of those approaches which investigate cerebral functions particularly in their dynamic interactions. It must be regarded as an open question, though, whether the distinction between the morphological and physiological tradition in modern clinical and basic neuroscience has now become obsolete with the most recent neuroimaging techniques, such as fMRI, PET scans, SPECT, etc. Taken at face value, these new imaging techniques seem to relate, overlap, and even identify the anatomical with the functional substrate, when mapping individual patterns of neural activity across the visually delineated morphological structures. The particular focus of this review article is primarily on the morphological tradition, beginning with German neuroanatomist Samuel Thomas Soemmerring and leading to recent approaches in the neurohistological work of neuroscience centres in the United States and morphophysiological neuroimaging techniques in Canada. Following some landmark research steps in neuroanatomy detailed in the first section, this article analyzes the changing trajectories to an integrative theory of the brain in its second section. An examination of the relationship between form and function within the material culture of neuroscience in the third and final part, will further reveal an astonishingly heterogeneous investigative and conceptual terrain.

Glia, including astrocytes, microglia and oligodendrocytes, are important components that maintain the architecture of the brain and in many ways contribute to the proper functioning of neurons. Glial cells vastly outnumber neurons in the brain and independently control several crucial brain functions. Impaired glial cells are the cause of several diseases, and pharmacological targeting to repair damaged glia will enable functional recovery in patients suffering from devastating neurological disorders. The interaction between glial cells and some patrolling immune cells in the brain comprise the brain-specific immune system that protects the brain from extraneous agents and repairs injured tissue. While this system can cope with minor insults and infections, when faced with significant challenges such as AIDS dementia, multiple sclerosis, Huntington’s disease, Parkinson’s disease, etc., an effective and balanced immune response that facilitates repair and protection is found wanting. Several debilitating neurological disorders are often associated with dysfunctional glial cells that have limited ability to repair the injured brain and even promote brain damage. In this discussion, specific signaling pathways in glia that are affected in AIDS dementia and periventricular white matter injury will be highlighted.

Brain-machine interfaces (BMIs) hold promise to treat neurological disabilities by linking intact brain circuitry to assistive devices, such as limb prostheses, wheelchairs, artificial sensors, and computers. BMIs have experienced very rapid development in recent years, facilitated by advances in neural recordings, computer technologies and robots. BMIs are commonly classified into three types: sensory, motor and bidirectional, which subserve motor, sensory and sensorimotor functions, respectively. Additionally, cognitive BMIs have emerged in the domain of higher brain functions. BMIs are also classified as noninvasive or invasive according to the degree of their interference with the biological tissue. Although noninvasive BMIs are safe and easy to implement, their information bandwidth is limited. Invasive BMIs hold promise to improve the bandwidth by utilizing multichannel recordings from ensembles of brain neurons. BMIs have a broad range of clinical goals, as well as the goal to enhance normal brain functions.