Functional neuroanatomy of the human eye movement network: a review and atlas.

The human eye movement network is a complex system that requires the integration of sensory, motor, attentional, and executive processes. Here, we review the neuroanatomy of the eye movement network with an emphasis on functional neuroimaging applications. We consolidate the literature into a concise resource designed to be immediately accessible and applicable to diverse research interests, and present the novel Functional Oculomotor System (FOcuS) Atlas-a tool in stereotaxic space that will simplify and standardize the inclusion of the eye movement network in future functional neuroimaging studies. We anticipate this review and the FOcuS Atlas will facilitate increased examination of the eye movement network across disciplines leading to a thorough understanding of how eye movement network function contributes to higher-order cognition and how it is integrated with other brain networks. Furthermore, functional examination of the eye movement network in patient populations offers the potential for deeper insight into the role of eye movement circuitry in functional network activity, diagnostic assessments, and the indications for augmentative communication systems that rely on eye movement control.

Effects of Amylin Against Amyloid-ß-Induced Tauopathy and Synapse Loss in Primary Neurons.

Recent studies demonstrate that peripheral amylin treatment reduces pathology in mouse models of Alzheimer's disease (AD). However, soluble and aggregated amylin are distinct species; while amylin is a physiological neuropeptide, amylin aggregation is a pathological factor for diabetes. We thus hypothesized that because of their similarity in secondary structures, amylin antagonizes amyloid-ß peptide (Aß)-induced AD pathology in neurons with a dose-dependent pattern. To test the hypothesis, we conducted both in vitro and in vivo experiments with different doses of amylin and with its analog, pramlintide. Here we report that a high concentration of either Aß or amylin alone induced tau phosphorylation (pTau) in primary neurons. Interestingly, with a low concentration, amylin had direct effects to reverse the Aß-induced pTau, as well as damaged neuronal synapses and neurite disorganization. However, when the concentration was high (10.24 µM), amylin lost the effects against the Aß-induced cellular AD pathology and, together with Aß, worsened tauopathy in neurons. In the 5XFAD AD mouse model, daily peripheral amylin treatment with a low dose (200 µg/kg) more effectively reduced amyloid burden, and increased synapse, but with a high dose (800 µg/kg), it more effectively reduced tauopathy. Correspondingly, amylin treatment improved learning and memory in these mice. It demonstrates that amylin has a dose-dependent U-shape effect against AD pathogenesis. Within a physiological range, amylin is a neuroprotective hormone against AD in neurons; but when both Aß and amylin concentrations are elevated, imbalance of Aß and amylin may contribute to brain AD pathogenesis.

Frontolimbic neural circuit changes in emotional processing and inhibitory control associated with clinical improvement following transference-focused psychotherapy in borderline personality disorder.

AIMS: Borderline personality disorder (BPD) is characterized by self-regulation deficits, including impulsivity and affective lability. Transference-focused psychotherapy (TFP) is an evidence-based treatment proven to reduce symptoms across multiple cognitive-emotional domains in BPD. This pilot study aimed to investigate neural activation associated with, and predictive of, clinical improvement in emotional and behavioral regulation in BPD following TFP. METHODS: BPD subjects (n = 10) were scanned pre- and post-TFP treatment using a within-subjects design. A disorder-specific emotional-linguistic go/no-go functional magnetic resonance imaging paradigm was used to probe the interaction between negative emotional processing and inhibitory control. RESULTS: Analyses demonstrated significant treatment-related effects with relative increased dorsal prefrontal (dorsal anterior cingulate, dorsolateral prefrontal, and frontopolar cortices) activation, and relative decreased ventrolateral prefrontal cortex and hippocampal activation following treatment. Clinical improvement in constraint correlated positively with relative increased left dorsal anterior cingulate cortex activation. Clinical improvement in affective lability correlated positively with left posterior-medial orbitofrontal cortex/ventral striatum activation, and negatively with right amygdala/parahippocampal activation. Post-treatment improvements in constraint were predicted by pre-treatment right dorsal anterior cingulate cortex hypoactivation, and pre-treatment left posterior-medial orbitofrontal cortex/ventral striatum hypoactivation predicted improvements in affective lability. CONCLUSIONS: These preliminary findings demonstrate potential TFP-associated alterations in frontolimbic circuitry and begin to identify neural mechanisms associated with a psychodynamically oriented psychotherapy.

An integrative neurocircuit perspective on psychogenic nonepileptic seizures and functional movement disorders: neural functional unawareness.

Functional neurological disorder (conversion disorder) is a neurobehavioral condition frequently encountered by neurologists. Psychogenic nonepileptic seizure (PNES) and functional movement disorder (FMD) patients present to epileptologists and movement disorder specialists respectively, yet neurologists lack a neurobiological perspective through which to understand these enigmatic groups. Observational research studies suggest that PNES and FMD may represent variants of similar (or the same) conditions given that both groups exhibit a female predominance, have increased prevalence of mood-anxiety disorders, frequently endorse prior abuse, and share phenotypic characteristics. In this perspective article, neuroimaging studies in PNES and FMD are reviewed, and discussed using studies of emotional dysregulation, dissociation and psychological trauma in the context of motor control. Convergent neuroimaging findings implicate alterations in brain circuits mediating emotional expression, regulation and awareness (anterior cingulate and ventromedial prefrontal cortices, insula, amygdala, vermis), cognitive control and motor inhibition (dorsal anterior cingulate, dorsolateral prefrontal, inferior frontal cortices), self-referential processing and perceptual awareness (posterior parietal cortex, temporoparietal junction), and motor planning and coordination (supplementary motor area, cerebellum). Striatal-thalamic components of prefrontal-parietal networks may also play a role in pathophysiology. Aberrant medial prefrontal and amygdalar neuroplastic changes mediated by chronic stress may facilitate the development of functional neurological symptoms in a subset of patients. Improved biological understanding of PNES and FMD will likely reduce stigma and aid the identification of neuroimaging biomarkers guiding treatment development, selection, and prognosis. Additional research should investigate neurocircuit abnormalities within and across functional neurological disorder subtypes, as well as compare PNES and FMD with mood-anxiety-dissociative disorders.