The neuropathological basis of anxiety in Parkinson’s disease

Evidence suggests that 24.5%–46.7% (mean 31%) of patients with Parkinson’s disease experience an anxiety disorder, a much higher prevalence than in controls. Anxiety does not appear to be a consequence of diagnosis or the motoric symptoms of the disorder and can manifest as Generalised Anxiety Disorder, phobias or panic attacks. At present, the neural underpinnings of anxiety disorders in Parkinson’s disease is unknown. Here, we make the novel proposal that the superior colliculus (SC), one component of a rapid, reflexive threat detection system in the brain, consisting of the colliculus, pulvinar and amygdala, becomes hyper-responsive to sensory stimuli following dopamine denervation of the striatum in Parkinson’s disease. This in turn leads to heightened responses to existing threat-related stimuli (giving rise to phobias and panic attacks), and heightened responses to anticipated threats (giving rise to Generalised Anxiety Disorder). This proposal is supported by a range of evidence, in particular elevated visual responses in the SC in an animal model of Parkinson’s disease and in Parkinson’s disease itself. Also facilitated saccadic eye movements (prosaccades, express saccades and fixational saccades) and increased distractibility in Parkinson’s disease, both of which involve the SC. Identifying one potential locus of change in the brain in Parkinson’s disease relevant to anxiety gives a potential target for interventions to combat a non-motor symptom that has a substantial negative effect on quality of life in the disorder

Prosthesis use is associated with reduced physical self-disgust in limb amputees

Self-disgust is an emotion schema negatively affecting people’s body image and is triggered by bodily imperfections and deviations from the “normal” body envelope. In this study, we explore the idea that “normalising” the body in those with limb amputations via the prosthesis would be linked to reduced self-directed disgust. An international clinical community sample (N = 83) with mostly lower limb amputations completed measures about their demographics, prosthesis, adjustment, body image disturbance, psychological distress, and self-directed disgust in a survey design. Consistent with the “normalising” hypothesis, correlation and bootstrapped regression models revealed, first, that frequency of prosthesis use was significantly and negatively associated with physical self-disgust. Second, prosthesis use significantly mediated the exogenous effect of time since amputation on physical self-disgust. These results emphasise the psychological value of the prosthesis beyond its functional use, and stress its importance in normalising the body envelope in those with limb amputations, which may in turn promote psychological well-being

Segregated anatomical input to sub-regions of the rodent superior colliculus associated with approach and defense

The superior colliculus (SC) is responsible for sensorimotor transformations required to direct gaze toward or away from unexpected, biologically salient events. Significant changes in the external world are signaled to SC through primary multisensory afferents, spatially organized according to a retinotopic topography. For animals, where an unexpected event could indicate the presence of either predator or prey, early decisions to approach or avoid are particularly important. Rodents’ ecology dictates predators are most often detected initially as movements in upper visual field (mapped in medial SC), while appetitive stimuli are normally found in lower visual field (mapped in lateral SC). Our purpose was to exploit this functional segregation to reveal neural sites that can bias or modulate initial approach or avoidance responses. Small injections of Fluoro-Gold were made into medial or lateral sub-regions of intermediate and deep layers of SC (SCm/SCl). A remarkable segregation of input to these two functionally defined areas was found. (i) There were structures that projected only to SCm (e.g., specific cortical areas, lateral geniculate and suprageniculate thalamic nuclei, ventromedial and premammillary hypothalamic nuclei, and several brainstem areas) or SCl (e.g., primary somatosensory cortex representing upper body parts and vibrissae and parvicellular reticular nucleus in the brainstem). (ii) Other structures projected to both SCm and SCl but from topographically segregated populations of neurons (e.g., zona incerta and substantia nigra pars reticulata). (iii) There were a few brainstem areas in which retrogradely labeled neurons were spatially overlapping (e.g., pedunculopontine nucleus and locus coeruleus). These results indicate significantly more structures across the rat neuraxis are in a position to modulate defense responses evoked from SCm, and that neural mechanisms modulating SC-mediated defense or appetitive behavior are almost entirely segregated

The NK1 antagonist L-733,060 facilitates sequence learning

Background: Although several brain regions and electrophysiological patterns have been related to sequence learning, less attention has been paid to the role that different neuromodulators play. Aims: Here we sought to investigate the role of substance P (SP) in sequence learning in an operant conditioning preparation, supported by a reinforcement learning model. Methods: Two experiments were performed to test the effects of an NK1 receptor (at which SP primarily acts) antagonist on learning and performing action sequences. In experiment 1, rats were trained to perform an action sequence until stable performance was achieved, and then, in phase 2, they were switched to perform the reverse sequence. In experiment 2, rats were trained to performed an action sequence, and in phase 2, they continued to do the same sequence. In both experiments in the first three days of phase 2, rats were injected with an NK1 receptor antagonist (L-733,060, i.p.) or with vehicle. Additionally, we developed a reinforcement learning model which allowed the in-silico replication of our experimental tasks. Results: We found that administering an NK1 receptor antagonist weakened the stable retention of a well-learned sequence, allowing the faster acquisition of a new sequence, without impairing the continued performance of a crystalized sequence. Using our reinforcement learning model, we suggest that SP could be acting through the state value learning rate, modulating the effects of the reward prediction error. Conclusions: Our results suggest that SP could be involved in the consolidation of a sequence representation through a modulatory effect on the reward prediction error

Self-disgust, loneliness and mental health outcomes in older adults: An eye-tracking study

© 2020 Background: Self-disgust has been associated with loneliness and mental health difficulties in clinical and non-clinical populations, but there is limited research on the role of self-disgust in loneliness and mental health outcomes in older adults. Methods: In Study 1 (N = 102; M age = 68.4 years, SD = 10.9, 68% females) we used a cross-sectional survey to explore the association between loneliness, self-disgust and mental health outcomes. In Study 2 (N = 80; M age = 68.8 years, SD = 11.4, 57% females) we used eye-tracking to investigate attentional vigilance, maintenance and avoidance in individuals with high (vs. low) self-disgust. Results: In study 1 we found that self-disgust mediated the associations of loneliness with anxiety and depressive symptoms, and in study 2 it was demonstrated that older adults with high (vs. low) self-disgust displayed attentional avoidance to their own faces, compared to the faces of unknown others, a process that may perpetuate loneliness. Limitations: The cross-sectional design used in Study 1 limits our potential to make causal inferences. Additionally, both studies included a wide age range of older adults. Conclusions: Our findings are novel and highlight the importance of self-disgust experiences in the context of loneliness and mental health outcomes in older adults. Implications for practice and interventions against loneliness in this age group are discussed

Contralateral dissociation between neural activity and cerebral blood volume during recurrent acute focal neocortical seizures

OBJECTIVE: Whether epileptic events disrupt normal neurovascular coupling mechanisms locally or remotely is unclear. We sought to investigate neurovascular coupling in an acute model of focal neocortical epilepsy, both within the seizure onset zone and in contralateral homotopic cortex. METHODS: Neurovascular coupling in both ipsilateral and contralateral vibrissal cortices of the urethane-anesthetized rat were examined during recurrent 4-aminopyridine (4-AP, 15 mm, 1 μl) induced focal seizures. Local field potential (LFP) and multiunit spiking activity (MUA) were recorded via two bilaterally implanted 16-channel microelectrodes. Concurrent two-dimensional optical imaging spectroscopy was used to produce spatiotemporal maps of cerebral blood volume (CBV). RESULTS: Recurrent acute seizures in right vibrissal cortex (RVC) produced robust ipsilateral increases in LFP and MUA activity, most prominently in layer 5, that were nonlinearly correlated to local increases in CBV. In contrast, contralateral left vibrissal cortex (LVC) exhibited relatively smaller nonlaminar specific increases in neural activity coupled with a decrease in CBV, suggestive of dissociation between neural and hemodynamic responses. SIGNIFICANCE: These findings provide insights into the impact of epileptic events on the neurovascular unit, and have important implications both for the interpretation of perfusion-based imaging signals in the disorder and understanding the widespread effects of epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here

Sensory regulation of dopaminergic cell activity: Phenomenology, circuitry and function

Dopaminergic neurons in a range of species are responsive to sensory stimuli. In the anesthetized preparation, responses to non-noxious and noxious sensory stimuli are usually tonic in nature, although long-duration changes in activity have been reported in the awake preparation as well. However, in the awake preparation, short-latency, phasic changes in activity are most common. These phasic responses can occur to unconditioned aversive and non-aversive stimuli, as well as to the stimuli which predict them. In both the anesthetized and awake preparations, not all dopaminergic neurons are responsive to sensory stimuli, however responsive neurons tend to respond to more than a single stimulus modality. Evidence suggests that short-latency sensory information is provided to dopaminergic neurons by relatively primitive subcortical structures – including the midbrain superior colliculus for vision and the mesopontine parabrachial nucleus for pain and possibly gustation. Although short-latency visual information is provided to dopaminergic neurons by the relatively primitive colliculus, dopaminergic neurons can discriminate between complex visual stimuli, an apparent paradox which can be resolved by the recently discovered route of information flow through to dopaminergic neurons from the cerebral cortex, via a relay in the colliculus. Given that projections from the cortex to the colliculus are extensive, such a relay potentially allows the activity of dopaminergic neurons to report the results of complex stimulus processing from widespread areas of the cortex. Furthermore, dopaminergic neurons could acquire their ability to reflect stimulus value by virtue of reward-related modification of sensory processing in the cortex. At the forebrain level, sensory-related changes in the tonic activity of dopaminergic neurons may regulate the impact of the cortex on forebrain structures such as the nucleus accumbens. In contrast, the short latency of the phasic responses to sensory stimuli in dopaminergic neurons, coupled with the activation of these neurons by non-rewarding stimuli, suggests that phasic responses of dopaminergic neurons may provide a signal to the forebrain which indicates that a salient event has occurred (and possibly an estimate of how salient that event is). A stimulus-related salience signal could be used by downstream systems to reinforce behavioral choices

Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at √S^{S}NN = 5.02 TeV

The second-order Fourier coefficients (υ$_{2}$) characterizing the azimuthal distributions of Υ(1S) and Υ(2S) mesons produced in PbPb collisions at $\sqrt{s_{NN}}$ = 5.02 TeV are studied. The Υmesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb$^{-1}$. The scalar product method is used to extract the υ$_{2}$ coefficients of the azimuthal distributions. Results are reported for the rapidity range |y| < 2.4, in the transverse momentum interval 0 < p$_{T}$ < 50 GeV/c, and in three centrality ranges of 10–30%, 30–50% and 50–90%. In contrast to the J/ψ mesons, the measured υ$_{2}$ values for the Υ mesons are found to be consistent with zero

Measurement of prompt D0^{0} and D‾\overline{D}0^{0} meson azimuthal anisotropy and search for strong electric fields in PbPb collisions at root SNN\sqrt{S_{NN}} = 5.02 TeV

The strong Coulomb field created in ultrarelativistic heavy ion collisions is expected to produce a rapiditydependent difference (Av2) in the second Fourier coefficient of the azimuthal distribution (elliptic flow, v2) between D0 (uc) and D0 (uc) mesons. Motivated by the search for evidence of this field, the CMS detector at the LHC is used to perform the first measurement of Av2. The rapidity-averaged value is found to be (Av2) = 0.001 ? 0.001 (stat)? 0.003 (syst) in PbPb collisions at ?sNN = 5.02 TeV. In addition, the influence of the collision geometry is explored by measuring the D0 and D0mesons v2 and triangular flow coefficient (v3) as functions of rapidity, transverse momentum (pT), and event centrality (a measure of the overlap of the two Pb nuclei). A clear centrality dependence of prompt D0 meson v2 values is observed, while the v3 is largely independent of centrality. These trends are consistent with expectations of flow driven by the initial-state geometry. ? 2021 The Author. Published by Elsevier B.V. This is an open access article under the CC BY licens