Early Pliocene Mice and Rats from the Gray Fossil Site of Eastern Tennessee: Implications for the Evolution of Cricetidae and Understanding of the Past Ecosystem

Cricetidae ranks as the second-most species-rich and abundant mammalian family, with limited studies on eastern North American records prior to the Pleistocene. While cricetids has been previously noted at the early Pliocene Gray Fossil Site (GFS), this study provides a detailed description of eight taxa: Postcopemys (two species), Symmetrodontomys, Oryzomyini, Peromyscus, Neotoma, Neotomodon, and Xenomys. Postcopemys is the most common cricetid taxon at GFS, followed by Peromyscus and Neotoma. These records expand the stratigraphic and geographic range of multiple genera. Distinctive morphological features of GFS taxa suggest presence of several new species. The GFS cricetid assemblage exhibits diverse body sizes and dietary preferences, setting GFS apart from other contemporaneous sites and emphasizing its spatial and temporal uniqueness. The Appalachian region represents a biodiversity hotspot today, and GFS was likely an important habitat for cricetid evolution during the Pliocene

Neuroanatomical and cellular degeneration associated with a social disorder characterized by new ritualistic belief systems in a TDP-C patient vs. a Pick patient

Frontotemporal dementia (FTD) is a spectrum of clinically and pathologically heterogenous neurodegenerative dementias. Clinical and anatomical variants of FTD have been described and associated with underlying frontotemporal lobar degeneration (FTLD) pathology, including tauopathies (FTLD-tau) or TDP-43 proteinopathies (FTLD-TDP). FTD patients with predominant degeneration of anterior temporal cortices often develop a language disorder of semantic knowledge loss and/or a social disorder often characterized by compulsive rituals and belief systems corresponding to predominant left or right hemisphere involvement, respectively. The neural substrates of these complex social disorders remain unclear. Here, we present a comparative imaging and postmortem study of two patients, one with FTLD-TDP (subtype C) and one with FTLD-tau (subtype Pick disease), who both developed new rigid belief systems. The FTLD-TDP patient developed a complex set of values centered on positivity and associated with specific physical and behavioral features of pigs, while the FTLD-tau patient developed compulsive, goal-directed behaviors related to general themes of positivity and spirituality. Neuroimaging showed left-predominant temporal atrophy in the FTLD-TDP patient and right-predominant frontotemporal atrophy in the FTLD-tau patient. Consistent with antemortem cortical atrophy, histopathologic examinations revealed severe loss of neurons and myelin predominantly in the anterior temporal lobes of both patients, but the FTLD-tau patient showed more bilateral, dorsolateral involvement featuring greater pathology and loss of projection neurons and deep white matter. These findings highlight that the regions within and connected to anterior temporal lobes may have differential vulnerability to distinct FTLD proteinopathies and serve important roles in human belief systems

Physiology and neuroanatomy of emotional reactivity in frontotemporal dementia

ABSTRACT AND SUMMARY OF EXPERIMENTAL FINDINGS The frontotemporal dementias (FTD) are a heterogeneous group of neurodegenerative diseases that cause variable profiles of fronto-insulo-temporal network disintegration. Loss of empathy and dysfunctional social interaction are a leading features of FTD and major determinants of care burden, but remain poorly understood and difficult to measure with conventional neuropsychological instruments. Building on a large body of work in the healthy brain showing that embodied responses are important components of emotional responses and empathy, I performed a series of experiments to examine the extent to which the induction and decoding of somatic physiological responses to the emotions of others are degraded in FTD, and to define the underlying neuroanatomical changes responsible for these deficits. I systematically studied a range of modalities across the entire syndromic spectrum of FTD, including daily life emotional sensitivity, the cognitive categorisation of emotions, interoceptive accuracy, automatic facial mimicry, autonomic responses, and structural and functional neuroanatomy to deconstruct aberrant emotional reactivity in these diseases. My results provide proof of principle for the utility of physiological measures in deconstructing complex socioemotional symptoms and suggest that these warrant further investigation as clinical biomarkers in FTD. Chapter 3: Using a heartbeat counting task, I found that interoceptive accuracy is impaired in semantic variant primary progressive aphasia, but correlates with sensitivity to the emotions of others across FTD syndromes. Voxel based morphometry demonstrated that impaired interoceptive accuracy correlates with grey matter volume in anterior cingulate, insula and amygdala. Chapter 4: Using facial electromyography to index automatic imitation, I showed that mimicry of emotional facial expressions is impaired in the behavioural and right temporal variants of FTD. Automatic imitation predicted correct identification of facial emotions in healthy controls and syndromes focussed on the frontal lobes and insula, but not in syndromes focussed on the temporal lobes, suggesting that automatic imitation aids emotion recognition only when social concepts and semantic stores are intact. Voxel based morphometry replicated previously identified neuroanatomical correlates of emotion identification ability, while automatic imitation was associated with grey matter volume in a visuomotor network including primary visual and motor cortices, visual motion area (MT/V5) and supplementary motor cortex. Chapter 5: By recording heart rate during viewing of facial emotions, I showed that the normal cardiac reactivity to emotion is impaired in FTD syndromes with fronto-insular atrophy (behavioural variant FTD and nonfluent variant primary progressive aphasia) but not in syndromes focussed on the temporal lobes (right temporal variant FTD and semantic variant primary progressive aphasia). Unlike automatic imitation, cardiac reactivity dissociated from emotion identification ability. Voxel based morphometry revealed grey matter correlates of cardiac reactivity in anterior cingulate, insula and orbitofrontal cortex. Chapter 6: Subjects viewed videos of facial emotions during fMRI scanning, with concomitant recording of heart rate and pupil size. I identified syndromic profiles of reduced activity in posterior face responsive regions including posterior superior temporal sulcus and fusiform face area. Emotion identification ability was predicted by activity in more anterior areas including anterior cingulate, insula, inferior frontal gyrus and temporal pole. Autonomic reactivity related to activity in both components of the central autonomic control network and regions responsible for processing the sensory properties of the stimuli

Social Signal Decoding in Frontotemporal Lobar Degeneration

Frontotemporal lobar degeneration (FTLD) is associated with progressive social cognitive impairment. Currently a comprehensive pathophysiological model allowing disease effects to be understood and anticipated at the level of the whole brain is lacking. In this thesis I explored candidate cognitive operations underpinning complex behaviours in patients with the canonical syndromes of FTLD; behavioural variant frontotemporal dementia (bvFTD) and semantic dementia (SD). I correlated behavioural deficits with brain network disintegration using the structural magnetic resonance imaging (MRI) technique, voxel based morphometry (VBM). I created synthetic scenes to manipulate congruity across semantic and emotional domains (Chapter 3) and showed deficits across both patient groups. The deficits have grey matter correlates in prefronto-parieto-temporo-insular network and a temporo-insulo-striatal network. I used music as a non-verbal syntactic probe to investigate reward anticipation and valuation (Chapter 4) and demonstrated dissociable deficits across dementias. Performance was associated with grey matter in a distributed network including anterior temporal cortex and orbitofrontal cortex (OFC), previously implicated in computing diverse rewards. I created a novel neuropsychological test of humorous intent (Chapter 5) to model incongruity processing. bvFTD demonstrates a particular difficulty decoding novel humorous situations while SD produces a more general deficit of humour detection. Humour detection accuracy was associated with temporoparietal junction (TPJ) and anterior superior temporal cortical volume which are hubs for processing incongruity and semantic associations. To assess the relevance of these findings (Chapter 5) to daily life behaviour I explored humour preferences across dementias (Chapter 6). Altered sense of humour is particularly salient in bvFTD and SD, but also frequent in AD and may predate more typical symptoms. In conclusion, impairment in incongruity processing and reward allocation was shown across paradigms. The neuroanatomical networks underpinning these processes overlapped with areas known to be targeted by FTLD. These processes have implications for our understanding of the social dysfunction that defines bvFTD

Measurement of the diffractive cross-section in deep inelastic scattering

Diffractive scattering of $\gamma^* p \to X + N$, where $N$ is either a proton or a nucleonic system with $M_N~<~4$~GeV has been measured in deep inelastic scattering (DIS) at HERA. The cross section was determined by a novel method as a function of the $\gamma^* p$ c.m. energy $W$ between 60 and 245~GeV and of the mass $M_X$ of the system $X$ up to 15~GeV at average $Q^2$ values of 14 and 31~GeV$^2$. The diffractive cross section $d\sigma^{diff} /dM_X$ is, within errors, found to rise linearly with $W$. Parameterizing the $W$ dependence by the form d\sigma^{diff}/dM_X \propto (W^2)^{(2\overline{\mbox{\alpha_{_{I\hspace{-0.2em}P}}}} -2)} the DIS data yield for the pomeron trajectory \overline{\mbox{\alpha_{_{I\hspace{-0.2em}P}}}} = 1.23 \pm 0.02(stat) \pm 0.04 (syst) averaged over $t$ in the measured kinematic range assuming the longitudinal photon contribution to be zero. This value for the pomeron trajectory is substantially larger than \overline{\mbox{\alpha_{_{I\hspace{-0.2em}P}}}} extracted from soft interactions. The value of \overline{\mbox{\alpha_{_{I\hspace{-0.2em}P}}}} measured in this analysis suggests that a substantial part of the diffractive DIS cross section originates from processes which can be described by perturbative QCD. From the measured diffractive cross sections the diffractive structure function of the proton F^{D(3)}_2(\beta,Q^2, \mbox{x_{_{I\hspace{-0.2em}P}}}) has been determined, where $\beta$ is the momentum fraction of the struck quark in the pomeron. The form F^{D(3)}_2 = constant \cdot (1/ \mbox{x_{_{I\hspace{-0.2em}P}}})^a gives a good fit to the data in all $\beta$ and $Q^2$ intervals with $a = 1.46 \pm 0.04 (stat) \pmComment: 45 pages, including 16 figure