Characterizing Spoken Discourse in Individuals with Parkinson Disease Without Dementia

Background: The effects of disease (PD) on cognition, word retrieval, syntax, and speech/voice processes may interact to manifest uniquely in spoken language tasks. A handful of studies have explored spoken discourse production in PD and, while not ubiquitously, have reported a number of impairments including: reduced words per minute, reduced grammatical complexity, reduced informativeness, and increased verbal disruption. Methodological differences have impeded cross-study comparisons. As such, the profile of spoken language impairments in PD remains ambiguous. Method: A cross-genre, multi-level discourse analysis, prospective, cross-sectional between groups study design was conducted with 19 PD participants (Mage = 70.74, MUPDRS-III = 30.26) and 19 healthy controls (Mage = 68.16) without dementia. The extensive protocol included a battery of cognitive, language, and speech measures in addition to four discourse tasks. Two tasks each from two discourse genres (picture sequence description; story retelling) were collected. Discourse samples were analysed using both microlinguistic and macrostructural measures. Discourse variables were collapsed statistically to a primal set of variables used to distinguish the spoken discourse of PD vs. controls. Results: Participants with PD differed significantly from controls along a continuum of productivity, grammar, informativeness, and verbal disruption domains including total words F(1,36) = 3.87, p = .06; words/minute F(1,36) = 7.74, p = .01 , % grammatical utterances F(1,36) = 11.92, p = .001, total CIUs F(1,36) = 13.30, p = .001, % CIUs (Correct Information Units) F(1,36) = 9.35, p = .004, CIUs/minute F(1,36) = 14.06, p = .001, and verbal disruptions/100 words F(1,36) = 3.87, p = .06 (α = .10). Discriminant function analyses showed that optimally weighted discourse variables discriminated the spoken discourse of PD vs. controls with 81.6% sensitivity and 86.8% specificity. For both discourse genres, discourse performance showed robust, positive, correlations with global cognition. In PD (picture sequence description), more impaired discourse performance correlated significantly with more severe motor impairment, more advanced disease staging, and higher doses of PD medications. Conclusions: The spoken discourse in PD without dementia differs significantly and predictably from controls. Results have both research and clinical implications

Beyond the Medial Regions of Prefrontal Cortex in the Regulation of Fear and Anxiety.

Fear and anxiety are adaptive responses but if left unregulated, or inappropriately regulated, they become biologically and socially maladaptive. Dysregulated emotions are manifest in a wide variety of psychiatric and neurological conditions but the external expression gives little indication of the underlying causes, which are inevitably multi-determined. To go beyond the overt phenotype and begin to understand the causal mechanisms leading to conditions characterized by anxiety and disorders of mood, it is necessary to identify the base psychological processes that have become dysregulated, and map them on to their associated neural substrates. So far, attention has been focused primarily on the medial regions of prefrontal cortex (PFC) and in particular their contribution to the expression and extinction of conditioned fear. However, functional neuroimaging studies have shown that the sphere of influence within the PFC is not restricted to its medial regions, but extends into dorsal, ventrolateral (vlPFC) and orbitofrontal (OFC) regions too; although the causal role of these other areas in the regulation of fear and anxiety remains to be determined and in the case of the OFC, existing findings are conflicting. Here, we review the evidence for the contribution of these other regions in negative emotion regulation in rodents and old world and new world monkeys. We consider a variety of different contexts, including conditioned and innate fear, learned and unlearned anxiety and cost-benefit decision-making, and a range of physiological and behavioral measures of emotion. It is proposed that both the OFC and vlPFC contribute to emotion regulation via their involvement, respectively, in the prediction of future outcomes and higher-order attentional control. The fractionation of these neurocognitive and neurobehavioral systems that regulate fear and anxiety opens up new opportunities for diagnostic stratification and personalized treatment strategies.This research was supported by a Medical Research Programme Grant (G0901884) from the Medical Research Council (MRC), UK to ACR and carried out within the Behavioral and Clinical Neurosciences Institute supported by a consortium award from the Wellcome Trust and the MRC.This is the final version of the article. It first appeared from Frontiers via http://dx.doi.org/10.3389/fnsys.2016.0001

Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making.

Dysregulation of the orbitofrontal and ventrolateral prefrontal cortices is implicated in anxiety and mood disorders, but the specific contributions of each region are unknown, including how they gate the impact of threat on decision making. To address this, the effects of GABAergic inactivation of these regions were studied in marmoset monkeys performing an instrumental approach-avoidance decision-making task that is sensitive to changes in anxiety. Inactivation of either region induced a negative bias away from punishment that could be ameliorated with anxiolytic treatment. However, whereas the effects of ventrolateral prefrontal cortex inactivation on punishment avoidance were seen immediately, those of orbitofrontal cortex inactivation were delayed and their expression was dependent upon an amygdala-anterior hippocampal circuit. We propose that these negative biases result from deficits in attentional control and punishment prediction, respectively, and that they provide the basis for understanding how distinct regional prefrontal dysregulation contributes to the heterogeneity of anxiety disorders with implications for cognitive-behavioral treatment strategies.All authors contributed extensively to the work presented in this article, and we thank Rudolf Cardinal for helpful advice and discussion and Mercedes Arroyo for histology. This research was funded by a Medical Research Council Programme Grant (to A.C.R.) and Career Development Award (to H.F.C.). The research was conducted at the Behavioural and Clinical Neuroscience Institute, which is supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354).This is the accepted manuscript of a paper published in PNAS (Clarke HF, Horst NK, Roberts AC, PNAS 2015, 112, 13, 4176-4181, doi:10.1073/pnas.1422440112). The final version is available at http://dx.doi.org/10.1073/pnas.142244011

Lesions of either anterior orbitofrontal cortex or ventrolateral prefrontal cortex in marmoset monkeys heighten innate fear and attenuate active coping behaviors to predator threat.

The ventral prefrontal cortex is an integral part of the neural circuitry that is dysregulated in mood and anxiety disorders. However, the contribution of its distinct sub-regions to the regulation of negative emotion are poorly understood. Recently we implicated both the ventrolateral prefrontal cortex (vlPFC) and anterior orbitofrontal cortex (antOFC) in the regulation of conditioned fear and anxiety responses to a social stimulus, i.e., human intruder, in the marmoset monkey. In the present study we extend our investigations to determine the role of these two regions in regulating innate responses and coping strategies to a predator stimulus, i.e., a model snake. Both the vlPFC and antOFC lesioned groups exhibited enhanced anxiety-related responses to the snake in comparison to controls. Both groups also showed a reduction in active coping behavior. These results indicate that the vlPFC and antOFC contribute independently to the regulation of both innate fear and, as previously reported, conditioned fear, and highlight the importance of these regions in producing stimulus-appropriate coping responses. The finding that dysregulation in two distinct prefrontal regions produces the apparently similar behavioral phenotype of heightened negative emotion provides insight into the varied etiology that may underlie this symptom across a wide variety of neuropsychiatric conditions with implications for personalized treatment strategies.This research was supported by a Medical Research Programme Grant (G0901884) from the Medical Research Council (MRC), UK to Angela C. Roberts. Yoshiro Shiba was supported by the Long Term Student Support Program provided by Osaka University and the Ministry of Education, Culture, Sports, Science and Technology of Japan and currently by the MRC Programme grant (G0901884). Andrea M. Santangelo, until October 2011, by a J. S. McDonnell Foundation grant (Principle Investigators; E. Phelps, T. W. Robbins, co-investigators; J. E. LeDoux, and Angela C. Roberts) and currently by the MRC Programme grant (G0901884). Work was carried out within the Behavioral and Clinical Neurosciences Institute supported by a consortium award from the Wellcome Trust and the MRC. We thank Dr. Carmen Agustín-Pavón for conducting the lesion surgeries, Dr. Katrin Braesicke for help with statistical analyses and Dr. Mercedes Arroyo for the preparation of histological material.This is the final published version of the paper, which first appeared in Frontiers Systems Neuroscience, 21 January 2015, doi: 10.3389/fnsys.2014.0025

Quantifying anhedonia-like symptoms in marmosets using appetitive Pavlovian conditioning.

Blunted reward responsivity is associated with anhedonia in humans and is a core feature of depression. This protocol describes how to train the common marmoset, Callithrix jacchus, on an appetitive Pavlovian conditioning paradigm to measure behavioral and cardiovascular correlates of anticipatory and consummatory phases of reward processing. We describe how to use intracerebral infusions to manipulate brain regions whose activity is relevant to impaired reward processing in depression and how the paradigm can be used to test antidepressant efficacy. For complete details on the use and execution of this protocol, please refer to Alexander et al. (2019)

Role of the Perigenual Anterior Cingulate and Orbitofrontal Cortex in Contingency Learning in the Marmoset.

Two learning mechanisms contribute to decision-making: goal-directed actions and the "habit" system, by which action-outcome and stimulus-response associations are formed, respectively. Rodent lesion studies and human neuroimaging have implicated both the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC) in the neural basis of contingency learning, a critical component of goal-directed actions, though some published findings are conflicting. We sought to reconcile the existing literature by comparing the effects of excitotoxic lesions of the perigenual anterior cingulate cortex (pgACC), a region of the mPFC, and OFC on contingency learning in the marmoset monkey using a touchscreen-based paradigm, in which the contingent relationship between one of a pair of actions and its outcome was degraded selectively. Both the pgACC and OFC lesion groups were insensitive to the contingency degradation, whereas the control group demonstrated selectively higher performance of the nondegraded action when compared with the degraded action. These findings suggest the pgACC and OFC are both necessary for normal contingency learning and therefore goal-directed behavior.This research was supported by a Programme Grant [G0901884] from the Medical Research Council UK (MRC) to ACR, and a Wellcome Trust Senior Investigator Award [104631 /Z/14/Z] to TWR. SAWJ was supported by a BCNI-MRC studentship. The authors wish to thank C. H Parkinson and R. Underwood for preparation of the histological material. T.W.R. consults for Cambridge Cognition, Lilly, Lundbeck, Teva, Shire Pharmaceuticals and Merck, Sharp and Dohme. He has received research grants from Lilly, Lundbeck and GSK. The remaining authors have no potential competing financial interests to disclose.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/cercor/bhw06

Woman-centred maternity care: what do women say? Protocol for a survey of women receiving maternity care in NSW

Background: Over the past decade or so, recommendations for improvements in maternity care have emphasised the importance of providing woman-centred care. Feedback from women about existing maternity services can help to identify whether services are currently meeting women’s needs. The present study aims to capture women’s expectations of, and experiences with maternity care, and to explore whether maternal and birth characteristics are associated with those experiences. Methods: A survey will be undertaken with a sample of approximately 2,000 women who have given birth over a 3-month period at seven public maternity units in two neighbouring health districts in New South Wales (NSW), Australia. The survey will be mailed out three-four months after birth. The study will also examine two strategies intended to increase survey response rates: use of two types of pre-notification letters, and request for consent from women to link survey responses with health information recorded at the time of birth. Data analysis will examine response rate, evidence of sample bias and effect of pre-notification letters; describe expectations and experiences with maternity care and associations with maternal and/or health characteristics; and where possible, compare results with maternity satisfaction data reported by others. Discussion: This study will provide, for the first time in NSW, comprehensive information about women’s expectations, experiences and satisfaction with maternity services in two local health districts. It will identify aspects of care that are meeting women’s needs, and areas where care and service provision may be improved in line with the aspirations of Towards Normal Birth. The survey tool may also prove to be appropriate for use by other health districts and/or state-wide.NHMR

Woman-centred maternity care: what do women say? Protocol for a survey of women receiving maternity care in NSW

Background: Over the past decade or so, recommendations for improvements in maternity care have emphasised the importance of providing woman-centred care. Feedback from women about existing maternity services can help to identify whether services are currently meeting women’s needs. The present study aims to capture women’s expectations of, and experiences with maternity care, and to explore whether maternal and birth characteristics are associated with those experiences. Methods: A survey will be undertaken with a sample of approximately 2,000 women who have given birth over a 3-month period at seven public maternity units in two neighbouring health districts in New South Wales (NSW), Australia. The survey will be mailed out three-four months after birth. The study will also examine two strategies intended to increase survey response rates: use of two types of pre-notification letters, and request for consent from women to link survey responses with health information recorded at the time of birth. Data analysis will examine response rate, evidence of sample bias and effect of pre-notification letters; describe expectations and experiences with maternity care and associations with maternal and/or health characteristics; and where possible, compare results with maternity satisfaction data reported by others. Discussion: This study will provide, for the first time in NSW, comprehensive information about women’s expectations, experiences and satisfaction with maternity services in two local health districts. It will identify aspects of care that are meeting women’s needs, and areas where care and service provision may be improved in line with the aspirations of Towards Normal Birth. The survey tool may also prove to be appropriate for use by other health districts and/or state-wide.NHMR

Avoidant Coping Style to High Imminence Threat Is Linked to Higher Anxiety-Like Behavior.

Human studies with self-reported measures have suggested a link between an avoidant coping style and high anxiety. Here, using the common marmoset as a model, we characterize the latent factors underlying behavioral responses of these monkeys towards low and high imminence threat and investigate if a predominantly avoidant behavioral response to high imminence threat is associated with greater anxiety-like behavior in a context of low imminence threat. Exploratory factor analysis (EFA) of the human intruder test of low imminence threat revealed a single factor in which a combination of active vigilance and avoidance responses underpinned anxiety-like behavior. In contrast, two negatively-associated factors were revealed in the model snake test reflecting active and avoidant coping to high imminence threat. Subsequent analysis showed that animals with a predominantly avoidant coping style on the model snake test displayed higher anxiety-like behavior on the human intruder test, findings consistent with those described in humans. Together they illustrate the richness of the behavioral repertoire displayed by marmosets in low and high imminence threatening contexts and the additional insight that factor analysis can provide by identifying the latent factors underlying these complex behavioral datasets. They also highlight the translational value of this approach when studying the neural circuits underlying complex anxiety-like states in this primate model