Relationship between Freezing of Gait and Anxiety in Parkinson\u27s Disease Patients: A Systemic Literature Review

Freezing of gait (FOG) is experienced by a significant number of patients with Parkinson\u27s disease (PD). The pathophysiology of this disabling motor symptom remains unclear, and there are no effective therapies. Anxiety has previously been posited as a contributing factor to gait freezing. There have been few studies directly investigating this topic, and a comprehensive literature review is lacking. The objective of this paper was to systematically review the evidence associating anxiety with the presence, severity, and progression of FOG in PD patients. The PubMed, EMBASE, and PsycINFO databases were searched up to September 19, 2018, for English-language, peer-reviewed articles that explored anxiety and FOG as outcome measures in a PD population base. Review articles, case reports, and articles that assessed gait disorders other than FOG were excluded, yielding a total of 26 articles in the final analysis. Of these 26 studies, 16 had a significant relationship between anxiety outcome measure and either presence or severity of FOG. There was great variability among studies in terms of outcome measures for both FOG and anxiety. Despite this heterogeneity, most studies relate anxiety and FOG. Standardized, high-validity outcome measures of anxiety and FOG are needed. Future exploration should aim to clarify the role of anxiety in FOG as a causal factor, pathophysiological marker, and manifestation of a common pathophysiological process versus a consequence of FOG itself. Clarifying the relationship between anxiety and FOG could reveal anxiety reduction as a therapy for FOG

Burning pain secondary to clozapine use: a case report.

BACKGROUND: The first of the atypical antipsychotics introduced in the 1970s, clozapine remains the most efficacious neuroleptic to this day. However, serious and potentially fatal side effects have necessitated careful regular monitoring among prescribing clinicians. Some adverse effects (e.g. ischaemic bowel) remain under recognized, while newly identified adverse effects continue to be described in the literature. CASE PRESENTATION: In this report, we describe a healthy 43-year old Caucasian male who experienced onset of a full body deep burning pain several months after the onset of treatment with clozapine. The pain worsened over time, ceased with cessation of treatment, and returned soon after the patient was rechallenged. CONCLUSION: We describe an unusual adverse effect from clozapine treatment that has not been described elsewhere to our knowledge. We present the time course of the pain symptom, relationship to dose, associated laboratory results, and ultimately how it was dealt with and how it improved for the benefit of clinicians who may encounter it in the future

Investigating the relation between striatal volume and IQ.

The volume of the input region of the basal ganglia, the striatum, is reduced with aging and in a number of conditions associated with cognitive impairment. The aim of the current study was to investigate the relation between the volume of striatum and general cognitive ability in a sample of 303 healthy children that were sampled to be representative of the population of the United States. Correlations between the WASI-IQ and the left striatum, composed of the caudate nucleus and putamen, were significant. When these data were analyzed separately for male and female children, positive correlations were significant for the left striatum in male children only. This brain structure-behavior relation further promotes the increasingly accepted view that the striatum is intimately involved in higher order cognitive functions. Our results also suggest that the importance of these brain regions in cognitive ability might differ for male and female children

Dopaminergic therapy affects learning and impulsivity in Parkinson\u27s disease.

OBJECTIVE: The aim was to examine the effect of dopaminergic medication on stimulus-response learning versus performing decisions based on learning. METHOD: To see the effect of dopaminergic therapy on stimulus-response learning and response selection, participants with Parkinson\u27s disease (PD) were either tested on and/or off their prescribed dose of dopaminergic therapy during different testing days. Forty participants with PD and 34 healthy controls completed the experiment on consecutive days. On Day 1, participants learned to associate abstract images with spoken, right or left responses via feedback (Session 1). On Day 2, participants recalled these responses (Session 2) and indicated the location (i.e., right or left of center) of previously studied images intermixed with new images (Session 3). RESULTS: Participants with PD off medication learned stimulus-response associations equally well compared to healthy controls. Learning was impaired by dopaminergic medication. Regardless of medication status, patients recalled the stimulus-response associations from Day 1 as well as controls. In Session 3 off medication, patients demonstrated enhanced facilitation relative to controls and patients on medication, when the stimulus location was congruent with the spoken response that was learned for the stimulus in Session 1. INTERPRETATION: Learning in PD was comparable to that of healthy controls off medication. Learning was worsened by dopaminergic therapy in PD. We interpret greater facilitation in participants with PD off medication for congruent responses as evidence of greater impulsivity. This motor or reflexive impulsivity was normalized by medication in PD. These findings shed light on the cognitive profile of PD and have implications for dopaminergic treatment

Assessing trauma in a transcultural context: Challenges in mental health care with immigrants and refugees

The growing numbers of refugees and immigrants from conflict-prone areas settling throughout the world bring several challenges for those working in the mental health care system. Immigrants and refugees of all ages arrive with complex and nuanced mental health histories of war, torture, and strenuous migration journeys. Many of the challenges of addressing the health care needs for this growing population of immigrants and refugees are often unfamiliar, and thus practices to address these challenges are not yet routine for care providers and health care organizations. In particular, complex trauma can make mental health assessments difficult for health care organizations or care providers with limited experience and training in transcultural or trauma-informed care. Using a transcultural approach can improve assessment and screening processes, leading to more effective and high-quality care for immigrant and refugee families experiencing mental health disorders. This paper presents findings from an assessment of current mental health services focusing on current practices and experiences with immigrant and refugee patients and families. The difficulties in developing shared understandings about mental health can hinder the therapeutic process; therefore, it is imperative to ensure an effective assessment right from the beginning, yet there is limited use of existing cultural formulation tools from the DSM-IV or DSM-5. The paper outlines current practices, approaches, challenges, and recommendations shared by mental health care providers and program leaders in addressing the mental health care needs of immigrants and refugees. The results from this study demonstrate that there are many challenges and inconsistencies in providing transcultural, trauma-informed care. Respondents emphasized the need for a thorough yet flexible and adaptive approach that allows for an exploration of differences in cultural interpretations of mental health. Our study concluded that ensuring a mindful, reflexive, transcultural, and trauma-informed health care workforce, and a learning environment to support staff with education, resources, and tools will improve the health care experiences of immigrants and refugees in the mental health care system

Negative Associations between Corpus Callosum Midsagittal Area and IQ in a Representative Sample of Healthy Children and Adolescents

Documented associations between corpus callosum size and cognitive ability have heretofore been inconsistent potentially owing to differences in sample characteristics, differing methodologies in measuring CC size, or the use of absolute versus relative measures. We investigated the relationship between CC size and intelligence quotient (IQ) in the NIH MRI Study of Normal Brain Development sample, a large cohort of healthy children and adolescents (aged six to 18, n = 198) recruited to be representative of the US population. CC midsagittal area was measured using an automated system that partitioned the CC into 25 subregions. IQ was measured using the Wechsler Abbreviated Scale of Intelligence (WASI). After correcting for total brain volume and age, a significant negative correlation was found between total CC midsagittal area and IQ (r = −0.147; p = 0.040). Post hoc analyses revealed a significant negative correlation in children (age<12) (r = −0.279; p = 0.004) but not in adolescents (age $\geq$ 12) (r = −0.005; p = 0.962). Partitioning the subjects by gender revealed a negative correlation in males (r = −0.231; p = 0.034) but not in females (r = 0.083; p = 0.389). Results suggest that the association between CC and intelligence is mostly driven by male children. In children, a significant gender difference was observed for FSIQ and PIQ, and in males, a significant age-group difference was observed for FSIQ and PIQ. These findings suggest that the correlation between CC midsagittal area and IQ may be related to age and gender

Differential effects of Parkinson\u27s disease and dopamine replacement on memory encoding and retrieval.

Increasingly memory deficits are recognized in Parkinson\u27s disease (PD). In PD, the dopamine-producing cells of the substantia nigra (SN) are significantly degenerated whereas those in the ventral tegmental area (VTA) are relatively spared. Dopamine-replacement medication improves cognitive processes that implicate the SN-innervated dorsal striatum but is thought to impair those that depend upon the VTA-supplied ventral striatum, limbic and prefrontal cortices. Our aim was to examine memory encoding and retrieval in PD and how they are affected by dopamine replacement. Twenty-nine PD patients performed the Rey Auditory Verbal Learning Test (RAVLT) and a non-verbal analogue, the Aggie Figures Learning Test (AFLT), both on and off dopaminergic medications. Twenty-seven, age-matched controls also performed these memory tests twice and their data were analyzed to correspond to the ON-OFF order of the PD patients to whom they were matched. We contrasted measures that emphasized with those that accentuated retrieval and investigated the effect of PD and dopamine-replacement on these processes separately. For PD patients relative to controls, encoding performance was normal in the off state and was impaired on dopaminergic medication. Retrieval was impaired off medication and improved by dopamine repletion. This pattern of findings suggests that VTA-innervated brain regions such as ventral striatum, limbic and prefrontal cortices are implicated in encoding, whereas the SN-supplied dorsal striatum mediates retrieval. Understanding this pattern of spared functions and deficits in PD, and the effect of dopamine replacement on these distinct memory processes, should prompt closer scrutiny of patients\u27 cognitive complaints to inform titration of dopamine replacement dosages along with motor symptoms

The effect of dopamine therapy on ventral and dorsal striatum-mediated cognition in Parkinson\u27s disease: support from functional MRI.

The central aim of our study was to elucidate functions mediated by the ventral and dorsal striatum, respectively, to better understand the cognitive effects of dopamine replacement in Parkinson\u27s disease. We proposed that the ventral striatum underlies general learning of stimulus associations, whereas the dorsal striatum promotes integration of various influences on selecting. In Parkinson\u27s disease, dopamine depletion is substantially less notable in the ventral relative to the dorsal striatum, and therefore greater improvements are expected for dorsal striatum-mediated functions with dopamine replacement. Using a simple selection task, we found that dopamine replacement impaired encoding and facilitation of consistent stimulus-stimulus relations across trials. This finding was in line with our contention that ventral striatum mediates learning stimulus associations, even when explicit feedback or reward is not provided. In contrast, dopamine replacement enhanced interference related to assimilating conflicting influences on selection across trials, consistent with our hypothesis that the dorsal striatum supports deciding in ambiguous contexts. We further confirmed these separable roles for the ventral and dorsal striatum in our selection task with healthy young volunteers using functional magnetic resonance imaging. In summary, we present a within-subject, double dissociation of the effects of dopamine replacement in patients with Parkinson\u27s disease for ventral striatum-mediated facilitation and dorsal striatum-mediated interference, confirmed in a separate functional magnetic resonance imaging experiment. Defining the distinct functions of the ventral and dorsal striatum will have direct clinical implications. Titration of therapy in Parkinson\u27s disease is generally geared towards optimizing dorsal striatum-mediated motor symptoms, possibly at the expense of ventral striatum operations, a consequence that is only beginning to be recognized. Enhanced awareness of these different processes will translate into medication strategies that take into account those symptoms that dopamine replacement might hinder, as well as improve. Here, we show impairments in learning new stimulus associations compared with improvements in integrating varied influences related to selection. Ultimately, this knowledge will lead clinicians to survey a broader range of symptoms in determining optimal therapy based on individual patient priorities

Striatum-Mediated Deficits in Stimulus-Response Learning and Decision-Making in OCD

© Copyright © 2020 Hiebert, Lawrence, Ganjavi, Watling, Owen, Seergobin and MacDonald. Obsessive compulsive disorder (OCD) is a prevalent psychiatric disorder characterized by obsessions and compulsions. Studies investigating symptomatology and cognitive deficits in OCD frequently implicate the striatum. The aim of this study was to explore striatum-mediated cognitive deficits in patients with OCD as they complete a stimulus-response learning task previously shown to differentially rely on the dorsal (DS) and ventral striatum (VS). We hypothesized that patients with OCD will show both impaired decision-making and learning, coupled with reduced task-relevant activity in DS and VS, respectively, compared to healthy controls. We found that patients with OCD (n = 14) exhibited decision-making deficits and learned associations slower compared to healthy age-matched controls (n = 16). Along with these behavioral deficits, OCD patients had reduced task-relevant activity in DS and VS, compared to controls. This study reveals that responses in DS and VS are altered in OCD, and sheds light on the cognitive deficits and symptoms experienced by patients with OCD

Dorsal striatum does not mediate feedback-based, stimulus-response learning: An event-related fMRI study in patients with Parkinson\u27s disease tested on and off dopaminergic therapy

© 2018 Learning associations between stimuli and responses is essential to everyday life. Dorsal striatum (DS) has long been implicated in stimulus-response learning, though recent results challenge this contention. We have proposed that discrepant findings arise because stimulus-response learning methodology generally confounds learning and response selection processes. In 19 patients with Parkinson\u27s disease (PD) and 18 age-matched controls, we found that dopaminergic therapy decreased the efficiency of stimulus-response learning, with corresponding attenuation of ventral striatum (VS) activation. In contrast, exogenous dopamine improved response selection accuracy related to enhanced DS BOLD signal. Contrasts between PD patients and controls fully support these within-subject patterns. These double dissociations in terms of behaviour and neural activity related to VS and DS in PD and in response to dopaminergic therapy, strongly refute the view that DS mediates stimulus-response learning through feedback. Our findings integrate with a growing literature favouring a role for DS in decision making rather than learning, and unite two literature that have been evolving independently