Frank M. Skidmore

Connectivity brain networks based on wavelet correlation analysis in Parkinson fMRI data.

Recent studies have shown that aging, psychiatric and neurologic diseases, and dopaminergic blockade all result in altered brain network efficiency. We investigated the efficiency of human brain functional networks as measured by fMRI in individuals with idiopathic Parkinsons disease (N=14) compared to healthy age-matched controls (N=15). Functional connectivity between 116 cortical and subcortical regions was estimated by wavelet correlation analysis in the frequency interval of 0.06-0.12 Hz. Efficiency of the associated network was analyzed, comparing PD to healthy controls. We found that individuals with Parkinsons disease had a marked decrease in nodal and global efficiency compared to healthy age-matched controls. Our results suggest that algorithmic approach and graph metrics might be used to identify and track neurodegenerative diseases, however more studies will be needed to evaluate utility of this type of analysis for different disease states.

Ventral tegmental area/midbrain functional connectivity and response to antipsychotic medication in schizophrenia.

Medication management in schizophrenia is a lengthy process, as the lack of clinical response can only be confirmed after at least 4 weeks of antipsychotic treatment at a therapeutic dose. Thus, there is a clear need for the discovery of biomarkers that have the potential to accelerate the management of treatment. Using resting-state functional MRI, we examined the functional connectivity of the ventral tegmental area (VTA), the origin of the mesocorticolimbic dopamine projections, in 21 healthy controls and 21 unmedicated patients with schizophrenia at baseline (pre-treatment) and after 1 week of treatment with the antipsychotic drug risperidone (1-week post-treatment). Group-level functional connectivity maps were obtained and group differences in connectivity were assessed on the groups’ participant-level functional connectivity maps. We also examined the relationship between pre-treatment/1-week post-treatment functional connectivity and treatment response. Compared with controls, patients exhibited significantly reduced pre-treatment VTA/midbrain connectivity to multiple cortical and subcortical regions, including the dorsal anterior cingulate cortex (dACC) and thalamus. After 1 week of treatment, VTA/midbrain connectivity to bilateral regions of the thalamus was re-established. Pre-treatment VTA/midbrain connectivity strength to dACC was positively correlated with good response to a 6-week course of risperidone, whereas pre-treatment VTA/midbrain connectivity strength to the default mode network was negatively correlated. Our findings suggest that VTA/midbrain resting-state connectivity may be a useful biomarker for the prediction of treatment response.

Limb-kinetic apraxia in Parkinson disease

To learn if limb-kinetic apraxia (LKA) is associated with Parkinson disease (PD), participants with PD (on medications) and control subjects performed finger tapping (FT), measuring movement speed, and performed coin rotation (CR), measuring precise coordinated but independent finger movements and speed. There were no group differences in FT, a measure of bradykinesia–rigidity, but CR rotation was impaired in PD. Thus, LKA, not related to bradykinesia–rigidity, is associated with PD.

Aceruloplasminaemia with progressive atrophy without brain iron overload: treatment with oral chelation

Background: Hereditary aceruloplasminaemia is a disorder of iron metabolism that is characterised by iron accumulation in the brain and other visceral organs. In previously reported cases, individuals with the disorder were noted to have evidence of iron accumulation in the brain. Oral chelating agents have not been used in neurological diseases of iron metabolism. Methods: A 54-year-old woman who presented with ataxia, lower extremity spasticity and chorea was evaluated for evidence of the source of neurological dysfunction. Results: Blood studies revealed no detectable ceruloplasmin. Marked iron overload was defined by a liver biopsy, which showed a variegated pattern consistent with a primary cause of iron overload. Review of MRI scans showed progressive brain atrophy without visible iron accumulation occurring over a 5-year period. The history suggested that neurodegeneration was coincident with aggressive oral iron replacement. Oral chelation improved many symptoms. Conclusions: Our findings in this patient suggest that disorders of iron transport such as aceruloplasminaemia can be a cause of neurological symptoms such as chorea and cognitive decline, as well as progressive neurodegeneration in the absence of visible iron on MRI scans. We found that oral iron chelation was effective at improving symptoms.

Anxiety and depression severity are related to right but not left onset Parkinson's disease duration

Depression and anxiety have both been associated with relative left frontal hypoactivation and the motor symptoms of Parkinsons disease typically begin in a lateral or asymmetrical fashion. Hence, PD patients with right hemibody onset may experience heightened depression and anxiety. However, research is mixed regarding whether right or left hemibody onset PD is associated with elevated levels of depression and anxiety. This literature, though, has not considered the potential moderating variable of disease duration. We hypothesized that disease duration would be positively correlated with measures of depression and anxiety in right but not left hemibody onset PD patients. The results indicated that scores on the Geriatric Depression Scale, Beck Depression Inventory-II, and the State Trait Anxiety Scale - State correlated positively with disease duration, but only in the right hemibody onset group of PD patients. Thus, right hemibody onset PD is associated with more severe depressive and anxiety symptoms, but only when disease duration is considered.

Creativity in Parkinson's disease as a function of right versus left hemibody onset.

OBJECTIVE Creativity is heavily dependent on divergent thinking and divergent thinking appears to be strongly dependent on fontal lobe function. Since patients with Parkinsons disease (PD) often have evidence of frontal lobe dysfunction we wanted to learn if these patients have a reduction of creativity, as well as learning if the side of onset (right versus left) influences the type (verbal versus visuospatial) of decrement in creativity. DESIGN Participants of this study were patients with right (RHO) or left (LHO) onset PD as well as matched controls. All subjects were given the Abbreviated Torrance Test of Creative Thinking for Adults (ATTA), a widely used test to assess creativity that examines Fluency, Originality, Flexibility and Elaboration. Subjects were also assessed with the Controlled Word Association Test (COWAT). RESULTS/CONCLUSIONS When compared to controls the patients with RHO, but not LHO, had a decrease of verbal creative fluency. Patients with PD often have a decrease on the COWAT, but performance on the COWAT did not differ between the RHO and the LHO patients. This suggests that patients with PD who have RHO have a decrease in verbal creativity and this decrement does not appear to be related to decreased fluency.

Verbal and visuospatial memory in lateral onset Parkinson disease: time is of the essence.

ObjectiveThis investigation sought to study immediate and delayed verbal and visuospatial recall in Parkinson disease (PD) patients with left hemibody (LHO) and right hemibody (RHO) onset of motor symptoms and to examine the role of mental processing speed in recall of this information. BackgroundResearch is mixed regarding material specific memory impairments in LHO and RHO PD. However, earlier research has not used a factorial approach in investigating material specific memory in LHO and RHO PD. We hypothesized that LHO PD patients would exhibit an increase in performance following the delayed verbal free recall trial and either decline or stability in performance on the delayed visuospatial free recall trial. The opposite pattern was hypothesized for RHO PD patients. MethodThe Hopkins Verbal Learning Test-revised (HVLT-R) and the Brief Visuospatial Memory Test-revised (BVMT-R) were administered to a sample of 28 LHO PD patients and 36 RHO PD patients. The Stroop Color-word Test was administered as a measure of mental processing speed. ResultsThe results indicated that the RHO group experienced a significant decline in performance on verbal free recall from the immediate to the delayed trials and a significant improvement in performance from the immediate to the delayed visuospatial free recall trials. Additionally, a significant negative correlation was found between mental processing speed and changes in recall from the immediate to the delayed conditions for the RHO group. ConclusionsThese results indicate that the RHO PD group experienced a significant decline in verbal free recall and a significant improvement in visuospatial free recall from the immediate to the delayed trials and that the LHO PD patients experienced no significant changes. Further, mental processing speed appears to influence the recall of information from the immediate to the delayed conditions.

Anxiety Affects Working Memory Only in Left Hemibody Onset Parkinson Disease Patients

ObjectiveThis investigation sought to examine the potential moderating influence of heightened anxiety on working memory in Parkinson disease (PD) patients. Further, we wanted to determine whether this moderating influence of anxiety differentially affects PD patients with left hemibody (LBH) versus right hemibody (RHB) onset of motor symptoms. BackgroundResearch has examined the neurocognitive effects of depression in PD. However, a paucity of research has examined the effects of heightened anxiety in PD. We predicted that LHB PD patients with heightened anxiety would perform worse on a measure of working memory than RHB PD patients. MethodA total of 59 PD patients completed the state-trait anxiety inventory and were also administered the digit span subtest of the Wechsler Memory Scale—III. ResultsThe results supported the hypotheses, indicating that the LHB PD patients with heightened anxiety performed significantly worse than the RHB PD patients with heightened anxiety and the LHB PD patients with low anxiety. ConclusionsThese findings suggest that left hemibody onset PD patients may experience more disability in their activities of daily living. Future research should explore whether differences also exist between PD patients with and without the diagnosed anxiety disorders.

Turning off artistic ability: The influence of left DBS in art production

BACKGROUND The influence of Parkinsons disease (PD) as well as deep brain stimulation (DBS) on visual-artistic production of people who have been artists is unclear. We systematically assessed the artistic-creative productions of a patient with PD who was referred to us for management of a left subthalamic region (STN) DBS. The patient was an artist before her disease started, permitting us to analyze changes in her artistic-creative production over the course of the illness and during her treatment with DBS. METHODS We collected her paintings from four time periods: Time 1 (Early Pre-Presymptomatic), Time 2 (Later Presymptomatic), Time 3 (Symptomatic), and Time 4 (DBS Symptomatic). A total of 59 paintings were submitted to a panel of judges, who rated the paintings on 6 different artistic qualities including: aesthetics, closure, evocative impact, novelty, representation, technique. RESULTS Aesthetics and evocative impact significantly declined from Time 2 to Time 4. Representation and technique indicated a curvilinear relationship, with initial improvement from Time 1 to Time 2 followed by a decline from Time 2 to Time 4. CONCLUSIONS These results suggest that left STN/SNR-DBS impacted artistic performances in our patient. The reason for these alterations is not known, but it might be that alterations of left hemisphere functions induce a hemispheric bias reducing the influence the right hemisphere which is important for artistic creativity. The left hemisphere itself plays a critical role in artistic creativity and DBS might have altered left hemisphere functions or altered the mesolimbic system which might have also influenced creativity. Future studies will be required to learn how PD and DBS influence creativity.

Conceptual Hypometria? An evaluation of conceptual mapping of space in Parkinson's disease

When interacting with objects in their environment, patients with Parkinsons disease (PD) often make hypometric movements (e.g., micrographia). The purpose of this study was to learn if patients with PD, in the absence of overt actions or environmental stimuli, have egocentric (body-centered) conceptual (representational) hypometria. Actions can take place in either proximal or distal peri-personal space. Normally, the right hemisphere has a distal and the right a proximal attentional bias. We also want to learn if a patient with onset of disease in the right hemisphere would have a greater conceptual action hypometria than individuals with left hemispheric onset. Seventeen subjects with PD and 15 age-matched controls were given a questionnaire evaluating subjective perception of personal action space. The questionnaire asked individuals to rate, using a 0–5 scale, the distances between their body and hand when performing the various actions that take place in peri-personal space. When compared to control participants, participants with PD, and especially those with predominant left sided symptoms (right greater than left hemispheric dysfunction) had hypometric mental perceptions for actions that normally occur in far peri-personal space. Individuals with PD appear to demonstrate a conceptual hypometria, suggesting that there is a perturbation of their interactive representational maps and these maps appear to be more disordered by right than left hemisphere dysfunction. However, it is also possible that when making action distance computations, participants used covert actions and it was the hypometric covert actions that induced the computational hypometria.