Translating the Cluster Headache Quality of Life Questionnaire (CHQ) from English to Dutch with the TRAPD method.

OBJECTIVE: Cluster headache is associated with a decreased quality of life (QoL). The increased focus on patient-reported outcome measures (PROMS) has led to the creation of a tailored Cluster Headache Quality of Life scale (CHQ). Our objective was to create and authenticate a Dutch version of the CHQ (CHQ-D). METHODS: The TRAPD model (Translation, Review, Adjudication, Pretesting, Documentation) was used to translate the CHQ from English to Dutch and ensure cross-cultural adaption. Pre-testing was performed in n = 31 participants, and validity was in a new sample of n = 40 participants who completed the CHQ twice at a 2-day interval. Intraclass correlation coefficient (ICC) and Cronbach's alpha were used to assess the validity and reproducibility of the CHQ-D. RESULTS: To produce the CHQ-D, we made five modifications based on pretesting. Participants finished the questionnaire in a median time of 10 min (IQR:10.0, 17.5) and 90% within 20 min. The majority of participants (74.2%) did not find it burdensome at all. The reliability of the CHQ-D was excellent (Cronbach's alpha: 0.94; ICC: 0.94). CONCLUSION: The CHQ-D is a valid and practical instrument for QoL in individuals with cluster headache. We aim to use CHQ-D as PROM in clinical research in the Netherlands to enforce international collaborations and comparisons of studies.

Deep brain stimulation in the ALIC-BNST region targeting the bed nucleus of stria terminalis in patients with obsessive-compulsive disorder: effects on cognition after 12 months.

PURPOSE: The aim of this study was to evaluate cognitive effects 12 months after Deep Brain Stimulation (DBS) of the Bed Nucleus of Stria Terminalis (BNST) in patients with refractory Obsessive-Compulsive Disorder (OCD). METHODS: Eight patients (5 female; mean ± SD age 36 ± 15) with OCD were included. A neuropsychological test battery covering verbal and spatial episodic memory, executive function, and attention was administered preoperatively and 12 months after surgery. Medical records were used as a source for descriptive data to probe for any changes not covered by standardized checklists and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the primary outcome measure. RESULTS: At 12 months, seven patients showed response to DBS: three were full responders (i.e., Y-BOCS ≥ 35% improvement), and four were partial responders (Y-BOCS 25-34% improvement). Relative to baseline, there was a slight decline on visuo-spatial learning (p = 0.027), and improved performance on the Color-Word Interference inhibition/switching subtest (p = 0.041), suggesting improvement in cognitive flexibility. CONCLUSIONS: DBS in the BNST for treatment refractory OCD generates very few adverse cognitive effects and improves cognitive flexibility after 12 months of stimulation. The improvement in Y-BOCS and the absence of major cognitive side effects support the BNST as a potential target for DBS in severe OCD.

Proactive inhibition is marked by differences in the pattern of motor cortex activity during movement preparation and execution.

Successful human behavior relies on the ability to flexibly alter movements depending on the context in which they are made. One such context-dependent modulation is proactive inhibition, a type of behavioral inhibition used when anticipating the need to stop or change movements. We investigated how the motor cortex might prepare and execute movements made under different contexts. We used transcranial magnetic stimulation (TMS) in different coil orientations [postero-anterior (PA) and antero-posterior (AP) flowing currents] and pulse widths (120 and 30 µs) to probe the excitability of different inputs to corticospinal neurons while participants performed two reaction time tasks: a simple reaction time task and a stop-signal task requiring proactive inhibition. We took inspiration from state space models to assess whether the pattern of motor cortex activity changed due to proactive inhibition (PA and AP neuronal circuits represent the x and y axes of a state space upon which motor cortex activity unfolds during motor preparation and execution). We found that the rise in motor cortex excitability was delayed when proactive inhibition was required. State space visualizations showed altered patterns of motor cortex activity (combined PA120 and AP30 activity) during proactive inhibition, despite adjusting for reaction time. Overall, we show that the pattern of neural activity generated by the motor cortex during movement preparation and execution is dependent upon the context under which the movement is to be made.NEW & NOTEWORTHY Using directional TMS, we find that the human motor cortex flexibly changes its pattern of neural activity depending on the context in which a movement is due to be made. Interestingly, this occurs despite adjusting for reaction time. We also show that state space and dynamical systems models of movement can be noninvasively visualized in humans using TMS, thereby offering a novel method to study these powerful models in humans.

Cortical connectivity of the nucleus basalis of Meynert in Parkinson's disease and Lewy body dementias.

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are related conditions that are associated with cholinergic system dysfunction. Dysfunction of the nucleus basalis of Meynert (NBM), a basal forebrain structure that provides the dominant source of cortical cholinergic innervation, has been implicated in the pathogenesis of both PDD and DLB. Here we leverage the temporal resolution of magnetoencephalography with the spatial resolution of MRI tractography to explore the intersection of functional and structural connectivity of the NBM in a unique cohort of PDD and DLB patients undergoing deep brain stimulation of this structure. We observe that NBM-cortical structural and functional connectivity correlate within spatially and spectrally segregated networks including: (i) a beta band network to supplementary motor area, where activity in this region was found to drive activity in the NBM; (ii) a delta/theta band network to medial temporal lobe structures encompassing the parahippocampal gyrus; and (iii) a delta/theta band network to visual areas including lingual gyrus. These findings reveal functional networks of the NBM that are likely to subserve important roles in motor control, memory and visual function, respectively. Furthermore, they motivate future studies aimed at disentangling network contribution to disease phenotype.

STN-DBS Increases Proactive but Not Retroactive Interference During Verbal Learning in PD.

BACKGROUND: Proactive interference (PI) refers to the interference of previously learned materials with new learning and reflects the failure of inhibitory processes in memory. Retroactive interference (RI) refers to the unfavorable effect of new learning on the later recall of previously learned information. Although subthalamic nucleus deep brain stimulation (STN-DBS) does not affect global cognition in Parkinson's disease (PD), it has negative effects on specific aspects of cognition, including verbal fluency and executive inhibitory control of action.To this end, we set to test the acute effect of STN-DBS on PI and RI during verbal learning. METHODS: Twenty PD patients with STN-DBS were tested on the California Verbal Learning Test-II using an ON/OFF stimulation design. RESULTS: The results showed that stimulation increased PI ON stimulation (P = 0.012) but had no effect on RI (P = 0.816). CONCLUSIONS: Our results extend the role of STN to the inhibitory control that is required during memory encoding or recall for prevention of PI. © 2020 International Parkinson and Movement Disorder Society.

Impaired automatic but intact volitional inhibition in primary tic disorders.

The defining character of tics is that they can be transiently suppressed by volitional effort of will, and at a behavioural level this has led to the concept that tics result from a failure of inhibition. However, this logic conflates the mechanism responsible for the production of tics with that used in suppressing them. Volitional inhibition of motor output could be increased to prevent the tic from reaching the threshold for expression, although this has been extensively investigated with conflicting results. Alternatively, automatic inhibition could prevent the initial excitation of the striatal tic focus-a hypothesis we have previously introduced. To reconcile these competing hypotheses, we examined different types of motor inhibition in a group of 19 patients with primary tic disorders and 15 healthy volunteers. We probed proactive and reactive inhibition using the conditional stop-signal task, and applied transcranial magnetic stimulation to the motor cortex, to assess movement preparation and execution. We assessed automatic motor inhibition with the masked priming task. We found that volitional movement preparation, execution and inhibition (proactive and reactive) were not impaired in tic disorders. We speculate that these mechanisms are recruited during volitional tic suppression, and that they prevent expression of the tic by inhibiting the nascent excitation released by the tic generator. In contrast, automatic inhibition was abnormal/impaired in patients with tic disorders. In the masked priming task, positive and negative compatibility effects were found for healthy controls, whereas patients with tics exhibited strong positive compatibility effects, but no negative compatibility effect indicative of impaired automatic inhibition. Patients also made more errors on the masked priming task than healthy control subjects and the types of errors were consistent with impaired automatic inhibition. Errors associated with impaired automatic inhibition were positively correlated with tic severity. We conclude that voluntary movement preparation/generation and volitional inhibition are normal in tic disorders, whereas automatic inhibition is impaired-a deficit that correlated with tic severity and thus may constitute a potential mechanism by which tics are generated.

Pedunculopontine Nucleus Deep Brain Stimulation for Parkinsonian Disorders: A Case Series.

BACKGROUND: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been investigated for the treatment of levodopa-refractory gait dysfunction in parkinsonian disorders, with equivocal results so far. OBJECTIVES: To summarize the clinical outcomes of PPN-DBS-treated patients at our centre and elicit any patterns that may guide future research. MATERIALS AND METHODS: Pre- and post-operative objective overall motor and gait subsection scores as well as patient-reported outcomes were recorded for 6 PPN-DBS-treated patients, 3 with Parkinson's disease (PD), and 3 with progressive supranuclear palsy (PSP). Electrodes were implanted unilaterally in the first 3 patients and bilaterally in the latter 3, using an MRI-guided MRI-verified technique. Stimulation was initiated at 20-30 Hz and optimized in an iterative manner. RESULTS: Unilaterally treated patients did not demonstrate significant improvements in gait questionnaires, UPDRS-III or PSPRS scores or their respective gait subsections. This contrasted with at least an initial response in bilaterally treated patients. Diurnal cycling of stimulation in a PD patient with habituation to the initial benefit reproduced substantial improvements in freezing of gait (FOG) 3 years post-operatively. Among the PSP patients, 1 with a parkinsonian subtype had a sustained improvement in FOG while another with Richardson syndrome (PSP-RS) did not benefit. CONCLUSIONS: PPN-DBS remains an investigational treatment for levodopa-refractory FOG. This series corroborates some previously reported findings: bilateral stimulation may be more effective than unilateral stimulation; the response in PSP patients may depend on the disease subtype; and diurnal cycling of stimulation to overcome habituation merits further investigation.

The sensitivity to change of the cluster headache quality of life scale assessed before and after deep brain stimulation of the ventral tegmental area.

BACKGROUND: Cluster headache (CH) is a trigeminal autonomic cephalalgia (TAC) characterized by a highly disabling headache that negatively impacts quality of life and causes limitations in daily functioning as well as social functioning and family life. Since specific measures to assess the quality of life (QoL) in TACs are lacking, we recently developed and validated the cluster headache quality of life scale (CH-QoL). The sensitivity of CH-QoL to change after a medical intervention has not been evaluated yet. METHODS: This study aimed to test the sensitivity to change of the CH-QoL in CH. Specifically we aimed to (i) assess the sensitivity of CH-QoL to change before and following deep brain stimulation of the ventral tegmental area (VTA-DBS), (ii) evaluate the relationship of changes on CH-QoL with changes in other generic measures of quality of life, as well as indices of mood and pain. Ten consecutive CH patients completed the CH-QoL and underwent neuropsychological assessment before and after VTA-DBS. The patients were evaluated on headache frequency, severity, and load (HAL) as well as on tests of generic quality of life (Short Form-36 (SF-36)), mood (Beck Depression Inventory, Hospital Anxiety and Depression Rating Scale), and pain (McGill Pain Questionnaire, Headache Impact Test, Pain Behaviour Checklist). RESULTS: The CH-QoL total score was significantly reduced after compared to before VTA-DBS. Changes in the CH-QoL total score correlated significantly and negatively with changes in HAL, the SF-36, and positively and significantly with depression and the evaluative domain on the McGill Pain Questionnaire. CONCLUSIONS: Our findings demonstrate that changes after VTA-DBS in CH-QoL total scores are associated with the reduction of frequency, duration, and severity of headache attacks after surgery. Moreover, post VTA-DBS improvement in CH-QoL scores is associated with an amelioration in quality of life assessed with generic measures, a reduction of depressive symptoms, and evaluative pain experience after VTA-DBS. These results support the sensitivity to change of the CH-QoL and further demonstrate the validity and applicability of CH-QoL as a disease specific measure of quality of life for CH.

Resting state activity and connectivity of the nucleus basalis of Meynert and globus pallidus in Lewy body dementia and Parkinson's disease dementia.

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are two related diseases which can be difficult to distinguish. There is no objective biomarker which can reliably differentiate between them. The synergistic combination of electrophysiological and neuroimaging approaches is a powerful method for interrogation of functional brain networks in vivo. We recorded bilateral local field potentials (LFPs) from the nucleus basalis of Meynert (NBM) and the internal globus pallidus (GPi) with simultaneous cortical magnetoencephalography (MEG) in six PDD and five DLB patients undergoing surgery for deep brain stimulation (DBS) to look for differences in underlying resting-state network pathophysiology. In both patient groups we observed spectral peaks in the theta (2-8 Hz) band in both the NBM and the GPi. Furthermore, both the NBM and the GPi exhibited similar spatial and spectral patterns of coupling with the cortex in the two disease states. Specifically, we report two distinct coherent networks between the NBM/GPi and cortical regions: (1) a theta band (2-8 Hz) network linking the NBM/GPi to temporal cortical regions, and (2) a beta band (13-22 Hz) network coupling the NBM/GPi to sensorimotor areas. We also found differences between the two disease groups: oscillatory power in the low beta (13-22Hz) band was significantly higher in the globus pallidus in PDD patients compared to DLB, and coherence in the high beta (22-35Hz) band between the globus pallidus and lateral sensorimotor cortex was significantly higher in DLB patients compared to PDD. Overall, our findings reveal coherent networks of the NBM/GPi region that are common to both DLB and PDD. Although the neurophysiological differences between the two conditions in this study are confounded by systematic differences in DBS lead trajectories and motor symptom severity, they lend support to the hypothesis that DLB and PDD, though closely related, are distinguishable from a neurophysiological perspective.

Crystallized and fluid intelligence are predicted by microstructure of specific white-matter tracts.

Studies of the neural basis of intelligence have focused on comparing brain imaging variables with global scales instead of the cognitive domains integrating these scales or quotients. Here, the relation between mean tract-based fractional anisotropy (mTBFA) and intelligence indices was explored. Deterministic tractography was performed using a regions of interest approach for 10 white-matter fascicles along which the mTBFA was calculated. The study sample included 83 healthy individuals from the second wave of the Cuban Human Brain Mapping Project, whose WAIS-III intelligence quotients and indices were obtained. Inspired by the "Watershed model" of intelligence, we employed a regularized hierarchical Multiple Indicator, Multiple Causes model (MIMIC), to assess the association of mTBFA with intelligence scores, as mediated by latent variables summarizing the indices. Regularized MIMIC, used due to the limited sample size, selected relevant mTBFA by means of an elastic net penalty and achieved good fits to the data. Two latent variables were necessary to describe the indices: Fluid intelligence (Perceptual Organization and Processing Speed indices) and Crystallized Intelligence (Verbal Comprehension and Working Memory indices). Regularized MIMIC revealed effects of the forceps minor tract on crystallized intelligence and of the superior longitudinal fasciculus on fluid intelligence. The model also detected the significant effect of age on both latent variables.

A fronto-striato-subthalamic-pallidal network for goal-directed and habitual inhibition.

Classically, the basal ganglia have been considered to have a role in producing habitual and goal-directed behaviours. In this article, we review recent evidence that expands this role, indicating that the basal ganglia are also involved in neural and behavioural inhibition in the motor and non-motor domains. We then distinguish between goal-directed and habitual (also known as automatic) inhibition mediated by fronto-striato-subthalamic-pallido-thalamo-cortical networks. We also suggest that imbalance between goal-directed and habitual action and inhibition contributes to some manifestations of Parkinson's disease, Tourette syndrome and obsessive-compulsive disorder. Finally, we propose that basal ganglia surgery improves these disorders by restoring a functional balance between facilitation and inhibition.

Long-term GPi-DBS improves motor features in myoclonus-dystonia and enhances social adjustment.

BACKGROUND: Good short-term results of pallidal deep brain stimulation have been reported in myoclonus-dystonia. Efficacy and safety in the long term remain to be established. In addition, the actual impact of DBS treatment on social inclusion is unknown. The objective of this study was to assess the long-term clinical outcome, quality of life, and social adjustment of GPi-DBS in patients with ε-sarcoglycan (DYT11)-positive myoclonus-dystonia. METHODS: Consecutive myoclonus-dystonia patients with ε-sarcoglycan mutations who underwent GPi-DBS were evaluated at least 5 years postoperatively. Motor symptoms were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale including the Disability Scale, a composite score combining the rest and action parts of the Unified Myoclonus Rating Scale and modified Abnormal Involuntary Movement Scale. Standardized video-protocols were assessed by a blinded and external movement disorder specialist. Social adjustment, cognition, and mood were evaluated. RESULTS: Nine patients (5 women) with long-term GPi-DBS (8.7 ± 3.1 years) were included. There was significant improvement in the composite myoclonus score (94.1% ± 4% improvement; P = 0.008). Dystonia severity was also markedly improved (71.4% ± 28.33% improvement; P = 0.008) as well as motor disability (88.3% ± 20% improvement; P = 0.008) and abnormal involuntary movement score (71.1% ± 15.0% improvement; P = 0.008). No patients experienced postoperative speech or gait problems or any permanent adverse effects. Eight of the 9 patients had fully enhanced social adjustment and personal achievement, with little or no mood or behavioral disorders. CONCLUSIONS: GPi-DBS seems to be a safe and efficacious treatment for medically refractory ɛ-sarcoglycan myoclonus-dystonia, with sustained motor benefit, good quality of life, and social adjustment in long-term follow-up. © 2018 International Parkinson and Movement Disorder Society.

Ventral tegmental area deep brain stimulation for chronic cluster headache: Effects on cognition, mood, pain report behaviour and quality of life.

BACKGROUND: Deep brain stimulation in the ventral tegmental area (VTA-DBS) has provided remarkable therapeutic benefits in decreasing headache frequency and severity in patients with medically refractory chronic cluster headache (CH). However, to date the effects of VTA-DBS on cognition, mood and quality of life have not been examined in detail. METHODS: The aim of the present study was to do so in a case series of 18 consecutive patients with cluster headache who underwent implantation of deep brain stimulation electrodes in the ventral tegmental area. The patients were evaluated preoperatively and after a mean of 14 months of VTA-DBS on tests of global cognition (Mini Mental State Examination), intelligence (Wechsler Abbreviated Scale of Intelligence), verbal memory (California Verbal Learning Test-II), executive function (Delis-Kaplan Executive Function System), and attention (Paced Auditory Serial Addition Test). Depression (Beck Depression Inventory and Hospital Anxiety and Depression Rating Scale-D), anxiety (Hospital Anxiety and Depression Rating Scale-A), apathy (Starkstein Apathy Scale), and hopelessness (Beck Hopelessness Scale) were also assessed. Subjective pain experience (McGill Pain Questionnaire), behaviour (Pain Behaviour Checklist) and quality of life (Short Form-36) were also evaluated at the same time points. RESULTS: VTA-DBS resulted in significant improvement of headache frequency (from a mean of five to two attacks daily, p < .001) and severity (from mean Verbal Rating Scale [VRS] of 10 to 7, p < .001) which was associated with significant reduction of anxiety (from mean HADS-A of 11.94 to 8.00, p < .001) and help-seeking behaviours (from mean PBC of 4.00 to 2.61, p < .001). VTA-DBS did not produce any significant change to any tests of cognitive function and any other outcome measures (BDI, HADS-D, SAS, BHS, McGill Pain Questionnaire, Short Form-36). CONCLUSION: We confirm the efficacy of VTA-DBS in the treatment of medically refractory chronic cluster headache. The reduction of headache frequency and severity was associated with a significant reduction of anxiety. Furthermore, the result suggests that VTA-DBS for chronic cluster headache improves pain-related help-seeking behaviours and does not produce any change in cognition.

Deep Brain Stimulation of the Subthalamic Nucleus Does Not Affect the Decrease of Decision Threshold during the Choice Process When There Is No Conflict, Time Pressure, or Reward.

During a decision process, the evidence supporting alternative options is integrated over time, and the choice is made when the accumulated evidence for one of the options reaches a decision threshold. Humans and animals have an ability to control the decision threshold, that is, the amount of evidence that needs to be gathered to commit to a choice, and it has been proposed that the subthalamic nucleus (STN) is important for this control. Recent behavioral and neurophysiological data suggest that, in some circumstances, the decision threshold decreases with time during choice trials, allowing overcoming of indecision during difficult choices. Here we asked whether this within-trial decrease of the decision threshold is mediated by the STN and if it is affected by disrupting information processing in the STN through deep brain stimulation (DBS). We assessed 13 patients with Parkinson disease receiving bilateral STN DBS six or more months after the surgery, 11 age-matched controls, and 12 young healthy controls. All participants completed a series of decision trials, in which the evidence was presented in discrete time points, which allowed more direct estimation of the decision threshold. The participants differed widely in the slope of their decision threshold, ranging from constant threshold within a trial to steeply decreasing. However, the slope of the decision threshold did not depend on whether STN DBS was switched on or off and did not differ between the patients and controls. Furthermore, there was no difference in accuracy and RT between the patients in the on and off stimulation conditions and healthy controls. Previous studies that have reported modulation of the decision threshold by STN DBS or unilateral subthalamotomy in Parkinson disease have involved either fast decision-making under conflict or time pressure or in anticipation of high reward. Our findings suggest that, in the absence of reward, decision conflict, or time pressure for decision-making, the STN does not play a critical role in modulating the within-trial decrease of decision thresholds during the choice process.

Global scales for cognitive screening in Parkinson's disease: Critique and recommendations.

BACKGROUND: Cognitive impairment is a common nonmotor manifestation of Parkinson's disease, with deficits ranging from mild cognitive difficulties in 1 or more of the cognitive domains to severe dementia. The International Parkinson and Movement Disorder Society commissioned the assessment of the clinimetric properties of cognitive rating scales measuring global cognitive performance in PD to make recommendations regarding their use. METHODS: A systematic literature search was conducted to identify the scales used to assess global cognitive performance in PD, and the identified scales were reviewed and rated as "recommended," "recommended with caveats," "suggested," or "listed" by the panel using previously established criteria. RESULTS: A total of 12 cognitive scales were included in this review. Three scales, the Montreal Cognitive Assessment, the Mattis Dementia Rating Scale Second Edition, and the Parkinson's Disease-Cognitive Rating Scale, were classified as "recommended." Two scales were classified as "recommended with caveats": the Mini-Mental Parkinson, because of limited coverage of executive abilities, and the Scales for Outcomes in Parkinson's Disease-Cognition, which has limited data on sensitivity to change. Six other scales were classified as "suggested" and 1 scale as "listed." CONCLUSIONS: Because of the existence of "recommended" scales for assessment of global cognitive performance in PD, this task force suggests that the development of a new scale for this purpose is not needed at this time. However, global cognitive scales are not a substitute for comprehensive neuropsychological testing. © 2017 International Parkinson and Movement Disorder Society.

Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson's disease.

OBJECTIVES: Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy. METHODS: High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy. RESULTS: All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -13(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity. INTERPRETATION: These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.

The cognitive features of idiopathic and DYT1 dystonia.

Dystonia is a common movement disorder. In this paper, we review the literature on cognitive function in idiopathic and DYT1 dystonia. In idiopathic or DYT1 dystonia, cognition is largely intact with only isolated executive dysfunction. Dystonia patients also have increased temporal and spatial discrimination thresholds, considered endophenotypes of the disorder because deficits are also shown by unaffected relatives and nonmanifesting carriers of the DYT1 mutation. Anticholinergic medication in high doses can be associated with memory impairment in dystonia. The successful treatment of dystonia with botulinum toxin injections or deep brain stimulation does not produce any major adverse effects on cognition. The aspects of cognition that require further investigation in future studies of dystonia include inhibitory control, decision making, and social cognition. © 2017 International Parkinson and Movement Disorder Society.

l-Dopa responsiveness is associated with distinctive connectivity patterns in advanced Parkinson's disease.

BACKGROUND: Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. METHODS: To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to l-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3 × 3 × 2.5 mm3 voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an l-dopa challenge. False discovery rate-corrected P was set at < 0.05 for a 2-tailed t test. RESULTS: A greater improvement in UPDRS-III scores following l-dopa administration was characterized by higher resting-state functional connectivity between the prefrontal cortex and the striatum (P = 0.001) and lower resting-state functional connectivity between the pallidum (P = 0.001), subthalamic nucleus (P = 0.003), and the paracentral lobule (supplementary motor area, mesial primary motor, and primary sensory areas). CONCLUSIONS: Our findings show characteristic basal ganglia resting-state functional connectivity patterns associated with different degrees of l-dopa responsiveness in patients with advanced Parkinson's disease. l-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response. © 2017 International Parkinson and Movement Disorder Society.

Quality of life in primary headache disorders: A review.

BACKGROUND: Health-related quality of life (HRQoL) is emerging as an important element of clinical research in primary headache disorders, allowing a measure of the impact of headache on patients' well-being and daily life. A better understanding of this may contribute to improved resource allocations and treatment approaches. OBJECTIVE: The objective of this study is to review available data on HRQoL in primary headache disorders and identify any influencing factors. METHODS: Database searches including MEDLINE, PsycINFO and EMBASE were performed. Studies that investigated HRQoL in patients with primary headache disorders were included and reviewed. Trials that evaluated the efficacy of medications or interventions were excluded. RESULTS: A total of 80 articles were included in the review. Both physical and emotional/mental aspects of HRQoL were impaired across headache subtypes, although the extent varied depending on headache type. A number of factors influencing HRQoL were also identified. CONCLUSION: This narrative review suggests that headache, particularly in its chronic form, has a great impact on HRQoL. Clinical practice should not solely focus on pain alleviation but rather adopt routine assessment of HRQoL. Furthermore, identification and management of associated psychological comorbidities, which can significantly influence HRQoL in headache sufferers, are essential for optimal clinical management.

In Parkinson's disease on a probabilistic Go/NoGo task deep brain stimulation of the subthalamic nucleus only interferes with withholding of the most prepotent responses.

The evidence on the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on action restraint on Go/NoGO reaction time (RT) tasks in Parkinson's disease (PD) is inconsistent; with some studies reporting no effect and others finding that STN stimulation interferes with withholding of responses and results in more commission errors relative to STN-DBS off. We used a task in which the probability of Go stimuli varied from 100% (simple RT task) to 80, 50 and 20% (probabilistic Go/NoGo RT task), thus altering the prepotency of the response and the difficulty in withholding it on NoGo trials. Twenty PD patients with STN-DBS, ten unoperated PD patients and ten healthy controls participated in the study. All participants were tested twice; the order of on versus off stimulation for STN-DBS PD patients was counterbalanced. Both STN-DBS and unoperated PD patients were tested on medication. The results indicated that STN-DBS selectively decreased discriminability when the response was most prepotent (high--80%, as compared to low Go probability trials--50 and 20%). Movement times were faster with STN stimulation than with DBS off across different Go probability levels. There was neither an overall nor a selective effect of STN-DBS on RTs depending on the level of Go probability. Furthermore, compared to healthy controls, both STN-DBS and unoperated PD patients were more prone to making anticipatory errors; which was not influenced by STN stimulation. The results provide evidence for 'load-dependent' effects of STN stimulation on action restraint as a function of the prepotency of the Go response.