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Article: Bilateral deep transcranial magnetic stimulation of motor and prefrontal cortices in Parkinson's disease: a comprehensive review.

Hanlon, Colleen A / Lench, Daniel H / Pell, Gaby / Roth, Yiftach / Zangen, Abraham / Tendler, Aron

2024 Volume 17, Page(s) 1336027

Abstract: Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by both motor and non-motor symptoms, many of which are resistant to currently available treatments. Since the discovery that non-invasive transcranial magnetic stimulation ( ...

Abstract	Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by both motor and non-motor symptoms, many of which are resistant to currently available treatments. Since the discovery that non-invasive transcranial magnetic stimulation (TMS) can cause dopamine release in PD patients, there has been growing interest in the use of TMS to fill existing gaps in the treatment continuum for PD. This review evaluates the safety and efficacy of a unique multifocal, bilateral Deep TMS protocol, which has been evaluated as a tool to address motor and non-motor symptoms of PD. Six published clinical trials have delivered a two-stage TMS protocol with an H-Coil targeting both the prefrontal cortex (PFC) and motor cortex (M1) bilaterally (220 PD patients in total; 108 from two randomized, sham-controlled studies; 112 from open label or registry studies). In all studies TMS was delivered to M1 bilaterally (Stage 1) and then to the PFC bilaterally (Stage 2) with approximately 900 pulses per stage. For Stage 1 (M1), two studies delivered 10 Hz at 90% motor threshold (MT) while four studies delivered 1 Hz at 110% MT. For Stage 2 (PFC), all studies delivered 10 Hz at 100% MT. The results suggest that this two-stage Deep TMS protocol is a safe, moderately effective treatment for motor symptoms of PD, and that severely impaired patients have the highest benefits. Deep TMS also improves mood symptoms and cognitive function in these patients. Further research is needed to establish optimal dosing and the long-term durability of treatment effects.
Language	English
Publishing date	2024-01-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2425477-0
ISSN	1662-5161
ISSN	1662-5161
DOI	10.3389/fnhum.2023.1336027
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Article: Deep brain stimulation for essential tremor versus essential tremor plus: should we target the same spot in the thalamus?

Yu, Cherry H / Lench, Daniel H / Cooper, Christine / Rowland, Nathan C / Takacs, Istvan / Revuelta, Gonzalo

Frontiers in human neuroscience

2023 Volume 17, Page(s) 1271046

Abstract: Background: Although ET is a phenomenologically heterogeneous condition, thalamic DBS appears to be equally effective across subtypes. We hypothesized stimulation sites optimized for individuals with essential tremor (ET) would differ from individuals ... ...

Abstract	Background: Although ET is a phenomenologically heterogeneous condition, thalamic DBS appears to be equally effective across subtypes. We hypothesized stimulation sites optimized for individuals with essential tremor (ET) would differ from individuals with essential tremor plus syndrome (ET-plus). We examined group differences in optimal stimulation sites within the ventral thalamus and their overlap of with relevant white matter tracts. By capturing these differences, we sought to determine whether ET subtypes are associated with anatomically distinct neural pathways. Methods: A retrospective chart review was conducted on ET patients undergoing VIM DBS at MUSC between 01/2012 and 02/2022. Clinical, demographic, neuroimaging, and DBS stimulation parameter data were collected. Clinical characteristics and pre-DBS videos were reviewed to classify ET and ET-plus cohorts. Patients in ET-plus cohorts were further divided into ET with dystonia, ET with ataxia, and ET with others. DBS leads were reconstructed using Lead-DBS and the volume of tissue activated (VTA) overlap was performed using normative connectomes. Tremor improvement was measured by reduction in a subscore of tremor rating scale (TRS) post-DBS lateralized to the more affected limb. Results: Sixty-eight ET patients were enrolled after initial screening, of these 10 ET and 24 ET-plus patients were included in the final analyses. ET group had an earlier age at onset ( Conclusion: VIM DBS therapy is efficacious in patients with ET and ET-plus. There were no significant differences in optimal stimulation site or VTA overlap with white-matter tracts between ET, ET-plus and ET-plus subgroups.
Language	English
Publishing date	2023-10-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2425477-0
ISSN	1662-5161
ISSN	1662-5161
DOI	10.3389/fnhum.2023.1271046
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Article ; Online: Subthalamic functional connectivity associated with freezing of gait dopa-response.

Lench, Daniel H / Doolittle, Jade D / Ramakrishnan, Viswanathan / Rowland, Nathan / Revuelta, Gonzalo J

Parkinsonism & related disorders

2023 Volume 118, Page(s) 105952

Abstract: Introduction: Freezing of gait (FOG) is a prevalent and debilitating feature of Parkinson's Disease (PD). The subthalamic nucleus (STN) is a center for controlled locomotion and a common DBS target. The objective of this study was to identify STN ... ...

Abstract	Introduction: Freezing of gait (FOG) is a prevalent and debilitating feature of Parkinson's Disease (PD). The subthalamic nucleus (STN) is a center for controlled locomotion and a common DBS target. The objective of this study was to identify STN circuitry associated with FOG response to dopaminergic medication. In this study, we compare BOLD functional connectivity of the subthalamic nucleus (STN) in participants with and without dopa-responsive FOG. Methods: 55 PD participants either with FOG (n = 38) or without FOG (n = 17) were recruited. Among FOG participants 22 were dopa-responsive and 16 were dopa-unresponsive. STN whole-brain connectivity was performed using CONN toolbox. The relationship between the degree of self-reported FOG dopa-response and STN connectivity was evaluated using partial correlations corrected for age, disease duration, and levodopa equivalent daily dose. Results: Right STN connectivity with the cerebellar locomotor region and the temporal/occipital cortex was greater in the dopa-responsive FOG group (voxel threshold p < 0.01, FWE corrected p < 0.05). Left STN connectivity with the occipital cortex was greater in the dopa-responsive FOG group and connectivity with the postcentral gyrus was greater in the dopa-unresponsive FOG group. Strength of connectivity to these regions correlated with l-dopa induced improvement in UPDRS Item-14 (FOG), but not UPDRS Part-III (overall motor score). Discussion: We demonstrate that dopa-unresponsive FOG is associated with changes in BOLD functional connectivity between the STN and locomotor as well as sensory processing regions. This finding supports the conceptual framework that effective treatment for freezing of gait likely requires the engagement of both locomotor and sensory brain regions.
MeSH term(s)	Humans ; Parkinson Disease/complications ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/drug therapy ; Gait Disorders, Neurologic/diagnostic imaging ; Gait Disorders, Neurologic/drug therapy ; Gait Disorders, Neurologic/etiology ; Deep Brain Stimulation ; Levodopa/pharmacology ; Levodopa/therapeutic use ; Gait/physiology
Chemical Substances	Levodopa (46627O600J)
Language	English
Publishing date	2023-12-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1311489-x
ISSN	1873-5126 ; 1353-8020
ISSN (online)	1873-5126
ISSN	1353-8020
DOI	10.1016/j.parkreldis.2023.105952
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Zs.A 4553: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Are Standardized Tests Sensitive to Early Cognitive Change in Parkinson's Disease?

Turner, Travis H / Lench, Daniel H / Adams, Robin / Wilson, Sandra / Marsicano, Christina / Rodriguez-Porcel, Federico

Psychopharmacology bulletin

2023 Volume 53, Issue 1, Page(s) 19–29

Abstract: Introduction: Cognitive deficits within the first years of Parkinson's disease (PD) diagnosis are commonly reported, and progression to dementia greatly impacts independence. Identifying measures sensitive to early changes is critical for trials of ... ...

Abstract	Introduction: Cognitive deficits within the first years of Parkinson's disease (PD) diagnosis are commonly reported, and progression to dementia greatly impacts independence. Identifying measures sensitive to early changes is critical for trials of symptomatic therapies and neuroprotection. Methods: A sample of 253 newly diagnosed PD patients and 134 Health Controls (HC) completed a brief cognitive battery annually over a 5-year period through the Parkinson's Progression Markers Initiative (PPMI). The battery included standardized measures of memory, visuospatial functions, processing speed, working memory, and verbal fluency. Inclusion criterion for HCs was performance above a cutoff for possible Mild Cognitive Impairment (pMCI) on cognitive screening (MoCA ⩾ 27) The PD sample was therefore divided to match HCs on baseline cognitive testing (PD-normal n = 169; PD-pMCI n = 84). The multivariate approach to repeated measures examined rates of change between groups on cognitive measures. Results: An interaction indicating slightly greater decline over time in PD-normal relative to HCs was observed on a measure of working memory: letter-number sequencing. Differential rates of change were not observed on any other measures. Motor symptoms on the dominant right upper extremity accounted for performance differences on a test with writing demands (Symbol-Digit Modality Test). PD-pMCI performed worse than PD-normal on all cognitive measures at baseline, but did not decline faster. Discussion: Working memory appears to decline slightly faster in early PD compared to HCs, while other domains remain similar. Within PD, faster decline was not associated with lower baseline cognition. These findings have implications for clinical trial outcome selection and study design.
MeSH term(s)	Humans ; Parkinson Disease ; Cognition ; Processing Speed ; Research Design ; Social Group
Language	English
Publishing date	2023-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	4113-0
ISSN	2472-2448 ; 0048-5764 ; 0376-0162
ISSN (online)	2472-2448
ISSN	0048-5764 ; 0376-0162
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Zs.A 958: Show issues

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Article ; Online: Integrity of the nucleus basalis of meynert and self-reported cognitive dysfunction during wearing-off periods in parkinson's disease.

Lench, Daniel H / Turner, Travis H / Wetmore, Emma / Rodriguez-Porcel, Federico J / Revuelta, Gonzalo J

Brain imaging and behavior

2023 Volume 18, Issue 1, Page(s) 256–261

Abstract: Background: Cognition in Parkinson's Disease can be impacted by the wearing-off phenomenon which results from changes in dopaminergic tone throughout the day. Given the well-established role of the cholinergic basal forebrain in cognition, we ... ...

Abstract	Background: Cognition in Parkinson's Disease can be impacted by the wearing-off phenomenon which results from changes in dopaminergic tone throughout the day. Given the well-established role of the cholinergic basal forebrain in cognition, we hypothesized that the Nucleus Basalis of Meynert may support cognitive processes during wearing-off periods. Specifically, we evaluated whether worsening of cognitive symptoms during wearing-off is more likely to occur with structural degeneration of the Nucleus Basalis of Meynert. Methods: Cognitive wearing-off was evaluated via the Movement Disorders Society Non-Motor Fluctuation Assessment Questionnaire in 33 Parkinson's Disease participants undergoing evaluation for deep brain stimulation. Pre-operative diffusion MRIs were used to measure brain diffusion metrics of the Nucleus Basalis of Meynert and control regions (caudate and putamen). Results: The number of cognitive symptoms which worsened during OFF periods positively correlated with mean diffusivity (ρ = 0.561, p = 0.0007) and generalized fractional anisotropy (ρ=-0.447, p = 0.009) within the Nucleus Basalis of Meynert but not in the caudate or putamen. Meanwhile, stable cognitive symptoms, and ON-state cognitive performance as measured by the DRS-2 did not correlate with Nucleus Basalis of Meynert metrics. Correlations were corrected for age, sex, scanner type, disease duration, education and LEDD. Conclusions: Our study suggests that reduced structural integrity of the Nucleus Basalis of Meynert is associated with worsening of participant-reported cognitive deficits during OFF periods, but not overall cognitive functioning in the ON-state. These findings support the hypothesis that structural integrity of the cholinergic Nucleus Basalis of Meynert may provide resilience to cognitive worsening during dopamine-related wearing-off.
MeSH term(s)	Humans ; Basal Nucleus of Meynert ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/complications ; Self Report ; Magnetic Resonance Imaging ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/complications ; Cholinergic Agents
Chemical Substances	Cholinergic Agents
Language	English
Publishing date	2023-10-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2377165-3
ISSN	1931-7565 ; 1931-7557
ISSN (online)	1931-7565
ISSN	1931-7557
DOI	10.1007/s11682-023-00817-y
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Article ; Online: Kinematic Measures of Bimanual Performance are Associated With Callosum White Matter Change in People With Chronic Stroke.

Lench, Daniel H / Hutchinson, Scott / Woodbury, Michelle L / Hanlon, Colleen A

Archives of rehabilitation research and clinical translation

2020 Volume 2, Issue 4, Page(s) 100075

Abstract: Objectives: To investigate the relationship between bimanual performance deficits measured using kinematics and callosum (CC) white matter changes that occur in people with chronic stroke.: Design: Cross-sectional, observational study of participants ...

Abstract	Objectives: To investigate the relationship between bimanual performance deficits measured using kinematics and callosum (CC) white matter changes that occur in people with chronic stroke. Design: Cross-sectional, observational study of participants with chronic stroke and age-matched controls. Setting: Recruitment and assessments occurred at a stroke recovery research center. Behavioral assessments were performed in a controlled laboratory setting. Magnetic resonance imaging scans were performed at the Center for Biomedical Imaging. Participants: Individuals were enrolled and completed the study (N=39; 21 participants with chronic stroke; 18 age-matched controls with at least 2 stroke risk factors). Main outcome measures: Diffusion imaging metrics were obtained for each individual's CC and corticospinal tract (CST), including mean kurtosis (MK) and fractional anisotropy (FA). A battery of motor assessments, including bimanual kinematics, were collected from individuals while performing bimanual reaching. Results: Participants with stroke had lower FA and MK in the CST of the lesioned hemisphere when compared with the non-lesioned hemisphere. The FA and MK values in the CST were correlated with measures of unimanual hand performance. In addition, participants with stroke had significantly lower FA and MK in the CC than matched controls. CC diffusion metrics positively correlated with hand asymmetry and trunk displacement during bimanual performance, even when correcting for age and lesion volume. Conclusions: These data confirm previous studies that linked CST integrity to unimanual performance and provide new data demonstrating a link between CC integrity and both bimanual motor deficits and compensatory movements.
Language	English
Publishing date	2020-07-18
Publishing country	United States
Document type	Journal Article
ISSN	2590-1095
ISSN (online)	2590-1095
DOI	10.1016/j.arrct.2020.100075
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Article ; Online: Feasibility of remote transcranial direct current stimulation for pediatric cerebral palsy during the COVID-19 pandemic.

Lench, Daniel H / Simpson, Emma / Sutter, Ellen N / Gillick, Bernadette T

Brain stimulation

2020 Volume 13, Issue 6, Page(s) 1803–1804

Keywords	covid19
Language	English
Publishing date	2020-10-23
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2394410-9
ISSN	1876-4754 ; 1935-861X
ISSN (online)	1876-4754
ISSN	1935-861X
DOI	10.1016/j.brs.2020.10.010
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Zs.A 6740: Show issues

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Article ; Online: Remotely monitored transcranial direct current stimulation in pediatric cerebral palsy: open label trial protocol.

Simpson, Emma A / Saiote, Catarina / Sutter, Ellen / Lench, Daniel H / Ikonomidou, Chrysanthy / Villegas, Melissa A / Gillick, Bernadette T

BMC pediatrics

2022 Volume 22, Issue 1, Page(s) 566

Abstract: Background: Pediatric applications of non-invasive brain stimulation using transcranial direct current stimulation (tDCS) have demonstrated its safety with few adverse events reported. Remotely monitored tDCS, as an adjuvant intervention to ... ...

Abstract	Background: Pediatric applications of non-invasive brain stimulation using transcranial direct current stimulation (tDCS) have demonstrated its safety with few adverse events reported. Remotely monitored tDCS, as an adjuvant intervention to rehabilitation, may improve quality of life for children with cerebral palsy (CP) through motor function improvements, reduced treatment costs, and increased access to tDCS therapies. Our group previously evaluated the feasibility of a remotely monitored mock tDCS setup in which families and children successfully demonstrated the ability to follow tDCS instructional guidance. Methods and design: Here, we designed a protocol to investigate the feasibility, safety, and tolerability of at-home active transcranial direct current stimulation in children with CP with synchronous supervision from laboratory investigators. Ten participants will be recruited to participate in the study for 5 consecutive days with the following sessions: tDCS setup practice on day 1, sham tDCS on day 2, and active tDCS on days 3-5. Sham stimulation will consist of an initial 30-second ramp up to 1.5 mA stimulation followed by a 30-second ramp down. Active stimulation will be delivered at 1.0 - 1.5 mA for 20 minutes and adjusted based on child tolerance. Feasibility will be evaluated via photographs of montage setup and the quality of stimulation delivery. Safety and tolerability will be assessed through an adverse events survey, the Box and Blocks Test (BBT) motor assessment, and a setup ease/comfort survey. Discussion: We expect synchronous supervision of at-home teleneuromodulation to be tolerable and safe with increasing stimulation quality over repeated sessions when following a tDCS setup previously determined to be feasible. The findings will provide opportunity for larger clinical trials exploring efficacy and illuminate the potential of remotely monitored tDCS in combination with rehabilitation interventions as a means of pediatric neurorehabilitation. This will demonstrate the value of greater accessibility of non-invasive brain stimulation interventions and ultimately offer the potential to improve care and quality of life for children and families with CP. Trial registration: October 8, 2021( https://clinicaltrials.gov/ct2/show/NCT05071586 ).
MeSH term(s)	Child ; Humans ; Cerebral Palsy/therapy ; Monitoring, Physiologic ; Quality of Life ; Transcranial Direct Current Stimulation
Language	English
Publishing date	2022-09-29
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041342-7
ISSN	1471-2431 ; 1471-2431
ISSN (online)	1471-2431
ISSN	1471-2431
DOI	10.1186/s12887-022-03612-8
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Article ; Online: Neurodegeneration of the Globus Pallidus Internus as a Neural Correlate to Dopa-Response in Freezing of Gait.

Lench, Daniel H / Keith, Kathryn / Wilson, Sandra / Padgett, Lucas / Benitez, Andreana / Ramakrishnan, Viswanathan / Jensen, Jens H / Bonilha, Leonardo / Revuelta, Gonzalo J

Journal of Parkinson's disease

2022 Volume 12, Issue 4, Page(s) 1241–1250

Abstract: Background: Background: Parkinson's disease (PD) patients who develop freezing of gait (FOG) have reduced mobility and independence. While some patients experience improvement in their FOG symptoms with dopaminergic therapies, a subset of patients have ... ...

Abstract	Background: Background: Parkinson's disease (PD) patients who develop freezing of gait (FOG) have reduced mobility and independence. While some patients experience improvement in their FOG symptoms with dopaminergic therapies, a subset of patients have little to no response. To date, it is unknown what changes in brain structure underlie dopa-response and whether this can be measured using neuroimaging approaches. Objective: We tested the hypothesis that structural integrity of brain regions (subthalamic nucleus and globus pallidus internus, GPi) which link basal ganglia to the mesencephalic locomotor region (MLR), a region involved in automatic gait, would be associated with FOG response to dopaminergic therapy. Methods: In this observational study, thirty-six participants with PD and definite FOG were recruited to undergo diffusion kurtosis imaging (DKI) and multiple assessments of dopa responsiveness (UPDRS scores, gait times ON versus OFF medication). Results: The right GPi in participants with dopa-unresponsive FOG showed reduced fractional anisotropy, mean kurtosis (MK), and increased radial diffusivity relative to those with dopa-responsive FOG. Furthermore, using probabilistic tractography, we observed reduced MK and increased mean diffusivity along the right GPi-MLR tract in dopa-unresponsive FOG. MK in the right GPi was associated with a subjective dopa-response for FOG (r = -0.360, df = 30, p = 0.043) but not overall motor dopa-response. Conclusion: These results support structural integrity of the GPi as a correlate to dopa-response in FOG. Additionally, this study suggests DKI metrics may be a sensitive biomarker for clinical studies targeting dopaminergic circuitry and improvements in FOG behavior.
MeSH term(s)	Dihydroxyphenylalanine ; Dopamine ; Gait ; Gait Disorders, Neurologic/diagnostic imaging ; Gait Disorders, Neurologic/drug therapy ; Gait Disorders, Neurologic/etiology ; Globus Pallidus/diagnostic imaging ; Humans ; Parkinson Disease/complications ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/drug therapy
Chemical Substances	Dihydroxyphenylalanine (63-84-3) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2022-03-31
Publishing country	Netherlands
Document type	Journal Article ; Observational Study ; Research Support, N.I.H., Extramural
ZDB-ID	2620609-2
ISSN	1877-718X ; 1877-7171
ISSN (online)	1877-718X
ISSN	1877-7171
DOI	10.3233/JPD-213062
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Zs.A 6964: Show issues

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Article ; Online: Neural Architecture Influences Repetitive Transcranial Magnetic Stimulation-Induced Functional Change: A Diffusion Tensor Imaging and Functional Magnetic Resonance Imaging Study of Cue-Reactivity Modulation in Alcohol Users.

Hanlon, Colleen A / Lench, Daniel H / Dowdle, Logan T / Ramos, Tonisha Kearney

Clinical pharmacology and therapeutics

2019 Volume 106, Issue 4, Page(s) 702–705

MeSH term(s)	Adult ; Alcoholism/physiopathology ; Alcoholism/psychology ; Alcoholism/therapy ; Connectome ; Cues ; Diffusion Tensor Imaging ; Female ; Functional Neuroimaging/methods ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Neural Pathways/pathology ; Neural Pathways/physiopathology ; Outcome Assessment, Health Care ; Prefrontal Cortex/pathology ; Prefrontal Cortex/physiopathology ; Putamen/pathology ; Putamen/physiopathology ; Transcranial Direct Current Stimulation/methods
Language	English
Publishing date	2019-08-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.1545
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