Thalamic volume mediates associations between cardiorespiratory fitness (VO2max) and cognition in Parkinson's disease

IntroductionCognitive deficits occur in Parkinson's disease (PD). Cardiorespiratory fitness (CRF) is associated with better cognitive performance in aging especially in executive function (EF) and memory. The association between CRF and cognitive performance is understudied in people with PD. Brain structures underlying associations also remains unknown. This cross-sectional study examined the associations between CRF and cognitive performance in PD. We also examined associations between CRF and brain structures impacted in PD. Mediation analysis were conducted to examine whether brain structures impacted in PD mediate putative associations between CRF and cognitive performance.MethodsIndividuals with PD (N = 33) underwent magnetic resonance imaging (MRI), CRF evaluation (estimated VO₂max), and neuropsychological assessment. Composite cognitive scores of episodic memory, EF, attention, language, and visuospatial functioning were generated. Structural equation models were constructed to examine whether MRI volume estimates (thalamus and pallidum) mediated associations between CRF and cognitive performance (adjusting for age, education, PD disease duration, sex, MDS-UPDRS motor score, and total intracranial volume).ResultsHigher CRF was associated with better episodic memory (Standardized β = 0.391; p = 0.008), EF (Standardized β = 0.324; p = 0.025), and visuospatial performance (Standardized β = 0.570; p = 0.005). Higher CRF was associated with larger thalamic (Standardized β = 0.722; p = 0.004) and pallidum (Standardized β = 0.635; p = 0.004) volumes. Thalamic volume mediated the association between higher CRF and better EF (Indirect effect = 0.309) and episodic memory (Indirect effect = 0.209) performance (p < 0.05). The pallidum did not significantly mediate associations between CRF and cognitive outcomes.ConclusionThe thalamus plays an important role in the association between CRF and both EF and episodic memory in PD.     

Neurovascular coupling during deep brain stimulation

BackgroundDeep brain stimulation (DBS) is an effective treatment for movement disorders, yet its mechanisms of action remain unclear. One method used to study its circuit-wide neuromodulatory effects is functional magnetic resonance imaging (fMRI) which measures hemodynamics as a proxy of neural activity. To interpret functional imaging data, we must understand the relationship between neural and vascular responses, which has never been studied with the high frequencies used for DBS.ObjectiveTo measure neurovascular coupling in the rat motor cortex during thalamic DBS.MethodSimultaneous intrinsic optical imaging and extracellular electrophysiology was performed in the motor cortex of urethane-anesthetized rats during thalamic DBS at 7 different frequencies. We related Maximum Change in Reflectance (MCR) from the imaging data to Integrated Evoked Potential (IEP) and change in broadband power of multi-unit (MU) activity, computing Spearman’s correlation to determine the strength of these relationships. To determine the source of these effects, we studied the contributions of antidromic versus orthodromic activation in motor cortex perfusion using synaptic blockers.ResultsMCR, IEP and change in MU power increased linearly to 60 Hz and saturated at higher frequencies of stimulation. Blocking orthodromic transmission only reduced the DBS-induced change in optical signal by ∼25%, suggesting that activation of corticofugal fibers have a major contribution in thalamic-induced cortical activation.ConclusionDBS-evoked vascular response is related to both evoked field potentials as well as multi-unit activity.     

Effects of ventral intermediate nucleus deep brain stimulation across multiple effectors in essential tremor

ObjectiveEssential tremor (ET) prominently affects the upper-limbs during voluntary movements, but can also affect the lower-limbs, head, and chin. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of thalamus improves both clinical ratings and quantitative measures of tremor, no study has quantified effects of DBS on tremor across multiple body parts. Our objective was to quantify therapeutic effects of DBS across multiple body parts in ET.MethodsWe performed quantitative assessment of tremor in ET patients who had DBS for at least one year. We assessed tremor on and off VIM-stimulation using triaxial accelerometers on the upper-limbs, lower-limbs, head and chin during seated and standing tasks.ResultsVIM-DBS significantly reduced tremor, but there was no statistical difference in degree of tremor reduction across the measured effectors. Compared to healthy controls, ET patients treated with DBS showed significantly greater tremor power (4–8 Hz) across all effectors during seated and standing tasks.ConclusionsVIM-DBS reduced tremor in ET patients. There was no significant difference in the degree of tremor reduction across the measured effectors.SignificanceThis study provides new quantitative evidence that VIM-DBS is effective at reducing tremor across multiple parts of the body.     

Distinct perceptive pathways selected with tonic and bursting patterns of thalamic stimulation

BackgroundNovel patterns of electrical stimulation of the brain and spinal cord hold tremendous promise to improve neuromodulation therapies for diverse disorders, including tremor and pain. To date, there are limited numbers of experimental studies in human subjects to help explain how stimulation patterns impact the clinical response, especially with deep brain stimulation.We propose using novel stimulation patterns during electrical stimulation of somatosensory thalamus in awake deep brain stimulation surgeries and hypothesize that stimulation patterns will influence the sensory percept without moving the electrode.MethodsIn this study of 15 fully awake patients, the threshold of perception as well as perceptual characteristics were compared for tonic (trains of regularly-repeated pulses) and bursting stimulation patterns.ResultsIn a majority of subjects, tonic and burst percepts were located in separate, non-overlapping body regions (i.e., face vs. hand) without moving the stimulating electrode (p < 0.001; binomial test). The qualitative features of burst percepts also differed from those of tonic-evoked percepts as burst patterns were less likely to evoke percepts described as tingling (p = 0.013; Fisher’s exact test).ConclusionsBecause somatosensory thalamus is somatotopically organized, percept location can be related to anatomic thalamocortical pathways. Thus, stimulation pattern may provide a mechanism to select for different thalamocortical pathways. This added control could lead to improvements in neuromodulation - such as improved efficacy and side effect attenuation - and may also improve localization for sensory prostheses.     

Recollection and familiarity in the human thalamus

Recollection and familiarity are two distinct forms of recognition memory that differ in terms of the associative richness of the memory experience. In recollection, exposure to a previously encountered item cues the recollection of a number of contextual, temporal and other associative information. In the case of familiarity, instead, the item is recognized as previously encountered, but it does not cue any associative information. According to the dual-process theory, the memory processes that underlie recollection and familiarity are qualitatively different and this distinction is reflected in the existence of different neural substrates underlying the two processes. Thus far, research has primarily focused on distinct regions of the medial temporal lobe as implicated mostly in recollection (hippocampus) or familiarity (perirhinal cortex). Aggleton and Brown (1999) suggested extending the neuroanatomical distinction to other cortical and subcortical areas of the brain, including the thalamus. In particular, they proposed the existence of two reciprocally independent neural circuits for recollection and familiarity. The former would include the hippocampus, the fornix, the mammillary bodies and the anterior thalamic nuclei. The second would involve the mesial magnocellular portion of the mediodorsal nucleus connected to the perirhinal cortex through the ventroamygdalofugal pathway. Here we review neuropsychological evidence in experimental animals and brain-damaged individuals and functional neuroimaging evidence in healthy humans that supports Aggleton and Brown's model at the level of the thalamus. The evidence substantially supports the functional relationship between recollection processes and integrity of the thalamic anterior nuclei. Additional evidence, not predicted by the model, has been provided in favour of the reliance of recollection on the integrity of the lateral portion (parvocellular) of the mediodoral nucleus. Finally, there is sparse and controversial evidence in support of the reliance of familiarity on the integrity of the mesial portion of the mediodorsal nucleus, possibly due to neuroimaging methodological limits which did not satisfactorily distinguish between the medial and lateral portions of the mediodorsal nucleus.     

An investigation of thalamic nuclei volumes and the intrinsic thalamic structural network based on motor subtype in drug naïve patients with Parkinson's disease

IntroductionThis study aimed to investigate the alterations in thalamic nuclei volumes and the intrinsic thalamic structural network in patients with de novo Parkinson's disease (PD) based on their predominant symptoms.MethodsWe enrolled 65 patients with de novo PD (44 patients with tremor-dominant [TD] subtype and 21 patients with postural instability and gait disturbance [PIGD] subtype) and 20 healthy controls. All subjects underwent three-dimensional T1-weighted magnetic resonance imaging. The thalamic nuclei were segmented using the FreeSurfer program.ResultsWe obtained volumetric differences in the thalamic nuclei of each subtype of PD in comparison of healthy control. Volumes of the right and left suprageniculate nuclei were significantly increased, whereas that of the left parafascicular nucleus was decreased in patients with the TD subtype. Volumes of the right and left suprageniculate nuclei and right ventromedial nucleus were significantly increased, whereas those of the right and left parafascicular nuclei volumes were decreased in patients with the PIGD subtype. The measures of the intrinsic thalamic global network were not different between patients with TD PD and healthy controls. However, in patients with the PIGD subtype, the global and local efficiencies were significantly increased compared to healthy controls. Moreover, although there were no differences in thalamic volume and intrinsic thalamic global network between patients with the TD and PIGD variants, we identified significant differences in the intrinsic thalamic local network between the two groups.ConclusionsAlterations in thalamic nuclei volumes and the intrinsic thalamic network in patients with PD differed based on their predominant symptoms. These findings might be related to the underlying pathogenesis and suggest that PD is a heterogeneous syndrome.     

Outcomes of basal ganglia and thalamic cavernous malformation surgery: A meta-analysis

Surgical resection of basal ganglia (BG) and thalamic cavernous malformations (CMs) has not yet become standardized in the field of neurosurgery due to the eloquent location of these lesions and the relative paucity of literature on the subject. This review presents a consolidation of the available literature on outcomes and complication rates after surgical resection of these lesions. A systematic literature review was performed via PubMed database for articles published between 1985 and 2019. Studies comprising ≥2 patients receiving surgery for BG or thalamic CMs with available follow-up data were included. Pooled data included patient demographics, CM preoperative characteristics, and surgical outcomes Twenty studies comprising 227 patients were included for analysis. Complete resection was achieved in 94.7% (fixed-effects pooled estimate [FE]: 94.9%[91.0%–97.8%]; random-effects pooled estimate [RE]: 90.0%[79.8%–96.9%]), and hemorrhage of incompletely resected CMs occurred in 50% (FE: 55.9%[25.9%–83.6%]; RE: 55.9%[25.9%–83.6%]) of patients. Early morbidity was observed in 24.0% (FE: 24.9%[17.8%–32.6%]; RE: 24.9%[17.8%–32.6%]). At final follow-up, 67.3% (FE: 67.7%[58.8%–76.0%]; RE: 67.8%[52.2%–81.6%]) and 20.6% (FE: 20.6%[13.6%–28.6%]; RE: 20.9%[9.8%–34.9%]) had improvement and stability of preoperative symptoms, respectively. Mortality rate was 1.3% (FE: 2.3%[0.6%–5.1%]; RE: 2.3%[0.6%–5.1%]). Therefore, high cure rates with low rates of postoperative morbidity can be achieved in BG or thalamic CM surgery. Most patients had improved neurological function at final follow-up. Complete resection should be attempted to reduce rates of repeat hemorrhage.     

Physiological properties of periodontal mechanosensitive neurones in the posteromedial ventral nucleus of rat thalamus

Unitary discharges of periodontal mechanosensitive (PM) neurones responding to mechanical tooth stimulation were recorded from the posteromedial ventral nucleus (VPM) of rat thalamus. PM neurones are distributed in the ventromedial area in the rostral two-thirds of the VPM nucleus. Maxillary and mandibular tooth-sensitive neurones are arranged in dorsoventral sequence. Of the PM neurones, 36% were slowly adapting to pressure applied to the tooth and 67% were rapidly adapting. The majority of PM units were sensitive to the contralateral incisor tooth. Response magnitudes of the slowly adapting neurones varied with stimulus direction and were directionally selective to mechanical tooth stimulation. The optimal stimulus direction was labiolingual or linguolabial. Rapidly adapting neurones were directionally non-selective to tooth stimulation. The threshold for mechanical stimulation was <0.05 N. Mean response latencies evoked by electrical stimulation of the peripheral receptive fields were 4.6 ms in the slowly adapting neurones and 5.8 ms in the rapidly adapting neurones.