Clinical and Brain Morphometry Predictors of Deep Brain Stimulation Outcome in Parkinson's Disease.

Subthalamic deep brain stimulation (STN-DBS) is known to improve motor function in advanced Parkinson's disease (PD) and to enable a reduction of anti-parkinsonian medication. While the levodopa challenge test and disease duration are considered good predictors of STN-DBS outcome, other clinical and neuroanatomical predictors are less established. This study aimed to evaluate, in addition to clinical predictors, the effect of patients' individual brain topography on DBS outcome. The medical records of 35 PD patients were used to analyze DBS outcomes measured with the following scales: Part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) off medication at baseline, and at 6-months during medication off and stimulation on, use of anti-parkinsonian medication (LED), Abnormal Involuntary Movement Scale (AIMS) and Non-Motor Symptoms Questionnaire (NMS-Quest). Furthermore, preoperative brain MRI images were utilized to analyze the brain morphology in relation to STN-DBS outcome. With STN-DBS, a 44% reduction in the UPDRS-III score and a 43% decrease in the LED were observed (p<0.001). Dyskinesia and non-motor symptoms decreased significantly [median reductions of 78,6% (IQR 45,5%) and 18,4% (IQR 32,2%) respectively, p=0.001 - 0.047]. Along with the levodopa challenge test, patients' age correlated with the observed DBS outcome measured as UPDRS-III improvement (ρ= -0.466 - -0.521, p<0.005). Patients with greater LED decline had lower grey matter volumes in left superior medial frontal gyrus, in supplementary motor area and cingulum bilaterally. Additionally, patients with greater UPDRS-III score improvement had lower grey matter volume in similar grey matter areas. These findings remained significant when adjusted for sex, age, baseline LED and UPDRS scores respectively and for total intracranial volume (p=0.0041- 0.001). However, only the LED decrease finding remained significant when the analyses were further controlled for stimulation amplitude. It appears that along with the clinical predictors of STN-DBS outcome, individual patient topographic differences may influence DBS outcome. Clinical Trial Registration Number: NCT06095245, registration date October 23, 2023, retrospectively registered.

Thalamic pain: anatomical and physiological indices of prediction.

Thalamic pain is a severe and treatment-resistant type of central pain that may develop after thalamic stroke. Lesions within the ventrocaudal regions of the thalamus carry the highest risk to develop pain, but its emergence in individual patients remains impossible to predict. Because damage to the spino-thalamo-cortical system is a crucial factor in the development of central pain, in this study we combined detailed anatomical atlas-based mapping of thalamic lesions and assessment of spinothalamic integrity using quantitative sensory analysis and laser-evoked potentials in 42 thalamic stroke patients, of whom 31 had developed thalamic pain. More than 97% of lesions involved an area between 2 and 7 mm above the anterior-posterior commissural plane. Although most thalamic lesions affected several nuclei, patients with central pain showed maximal lesion convergence on the anterior pulvinar nucleus (a major spinothalamic target) while the convergence area lay within the ventral posterior lateral nucleus in pain-free patients. Both involvement of the anterior pulvinar nucleus and spinothalamic dysfunction (nociceptive thresholds, laser-evoked potentials) were significantly associated with the development of thalamic pain, whereas involvement of ventral posterior lateral nucleus and lemniscal dysfunction (position sense, graphaesthesia, pallaesthesia, stereognosis, standard somatosensory potentials) were similarly distributed in patients with or without pain. A logistic regression model combining spinothalamic dysfunction and anterior pulvinar nucleus involvement as regressors had 93% sensitivity and 87% positive predictive value for thalamic pain. Lesion of spinothalamic afferents to the posterior thalamus appears therefore determinant to the development of central pain after thalamic stroke. Sorting out of patients at different risks of developing thalamic pain may be achievable at the individual level by combining lesion localization and functional investigation of the spinothalamic system. As the methods proposed here do not need complex manipulations, they can be added to routine patients' work up, and the results replicated by other investigators in the field.

[Imaging of brain changes in chronic pain]. / Krooniseen kipuun liittyvien aivomuutosten kuvantaminen.

Modern methods of brain imaging have enabled objective measurements of functional and structural brain changes associated with chronic pain conditions. According to recent investigations, chronic pain is not only associated with abnormally strong or prolonged activity of regions processing acute pain, but also with activation of brain networks that are characteristic for each pain state, changes in cortical remodeling, as well as local reduction of grey matter in several regions of the brain. Brain changes associated with chronic pain facilitate the understanding of mechanisms of various chronic pain conditions.

Aberrant temporal and spatial brain activity during rest in patients with chronic pain.

In the absence of external stimuli, human hemodynamic brain activity displays slow intrinsic variations. To find out whether such fluctuations would be altered by persistent pain, we asked 10 patients with unrelenting chronic pain of different etiologies and 10 sex- and age-matched control subjects to rest with eyes open during 3-T functional MRI. Independent component analysis was used to identify functionally coupled brain networks. Time courses of an independent component comprising the insular cortices of both hemispheres showed stronger spectral power at 0.12 to 0.25 Hz in patients than in control subjects, with the largest difference at 0.16 Hz. A similar but weaker effect was seen in the anterior cingulate cortex, whereas activity of the precuneus and early visual cortex, used as a control site, did not differ between the groups. In the patient group, seed point-based correlation analysis revealed altered spatial connectivity between insulae and anterior cingulate cortex. The results imply both temporally and spatially aberrant activity of the affective pain-processing areas in patients suffering from chronic pain. The accentuated 0.12- to 0.25-Hz fluctuations in the patient group might be related to altered activity of the autonomic nervous system.

Subtemporal approach for cavernous sinus meningiomas - Simple and effective.

Background: Over the past few decades, there has been a paradigm shift in treatment strategy for cavernous sinus meningiomas (CSMs). Preserving neurological function and cranial nerve (CN) decompression have become the primary goal of cases eligible for surgical treatment. Extensive skull base dissection and drilling can be avoided by approaching these lesions through a subtemporal route. Methods: We describe the subtemporal approach in a step-by-step fashion illustrating its advantages and pitfalls through and illustrative case. Results: The subtemporal approach to CSMs is a valuable alternative for CN decompression and maximal safe resection. We describe the technique in comparison to classical skull base approaches. Although rare, recurrence after adjuvant maximal radiation is possible leaving reoperation as the only treatment option. Conclusion: The subtemporal approach offers a less invasive alternative for initial and redo CN decompression and successful symptom control in patients suffering from CSM.

Real-Life Experience on Directional Deep Brain Stimulation in Patients with Advanced Parkinson's Disease.

Directional deep brain stimulation (dDBS) is preferred by patients with advanced Parkinson's disease (PD) and by programming neurologists. However, real-life data of dDBS use is still scarce. We reviewed the clinical data of 53 PD patients with dDBS to 18 months of follow-up. Directional stimulation was favored in 70.5% of dDBS leads, and single segment activation (SSA) was used in 60% of dDBS leads. Current with SSA was significantly lower than with other stimulation types. During the 6-month follow-up, a 44% improvement in the Unified Parkinson's Disease Rating Scale (UPDRS-III) points and a 43% decline in the levodopa equivalent daily dosage (LEDD) was observed. After 18 months of follow-up, a 35% LEDD decrease was still noted. The Hoehn and Yahr (H&Y) stages and scores on item no 30 "postural stability" in UPDRS-III remained lower throughout the follow-up compared to baseline. Additionally, dDBS relieved non-motor symptoms during the 6 months of follow-up. Patients with bilateral SSA had similar clinical outcomes to those with other stimulation types. Directional stimulation appears to effectively reduce both motor and non-motor symptoms in advanced PD with minimal adverse effects in real-life clinical care.

Removal of imaging artifacts in EEG during simultaneous EEG/fMRI recording: reconstruction of a high-precision artifact template.

Functional magnetic resonance imaging (fMRI) induces coarse electromagnetic artifacts into the simultaneously recorded electroencephalogram (EEG). The problem in the signal processing framework is to model the underlying artifact, which is time-continuous, as a discretely sampled waveform. To build up an artifact template, the EEG sampling in relation to the phase of the imaging artifacts should be known. If the MR scanner and EEG sampling are not synchronized, this relation is not constant and a time adjustment of the template with the individual slice artifacts becomes essential. However, lack of synchrony opens up the possibility for approximating a high-precision and continuous artifact template by using the samples acquired from slightly different phases of the induced artifact. In this work, methodology for reconstructing such a template was developed using EEG data recorded simultaneously with fMRI at 3 T. A time-continuous cubic spline approximation was used as the slice artifact model. To overcome the problem of non-synchronized clocks, two methods were proposed to find the starting times of the slice artifacts at sub-sample precision. This approach yielded efficient imaging artifact reduction: the amplitude at the dominant frequency was attenuated by 55-70 dB (the median values over EEG channels) and the residual signal, at its best, was practically free from sharp transients even with 5000 Hz sampling frequency and without further residual artifact reduction algorithms. The presented methods may reduce the need for post-processing of the residual signal after the template subtraction and may help to preserve the EEG bandwidth.

Central processing of tactile and nociceptive stimuli in complex regional pain syndrome.

OBJECTIVE: Patients with complex regional pain syndrome (CRPS) suffer from continuous regional limb pain and from hyperesthesia to touch and pain. To better understand the pathophysiological mechanisms underlying the hyperesthesia of CRPS patients, we investigated their cortical processing of touch and acute pain. METHODS: Cortical responses to tactile stimuli applied to the thumbs, index and little fingers (D1, D2, and D5) and nociceptive stimuli delivered to dorsa of the hands were recorded with a whole-scalp neuromagnetometer from eight chronic CRPS patients and from nine healthy control subjects. RESULTS: In the patients, primary somatosensory (SI) cortex activation to tactile stimulation of D2 was significantly stronger, and the D1-D5 distance in SI was significantly smaller for the painful hand compared to the healthy hand. The PPC activation to tactile stimulation was significantly weaker in the patients than in the control subjects. To nociceptive stimulation with equal laser energy, the secondary somatosensory (SII) cortices and posterior parietal cortex (PPC) were similarly activated in both groups. The PPC source strength correlated with the pain rating in the control subjects, but not in the patients. CONCLUSIONS: The enhanced SI activation in hyperesthetic CRPS patients may reflect central sensitization to touch. The decreased D1-D5 distance implies permanent changes in SI hand representations in chronic CRPS. The defective PPC activation could be associated with the neglect-like symptoms of the patients. As the SII and PPC responses were not enhanced in the CRPS patients, other brain areas are likely to contribute to the observed hyperesthesia to pain. SIGNIFICANCE: Our results indicate changes of somatosensory processing at cortical level in CRPS.

Effects of interstimulus interval on cortical responses to painful laser stimulation.

Short laser pulses applied to the skin are used increasingly in both clinical and basic assessment of nociceptive brain mechanisms. The authors aimed to characterize further the cortical responses to noxious laser stimuli and to define the interstimulus interval (ISI) for the optimum signal-to-noise ratio during a fixed measurement time. Three hundred six-channel whole-scalp magnetoencephalographic (MEG) and midline EEG signals were recorded from nine healthy adults during painful thulium laser stimulation. The stimuli were delivered on the dorsum of the left hand at ISIs of 0.5, 1, 2, 4, 8, and 16 seconds. The MEG responses peaked at 160 to 195 msec around the contralateral primary somatosensory (SI) cortex, at 150 to 190 msec in the contralateral secondary somatosensory (SII) cortex, and at 160 to 205 msec in the ipsilateral SII cortex. The simultaneously measured electrical vertex potentials peaked at 190 to 230 msec and 310 to 330 msec (N200-P300). All these responses showed rather similar refractory times: The amplitudes increased strongly from 0.5 to 4-second ISIs and thereafter saturated at ISIs of 8 to 16 seconds. On the basis of the time constants of the recovery cycles, the optimum ISI for obtaining the best signal-to-noise ratio for laser-evoked MEG and EEG responses during a fixed measurement interval is 4 to 5 seconds.

A Functional MRI Study of Happy and Sad Emotions in Music with and without Lyrics.

Musical emotions, such as happiness and sadness, have been investigated using instrumental music devoid of linguistic content. However, pop and rock, the most common musical genres, utilize lyrics for conveying emotions. Using participants' self-selected musical excerpts, we studied their behavior and brain responses to elucidate how lyrics interact with musical emotion processing, as reflected by emotion recognition and activation of limbic areas involved in affective experience. We extracted samples from subjects' selections of sad and happy pieces and sorted them according to the presence of lyrics. Acoustic feature analysis showed that music with lyrics differed from music without lyrics in spectral centroid, a feature related to perceptual brightness, whereas sad music with lyrics did not diverge from happy music without lyrics, indicating the role of other factors in emotion classification. Behavioral ratings revealed that happy music without lyrics induced stronger positive emotions than happy music with lyrics. We also acquired functional magnetic resonance imaging data while subjects performed affective tasks regarding the music. First, using ecological and acoustically variable stimuli, we broadened previous findings about the brain processing of musical emotions and of songs versus instrumental music. Additionally, contrasts between sad music with versus without lyrics recruited the parahippocampal gyrus, the amygdala, the claustrum, the putamen, the precentral gyrus, the medial and inferior frontal gyri (including Broca's area), and the auditory cortex, while the reverse contrast produced no activations. Happy music without lyrics activated structures of the limbic system and the right pars opercularis of the inferior frontal gyrus, whereas auditory regions alone responded to happy music with lyrics. These findings point to the role of acoustic cues for the experience of happiness in music and to the importance of lyrics for sad musical emotions.

Motor cortex dysfunction in complex regional pain syndrome.

OBJECTIVE: Most patients with complex regional pain syndrome (CRPS) exhibit debilitating motor symptoms. The effect of continuous pain on motor system in CRPS, however, is not well known. We searched for signs of motor cortex dysfunction in chronic CRPS type 1 patients with motor impairment. METHODS: We recorded rhythmic brain activity with magnetoencephalography (MEG) during noxious thulium-laser stimulation of both hands in eight CRPS patients and eight control subjects. We measured excitability of the motor cortex by monitoring the reactivity of the approximately 20-Hz motor cortex rhythm to laser stimuli. The reactivity was defined as a sum of the stimulus-induced suppression and the subsequent rebound of the approximately 20-Hz rhythm. RESULTS: In CRPS, the reactivity of the approximately 20-Hz rhythm in the hemisphere contralateral to the painful hand was significantly weaker than in control subjects. The reactivity correlated with the mean level of the spontaneous pain (r=-0.64, P=0.04). Suppression of the approximately 20-Hz rhythm correlated with the grip strength in the painful hand (r=0.66, P=0.04). CONCLUSION: Continuous pain in CRPS is associated with attenuated motor cortex reactivity. SIGNIFICANCE: Abnormal motor cortex reactivity may be linked with motor dysfunction of the affected hand in CRPS.

Cortical reorganization in primary somatosensory cortex in patients with unilateral chronic pain.

UNLABELLED: Bodily representations of the primary somatosensory (SI) cortex are constantly modified according to sensory input. Increased input due to training as well as loss of input due to deafferentation are reflected as changes in the extent of cortical representations. Recent studies in complex regional pain syndrome (CRPS) patients have indicated that the chronic pain itself is associated with cortical reorganization. However, it is unclear whether the observed reorganization is specific for CRPS or if it can be detected also in other types of chronic pain. We therefore searched for signs of cortical reorganization in a group of 8 patients who suffered from chronic pain associated with herpes simplex virus infections. The pain was widespread but restricted to unilateral side of the body and included the upper limb. We recorded neuromagnetic responses to tactile stimulation of fingers of both hands in patients and in a group of healthy, matched control subjects. In the patients, the distance between the thumb (D1) and little finger (D5) representations in SI cortex was statistically significantly smaller in the hemisphere contralateral to painful side than in the hemisphere contralateral to healthy side. In the control subjects, the D1-D5 distance was the same in both hemispheres. PERSPECTIVE: The present results indicate that cortical reorganization occurs in chronic neuropathic pain patients even without peripheral nerve damage. It is possible that cortical reorganization is related to chronic pain, regardless of its etiology. Causality between reorganization and chronic pain should be examined further to develop therapeutic approaches for chronic pain.

Changes in brain function and morphology in patients with recurring herpes simplex virus infections and chronic pain.

A recent study described for the first time a patient group that suffered from spontaneous chronic pain and from recurrent herpes simplex virus (HSV) infections. The patients had pain in widespread areas on one side of the body and were--due to subtle immunological abnormalities--susceptible to HSV infections. Although the clinical features of the pain suggested involvement of the central nervous system, supporting evidence for this was lacking. The objective of this study was to search for changes in the central nervous system that could account for the chronic pain in these patients. We monitored the central processing of pain and touch in eight patients and 11 healthy control subjects, who received painful heat and innocuous tactile stimuli to the hands during functional magnetic resonance imaging. Possible changes in the gray matter density of the brain were assessed with voxel-based morphometry. We found functional changes in the patients' central pain circuitry: activation to heat pain was weaker than in control subjects in the insular cortices, anterior cingulate cortex (ACC), and thalamus, while the activations to innocuous tactile stimuli were similar in both groups. Gray matter density was decreased in the patients' frontal and prefrontal cortices and in the ACC. The observed functional and structural changes in the central pain circuitry, together with the clinical features of the chronic pain support the hypothesis for central involvement in the development of chronic pain in these patients.

Removal of ballistocardiogram artifact from EEG data acquired in the MRI scanner: selection of ICA components.

The removal of ballistocardiogram (BCG) artifact from the EEG recorded in the MRI scanner is challenging. Few studies have utilized independent component analysis (ICA) in this task. A drawback of ICA has been the proper selection of the BCG related components. The key idea in this work is to use the difference between the power spectrum of the artifact-processed data and the spectrum of data recorded outside the scanner as a cost function in the selection of the BCG related independent components. Forward floating selection algorithm was implemented to find the components to minimize this criterion. Also, the typical component selection criteria based on the correlation with electrocardiogram (ECG) signal and on explained variance were compared in this respect. The correlation criterion was least successful leaving considerable residual artifact in the signal. With the first few removed components the variance criterion performed as well as the minimum spectral difference criterion. With the variance criterion alone, however, the number of the components to be removed cannot be determined. The suggested methods may provide objective means to validate residual artifact or the possible loss of physiological signal due to artifact removal and to help selecting the proper artifact-related components.