A partial loss of effectiveness of deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM) has been reported in some patients with essential tremor (ET), possibly due to ...habituation to permanent stimulation. This study focused on the evolution of VIM local-field potentials (LFPs) data over time to assess the long-term feasibility of closed-loop therapy based on thalamic activity. We performed recordings of thalamic LFPs in 10 patients with severe ET using the ACTIVA™ PC + S (Medtronic plc.) allowing both recordings and stimulation in the same region. Particular attention was paid to describing the evolution of LFPs over time from 3 to 24 months after surgery when the stimulation was Off. We demonstrated a significant decrease in high-beta LFPs amplitude during movements inducing tremor in comparison to the rest condition 3 months after surgery (1.91 ± 0.89 at rest vs. 1.27 ± 1.37 µV
/Hz during posture/action for N = 8/10 patients; p = 0.010), 12 months after surgery (2.92 ± 1.75 at rest vs. 2.12 ± 1.78 µV
/Hz during posture/action for N = 7/10 patients; p = 0.014) and 24 months after surgery (2.32 ± 0.35 at rest vs 0.75 ± 0.78 µV
/Hz during posture/action for 4/6 patients; p = 0.017). Among the patients who exhibited a significant decrease of high-beta LFP amplitude when stimulation was Off, this phenomenon was observed at least twice during the follow-up. Although the extent of this decrease in high-beta LFPs amplitude during movements inducing tremor may vary over time, this thalamic biomarker of movement could potentially be usable for closed-loop therapy in the long term.
Many voxel-based morphometry (VBM) studies have found abnormalities in gray matter density (GMD) in obsessive-compulsive disorder (OCD). Here, we performed a quantitative meta-analysis of VBM studies ...contrasting OCD patients with healthy controls (HC). A literature search identified 10 articles that included 343 OCD patients and 318 HC. Anatomic likelihood estimation meta-analyses were performed to assess GMD changes in OCD patients relative to HC. GMD was smaller in parieto-frontal cortical regions, including the supramarginal gyrus, the dorsolateral prefrontal cortex, and the orbitofrontal cortex, and greater in the basal ganglia (putamen) and the anterior prefrontal cortex in OCD patients relative to HC. No significant differences were found between children and adults. Our findings indicate differences in GMD in parieto-frontal areas and the basal ganglia between OCD patients and HC. We conclude that structural abnormalities within the prefrontal-basal ganglia network are involved in OCD pathophysiology.
Lack of insight, i.e., unawareness of one's mental illness, is frequently encountered in psychiatric conditions. Insight is the capacity to recognize (psychical insight) and accept one's mental ...illness (emotional insight). Insight growth necessitates developing an objective perspective on one's subjective pathological experiences. Therefore, insight has been posited to require undamaged self-reflexion and cognitive perspective-taking capacities. These enable patients to look objectively at themselves from the imagined perspective of someone else. Preserved theory-of-mind performances have been reported to positively impact insight in psychosis. However, some patients with schizophrenia or obsessive-compulsive disorders, although recognizing their mental disease, are still not convinced of this and do not accept it. Hence, perspective-taking explains psychical insight (recognition) but not emotional insight (acceptance). Here, we propose a new conceptual model. We hypothesize that insight growth relies upon the association of intact self-reflexion and empathic capacities. Empathy (feeling into someone else) integrates heterocentered visuo-spatial perspective (feeling
), embodiment, affective (
into) and cognitive processes, leading to internally experience the other's thought. We posit that this subjective experience enables to better understand the other's thought about oneself and to affectively adhere to this. We propose that the process of objectification, resulting from empathic heterocentered, embodiment, and cognitive processes, generates an objective viewpoint on oneself. It enables to recognize one's mental illness and positively impacts psychical insight. The process of subjectification, resulting from empathic affective processes, enables to accept one's illness and positively impacts emotional insight. That is, affectively experiencing the thought of another person about oneself reinforces the adhesion of the emotional system to the objective recognition of the disease. Applying our model to different psychiatric disorders, we predict that the negative effect of impaired self-reflexion and empathic capacities on insight is a transnosographic state and that endophenotypical differences modulate this common state, determining a psychiatric disease as specific.
Early-onset torsion dystonia (TOR1A/DYT1) is a devastating hereditary motor disorder whose pathophysiology remains unclear. Studies in transgenic mice suggested abnormal cholinergic transmission in ...the putamen, but this has not yet been demonstrated in humans. The role of the cerebellum in the pathophysiology of the disease has also been highlighted but the involvement of the intrinsic cerebellar cholinergic system is unknown. In this study, cholinergic neurons were imaged using PET with 18F-fluoroethoxybenzovesamicol, a radioligand of the vesicular acetylcholine transporter (VAChT). Here, we found an age-related decrease in VAChT expression in the posterior putamen and caudate nucleus of DYT1 patients versus matched controls, with low expression in young but not in older patients. In the cerebellar vermis, VAChT expression was also significantly decreased in patients versus controls, but independently of age. Functional connectivity within the motor network studied in MRI and the interregional correlation of VAChT expression studied in PET were also altered in patients. These results show that the cholinergic system is disrupted in the brain of DYT1 patients and is modulated over time through plasticity or compensatory mechanisms.
Deciding between different voluntary movements implies a continuous control of the competition between potential actions. Many theories postulate a leading role of prefrontal cortices in this ...executive function, but strong evidence exists that a motor region like the primary motor cortex (M1) is also involved, possibly
inhibitory mechanisms. This was already shown during the pre-movement decision period, but not after movement onset. For this pilot experiment we designed a new task compatible with the dynamics of post-onset control to study the silent period (SP) duration, a pause in electromyographic activity after single-pulse transcranial magnetic stimulation that reflects inhibitory mechanisms. A careful analysis of the SP during the ongoing movement indicates a gradual increase in inhibitory mechanisms with the level of competition, consistent with an increase in mutual inhibition between alternative movement options. However, we also observed a decreased SP duration for high-competition trials associated with change-of-mind inflections in their trajectories. Our results suggest a new post-onset adaptive process that consists in a transient reduction of GABAergic inhibition within M1 for highly conflicting situations. We propose that this reduced inhibition softens the competition between concurrent motor options, thereby favoring response vacillation, an adaptive strategy that proved successful at improving behavioral performance.
Repetitive transcranial magnetic stimulation (rTMS) has proven to be an efficient treatment option for patients with treatment-resistant depression (TRD). However, the success rate of this method is ...still low, and the treatment outcome is unpredictable. The objective of this study was to explore clinical and structural neuroimaging factors as potential biomarkers of the efficacy of high-frequency (HF) rTMS (20 Hz) over the left dorso-lateral pre-frontal cortex (DLPFC).
We analyzed the records of 131 patients with mood disorders who were treated with rTMS and were assessed at baseline at the end of the stimulation and at 1 month after the end of the treatment. The response is defined as a 50% decrease in the MADRS score between the first and the last assessment. Each of these patients underwent a T1 MRI scan of the brain, which was subsequently segmented with FreeSurfer. Whole-brain analyses Query, Design, Estimate, Contrast (QDEC) were conducted and corrected for multiple comparisons. Additionally, the responder status was also analyzed using binomial multivariate regression models. The explored variables were clinical and anatomical features of the rTMS target obtained from T1 MRI: target-scalp distance, DLPFC gray matter thickness, and various cortical measures of interest previously studied.
The results of a binomial multivariate regression model indicated that depression type (
= 0.025), gender (
= 0.010), and the severity of depression (
= 0.027) were found to be associated with response to rTMS. Additionally, the resistance stage showed a significant trend (
= 0.055). Whole-brain analyses on volume revealed that the average volume of the left part of the superior frontal and the caudal middle frontal regions is associated with the response status. Other MRI-based measures are not significantly associated with response to rTMS in our population.
In this study, we investigated the clinical and neuroimaging biomarkers associated with responsiveness to high-frequency rTMS over the left DLPFC in a large sample of patients with TRD. Women, patients with bipolar depressive disorder (BDD), and patients who are less resistant to HF rTMS respond better. Responders present a lower volume of the left part of the superior frontal gyrus and the caudal middle frontal gyrus. These findings support further investigation into the use of clinical variables and structural MRI as possible biomarkers of rTMS treatment response.
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