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Religious fundamentalism, characterized by rigid adherence to a set of beliefs putatively revealing inerrant truths, is ubiquitous across cultures and has a global impact on society. Understanding the psychological and neurobiological processes producing religious fundamentalism may inform a variety of scientific, sociological, and cultural questions. Research indicates that brain damage can alter religious fundamentalism. However, the precise brain regions involved with these changes remain unknown. Here, we analyzed brain lesions associated with varying levels of religious fundamentalism in two large datasets from independent laboratories. Lesions associated with greater fundamentalism were connected to a specific brain network with nodes in the right orbitofrontal, dorsolateral prefrontal, and inferior parietal lobe. This fundamentalism network was strongly right hemisphere lateralized and highly reproducible across the independent datasets (r = 0.82) with cross-validations between datasets. To explore the relationship of this network to lesions previously studied by our group, we tested for similarities to twenty-one lesion-associated conditions. Lesions associated with confabulation and criminal behavior showed a similar connectivity pattern as lesions associated with greater fundamentalism. Moreover, lesions associated with poststroke pain showed a similar connectivity pattern as lesions associated with lower fundamentalism. These findings are consistent with the current understanding of hemispheric specializations for reasoning and lend insight into previously observed epidemiological associations with fundamentalism, such as cognitive rigidity and outgroup hostility.
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Red Nerviosa , Humanos , Masculino , Femenino , Red Nerviosa/fisiopatología , Red Nerviosa/patología , Persona de Mediana Edad , Encéfalo/fisiopatología , Encéfalo/patología , Adulto , Religión , Imagen por Resonancia Magnética , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , AncianoRESUMEN
OBJECTIVE: Alice in Wonderland syndrome (AIWS) profoundly affects human perception of size and scale, particularly regarding one's own body and the environment. Its neuroanatomical basis has remained elusive, partly because brain lesions causing AIWS can occur in different brain regions. Here, we aimed to determine if brain lesions causing AIWS map to a distributed brain network. METHODS: A retrospective case-control study analyzing 37 cases of lesion-induced AIWS identified through systematic literature review was conducted. Using resting-state functional connectome data from 1,000 healthy individuals, the whole-brain connections of each lesion were estimated and contrasted with those from a control dataset comprising 1,073 lesions associated with 25 other neuropsychiatric syndromes. Additionally, connectivity findings from lesion-induced AIWS cases were compared with functional neuroimaging results from 5 non-lesional AIWS cases. RESULTS: AIWS-associated lesions were located in various brain regions with minimal overlap (≤33%). However, the majority of lesions (≥85%) demonstrated shared connectivity to the right extrastriate body area, known to be selectively activated by viewing body part images, and the inferior parietal cortex, involved in size and scale judgements. This pattern was uniquely characteristic of AIWS when compared with other neuropsychiatric disorders (family-wise error-corrected p < 0.05) and consistent with functional neuroimaging observations in AIWS due to nonlesional causes (median correlation r = 0.56, interquartile range 0.24). INTERPRETATION: AIWS-related perceptual distortions map to one common brain network, encompassing regions critical for body representation and size-scale processing. These findings lend insight into the neuroanatomical localization of higher-order perceptual functions, and may inform future therapeutic strategies for perceptual disorders. ANN NEUROL 2024.
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Characterizing human thalamocortical network is fundamental for understanding a vast array of human behaviors since the thalamus plays a central role in cortico-subcortical communication. Over the past few decades, advances in functional magnetic resonance imaging have allowed for spatial mapping of intrinsic resting-state functional connectivity (RSFC) between both cortical regions and in cortico-subcortical networks. Despite these advances, identifying the electrophysiological basis of human thalamocortical network architecture remains challenging. By leveraging stereoelectroencephalography electrodes temporarily implanted into distributed cortical regions and the anterior nucleus of the thalamus (ANT) of 10 patients with refractory focal epilepsy, we tested whether ANT stimulation evoked cortical potentials align with RSFC from the stimulation site, derived from a normative functional connectome (n = 1000). Our study identifies spatial convergence of ANT stimulation evoked cortical potentials and normative RSFC. Other than connections to the Papez circuit, the ANT was found to be closely connected to several distinct higher-order association cortices, including the precuneus, angular gyrus, dorsal lateral prefrontal cortex, and anterior insula. Remarkably, we found that the spatial distribution and magnitude of cortical-evoked responses to single-pulse electrical stimulation of the ANT aligned with the spatial pattern and strength of normative RSFC of the stimulation site. The present study provides electrophysiological evidence that stimulation evoked electrical activity flows along intrinsic brain networks connected on a thalamocortical level.
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Núcleos Talámicos Anteriores , Epilepsias Parciales , Humanos , Corteza Cerebral/fisiología , Lóbulo Parietal , Imagen por Resonancia Magnética , Estimulación Eléctrica , Potenciales Evocados/fisiologíaRESUMEN
Structural brain lesions are the most common cause of adult-onset epilepsy. The lesion location may contribute to the risk for epileptogenesis, but whether specific lesion locations are associated with a risk for secondary seizure generalization from focal to bilateral tonic-clonic seizures, is unknown. We identified patients with a diagnosis of adult-onset epilepsy caused by an ischemic stroke or a tumor diagnosed at the Turku University Hospital in 2004-2017. Lesion locations were segmented on patient-specific MR imaging and transformed to a common brain atlas (MNI space). Both region-of-interest analyses (intersection with the cortex, hemisphere, and lobes) and voxel-wise analyses were conducted to identify the lesion locations associated with focal to bilateral tonic-clonic compared to focal seizures. We included 170 patients with lesion-induced epilepsy (94 tumors, 76 strokes). Lesions predominantly localized in the cerebral cortex (OR 2.50, 95% C.I. 1.21-5.15, p = .01) and right hemisphere (OR 2.22, 95% C.I. 1.17-4.20, p = .01) were independently associated with focal to bilateral tonic-clonic seizures. At the lobar-level, focal to bilateral tonic-clonic seizures were associated with lesions in the right frontal cortex (OR 4.41, 95% C.I. 1.44-13.5, p = .009). No single voxels were significantly associated with seizure type. These effects were independent of lesion etiology. Our results demonstrate that lesion location is associated with the risk for secondary generalization of epileptic seizures. These findings may contribute to identifying patients at risk for focal to bilateral tonic-clonic seizures.
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Epilepsia , Neoplasias , Accidente Cerebrovascular , Adulto , Humanos , Convulsiones/diagnóstico por imagen , Convulsiones/etiología , Epilepsia/diagnóstico por imagen , Epilepsia/etiología , Encéfalo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , ElectroencefalografíaRESUMEN
OBJECTIVE: Here, we report a retrospective, single-center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug-resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking. METHODS: Five patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead-DBS software. Local field potentials recorded over 12-18 months were tracked, and changes in power were associated with patient events, medication changes, and stimulation. We utilized a combination of lead localization, in-clinic broadband LFP recordings, real-time LFP response to stimulation, and chronic recordings to guide DBS programming. RESULTS: Four patients (80%) experienced a >50% reduction in seizure frequency, whereas one patient had no significant reduction. Peaks in the alpha and/or beta frequency range were observed in the thalamic LFPs of each patient. Stimulation suppressed these LFP peaks in a dose-dependent manner. Chronic timeline data identified changes in LFP amplitude associated with stimulation, seizure occurrences, and medication changes. We also noticed a circadian pattern of LFP amplitudes in all patients. Button-presses during seizure events via a mobile application served as a digital seizure diary and were associated with elevations in LFP power. SIGNIFICANCE: We describe an initial cohort of patients with DRE utilizing a novel sensing DBS device to characterize potential LFP biomarkers of epilepsy that may be associated with seizure control after DBS in DRE. We also present a new workflow utilizing the Percept device that may optimize DBS programming using real-time and chronic LFP recording.
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Estimulación Encefálica Profunda , Epilepsia Refractaria , Epilepsia , Humanos , Estimulación Encefálica Profunda/efectos adversos , Estudios Retrospectivos , Estudios de Factibilidad , Epilepsia Refractaria/terapia , Epilepsia Refractaria/etiología , Epilepsia/terapia , Convulsiones/etiología , BiomarcadoresRESUMEN
Deep brain stimulation is an effective treatment for Parkinson's disease but can be complicated by side-effects such as cognitive decline. There is often a delay before this side-effect is apparent and the mechanism is unknown, making it difficult to identify patients at risk or select appropriate deep brain stimulation settings. Here, we test whether connectivity between the stimulation site and other brain regions is associated with cognitive decline following deep brain stimulation. First, we studied a unique patient cohort with cognitive decline following subthalamic deep brain stimulation for Parkinson's disease (n = 10) where reprogramming relieved the side-effect without loss of motor benefit. Using resting state functional connectivity data from a large normative cohort (n = 1000), we computed connectivity between each stimulation site and the subiculum, an a priori brain region functionally connected to brain lesions causing memory impairment. Connectivity between deep brain stimulation sites and this same subiculum region was significantly associated with deep brain stimulation induced cognitive decline (P < 0.02). We next performed a data-driven analysis to identify connections most associated with deep brain stimulation induced cognitive decline. Deep brain stimulation sites causing cognitive decline (versus those that did not) were more connected to the anterior cingulate, caudate nucleus, hippocampus, and cognitive regions of the cerebellum (PFWE < 0.05). The spatial topography of this deep brain stimulation-based circuit for cognitive decline aligned with an a priori lesion-based circuit for memory impairment (P = 0.017). To begin translating these results into a clinical tool that might be used for deep brain stimulation programming, we generated a 'heat map' in which the intensity of each voxel reflects the connectivity to our cognitive decline circuit. We then validated this heat map using an independent dataset of Parkinson's disease patients in which cognitive performance was measured following subthalamic deep brain stimulation (n = 33). Intersection of deep brain stimulation sites with our heat map was correlated with changes in the Mattis dementia rating scale 1 year after lead implantation (r = 0.39; P = 0.028). Finally, to illustrate how this heat map might be used in clinical practice, we present a case that was flagged as 'high risk' for cognitive decline based on intersection of the patient's deep brain stimulation site with our heat map. This patient had indeed experienced cognitive decline and our heat map was used to select alternative deep brain stimulation parameters. At 14 days follow-up the patient's cognition improved without loss of motor benefit. These results lend insight into the mechanism of deep brain stimulation induced cognitive decline and suggest that connectivity-based heat maps may help identify patients at risk and who might benefit from deep brain stimulation reprogramming.
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Disfunción Cognitiva , Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Encéfalo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/terapia , Estimulación Encefálica Profunda/efectos adversos , Estimulación Encefálica Profunda/métodos , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapiaRESUMEN
Sleep spindles (8 - 16 Hz) are transient electrophysiological events during non-rapid eye movement sleep. While sleep spindles are routinely observed in the cortex using scalp electroencephalography (EEG), recordings of their thalamic counterparts have not been widely studied in humans. Based on a few existing studies, it has been hypothesized that spindles occur as largely local phenomena. We investigated intra-thalamic and thalamocortical spindle co-occurrence, which may underlie thalamocortical communication. We obtained scalp EEG and thalamic recordings from 7 patients that received bilateral deep brain stimulation (DBS) electrodes to the anterior thalamus for the treatment of drug resistant focal epilepsy. Spindles were categorized into subtypes based on their main frequency (i.e., slow (10±2 Hz) or fast (14±2 Hz)) and their level of thalamic involvement (spanning one channel, or spreading uni- or bilaterally within the thalamus). For the first time, we contrasted observed spindle patterns with permuted data to estimate random spindle co-occurrence. We found that multichannel spindle patterns were systematically coordinated at the thalamic and thalamocortical level. Importantly, distinct topographical patterns of thalamocortical spindle overlap were associated with slow and fast subtypes of spindles. These observations provide further evidence for coordinated spindle activity in thalamocortical networks.
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Núcleos Talámicos Anteriores , Epilepsia Refractaria , Humanos , Corteza Cerebral/fisiología , Sueño/fisiología , Electroencefalografía , Tálamo/fisiología , Epilepsia Refractaria/terapiaRESUMEN
Deep brain stimulation (DBS) has shown to have antidepressant effects in both human trials and animal studies. However, the optimal target and the underlying therapeutic mechanisms remain to be determined. In this study, we investigated if high frequency (HF) DBS in the dorsal peduncular cortex (DPC) alleviates depressive-like behavior in an experimental model of depression. Surprisingly, HF DBS in the DPC caused acute induction of seizures in ~40% of animals stimulated with clinically relevant stimulation parameters. Reducing the stimulation's amplitude by 50% did not alter seizure occurrence. Electroencephalographic (EEG) recordings showed seizures up to Racine stage IV lasting up to 4â¯min after cessation of stimulation. We conclude that HF DBS in the DPC is not suitable for mood-related experiments in rats but could be a potential model for seizure induction.
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Corteza Cerebral/fisiopatología , Pedúnculo Cerebral/fisiopatología , Estimulación Encefálica Profunda/efectos adversos , Depresión/fisiopatología , Modelos Animales de Enfermedad , Convulsiones/fisiopatología , Animales , Estimulación Encefálica Profunda/métodos , Depresión/terapia , Conducta Exploratoria/fisiología , Masculino , Ratas , Ratas Sprague-Dawley , Convulsiones/etiologíaRESUMEN
Despite the use of first-choice anti-epileptic drugs and satisfactory seizure outcome rates after resective epilepsy surgery, a considerable percentage of patients do not become seizure free. ANT-DBS may provide for an alternative treatment option in these patients. This literature review discusses the rationale, mechanism of action, clinical efficacy, safety, and tolerability of ANT-DBS in drug-resistant epilepsy patients. A review using systematic methods of the available literature was performed using relevant databases including Medline, Embase, and the Cochrane Library pertaining to the different aspects ANT-DBS. ANT-DBS for drug-resistant epilepsy is a safe, effective and well-tolerated therapy, where a special emphasis must be given to monitoring and neuropsychological assessment of both depression and memory function. Three patterns of seizure control by ANT-DBS are recognized, of which a delayed stimulation effect may account for an improved long-term response rate. ANT-DBS remotely modulates neuronal network excitability through overriding pathological electrical activity, decrease neuronal cell loss, through immune response inhibition or modulation of neuronal energy metabolism. ANT-DBS is an efficacious treatment modality, even when curative procedures or lesser invasive neuromodulative techniques failed. When compared to VNS, ANT-DBS shows slightly superior treatment response, which urges for direct comparative trials. Based on the available evidence ANT-DBS and VNS therapies are currently both superior compared to non-invasive neuromodulation techniques such as t-VNS and rTMS. Additional in-vivo research is necessary in order to gain more insight into the mechanism of action of ANT-DBS in localization-related epilepsy which will allow for treatment optimization. Randomized clinical studies in search of the optimal target in well-defined epilepsy patient populations, will ultimately allow for optimal patient stratification when applying DBS for drug-resistant patients with epilepsy.
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Estimulación Encefálica Profunda , Epilepsia Refractaria/terapia , Tálamo , HumanosRESUMEN
OBJECTIVE: Antiglutamate decarboxylase (anti-GAD) antibodies are associated with several neurological manifestations, like epilepsy and movement disorders. However, in daily neurological practice, it remains hard to define when to test for anti-GAD antibodies in patients with neurologic and/or psychiatric symptoms. Therefore, here, we report the patient characteristics of a large retrospective cohort of patients tested for anti-GAD antibodies in clinical practice and compare the characteristics of anti-GAD positive and anti-GAD negative patients. METHODS: We blindly assessed relevant clinical symptoms and comorbidities and functional outcome with the modified Rankin Scale (mRS) in a retrospective observational cohort of all patients in which the decision to assess anti-GAD levels had been made based solely on the presence of possible associated neurological and/or psychiatric symptoms (N=119). RESULTS: Out of 119 patients, 17 (14.3%) were anti-GAD positive. The anti-GAD positive patients had a median age of 30years (range: 3-64; 2 children). They all had epilepsy, with 8 (47%) patients reporting cognitive complaints. Psychiatric symptoms were less prevalent in anti-GAD positive patients, only 1 anti-GAD positive patient (6%) versus 34 anti-GAD negative patients (33%) reported psychiatric symptoms (p=0.021). The most frequent comorbidity of anti-GAD positive patients was diabetes mellitus type 1 (n=8). Twelve (71%) and 13 (78%) of the anti-GAD positive patients were functionally independent at the time of diagnosis and after one year, respectively (mRS score: 0 to 2). There was no significant difference in functional status at any time during follow-up compared with the anti-GAD negative group. CONCLUSION: Antiglutamate decarboxylase (anti-GAD) antibodies relate to epilepsy with or without cognitive complaints. However, psychiatric symptoms were almost absent in anti-GAD positive patients, and the presence of anti-GAD antibodies contributed little to the prognosis in our cohort.
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Autoanticuerpos/sangre , Epilepsia/sangre , Glutamato Descarboxilasa/sangre , Trastornos Mentales/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Niño , Preescolar , Estudios de Cohortes , Comorbilidad , Epilepsia/diagnóstico , Epilepsia/inmunología , Femenino , Estudios de Seguimiento , Glutamato Descarboxilasa/inmunología , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/inmunología , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson disease (PD) is associated with postoperative cognitive decline. One of the proposed underlying mechanisms is the surgical procedure with the lead trajectory penetrating the caudate nucleus. OBJECTIVE: To study whether penetration of the caudate nucleus affects neuropsychological outcome. METHODS: Neuropsychological and imaging data of 30 PD patients who underwent bilateral STN DBS were analysed. Lead trajectories were evaluated leading to a group with (n = 10) and a group without penetration of the caudate nucleus (n = 20). The neuropsychological performance of each group was compared to baseline, both at 3 and 12 months postoperatively. RESULTS: Only the Trail-Making Test part B (TMT-B) showed an interaction effect within the groups over time at 3 months postoperatively. At 12 months postoperatively, there was only a main effect of time with a decrease in performance in TMT-B for both groups. Also verbal fluency showed a significant decrease over time for both groups at 3 and 12 months postoperatively. CONCLUSION: Caudate nucleus penetration affects cognitive flexibility only in the short term after surgery.
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Núcleo Caudado/cirugía , Estimulación Encefálica Profunda/tendencias , Electrodos Implantados , Pruebas Neuropsicológicas , Núcleo Subtalámico/cirugía , Anciano , Núcleo Caudado/diagnóstico por imagen , Estimulación Encefálica Profunda/instrumentación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Desempeño Psicomotor/fisiología , Estudios Retrospectivos , Núcleo Subtalámico/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Recent epidemiological studies propose an association between parkinsonism and seizures, but the direction of this association is unclear. Focal brain lesions causing new-onset parkinsonism versus seizures may provide a unique perspective on the causal relationship between the two symptoms and involved brain networks. We studied lesions causing parkinsonism versus lesions causing seizures and utilized human connectome data to identify their connected brain networks. Brain networks for parkinsonism and seizures were compared using spatial correlations on a group and individual lesion level. Lesions not associated with either symptom were used as controls. Lesion locations from 29 patients with parkinsonism were connected to a brain network with the opposite spatial topography (spatial r =-0.85) compared to 347 patients with lesions causing seizures. A similar inverse relationship was found when comparing the connections that were most specific for lesions causing parkinsonism versus seizures on a group level (spatial r =- 0.51) and on an individual lesion level (average spatial r =-0.042; p<0.001). The substantia nigra was found to be most positively correlated to the parkinsonism network but most negatively correlated to the seizure network (spatial r >0.8). Brain lesions causing parkinsonism versus seizures map to opposite brain networks, providing neuroanatomical insight into conflicting epidemiological evidence.
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Recent epidemiological studies propose an association between parkinsonism and seizures, but the direction of this association is unclear. Focal brain lesions causing new-onset parkinsonism versus seizures may provide a unique perspective on the causal relationship between the two symptoms and involved brain networks. We studied lesions causing parkinsonism versus lesions causing seizures and used the human connectome to identify their connected brain networks. Brain networks for parkinsonism and seizures were compared using spatial correlations on a group and individual lesion level. Lesions not associated with either symptom were used as controls. Lesion locations from 29 patients with parkinsonism were connected to a brain network with the opposite spatial topography (spatial r = -0.85) compared to 347 patients with lesions causing seizures. A similar inverse relationship was found when comparing the connections that were most specific on a group level (spatial r = -0.51) and on an individual lesion level (average spatial r = -0.042; P < 0.001). The substantia nigra was found to be most positively correlated to the parkinsonism network but most negatively correlated to the seizure network (spatial r > 0.8). Brain lesions causing parkinsonism versus seizures map to opposite brain networks, providing neuroanatomical insight into conflicting epidemiological evidence.
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This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown. We aimed to identify a cortical target by synthesizing prior neuroimaging studies, and to use this knowledge to advance a dual thalamic (centromedian) and cortical (frontal) approach for closed-loop stimulation. Multi-modal brain network maps from three group-level studies of Lennox-Gastaut syndrome were averaged to define the area of peak overlap: simultaneous EEG-functional MRI of generalized paroxysmal fast activity, [18F]fluorodeoxyglucose PET of cortical hypometabolism and diffusion MRI structural connectivity associated with clinical efficacy in a previous trial of thalamic deep brain stimulation. The resulting 'hotspot' was used as a seed in a normative functional MRI connectivity analysis to identify connected networks. Intracranial electrophysiology was reviewed in the first two trial patients undergoing bilateral implantations guided by this hotspot. Simultaneous recordings from cortex and thalamus were analysed for presence and synchrony of epileptiform activity. The peak overlap was in bilateral premotor cortex/caudal middle frontal gyrus. Functional connectivity of this hotspot revealed a distributed network of frontoparietal cortex resembling the diffuse abnormalities seen on EEG-functional MRI and PET. Intracranial electrophysiology showed characteristic epileptiform activity of Lennox-Gastaut syndrome in both the cortical hotspot and thalamus; most detected events occurred first in the cortex before appearing in the thalamus. Premotor frontal cortex shows peak involvement in Lennox-Gastaut syndrome and functional connectivity of this region resembles the wider epileptic brain network. Thus, it may be an optimal target for a range of neuromodulation therapies, including thalamocortical stimulation and emerging non-invasive treatments like focused ultrasound or transcranial magnetic stimulation. Compared to thalamus-only approaches, the addition of this cortical target may allow more rapid detections of seizures, more diverse stimulation paradigms and broader modulation of the epileptic network. A prospective, multi-centre trial of closed-loop thalamocortical stimulation for Lennox-Gastaut syndrome is currently underway.
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OBJECTIVE: Chronic tinnitus is a clinical symptom that affects 10% to 15% of the adult population. Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment, but significant heterogeneity exists in the treatment outcomes and stimulation parameters. In this study, we perform a qualitative systematic review to determine if there is an optimal rTMS site to treat tinnitus. DATA SOURCES: A literature search was performed by searching the MEDLINE, Embase, Web of Science, and Cochrane databases. REVIEW METHODS: Sham-controlled studies in adults were included that contained >10 patients with tinnitus for >3 months and utilized 10 to 20 electroencephalography coordinates. Study outcomes were considered positive if the treatment arm reported a significant reduction in the primary tinnitus score relative to sham. RESULTS: There were 1211 studies screened. Nineteen studies met the inclusion criteria, and 8 unique stimulation sites were reported. Studies had 53.7 ± 46.0 patients (mean ± SD). The mean duration of follow-up was 10.3 ± 9.6 weeks. Positive outcomes regarding tinnitus suppression were reported in 5 of 5 (100%) studies stimulating the temporoparietal junction midway between T3 and P3 or between T4 and P4. Tinnitus suppression at all other sites was less frequent with a combined success rate of only 8 of 14 (57.1%). CONCLUSION: Significant heterogeneity exists in the literature in regard to the optimal transcranial magnetic stimulation target. These preliminary findings suggest that the temporoparietal junction midway between T3 and P3 or T4 and P4 is a promising nonauditory rTMS target in the setting of chronic tinnitus. Future research should elucidate the effectiveness of this site for tinnitus suppression.
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Acúfeno , Estimulación Magnética Transcraneal , Adulto , Humanos , Electroencefalografía , Acúfeno/terapia , Acúfeno/diagnóstico , Resultado del TratamientoRESUMEN
Psychiatric disorders share neurobiology and frequently co-occur. This neurobiological and clinical overlap highlights opportunities for transdiagnostic treatments. In this study, we used coordinate and lesion network mapping to test for a shared brain network across psychiatric disorders. In our meta-analysis of 193 studies, atrophy coordinates across six psychiatric disorders mapped to a common brain network defined by positive connectivity to anterior cingulate and insula, and by negative connectivity to posterior parietal and lateral occipital cortex. This network was robust to leave-one-diagnosis-out cross-validation and specific to atrophy coordinates from psychiatric versus neurodegenerative disorders (72 studies). In 194 patients with penetrating head trauma, lesion damage to this network correlated with the number of post-lesion psychiatric diagnoses. Neurosurgical ablation targets for psychiatric illness (four targets) also aligned with the network. This convergent brain network for psychiatric illness may partially explain high rates of psychiatric comorbidity and could highlight neuromodulation targets for patients with more than one psychiatric disorder.
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Trastornos Mentales , Humanos , Trastornos Mentales/diagnóstico , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Atrofia/patología , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/patología , ComorbilidadRESUMEN
Vertigo is a common neurological complaint, which can result in significant morbidity and decreased quality of life. While pathology to peripheral and subtentorial brain structures is a well-established cause of vertigo, cortical lesions have also been linked to vertigo and may lend insight into relevant neuroanatomy. Here, we investigate the supratentorial lesion locations associated with vertigo and test whether they map to a common brain network. We performed a systematic literature search and identified 23 cases of supratentorial brain lesions associated with vertigo. We mapped the lesion locations to a standard brain template and computed the network of brain regions functionally connected to each lesion location, using a 'wiring diagram' of the human brain termed the human connectome (n = 1000). Sensitivity was assessed by identifying the most common connection to lesion locations associated with vertigo, and specificity was assessed through comparison with control lesions associated with symptoms other than vertigo (n = 68). We found that functional connectivity between lesion locations and the bilateral ventral posterior insula was both sensitive (22/23 lesions) and specific (voxel-wise family-wise error-corrected P < 0.05) for lesion-induced vertigo. We computed connectivity with this hub region to define a lesion-based vertigo network, which included regions in the bilateral insula, somatosensory cortex, higher-level visual areas, cingulate sulcus, thalamus and multiple cerebellar regions in the territory of the posterior inferior cerebellar artery. Next, we used stereo-electroencephalography (80 stimulation sites across 17 patients) to test whether stimulation sites associated with vertigo mapped to this same network. We found that 36/42 (86%) of stimulation sites eliciting vertigo fell within the lesion-based vertigo network in contrast to 16/39 (41%) of stimulation sites that did not elicit vertigo. Connectivity between stimulation sites and our lesion-based hub in the ventral posterior insula was also significantly associated with vertigo (P < 0.0001). We conclude that cortical lesions and direct electrical stimulation sites associated with vertigo map to a common brain network, offering insights into the causal neuroanatomical substrate of vertigo.
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BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an effective treatment for refractory epilepsy; however, seizure outcome varies among individuals. Identifying a reliable noninvasive biomarker to predict good responders would be helpful. OBJECTIVES: To test whether the functional connectivity between the ANT-DBS sites and the seizure foci correlates with effective seizure control in refractory epilepsy. METHODS: We performed a proof-of-concept pilot study of patients with focal refractory epilepsy receiving ANT-DBS. Using normative human connectome data derived from 1000 healthy participants, we investigated whether intrinsic functional connectivity between the seizure foci and the DBS site was associated with seizure outcome. We repeated this analysis controlling for the extent of seizure foci, distance between the seizure foci and DBS site, and using functional connectivity of the ANT instead of the DBS site to test the contribution of variance in DBS sites. RESULTS: Eighteen patients with two or more seizure foci were included. Greater functional connectivity between the seizure foci and the DBS site correlated with more favorable outcome. The degree of functional connectivity accounted for significant variance in clinical outcomes (DBS site: |r| = 0.773, p < 0.001 vs ANT-atlas: |r| = 0.715, p = 0.001), which remained significant when controlling for the extent of the seizure foci (|r| = 0.773, p < 0.001) and the distance between the seizure foci and DBS site (|r| = 0.777, p < 0.001). Significant correlations were independent of variance in the DBS sites (|r| = 0.148, p = 0.57). CONCLUSION: These findings suggest that functional connectomic profile is a potential reliable non-invasive biomarker to predict ANT-DBS outcomes. Accordingly, the identification of ANT responders could decrease the surgical risk for patients who may not benefit and optimize the cost-effective allocation of health care resources.
Asunto(s)
Núcleos Talámicos Anteriores , Conectoma , Estimulación Encefálica Profunda , Epilepsia Refractaria , Epilepsias Parciales , Humanos , Epilepsia Refractaria/terapia , Proyectos Piloto , Núcleos Talámicos Anteriores/fisiología , Convulsiones/terapia , Biomarcadores , Epilepsias Parciales/terapiaRESUMEN
Importance: It remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions. Objective: To assess whether lesion locations associated with epilepsy map to specific brain regions and networks. Design, Setting, and Participants: This case-control study used lesion location and lesion network mapping to identify the brain regions and networks associated with epilepsy in a discovery data set of patients with poststroke epilepsy and control patients with stroke. Patients with stroke lesions and epilepsy (n = 76) or no epilepsy (n = 625) were included. Generalizability to other lesion types was assessed using 4 independent cohorts as validation data sets. The total numbers of patients across all datasets (both discovery and validation datasets) were 347 with epilepsy and 1126 without. Therapeutic relevance was assessed using deep brain stimulation sites that improve seizure control. Data were analyzed from September 2018 through December 2022. All shared patient data were analyzed and included; no patients were excluded. Main Outcomes and Measures: Epilepsy or no epilepsy. Results: Lesion locations from 76 patients with poststroke epilepsy (39 [51%] male; mean [SD] age, 61.0 [14.6] years; mean [SD] follow-up, 6.7 [2.0] years) and 625 control patients with stroke (366 [59%] male; mean [SD] age, 62.0 [14.1] years; follow-up range, 3-12 months) were included in the discovery data set. Lesions associated with epilepsy occurred in multiple heterogenous locations spanning different lobes and vascular territories. However, these same lesion locations were part of a specific brain network defined by functional connectivity to the basal ganglia and cerebellum. Findings were validated in 4 independent cohorts including 772 patients with brain lesions (271 [35%] with epilepsy; 515 [67%] male; median [IQR] age, 60 [50-70] years; follow-up range, 3-35 years). Lesion connectivity to this brain network was associated with increased risk of epilepsy after stroke (odds ratio [OR], 2.82; 95% CI, 2.02-4.10; P < .001) and across different lesion types (OR, 2.85; 95% CI, 2.23-3.69; P < .001). Deep brain stimulation site connectivity to this same network was associated with improved seizure control (r, 0.63; P < .001) in 30 patients with drug-resistant epilepsy (21 [70%] male; median [IQR] age, 39 [32-46] years; median [IQR] follow-up, 24 [16-30] months). Conclusions and Relevance: The findings in this study indicate that lesion-related epilepsy mapped to a human brain network, which could help identify patients at risk of epilepsy after a brain lesion and guide brain stimulation therapies.
Asunto(s)
Epilepsia , Accidente Cerebrovascular , Humanos , Masculino , Persona de Mediana Edad , Adulto , Femenino , Estudios de Casos y Controles , Encéfalo/patología , Epilepsia/etiología , Epilepsia/patología , Convulsiones/fisiopatología , Accidente Cerebrovascular/fisiopatologíaRESUMEN
Previous research has shown an interplay between the thalamus and cerebral cortex during NREM sleep in humans, however the directionality of the thalamocortical synchronization is as yet unknown. In this study thalamocortical connectivity during different NREM sleep stages using sleep scalp electroencephalograms and local field potentials from the left and right anterior thalamus was measured in three epilepsy patients implanted with deep brain stimulation electrodes. Connectivity was assessed as debiased weighted phase lag index and granger causality between the thalamus and cortex for the NREM sleep stages N1, N2 and N3. Results showed connectivity was most prominently directed from cortex to thalamus. Moreover, connectivity varied in strength between the different sleep stages, but barely in direction or frequency. These results imply relatively stable thalamocortical connectivity during NREM sleep directed from the cortex to the thalamus.