Thalamocortical dysrhythmia detected by machine learning

Abstract

Thalamocortical dysrhythmia (TCD) is a model proposed to explain divergent neurological disorders. It is characterized by a common oscillatory pattern in which resting-state alpha activity is replaced by cross-frequency coupling of low- and high-frequency oscillations. We undertook a data-driven approach using support vector machine learning for analyzing resting-state electroencephalography oscillatory patterns in patients with Parkinson’s disease, neuropathic pain, tinnitus, and depression. We show a spectrally equivalent but spatially distinct form of TCD that depends on the specific disorder. However, we also identify brain areas that are common to the pathology of Parkinson’s disease, pain, tinnitus, and depression. This study therefore supports the validity of TCD as an oscillatory mechanism underlying diverse neurological disorders.

Hallucinations, somatic‐functional disorders of PD‐DLB as expressions of thalamic dysfunction

“…The original TCD study suggested that the theta burst mode shown by thalamic neurons, replacing alpha and gamma frequencies, is because of activation of low‐threshold calcium spike bursts that are induced by long‐lasting hyperpolarization generated on altered projections from the globus pallidus or the pedunculopontine nuclei (PPN) to the thalamoreticular nuclei (TRN). Contrary to earlier studies that have proposed TCD as the mechanism for PD motor symptoms, more recent evidence indicates that PD‐related theta‐pre‐alpha EEG activity only correlates with ongoing cognitive decline and not with motor symptoms . We therefore suggest that the TCD theory should be repositioned from being the conceptual framework of PD motor symptoms to a central role in driving DMN decoupling and ensuing disconnections from contextual and consensual reality, that is, hallucinations, SFDs, delusions, and fluctuating cognition.…”

“…DMN decoupling should be linked with the (now) uncontroversial evidence of EEG abnormalities in PDD and DLB, consisting of the progressive appearance of theta rhythms . These rhythms are the core features of the thalamocortical dysrhythmia (TCD) theory, which postulates that in several disorders including PD, thalamocortical neurons enter into a state of theta burst mode that drives cortical EEG theta and dysfunctional cortical activity . These theta rhythms, now used as a diagnostic biomarker, are the hallmark of thalamocortical dysfunction, as EEG rhythmic activity needs a thalamic pacer, only arrhythmic activities depend on focal cortical alterations .…”

“…Instead, continuous theta activity is observed during REM sleep in PD patients and REM sleep behavior disorder of PD‐RBD . Detection of the theta‐pre‐alpha rhythm in PD is now a core feature of machine‐learning projects developed for assessment of PD and RBD …”

“…6,[27][28][29] These rhythms are the core features of the thalamocortical dysrhythmia (TCD) theory, which postulates that in several disorders including PD, thalamocortical neurons enter into a state of theta burst mode that drives cortical EEG theta and dysfunctional cortical activity. 30,31,103 These theta rhythms, now used as a diagnostic biomarker, are the hallmark of thalamocortical dysfunction, as EEG rhythmic activity needs a thalamic pacer, 30 only arrhythmic activities depend on focal cortical alterations. 104 The presence of theta rhythm, also called pre-alpha or fast theta 6 predicts the occurrence of cognitive decline or progression of mild cognitive impairment to dementia in PDD and correlates with the severity of cognitive fluctuations in DLB.…”

“…109 Instead, continuous theta activity is observed during REM sleep in PD patients and REM sleep behavior disorder of PD-RBD. 110 Detection of the theta-pre-alpha rhythm in PD is now a core feature of machine-learning projects developed for assessment of PD 103,111 and RBD. 112 The TCD theory 30 originally postulated that portions of the thalamocortical system become locked in spindle-like, waking to sleep status theta activity, 31,113 whereas other parts of the brain remain in a waking state, a condition similar to a parasomnia.…”