LOST OF HIGH-LEVEL TOP-DOWN ANTICIPATORY SIGNALS ARE NOT MODULATED BY DIRECT CURRENT STIMULATION IN CHRONIC STAGES OF TRAUMATIC BRAIN INJURY

G. Rivera-Lillo^1,2, F. Covarrubias²

Background: Psychomotor slowness is one of the main causes of disability reported by people suffering chronically from moderate to severe traumatic brain injury (CMS-TBI). The lack of a common theoretical framework to explain this deficit has hampered the development of new therapeutic strategies leading to a reduced set of therapeutic tools to be used for physiotherapists in clinical practice. Impairment in anticipatory control has been proposed as a central aspect of the psychomotor slowness to explain the difficulty of the subjects to implement a normal timing in the sensory-motor response. Under the predictive coding framework, the ability to anticipate events depends on the capacity to generate predictions at successive hierarchical levels and can be explored through neurophysiological correlates of prediction error signals. Analysis of event-related potentials (ERP) allows us to dissect at least 3 hierarchical levels of prediction error signals: the mismatch negativity (MMN; low-level), the P3a (intermediate level), and the P3b (high-level). On the other side, previous reports have shown that non-invasive brain stimulation is useful to improve the motor reaction time. We hypothesize that psychomotor slowness in CMS-TBI is related to the impairment of the normal generation of high-level top-down prediction, which is improved by an external modulation of the excitability of the frontal areas.

Purpose: To determine if CMS-TBI subjects have disturbances to generate high-level top-down predictions and to explore if these disturbances are modulated through temporary incrementation of neural excitability induced by external, non-invasive neuromodulation.

Methods: Electroencephalography recordings were collected from 16 CMS-TBI subjects. Psychomotor slowness and other cognitive aspects were explored through a neuropsychological battery assessment. Behavioural measures related to psychomotor slowness were collected throw simple motor reaction time task. ERP's were collected under the global-local paradigm, a task used to manipulate top-down expectations along with changes in the predictability of bottom-up information. Differences in the ERP were estimated through non-parametric statistical testing. Transcranial direct current stimulation (tDCS) was applied to manipulate the excitability of the frontal areas. Sham tDCS was used as a control condition. For the contrasts between real and sham effects, we used parametric statistical analysis.

Results: CMS-TBI subjects have a preserved capacity to generate top-down prediction at low hierarchical levels, indexed by the MMN response (N=16,clusterstat=-189.9,p=0.016,corrected). However, top-down predictions at high-hierarchical levels, indexed by the P3b are absent. Interestingly, P3a related to novelty detection is present (N=16,clusterstat=266.4,p=0.02,corrected). The tDCS does not have an effect on electrophysiological markers or behavioural measures.

Conclusion(s): CMS-TBI subjects have an impairment of the normal generation of high-level top-down prediction with a preserved responses at low-hierarchical levels. These results suggest an impairment in the generation of high order expectation, which could explain psychomotor slowness reported by CMS-TBI subjects. The tDCS over frontal areas do not have an effect on the electrophysiological or behavioural measures.

Implications: Our works contribute to understanding the neurophysiological mechanisms related to the psychomotor slowing, as one of the main deficits reported by CMS-TBI people. At the same time, our results allow us to explore therapeutic tools used in physiotherapy research related to the effect of tDCS. 

Funding, acknowledgements: Supported by FONDECYT. N° 11191161.
Agencia Nacional de Investigación y Desarrollo. Chile.

Keywords: Traumatic brain injury, Transcranial direct current stimulation, Electroencephalography (EEG)

Topic: Neurology

Did this work require ethics approval? Yes

Institution: Facultad de Medicina. Universidad de Chile.

Committee: Comité de Ética para la Investigación en Seres Humanos

Ethics number: 169-2019. 118