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sponses in three PD patients in four DBS conditions: left Department of Clinical Neurosciences, Cambridge Biomedi-
unilateral STN-DBS, right unilateral STN-DBS, bilateral cal Campus, University of Cambridge, Cambridge CB2 0QQ,
STN-DBS, and no STN-DBS. To ensure that any observed UK; MMRC Cognition and Brain Sciences Unit, Cambridge
effects of DBS on the neuromagnetic responses could CB2 7EF, UK; Cambridge University Hospitals, Cambridge,
be attributed to the linguistic context per se and were CB2 0QQ, UK; Wellcome Centre for Human Neuroimaging,
not merely induced by the electrical stimulation, we University College London, London WC1N 3AR, UK
assessed the effects of STN-DBS on linguistic contrasts
within each stimulation condition. Hence, we contrast- ABSTRACT The clinical syndromes caused by fron-
ed the processing of action vs. abstract verbs as well as totemporal lobar degeneration are heterogeneous,
the processing of correct vs. incorrect morphosyntactic including the behavioural variant frontotemporal
inflections within each DBS condition. dementia (bvFTD) and progressive supranuclear palsy.
Although pathologically distinct, they share many
RESULTS The results revealed that, compared to the behavioural, cognitive and physiological features,
DBS-off state, both bilateral and right unilateral stimu- which may in part arise from common deficits of
lation of the STN yielded significant dissociations in the major neurotransmitters such as γ-aminobutyric acid
processing of action and abstract verbs, with greater (GABA). Here, we quantify the GABAergic impairment
neuromagnetic responses for action verbs compared to and its restoration with dynamic causal modelling of a
abstract verbs. For morphosyntax processing, only left double-blind placebo-controlled crossover pharmaco-
unilateral stimulation yielded significant dissociations magnetoencephalography study. We analysed 17
(relative to the DBS-off state), with greater neuromag- patients with bvFTD, 15 patients with progressive
netic responses to the incorrect inflections compared supranuclear palsy, and 20 healthy age- and gender-
to the correct inflections. matched controls. In addition to neuropsychological
assessment and structural MRI, participants undertook
CONCLUSION The results reflect differential effects two magnetoencephalography sessions using a rov-
of unilateral and bilateral STN-DBS on neuromagnetic ing auditory oddball paradigm: once on placebo and
responses associated with the processing of spoken once on 10 mg of the oral GABA reuptake inhibitor
language. They suggest that different specific aspects tiagabine. A subgroup underwent ultrahigh-field mag-
of linguistic information processing in PD are affected netic resonance spectroscopy measurement of GABA
differently by STN-DBS. concentration, which was reduced among patients.
We identified deficits in frontotemporal processing
Keywords: Parkinson's disease, action verb, bilateral, deep using conductance-based biophysical models of local
brain stimulation, language, magnetoencephalography, and global neuronal networks. The clinical relevance
morphosyntax, unilateral of this physiological deficit is indicated by the correla-
tion between top-down connectivity from frontal to
Acta neurologica Scandinavica (2021), Vol. 144, No. 2 temporal cortex and clinical measures of cognitive and
(33961289) (2 citations) behavioural change. A critical validation of the biophys-
ical modelling approach was evidence from parametric
empirical Bayes analysis that GABA levels in patients,
GABAergic cortical network physiology in measured by spectroscopy, were related to posterior
frontotemporal lobar degeneration (2021) estimates of patients' GABAergic synaptic connectivity.
Further evidence for the role of GABA in frontotempo-
Adams, Natalie E; Hughes, Laura E; Rouse, Matthew ral lobar degeneration came from confirmation that the
A; Phillips, Holly N; Shaw, Alexander D; Murley, effects of tiagabine on local circuits depended not only
Alexander G; Cope, Thomas E; Bevan-Jones, W Richard; on participant group, but also on individual baseline
Passamonti, Luca; Street, Duncan; Holland, Negin; GABA levels. Specifically, the phasic inhibition of deep
Nesbitt, David; Friston, Karl; Rowe, James B cortico-cortical pyramidal neurons following tiagabine,

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