Table 2.

Characteristics and results of NBM DBS clinical studies reporting cognitive outcomes.

No	Author, year	Study design	Patient diagnosis, number, age	Bilateral / unilateral	Stimulation parameter	Mentioned additional treatment	Study duration with active NBM DBS	Results
1	Turnbull et al., 198558	Case report	AD, 1, 74 years	Unilateral (Left)	Intermittent (15-s-ON & 12-min-OFF); 50 Hz, 3 V, 210 ms	Not reported	9 months	the decline of the cortical glucose metabolism after 9 months was smaller in the ipsilateral than the contralateral hemisphere
2	Freund et al., 200910	Case report	PDD, 1, 71 years	Bilateral	Continuous, 20 Hz, 120 µs, 1.0 V	DBS of the subthalamic nucleus, dopaminergic medication with levodopa equivalent dose 312.5 mg/day	13 weeks	scores in neuropsychological testing improved during stimulation and worsened after one week without NBM stimulation
3	Barnikol et al., 20109	Case report	PDD, 1, 71 years	Bilateral	Continuous, 20 Hz, 120 µs, 1.0 V	DBS of the subthalamic nucleus	16 months	NBM DBS significantly improved apraxia symptoms
4	Kuhn et al., 2015a1	Double-blind crossover study (2 weeks ON-2 weeks OFF), followed by 48-week open label study	AD, 6, 57–79 years	Bilateral	Continuous, 10/20 Hz, 90–150 µs, 2.0–4.5 V	Galantamine, Mirtazapine, Donepezil, Lorazepam, Memantine, Escitalopram (combination varried across patients)	50 weeks	changes (improvement and worsening) of cognitive performance based on neuropsychological testing varried across patients, cerebral glucose metabolism increased in three patients
5	Kuhn et al., 2015b94	Case report	AD, 2, 61 & 67 years	Bilateral	Continuous, 20 Hz, pulse width and amplitude were not reported	Not reported	26–28 months	general neuropsychological testing using ADAS-Cog showed stable or improved results while fluctuative results were observed in the other tests
6	Gratwicke et al., 20182	Double-blind crossover study	PDD, 6, 65.2 [10.7] years	Bilateral	Continuous, 20 Hz, 60 µs, 1.5–3 V	Dopaminergic medication, Rivastigmine, Citalopram, Fesoteradine, Quetiapine, Venlafaxine	6 weeks	cognitive performance was insignificantly different between ON and OFF DBS state. Statistically significant improvement of hallucination subscale of the NPI was observed in NBM DBS state which was driven by the results of two patients
7	Nombela et al., 201962	Case report	PD-MCI, 1, 68 years	Bilateral	Continuous, 20 Hz, 60 µs, 2 mA	DBS of the internal pallidum	3 months	Improvement in spatial memory test (ROCF), two out of four tests in executive function (TMT-A and subscale similarities of WAIS IV), and a phonological verbal fluency for letter P, compared to baseline
8	Gratwicke et al., 20203	Double-blind crossover study	DLB, 6, 65–75 years	Bilateral	Continuous, 20 Hz, 60 µs, 2–3.5 V	Dopaminergic medication, Rivastigmine, Donepezil, Citalopram, Sertraline, Amytriptylline, Clonazepam, Venlafaxine	6 weeks	Group-wise, no significant difference was observed between NBM and sham stimulation. The neuropsychiatric complains reduced in 3/5 patients
9	Maltête et al., 202061	Double-blind crossover study	DLB, 6, 50–69 years	Bilateral	Continuous, 20/50/100 Hz, 60–90 µs, 2.5–3 V	Rivastigmine	3 months	No significant difference on cognitive performance between sham versus NBM DBS

ADAS-Cog Alzheimer’s Disease Assessment Scale Cognitive Subscale, ROCF Rey-Osterrieth Complex Figure, TMT-A Trail Making Test A, WAIS IV Wechsler Adult Intelligence Scale IV.