Neuro-Gerontechnology

Prof. Valentina AGOSTINI Week 1

Lesson 2 (3 hours)
Outline
Active time for
students

Introduction to
NE & biological
senescence BCIs Neuromodulation

Neural Neurorehab.
prostheses through
exoskeletons

2
Neuroengineering: keywords
From SciVal

3
 Aging: changes due to “healthy” or “pathological”
senescence

• Age-specific mild-to-severe progressive impairments to

cognitive, sensory, and motor skills because of multiple
health conditions.
• Neurodegenerative processes (Parkinson, dementia),
cerebrovascular diseases (stroke), age-related macular
degeneration (AMD), hearing loss,...
• “Gerontechs” are conceived for improving the QoL in
daily contexts: telerehabilitation, IoT, enabling
technologies for seniors.
• “Neurogerontechs” target the CNS (brain + spinal cord)
of aging persons.

4
Example of neuroprothesis: Cochlear inplant

• The cochlear implant systems

market share from the adult
segment had reached 750
million USD in 2020.
• It is expected to grow due to
high geriatric population and
the prevalence of impaired
hearing.
• Unilateral implant (> 88%).

https://youtu.be/LhSpb36_1s4

5
 Example of neuroprothesis: «Bionic eye»

• Argus II visual prostheses (60-electrode array, fixed to the

retina)
EXTERNAL MODULE INTERNAL MODULE
2011 CE approved
2013 FDA approved
under a humanitarian device
exemption (can be marketed
without requiring evidence of
effectiveness)
Image by Second
Sight Medical
Products Inc.

6
 Example of neuroprothesis: «Bionic eye»

• Argus II visual prostheses (60-electrode array, fixed to the

retina)
EXTERNAL MODULE INTERNAL MODULE

https://spectrum.ieee.org/bionic-eye-obsolete

2022
Image by Second
Sight Medical
Products Inc.

2011 CE
2013 FDA approved 7
 Brain-Computer Interfaces (BCI)

BCI classification: Invasive,

semi-invasive, non-invasive,
stimulating, bi-directional
https://www.youtube.com/watch?v=QRt8QCx3BCo

8
 Any hardware & software communications system that permits
cerebral activity alone to control external devices (computers,
speech synthesizers, assistive appliances and neural prostheses).

It creates a new non-muscular channel for relying a person’s

intentions to external devices.

It provides communications capabilities to severely disabled

people (“locked-in” syndrome, amyotrophic lateral sclerosis
(ALS), brain stem stroke, spinal cord injury,…).

Nicolas-Alonso & Gomez-Gil. Brain Computer interfaces, a Review, Sensors 2012.

9
 Electrical signals reflecting brain
Signal acquisition activity are acquired from the
scalp, from the cortical surface,
or from within the brain.

Pre-processing & Feature extraction,

signal enhancement classification
The signals are analyzed to extract
signal features (such as amplitudes of
EEG rhythms or firing rates of single
neurons) that reflect the user’s intent.

Features are translated into

commands that operate application
Chapter 1 of Wolpaw 2012: Brain Computer Interfaces:
Principles and Practice.
devices that replace, restore, enhance,
supplement, or improve natural CNS Control interface
outputs.
10
Neuralink: beyond the hype
and into the science (and
history)
August 28, 2020 March 2, 2023
• Elon Musk presenting Neuralink pig • FDA Rejected Musk's Bid To Test
brain implant
Brain Chip Implants In Humans

https://www.forbes.com/sites/dereksau
l/2023/03/02/fda-rejected-musks-bid-
to-test-brain-chip-implants-in-humans-
https://youtu.be/eFUmbA71wbU report-says/?sh=4009d8cc255c

11
Neuralink: beyond the hype
and into the science (if any…)
https://www.youtube.com/watch?v=LfwzfP8cp3A
May 25, 2023 January 29, 2024
• United States regulators (US • First Neuralink human trial
FDA) have given approval to test subject can control a computer
brain-chip implants on humans. mouse with brain implant, Elon
Musk says (CNN).
• Researchers are concerned
about a lack of transparency
surrounding the implant
(Nature)
https://www.nature.com/articles/d41586-024-00304-4
12
 Neurotechnology for spinal lesion therapy

Electrical stimulation of the spinal cord

https://youtu.be/4wUADfnCMdc
• Michel Roccati, SCI patient (on a wheelchair)
after a motorcycle accident in 2017
• Jocelyne Block, neurosurgeon, CHUV (Centre
Hospitalier Universitaire Vaudois)
• Grégoire Courtin, neuroscientist, EPFL (École
https://www.onwd.com/
Polytechnique Fédérale de Lausanne)
13
 Neurotechnology for spinal lesion therapy

https://www.nature.com/articles/s41586-023-06094-5
14
Neurorehabilitation: Exoskeletons for the elderly
An overview of the market (1)

• ReWalk Robotics: https://youtu.be/aBD6Chf0Hoc

• Wandercraft: https://youtu.be/-yBfUcFRZ-I
• Rex Bionics: https://www.rexbionics.com/
• Ekso, H2, HAL, Indego,...

15
Exoskeletons for the elderly
An overview of the market (2)

16
Neuromodulation
Stimulating the brain

tACS tFUS
transcranial transcranial TMS
Alternating Current Focused
Transcranial
Stimulation Ultrasound
tDCS Magnetic
transcranial Stimulation
Direct Current
Stimulation Neuromodulation
DBS ICS VNS
Deep Brain Intracranial Cortical Vague Nerve
Stimulation Stimulation Stimulation

17
Deep Brain Stimulation (DBS)

Implanted Pulse
Generator (IPG)
Battery powered device that sends
pulsed electricity through an insulated
wire to an electrode 18
Deep Brain Stimulation (DBS)

• Surgical implantation of a neurostimulator: leads are

positioned using a neuronavigator.
• The electrode is connected to a wire that runs under the skin to
a pulse generator (implanted under the collarbone).
• When IPG is turned on, it emits electrical impulses that alter
neural functiong.
• After IPG implant, stimulation parameters are telemetrically
configured.

Facts to be considerd
The DBS journey of a
• > 100.000 patients have been implanted with DBS worldwide patient with essential
• DBS is a major brain surgery (risks associated with the tremor at Saint Louis
procedure) Univ. Hospital, Missoury
• Therapeutic mechanism of DBS is still unclear. (USA):
https://youtu.be/ksjHNb
b6NFQ

19
DBS
Clinical applications

• FDA approval for the treatment of medication-refractory Parkinson’s

Disease (PD) and essential tremor.
• PD: It can improve QoL in patients by blocking the abnormal nerve signals
that cause symptoms of disease (e.g., tremors, rigidity, bradykinesia, and
postural instability). Electrodes are placed in the STN whose overactivity is
thought to contribute to motor problems (e.g. initiating movement).
Modifying the activity of these overly excitable regions can alleviate the
symtomps of PD.
• Resting tremor is suppressed within seconds, while relief from bradykinesia
takes minutes, and improvement in gait & posture can require continuous
stimulation for hours to days before achieving a maximum effect.
• DBS is also used in depression, obsessive-compulsive disorder, Tourette
syndrome, and other disorders relating to motor irregularities.

20
Open-Loop and Closed-Loop DBS
• OL (conventional): stimulation parameters
(e.g. duration, amplitude, frequency of the
pulse train) remain constant, regardless of • CL (adaptive): it requires a control algorithm to
fluctuations in the disease state. learn and optimize the stimulation parameters
according to the brain clinical state. (Early stage of
development).

M. Parastarfeizabadi & A. Z. Kouzani, “Advances in closed-

loop deep brain stimulation devices”, Journal of
NeuroEngineering and Rehabilitation, 2017.

21
 Explore different POVs and interpret different roles in the design of a
closed-loop DBS devise to treat PD patients. Which are the questions
the comes to your mind reasoning about this technology? Example of
game roles:
- Neurosurgeon
- Neuropsychologist
- PD Patient
- PD patient’s caregiver
- Biomedical engineer/Expert on medical device regulations
- Researcher
- Producer/stackholder
- President of associations (PD patients, neurodiversity)
- National Health Service (NHS) representative
- Bioethicist

22

Active time for the students...

Role playing
 1. Choose your «role» within the students’ team
2. Reason about issues related to your specific role/POV (alone)
3. Discuss/Negotiate with others in the team
4. Each team reports the keypoints emerged from the discussion on
the Telegram.

Active time for the students... 23

Role playing: guidelines
 Meet your group!

Each of you was

• In the folder «LAB» there is assigned to a team
the list of LAB groups
(students’ teams)

• Problems with the lab

group? Contact the tutor by
e-mail:
[email protected]

24
Evaluation of motor changes in PD patients
after DBS neurosurgery
Experimental protocol

T0 – PD before surgery (baseline)

T1 – PD @3 months after DBS implant
T2 – PD @12 months after DBS implant
Control subjects (caregivers)
25
Ghislieri, M., Lanotte, M., Knaflitz, M., Rizzi, L., Agostini, V., Muscle synergies in Parkinson’s disease before and
after the deep brain stimulation of the bilateral subthalamic nucleus. Sci Rep 13, 6997 (2023).
https://doi.org/10.1038/s41598-023-34151-6
26
Deep Brain Stimulation
Neuroethics

• Three years after the implantation of electrodes in the STN and the start of
DBS for advanced Parkinson's disease, a 62-year-old man was admitted
because of a stimulation-related maniac state that did not respond to
treatment with a mood stabiliser and that led to chaotic behaviour,
megalomania, serious financial debts and mental incompetence. Although
adjustment of the stimulation parameters resulted in a normophoric state
with a return of insight and capacity to judge, this was only at the cost of a
serious exacerbation of his motor symptoms that left the patient
bedridden. There was no therapeutic margin between the 2 states.
• Ultimately, there seemed to be only 2 alternatives: to admit the patient to
a nursing home because of serious invalidity, but mentally in good
condition, or to admit the patient to a chronic psychiatric ward because of
a manic state, but with acceptable motor capacity and ADL functions.
Leentjenset al., 2004, “Manipulation of mental competence: An ethical problem in case of electrical stimulation of the
subthalamicnucleus for severe Parkinson’s disease,” NederlandsTijdschriftvoorGeneeskunde, 148(28): 1394 –98.

27
Transcranial Magnetic Stimulation

TMS uses electromagnetic induction to generate

an electric current across the scalp and skull
without physical contact.

Pulsed current is discharged through a coil

placed near the surface of the scalp,
creating a time-varying magnetic field
perpendicular to the plane of the coil →
eddy currents modulate neuronal activity
within the cortex.

28
TMS – Examples of coils

Circular coils Figure-8 coils Double-cone coil

29
TMS
Clinical applications and safety concerns

✓ FDA approved for stimulation of peripheral

nerves, pre-surgical language mapping &
medication-refractory depression.

✓ It is also emerging for stroke rehabilitation,

shizofrenia, pain…

rTMS is known to carry a risk of seizures

→ safety guidelines have been established

30
 TMS in stroke

Infarct
Peri-infarct
zone

Interhemispheric Balance Is Altered

Hemiparesis after stroke: not only neuronal death after Stroke and Can Be Corrected with
within the lesioned hemisphere, but also down- brain stimulation
regulation of surviving neurons within the peri-
infact zone and other areas remote from the lesion
31
(diaschisis).
TDCS
Transcranial Direct Current Stimulation

Portable, non-invasive neuromodulatory

technique
It delivers a weak constant electric current
Saline-soaked sponge (1-2 mA) via electrodes to an area of the
electrodes scalp (e.g. DLPFC)

32
TDCS
Clinical applications

SCHIZOFRENIA: aberrations in cortical functional connectivity

→ stim. significantly reduced the occurrence of auditory verbal hallucinations
and the reduction persisted for 3 months.

ADDICTION: increased impulsivity and risk-taking behavior

associated with drug abuse significantly decreased after bilateral
stimulation of the DLPFC.

DEPRESSION: controversy remains around its efficacy. Some tDCS studies have
noted that anodic stim. of the left DLPFC can significantly reduce depression
scores for up to 30 days. Optimizing stimulation in a subject-specific manner and
investigating additional tDCS cortical regions involved in mood and emotion
could improve efficacy.
33
TDCS
Effect of neurorehabilitation through tDCS

PD patient @PolitoBIOMedLab for gait analysis, in collaboration with a neurologist

Pre tDCS Post tDCS

34
 GAIT ANALISYS: A subset of gait (basographic) parameters…

Pre tDCS Post tDCS Pre tDCS Post tDCS

Left lower limb Right lower limb

✓  Cadence (from 43 to 48 gait cycles/min.)

✓  % Double support (from 27 to 24 % GC)
✓   % of “atypical” gait cycles (= different from HFPS)

35
Which of the following statements about "neuro-
gerontechnologies" is NOT correct:

ⓘ Start presenting to display the poll results on this slide.

36