CNS Plasticity

& Cognitive Remediation

•••••••••••••••••••••••••••••••••••••••••••••

Rifky Mubarak
Background
Nervous system was “fixed and immutable”, CNS were incapable of any more
than very limited and abortive growth (Ramon y Cajal, 1959)

Formation of novel synaptic connections following CNS injury. Landmark study

(Raisman, 1969)

After CNS injury , new connections are capable of synaptic transmission, and that
reorganization of circuitry can contribute to functional recovery (Steward, 1982).

Neuroplasticity

Michael Selzer,Stephanie Clarke. Neural Repair & Rehabilitation Vol 1, 2002

Neural Plasticity
• Ability of neurons and neuron aggregates to adjust their activity and even their morphology to
alterations in their environment or patterns of use.
• As from learning and memory in the execution of normal activities of life, to dendritic pruning and
axonal sprouting in response to injury

Neural Repair
• Describe range of interventions by which neuronal circuits lost to injury or disease can be restored
• Included in this term are means to enhance axonal regeneration, the transplantation of a variety of
tissues and cells to replace lost neurons, and the use of prosthetic neuronal circuits to bridge parts of
the nervous system that have become functionally separated by injury or disease
• Generally refers to processes that do not occur spontaneously in humans to a degree sufficient to result
in functional recovery. Thus therapeutic intervention is necessary.

Michael Selzer,Stephanie Clarke. Neural Repair & Rehabilitation Vol 1, 2002

How injuries affect neurons and their
connections
Trauma
• Damage cell populations in the
brain  neurons, glia, ependymal Changes in metabolism, and
cells, vascular elements, etc damage myelin-forming
• Disrupt blood flow, blood–brain oligodendrocytes
barrier, manufacture- distribution-
reabsorption of CSF

Injuries trigger delayed

Directly or indirectly to
death of neurons and glia
alterations in neuronal
through apoptotic and other
function
mechanisms
CNS Trauma

• Interrupting axonal projections

CNS Trauma • Denervating certain populations
of neurons
• Removing some neurons
entirely
The fate of neurons that lose their normal
inputs
changes in specific receptive elements (increased sensitivity to
neurotransmitters, disappearance of dendritic spines, etc)

changes that culminate in the disappearance of entire dendrites

the death of the denervated neurons (transneuronal atrophy or

degeneration)
Physiological Plasticity

Denervation Supersensitivity

Long – Term Potentiation

Long-Term Depression & Habituation

Collateral Sprouting

Dendritic Pruning

Downey&Darling's Physiological Basis of Rehabilitation,3rd ed,2001

 Denervation Supersensitivity
• a phenomenon in which the postsynaptic cell becomes more
sensitive to a neurotransmitter following denervation
• receptors are localized at the end plate beneath the motor nerve
terminal
• Denervation  induction of Ach receptor
• the levels of RNA coding for ACh receptors was increased 100 fold
in denervated mouse muscles  Increase in the number of
extrajunctional acetylcholine receptors
• Reversed if it is innervated again

Michael Selzer,Stephanie Clarke. Neural Repair & Rehabilitation Vol 1, 2002

Downey&Darling's Physiological Basis of Rehabilitation,3rd ed,2001
 Long Term Potentiation (LTP)
• Repeated high-frequency stimulation of
excitatory glutamatergic pathways to the
pyramidal cells of the CA1 region of
hippocampus  a large increase in
synaptic efficacy that may last hours or
even days  LONG TERM POTENTIATION
(LTP)

•Important aspects of LTP can be activated either via homosynaptic or heterosynaptic

mechanisms
•Basic physiology of memory
Downey&Darling's Physiological Basis of Rehabilitation,3rd ed,2001
Mekanisme homosinaptik
• Adanya stimulasi di membran post sinap yang sangat kuat karena jumlah ikatan
glutamat yang sangat besar di membran post sinap terjadi Depolarisasi yang
cukup besar

• Penting dalam mekanisme motor learning menghasilkan keterampilan baru

Mekanisme heterosinaptik
• Aktivasi jalur glutamat  depolarisasi pada membran post sinap

• Pada waktu yang sama terjadi depolarisasi pada membran post sinap yang
sama oleh jalur neurotransmitter lain (Ach, NE)  aktivasi motor learning lain
yg baru
Downey&Darling's Physiological Basis of Rehabilitation,3rd ed,2001
 Long term depression (LTD) & Habituation
Sti mulati on of some synapti c pathways may lead to long term depression
Homosynapti c LTD  results from low-frequency sti mulati on of the
depressed pathway & acti vati on of NMDA receptors (Habituati on Learning)
Heterosynapti c LTD  high-frequency acti vati on of one pathway produces
a reducti on in response of the postsynapti c neuron to sti mulati on of the
second pathway

Downey&Darling's Physiological Basis of Rehabilitation,3rd ed,2001

 Collateral Sprouting
• Partial denervation of muscle  followed by
sprouting of neurites from neighboring spared axons
& reinnervation of the denervated muscle fibers by
the sprouts
• When a nerve undergoes partial injury, the
Schwann’s cells that cap degenerated nerve terminals
send out processes to adjacent neuromuscular
junctions
• In the brain  collateral sprouting demonstrated in
the septal nucleus, dentate gyrus, and CA3 region of
the hippocampus
• Correlate with hyper reflex and increased muscle
tone

Downey&Darling's Physiological Basis of Rehabilitation,3rd ed,2001

 Dendritic Pruning

• Loss innervation  kurangnya

innervasi pada neuron post sinap

• Dendritic arbor : yaitu berkurangnya

cabang neuron yang mengalami
trauma akibat dari berkurangnya
impuls

• Perubahan morfologi neuron post

sinap  atropi neuron post sinap

Downey&Darling's Physiological Basis of Rehabilitation,3rd ed,2001

Anterograde and Retrograde Degeneration

Kandel, Principle of NeuroScience, 4th ed

Neuron growth after injury
There is always recovery due to Neuroplasticity

Rosenzweig et al., 2002

Learning and Memory
Learning and memory
• Ultimate aim of neural repair and rehabilitation is to restore functions
vital to an individual’s ability to live independently
• Restoration of the capacity to learn and remember is of tremendous
importance.
• Ability to learn  acquisition of novel information, relationships and
strategies, and the ability to remember and act upon what has been
learned, are essential for successful negotiation of our dynamic
environment
Definition

• The process by which we acquire

Learning
knowledge about the world

• The process by which that knowledge

Memory
is encoded, stored, and later retrieved.
 Memory

• Non-declarative, or implicit memories are those that can be expressed without awareness or conscious recollection.
• Declarative, or explicit,  memories are subject to conscious recall and generally involve awareness that the memory is
being invoked during expression
Declarative
Declarative memories include
• direct experiential knowledge that you remember acquiringepisodic memory,
• (i.e., what you had for breakfast, where you went to high school) knowledge of
facts

• the world facts  semantic memory.

• (i.e., the name of the President of the US, the sum of two plus two)
 Non Declarative (Implicit)
Non Associative Learning
• Habituation
• Decrease response result from
repetitive stimulus
• Homosynaptic
• Sensitization
• A supranormal response to a
stimulus induced by a preceding
strong stimulus
• Heterosynaptic
Priming
• A form of memory that results from exposure
to stimuli prior to a testing session
• Contohnya: bila seseorang diminta untuk
mengingat cepat: bola, mata, lemari. Lalu
diminta menyebutkan kata apa saja dengan
menggunakan huruf awal: bo...ma..le.. 
menggunakan kata dari yang pertama
diberikan
• Can be expressed without awareness
 PROCEDURAL ASSOCIATIVE LEARNING
• Classical Conditioning
• Learning of sensorimotor or cognitive Skills Association between 2 stimuli
• This type of memory is capable of being Pavlov experiment on dogs
formed and expressed without awareness • Meat  Salivation
• Example tying shoes • Metronom  Meat  Salivation
• Metronom  Salivation

• Contiguity (time)
• Contingency (always)
 Non Declarative Memory (Implicit)
• Implicit memories are stored differently depending upon how they are
acquired

• Fear conditioning (Emotional)  Amygdala

• Classical & Operant conditioning (Sceletal musculature)  Nucleus IP in
Cerebellum
 Principles of Neuroplasticity as Applied to
Rehabilitation
Requisites for learning : Guidelines for applying the principles of Evidence of measurable neuroplastic changes after intervention :
neuroplasticity in treatment anatomic/physiological
Activities must be attended, goal directed Increase in the area of representation
Behavior must be motivating/fun Smaller receptive fields
Behavior must be repeated Improved organization
Behaviors must be rewarded Increased myelination
Give feedback on performance accuracy Increased complexity of dendrites
Make stimulus strength adequate for detection Increased strength (amplitude) of evoked responses
Stimulus and behavioral expectation must be progressive in Decreased latency of response
difficulty
Stimulus induced behaviors need to be integrated into meaningful Increased consistency of response
function
Behaviors should be age appropriate Improved selective excitation
Behaviors should be integrated across sensory modalities Improved autogenic and surround inhibition
 Principles of Neuroplasticity as Applied to
Rehabilitation
Make sensory relevant to desired outputs
Repeat behaviors over time
Match training behaviors with recovery/developmental periods
Strengthen responses with multisensory modalities
Begin stimulation by using the most mature or capable sensory
receptors
Behaviors should be performed in different environmental
context
Do training in the gravitational positions that facilitate task
achievement
Preferred behaviors should be rewarded, negative behaviors
punished
Accurate behaviors should be repeated
Improved neurochemical transmission
Normalized alocation/translocation
Normalized pattern of responses
Increased interconnectedness
Spread of healthy neurons to take over function in areas where
damage occurred
Early achievement of developmental milestones
Increased specificity of neuronal firing
Increased synchrony of neuronal firing
Spatial representational mapping consistent with coincident temporal
event
Increase interrelatedness of temporally related neuronal firing
Change in number and complexity of synapses
Improved resistance to representational degradation
Cognitive Remediation
 Cognitive Remediation
• Cognition is the ability to perform the brain functions
of Attention, Memory, Language, Visual Spatial Skills and Executive Function.
• Cognitive remediation is a type of rehabilitation treatment offering exercises with an
aim at improving cognitive function

http://www.cognitive-remediation.com/
Cognitive remediation subject
• Stroke
Traumatic Brain • Tumor
injury • Head Injury

Generalize • Depression
• Schizophrenia
Condition

• ADHD
Learning disabilities • etc

http://www.scientificbraintrainingpro.com/science/remediation
 THE TERMS and CONDITION

• Cognitive remediation can only be used with clinically stable patients who
can be actively involved in their own treatment
• Able to concentrate during therapy sessions that last twenty minutes or
more
• Cognition status first has to be accurately assessed
• Define the deficient cognitive areas and the nature of these deficits

to set objectives focused on everyday situations before the treatment even

begins

http://www.cognitive-remediation.com/
Nilai: 24 -30: normal/tidak ada gangguan fungsi luhur
Nilai: 0-23 : ada gangguan fungsi luhur
Evaluasi kognitif
Orientasi
Waktu dan tepat
Atensi
- Digit pan forward  1, 3-7, 4-6-3, 5-1-9-2
- Continuous performance test:
 Menyebutkan nama bulan dalam urutan terbalik
 serial substraction
Memori
Minta pasien untuk menyebutkan 3 kata lalu minta pasien mengulangi lagi 3 menit
recall informasi umum  berdasarkan umur, budaya dan status pendidikan
IDIOM
• Pepatah/peribahasa (proverb): menjelaskan 3 proverb  konkrit/abstrak
• Pendapat (judgment)
• 3 masalah dan bagaimana mengatasinya  mencari rumah teman di kota
yang tak dikenal

KEMAMPUAN VISUOSPASIAL
a. Minta pasien untuk menggambar jam dengan waktu spesifik
Gangguan eksekusi  gambar jam terlalu kecil utk meletakkkan angka yang
direncakan
Unilateral neglect  hanya menggambar sebelah sisi dari jam
 Impairment Neurokognitif & Tehnik Intervensi

Gangguan atensi dan konsentrasi

• Pastikan pasien full-attention sebelum latihan
• Distraksi lingkungan ↓  duduk menghadap dinding, pakai earplug, bersihkan meja
• Hindarkan interupsi  beri tanda don’t disturb
• Pertahankan atensi dengan waktu yang lebih lama  tehnik yang menarik, ubah
aktivitas
• Jadwal istirahat selama sehari  cegah lelah
• Hindarkan multitasking
• Pertimbangkan alternatif obat psikostimulan

Braddom
Gangguan belajar dan memori
• Gunakan alat bantu  notes, kalender, kamera, tape recorder
• Buat struktur yang tetap dan rutin
• Informasi dalam beberapa bentuk (auditori, visual, kinetik)
• Ulangi informasi
• Rekam dan dengarkan informasi beberapa kali
• Gunakan strategi mnemonic (hafalan), tehnik perumpamaan dan rhyme (sajak) 
recall info penting
• Libatkan keluarga/caregiver

Braddom
Gangguan planning, organization, and problem solving
• Bagaimana memulai suatu rencana & evaluasinya
• Berfikir sebelum bertindak
• Ajarkan struktur problem solving  tentukan masalah, alternatif, pilih terbaik, evaluasi,
solusi sukses
• Menyediakan petunjuk dapat melakukan aktivitas step by step (misal: checklist, alarm)
• Internal compensatory strategies  self-talk (plan what to say saat akan
menelpon/mengikuti pertemuan, slowdown saat belanja
• Ajarkan pasien mengembangkan dan menjaga hubungan dengan anggota keluarga/teman
yang dapat dipercaya yang memberikan feedback baik

Braddom
Gangguan Inisiatif
• Edukasi keluarga  gangguan inisiatif vs malas
• Buat tugas menjadi beberapa komponen
• Berikan dorongan secara verbal, tulisan, atau eksternal  checklist kegiatan yang
sudah dikerjakan, alarm mengingatkan melakukan kegiatan
• Berikan tugas penting  beri tanggung jawab
• Biarkan pasien mengalami kegagalan dalam melakukan tugas  follow up
dengan feedback dan diskusi
• Berikan motivasi

Braddom
Gangguan insight/self awareness
• Memberikan informasi mengenai masalah yang ada dan fokus pada aktivitas sehari-
hari
• Monitoring dan catat perilaku spesifik ketika melakukan tugas
• Logbook terapi, domestic, dan/atau aktivitas kelompok  sukses/gagal dalam
aktivitas sehari-hari, diskusi kelebihan & kekurangan
• Beri feedback secepatnya dan beri komentar negatif dulu kemudian positif
• Edukasi keluarga dan teman untuk memberikan feedback dan supervisi

Braddom
Gangguan Bahasa
• Gunakan kalimat pendek dan sederhana, ucapkan jelas
• Instruksi dengan berbagai bentuk (oral, tulis)
• Ulang informasi dan uraikan dengan kalimat sendiri untuk memastikan telah
mendengarkan dengan baik
• Ajarkan pasien untuk meminta seseorang mengulang informasi dengan bicara lambat
dan jelas
• Beri pasien waktu untuk menemukan kata dan kalimat lengkap
• Gunakan gesture, gambar, dan isyarat saat bicara
• Edukasi keluarga dan caregiver

Braddom
Gangguan Akademik
• Cek semua pekerjaan dengan hati-hati

• Manajemen finansial diatur keluarga

• Buat catatan dan highlight atau garis bawahi kata kunci saat membaca

• Sukar mengeja  kamus / alat elektronik

• Buat flashcard  review kata yang sering lupa

• Main scrabble, puzzle, dan crossword

• Fokus kualitas vs kuantitas

Braddom
 Cognitive remediation program approach
CRP Individual Sessions CRP Group Modules
• Clients participate in individual treatment • Clients participate in five hours per day, three to
weekly five days per week
• Treatment focuses on fine-tuning specific skills • Groups address reasoning skills, generalization
to enable the client to return to work, to school of learning, and executive functioning
or to community/volunteer activities • Specialized modules focus on goal setting,
• Compensatory strategies are introduced and problem solving, strategy development,
long-term psychosocial adjustment is personal adjustment, communication, and
emphasized education
• Program includes occupational, speech and
vocational therapies
• Individual challenges, including such issues as
community/work re-integration, driving and
advocacy, are addressed
• Psychotherapy is available if indicated
 Cognitive remediation team
• Physiatrist
• Neuropsychologist
• Occupational Therapist
• Speech-Language Pathologist
• Certified Rehabilitation Vocational Counselor
• Cognitive Therapist
• Physical Therapist
• Nurse Case Manager
TERIMA KASIH