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Content uploaded by Gottfried Treviranus
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All content in this area was uploaded by Gottfried Treviranus on Oct 17, 2023
Content may be subject to copyright.
How the inflamed
skull-box might ruin
the cerebello-cerebral
social repertoire:
imaging, testing,
rescuing with currents.
www.biposuisse.ch/mons
Centre de Formation «Formehos» ::
Mons 6 - 8th Oct. 2023
Gottfried R. S. Treviranus
Psychiatrist Psychotherapist GP, praxis51, Sahlistr. 51
CH 3012 Berne, Switzerland. biposuisse@bluewin.ch
2023! Nearly post-pandemic, but… non-stop
«Emergencies» ➔
«Thoughtful Care»!
New vistas:
Cerebellum
Tangible PNEI 2.0
Infectious PNEI 2.0
Medical convergence
Roberto delle Chiaie
6000 civilian Belgians killed: including 248 arrested in Louvain.
Academical PROPAGANDA …
“To the world of culture! An appeal! (…) It is NOT TRUE that our
troops raged brutally against Löwen. With a heavy heart, THEY HAD
TO take revenge on a frenzied population that treacherously
attacked them in the neighborhood by shelling part of the city.” etc.
pp. –German martial law at the time allowed for instant executions
of “suspected” civilians.
Signed by 3000+ German academical teachers, Max Planck…
1909- 1918 Navy
1966
HS 301
«Emergencies» -The invasion of neutral Belgium
1914
37; Father politician. War child in Bosnia,
parental violence -11;0; 16;0 brother dies
in RTA. Divorced 2 children,F19 Opiates
etc. OP prognatia (? 22q11.2 DS). Severe
BP-2 Depression in remissione, but
fluctuating chronic FATIGUE.
ARACHNOID CYST near Cerebellum
SCALP, middle 3rd layer: Galea Veins
congested Radiopaedia.org
Nasal Polyps ➔Helicobacter pyloridis ➔BBB up via CagA.
E L S
➔AC ?
Profil
Whatsapp
of
patient
Ewald VAM, (..) Posterior Fossa Sub-
Arachnoid Cysts Bipolar. Cerebellum.
2023 PMID: 35568792.
F
C
R
/C
F
S
… in daily care: Cerebellar Social Phobia “plus” ➔
conspecific inaptitude SCZ-Prodromata (Porcelli 2019)
•“I don’t go anywhere because I do not know what to expect and how I then
should react”
•Social Phobia &Anergia & Hyperthymic affective temperament
•Some: F10 OH & F13 Sedatives (Karam 2023): ➔hyperthymia “treats” SAD (Valença 2005).
Several: Mixed Bipolar Spectrum (Tavormina 2021, Cervone 2022): SAD ?often fluctuate in
low register –?because of conjunction of segregated
•>> Cortico-Subcortico-Thalamo-Cortical loops -with segregated
•>> Cerebello-Thalamo/Pontine-Cortical loops (Treviranus 2022) ”reinforcing”
➔the orthogonal appropriative 4D-Thought-5+D-Action-Mood space
cognitive alternation of: INTENTIONAL least-EFFORT-anticipation ➔with
MOOD-determining evaluative PERCEPTION of effort (Treviranus 2017 ff.)
“I don’t go anywhere because I do not know…”
➔
“meta-fears” loom…
inexperience, but also “meta-fears” loom… & e.g.
≡Cognitive Disengangement Syndrome≡“Sluggish
Cognitive Tempo” (Russell Barkley)
➔
Frederick & Becker 2023 www.stephenpbecker.com:
•pervasively slipping focus “concentration”
•+ mini-narcolepsy
•+ short depressive dips = 2% pop.
•➔Atomoxetine! Cerebellum (Bareš 2018) GM(Nivins & Klingberg 2023).
•Schooler cohort SWITCHED into / out of CDS (Mayes 2023).
•ADHD (Cerebellum marrowShaw 2018) & ADHD with CDS more autistic
≡Developmental sens.-mot. Coordination Disorder ≡
Dislike: motor imagery ➔tasks, balance Cx-CBELL-loop
& post. Cortico-striatal.loop not in & Dyslexia, osmotic (Meisler & Gabrieli 2020)
MRI skull in such patients show not well
defined “hypotrophies” of the
lateralmost parts of the cerebellum
Crus-I/II near to
A) “scarred” sinus venosus transversus
& sigmoideus
(w/ parallel lymphatics) &
B) the mastoïds/petrous bones –often
in an evocative context of early, former
or present ORL-infections.
Cerebellum -?
•emerged with sharks ➔new
“central patterns”
•In humans harbors 80% of
neurons (S. Herculano-Houzel 2009)
•2x-folding ➔surface 80 % of
cerebrum`s (Gruol 2023)
•repetively simpl but & slowly
maturing +++ sophistication
(Hull & Regehr 2021)
•Output (negative) by Purkinje cells
(2nd layer, 0,2 mm) ➔arborization
into subpial molecular layer fans
(cutting mini-foldings) restoring
500 synapses per one climbing
fibre olivary nucl. or medulla.
•unipolar brush cells add lasting
reactions to rapid transiencies.
•ultrafast extracellular
“ephaptic”modulation
➔Italo-Belgian extention
of MGH- ataxiology…
Prof. Marco Molinari
Translational Res.
Fond Santa Lucia Rome
Jeremy Schmahmann
Prof. Neurology MGH
Harvard - Ataxiology
Prof. emer. Jean Mariani
Paris Sorbonne
Dir. Institute longevity
A-prof. PhD
Marie-Anne
Vanderhasselt
psychologist
gGhep Ghent
Xavier Guëll
MGH
Harvard - Ataxiology
Frank Van Overwalle (VUB): Key hypothesis :
posterior cerebellar dysfunction
➔under- OR overuse of INFLEXIBLE social routines
➔LACK of plasticity for LEARNING new, more
adaptive, SOCIAL AUTOMATISMS.
Van Overwalle, F., Baeken, C., The Role of the Posterior Cerebellum in Dysfunctional Social Sequencing 2021
Young children dispose of a maximum of cerebellar social ressources.
++++ of Working memory: R&L VI, VII, VIIA :: Executive Function : R&L VII, Crus-I, VIIB
Emotion: VII Crus-I, VIIIA
++++
Social “little” brain generates:
© Umass Developmental Sciences
Spatial navigation &
defence (da Silva 2023)
➔„comfort zone“ (CID)
(Sopp 2023).
Sopp R. et al.: Childhood Maltreatment is
Linked to Larger Preferred Interpersonal
Distances Towards Friends and Strangers
Across the Globe, 2023
If mother freezes her mimics a baby soon displays a full array of inborn
behaviors in order to reactivate the relation –despairing if this fails.
“Mentalizing”, i.e. interactively conceiving mental states (ToM, Theory-of-mind, Baron-Cohen 1985; Luyten et al.
2020), through still enigmatic computations (and tests) encompasses:
conceptual (false-belief), perceptual (face-based), affective (empathy), cognitive (perspective), and
motoric (mirror-moves linking with anterior cerebellum (Rizzolatti 2014).
The maturation of repertoires sustaining early ToM (Beuriat 2022) emerged as a needed for
cerebrally trainable optimizations in adults, hampered by early scars (Olson 2023).
The posterior cerebellum moved centerfold (Van Overwalle 2011-2023). The “sequential” ToM-
faculties are largely provided with the Crus-II and sustained mainly by the Crus-I (Ito 2008; Guell
2018; Schmahmann 2019). Conserved mentalizing –especially for sequential tasks –after several
damages requires merely the left superior posterior cerebellum, uniquely connected to all the five
frontal mentalizing areas, especially to the lateralized right ones, via a stronger thala-mo-cortical
and a still weaker cortico-pontine loop (Metoki 2022). A meta-analysis starting inversely from
functional activations (by ToM-subtasks) revealed that those at Crus-II drove 57% of the studies
involving true ToM, and even 74% adding emotional introspection (Van Overwalle 2020). Cerebellar
degeneration (with cerebral shrinkage above the tentorium cerebelli and also the sphenoid sinus)
caused losses in both cerebellar upper halfs, but autism just in the right-sided lower half (Clausi
2021). Delle Chiaie and the ataxia team discovered that BPAD-II patients showed a broader
diminution of ToM-skills and cerebellum than BPAD-I-patients (Olivito 2022), while commonalities
with schizophrenia (SCZ) appear as “pedun-culo-cerebellar” (Fig. 2).
Flatmap of the cerebellum
Functional flatmaps
Van Overwalle F (…) Leggio M. Consensus Paper: Cerebellum
and Social Cognition. Cerebellum. 2020 PMID: 32632709
How the inflamed skull-box might ruin…
the cerebello-cerebral social repertoire: imaging, testing, currents…
•Nascent cerebellar neuropsychiatry is rewriting complex human
relations:
•Humans affected by “social dysmetria” often lead minimal lives,
strongly dislike exposition, suffer fatiguability also from immune
dysfunctions, and anhedonia. Such therapy-resistant also psychotic
patients, are hampered by a lack of skills in predictively pre-
sensing the trajectories to where especially their interpersonal
„appropriations“ might end up.
•The cerebellum, and the basal ganglia together, discipline the
cortex through segregated parallel closed circuits partly
interconnected through the thalamus.
•“Patho-trajectories” of the cerebellum in daily care emerge
through also neurological ataxiology and MRI-imaging.
Cerebellar DA-system in… Schizophrenia:
> vermis cortex (Weinberger et al., 1980; … gyrification index
(Schmitt, 2011), cortical volumes
> crus I & II grey matter (Kühn et al., 2012)
> Purkinje neurons number size (Stevens, 1982; Tran, 1998)
> negative symptoms: Sp transcription factors DRD2
(Pinacho, 2013).
Autism:
> Purkinje neurons number stain (Bauman, Kemper, 1985; 1993)
Furthermore, in
the cerebellum of ASD patients, we also found a reduced
Purkinje
neuron density (Whitney et al., 2008; Skefos et al., 2014)
together
Flace P, Livrea P, Basile GA, Galletta D, Bizzoca A, Gennarini G, Bertino S, Branca
JJV, Gulisano M, Bianconi S, Bramanti A, Anastasi G. The Cerebellar
Dopaminergic System. Front Syst Neurosci. 2021 PMID: 34421548
The above mainly Italo-Belgian network explores the socio-cognitive
cerebellum within an extended mentalizing network connecting cortical areas
of all cerebral lobes & the amygdala with functional. (Van Overwalle 2020)
“Social brain” (R. Dunbar 2009): amygdala &
prefrontal (dlPFC) ➔THOUGHT anterior cingulate (ACC) cortex
➔ACTION orbitofrontal (OFC) ➔MOOD
3 medial CSTCs (Cortico-Subcortico-Thalamo-Cerebral loops) by being segregated
orthogonally modulate the appropriative dyn4TAM-engine of: abstract 4D-THOUGHT(G.
Halford), will-full neuro-economy of 5+D-ACTION (effort), MOOD valence mirroring growth
generating the temperamental and bipolar spectra since the sensualist tradition (E. Condillac
1754; Fig. XXIV in E. Kraepelin 1904; G. Treviranus 2017 ff.).
Dunbar, R.I. The social brain hypothesis and its implications for social evolution. Ann. Hum. Biol. 2009, 36, 562–572.
de Condillac EB (1754) Traité des sensations (tome I). De Bure l’aîné, Londres.
G. Carr (trans.), London: Favil Pr., 1930; School of Philosophy, Univ. South. Calif., 1930.
https://plato.stanford.edu/entries/condillac/#Bib
How the inflamed skull-box might ruin…
the cerebello-cerebral social repertoire: imaging, testing, currents…
•A uniquely pontine axonal diffusive damage to an executive-control-
loop as core of “p-factor”, the prime broad risk factor (Hariri 2019),
points to an immune-arterial hotspot at the root of cerebellar arterial
supply, as supported by the pediatric mostly inflammatory somatic “d-
factor”.
•F. G. Gall’s contention, that skulls, plausibly via mycobacteria, were
relevant, are rehabilitated by calvario-menigeal vessels (Hisayuki Yao
2018, Herisson 2018), which added the skull to the new brain logistics.
•Mast cells are uniquely positioned to cause superficial and deep cortical
pathologies, and, en-closed in its subtentorial posterior fossa, also the
cerebellum is exposed to various, often intracellular, smoldering
originally dental or ORL-infections exemplifying non-neural psychiatric
etiologies (Treviranus 2022).
Cerebellum to ongoing tasks provides an actual support through readied pertinent
alternative or complementary behavioral schemes in THOUGHT, ACTION, MOOD
with overall sensed reassurance: “Whatever happens I’ll know how to react!”.
Other “SUPPORTS” to the “self”:
felt self-competence, spatial comfort zone, bodily presence in conspecific
interactions, under reassurance or threat, rewarding habits, parental or other
«introjected» significant objects denoting emotionally accessible complexes of not
only episodic memories, textual commands etc., and the complex relations
between the own identity as a comprehensive auto-representation of the self.
Identity is usually rapidly and strongly imbued by psychiatric experiences in
subjectively both positive and negative ways. This is particularly apparent in bipolar
disorder, while schizophrenics are more inclined to refer to external threats while
suffering from shattered identities.
transcranial Direct Current Stimulation: removing IL-1beta?
Cerebellar tDCS changes cerebello-thalamo-cortical circuits during (visuo-)motor and
cognitive tasks in a polarity-specific manner, but also resting-state intrinsically
connected networks (ICNs)
https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=33627197
Grami F, de Marco G, Bodranghien F, Manto M, Habas C. Cerebellar transcranial direct current stimulation reconfigurates static
and dynamic functional connectivity of the resting-state networks. Cerebellum Ataxias. 2021 Feb 24;8(1):7. doi: 10.1186/s40673-
021-00132-6.
The cerebellum –what for?
•Specific areas guarantee seamless fluidity to tasks, beyond “models of sequenced
movements”. Disruptions of such revealed 3 ataxiological domains (Cabaraux & Monti 2023):
❖Anterior sensorimotor lobe (w/ lobule VIII): dysarthria, bad gait, posture (Dijkstra 2020)
❖Posterior lobe for eye movement & vestibular balance (vermal IX-X, flocculus)
❖Cerebellar Cognitive-Affective Syndrome (CCAS) (Schmahmann 1998) with bad
cognition, also linguistic behavior, and affect.
Psychiatric ataxiology has caught up (Eccles 1967; Guell & Schmahmann 2020; Schmahmann 2019)
at first via neuro-clinical overlap (Dekeyzer 2023).
Through fMRI new essential cerebellar contributions for attention,
working memory, executive control, and learning emerged, whereby
“predictive errors” slowly shape a repertoire of ready-made realistic
models (Manto & Shaikh 2020). This led to a further extension to the demanding
interactions with conspecifics. ➔
1) A uniform cortex hiding a universally applicable
computation ➔“dysmetria of thought theory”
(J. Schmahmann 1998 ff.) : trajectories of thoughts /
inter-conspecific encounters in computational terms
of movement.
2)
3) Ongoing U.S.-interest in autism and mast cells (Fatemi 2012; T. Theoharides 2023)
4) Convergent psychiatry
Spontan. CSF leaks of temporal bone ➔ obesity,
calvarial thinning, OSAS: incidence x 2 10y. & IIH
Rabbani C et al. JAMA OL HN Surg. PMID: 29801027 {& Rabbani C et al. & IIH Otol Neurotol 2019 PMID: 31045889}
Mastoïd roof
thinned & broke!
37%20%
Cortical localizations derided
phrenologist Franz Joseph Gall2018
long-overlooked calvario-meningeal
vessels skulls are relevant to the brain
https://becker.wustl.edu/news/franz-joseph-gall-and-the-origins-of-phrenology/
The core of SCZ instead seems largely caused by cortical events, and plausibly through calvario-
meningeal adventitial intrusions of mast cells liberating tryptase-carrying vesicles. Tryptase causes
damage to the cytoskeleton not only of oligodendrocytes (Medic 2009), but likely also to axonal
dendrites transiently de-structured during Cortical Spreading Depression (Kirov 2020; G. Dussor
2019). Medic N, Lorenzon P, Vita F, Trevisan E, Marchioli A, Soranzo MR, Fabbretti E, Zabucchi G.
Mast cell adhesion induces cytoskeletal modifications and programmed cell death in
oligodendrocytes. J Neuroimmunol. 2010; 218(1-2):57-66. doi: 10.1016/j.jneuroim.2009.10.011.
Kirov SA, Fomitcheva IV, Sword J. Rapid Neuronal Ultrastructure Disruption and Recovery during
Spreading Depolarization-Induced Cytotoxic Edema. Cereb Cortex. 2020 Sep 3;30(10):5517-5531.
doi: 10.1093/cercor/bhaa134.
Dussor G. New discoveries in migraine mechanisms and therapeutic targets. Curr Opin Physiol. 2019
Oct;11:116-124. doi: 10.1016/j.cophys.2019.10.013
Franz-Josef Gall
Finger S. Chapter 10: the birth of
localization theory. Handb Clin Neurol.
2010;95:117-28.
possibly related to calvarial
tuberculosis, has recently
been confirmed by the
calvario-meningeal vessels
and clinical psychiatric
associations with smoldering
intracellular ORL-infections
(Treviranus 2022) and
tuberculotic “bumps”.
Treviranus 2022
Calvarium (skull): 22 bones, trabecular diploë between
laminae, housing perivascular hemato-poietic stem cell
niche = vascular endothel cells: arterial aBMEC close to
bone with pericytes OR sinusoidal: NO RBC, NO platelets!
& mesenchymal stromal cells.
Yao, Hisayaku et al. Nature 2018 PMID: 30022166
Cai R et al. Nat Neurosci. 2019 PMID: 30598527
Calvario-meningeal
vessels: leucemia,
transparency,
infection,… also
around
Cerebel-
lum?
Pulous FE et al. CSF exit into the skull bone marrow
instruct hematopoiesis (…) Nat Neurosci. 2022
PMID: 35501382
Herisson F et al. (…) vascular channels skull bone marrow and brain surface (…) myeloid cell
migration Nat Neurosci. 2018 PMID: 30150661.
Neutrophils crawled against the flow towards the dura
mater after induction of stroke (in mice)
ALL m, 22
Desideri 2014
PMID: 25196617
Cugurra A et al. Skull (…) bone marrow myeloid cell reservoirs for meninges and
CNS. Science. 2021 PMID: 34083447
Not a SURPRISE? inflamed marrow in migraine
PET tracer uptake in the skull marrow/meninges in 4 migraine patients:
photophobia (all), phonophobia (some). Hadjikhani N PET Parameninges in Migraine WVA.
Ann Neurol. 2020 PMID: 32239542. … Migraine: Dendrocyte Cytoskeleton
Transiently Interrupted during
Cortical Spreading Depression
Kirov et al. Cereb Cortex 2020
“Cerebellar migraine” could also derive from calvario-meningeally
intruding mastocytes sowing vesicles carrying tryptase.
Review: Wang M (…) Sowers LP. Involvement of the cerebellum in migraine.
Front Syst Neurosci. 2022 PMID: 36313527.
R&L post. lobe less spontaneous activity (Wang J.-J. et al., 2016).
L superior cerebellum proportional to headache (Yin et al., 2020).
R&L cerebellum interictal activity was higher in the aura group
(Farago et al.,2017).
Only in women ictal phase more active (Afridi et al., 2005).
Vestibular migraine +++ ictal phase Metab. R&L (Shin et al., 2014).
Vestibular rehabilitation ➔L posterior cerebellum more
spontaneous activity.?: L cerebellar hyperactivity might
compensate for vestibular deficits(Liu L. et al., 2020)
Infections, cerebellum and Severe Mental illness
Neurotoxocariosis (& cat ownership) constitute
risk-factors for SMI. Toxocara cati/myrtax in mice
prefers the cerebellum, T. canis the cerebrum
(Janecek 2014, 2019; Waindok 2022).
Parainfectious cerebellar swelling can occur in early childhood and
results e. g. in an atrophic Crus-I/II, widening subarachnoïd space
and (non-agraphic, isolated) sloping spatial dysgraphia with
inappropriate lettering (Fournier del Castillo 2010)
Waindok P, et al. Toxocara canis- and Toxocara cati-Induced Neurotoxocarosis Is Associated
with Comprehensive Brain Transcriptomic Alterations. Microorganisms. 2022
CDK5?Gyration
CIMURAF-push-back
PET: CBF
Wind-instruments
MYCOB. Chelonae ?
HIDRADENITIS
Supp.
BBB
Dive!
Meninges: enhanced
HypoGyration CDK5
Otitis
externa NTM
SKULL
BASE :: CIMURAF: Pericallosal «push-back»-
wathershed
#1 Social phobia
#2 OH & BenzoDZs
#3 Fatigue / (Sjögren´s)
#4 BPAD2 (Cognition)
#5 Insommnia / halluc.
Dentogenic
MAXILLITIS
Granulicatella
adiaciens &
EBV norma
l
-5 to
-7
-5 to -
7*
*
Rehabilitation…