The Cerebellar Vermis in Psychopathology: Historical and Functional Imaging Perspectives.
Developmental Biopsychiatry Research Program Martin Teicher Ann Polcari Cynthia McGreenery Rebecca Feldman Steven Lowen Afaf Stevens Elizabeth Valente Danielle Webster Frederic Schiffer Brain Imaging Center Perry Renshaw Luis Maas Eileen Connolly Anne Smith Blaise Frederick Chrissy Cintron Constance Moore Larry Wald Sue Babb Marc Kaufman
Vermis: a midline region of the cerebellum. http://medstat.med.utah.edu/kw/sol/sss/mml/sol02853.jpg
Cerebellar vermis a.k.a. arborvitae “the tree of life”
Functional anatomy of the vermis
http://medstat.med.utah.edu/kw/sol/sss/mml/sol02077.jpg
Lesions of the Vermis
From Harlow, “The nature of love.” American Psychologist 13;673-85, 1958
(from Larsell & Jansen, 1972)
Berman (1971) and others found that lesions of the vermis made aggressive Harlow monkeys docile.
Robert G. Heath, Chairman of Psychiatry at Tulane University
PPT Slide
From Heath et al., (1983) Cerebellar stimulation for treatment of intractable behavioral disorders and epilepsy. In Neural Stimulation, Volume II, CRC press, Boca Raton, Fl.
Summary of Patient Improvement with Cerebellar Stimulation
Functional Imaging of the Vermis Early Abuse and Corticolimbic Development Dose-Dependent Effects of Methylphenidate in Children with ADHD
LIMBIC SYSTEM CHECKLIST-33 (LSCL-33) The LSCL-33, was designed to measure somatic, sensory, behavioral, and memory symptoms suggestive of temporal lobe epilepsy. Child abuse can be likened to a kindling phenomena (Teicher, Ito et al. 1997). In a study of over 250 outpatients (Teicher, Glod et al. 1993), physical abuse was found to be associated with a 38% increase in LSCL-33 scores (P < 0.01), sexual abuse with a 49% increase (P < 0.02), and combined abuse with a 113% increase (P < 0.0001). Physical or sexual abuse alone was associated with elevated LSCL-33 scores only if the abuse occurred before age 18.
Human Vermis 18 weeks - 10 years
Subjects: Thirty seven young adults (9M/28F; 18-22 yr) participated, including17 (3M/14F) with a history of sexual or verbal child abuse exclusive of physical trauma. All subjects were recruited by advertisement and were not using illicit substances or medications. Exclusion factors: History of DSM-IV axis I psychiatric disorder neurological disease or complications during delivery or perinatal period. Subjects with seizure disorders or head injuries were excluded if the injury resulted in loss of consciousness for more than 2 hours, or fractured the skull. Inclusion criterium: Satisfactory completion of the following assessment tests: Abuse Trauma Questionnaire (ATQ), Parental Bonding Instrument (PBI), Dissociative Experience Scale (DES), Limbic System Check List (LSCL-33), and Medical History-Birth Questionnaire.
T2 Relaxometry
A robust correlation was observed between blood flow in the midline vermis and LSCL-33 scores.
WORKING HYPOTHESES: Abnormally elevated resting blood flow in the vermis, in association with high LSCL-33 scores, may be a marker of early abuse or trauma, as well as, an irritable limbic system (lower threshold for limbic seizures). Is abnormally elevated blood flow associated with other psychiatric disorders?
The Vermis and ADHD?
Effective Treatments: Julie Schweitzer et al (1998) and our group have demonstrated that blood flow in the cerebellar vermis is unusually responsive to methylphenidate administration and highly correlated with improved measures of attention and behavior.
Clinical Signs in ADHD
Dose-Dependent Effects of Methylphenidate in ADHD
Objective Measures of Hyperactivity
ROI’s (regions of interest)
Typical vermial slice sampled by T2 relaxometry
Dose-Dependent Changes in T2
Behavior vs. Vermial T2
RESULTS: • A significant dose-dependent resting blood flow decrease was observed only in the vermis [F 3,21 = 5.123, p< .01]. • Trend analysis supported a dose-dependent linear decline of blood flow (reflected in elevated T2 values) in the vermis [F 1,27 = 13.676, p< .001].
RESULTS: • Objective measures of attention and activity collected within 1 - 3 hours of methylphenidate adminstration exhibited significant dose-dependent effects that paralled vermal blood flow alterations.
RESULTS: -The SD of CPT performance was significantly lowered in a dose-dependent fashion, indicating an association between attention and vermal blood flow.
The Vermis and Behavior (un-medicated)
The Vermis and Behavior (medicated)
CONCLUSIONS AND SPECULATIONS----CHILD ABUSE: • The LSCL-33 appears to provide an indirect assessment of vermal blood flow. • The use of chronic electrical stimulation of the vermis to treat human epilepsy is consistent with our findings and with the kindling hypothesis of child abuse. • The extended postnatal development of the vermal cortex (Isumi et al., 1997) could increase its susceptibility to early environmental insults.
CONCLUSIONS AND SPECULATIONS: • Abnormal vermal blood flow or metabolism is associated with psychiatric symptoms in ADHD, Early Child Abuse, Bipolar Disorder, PTSD, and schizophrenia. • The vermis may function in motor and emotional coordination through bihemispheric influences on dopamine release in the basal ganglia, amygdala and accumbens (Snider and Maiti, 1976; Supple and Kapp, 1994) via fastigial nucleus projections (Heath and Harper, 1974) to pontine and mesencephalic and hypothalamic nuclear groups.
Other ROI’s (regions of interest)
Email: carl_anderson@hms.harvard.edu
Home Page: http://remfractal.mclean.org:8080/
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