The Cerebellum: Circuitry of the Great Comparator

01Intention against execution

The cerebellum measures a predicted movement against the one the body actually made

An efference copy of the motor command arrives from the cerebral cortex, the sensory report of the movement arrives from the periphery, and the cerebellum subtracts one from the other before the movement ends. The literature calls this a forward internal model. The Unified Model of Tone names the operation the great comparator.

Feedback alone cannot steer this, and the reason it cannot, along with the forward model and the model of the loop's own delays, is worked out in the neurology of movement. The cerebellum is the structure that holds those models. The hardware is countable. Two spike codes leave the Purkinje cell, and one slow error line arrives from the olive.

The comparison happens on a single cell

Everything the cerebellum compares converges onto one cell type. Stereological electron microscopy of the rat molecular layer counted some 175,000 parallel fiber synapses on a single Purkinje cell dendritic tree Napper 1988. The density behind that count is about 817 million synapses per microliter of molecular layer. Each one carries a fragment of the body's report. A single climbing fiber wraps the same tree and carries the verdict on it. One dendritic tree holds the whole comparison, which is why cerebellar arithmetic can be read cell by cell.

Remove the cortex and the timing goes first

Rabbits were trained to produce differently timed eyelid responses to a high frequency and a low frequency tone. Before the lesion each response peaked near the moment its unconditioned stimulus was due. After lesions of the cerebellar cortex both tones elicited similarly timed responses that peaked at inappropriately short latencies Perrett 1993. The size of the change tracked the rostral-caudal extent of the lesion. The movement survived and its schedule did not. The authors read that as two sites of plasticity, one in the cortex holding learned timing and one in the nuclei holding the response itself.

When prediction and reality diverge, the cerebellum corrects the movement in flight. When the divergence persists, it rewrites the forward model, so the next attempt begins already adjusted. The activation order differs by zone. In the medial zone the cortex fires, then the cerebellum, then the muscle. In the lateral zone the cerebellum often leads, feeding forward before the cortical command fully commits.

02Findings

What the research shows

03Three layers, four nuclei

Cerebellar output leaves through four deep nuclei that Purkinje cells hold under inhibition

The dentate sits laterally, the emboliform and globose between, and the fastigial medially, and every signal leaving them is an excitation with Purkinje inhibition already taken out of it. Four nuclei strike that balance, and the three-layer cortex above them exists to modulate the traffic passing through. Purkinje cells are the sole output cells of the cerebellar cortex Zhou 2014. That cortex reaches the cerebellar and the vestibular nuclei through one GABAergic, inhibitory projection Zhou 2015.

One region skips the deep nuclei entirely. Purkinje cell axons of the flocculonodular lobe synapse directly onto the vestibular nuclei in the brainstem, which makes those brainstem nuclei the functional analog of a fifth output station. What they receive from the labyrinth is covered in the vestibular system.

Both afferent systems excite cortex and nuclei together. Mossy fibers reach Purkinje cells through granule cells and their parallel fibers while their collaterals drive the nuclei directly. Climbing fibers reach Purkinje cells without a relay. The cortex then inhibits the deep nuclei during the same window in which the collaterals are driving them, so every cerebellar output is a live subtraction performed on an excitation.

The brake works by timing

Cerebellar nuclear cells fire at about 60 spikes per second, and the synchrony of Purkinje inhibition decides whether mossy fiber excitation can lift that rate. Dynamic clamp recordings in cerebellar slices from weanling mice put the numbers on it Wu 2017. Holding that rate against inhibition from spontaneously active Purkinje cells takes a few hundred mossy fibers, each running at a few tens of spikes per second. With the amount of inhibition held constant, coherence of at least 10 inhibitory inputs within 2 to 4 milliseconds lets excitation raise nuclear firing, while maximally asynchronous inhibition suppresses spiking most. The timing of the brake sets both the rate and the pattern of the output.

The cortex above is not physiologically uniform either. Interspike interval distributions and short pauses under 500 ms differ by lobule and by zebrin module in awake mice Zhou 2015. Pauses longer than 500 ms are rare, and they track tissue damage and lower recording temperature.

04Counting the cerebellum

Most of the neurons in the human brain sit in the cerebellum rather than the cerebral cortex

Granule cells outnumber every other neuron in the brain by two orders of magnitude. Unbiased stereology in five elderly men put total cerebellar cells at 105 billion, of which 101 billion were granule cells, alongside 30.5 million Purkinje cells Andersen 1992. A later human series counted 109 billion granule cells and 28 million Purkinje cells Andersen 2003. The 2003 series works out to roughly 3,900 granule cells for every Purkinje cell, the 1992 series to roughly 3,300.

The dentate nucleus holds 5.01 million neurons Andersen 1992. All of that cortex speaks through four nuclei whose neuron counts sit roughly four orders of magnitude below the granule cell population reporting into them.

Isotropic fractionation counts 3.6 cerebellar neurons for every cortical neuron across 19 mammalian species

Isotropic fractionation returns a lower cerebellar number and the same verdict. The adult male human brain contains on average 86.1 billion neurons, and only 19 percent of them sit in the cerebral cortex Azevedo 2009. Across 19 mammalian species from four orders, the cerebellum holds 3.6 neurons for every neuron in the cerebral cortex Herculano-Houzel 2010. Applied to those 86.1 billion, the ratio places roughly 59 billion neurons in the cerebellum. Stereology and fractionation disagree on the absolute figure and agree on the arithmetic that matters.

What age takes and what it leaves

Aging empties the cerebellum unevenly. No global loss of Purkinje or granule cells was detected with age in the human stereological series Andersen 2003. White matter fell by 26 percent and the mean Purkinje cell body shrank by 33 percent, while the volume of the Purkinje nucleus held. The anterior lobe lost about 40 percent of both its Purkinje and its granule cells while the rest of the cortex held its numbers. That lobe carries a known job in this circuit. Aspiration lesions of it in rabbits left conditioned eyelid responses with no significant decline across ten training sessions, an animal that could no longer extinguish what it had learned Perrett 1995.

05Vestibulo, spino, neo

The cerebellum divides three ways at once, by evolutionary age and by the loop each division joins

The vestibulocerebellum, the spinocerebellum, and the neocerebellum answer to the vestibular nuclei, the spinal cord, and the cerebral cortex respectively. The vestibulocerebellum is the flocculonodular lobe, and it governs eye movements and posture. The spinocerebellum is the vermis and paravermis, and it manages posture and limb movement through the fastigial nucleus and through the emboliform and globose nuclei. The neocerebellum is the lateral posterior lobe, and it handles motor planning and executive function through the dentate. The vermis is folded into lobules numbered I to X.

The archicerebellum is the oldest tier, the paleocerebellum the second, and the neocerebellum the newest and uniquely enlarged in the human brain. The neocerebellum draws its input from the contralateral pontine nuclei, which relay the youngest cortical territory. Its output threads the long dentato-rubro-thalamo-cortico-ponto-cerebellar loop. That loop coordinates fine finger movement of the kind typing demands. It also reaches speech and affect.

Human topography follows the same split. The sensorimotor cerebellum occupies the anterior lobe with a second representation in lobule VIII, and the cognitive cerebellum has three separate topographic representations in the posterior lobe Schmahmann 2019. The division runs in the coordinate frame of the prediction as well. Lateral regions predict in visual, egocentric or peripersonal coordinates, while intermediate regions predict in motor coordinates Miall 1993. Position inside the cerebellum predicts which loop a Purkinje cell belongs to and therefore which kind of error its output corrects.

The loops are closed, and one of them serves thought

Retrograde transneuronal transport of rabies virus in a nonhuman primate showed that cerebro-cerebellar communication is built from closed circuits Kelly 2003. The arm area of M1 receives input from Purkinje cells located primarily in lobules IV to VI. Prefrontal area 46 receives input from Purkinje cells located primarily in Crus II of the ansiform lobule. Each cortical area sends input through the pons to the cerebellar territory that projects back to it. One loop serves motor cortex and a separate loop serves dorsolateral prefrontal cortex, which is the anatomy under every claim that the cerebellum reaches cognition.

06Two spike codes

Purkinje cells speak in two spike codes whose rates differ by a factor of roughly forty

Simple spikes run at 37 plus or minus 21 Hz across the full sample of anesthetized cat flocculus cells, close to the rate seen in the alert cat Demer 1985. They arise spontaneously and through the mossy fiber to granule cell to parallel fiber pathway. Complex spikes are rarer and stranger, an initial action potential trailed by a series of smaller spikelets, generated by the climbing fiber system arising from the inferior olive. In the awake monkey ventral paraflocculus the complex spike rate is 1 Hz Kobayashi 1998.

A channel firing once per second still conveys information about high frequency sensory and motor events, and in those monkeys complex spikes and simple spikes were negatively correlated cell by cell Kobayashi 1998. Simple spikes report what the body is doing. Complex spikes report that the prediction missed.

The olive is a population clock

The cerebellum takes its error clock from the inferior olive. Olivary neurons generate synchronous subthreshold oscillations of their membrane potential at 1 to 10 Hz, and they are electrically coupled through gap junctions Leznik 2005. The oscillation is intrinsic to each neuron. The gap junctions exist to synchronize the population, and blocking them in rat brainstem slices leaves every cell oscillating while destroying coherent ensemble timing. The coupled population is capable of fast and reliable phase resetting, and that reset is the error correcting event Llinás 2009. One slow clock times error across a cortex whose own chatter runs far faster.

Silencing the error channel changes the other one

The olive sets the working point of the cells it corrects. In the anesthetized cat, the 11 Purkinje cells tested ran at 23 plus or minus 13 Hz before the block Demer 1985. Reversible block of the olivocerebellar pathway raised mean simple spike rate to 40 plus or minus 18 Hz and cut the variability of that rate by half. Driving complex spikes electrically in the same cats suppressed simple spike firing completely at or above a cut-off frequency of evoked complex spikes. That cut-off ran at a median of 5 Hz across a range of 1 to 10 Hz in 15 cells. Remove a signal arriving once a second, and a signal arriving twenty times a second nearly doubles its rate and halves its variability.

What a climbing fiber burst writes

Pairing the two inputs depresses the synapse. When a climbing fiber input and a set of granule cell axons are repeatedly associated, the efficacy of those granule cell axons in exciting the Purkinje cell is persistently depressed Ito 2001. Long-term depression eliminates the synaptic connections associated with errors during repeated exercises while preserving those leading to successful execution of movements.

Three hundred conjunctive pulses at 1 Hz induce long-term depression most strongly in rat Purkinje cells in vitro Karachot 1994. Induction is inhibited when the parallel fiber stimulus precedes the climbing fiber by 10 to 100 ms, and it still occurs when the parallel fiber lags by as much as 2 seconds. The optimal frequency is the olive's own complex spike rate, and the order of arrival decides the outcome.

A learned task shows up as increased Purkinje simple spike output during smooth performance. The moment an obstacle interrupts, the olive fires a complex burst flagging the error, and the burst rewrites the parallel fiber synapses that were active. Several forms of long-term plasticity coexist in this circuit alongside mechanisms regulating spike timing and oscillation, which is what permits complex learning instead of one stored correction. That division of labor is what the rabbit lesions exposed. The cortex holds when a correction should fire, and the nuclei hold the correction itself.

07Pressure and cognition

The cerebellum runs the same correction on blood pressure and on cognition that it runs on limbs

Through the fastigial nucleus the cerebellum reaches arterial pressure, cerebral blood flow, feeding, and breathing. Fastigial stimulation in anesthetized cats raised arterial pressure from 94 plus or minus 10 to 133 plus or minus 6 mmHg, and to 189 plus or minus 9 mmHg at higher intensity Williams 1990. Cerebral blood flow did not change during the smaller rise. Cerebral vascular resistance climbed about 40 percent and autoregulation held, so a large input reached the cerebral vessels and their own regulation absorbed it.

Removing the same nucleus changes the recovery and not the challenge. Bilateral rostral fastigial lesions in anesthetized cats did not alter the rate or extent of the pressure fall induced by nitroprusside Chen 1994. Those lesions cut the reflex heart rate increase per unit fall in pressure by 39 percent and prolonged the time to 50 percent pressure recovery by 93 percent. During a phenylephrine-induced pressure rise the same lesions augmented reflex gain by 68 percent. The authors concluded that the cerebellum modifies baroreflex sensitivity by augmenting sympathetically mediated cardiovascular responses and inhibiting parasympathetically mediated ones.

One direction lost gain and the other gained it. The lesion left the size of the cardiovascular response intact and removed the trimming that keeps it proportional in both directions.

A direct wire to the hypothalamus

Cerebellar nuclei and hypothalamus wire to each other in both directions. Horseradish peroxidase tracing in laboratory mammals identified connections between the cerebellar nuclei and the hypothalamus, and between several hypothalamic regions and the cerebellar cortex Haines 1984. Axons from all four deep nuclei run up through the superior cerebellar peduncle, cross the midline, and enter the hypothalamus. These connections place the cerebellum inside the visceral functions that accompany somatomotor activity.

Retrograde tracing in the rat located the descending arm of that axis Dietrichs 1992. Hypothalamo-cerebellar fibers originate mainly in the lateral, dorsal and posterior hypothalamic areas and in the tubero-mammillary nucleus. Smaller numbers of cells sit in tuber cinereum, the anterior hypothalamic area, and the periventricular and paraventricular nuclei. The authors concluded that part of the pathway uses histamine or GABA, and the absence of D-aspartate labeling argued against excitatory amino acids.

Dysmetria of thought

Impairment of the lateral neocerebellum degrades planned voluntary movement into intention tremor, dysmetria, and dysarthria, and the deficit crosses into the mind. Neurological examination, bedside mental state testing, neuropsychological study and imaging in 20 patients with disease confined to the cerebellum defined the cerebellar cognitive affective syndrome Schmahmann 1998. Deficits appeared in executive function, spatial cognition, personality and affect, and language. Behavioral change followed posterior lobe and vermis lesions, while anterior lobe lesions produced only minor executive and visual-spatial change.

Schmahmann named the claim beneath that syndrome the universal cerebellar transform Schmahmann 2010. What the cerebellum does for sensorimotor and vestibular control it also does for cognition, emotion, and autonomic function Schmahmann 2019. It maintains behavior around a homeostatic baseline, automatically and without conscious awareness. Dysmetria of thought is the overshoot a damaged cerebellum shows in checking a movement, reappearing as a mismatch between reality and perceived reality. Capacity, consistency, and appropriateness of cognition all bend.

08Spinal input to the comparator

The cerebellum can only correct against the body report it receives, and the spine supplies a large share of that report

Proprioceptive traffic reaches the cerebellum by more than one route. Clarke's column is the major contributor to the direct spinocerebellar pathway. Genetic tracing in mice showed its mossy fiber terminals diversifying extensively in the cerebellar cortex and terminating bilaterally Pop 2022. Those axons left no significant collaterals in the spinal cord, the medulla, or the cerebellar nuclei. Indirect routes run through the spino-lateral reticular and spino-olivary tracts, derived in part from cervical neurons of the Atoh1 lineage. The cervical spinal cord feeds the inferior olive, and the olive is the source of the climbing fibers that carry error.

Neck position is measurable at the Purkinje cell itself. In the decerebrate cat, rotating the body relative to the head rotates the preferred direction of the forelimb triceps response to labyrinthine stimulation Manzoni 2004. Purkinje cells rotate their own preferred directions in the same direction and by the same angle as the body. Functional inactivation of the ipsilateral cerebellar vermis greatly reduced that rotation. Cervical somatic input tunes the vestibular channels impinging on Purkinje cells and shifts the reference frame during sensorimotor transformations.

The cerebellum can hold a stale account

The Unified Model of Tone stakes its claim about the cerebellum here. The comparator holds an account of the body and updates that account only where a climbing fiber burst coincides with active parallel fibers inside the window Karachot measured. Distort the body report at its source and the correction is written against an account the body no longer matches. The forward model drifts, and the drift is stable, because nothing arriving in the circuit contradicts it.

Two consequences follow. The first is that the mismatch persists with nothing broken. No cell has died and no fiber has degenerated. What has failed is correspondence between the account and the body. The second is that the repair is made by timing. Pairing decides which synapses change, and an unpaired volley, however large, changes none. The model develops that condition as a standing prediction error held in tone on the research page on predictive processing. The cerebellum supplies the machinery that writes and rewrites it, the climbing fiber, the pairing window, and the olivary clock that times both.

Where care enters this circuit

Chiropractic care reaches this circuit through the afferents the spinocerebellar and spino-olivary tracing follows. They arrive at Clarke's column, the lateral reticular nucleus, and the inferior olive, the origin of every climbing fiber in the cerebellum. That is access to the body report and to the error line rather than to the output, and the model's claim is correspondingly narrow. An input whose timing falls inside the climbing fiber and parallel fiber coincidence window changes which synapses are rewritten. An input outside that window changes what the comparator is told about the body. Cerebellar output follows both.

Read through this circuit, a movement problem is a report problem before it is a muscle problem. The cerebellum will faithfully execute a correction computed against whatever account it has been given, so the fidelity of the report decides the quality of the movement. A cerebellum updating against a truthful report keeps the body free to adapt, and that freedom is what the model calls health. A cerebellum updating against a stale one holds tone outside its range. The drift surfaces as clumsiness and tremor. It surfaces too in the autonomic and cognitive channels this same circuit trims.

09Tone

How this system expresses tone

The cerebellum expresses all of tone in units of time rather than force. The signature runs through prediction, through the fidelity of the body report arriving, and through the coupling that keeps error timed across the whole cortex.

Run the rest of the foundations through these three layers and each one returns a number. Gain: blocking the climbing fiber pathway lifted mean simple spike rate from 23 to 40 Hz in the cat, so one input sets how loudly another speaks. Oscillation: the olivary rhythm is the carrier, and a fast reliable phase reset of it is the event that writes a correction. Time course: a complex spike lasts milliseconds, long-term depression needs 300 pairings at 1 Hz, and the anterior lobe gives up about 40 percent of its Purkinje and granule cells across a lifetime. Load: the cerebellum samples the body through 101 to 109 billion granule cells, and that sampling runs whether or not anything is moving. Set point: the fastigial nucleus leaves the size of a pressure fall alone and tunes the recovery, cutting baroreflex gain 39 percent in one direction and raising it 68 percent in the other. Constraint: Purkinje cells release GABA at every target they reach, so a cerebellar correction can only be a withdrawal of inhibition and the deep nuclei must supply the excitation themselves.

10Across the library

How this page relates to the rest of the library

11Frequently asked

Questions about this topic

12The sources

References

Sources: primary literature, linked inline.