Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state tests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum.

/pdf/the-cerebellar-cognitive-affective-syndrome-2qlts0j1w1.pdf

The cerebellar cognitive affective syndrome.

Does the cerebellum influence nonmotor behavior? Recent anatomical studies demonstrate that the output of the cerebellum targets multiple nonmotor areas in the prefrontal and posterior parietal cortex, as well as the cortical motor areas. The projections to different cortical areas originate from distinct output channels within the cerebellar nuclei. The cerebral cortical area that is the main target of each output channel is a major source of input to the channel. Thus, a closed-loop circuit represents the major architectural unit of cerebro-cerebellar interactions. The outputs of these loops provide the cerebellum with the anatomical substrate to influence the control of movement and cognition. Neuroimaging and neuropsychological data supply compelling support for this view. The range of tasks associated with cerebellar activation is remarkable and includes tasks designed to assess attention, executive control, language, working memory, learning, pain, emotion, and addiction. These data, along with the revelations about cerebro-cerebellar circuitry, provide a new framework for exploring the contribution of the cerebellum to diverse aspects of behavior.

/pdf/cerebellum-and-nonmotor-function-55lxgbwnri.pdf

Cerebellum and Nonmotor Function

Many diseases involve the cerebellum and produce ataxia, which is characterized by incoordination of balance, gait, extremity and eye movements, and dysarthria. Cerebellar lesions do not always manifest with ataxic motor syndromes, however. The cerebellar cognitive affective syndrome (CCAS) includes impairments in executive, visual-spatial, and linguistic abilities, with affective disturbance ranging from emotional blunting and depression, to disinhibition and psychotic features. The cognitive and psychiatric components of the CCAS, together with the ataxic motor disability of cerebellar disorders, are conceptualized within the dysmetria of thought hypothesis. This concept holds that a universal cerebellar transform facilitates automatic modulation of behavior around a homeostatic baseline, and the behavior being modulated is determined by the specificity of anatomic subcircuits, or loops, within the cerebrocerebellar system. Damage to the cerebellar component of the distributed neural circuit subserving sensorimotor, cognitive, and emotional processing disrupts the universal cerebellar transform, leading to the universal cerebellar impairment affecting the lesioned domain. The universal cerebellar impairment manifests as ataxia when the sensorimotor cerebellum is involved and as the CCAS when pathology is in the lateral hemisphere of the posterior cerebellum (involved in cognitive processing) or in the vermis (limbic cerebellum). Cognitive and emotional disorders may accompany cerebellar diseases or be their principal clinical presentation, and this has significance for the diagnosis and management of patients with cerebellar dysfunction.

https://neuro.psychiatryonline.org/doi/pdfplus/10.1176/jnp.16.3.367

Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome

The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat

The cerebellum and cognition.

Bilateral electrolytic lesions of the nucleus tractus solitarii in the rat at the level of the obex abolished baroreceptor reflexes and resulted in an immediate, marked elevation in systemic blood pressure without a change in heart rate. In unanesthetized rats the hypertension was associated with a marked increase in total peripheral resistance, a reduction in blood flow in the abdominal aorta, and an increase in central venous pressure. The cardiac output was reduced to 62% of control as a consequence of reduced stroke volume, which was reflected, in turn, by increased end-diastolic pressure. The hypertension was abolished and the end-diastolic pressure lowered by blockade of alpha receptors with phentolamine. The hypertension was not due to changes in blood gases or to release of agents from the kidneys or the adrenal glands; it was very sensitive to anesthetics and was abolished or aborted by midcollicular decerebration. Within hours after lesioning, the rats developed progressive congestive heart failure and died in shock, often in association with pulmonary edema. We concluded that the fulminating hypertension evoked by lesions of the nucleus tractus solitarii was due to the increased vasoconstriction caused by the augmented discharge of sympathetic nerves in response to central deafferentation of baroreceptor reflexes; the hypertension was mediated by alpha receptors and depended on the integrity of structures lying above the midbrain.

Acute Fulminating Neurogenic Hypertension Produced by Brainstem Lesions in the Rat

Electrical stimulation at single sites in the rostral fastigial nucleus elicits hypertension, grooming, feeding, and attack behaviors in the cat. The stimulus intensity and availability of suitable goal objects determines the behavior. Bilateral lesions of the area fail to produce motor deficits. The rostral fastigial nucleus may be a cerebellar area for behavioral and autonomic regulation.

https://science.sciencemag.org/content/sci/182/4114/845.full.pdf

Predatory Attack, Grooming, and Consummatory Behaviors Evoked by Electrical Stimulation of Cat Cerebellar Nuclei

The contribution of the fastigial nucleus and the vestibular nerves (eighth cranial nerves) to the orthostatic reflexes in anesthetized, paralyzed cats was studied. Bilateral lesions of the rostral fastigial nucleus resulted in impairment of the reflex changes in blood pressure, femoral arterial flow, and resistance evoked by head-up tilting to 30 deg or 60 deg. The rostral fastigial nucleus, which might be triggered by the vestibular apparatus, appears to participate in concert with the baroreceptors in the initiation and possibly the maintenance of the orthostatic reflexes.

Role of the Cerebellum and the Vestibular Apparatus in Regulation of Orthostatic Reflexes in the Cat

Bilateral lesions of the nucleus tractus solitarius (NTS) in rats result in acute fulminating hypertension (NTS hypertension) as a consequence of central deafferentation of baroreceptors. The hypertension is due to increased peripheral resistance and decreased cardiac output. The hypertension is blocked and cardiac output is increased by phentolamine, trimethaphan (Arfonad), and reserpine but not by propranolol. In the present experiment, systemically administered 6-hydroxydopamine (6-OH-DA) did not alter NTS hypertension if the adrenal glands were intact. Adrenalectomy, however, blocked the lesion-induced rise in blood pressure in 6-OH-DA-treated rats. Intracisternally administered 6-OH-DA (600 µg) lowered the concentration of norepinephrine only in the spinal cord and blocked the development of NTS hypertension. Local injection of 6-OH-DA into the lateral hypothalamus did not affect the hypertension. Injection of 6-OH-DA into the NTS resulted in a mild, transient elevation in blood pressure. The results...

Role of Central and Peripheral Adrenergic Mechanisms in Neurogenic Hypertension Produced by Brainstem Lesions in Rat

1. Changes in regional blood flow and cardiodynamics were measured in anaesthetized paralysed cats during electrical stimulation of the rostral fastigial nucleus.

2. Fastigial stimulation results in a graded, highly reproducible and stereotyped cardiovascular response characterized by (a) increased systolic, diastolic and mean arterial pressures without changes in central venous or occluded vein pressure, (b) decreased blood flow and increased vascular resistance in the axillary, renal, femoral and mesenteric arteries, increased flow without any change in vascular resistance in the common carotid artery, and increase in total peripheral resistance, (c) a small increase in heart rate and myocardial contractile force, decrease in calculated stroke volume, and no change in the cardiac output.

3. Changes in regional arterial flow were abolished by transection of sympathetic nerves or blockade of α-adrenergic receptors by systemic administration of phentolamine.

4. Changes in heart rate and myocardial contractility were abolished by stellate ganglionectomy or blockade of β-adrenergic receptors by propranolol.

5. No changes in pupillary diameter or retraction of the nictitating membrane were seen during fastigial stimulation with stimuli producing substantial changes in blood pressure.

6. The fastigial pressor response represents a highly reproducible, stereotyped, graded, and differentiated pattern of activation of sympathetic preganglionic neurones.

7. The pattern of cardiovascular effects of fastigial stimulation simulates the compensatory (orthostatic) reflex response to maintenance of an upright posture.

8. Fastigial stimulation appears to excite the neural network subserving orthostatic reflexes.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1972.sp010056

Changes in regional blood flow and cardiodynamics evoked by electrical stimulation of the fastigial nucleus in the cat and their similarity to orthostatic reflexes

Nobutaka Doba

Papers

Acute Fulminating Neurogenic Hypertension Produced by Brainstem Lesions in the Rat

Predatory Attack, Grooming, and Consummatory Behaviors Evoked by Electrical Stimulation of Cat Cerebellar Nuclei

Role of the Cerebellum and the Vestibular Apparatus in Regulation of Orthostatic Reflexes in the Cat

Role of Central and Peripheral Adrenergic Mechanisms in Neurogenic Hypertension Produced by Brainstem Lesions in Rat

Changes in regional blood flow and cardiodynamics evoked by electrical stimulation of the fastigial nucleus in the cat and their similarity to orthostatic reflexes