MRI Shrimp Sign in Cerebellar Progressive Multifocal Leukoencephalopathy: Description and Validation of a Novel Observation.

BACKGROUND AND PURPOSE: There are no validated imaging criteria for the diagnosis of progressive multifocal leukoencephalopathy in the cerebellum. Here we introduce the MR imaging shrimp sign, a cerebellar white matter lesion identifiable in patients with cerebellar progressive multifocal leukoencephalopathy, and we evaluate its sensitivity and specificity. MATERIALS AND METHODS: We first identified patients with progressive multifocal leukoencephalopathy seen at Massachusetts General Hospital between 1998 and 2019 whose radiology reports included the term "cerebellum." Drawing on a priori knowledge, 2 investigators developed preliminary diagnostic criteria for the shrimp sign. These criteria were revised and validated in 2 successive stages by 4 additional blinded investigators. After defining the MR imaging shrimp sign, we assessed its sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: We identified 20 patients with cerebellar progressive multifocal leukoencephalopathy: 16 with definite progressive multifocal leukoencephalopathy (mean, 46.4 [SD, 9.2] years of age; 5 women), and 4 with possible progressive multifocal leukoencephalopathy (mean, 45.8 [SD, 8.5] years of age; 1 woman). We studied 40 disease controls (mean, 43.6 [SD, 21.0] years of age; 16 women) with conditions known to affect the cerebellar white matter. We defined the MR imaging shrimp sign as a T2- and FLAIR-hyperintense, T1-hypointense, discrete cerebellar white matter lesion abutting-but-sparing the dentate nucleus. MR imaging shrimp sign sensitivity was 0.85; specificity, 1; positive predictive value, 1; and negative predictive value, 0.93. The shrimp sign was also seen in fragile X-associated tremor ataxia syndrome, but radiographic and clinical features distinguished it from progressive multifocal leukoencephalopathy. CONCLUSIONS: In the right clinical context, the MR imaging shrimp sign has excellent sensitivity and specificity for cerebellar progressive multifocal leukoencephalopathy, providing a new radiologic marker of the disease.

Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders.

Cerebellar reserve refers to the capacity of the cerebellum to compensate for tissue damage or loss of function resulting from many different etiologies. When the inciting event produces acute focal damage (e.g., stroke, trauma), impaired cerebellar function may be compensated for by other cerebellar areas or by extracerebellar structures (i.e., structural cerebellar reserve). In contrast, when pathological changes compromise cerebellar neuronal integrity gradually leading to cell death (e.g., metabolic and immune-mediated cerebellar ataxias, neurodegenerative ataxias), it is possible that the affected area itself can compensate for the slowly evolving cerebellar lesion (i.e., functional cerebellar reserve). Here, we examine cerebellar reserve from the perspective of the three cornerstones of clinical ataxiology: control of ocular movements, coordination of voluntary axial and appendicular movements, and cognitive functions. Current evidence indicates that cerebellar reserve is potentiated by environmental enrichment through the mechanisms of autophagy and synaptogenesis, suggesting that cerebellar reserve is not rigid or fixed, but exhibits plasticity potentiated by experience. These conclusions have therapeutic implications. During the period when cerebellar reserve is preserved, treatments should be directed at stopping disease progression and/or limiting the pathological process. Simultaneously, cerebellar reserve may be potentiated using multiple approaches. Potentiation of cerebellar reserve may lead to compensation and restoration of function in the setting of cerebellar diseases, and also in disorders primarily of the cerebral hemispheres by enhancing cerebellar mechanisms of action. It therefore appears that cerebellar reserve, and the underlying plasticity of cerebellar microcircuitry that enables it, may be of critical neurobiological importance to a wide range of neurological/neuropsychiatric conditions.

Correlations between MRI white matter lesion location and executive function and episodic memory.

OBJECTIVES: MRI white matter hyperintensity (WMH) volume is associated with cognitive impairment. We hypothesized that specific loci of WMH would correlate with cognition even after accounting for total WMH volume. METHODS: Subjects were identified from a prospective community-based study: 40 had normal cognition, 94 had mild impairment (defined here as a Clinical Dementia Rating [CDR] score of 0.5 without dementia), and 11 had mild Alzheimer's dementia. Factor analysis of a 22-item neuropsychological battery yielded 4 factors (episodic memory, executive function, spatial skills, and general knowledge). MRI WMH segmentation and analysis was performed using FreeSurfer software. RESULTS: Higher WMH volume was independently associated with lower executive function and episodic memory factor scores. Voxel-based general linear models showed loci where WMH was strongly inversely associated with specific cognitive factor scores (p < 0.001), controlling for age, education, sex, APOE genotype, and total WMH volume. For episodic memory, clusters were observed in bilateral temporal-occipital and right parietal periventricular white matter, and the left anterior limb of the internal capsule. For executive function, clusters were observed in bilateral inferior frontal white matter, bilateral temporal-occipital and right parietal periventricular white matter, and the anterior limb of the internal capsule bilaterally. CONCLUSIONS: Specific WMH loci are closely associated with executive function and episodic memory, independent of total WMH volume. The anatomic locations suggest that WMH may cause cognitive impairment by affecting connections between cortex and subcortical structures, including the thalamus and striatum, or connections between the occipital lobe and frontal or parietal lobes.

Cerebellar stroke without motor deficit: clinical evidence for motor and non-motor domains within the human cerebellum.

OBJECTIVE: To determine whether there are non-motor regions of cerebellum in which sizeable infarcts have little or no impact on motor control. EXPERIMENTAL PROCEDURES: We evaluated motor deficits in patients following cerebellar stroke using a modified version of the International Cooperative Ataxia Rating Scale (MICARS). Lesion location was determined using magnetic resonance imaging (MRI) and computerized axial tomography (CT). Patients were grouped by stroke location-Group I, stroke within the anterior lobe (lobules I-V); Group 2, anterior lobe and lobule VI; Group 3, posterior lobe (lobules VI-IX; including flocculonodular lobe, lobule X); Group 4, posterior lobe but excluding lobule VI (i.e. lobules VII-X); Group 5, stroke within anterior lobe plus posterior lobe. RESULTS: Thirty-nine patients were examined 8.0+/-6.0 days following stroke. There were no Group 1 patients. As mean MICARS scores for Groups 2 through 5 differed significantly (one-way analysis of variance, F(3,35)=10.9, P=0.000 03), post hoc Tukey's least significant difference tests were used to compare individual groups. Group 2 MICARS scores (n=6; mean+/-SD, 20.2+/-6.9) differed from Group 3 (n=6; 7.2+/-3.8; P=0.01) and Group 4 (n=13; 2.5+/-2.0; P=0.000 02); Group 5 (n=14; 18.6+/-12.8) also differed from Group 3 (P=0.009) and Group 4 (P=0.000 02). There were no differences between Groups 2 and 5 (P=0.71), or between Group 3 and Group 4 (P=0.273). However, Group 3 differed from Group 4 when analyzed with a two-sample t-test unadjusted for multiple comparisons (P=0.03). Thus, the cerebellar motor syndrome resulted from stroke in the anterior lobe, but not from stroke in lobules VII-X (Groups 2 plus 5, n=20, MICARS 19.1+/-11.2, vs. Group 4; P=0.000 002). Strokes involving lobule VI produced minimal motor impairment. CONCLUSION: These findings demonstrate that cerebellar stroke does not always result in motor impairment, and they provide clinical evidence for topographic organization of motor versus nonmotor functions in the human cerebellum.

Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers.

MRI tractography is the mapping of neural fiber pathways based on diffusion MRI of tissue diffusion anisotropy. Tractography based on diffusion tensor imaging (DTI) cannot directly image multiple fiber orientations within a single voxel. To address this limitation, diffusion spectrum MRI (DSI) and related methods were developed to image complex distributions of intravoxel fiber orientation. Here we demonstrate that tractography based on DSI has the capacity to image crossing fibers in neural tissue. DSI was performed in formalin-fixed brains of adult macaque and in the brains of healthy human subjects. Fiber tract solutions were constructed by a streamline procedure, following directions of maximum diffusion at every point, and analyzed in an interactive visualization environment (TrackVis). We report that DSI tractography accurately shows the known anatomic fiber crossings in optic chiasm, centrum semiovale, and brainstem; fiber intersections in gray matter, including cerebellar folia and the caudate nucleus; and radial fiber architecture in cerebral cortex. In contrast, none of these examples of fiber crossing and complex structure was identified by DTI analysis of the same data sets. These findings indicate that DSI tractography is able to image crossing fibers in neural tissue, an essential step toward non-invasive imaging of connectional neuroanatomy.

Human cerebellar responses to brush and heat stimuli in healthy and neuropathic pain subjects.

Though human pain imaging studies almost always demonstrate activation in the cerebellum, the role of the cerebellum in pain function is not well understood. Here we present results from two studies on the effects of noxious thermal heat and brush applied to the right side of the face in a group of healthy subjects (Group I) and a group of patients with neuropathic pain (Group II) who are more sensitive to both thermal and mechanical stimuli. Statistically significant activations and volumes of activations were defined in the cerebellum. Activated cerebellar structures were identified by colocalization of fMRI activation with the 'MRI Atlas of the Human Cerebellum'. Functional data (obtained using a 3T magnet) were defined in terms of maximum voxels and volume of activation in the cerebellum. Volume maps were then mapped onto two millimeter serial slices taken through the cerebellum in order to identify activation within regions defined by the activation volume. The data indicate that different regions of the cerebellum are involved in acute and chronic pain processing. Heat produces greater contralateral activation compared with brush, while brush resulted in more ipsilateral/bilateral cerebellar activation. Further, innocuous brush stimuli in healthy subjects produced decreased cerebellar activation in lobules concerned with somatosensory processing. The data also suggest a dichotomy of innocuous stimuli/sensorimotor cerebellum activation versus noxious experience/cognitive/limbic cerebellum activation. These results lead us to propose that the cerebellum may modulate the emotional and cognitive experience that distinguishes the perception of pain from the appreciation of innocuous sensory stimulation.

Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population.

Acquired cerebellar lesions in adults have been shown to produce impairments in higher function as exemplified by the cerebellar cognitive affective syndrome. It is not yet known whether similar findings occur in children with acquired cerebellar lesions, and whether developmental factors influence their presentation. In studies to date, survivors of childhood cerebellar tumours who demonstrate long-term deficits in cognitive functions have undergone surgery as well as cranial irradiation or methotrexate treatment. Investigation of the effects of the cerebellar lesion independent of the known deleterious effects of these agents is important for understanding the role of the cerebellum in cognitive and affective development and for informing treatment and rehabilitation strategies. If the cerebellar contribution to cognition and affect is significant, then damage in childhood may influence a wide range of psychological processes, both as an immediate consequence and as these processes fail to develop normally later on. In this study we evaluated neuropsychological data in 19 children who underwent resection of cerebellar tumours but who received neither cranial irradiation nor methotrexate chemotherapy. Impairments were noted in executive function, including planning and sequencing, and in visual-spatial function, expressive language, verbal memory and modulation of affect. These deficits were common and in some cases could be dissociated from motor deficits. Lesions of the vermis in particular were associated with dysregulation of affect. Behavioural deficits were more apparent in older than younger children. These results reveal that clinically relevant neuropsychological changes may occur following cerebellar tumour resection in children. Age at the time of surgery and the site of the cerebellar lesion influence the neurobehavioural outcome. The results of the present study indicate that the cerebellar cognitive affective syndrome is evident in children as well as in adults, and they provide further clinical evidence that the cerebellum is an essential node in the distributed neural circuitry subserving higher-order behaviours.

Three-dimensional MRI atlas of the human cerebellum in proportional stereotaxic space.

We have prepared an atlas of the human cerebellum using high-resolution magnetic resonance-derived images warped into the proportional stereotaxic space of Talairach and Tournoux. Software that permits simultaneous visualization of the three cardinal planes facilitated the identification of the cerebellar fissures and lobules. A revised version of the Larsell nomenclature facilitated a simple description of the cerebellum. This atlas derived from a single individual was instrumental in addressing longstanding debates about the gross morphologic organization of the cerebellum. It may serve as the template for more precise identification of cerebellar topography in functional imaging studies in normals, for investigating clinical-pathologic correlations in patients, and for the development of future probabilistic maps of the human cerebellum.

The cerebellar cognitive affective syndrome.

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.

Dysmetria of thought: clinical consequences of cerebellar dysfunction on cognition and affect.

Cognitive and emotional changes might be prominent or even principal manifestations of cerebellar lesions. This realization supports evidence suggesting that the cerebellum is an important part of a set of distributed neural circuits that subserve higher-order processing. Early anecdotal clinical accounts described aberrant mental or intellectual functions in the setting of cerebellar atrophy. Later systematic analyses showed that the cerebellum is able to influence autonomic, vasomotor, and emotional behaviors, and further studies revealed neuropsychological deficits in patients with degenerative diseases. Current descriptions of behavioral changes in adults and children with acquired cerebellar lesions bring the debate about the cerebellar role in neural function within the realm of clinically relevant cognitive neuroscience. The activation of focal cerebellar regions by cognitive tasks on functional neuroimaging studies, and morphologic abnormalities of cerebellum in psychiatric diseases such as autism and schizophrenia further support this view. Anatomical substrates have been elucidated that could support a cerebellar role in cognition and emotion. Our concept of `dysmetria of thought' draws an analogy with the motor system to describe and explain the impairments of higher-order behavior that result when the distributed neural circuits subserving cognitive operations are deprived of cerebellar modulation.

Normal-pressure hydrocephalus with misleading features of irreversible dementias: a case report.

An 85-year-old man presented with the clinical triad (gait instability, dementia, and bladder and bowel incontinence), the ventriculomegaly, and the normal CSF pressure that characterize normal-pressure hydrocephalus (NPH). Diagnostic uncertainty was raised by an unusually rapid onset and a lack of initial response to CSF tap tests. Additionally, periodic sharp waves on EEG suggested the possibility of Creutzfeldt-Jakob disease, and positron emission tomography (PET) demonstrated a pattern of cerebral hypometabolism typical of Alzheimer's disease. Nevertheless, the diagnosis of NPH was supported by delayed improvement following CSF tap tests, and it was confirmed by a dramatic clinical recovery after CSF shunting, resolution of the EEG and PET abnormalities, and a normal brain biopsy. NPH remains one of the few reversible causes of dementia, and the presence of its core features, regardless of rate of onset or ancillary test results, warrants careful consideration of therapeutic intervention.

Anatomic organization of the basilar pontine projections from prefrontal cortices in rhesus monkey.

In our ongoing attempt to determine the anatomic substrates that could support a cerebellar contribution to cognitive processing, we investigated the prefrontal cortical projections to the basilar pons. A detailed understanding of these pathways is needed, because the prefrontal cortex is critical for a number of complex cognitive operations, and the corticopontine projection is the obligatory first step in the corticopontocerebellar circuit. Prefrontopontine connections were studied using the autoradiographic technique in rhesus monkey. The pontine projections were most prominent and occupied the greatest rostrocaudal extent of the pons when derived from the dorsolateral prefrontal convexity, including areas 8Ad, 9/46d, and 10. Lesser pontine projections were observed from the medial prefrontal convexity and area 45B in the inferior limb of the arcuate sulcus. In contrast, ventral prefrontal and orbitofrontal cortices did not demonstrate pontine projections. The prefrontopontine terminations were located preferentially in the paramedian nucleus and in the medial parts of the peripeduncular nucleus, but each cortical area appeared to have a unique complement of pontine nuclei with which it is connected. The existence of these corticopontine pathways from prefrontal areas concerned with multiple domains of higher-order processing is consistent with the hypothesis that the cerebellum is an essential node in the distributed corticosubcortical neural circuits subserving cognitive operations.

Rediscovery of an early concept.

The study of the cerebellum has been dominated by interest in its role in movement and motor control. From the earliest days of the neuroscientific era, however, clinical reports and physiological and behavioral investigations have suggested that overt motor dysfunction is but one manifestation of cerebellar disease. The nature of cerebellar involvement in autonomic, sensory, and cognitive functions has been investigated for many years, and possible mechanisms that could subserve this relationship have been specifically addressed. This work has not been incorporated into the mainstream of neuroscience or clinical neurological thinking. This chapter traces the history of these early investigations that demonstrated the need to revise the notion that cerebellar function is confined to the motor realm. The collaboration across disciplines and the advances in the methods and concepts of contemporary neuroscience have facilitated the maturation of this field of inquiry. The "new" story of the cerebellum and cognition, in fact, represents the evolution of a century-old revolutionary concept.

The cerebrocerebellar system.

If there is a cerebellar contribution to nonmotor function, particularly to cognitive abilities and affective states, then there must be corresponding anatomic substrates that support this. The cerebellum is strongly interconnected with the cerebral hemispheres in both feedforward (cerebral hemispheres to cerebellum) and feedback directions. This relationship has long been recognized, particularly with respect to the motor and sensory cortices. Investigations performed over the last decade however, have demonstrated for the first time the organization and strength of the connections that link the cerebellum with areas of the cerebral cortex known to be concerned with higher order behavior rather than with motor control. The feedforward projections from these higher order areas, namely the associative and paralimbic cortices, seem to be matched, at least in the limited but definite demonstrations to date, by cerebellar projections back to these same areas. These observations are important because they are congruent with the notion that cognitive functions are distributed among multiple cortical and subcortical nodes, each of which functions in concert but in a unique manner to produce an ultimate behavior pattern. This chapter describes the neural circuitry postulated to subserve the cerebellar contribution to nonmotor processing, particularly cognitive and affective modulation, and discusses the theoretical implications of these anatomic findings.

Cerebellar cognitive affective syndrome.

There has been persistent uncertainty as to whether lesions of the cerebellum are associated with clinically significant disturbances of behavior and cognition. To address this question, 20 patients with diseases confined to the cerebellum were studied prospectively over a 7-year period and the nature and severity of the changes in neurological and mental function were evaluated. Neurological examination, bedside mental state testing, neuropsychological studies, and anatomic neuroimaging were administered at the time of presentation and during follow-up assessments. Behavioral changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis and, in some cases, overwhelmed other aspects of the presentation. These changes were characterized by an impairment of working memory, planning, set shifting, verbal fluency, abstract reasoning, and perseveration; visual-spatial disorganization, visual memory deficits, and logical sequencing; and a bland or frankly inappropriate affect. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. This newly defined clinical entity is called the cerebellar cognitive affective syndrome. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits than link frontal, parietal, temporal, and limbic cortices with the cerebellum.

Therapeutic and research implications.

Investigations into the relationship between the cerebellum and nonmotor processing have produced a substantial body of evidence which seems to require a revision of accepted notions about the functional role of the cerebellum. This chapter presents a perspective on the contemporary and possible future therapeutic and research implications of these findings. These include the need for patients and their families to know of the behavioral consequences of cerebellar disease processes; potential approaches for improvement through rehabilitation therapies; and future treatment strategies, such as electrical stimulation of the cerebellum and psychosurgical approaches applied to the cerebellum. In addition, some areas of basic science investigation that could prove informative in understanding this relationship are addressed. It will be important to obtain a more complete characterization of the anatomy, physiology, and functional topography of the cerebellum in humans and in animal models, and a greater understanding of the clinical consequences of cerebellar lesions.

From movement to thought: anatomic substrates of the cerebellar contribution to cognitive processing.

The cerebellar contribution to cognitive operations and emotional behavior is critically dependent upon the existence of plausible anatomic substrates. This paper explores these anatomic substrates, namely, the incorporation of the associative and paralimbic cerebral areas into the cerebrocerebellar circuitry in nonhuman primates. Using the novel information that has emerged concerning this system, proposed rules are derived and specific hypotheses offered concerning cerebellar function and the relationship between cerebellum and nonmotor behavior, as follow. (1) The associative and paralimbic incorporation into the cerebrocerebellar circuit is the anatomic underpinning of the cerebellar contribution to cognition and emotion. (2) There is topographic organization of cognitive and behavioral functions within the cerebellum. The archicerebellum, vermis, and fastigial nucleus are principally concerned with affective and autonomic regulation and emotionally relevant memory. The cerebellar hemispheres and dentate nucleus are concerned with executive, visual-spatial, language, and other mnemonic functions. (3) The convergence of inputs from multiple associative cerebral regions to common areas within the cerebellum facilitates cerebellar regulation of supramodal functions. (4) The cerebellar contribution to cognition is one of modulation rather than generation. Dysmetria of (or ataxic) thought and emotion are the clinical manifestations of a cerebellar lesion in the cognitive domain. (5) The cerebellum performs the same computations for associative and paralimbic functions as it does for the sensorimotor system. These proposed rules and the general and specific hypotheses offered in this paper are testable using functional neuroimaging techniques. Neuroanatomy and functional neuroimaging may thus be mutually advantageous in predicting and explaining new concepts of cerebellar function.

Prefrontal cortex projections to the basilar pons in rhesus monkey: implications for the cerebellar contribution to higher function.

The feedforward limb of the cerebrocerebellar system is directed largely through the corticopontine pathway. We determined the extent to which higher order corticopontine projections are derived from prefrontal associative cortices by injecting anterograde tracers into multiple prefrontal regions in rhesus monkeys. Most prefrontopontine projections were derived from the dorsolateral and dorsomedial convexities, including areas 8A, 46 dorsal, 9, and 10; and lighter projections arose from medial and ventrolateral cortices. These findings strengthen the observation that the cerebrocerebellar system incorporates associative cerebral regions, and they enhance the notion that the cerebellum participates in the organization of cognitive function.

Therapy for paraneoplastic neurologic syndromes in six patients with protein A column immunoadsorption.

BACKGROUND: Paraneoplastic neurologic syndromes, although rare, cause significant morbidity and mortality. They are thought to be immunologically mediated, but to date those involving the central nervous system (CNS) have not been particularly responsive to immunologic therapy. The use of the novel immunomodulator, protein A immunoadsorption, was explored to address this question. METHODS: Six patients with neurologic paraneoplastic syndromes were treated with this technique, using the "off line" method. Two hundred fifty ml of plasma was perfused through a column containing protein A covalently attached to a silica matrix. The plasma was then returned to the patient. RESULTS: Five of the patients responded to the therapy, with complete and durable responses in three patients with opsoclonus-myoclonus, objective, though transient, improvement in one patient with paraneoplastic brainstem encephalitis associated with a Merkel cell tumor, and stabilization and partial improvement in one patient with paraneoplastic limbic encephalitis. The patient without response developed a cutaneous vasculitis after the second treatment, and therapy was discontinued. CONCLUSIONS: This therapy appears beneficial for a number of paraneoplastic syndromes, most dramatically in the opsoclonus/myoclonus syndrome.

Prelunate, occipitotemporal, and parahippocampal projections to the basis pontis in rhesus monkey.

We used tritiated amino acids to study projections to the basilar pons from prestriate cortices in 18 rhesus monkeys to determine how connectional and functional heterogeneity of these regions are reflected in corticopontine circuitry. Fibers travelled with those from other parasensory associative cortices before terminating in the pontine nuclei. Prelunate projections were derived from area 19 (OA) at the medial convexity (including areas V3 and PO) and from the lateral convexity dorsal to the caudal tip of the Sylvian fissure (including areas DP and the dorsal part of area V4d). Pontine projections also arose from area 19 (OA), and areas TF, TL, and TH in the posterior aspect of the parahippocampal gyrus. No pontine projections arose from the prelunate convexity ventral to the caudal tip of the Sylvian fissure (ventral part of area V4d and area V4v), area TEO, the inferior temporal gyrus, or the lateral ventral temporal region. Terminations in the pons were distributed in the dorsolateral and lateral nuclei, and the lateral part of the peripeduncular nucleus. Medial convexity injections produced more extensive rostrocaudal pontine labeling, as well as terminations in the extreme dorsolateral nucleus and the nucleus reticularis tegmenti pontis. Dorsal prelunate injections had additional terminations in the ventral pontine nucleus. Posterior parahippocampal gyrus injections resulted in discrete label in the lateral and dorsolateral nuclei. Corticopontine projections destined for the cerebellum appear to be derived from extrastriate areas concerned mainly with visual spatial parameters, visual motion, and the peripheral field of vision, but not from areas subserving visual object identification and the central field of vision. Pontine afferents from the posterior parahippocampal gyrus may facilitate a cerebellar contribution to visual spatial memory, particularly when invested with motivational valence.