Jonathan C. Horton

The cortical column: a structure without a function

This year, the field of neuroscience celebrates the 50th anniversary of Mountcastles discovery of the cortical column. In this review, we summarize half a century of research and come to the disappointing realization that the column may have no function. Originally, it was described as a discrete structure, spanning the layers of the somatosensory cortex, which contains cells responsive to only a single modality, such as deep joint receptors or cutaneous receptors. Subsequently, examples of columns have been uncovered in numerous cortical areas, expanding the original concept to embrace a variety of different structures and principles. A ‘column’ now refers to cells in any vertical cluster that share the same tuning for any given receptive field attribute. In striate cortex, for example, cells with the same eye preference are grouped into ocular dominance columns. Unaccountably, ocular dominance columns are present in some species, but not others. In principle, it should be possible to determine their function by searching for species differences in visual performance that correlate with their presence or absence. Unfortunately, this approach has been to no avail; no visual faculty has emerged that appears to require ocular dominance columns. Moreover, recent evidence has shown that the expression of ocular dominance columns can be highly variable among members of the same species, or even in different portions of the visual cortex in the same individual. These observations deal a fatal blow to the idea that ocular dominance columns serve a purpose. More broadly, the term ‘column’ also denotes the periodic termination of anatomical projections within or between cortical areas. In many instances, periodic projections have a consistent relationship with some architectural feature, such as the cytochrome oxidase patches in V1 or the stripes in V2. These tissue compartments appear to divide cells with different receptive field properties into distinct processing streams. However, it is unclear what advantage, if any, is conveyed by this form of columnar segregation. Although the column is an attractive concept, it has failed as a unifying principle for understanding cortical function. Unravelling the organization of the cerebral cortex will require a painstaking description of the circuits, projections and response properties peculiar to cells in each of its various areas.

An adult-like pattern of ocular dominance columns in striate cortex of newborn monkeys prior to visual experience

In macaque monkeys, the geniculocortical afferents serving each eye segregate in layer IVc of striate cortex during early life into a pattern of alternating inputs called ocular dominance columns. It has been disputed whether visual experience is necessary for the formation of ocular dominance columns. To settle this issue, fetal monkeys were delivered prematurely by Caesarean section at embryonic day 157 (E157), 8 d before the end of normal gestation. To avoid light exposure, the Caesarean section and all subsequent feedings and procedures were done in absolute darkness, using infrared night-vision goggles. Tritiated proline was injected into the right eye 1 d after delivery (E158). One week later at postnatal age 0 (P0), the equivalent of a full-term pregnancy (E165/P0), alternate sections of unfolded and flattened visual cortex were prepared for autoradiography or cytochrome oxidase (CO). All three newborns studied at E165/P0 had well segregated ocular dominance columns organized into the characteristic mosaic present in adults. In the upper layers, a mature pattern of CO patches (also known as blobs or puffs) was visible, aligned with the ocular dominance columns in layer IVc. Every other row of patches in layers II, III was labeled by [3H]proline. In V2, a distinct system of alternating thick- pale-thin-pale CO stripes was present. These findings indicate that stimulation of the retina by light is not necessary for the development of columnar systems in the visual cortex. Ocular dominance columns, patches, and V2 stripes all are well formed before visual experience. Even the thalamic input to the patches in the upper layers of striate cortex is segregated by eye in newborns.

Pregnancy and the Risk of Hemorrhage from Cerebral Arteriovenous Malformations

We conducted a retrospective analysis of 451 women with an arteriovenous malformation (AVM) of the brain to determine whether pregnancy is a risk factor for cerebral hemorrhages. A total of 540 pregnancies occurred among our patient population, resulting in 438 live births and 102 abortions. There were 17 pregnancies complicated by a cerebral hemorrhage. The hemorrhage rate during pregnancy for women with an unruptured AVM was 0.035 +/- 0.005 per person-year. The hemorrhage rate for nonpregnant women of childbearing age with an unruptured AVM was 0.031 +/- 0.002 per person-year. Pregnancy did not increase significantly the rate of first cerebral hemorrhage from an AVM (P = 0.35). We found that women with an AVM face a 3.5% risk of hemorrhage during pregnancy. Pregnancy is not a risk factor for hemorrhage in women without a previous hemorrhage. This conclusion assumes no selection bias exists in our study population; a bias would be introduced if the risk of fatal outcome after a hemorrhage were greater in pregnant women than in nonpregnant women.

Idiopathic Intracranial Hypertension

OBJECTIVEThe history, diagnosis, and therapy of idiopathic intracranial hypertension (IIH) (pseudotumor cerebri) are reviewed. Theories of pathogenesis are considered, the clinical presentation is described, and potential diagnostic and therapeutic challenges are explored. METHODSAn extensive literature review of IIH and related conditions (secondary pseudotumor syndromes) was performed. The history of and rationale for the diagnosis and medical and surgical approaches to treatment are reviewed. Available outcome studies are presented. RESULTSDiagnosis of IIH requires that the modified Dandy criteria be satisfied. Multiple potential contributing causes of intracranial hypertension must be identified or excluded. The clinical presentation most often includes headaches and papilledema, but many other findings have been described. The most important goal of therapy is to prevent or arrest progressive visual loss. Medical therapies include alleviation of associated systemic diseases, discontinuation of contributing medications, provision of carbonic anhydrase inhibitors, and weight loss. Surgical therapies include lumboperitoneal shunting, ventriculoperitoneal shunting, and optic nerve sheath fenestration. On the basis of the advantages and disadvantages of these treatment modalities, a suggested treatment paradigm is presented. CONCLUSIONIdiopathic intracranial hypertension is the term to be adopted instead of pseudotumor cerebri. IIH remains an enigmatic diagnosis of exclusion. However, prompt diagnosis and thorough evaluation and treatment are crucial for preventing visual loss and improving associated symptoms.

Complete pattern of ocular dominance columns in human primary visual cortex.

The occipital lobes were obtained after death from six adult subjects with monocular visual loss. Flat-mounts were processed for cytochrome oxidase (CO) to reveal metabolic activity in the primary (V1) and secondary (V2) visual cortices. Mean V1 surface area was 2643 mm2 (range, 1986–3477 mm2). Ocular dominance columns were present in all cases, having a mean width of 863 μm. There were 78–126 column pairs along the V1 perimeter. Human column patterns were highly variable, but in at least one person they resembled a scaled-up version of macaque columns. CO patches in the upper layers were centered on ocular dominance columns in layer 4C, with one exception. In this individual, the columns in a local area resembled those present in the squirrel monkey, and no evidence was found for column/patch alignment. In every subject, the blind spot of the contralateral eye was conspicuous as an oval region without ocular dominance columns. It provided a precise landmark for delineating the central 15° of the visual field. A mean of 53.1% of striate cortex was devoted to the representation of the central 15°. This fraction was less than the proportion of striate cortex allocated to the representation of the central 15° in the macaque. Within the central 15°, each eye occupied an equal territory. Beyond this eccentricity, the contralateral eye predominated, occupying 63% of the cortex. In one subject, monocular visual loss began at age 4 months, causing shrinkage of ocular dominance columns. In V2, which had a larger surface area than V1, CO stripes were present but could not be classified as thick or thin.

Emergence of ocular dominance columns in cat visual cortex by 2 weeks of age

Previous anatomic studies of the geniculocortical projection showed that ocular dominance columns emerge by 3 weeks of age in cat visual cortex, but recent optical imaging experiments have revealed a pattern of physiologic eye dominance by the end of the second week of life. We used two methods to search for an anatomic correlate of this early functional ocular dominance pattern. First, retrograde labeling of lateral geniculate nucleus (LGN) inputs to areas of cortex preferentially activated by one eye showed that the geniculocortical projection was already partially segregated by eye at postnatal day 14 (P14). Second, transneuronal label of geniculocortical afferents in flattened sections of cortex after a tracer injection into one eye showed a periodic pattern at P14 but not at P7. In the classic model for the development of ocular dominance columns, initially overlapping geniculocortical afferents segregate by means of an activity‐dependent competitive process. Our data are consistent with this model but suggest that ocular dominance column formation begins between P7 and P14, approximately a week earlier than previously believed. The functional and anatomic data also reveal an early developmental bias toward contralateral eye afferents. This initial developmental bias is not consistent with a strictly Hebbian model for geniculocortical afferent segregation. The emergence of ocular dominance columns before the onset of the critical period for visual deprivation also suggests that the mechanisms for ocular dominance column formation may be partially distinct from those mediating plasticity later in life. J. Comp. Neurol. 430:235–249, 2001.

Neurovisual Findings in the Syndrome of Spontaneous Intracranial Hypotension from Dural Cerebrospinal Fluid Leak

BACKGROUND Spontaneous intracranial hypotension has been considered a rare clinical entity, with less than 75 cases reported in the medical literature. With the advent of magnetic resonance imaging (MRI), spontaneous intracranial hypotension currently is being recognized more frequently. The authors report the neurovisual manifestations of this disorder in a consecutive series of three patients. METHODS Each patient underwent clinical examination, computerized visual field testing, and MRI. After treatment, each patient was re-examined, and MRI was repeated. RESULTS Two patients had transient visual obscurations and unusual binasal visual field defects on automated perimetry. A third patient had diplopia from an abducens nerve paresis. After treatment of spontaneous intracranial hypotension, these findings improved or resolved. CONCLUSIONS This case series, and a review of previously reported cases, indicates that neurovisual problems are common in patients with spontaneous intracranial hypotension. Findings may include diplopia from sixth nerve paresis, transient visual obscurations, blurred vision, visual field defects, photophobia, and nystagmus.

Transmission of Spike Trains at the Retinogeniculate Synapse

Retinal spikes impinging on relay neurons in the lateral geniculate nucleus (LGN) generate synaptic potentials, which sometimes produce spikes sent to visual cortex. We examined how signal transmission is regulated in the macaque LGN by recording the retinal input to a single LGN neuron while stimulating the receptive field center with a naturalistic luminance sequence. After extracting the EPSPs, which are often partially merged with spike waveforms, we found that >95% of spikes were associated with an EPSP from a single retinal ganglion cell. Each spike within a “burst” train was generated by an EPSP, indicating that LGN bursts are inherited from retinal bursts. LGN neurons rarely fired unless at least two EPSPs summated within 40 ms. This facilitation in EPSP efficacy was followed by depression. If a spike was generated by the first EPSP in a pair, it did not alter the efficacy of the second EPSP. Hence, the timing of EPSPs arising from the primary retinal driver governs synaptic efficacy and provides the basis for successful retinogeniculate transmission.

Disappointing results from Nova Vision’s visual restoration therapy

We should refocus our search for new treatments in a more fruitful direction Lesions posterior to the optic chiasm produce homonymous visual field loss—overlapping scotomas in the nasal field of one eye and the temporal field of the other eye. Patients retain normal acuity, but find their lives changed forever. A homonymous hemianopia, when complete, makes safe driving impossible and reading a chore. Although some patients experience partial, spontaneous improvement following the acute phase of an event, most remain handicapped by permanent field loss. No treatment was available before the recent advent of visual restoration therapy. In a sensational series of reports, Sabel and colleagues (Kasten et al ) have described partial recovery of homonymous visual field defects by intensive computer based rehabilitation therapy.1–3 Their approach is remarkably simple. Patients practise perimetry at home for an hour a day, 6 days a week, for 6 months, using a software program loaded on their personal computer. A chin support is used for head stability and a monitor is placed 30 cm away. Stimuli are white, suprathreshold lights measuring 0.15° in diameter shown against a dark background. Protocols are tailored for each patient to present most stimuli near the border of the field defect (“transition” zone) to maximise potential therapeutic benefit. Sabel has founded a company (NovaVision) that offers visual rehabilitation therapy for about €5000. The idea behind visual restoration therapy is that after stroke or traumatic brain injury, a region …

Capricious expression of cortical columns in the primate brain

Columns are widely thought be the elementary functional module of the cerebral cortex, but their exact purpose remains unknown. In a group of 12 normal squirrel monkeys, we have found enormous variability in the expression of ocular dominance columns. This finding implies that ocular dominance columns are not vital for any specific function, at least in this species.