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        <title>Hippocampal CA1 and CA3 neural recording in the human brain: validation of depth electrode placement through high-resolution imaging and electrophysiology</title>
        <author>Wicks</author>
        <author>Witcher</author>
        <author>Couture</author>
        <author>Laxton</author>
        <author>Popli</author>
        <author>Whitlow</author>
        <author>Fetterhoff</author>
        <author>Dakos</author>
        <author>Roeder</author>
        <author>Deadwyler</author>
        <author>Hampson</author>
      </titleStmt>
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        <p>Tag layer of the DHSS Meta-Tagging Project. The article text is reproduced from the
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        <bibl>
          <title>Hippocampal CA1 and CA3 neural recording in the human brain: validation of depth electrode placement through high-resolution imaging and electrophysiology</title>
          <date>2020</date>
          <publisher>Neurosurgical Focus</publisher>
          <idno type="DOI">10.3171/2020.4.focus20164</idno>
          
          <idno type="record">wicks2020-hippocampal-ca1-and-ca3-neural-rec</idno>
          <note type="staged-file">wicks2020-hippocampal-ca1-and-ca3-neural-rec.txt, the project's staged copy</note>
          <note type="text-sha1">6130d9bbbc3c3c694fb0c27e15248ebc8eae63fc</note>
          <note type="rights">open-access</note>
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      <textClass><keywords><term>neuroscience</term></keywords></textClass>
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        <person xml:id="paper"><p>the paper's own words</p></person>
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      <span xml:id="t0" type="claim_type" ana="#claim_type" resp="#paper">
        <label>method</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t1" type="phenomenon" ana="#phenomenon" resp="#paper">
        <label>localization of single-neuron recordings in human hippocampal CA1 and CA3</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t2" type="method" ana="#method" resp="#paper">
        <label>electrophysiology</label>
        <term>electrophysiology</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t3" type="mechanisms" ana="#mechanisms[0]" resp="#tagger">
        <label>mechanisms</label>
        <term>Monosynaptic Schaffer collateral transmission from CA3 to CA1 produces the 2-5 msec lagged firing correlation, while shared perforant path input to both subfields produces the 0-msec synchronous correlation.</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t4" type="limitations" ana="#limitations[0]" resp="#tagger">
        <label>Only the 2-5 msec feed-forward correlations can be taken as definitive evidence of CA3-to-CA1 synaptic connectivity; the synchronous and long-lag pairs are inferred to be correctly assigned rather than proven so.</label>
        <note>what this limits: the connectivity claim, separated from the suggestive part: ONLY THE 2- TO 5-MSEC FEED-FORWARD CORRELATIONS (20.3%) CAN BE DEFINITIVELY IDENTIFIED AS CA3-TO-CA1 SYNAPTIC CONNECTIVITY</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t5" type="limitations" ana="#limitations[1]" resp="#tagger">
        <label>The localization procedure used here is not a standardized stereotactic system, which the authors say would be needed for cross-centre standardization.</label>
        <note>what this limits: any comparison across surgical centres: LOCALIZATION USING STANDARDIZED TEMPORAL STEREOTACTIC SYSTEMS ... WOULD BE USEFUL FOR FUTURE ITERATIONS OR FOR STANDARDIZATION ACROSS SURGICAL CENTERS</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t6" type="limitations" ana="#limitations[2]" resp="#tagger" cert="1.0">
        <label>A cell type is inferred from a firing-rate threshold and those cells are excluded from the sample.</label>
        <note>what this limits: any proportion reported over these neurons: cells with steady-state resting firing rates above 20 Hz were treated as clearly interneurons and were not recorded</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t7" type="limitations" ana="#limitations[3]" resp="#tagger" cert="1.0">
        <label>The cell-type labels are confirmed by the connectivity pattern they are used to demonstrate.</label>
        <note>what this limits: the identification of these neurons as CA3 and CA1: cells were selected as candidates on waveform and firing-rate characteristics and then confirmed within the CA3-to-CA1 projection pathways via measures of functional connectivity</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t8" type="limitations" ana="#limitations[4]" resp="#tagger" cert="1.0">
        <label>The human proportion is validated by its resemblance to published animal numbers.</label>
        <note>what this limits: the 26% feed-forward correlation reported here: the authors support it by noting that it favourably compares to reports of 20%-25% feedforward CA3-CA1 correlation in published animal studies</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t9" type="controls" ana="#controls[0]" resp="#tagger" cert="0.85">
        <label>post-operative electrode placement verified by MRI</label>
        <note>eliminates: assigning CA1 and CA3 recordings to the wrong subfield, which is the entire distinction the paper rests on · outcome (stated by the tagger, no quotation): held</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t10" type="concepts" ana="#concepts[0]" resp="#paper">
        <label>interneurons</label>
        <term>interneurons</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t11" type="concepts" ana="#concepts[1]" resp="#paper">
        <label>principal neurons</label>
        <term>principal neurons</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t12" type="concepts" ana="#concepts[2]" resp="#paper">
        <label>functional connectivity</label>
        <term>functional connectivity</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t13" type="concepts" ana="#concepts[3]" resp="#paper">
        <label>inverse correlation</label>
        <term>inverse correlation</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t14" type="concepts" ana="#concepts[4]" resp="#paper">
        <label>synaptic connectivity</label>
        <term>synaptic connectivity</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t15" type="concepts" ana="#concepts[5]" resp="#paper">
        <label>feed-forward correlations</label>
        <term>feed-forward correlations</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t16" type="senses" ana="#senses[0]" resp="#tagger" cert="1.0">
        <label>an interneuron, here - A FIRING RATE ABOVE 20 Hz: the classification is made in a parenthesis and acted on in the main clause, so a rate threshold becomes a cell type and then an exclusion, and every proportion in the paper is computed over what remained</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t17" type="senses" ana="#senses[1]" resp="#tagger" cert="1.0">
        <label>a CA3 or CA1 principal neuron - CANDIDATE BY WAVEFORM, CONFIRMED BY CONNECTIVITY: the label is assigned from waveform and firing rate and then confirmed by the projection pattern it predicts, so the classification and the finding it supports rest on each other</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t18" type="senses" ana="#senses[2]" resp="#tagger" cert="1.0">
        <label>the argument for the labels - AN EXPECTED SIGNATURE OF ERROR: misidentification is said to be expected to yield a higher percentage of inverse correlation, so the low inverse rate is offered as evidence the labels are right - sound only if misidentification could not also produce the observed pattern</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t19" type="claim_relations" ana="#claim_relations[0]" resp="#tagger">
        <label>extends → Ulbert et al., intraoperative layer-specific human hippocampal recordings with postoperative histology</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t20" type="concept_edges" ana="#concept_edges[0]" resp="#tagger">
        <label>feed-forward correlations —operationalised-as→ synaptic connectivity</label>
        <term>feed-forward correlations</term>
        <term>synaptic connectivity</term>
        <note>holds when: only for correlations in the 2- to 5-msec window · strength of the relation: 1
Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span says the correlations can be IDENTIFIED as connectivity; operationalised-as is loose.</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t21" type="content_tags" ana="#content_tags.statistics[0]" resp="#tagger">
        <label>t-test</label>
        <term>t-test</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t22" type="content_tags" ana="#content_tags.statistics[1]" resp="#tagger">
        <label>cross-correlation</label>
        <term>cross-correlation</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t23" type="content_tags" ana="#content_tags.statistics[2]" resp="#tagger">
        <label>standard deviation</label>
        <term>standard deviation</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t24" type="content_tags" ana="#content_tags.statistics[3]" resp="#tagger">
        <label>p-value</label>
        <term>p-value</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t25" type="content_tags" ana="#content_tags.findings[0]" resp="#tagger">
        <label>Nearly 80% of putative CA3-to-CA1 cell pairs showed positive cross-correlations compatible with a feed-forward connection, whereas only 2.6% showed inverse (feedback) correlation.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t26" type="content_tags" ana="#content_tags.findings[1]" resp="#tagger">
        <label>Feed-forward correlation was found in 1,071 of 4,070 CA3-CA1 pairs (26%), a rate close to the 20%-25% reported in animal studies, even after synchronous and long-latency correlations were excluded.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t27" type="content_tags" ana="#content_tags.findings[2]" resp="#tagger">
        <label>In non-epileptic patients the CA1 region lay at an average depth of 36.06 mm from the outer table of the skull on the left and 34.84 mm on the right.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t28" type="content_tags" ana="#content_tags.findings[3]" resp="#tagger">
        <label>Only the 2-5 msec feed-forward correlations (20.3%) are definitive CA3-to-CA1 synaptic connectivity, but positive correlations dominated (77.8%) and inverse correlations were rare, which the authors read as evidence that the cells were correctly assigned to CA3 and CA1.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t29" type="content_tags" ana="#content_tags.findings[4]" resp="#tagger">
        <label>Anterior hippocampal neurons fired mainly at the sample response, whereas posterior hippocampal neurons fired at elevated rates in the interval between the sample and the match responses.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t30" type="content_tags" ana="#content_tags.findings[5]" resp="#tagger">
        <label>About five times as many recorded hippocampal neurons fired below 5.0 Hz as fired above 5.0 Hz.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t31" type="content_tags" ana="#content_tags.definitions[1]" resp="#tagger">
        <label>Delayed-Match-to-Sample</label>
        <term>Delayed-Match-to-Sample</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t32" type="content_tags" ana="#content_tags.variables[0]" resp="#tagger">
        <label>cross-correlograms</label>
        <term>cross-correlograms</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t33" type="content_tags" ana="#content_tags.variables[3]" resp="#tagger">
        <label>line noise</label>
        <term>line noise</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t34" type="content_tags" ana="#content_tags.quantities[0]" resp="#tagger">
        <label>2.6% — proportion of CA3-CA1 cell pairs showing feedback (inverse) correlation, taken as the misidentification rate</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t35" type="content_tags" ana="#content_tags.quantities[1]" resp="#tagger">
        <label>1071 (26%) of 4070 — number and share of cell pairs showing feed-forward CA3-to-CA1 correlation</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t36" type="content_tags" ana="#content_tags.quantities[2]" resp="#tagger">
        <label>77.8% — share of CA3-CA1 pairs showing any positive (synchronous, short-lag or long-lag) correlation</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t37" type="content_tags" ana="#content_tags.quantities[3]" resp="#tagger">
        <label>36.06 ± 2.88 mm — mean depth of left-hemisphere CA1 from the outer table of the skull in non-epileptic patients</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t38" type="content_tags" ana="#content_tags.quantities[4]" resp="#tagger">
        <label>744 — number of neurons recorded across the 23 implanted patients (per Table 1)</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <p><note type="rights">The full text of this article is not redistributable, so it is
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      grounding status remain. The article itself is at https://doi.org/10.3171/2020.4.focus20164.</note></p>
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